Journal of Biomarkers The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Cystatin-C as a Marker for Renal Impairment in Preeclampsia Tue, 11 Jul 2017 08:21:25 +0000 Preeclampsia is a devastating pregnancy-associated disorder characterized by the onset of hypertension, proteinuria, and edema with limited plausible pathophysiology known. Cystatin-C, a novel marker for the detection of renal impairment, is increased in preeclampsia at an early stage. This study was aimed to evaluate the diagnostic efficiency of Cystatin-C as an early marker of renal function in preeclampsia comparing it to the traditional renal markers. A hospital based comparative cross-sectional study was performed on 104 women (52 diagnosed cases of preeclampsia and 52 healthy pregnant women). Concentrations of Cystatin-C, creatinine, urea, and uric acid were measured in both the study groups. Mean serum Cystatin-C and uric acid levels were elevated in preeclampsia cases compared to controls (1.15 ± 0.37 versus 0.55 ± 0.12; 5.40 ± 1.44 versus 3.97 ± 0.68, resp.). ROC curve depicted that Cystatin-C had the highest diagnostic efficiency (sensitivity, 88.24%; specificity, 98.04%) compared to creatinine and uric acid. Serum Cystatin-C consequently seemed to closely reflect the renal functional changes, which are believed to lead to increased blood pressure levels and urinary excretion of albumin and may thus function as a marker for the stage of the transition between normal adaptive renal changes at term and preeclampsia. Apeksha Niraula, Madhab Lamsal, Nirmal Baral, Shankar Majhi, Seraj Ahmed Khan, Pritha Basnet, and Kashyap Dahal Copyright © 2017 Apeksha Niraula et al. All rights reserved. The Circadian Rhythm of Copeptin, the C-Terminal Portion of Arginine Vasopressin Thu, 01 Jun 2017 07:19:40 +0000 Background. Several studies have investigated copeptin as a prognostic marker of different acute diseases and as a diagnostic marker in disorders of water and salt homeostasis. However, no data of the normal circadian rhythm of copeptin in healthy subjects are available. Aim. To investigate the circadian rhythm of copeptin in healthy subjects under standardized conditions. Methods. 19 healthy volunteers aged 18 to 53 years, male and female, were studied in a prospective observational study. In all 19 participants, blood samples for copeptin were taken in regular intervals of 30 minutes for 24 hours after a fasting period of minimum 8 hours. Results. The mean values of copeptin showed a circadian rhythm, similar to that described for AVP release, with a trend towards higher levels ( pmol/L) at night and early morning between 4 am and 6 am and lowest levels ( pmol/L) in the late afternoon between 5 pm and 7 pm. This finding was only observed in individuals with initial higher copeptin levels, whereas in individuals with lower basal copeptin levels no circadian rhythm was observed. Conclusion. There is evidence for a circadian rhythm in copeptin release during 24 hours, however, of minor extent. These findings suggest that copeptin levels can be determined irrespectively of the time of the day. Svetlana Beglinger, Jürgen Drewe, and Mirjam Christ-Crain Copyright © 2017 Svetlana Beglinger et al. All rights reserved. Body Mass Index, Haemoglobin, and Total Lymphocyte Count as a Surrogate for CD4 Count in Resource Limited Settings Tue, 18 Apr 2017 09:10:22 +0000 Background. In view of the lack of evidence on the possibility of an economically viable, easy, and readily available biomarker to substitute the traditional role of CD4 counts in HIV disease progression, this study seeks to investigate the potential use of body mass index (BMI), haemoglobin (Hb), and total lymphocyte count (TLC) as surrogate biomarkers for monitoring the disease. Methods. This cross-sectional study was undertaken at the antiretroviral clinic (ART) of the Bomso Hospital, Kumasi, Ghana. We recruited 384 individuals who were 18 years or older and confirmed HIV seropositive patients. Blood samples were assayed for TLC and Hb. Weight and height were determined and BMI was calculated. Result. At a cut-off point of 12.15 g/dL, Hb had sensitivity and specificity of 73.9% and 56.8%, respectively, whereas BMI had 69.6% and 80.1% sensitivity and specificity, respectively. The sensitivity and specificity were also 100% among the studied participants at a cut-off point of 1200 mm−3 for TLC. There was a significant positive correlation between CD4 count and Hb (rho 0.262, ), BMI (rho 0.301, ), and TLC (rho 0.834, ). Conclusion. The study demonstrates that TLC, Hb, and BMI may provide some useful prognostic information independent of that provided by CD4 count. Louis Boafo Kwantwi, Bismark Kwame Tunu, Daniel Boateng, and Dan Yedu Quansah Copyright © 2017 Louis Boafo Kwantwi et al. All rights reserved. The Diagnostic Value of Serum C-Reactive Protein for Identifying Pneumonia in Hospitalized Patients with Acute Respiratory Symptoms Tue, 16 Aug 2016 10:03:27 +0000 Background. The clinical diagnosis of pneumonia is sometimes difficult since chest radiographs are often indeterminate. In this study, we aimed to assess whether serum C-reactive protein (CRP) could assist in identifying patients with pneumonia. Methods. For one winter, all consecutive patients with acute respiratory symptoms admitted to the emergency ward of a single center were prospectively enrolled. In addition to chest radiographs, basic laboratory tests, and microbiology, serum levels of CRP were measured at entry. Results. A total of 923 (62.3%) of 1473 patients hospitalized for acute respiratory symptoms were included. Subjects with a final diagnosis of pneumonia had higher serum CRP levels (median 187 mg/L) than those with exacerbations of chronic obstructive pulmonary disease (63 mg/L) or acute bronchitis (54 mg/L, ). CRP was accurate in identifying pneumonia (area under the curve 0.84, 95% CI 0.82–0.87). The multilevel likelihood ratio (LR) for intervals of CRP provided useful information on the posttest probability of having pneumonia. CRP intervals above 200 mg/L were associated with LR+ > 5, for which pneumonia is likely, whereas CRP intervals below 75 mg/L were associated with LR < 0.2, for which pneumonia is unlikely. Conclusion. Serum CRP may be a useful addition for diagnosing pneumonia in hospitalized patients with acute respiratory symptoms. Agustín Ruiz-González, Laia Utrillo, Silvia Bielsa, Miquel Falguera, and José M. Porcel Copyright © 2016 Agustín Ruiz-González et al. All rights reserved. The Predictive Role of Inflammatory Biomarkers in Atrial Fibrillation as Seen through Neutrophil-Lymphocyte Ratio Mirror Sun, 03 Jul 2016 12:28:18 +0000 Atrial fibrillation (AF) is the most common arrhythmia and is responsible for significant disease burden worldwide. Current evidence has suggested that systemic inflammatory response plays a crucial role in the initiation, maintenance, and progression of AF. So, recent efforts have been directed in search of measurable inflammatory biomarkers as additional tools in severity and prognosis assessment of AF. A simple, and easily obtainable, inflammatory marker is the neutrophil-lymphocyte ratio (NLR), which has shown good performance in preliminary studies as a potential prognostic biomarker in patients with AF. In this work, we performed a thorough review of clinical studies that evaluated the role of C-reactive protein (CRP), interleukin-6 (IL-6), and NLR as predictors of outcomes in AF. We gave a particular emphasis on the NLR because it is a simpler, widely available, and inexpensive biomarker. Feliciano Chanana Paquissi Copyright © 2016 Feliciano Chanana Paquissi. All rights reserved. Determination of Urinary Neopterin/Creatinine Ratio to Distinguish Active Tuberculosis from Latent Mycobacterium tuberculosis Infection Tue, 28 Jun 2016 12:11:49 +0000 Background. Biomarkers to distinguish latent from active Mycobacterium (M.) tuberculosis infection in clinical practice are lacking. The urinary neopterin/creatinine ratio can quantify the systemic interferon-gamma effect in patients with M. tuberculosis infection. Methods. In a prospective observational study, urinary neopterin levels were measured by enzyme linked immunosorbent assay in patients with active tuberculosis, in people with latent M. tuberculosis infection, and in healthy controls and the urinary neopterin/creatinine ratio was calculated. Results. We included a total of 44 patients with M. tuberculosis infection and nine controls. 12 patients had active tuberculosis (8 of them culture-confirmed). The median age was 15 years (range 4.5 to 49). Median urinary neopterin/creatinine ratio in patients with active tuberculosis was 374.1 micromol/mol (129.0 to 1072.3), in patients with latent M. tuberculosis infection it was 142.1 (28.0 to 384.1), and in controls it was 146.0 (40.3 to 200.0), with significantly higher levels in patients with active tuberculosis (). The receiver operating characteristics curve had an area under the curve of 0.84 (95% CI 0.70 to 0.97) (). Conclusions. Urinary neopterin/creatinine ratios are significantly higher in patients with active tuberculosis compared to patients with latent infection and may be a significant predictor of active tuberculosis in patients with M. tuberculosis infection. Michael Eisenhut, Dougal S. Hargreaves, Anne Scott, David Housley, Andrew Walters, and Rohinton Mulla Copyright © 2016 Michael Eisenhut et al. All rights reserved. Association Study between Promoter Polymorphism of TPH1 and Progression of Idiopathic Scoliosis Mon, 16 May 2016 13:22:15 +0000 The concept of disease-modifier genes as an element of genetic heterogeneity has been widely accepted and reported. The aim of the current study is to investigate the association between the promoter polymorphism TPH1 (rs10488682) and progression of idiopathic scoliosis (IS) in Eastern European population sample. A total of 105 patients and 210 healthy gender-matched controls were enrolled in this study. The TPH1 promoter polymorphism was genotyped by amplification followed by restriction. The statistical analysis was performed by Fisher’s Exact Test. The results indicated that the genotypes and alleles of TPH1 (rs10488682) are not correlated with curve severity, curve pattern, or bracing. Therefore, the examined polymorphic variant could not be considered as a genetic factor with modifying effect of IS. In conclusion, this case-control study revealed no statistically significant association between TPH1 (rs10488682) and progression of IS in Eastern European population sample. These preliminary results should be replicated in extended population studies including larger sample sizes. The identification of molecular markers for IS could be useful for a more accurate prognosis of the risk for a rapid progression of the curve. That would permit early stage treatment of the patient with the least invasive procedures. Vasil Yablanski, Svetla Nikolova, Evgeni Vlaev, Alexey Savov, and Ivo Kremensky Copyright © 2016 Vasil Yablanski et al. All rights reserved. A Sensitive IHC Method for Monitoring Autophagy-Specific Markers in Human Tumor Xenografts Tue, 10 May 2016 10:48:03 +0000 Objective. Use of tyramide signal amplification (TSA) to detect autophagy biomarkers in formalin fixed and paraffin embedded (FFPE) xenograft tissue. Materials and Methods. Autophagy marker regulation was studied in xenograft tissues using Amp HQ IHC and standard IHC methods. Results. The data demonstrate the feasibility of using high sensitivity TSA IHC assays to measure low abundant autophagy markers in FFPE xenograft tissue. Helen He, Yu Yang, Zhongmin Xiang, Lunyin Yu, Jouhara Chouitar, Jie Yu, Natalie Roy D’Amore, Ping Li, Zhi Li, Douglas Bowman, Matthew Theisen, James E. Brownell, and Stephen Tirrell Copyright © 2016 Helen He et al. All rights reserved. Association of Plasma Heat Shock Protein 70, Interleukin 6, and Creatine Kinase Concentrations in a Healthy, Young Adult Population Wed, 18 Nov 2015 13:47:46 +0000 Variations of baseline plasma concentrations of creatine kinase (CK), heat shock protein 70 (HSP70), and interleukin 6 (IL-6) have been reported. We report categorical associations which may influence these protein levels. Methods. Blood was harvested for DNA and plasma protein analysis from 567 adults. Mean protein levels of CK, HSP70, and IL-6 were compared by sex, ethnicity, genetic variants—CKMM Nco1 (rs1803285), HSPA1B +A1538G (rs1061581), and IL6 G-174C (rs1800795)—self-reported history of exercise, oral contraceptive use, and dietary supplement use. Results. SNP major allele frequencies for CKMM, HSPA1B, and IL6 were 70% A, 57% A, and 60%. Mean CK statistically differed by sex, ethnicity, oral contraceptives, and caffeine. Plasma HSP70 differed by caffeine and protein. Mean IL-6 concentration differed by sex, ethnicity, and genotype. Plasma IL-6 was significantly lower (29%) in males (1.92 ± 0.08 pg/mL) and higher (29%) among African Americans (2.85 ± 0.50 pg/mL) relative to the others. IL6 G-174C GG genotype (2.23 ± 0.14 pg/mL) was 19% greater than CG or CC genotypes. Conclusion. Differences in baseline CK and IL-6 plasma protein concentrations are associated with genetics, sex, ethnicity, and the use of oral contraceptives, caffeine, and protein supplements in this young and athletic population. Carmen Contreras-Sesvold, Bradley D. Revenis, Francis G. O’Connor, and Patricia A. Deuster Copyright © 2015 Carmen Contreras-Sesvold et al. All rights reserved. Role of Biomarkers in Diagnosis and Prognostic Evaluation of Acute Pancreatitis Wed, 05 Aug 2015 13:59:25 +0000 Acute pancreatitis is a potentially life threatening disease. The spectrum of severity of the illness ranges from mild self-limiting disease to a highly fatal severe necrotizing pancreatitis. Despite intensive research and improved patient care, overall mortality still remains high, reaching up to 30–40% in cases with infected pancreatic necrosis. Although little is known about the exact pathogenesis, it has been widely accepted that premature activation of digestive enzymes within the pancreatic acinar cell is the trigger that leads to autodigestion of pancreatic tissue which is followed by infiltration and activation of leukocytes. Extensive research has been done over the past few decades regarding their role in diagnosis and prognostic evaluation of severe acute pancreatitis. Although many standalone biochemical markers have been studied for early assessment of severity, C-reactive protein still remains the most frequently used along with Interleukin-6. In this review we have discussed briefly the pathogenesis and the role of different biochemical markers in the diagnosis and severity evaluation in acute pancreatitis. Susanta Meher, Tushar Subhadarshan Mishra, Prakash Kumar Sasmal, Satyajit Rath, Rakesh Sharma, Bikram Rout, and Manoj Kumar Sahu Copyright © 2015 Susanta Meher et al. All rights reserved. In Search of Biomarkers for Idiopathic Scoliosis: Leptin and BMP4 Functional Polymorphisms Sun, 02 Aug 2015 14:09:00 +0000 Idiopathic scoliosis (IS) is the most common spinal disorder in children and adolescents. The current consensus on IS maintains that it has a multifactorial etiology with genetic predisposition factors. In the present study the association of two functional polymorphisms of leptin (rs7799039) and BMP4 (rs4898820) with susceptibility to IS and curve severity was investigated in a Bulgarian population sample. The molecular detection of the genotypes was performed by amplification followed by restriction technology. The statistical analysis was performed by Pearson’s chi-squared test. This case-control study revealed no statistically significant association between the functional polymorphisms of leptin and BMP4 and susceptibility to IS or curve progression (). On the basis of these results the examined polymorphic variants of leptin and BMP4 could not be considered as genetic variants with predisposition effect or as risk factors for the progression of the curve. In addition, these results do not exclude a synergistic effect of the promoter polymorphisms of leptin and BMP4 in the etiology and pathogenesis of IS. The identification of molecular markers for IS could be useful for early detection and prognosis of the risk for a rapid progression of the curve. That would permit early stage treatment of the patient with the least invasive procedures. Svetla Nikolova, Vasil Yablanski, Evgeni Vlaev, Gergana Getova, Ventseslav Atanasov, Luben Stokov, Alexey Slavkov Savov, and Ivo Marinov Kremensky Copyright © 2015 Svetla Nikolova et al. All rights reserved. Current Challenges in Volatile Organic Compounds Analysis as Potential Biomarkers of Cancer Mon, 30 Mar 2015 11:47:53 +0000 An early diagnosis and appropriate treatment are crucial in reducing mortality among people suffering from cancer. There is a lack of characteristic early clinical symptoms in most forms of cancer, which highlights the importance of investigating new methods for its early detection. One of the most promising methods is the analysis of volatile organic compounds (VOCs). VOCs are a diverse group of carbon-based chemicals that are present in exhaled breath and biofluids and may be collected from the headspace of these matrices. Different patterns of VOCs have been correlated with various diseases, cancer among them. Studies have also shown that cancer cells in vitro produce or consume specific VOCs that can serve as potential biomarkers that differentiate them from noncancerous cells. This review identifies the current challenges in the investigation of VOCs as potential cancer biomarkers, by the critical evaluation of available matrices for the in vivo and in vitro approaches in this field and by comparison of the main extraction and detection techniques that have been applied to date in this area of study. It also summarises complementary in vivo, ex vivo, and in vitro studies conducted to date in order to try to identify volatile biomarkers of cancer. Kamila Schmidt and Ian Podmore Copyright © 2015 Kamila Schmidt and Ian Podmore. All rights reserved. Biomarkers for Detection and Monitoring of B16 Melanoma in Mouse Urine and Feces Mon, 23 Feb 2015 12:46:33 +0000 Melanoma is the most malignant type of skin cancer. Early detection of melanoma is thus critical for patient prognosis and survival. At present, examination by a skilled dermatologist followed by biopsy of suspicious lesions is the diagnostic gold standard. The aim of the present study was to examine an alternative and noninvasive method for the diagnosis of melanoma at an early stage. We identified and compared the volatile organic compounds (VOCs) in mouse urine and feces, before and after a subcutaneous injection of B16 melanoma cells. We identified a total of 16 VOCs in urine and 13 VOCs in feces that could serve as potential biomarkers. Statistical analysis significantly discriminated between the cancer and control groups. These results should be validated in a larger-scale animal study, after which a study could be designed in patients to develop a melanoma biomarker. Aviv Sever, Amir Abd elkadir, Yosef Matana, Jacob Gopas, and Yehuda Zeiri Copyright © 2015 Aviv Sever et al. All rights reserved. Portable XRF Technology to Quantify Pb in Bone In Vivo Thu, 27 Nov 2014 06:19:53 +0000 Lead is a ubiquitous toxicant. Bone lead has been established as an important biomarker for cumulative lead exposures and has been correlated with adverse health effects on many systems in the body. K-shell X-ray fluorescence (KXRF) is the standard method for measuring bone lead, but this approach has many difficulties that have limited the widespread use of this exposure assessment method. With recent advancements in X-ray fluorescence (XRF) technology, we have developed a portable system that can quantify lead in bone in vivo within 3 minutes. Our study investigated improvements to the system, four calibration methods, and system validation for in vivo measurements. Our main results show that the detection limit of the system is 2.9 ppm with 2 mm soft tissue thickness, the best calibration method for in vivo measurement is background subtraction, and there is strong correlation between KXRF and portable LXRF bone lead results. Our results indicate that the technology is ready to be used in large human population studies to investigate adverse health effects of lead exposure. The portability of the system and fast measurement time should allow for this technology to greatly advance the research on lead exposure and public/environmental health. Aaron James Specht, Marc Weisskopf, and Linda Huiling Nie Copyright © 2014 Aaron James Specht et al. All rights reserved. Urinary β2-Microglobulin Is a Good Indicator of Proximal Tubule Injury: A Correlative Study with Renal Biopsies Thu, 20 Nov 2014 08:16:46 +0000 Objective. After filtration through glomeruli, β2-microglobulin is reabsorbed in proximal tubules. Increased urinary β2-microglobulin indicates proximal tubule injury and measurement of β2-microglobulin in urine is useful to determine the source of renal injury. Kidney injury molecule-1 (KIM-1) has been characterized as a selective proximal tubule injury marker. This study was designed to evaluate the correlation of urinary β2-microglobulin concentration and KIM-1 expression as evidence of proximal tubule injury. Methods. Between 2009 and 2012, 46 patients with urine β2-microglobulin (RenalVysion) had follow-up kidney biopsy. Diagnoses included glomerular and tubule-interstitial disease. Immunohistochemical staining for KIM-1 was performed and the intensity was graded from 0 to 3+. Linear regression analysis was applied to correlate the values of urinary β2-microglobulin and KIM-1 staining scores. P < 0.05 was considered statistically significant. Results. Thirty patients had elevated urinary β2-microglobulin. KIM-1 staining was positive in 35 kidney biopsies. There was a significant correlation between urinary β2-microglobulin and KIM-1 staining (P < 0.05). Sensitivity was 86.6%, specificity was 43.7%, positive predictive value was 74.2%, and negative predictive value was 63.6%. Conclusion. Increased urinary β2-microglobulin is significantly correlated with KIM-1 staining in injured proximal tubules. Measurement of urine β2-microglobulin is a sensitive assay for proximal tubule injury. Xu Zeng, Deloar Hossain, David G. Bostwick, Guillermo A. Herrera, and Ping L. Zhang Copyright © 2014 Xu Zeng et al. All rights reserved. Day to Day Variability and Reliability of Blood Oxidative Stress Markers within a Four-Week Period in Healthy Young Men Wed, 15 Oct 2014 11:37:12 +0000 The present study aimed to determine the day to day variability and reliability of several blood oxidative stress markers at rest in a healthy young cohort over a four-week period. Twelve apparently healthy resistance trained males (24.6 ± 3.0 yrs) were tested over 7 visits within 4 weeks with at least 72 hrs between visits at the same time of day. Subjects rested 30 minutes prior to blood being obtained by vacutainer. Results. The highest IntraClass correlations (ICC’s) were obtained for protein carbonyls (PC) and oxygen radical absorbance capacity (ORAC) (PC = 0.785 and ORAC = 0.780). Cronbach’s α reliability score for PC was 0.967 and for ORAC was 0.961. The ICC’s for GSH, GSSG, and the GSSG/TGH ratio ICC were 0.600, 0.573, and 0.570, respectively, with Cronbach’s α being 0.913, 0.904, and 0.903, respectively. Xanthine oxidase ICC was 0.163 and Cronbach’s α was 0.538. Conclusions. PC and ORAC demonstrated good to excellent reliability while glutathione factors had poor to excellent reliability. Xanthine oxidase showed poor reliability and high variability. These results suggest that the PC and ORAC markers were the most stable and reliable oxidative stress markers in blood and that daily changes across visits should be considered when interpreting resting blood oxidative stress markers. A. H. Goldfarb, R. S. Garten, J. Waller, and J. D. Labban Copyright © 2014 A. H. Goldfarb et al. All rights reserved. A Study on MTHFR C677T Gene Polymorphism and Alcohol Dependence among Meiteis of Manipur, India Wed, 01 Oct 2014 07:34:33 +0000 Chronic alcohol consumption is reported to be associated with increase in plasma homocysteine levels which is further influenced by the polymorphism in methylenetetrahydrofolate reductase (MTHFR) gene. The present study aims to understand the extent of the MTHFR C677T polymorphism in alcohol dependent (AD) cases of Meiteis of Manipur, a Mendelian population of India. MTHFR C677T polymorphism was screened in 313 controls and 139 alcohol dependent (AD) cases who all met DSM-IV criteria for alcohol dependence. Both AD cases and controls were unrelated up to 1st cousin. Among the control group, different drinking patterns like abstainer/nondrinkers (NDs), occasional drinkers (ODs), and moderate drinkers (MDs) are included. Both the groups were found to be in Hardy-Weinberg equilibrium (). Genotypic and allelic frequency distribution of MTHFR C677T polymorphism did not differ significantly between AD cases and controls (). However, individuals carrying mutant (T) allele show more than 1-fold increased risk for AD though not significant (OR = 1.43; 95% CI 0.41–5.01, ). In conclusion, MTHFR C677T polymorphism is not found to be risk marker for AD in present studied population. However, higher prevalence of the mutant T allele may exacerbate deleterious health risk in future especially among alcohol drinkers. Huidrom Suraj Singh, Kabita Salam, and Kallur Nava Saraswathy Copyright © 2014 Huidrom Suraj Singh et al. All rights reserved. Relationships between Plasma Micronutrients, Serum IgE, and Skin Test Reactivity and Asthma among School Children in Rural Southwest Nigeria Mon, 26 May 2014 00:00:00 +0000 Objective. Increasing prevalence of asthma has been attributed to changes in lifestyle and environmental exposures. We conducted a case-control study to investigate the relationship between serum micronutrients and asthma in rural school children in Nigeria. Methods. We administered questionnaires to 1,562 children to identify children with asthma. Serum concentration levels of 12 micronutrients were determined in asthma cases () and controls (). Allergy skin prick test and spirometry were also performed. Results. Plasma levels of the following micronutrients were significantly different between cases and controls: calcium ( versus  mg/dL; ), manganese ( versus  mg/L; ), selenium ( versus  μg/L; ), and albumin ( versus  g/dL; ). Plasma concentrations of iron and selenium were positively correlated with lung function, ( in each case) while manganese serum concentration was negatively correlated with asthma (; ). Conclusions. Children with asthma had reduced levels of plasma manganese, calcium, and albumin but raised level of selenium. The protective or risk effects of these micronutrients on asthma warrant further investigation. Oluwafemi Oluwole, Olatunbosun G. Arinola, Mary D. Adu, Adedayo Adepoju, Babatunde O. Adedokun, Olufunmilayo I. Olopade, and Christopher O. Olopade Copyright © 2014 Oluwafemi Oluwole et al. All rights reserved. Biomarkers Predict Relapse in Granulomatosis with Polyangiitis Wed, 30 Apr 2014 07:34:43 +0000 Granulomatosis with polyangiitis (GPA) is a small blood vessel vasculitic disorder with a high mortality rate if undiagnosed or treated inadequately. Disease relapse is a key feature of this disease and early identification of relapse episodes is very important in limiting end-organ damage. The advent of indirect immunofluorescence to detect antineutrophil cytoplasmic antibody (ANCA) with specific reactivity against the enzyme proteinase-3 (PR3) has been very useful in the diagnosis of GPA but is less helpful in predicting relapse. Indeed, up to date no satisfactory biomarker has been identified that can reliably predict relapse. This study assessed the probability of the occurrence of a relapse when a change was noted in a range of commonly used laboratory tests. These tests included levels of C-reactive protein (CRP), anti-PR3 antibodies, ANCA titre, and the neutrophil count. A group of 30 GPA patients with a total of 66 relapse episodes was investigated and a novel clinical yield score was devised. When a combined rise in CRP, anti-PR3 antibodies, and neutrophil count was observed in the 6-month period before a relapse event, 59% of patient relapses could be predicted. Monitoring changes in this set of parameters helps identify disease relapse. Patrick C. P. Hogan, Robert M. O’Connell, Simone Scollard, Emmett Browne, Emer E. Hackett, and Conleth Feighery Copyright © 2014 Patrick C. P. Hogan et al. All rights reserved. Functional Epigenetic Analysis of Prostate Carcinoma: A Role for Seryl-tRNA Synthetase? Thu, 27 Mar 2014 14:27:44 +0000 Transcriptional silencing, as a result of aberrant promoter hypermethylation, is a common mechanism through which genes in cancer cells become inactive. Functional epigenetic screens using demethylating agents to reexpress transcriptional silenced genes may identify such inactivated genes for needing further evaluation. We aimed to identify genes so far not known to be inactivated by promoter hypermethylation in prostate cancer. DU-145 and LNCaP cells were treated with the DNMT inhibitor zebularine. Expression changes of total RNA from treated and untreated cells were compared using an RNA expression microarray. Genes upregulated more than 2-fold were evaluated by RT-qPCR in 50 cases of paired normal and tumor tissues of prostate cancer patients. SARS was found to be downregulated in prostate cancer in 42/50 cases (84%). In addition, GADD45A and SPRY4 showed a remarkable diminished expression (88% and 74%, resp.). The gold standard for promoter hypermethylation-inactivated genes in prostate cancer (GSTP1) was repressed in 90% of our patient samples. ROC analyses reported statistically significant AUC curves in SARS, GADD45A, and GSTP1 and positive Spearman correlations were found between these genes. SARS was discovered to be a novel gene that is repressed in prostate cancer and could therefore be recommended for its involvement in prostate carcinogenesis. Odiljon Ikromov, Imad Alkamal, Ahmed Magheli, Nadine Ratert, Mauricio Sendeski, Kurt Miller, Hans Krause, and Carsten Kempkensteffen Copyright © 2014 Odiljon Ikromov et al. All rights reserved. A Quest to Identify Prostate Cancer Circulating Biomarkers with a Bench-to-Bedside Potential Wed, 12 Mar 2014 08:30:36 +0000 Prostate cancer (PCA) is a major health concern in current times. Ever since prostate specific antigen (PSA) was introduced in clinical practice almost three decades ago, the diagnosis and management of PCA have been revolutionized. With time, concerns arose as to the inherent shortcomings of this biomarker and alternatives were actively sought. Over the past decade new PCA biomarkers have been identified in tissue, blood, urine, and other body fluids that offer improved specificity and supplement our knowledge of disease progression. This review focuses on superiority of circulating biomarkers over tissue biomarkers due to the advantages of being more readily accessible, minimally invasive (blood) or noninvasive (urine), accessible for sampling on regular intervals, and easily utilized for follow-up after surgery or other treatment modalities. Some of the circulating biomarkers like PCA3, IL-6, and TMPRSS2-ERG are now detectable by commercially available kits while others like microRNAs (miR-21, -221, -141) and exosomes hold potential to become available as multiplexed assays. In this paper, we will review some of these potential candidate circulating biomarkers that either individually or in combination, once validated with large-scale trials, may eventually get utilized clinically for improved diagnosis, risk stratification, and treatment. Jaspreet Singh Batra, Swati Girdhani, and Lynn Hlatky Copyright © 2014 Jaspreet Singh Batra et al. All rights reserved. A Panel of Cancer Testis Antigens and Clinical Risk Factors to Predict Metastasis in Colorectal Cancer Sun, 09 Mar 2014 12:29:55 +0000 Colorectal cancer (CRC) is the third common carcinoma with a high rate of mortality worldwide and several studies have investigated some molecular and clinicopathological markers for diagnosis and prognosis of its malignant phenotypes. The aim of this study is to evaluate expression frequency of PAGE4, SCP-1, and SPANXA/D cancer testis antigen (CTA) genes as well as some clinical risk markers to predict liver metastasis of colorectal cancer patients. The expression frequency of PAGE4, SCP-1, and SPANXA/D cancer/testis antigen (CTA) genes was obtained using reverse transcription polymerase chain reaction (RT-PCR) assay in 90 colorectal tumor samples including both negative and positive liver metastasis tumors. Statistical analysis was performed to assess the association of three studied genes and clinical risk factors with CRC liver metastasis. The frequency of PAGE4 and SCP-1 genes expression was significantly higher in the primary tumours with liver metastasis when statistically compared with primary tumors with no liver metastasis (). Among all clinical risk factors studied, the lymph node metastasis and the depth of invasion were statistically correlated with liver metastasis of CRC patients. In addition, using multiple logistic regression, we constructed a model based on PAGE4 and lymph node metastasis to predict liver metastasis of CRC. Ramyar Molania, Frouzandeh Mahjoubi, Rezvan Mirzaei, Saeed-Reza Khatami, and Bahar Mahjoubi Copyright © 2014 Ramyar Molania et al. All rights reserved. Diagnosis of Non-ST-Elevation Acute Coronary Syndrome by the Measurement of Heart-Type Fatty Acid Binding Protein in Serum: A Prospective Case Control Study Wed, 05 Feb 2014 14:07:08 +0000 A prospective case control study was undertaken to evaluate the diagnostic performance of serum heart-type fatty acid binding protein (HFABP) in comparison to cardiac TnT and TnI in 33 patients admitted with chest pain, diagnosed as NSTE-ACS (non ST elevation acute coronary syndrome) and 22 healthy controls. Area under the receiver operating curve (AUC) was highest for H-FABP (AUC 0.79; 95% CI 0.66–0.89) versus cTnI (AUC 0.73; 95% CI 0.59–0.84) and cTnT (AUC 0.71; 95% CI 0.57–0.83). The H-FABP level above 6.5 ng/mL showed 56.7% (CI 37.4–74.5) sensitivity, 0.5 (95% CI 0.3–0.7) negative likelihood ratio (−LR), 100% (CI 84.6–100.0) specificity, and 100% (CI 79.4–100.0) positive predictive value (PPV), 62.9% (CI 44.9–78.5) negative predictive value (NPV). cTnI level above 0.009 μg/L had 40% (CI 22.7–59.4) sensitivity, 0.6 (95% CI 0.4–0.8) −LR, 100% (CI 84.6–100.0) specificity, 100% (CI 73.5–100.0) PPV, and 55% (CI 38.5–70.7) NPV. cTnT showed 46.7% (CI 28.3–65.7) sensitivity, 0.5 (95% CI 0.4–0.7) −LR, 100% (CI 84.6–100.0) specificity, 100% (CI 76.8–100.0) PPV, and 57.9% (CI 40.8–73.7) NPV at level above 9 μg/L. +LR were 12.5 (95% CI 1.8–86.8), 1.7 (95% CI 1.0–3.0), and 1.2 (95% CI 0.8–1.9) for H-FABP, cTnI, and cTnT respectively. In conclusion measurement of H-FABP is a valuable tool in the early diagnosis of patients with chest pain (6–8 hrs) and seems to be a preferred biomarker in the differential diagnosis of NSTE-ACS. More studies are needed to determine whether serum H-FABP further improves diagnostic performance. Priscilla Abraham Chandran, Basharat Ara Wani, Oruganti Sai Satish, and Noorjahan Mohammed Copyright © 2014 Priscilla Abraham Chandran et al. All rights reserved. Glucose-6-Phosphate Dehydrogenase Activity and Protein Oxidative Modification in Patients with Type 2 Diabetes Mellitus Sun, 22 Dec 2013 10:35:46 +0000 Objectives. The aim of the present investigation was to study the activity of glucose-6-phosphate dehydrogenase (G6PD) and correlate its activity to protein oxidation markers in type 2 diabetic patients under poor glycemic control. Methods. G6PD activity, protein carbonyl group concentration, and total thiol group content were measured in blood samples of 40 patients with type 2 diabetes mellitus under poor glycemic control and 20 healthy control subjects. Results. G6PD activity and total thiol group content decreased significantly while glycated hemoglobin (HbA1C) and protein carbonyl group concentration increased significantly in diabetic patients than in the controls (). In addition, Obtained results revealed that, in diabetics, G6PD activity negatively correlated to protein carbonyl and HbA1C ( and −0.65, resp.), while positively correlated to total thiol () and protein carbonyl negatively correlated to total thiol (), while positively correlated to HbA1C (). Also in controls, G6PD activity negatively correlated to protein carbonyl and HbA1C ( and −0.56, resp.), while positively correlated to total thiol () and protein carbonyl negatively correlated to total thiol (), while positively correlated to HbA1C (). Conclusions. We concluded that G6PD activity decreased in diabetics than in controls and was negatively correlated to oxidative stress markers and HbA1C. G6PD activity can be taken as a biomarker of oxidative stress and poor glycemic control in type 2 diabetic patients. Aida A. Mahmoud and Amal K. A. Nor El-Din Copyright © 2013 Aida A. Mahmoud and Amal K. A. Nor El-Din. All rights reserved. Markers of Oxidative Stress during Diabetes Mellitus Tue, 17 Dec 2013 15:40:58 +0000 The prevalence of diabetes mellitus is rising all over the world. Uncontrolled state of hyperglycemia due to defects in insulin secretion/action leads to a variety of complications including peripheral vascular diseases, nephropathy, neuropathy, retinopathy, morbidity, and/or mortality. Large body of evidence suggests major role of reactive oxygen species/oxidative stress in development and progression of diabetic complications. In the present paper, we have discussed the recent researches on the biomarkers of oxidative stress during type 2 diabetes mellitus. Brahm Kumar Tiwari, Kanti Bhooshan Pandey, A. B. Abidi, and Syed Ibrahim Rizvi Copyright © 2013 Brahm Kumar Tiwari et al. All rights reserved. Urinary Measurement of Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1 Helps Diagnose Acute Pyelonephritis in a Preclinical Model Sat, 14 Dec 2013 12:32:52 +0000 Background. The study assessed whether measurement of urinary biomarkers of acute kidney injury could be helpful in diagnosing acute pyelonephritis and subsequent scarring. Method. Escherichia coli J96 (0.3 mL inoculum containing /mL) was directly injected into the renal cortex of 3-week-old female Sprague Dawley rats (), with saline substituted in a control group (). Following the injection, urine was collected 2, 7, 14, 28, and 42 days after injection. Urinary neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (Kim-1), and interleukin-18 were quantitatively measured using enzyme-linked immunosorbent assay (ELISA). The levels of the biomarkers were adjusted for creatinine. Time course changes within a group or between the groups were compared. Correlation analysis was performed to understand the relationship between urinary levels and histological scarring. Results. Significantly elevated urinary NGAL was evident at two and seven days after injection, and Kim-1 was elevated at two days after injection. Receiver operating characteristic analyses confirmed the sensitivity of these markers at these times. No urinary marker at acute stage of APN was correlated with the amount of future scarring, negating their predictive value. Conclusion. Urinary NGAL and Kim-1 could be helpful in diagnosing febrile urinary tract infection in children. Hahn-Ey Lee, Sun Hee Lee, Minki Baek, Hwang Choi, and Kwanjin Park Copyright © 2013 Hahn-Ey Lee et al. All rights reserved. Neopterin in Diagnosis and Monitoring of Infectious Diseases Sun, 08 Dec 2013 09:19:42 +0000 Neopterin is produced by activated monocytes, macrophages, and dendritic cells upon stimulation by interferon gamma produced by T-lymphocytes. Quantification of neopterin in body fluids has been achieved by standard high-performance liquid chromatography, radioimmunoassays, and enzyme-linked immunosorbent assays. Neopterin levels predict HIV-related mortality more efficiently than clinical manifestations. Successful highly active antiretroviral therapy is associated with a decrease in neopterin levels. Elevated neopterin levels were associated with hepatitis by hepatitis A, B, and C viruses. Serum neopterin levels were found to be a predictor of response to treatment of chronic HCV infection with pegylated interferon combined with ribavirin. Neopterin levels of patients with pulmonary tuberculosis were found to be higher in patients with more extensive radiological changes. Elimination of blood donors with elevated neopterin levels to reduce risk of transmission of infections with known and unknown viral pathogens has been undertaken. Neopterin measurement is hereby more cost effective but less sensitive than screening using polymerase chain reaction based assays. In conclusion neopterin is a nonspecific marker of activated T-helper cell 1 dominated immune response. It may be a useful marker for monitoring of infectious disease activity during treatment and for more accurate estimation of extent of disease and prognosis. Michael Eisenhut Copyright © 2013 Michael Eisenhut. All rights reserved. Population-Sequencing as a Biomarker for Sample Characterization Sun, 08 Dec 2013 09:04:45 +0000 Sequencing is accepted as the “gold” standard for genetic analysis and continues to be used as a validation and reference tool. The idea of using sequence analysis directly for sample characterization has been met with skepticism. However, herein, utility of direct use of sequencing to identify multiple genomes present in samples is presented and reviewed. All samples and “pure” isolates are populations of genomes. Population-Sequencing is the use of probabilistic matching tools in combination with large volumes of sequence information to identify genomes present, based on DNA analysis across entire genomes to determine genome assignments, to calculate confidence scores of major and minor genome content. Accurate genome identification from mixtures without culture purification steps can achieve phylogenetic classification by direct analysis of millions of DNA fragments. Genome sequencing data of mixtures can function as biomarkers for use to interrogate genetic content of samples and to establish a sample profile, inclusive of major and minor genome components, drill down to identify rare SNP and mutation events, compare relatedness of genetic content between samples, profile-to-profile, and provide a probabilistic or statistical scoring confidence for sample characterization and attribution. The application of Population-Sequencing will facilitate sample characterization and genome identification strategies. John P. Jakupciak Copyright © 2013 John P. Jakupciak. All rights reserved. T-Cell Response to Hepatitis B Core Antigen: Identification of Prior Exposure to and Confirmatory Testing for Screening for Anti-HBc Tue, 03 Dec 2013 09:33:05 +0000 Background. During routine donor screening in the blood bank, it is not uncommon to find isolated reactivity for anti-HBc in the absence of detectable HBV DNA in a first donation but absence of reactivity to anti-HBc in subsequent donations, suggesting a false-positive result for anti-HBc. Study Design and Methods. The blood donor population was screened between January 2010 and October 2011. We selected 2,126 donations positive only for anti-HBc from a total of 125,068 donations. During the process, OBI donors were identified, and their HBcAg-specific T-cell response was analyzed and compared to donors with chronic (HBsAg positive) and recovered (anti-HBc only) infection. We analyzed correlations between signal levels (Co/s) in the competitive assay for anti-HBc and HBV DNA detection. Results. In the 21-month study period, 21 blood donors with anti-HBc alone were identified as OBI (1 in each 5955 donors). The relevant finding was the observation that anti-HBc only subjects with did not have either HBcAg-specific T-cells or detectable HBV DNA and OBI subjects presented with and HBcAg T-cell response. In the subset of 21 OBI subjects, 9 donors remained positive for HBcAg T-cell response after four collections. In all 9 samples, we observed HBV DNA fluctuation. Conclusion. Our data suggest that HBcAg-specific T-cell response could be used to confirm anti-HBc serological status, distinguishing previous exposure to Hepatitis B virus from anti-HBc false-positive results. Patricia Araujo, Roger Y. Dodd, Flavia Latinni, Renata Souza, Ricardo Diaz, and Jose Augusto Barreto Copyright © 2013 Patricia Araujo et al. All rights reserved. Prostasin: An Epithelial Sodium Channel Regulator Tue, 02 Jul 2013 11:17:11 +0000 Prostasin is a glycophosphatidylinositol-anchored protein which is found in prostate gland, kidney, bronchi, colon, liver, lung, pancreas, and salivary glands. It is a serine protease with trypsin-like substrate specificity which was first purified from seminal fluid in 1994. In the last decade, its diverse roles in various biological and physiological processes have been elucidated. Many studies done to date suggest that prostasin is one of several membrane peptidases regulating epithelial sodium channels in mammals. A comprehensive literature search was conducted from the websites of Pubmed Central, the US National Library of Medicine’s digital archive of life sciences literature and the National Library of Medicine. The data was also assessed from journals and books that published relevant articles in this field. Understanding the mechanism by which prostasin and its inhibitors regulate sodium channels has provided a new insight into the treatment of hypertension and some other diseases like cystic fibrosis. Prostasin plays an important role in epidermal growth factor receptor (EGFR) signal modulation. Extracellular proteases have been implicated in tumor metastasis and local tissue invasion because of their ability to degrade extracellular matrices. Shakti Aggarwal, Pradeep K. Dabla, and Sarika Arora Copyright © 2013 Shakti Aggarwal et al. All rights reserved.