Disease Markers http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Longitudinal Relationship between Plasma Reactive Oxygen Metabolites and Periodontal Condition in the Maintenance Phase of Periodontal Treatment Wed, 16 Apr 2014 14:06:48 +0000 http://www.hindawi.com/journals/dm/2014/489292/ Aim. The present cohort study describes the longitudinal relationship between plasma oxidative status and periodontitis progression during the maintenance phase of treatment. Materials and Methods. Forty-five patients (mean age 58.8 years) were monitored from 2008 to 2013. Periodontal conditions, including probing pocket depth (PPD) and clinical attachment level (CAL), were recorded. Measurements of plasma reactive oxygen metabolites (ROM) and biologic antioxidant potential (BAP) were performed to evaluate plasma oxidative status. The patients were assigned into 2 groups as low and high plasma ROM level using a cut-off value which was median of plasma ROM level at baseline. Results. In the subjects with low plasma ROM level at baseline, changes in mean CAL were positively correlated with changes in plasma ROM levels, bleeding on probing, and plaque control record, but not with PPD. In the subjects with high plasma ROM at baseline, changes in CAL were significantly associated with only PPD at baseline. On the other hands there were no significant associations between changes in CAL and those in plasma BAP levels. Conclusions. When plasma ROM level in periodontitis patients was low, increases in plasma ROM level were associated with those in CAL during the maintenance phase of treatment. Tatsuya Machida, Takaaki Tomofuji, Daisuke Ekuni, Mayu Yamane, Toshiki Yoneda, Yuya Kawabata, Kota Kataoka, Naofumi Tamaki, and Manabu Morita Copyright © 2014 Tatsuya Machida et al. All rights reserved. The Role of TPA I/D and PAI-1 4G/5G Polymorphisms in Multiple Sclerosis Wed, 16 Apr 2014 11:58:26 +0000 http://www.hindawi.com/journals/dm/2014/362708/ Background. Previous studies have shown impaired fibrinolysis in multiple sclerosis (MS) and implicated extracellular proteolytic enzymes as important factors in demyelinating neuroinflammatory disorders. Tissue-type plasminogen activator (t-PA) and its inhibitor (PAI-1) are key molecules in both fibrinolysis and extracellular proteolysis. In the present study, an association of the TPA Alu I/D and PAI-1 4G/5G polymorphisms with MS was analyzed within the Genomic Network for Multiple Sclerosis (GENoMS). Methods. The GENoMS includes four populations (Croatian, Slovenian, Serbian, and Bosnian and Herzegovinian) sharing the same geographic location and a similar ethnic background. A total of 885 patients and 656 ethnically matched healthy blood donors with no history of MS in their families were genotyped using PCR-RFLP. Results. TPA DD homozygosity was protective (OR = 0.79, 95% CI 0.63–0.99, ) and PAI 5G5G was a risk factor for MS (OR = 1.30, 95% CI 1.01–1.66, ). A significant effect of the genotype/carrier combination was detected in 5G5G/I carriers (OR = 1.39 95% CI 1.06–1.82, ). Conclusions. We found a significantly harmful effect of the combination of the PAI-1 5G/5G genotype and TPA I allele on MS susceptibility, which indicates the importance of gene-gene interactions in complex diseases such as MS. Maja Živković, Nada Starčević Čizmarević, Luca Lovrečić, Inge Klupka-Sarić, Aleksandra Stanković, Iva Gašparović, Polona Lavtar, Evica Dinčić, Ljiljana Stojković, Gorazd Rudolf, Saša Šega Jazbec, Olivio Perković, Osman Sinanović, Juraj Sepčić, Miljenko Kapović, Borut Peterlin, and Smiljana Ristić Copyright © 2014 Maja Živković et al. All rights reserved. Accurate, Fast and Cost-Effective Diagnostic Test for Monosomy 1p36 Using Real-Time Quantitative PCR Tue, 15 Apr 2014 14:14:29 +0000 http://www.hindawi.com/journals/dm/2014/836082/ Monosomy 1p36 is considered the most common subtelomeric deletion syndrome in humans and it accounts for 0.5–0.7% of all the cases of idiopathic intellectual disability. The molecular diagnosis is often made by microarray-based comparative genomic hybridization (aCGH), which has the drawback of being a high-cost technique. However, patients with classic monosomy 1p36 share some typical clinical characteristics that, together with its common prevalence, justify the development of a less expensive, targeted diagnostic method. In this study, we developed a simple, rapid, and inexpensive real-time quantitative PCR (qPCR) assay for targeted diagnosis of monosomy 1p36, easily accessible for low-budget laboratories in developing countries. For this, we have chosen two target genes which are deleted in the majority of patients with monosomy 1p36: PRKCZ and SKI. In total, 39 patients previously diagnosed with monosomy 1p36 by aCGH, fluorescent in situ hybridization (FISH), and/or multiplex ligation-dependent probe amplification (MLPA) all tested positive on our qPCR assay. By simultaneously using these two genes we have been able to detect 1p36 deletions with 100% sensitivity and 100% specificity. We conclude that qPCR of PRKCZ and SKI is a fast and accurate diagnostic test for monosomy 1p36, costing less than 10 US dollars in reagent costs. Pricila da Silva Cunha, Heloisa B. Pena, Carla Sustek D’Angelo, Celia P. Koiffmann, Jill A. Rosenfeld, Lisa G. Shaffer, Martin Stofanko, Higgor Gonçalves-Dornelas, and Sérgio Danilo Junho Pena Copyright © 2014 Pricila da Silva Cunha et al. All rights reserved. Leptin Levels and Nutritional Status of Indigenous Tepehuán and Mestizo Subjects in Durango, Mexico Mon, 14 Apr 2014 07:01:20 +0000 http://www.hindawi.com/journals/dm/2014/974503/ The aim of this study was to assess differences in nutritional status and their association with circulating leptin levels in the indigenous Tepehuán people of Mezquital Durango and Mestizo populations of Durango City, Mexico. A group of 128 volunteers aged 18 through 59 years were recruited for the study: 60 indigenous Tepehuán from Mezquital and 68 Mestizo individuals from Durango City. The classification of nutritional status was through body mass index (BMI). Clinical evaluations, including anthropometry and lipid profiles, were performed to ascertain the health of the participants. Circulating leptin levels were determined in blood samples after at 08 hours of fasting. The healthy subjects were classified according to BMI: 32 Tepehuán and 30 Mestizo subjects were of normal weight (NW), and 28 Tepehuán and 38 Mestizo subjects were overweight or obese (OW/O). Both NW and OW/O Tepehuán subjects showed lower leptin concentrations than the comparable Mestizo subjects. Statistical analysis showed a negative Pearson’s correlation (; ) between BMI and leptin levels in NW Tepehuán subjects, but no significant correlation was found in other groups. The differences found in Tepehuán compared with Mestizo subjects might be explained by poor nutritional status, which leads to scarce adipose tissue and low levels of leptin synthesis. Leptin concentration and its relationship to BMI are associated with ethnicity. Dealmy Delgadillo Guzmán, Laurence Annie Marchat Marchau, José L. Reyes, Verónica Loera Castañeda, Martha Sosa Macías, Jessica García Vivas, and Ismael Lares Asseff Copyright © 2014 Dealmy Delgadillo Guzmán et al. All rights reserved. Absence of Correlation between IL-28B Gene Polymorphisms and the Clinical Presentation of Chronic Hepatitis B in an Amazon Brazilian Population Thu, 10 Apr 2014 17:41:29 +0000 http://www.hindawi.com/journals/dm/2014/534534/ Objective. The present study investigated the prevalence of the IL-28B polymorphisms rs12979860 and rs8099917 in chronic hepatitis B patients from a case study in Eastern Amazonia. Methods. In total, 65 chronically infected HBV patients and 97 healthy subjects who were anti-HBc and anti-HBs positive (control group) were evaluated between May 2011 and December 2012. The groups of patients were designated as inactive carriers, chronic hepatitis without cirrhosis, and chronic hepatitis with cirrhosis based on clinical, pathological, biochemical, hematological, and virological variables. The patients were genotyped using quantitative real-time PCR. Results. The frequencies of the rs12979860 polymorphism were similar between the infected group (32.3% CC, 41.5% CT, and 26.2 TT) and the control population (35% CC, 47.4% CT, and 17.6% TT), and the frequencies of the rs8099917 polymorphism (7.7% GG, 35.4% GT, and 56.9% TT versus 7.2% GG, 35.1% GT, and 57.7% TT) were also similar in both groups. The associations between the rs12979860 and rs8099917 polymorphisms and the clinical manifestations were not statistically significant. Conclusion. In conclusion, these polymorphisms had a similar distribution between infected and control groups, indicating that they were not associated with susceptibility and the clinical evolution of hepatitis B in the examined population. Simone Regina Souza da Silva Conde, Luciana L. Rocha, Vanessa M. Ferreira, Julius Caesar Mendes Soares Monteiro, Nathália Karla Fonseca Filgueiras, Pedro Alves de Almeida Lins, Bruna Tereza Silva dos Santos, Felipe Bonfim Freitas, Ednelza da Silva Graça, Sâmia Demachki, Marialva Tereza Ferreira de Araújo, Ricardo Ishak, and Antonio C. R. Vallinoto Copyright © 2014 Simone Regina Souza da Silva Conde et al. All rights reserved. MicroRNA-224 Suppresses Colorectal Cancer Cell Migration by Targeting Cdc42 Thu, 10 Apr 2014 11:42:54 +0000 http://www.hindawi.com/journals/dm/2014/617150/ The metastatic spread of tumor cells is the major risk factor affecting the clinical prognosis of colorectal cancer (CRC) patients. The metastatic phenotype can be modulated by dysregulating the synthesis of different structural and functional proteins of tumor cells. Micro(mi)RNAs are noncoding RNAs that recognize their cognate messenger (m)RNA targets by sequence-specific interactions with the 3′ untranslated region and are involved in the multistep process of CRC development. The objective of this study was to investigate the expression and biological roles of miR-224 in CRC. The miR-224 expression level was assessed by a quantitative real-time PCR in 79 CRC and 18 nontumor tissues. Expression levels of miR-224 in CRC tissues were significantly lower than those in nontumor tissues. Its expression level was associated with the mutation status of the APC gene. Ectopic expression of miR-224 suppressed the migratory ability of CRC cell line, but cell proliferation was less affected. Increased miR-224 diminished Cdc42 and SMAD4 expressions at both the protein and mRNA levels and inhibited the formation of actin filaments. Overall, this study indicated a role of miR-224 in negatively regulating CRC cell migration. The expression level of miR-224 may be a useful predictive biomarker for CRC progression. Tao-Wei Ke, Han-Lin Hsu, Yu-Hua Wu, William Tzu-Liang Chen, Ya-Wen Cheng, and Chao-Wen Cheng Copyright © 2014 Tao-Wei Ke et al. All rights reserved. Evaluation of Oxidative Stress Biomarkers in Patients with Fixed Orthodontic Appliances Thu, 10 Apr 2014 09:11:48 +0000 http://www.hindawi.com/journals/dm/2014/597892/ Aim. The aim of this study was to examine the changes in the levels of interleukine-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), malondialdehyde (MDA), nitric oxide (NO), and 8-hydroxydeoxyguanosine (8-OHdG) in saliva and IL-1β, TNF-α, and NO in gingival crevicular fluid (GCF) samples of patients with fixed orthodontic appliances. Material and Method. The subject population consisted of 50 volunteers who were in need of orthodontic treatment with fixed orthodontic appliances. GCF and saliva samples were obtained from all individuals before treatment, at 1st month of treatment and at 6th month of treatment. Periodontal clinical parameters were measured. Samples were investigated to detect IL-1β, TNF-α, and 8-OHdG levels using ELISA method and NO and MDA levels using spectrophotometric method. Results. Since IL-1β level detected in GCF at the 6th month of orthodontic treatment is statistically significant according to baseline (), all other biochemical parameters detected both in saliva and in GCF did not show any significant change at any measurement periods. Conclusion. Orthodontic tooth movement and orthodontic materials used in orthodontic treatment do not lead to a change above the physiological limits that is suggestive of oxidative damage in both GCF and saliva. Sevil Sema Atuğ Özcan, İsmail Ceylan, Erkan Özcan, Nezahat Kurt, İlhan Metin Dağsuyu, and Cenk Fatih Çanakçi Copyright © 2014 Sevil Sema Atuğ Özcan et al. All rights reserved. Serum YKL-40 Levels and Chitotriosidase Activity in Patients with Beta-Thalassemia Major Tue, 08 Apr 2014 00:00:00 +0000 http://www.hindawi.com/journals/dm/2014/965971/ Background. YKL-40 association with human disease has been the object of many years of investigation. β-thalassemia patients are affected by hepatic siderosis, which determines a fibrotic process and tissue remodelling. Chitotriosidase has been found to be increased in thalassemic patients returning to normal in patients submitted to bone marrow transplantation. YKL-40 is associated with macrophage activation in liver and in other tissues. The aim of the study was to analyse the level of serum YKL-40 and plasma chitotriosidase activity of patients with beta-thalassemia to assess whether their expression correlates with liver disease and degree of liver siderosis. Methods. Expression of YKL-40 and chitotriosidase as a marker of inflammation in 69 thalassemic patients were evaluated. We sought to investigate whether these two chitinases could be considered as a significant biomarker to evaluate therapy effectiveness. Results. Surprisingly we found normal value of YKL-40. We, also, analysed chitotriosidase activity in the same patients that was slightly increased as a consequence of macrophage activation. Conclusions. These data would suggest a good treatment for these patients. Maria Musumeci, Vincenzo Caruso, Emilia Medulla, Venerando Torrisi, Roberta Migale, Silvia Angeletti, and Salvatore Musumeci Copyright © 2014 Maria Musumeci et al. All rights reserved. p16INK4A and p14ARF Gene Promoter Hypermethylation as Prognostic Biomarker in Oral and Oropharyngeal Squamous Cell Carcinoma: A Review Mon, 07 Apr 2014 16:31:20 +0000 http://www.hindawi.com/journals/dm/2014/260549/ Head and neck squamous cell carcinoma is a heterogeneous group of tumors with each subtype having a distinct histopathological and molecular profile. Most tumors share, to some extent, the same multistep carcinogenic pathways, which include a wide variety of genetic and epigenetic changes. Epigenetic alterations represent all changes in gene expression patterns that do not alter the actual DNA sequence. Recently, it has become clear that silencing of cancer related genes is not exclusively a result of genetic changes such as mutations or deletions, but it can also be regulated on epigenetic level, mostly by means of gene promoter hypermethylation. Results from recent studies have demonstrated that DNA methylation patterns contain tumor-type-specific signatures, which could serve as biomarkers for clinical outcome in the near future. The topic of this review discusses gene promoter hypermethylation in oral and oropharyngeal squamous cell carcinoma (OSCC). The main objective is to analyse the available data on gene promoter hypermethylation of the cell cycle regulatory proteins and and to investigate their clinical significance as novel biomarkers in OSCC. Hypermethylation of both genes seems to possess predictive properties for several clinicopathological outcomes. We conclude that the methylation status of is definitely a promising candidate biomarker for predicting clinical outcome of OSCC, especially for recurrence-free survival. A. Al-Kaabi, L. W. van Bockel, A. J. Pothen, and S. M. Willems Copyright © 2014 A. Al-Kaabi et al. All rights reserved. Aquaporin-1 Protein Levels Elevated in Fresh Urine of Renal Cell Carcinoma Patients: Potential Use for Screening and Classification of Incidental Renal Lesions Sun, 06 Apr 2014 12:13:24 +0000 http://www.hindawi.com/journals/dm/2014/135649/ Introduction and Objectives. There are over 65,000 new cases of renal cell carcinoma (RCC) each year, yet there is no effective clinical screening test for RCC. A single report claimed no overlap between urine levels of aquaporin-1 (AQP1) in patients with and without RCC (Mayo Clin Proc. 85:413, 2010). Here, we used archived and fresh RCC patient urine to validate this report. Methods. Archived RCC, fresh prenephrectomy RCC, and non-RCC negative control urines were processed for Western blot analysis. Urinary creatinine concentrations were quantified by the Jaffe reaction (Nephron 16:31, 1976). Precipitated protein was dissolved in 1x SDS for a final concentration of 2 μg/µL creatinine. Results. Negative control and archived RCC patient urine failed to show any AQP1 protein by Western blot analysis. Fresh RCC patient urine is robustly positive for AQP1. There was no signal overlap between fresh RCC and negative control, making differentiation straightforward. Conclusions. Our data confirms that fresh urine of patients with RCC contains easily detectable AQP1 protein. However, archival specimens showed an absence of detectable AQP1 indistinguishable from negative control. These findings suggest that a clinically applicable diagnostic test for AQP1 in fresh urine may be useful for detecting RCC. Shilpa Sreedharan, John A. Petros, Viraj A. Master, Kenneth Ogan, John G. Pattaras, David L. Roberts, Fei Lian, and Rebecca S. Arnold Copyright © 2014 Shilpa Sreedharan et al. All rights reserved. Association of Fibrinogen with Severity of Stable Coronary Artery Disease in Patients with Type 2 Diabetic Mellitus Sun, 06 Apr 2014 06:48:18 +0000 http://www.hindawi.com/journals/dm/2014/485687/ Background. Some studies have suggested a relation of plasma fibrinogen to the severity of coronary artery disease (CAD). However, whether plasma fibrinogen can predict the presence and severity of CAD in patients with diabetes mellitus has not been determined. Methods. A total of consecutive 373 diabetic patients with typical angina pectoris who received coronary angiography were enrolled and classified into three groups by tertiles of Gensini score (GS, low group <8; intermediate group 8~28; high group >28). The relationship between fibrinogen and GS was evaluated. Results. There were correlations of fibrinogen with hemoglobin A1c, C-reactive protein, and GS (, , and , resp.; all ). Area under the receivers operating characteristic curve of fibrinogen was 0.62 (95% CI 0.56–0.68, ) for predicting a high GS. Multivariate analysis suggested that plasma fibrinogen was an independent predictor of a high GS for diabetic patients (, 95% CI 1.04–1.88, and ) after adjusting for traditional risk factors of CAD. Conclusions. The present data indicated that plasma fibrinogen, a readily measurable systematic inflammatory marker, appeared to be an independent predictor for the severity of CAD in diabetic patients. Li-Feng Hong, Xiao-Lin Li, Song-Hui Luo, Yuan-Lin Guo, Cheng-Gang Zhu, Ping Qing, Na-Qiong Wu, and Jian-Jun Li Copyright © 2014 Li-Feng Hong et al. All rights reserved. Assessment of Lipocalin 2, Clusterin, Soluble Tumor Necrosis Factor Receptor-1, Interleukin-6, Homocysteine, and Uric Acid Levels in Patients with Psoriasis Wed, 02 Apr 2014 14:17:52 +0000 http://www.hindawi.com/journals/dm/2014/541709/ Background. Chronic inflammation may play a role in psoriasis pathogenesis. Lipocalin 2, clusterin, soluble tumor necrosis factor receptor-1 (sTNFR-1), interleukin-6, homocysteine, and uric acid are inflammatory and/or biochemical markers. However, both the roles of these markers and the pathogenesis of psoriasis are unknown. Objective. The aim of this study was to investigate serum levels of lipocalin 2, clusterin, sTNFR-1, interleukin-6, homocysteine, and uric acid in patients and controls groups. Methods. Fifty-six patients with psoriasis and 33 healthy controls were included in the study. Serum concentrations of the markers were evaluated by ELISA. The Psoriasis Area and Severity Index (PASI) was evaluated in all psoriasis patients. Body mass index (BMI) was calculated by dividing weight (kg) by height (m) squared. Results. The serum value of lipocalin and sTNFR-1 were significantly higher in psoriasis patients than in controls (resp., , ). The others showed no significant differences between psoriasis and the control groups (all of them ). The mean PASI score in the patient group was . Conclusions. These findings suggest that lipocalin 2 and sTNFR-1 might play a role in the pathogenesis of psoriasis and can be used as markers of the disease. Arzu Ataseven, Recep Kesli, Gulcan Saylam Kurtipek, and Perihan Ozturk Copyright © 2014 Arzu Ataseven et al. All rights reserved. Matrix Metalloproteinase-9: Its Interplay with Angiogenic Factors in Inflammatory Bowel Diseases Mon, 31 Mar 2014 08:25:07 +0000 http://www.hindawi.com/journals/dm/2014/643645/ Matrix metalloproteinase- (MMP-) 9 is one of the main metalloproteinases reported to be involved in extracellular matrix degradation and recently also in triggering of angiogenic switch in the course of inflammatory bowel diseases (IBD). The goal of our studies was to estimate in one experimental setting the levels of MMP-9 in sera of Crohn’s Disease (CD) and ulcerative colitis (UC) patients and to evaluate its possible diagnostic potential in comparison with other biochemical markers and selected proinflammatory and angiogenic factors. The study group included 176 subjects (CD = 64, UC = 85, control = 27). Concentrations of serum MMP-9 were significantly higher in active than inactive forms of IBD, being higher in active UC than in active CD. Both in the case of CD and UC serum MMP-9 positively correlated with disease activity, IL-6 levels, platelet and leukocyte count, midkine, and PDGF-BB, as well as in UC with ESR and in CD with CRP, IL-1, and VEGF-A. Diagnostic accuracy of MMP-9 in distinguishing active UC from active CD was 66%, and displayed higher specificity than CRP (79.0% versus 61.6%, resp.). Evaluation of serum MMP-9 concentrations could aid in differentiation of active UC from active CD. MMP-9 correlated better with inflammatory and angiogenic parameters in CD than in UC. Malgorzata Matusiewicz, Katarzyna Neubauer, Magdalena Mierzchala-Pasierb, Andrzej Gamian, and Malgorzata Krzystek-Korpacka Copyright © 2014 Malgorzata Matusiewicz et al. All rights reserved. Can CA-125 Predict Lymph Node Metastasis in Epithelial Ovarian Cancers in Turkish Population? Tue, 25 Mar 2014 06:26:26 +0000 http://www.hindawi.com/journals/dm/2014/492537/ Objective. The role of single preoperative serum CA-125 levels in predicting pelvic or paraaortic lymph node metastasis in patients operated for epithelial ovarian cancer has been investigated. Methods. 176 patients diagnosed with epithelial ovarian carcinoma after staging laparotomy between January 2002 and May 2010 were evaluated retrospectively. Results. The mean, geometric mean, and median of preoperative serum CA-125 levels were 632,6, 200,29, and 191,5 U/mL, respectively. The cut-off value predicting lymph node metastases in the ROC curve was 71,92 U/mL, which is significant in logistic regression analysis (). The preoperative log CA-125 levels were also statistically significant in predicting lymph node metastasis in logistic regression analysis (). Conclusions. The tumor marker CA-125, which increases with grade independent of the effect of stage in EOC, is predictive of lymph node metastasis with a high rate of false positivity in Turkish population. The high false positive rate may obscure the predictive value of CA-125. Sinem Sudolmuş, Nadiye Köroğlu, Gökhan Yıldırım, Volkan Ülker, Ahmet Gülkılık, and Ramazan Dansuk Copyright © 2014 Sinem Sudolmuş et al. All rights reserved. Apolipoprotein E Gene Polymorphism and Serum Lipid Profile in Saudi Patients with Psoriasis Sun, 23 Mar 2014 11:31:55 +0000 http://www.hindawi.com/journals/dm/2014/239645/ Background/Aim. Apolipoprotein E (APOE) gene variants have been reported to influence psoriasis risk. However, data is limited to a few ethnicities and no similar study has been performed in middle eastern populations. We investigated this association in Saudi psoriasis patients. Methods. Saudi subjects (294) were genotyped for APOE gene using APOE StripAssay kit. Results. The frequencies of alleles ε2, ε4, and genotypes ε3/ε4 and ε3/ε2 were significantly higher in psoriasis patients compared with those in controls. The frequency of ε3 allele and ε3/ε3 genotype was significantly lower in patients. Other genotypes, ε2/ε4, ε2/ε2, and ε4/ε4, were absent in both groups. The serum cholesterol, triglycerides, and LDL levels were significantly higher in psoriasis patients contrary to HDL level. Patients with APOE ε4 had significantly higher levels of total cholesterol and LDL cholesterol, whereas those with the ε2 had higher HDL cholesterol, and triglycerides. Conclusion. APOE alleles ε2, ε4, and genotypes ε2/ε3 and ε4/ε3 are associated with psoriasis and can be a risk factor while allele ε3 and genotype ε3/ε3 may be protective for psoriasis in Saudis. Results of lipid profile support that psoriasis is one of the independent risk factors for hyperlipidemia and emphasize the need of screening cardiovascular diseases in psoriatic patients. Fahad Al Harthi, Ghaleb Bin Huraib, Abdulrahman Zouman, Misbahul Arfin, Mohammad Tariq, and Abdulrahaman Al-Asmari Copyright © 2014 Fahad Al Harthi et al. All rights reserved. Potential Novel Biomarkers for Diabetic Testicular Damage in Streptozotocin-Induced Diabetic Rats: Nerve Growth Factor Beta and Vascular Endothelial Growth Factor Thu, 20 Mar 2014 17:38:51 +0000 http://www.hindawi.com/journals/dm/2014/108106/ Background. It is well known that diabetes mellitus may cause testicular damage. Vascular endothelial growth factor (VEGF) and nerve growth factor beta (NGF-β) are important neurotrophic factors for male reproductive system. Objective. We aimed to investigate the correlation between testicular damage and testicular VEGF and NGF-β levels in diabetic rats. Methods. Diabetes was induced by streptozotocin (STZ, 45 mg/kg/i.p.) in adult rats. Five weeks later testicular tissue was removed; testicular VEGF and NGF-β levels were measured by ELISA. Testicular damage was detected by using hematoxylin and eosin staining and periodic acid-Schiff staining, and apoptosis was identified by terminal-deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL). Seminiferous tubular sperm formation was evaluated using Johnsen’s score. Results. In diabetic rats, seminiferous tubule diameter was found to be decreased; basement membrane was found to be thickened in seminiferous tubules and degenerated germ cells. Additionally, TUNEL-positive cells were increased in number of VEGF+ cells and levels of VEGF and NGF-β were decreased in diabetic testes. Correlation between VEGF and NGF-β levels was strong. Conclusion. These results suggest that the decrease of VEGF and NGF-β levels is associated with the increase of the apoptosis and testicular damage in diabetic rats. Testis VEGF and NGF-β levels could be potential novel biomarkers for diabetes induced testicular damage. Ali Rıza Sisman, Muge Kiray, Ulas Mehmet Camsari, Merve Evren, Mehmet Ates, Basak Baykara, Ilkay Aksu, Guven Guvendi, and Nazan Uysal Copyright © 2014 Ali Rıza Sisman et al. All rights reserved. The Use of Functional Genomics in Conjunction with Metabolomics for Mycobacterium tuberculosis Research Tue, 18 Mar 2014 00:00:00 +0000 http://www.hindawi.com/journals/dm/2014/124218/ Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a fatal infectious disease, resulting in 1.4 million deaths globally per annum. Over the past three decades, genomic studies have been conducted in an attempt to elucidate the functionality of the genome of the pathogen. However, many aspects of this complex genome remain largely unexplored, as approaches like genomics, proteomics, and transcriptomics have failed to characterize them successfully. In turn, metabolomics, which is relatively new to the “omics” revolution, has shown great potential for investigating biological systems or their modifications. Furthermore, when these data are interpreted in combination with previously acquired genomics, proteomics and transcriptomics data, using what is termed a systems biology approach, a more holistic understanding of these systems can be achieved. In this review we discuss how metabolomics has contributed so far to characterizing TB, with emphasis on the resulting improved elucidation of M. tuberculosis in terms of (1) metabolism, (2) growth and replication, (3) pathogenicity, and (4) drug resistance, from the perspective of systems biology. Conrad C. Swanepoel and Du Toit Loots Copyright © 2014 Conrad C. Swanepoel and Du Toit Loots. All rights reserved. MicroRNAs-Role in Lung Cancer Thu, 13 Mar 2014 15:57:13 +0000 http://www.hindawi.com/journals/dm/2014/218169/ Regulation of gene expression is essential for normal physiological functions; thus deregulation of gene expression is common in disease conditions. One level of regulation of gene expression is performed by noncoding RNAs, among which microRNAs (miRNA) are the best studied. Abnormal expression of these molecular players can lead to pathogenic processes such as heart disease, immune system abnormalities, and carcinogenesis, to name but a few. Of a length of 18–25 nucleotides miRNAs are involved in binding partial complementary sequences within the 3′-UTR (3′-untranslated region) of the target mRNAs. Depending on the type of neoplastic transformation, miRNAs can act both as oncogenes (oncomirs) or as tumor suppressors. Because of the great importance of miRNAs, most researches focus on either their role as biomarkers or their potential as therapeutic targets. Herein, we present the review of microRNA biology, function, and tumorigenic potential with emphasis on their role in lung cancer. Małgorzata Guz, Adolfo Rivero-Müller, Estera Okoń, Agnieszka Stenzel-Bembenek, Krzysztof Polberg, Maria Słomka, and Andrzej Stepulak Copyright © 2014 Małgorzata Guz et al. All rights reserved. Evaluation of Usefulness of hs-CRP and Ferritin Assays in Patients with Nasal Polyps Tue, 11 Mar 2014 13:04:15 +0000 http://www.hindawi.com/journals/dm/2014/794060/ Background. Chronic nature of the nasal polyps, tendency to recurrence, and lack of satisfying treatment need the diagnostic’s parameters which show early inflammatory state as ferritin and hs-CRP. The Aim of Study. Assessment of hs-CRP and ferritin blood levels in nasal polyps patients in evaluation of treatment efficacy. Methods. All 38 patients were divided into 2 groups. Group I included 19 patients with anti-inflammatory therapy 2 weeks after surgery. Group II included 19 patients without anti-inflammatory therapy 2 weeks after surgery. The levels of hs-CRP and ferritin have been assessed before and 2 and 6 weeks after surgical treatment. Results. Research showed statistically significant difference of ferritin’s concentration between examined groups 6 weeks after surgery () and statistically significant difference of hs-CRP concentration 2 and 6 weeks after surgery (). Conclusion. (1) The analysis of serum ferritin and hs-CRP concentrations can be useful in early postoperative detection of inflammatory state in patients with nasal polyps and for the effectiveness of therapy. (2) Lack of correlation between mean ferritin and hs-CRP serum levels, at each diagnostic and monitoring stage, shows that they are independent and cannot be determined interchangeably. Robert Partyka, Jacek Pałac, Zbigniew Paluch, Bożena Szyguła-Jurkiewicz, Grzegorz Namysłowski, Maciej Misiołek, Przemysław Jałowiecki, and Danuta Kokocińska Copyright © 2014 Robert Partyka et al. All rights reserved. Calcium Channel Autoantibodies Predicted Sudden Cardiac Death and All-Cause Mortality in Patients with Ischemic and Nonischemic Chronic Heart Failure Mon, 10 Mar 2014 08:44:34 +0000 http://www.hindawi.com/journals/dm/2014/796075/ The purpose of this study was to evaluate whether CC-AAbs levels could predict prognosis in CHF patients. A total of 2096 patients with CHF (841 DCM patients and 1255 ICM patients) and 834 control subjects were recruited. CC-AAbs were detected and the relationship between CC-AAbs and patient prognosis was analyzed. During a median follow-up time of 52 months, there were 578 deaths. Of these, sudden cardiac death (SCD) occurred in 102 cases of DCM and 121 cases of ICM. The presence of CC-AAbs in patients was significantly higher than that of controls (both ). Multivariate analysis revealed that positive CC-AAbs could predict SCD (HR 3.191, 95% CI 1.598–6.369 for DCM; HR 2.805, 95% CI 1.488–5.288 for ICM) and all-cause mortality (HR 1.733, 95% CI 1.042–2.883 for DCM; HR 2.219, 95% CI 1.461–3.371 for ICM) in CHF patients. A significant association between CC-AAbs and non-SCD (NSCD) was found in ICM patients (HR = 1.887, 95% CI 1.081–3.293). Our results demonstrated that the presence of CC-AAbs was higher in CHF patients versus controls and corresponds to a higher incidence of all-cause death and SCD. Positive CC-AAbs may serve as an independent predictor for SCD and all-cause death in these patients. Haiyun Yu, Juanhui Pei, Xiaoyan Liu, Jingzhou Chen, Xian Li, Yinhui Zhang, Ning Li, Zengwu Wang, Ping Zhang, Kejiang Cao, and Jielin Pu Copyright © 2014 Haiyun Yu et al. All rights reserved. Impact of Serum Biomarkers and Clinical Factors on Intensive Care Unit Mortality and 6-Month Outcome in Relatively Healthy Patients with Severe Pneumonia and Acute Respiratory Distress Syndrome Mon, 03 Mar 2014 09:20:15 +0000 http://www.hindawi.com/journals/dm/2014/804654/ Objectives. This study aimed to identify the independent biomarkers and clinical factors that could predict ICU mortality and 6-month outcomes in relatively healthy patients with severe pneumonia and acute respiratory distress syndrome (ARDS). Patients and Methods. We prospectively enrolled patients with severe pneumonia-related ARDS that required mechanical ventilation. Patients were excluded if they were unable to take care of themselves. Several biomarkers and clinical factors were evaluated prospectively on day 1 and day 3 after ICU admission. All biomarkers and clinical factors were collected for analysis. Results. 56 patients were enrolled in this study. We determined that the initial appropriate antibiotics use was an independent clinical factor and day 1 high-mobility group protein B1 (HMGB1) concentration was an independent biomarker for ICU mortality. Interestingly, we also found that a low day 1 albumin level was an independent biomarker for predicting patient life dependence 6 months after a pneumonia event. Conclusion. Patients with severe pneumonia and ARDS requiring mechanical ventilation experience high rates of ICU mortality or disability, even if they were quite healthy before. Initial appropriate antibiotics use and day 1 level of HMGB1 were independent factors for predicting ICU mortality. Day 1 albumin level was predictive of 6-month patient life dependence. Chia-Cheng Tseng, Wen-Feng Fang, Sum-Yee Leung, Hung-Chen Chen, Ya-Chun Chang, Chin-Chou Wang, Huang-Chih Chang, and Meng-Chih Lin Copyright © 2014 Chia-Cheng Tseng et al. All rights reserved. Human Paraoxonase-1 Activity Is Related to the Number of CD4+ T-Cells and Is Restored by Antiretroviral Therapy in HIV-1-Infected Individuals Thu, 27 Feb 2014 00:00:00 +0000 http://www.hindawi.com/journals/dm/2014/480201/ Background. Paraoxonase-1 (PON1) activity is suggested to be altered in individuals infected with human immunodeficiency virus type-1 (HIV-1). We investigated PON1 activity in individuals receiving different regimens of highly active antiretroviral therapy (HAART). Methods. PON1 activity was evaluated in 91 HIV-1 seronegative and 624 HIV-1 infected individuals (115 were not undergoing therapy (ART-naïve), and 509 were receiving HAART). HIV-1 infected individuals were treated with the following: efavirenz (EFV; ) or nevirapine (NVP; ) or lopinavir/ritonavir (LOP/r; ). Serum levels of total cholesterol (TC), HDL, and low-density lipoprotein (LDL) fractions and the atherogenic indices (AI, TC : HDL, and LDL : HDL ratios) were determined. Results. PON1 activity (U/L) was lower in the ART-naïve group compared with the other groups. PON1 activity correlated with CD4+ T-cell number of ART-naïve group (; ). The LOP/r group showed a reduction in HDL and an increase in AI (TC : HDL ratio) in comparison with other groups. Conclusion. PON1 activity was reduced in untreated individuals, but not in individuals receiving HAART. PON1 activity correlated with the number of CD4+ T-cells. The findings suggest that the activity of PON1 is associated with the immune status of HIV-1 infected individuals. Luciana Morganti Ferreira Maselli, Joel da Cunha, Eliana Battaggia Gutierrez, Raul Cavalcante Maranhão, Celso Spada, and Sérgio Paulo Bydlowski Copyright © 2014 Luciana Morganti Ferreira Maselli et al. All rights reserved. Renal Biopsy: Use of Biomarkers as a Tool for the Diagnosis of Focal Segmental Glomerulosclerosis Tue, 25 Feb 2014 08:53:12 +0000 http://www.hindawi.com/journals/dm/2014/192836/ Focal segmental glomerulosclerosis (FSGS) is a glomerulopathy associated with nephrotic syndrome and podocyte injury. FSGS occurs both in children and adults and it is considered the main idiopathic nephrotic syndrome nowadays. It is extremely difficult to establish a morphological diagnosis, since some biopsies lack a considerable quantifiable number of sclerotic glomeruli, given their focal aspect and the fact that FSGS occurs in less than half of the glomeruli. Therefore, many biological molecules have been evaluated as potential markers that would enhance the diagnosis of FSGS. Some of these molecules and receptors are associated with the pathogenesis of FSGS and have potential use in diagnosis. Crislaine Aparecida da Silva, Mariana Molinar Mauad Cintra, Eliângela de Castro Côbo, Marcos Vinícius da Silva, Fabiano Bichuette Custódio, Rosana Rosa Miranda Corrêa, Lúcio Roberto Castellano, Marlene Antônia dos Reis, and Juliana Reis Machado Copyright © 2014 Crislaine Aparecida da Silva et al. All rights reserved. Avocado Oil Supplementation Modifies Cardiovascular Risk Profile Markers in a Rat Model of Sucrose-Induced Metabolic Changes Tue, 25 Feb 2014 06:11:27 +0000 http://www.hindawi.com/journals/dm/2014/386425/ The purpose of this study was to evaluate the effects of avocado oil administration on biochemical markers of cardiovascular risk profile in rats with metabolic changes induced by sucrose ingestion. Twenty-five rats were divided into five groups: a control group (CG; basic diet), a sick group (MC; basic diet plus 30% sucrose solution), and three other groups (MCao, MCac, and MCas; basic diet plus 30% sucrose solution plus olive oil and avocado oil extracted by centrifugation or using solvent, resp.). Glucose, total cholesterol, triglycerides, phospholipids, low- and high-density lipoproteins (LDL, HDL), very low-density lipoprotein (VLDL), lactic dehydrogenase, creatine kinase, and high sensitivity C-reactive protein concentration were analyzed. Avocado oil reduces TG, VLDL, and LDL levels, in the LDL case significantly so, without affecting HDL levels. An effect was exhibited by avocado oil similar to olive oil, with no significant difference between avocado oil extracted either by centrifugation or solvent in myocardial injury biochemical indicators. Avocado oil decreased hs-CRP levels, indicating that inflammatory processes were partially reversed. These findings suggested that avocado oil supplementation has a positive health outcome because it reduces inflammatory events and produces positive changes in the biochemical indicators studied, related to the development of metabolic syndrome. Octavio Carvajal-Zarrabal, Cirilo Nolasco-Hipolito, M. Guadalupe Aguilar-Uscanga, Guadalupe Melo-Santiesteban, Patricia M. Hayward-Jones, and Dulce M. Barradas-Dermitz Copyright © 2014 Octavio Carvajal-Zarrabal et al. All rights reserved. Immunophenotype Expressions and Cytokine Profiles of Influenza A H1N1 Virus Infection in Pediatric Patients in 2009 Tue, 18 Feb 2014 12:30:28 +0000 http://www.hindawi.com/journals/dm/2014/195453/ Background. A novel swine-origin influenza A H1N1 virus (S-OIV) caused human infection and acute respiratory illness in 2009, resulting in an influenza pandemic. Objectives. This study characterized the immune responses of S-OIV infection in pediatric patients at risk of pulmonary complications. Methods. All enrolled pediatric patients were confirmed virologically for S-OIV infection in 2009-2010, prospectively. Changes in cellular immunophenotypes were analyzed using flow cytometry. Plasma cytokine levels associated with S-OIV infection by pulmonary and without pulmonary complications were measured using cytokine cytometric bead assay kits. Results. A total of 85 patients with a mean age of 10.3 years were recruited. The level of C-reactive protein (CRP) was high in patients exhibiting pulmonary complications. The percentage of cellular immunophenotypes did not change between patients with and without pulmonary complications. The absolute numbers of peripheral blood mononuclear cells (PBMC), CD3, CD8, and CD16CD56 decreased with acute S-OIV pulmonary complications. Acute influenza infection with pulmonary complications was associated with high plasma concentrations of IL-1β, IL-6, IL-12, and IFN-γ. Conclusion. Immunophenotype studies have reported variability in immune response to the severity of S-OIV infections. Acute phase cytokine profiles of the 2009 S-OIV infection might have contributed to the pathogenesis of the pulmonary complications. Shih-Min Wang, Yu-Ting Liao, Yu-Shiang Hu, Tzong-Shiann Ho, Ching-Fen Shen, Jen-Ren Wang, Yee-Shin Lin, and Ching-Chuan Liu Copyright © 2014 Shih-Min Wang et al. All rights reserved. Predictors of Disease Recurrence Post Living Donor Liver Transplantation in End Stage Chronic HCV Patients Tue, 18 Feb 2014 09:42:08 +0000 http://www.hindawi.com/journals/dm/2014/202548/ HCV recurrence represents a universal phenomenon after liver transplantation. In this study Fifty HCV patients who underwent living donor liver transplantation were enrolled and factors that may accelerate HCV reinfection of the allograft such as donor’s age and degree of liver steatosis, recipient’s age, gender, BMI, MELD score, liver functions, HCV viral load, type of immunosuppressive drug, and genetic polymorphisms of IL28B, OAS, and IL1B were studied. The results of disease-free survival (DFS) rates showed inverse correlation with the recipient’s postoperative levels of ALT, AST, ALP (, <0.001, and 0.006 resp.) as well as pre- and postoperative titers of HCV RNA ( and <0.001 resp.). Recipient’s IL28B SNP was a significant factor in predicting postoperative DFS (). However, SNPs in OAS and IL1B genes had no apparent correlation with DFS. Cox proportional hazards model revealed that patients with elevated levels of ALT, preoperative viral titers, IL28B CT, and IL28B TT were 8.28, 4.22, 3.35, and 1.36 times, respectively, more likely to develop recurrence. In conclusion IL28B SNP, ALT level, and preoperative HCV titer besides proper choice of immunosuppressant are helpful for predicting posttransplant HCV recurrence and DFS. Mostafa K. El Awady, Noha G. Bader El Din, Mahmoud Abdel Aziz Riad, Moataza H. Omran, Tawfeek H. Abdelhafez, Tamer Mahmoud Elbaz, Shereen Shoukry Hunter, Reham M. Dawood, and Ashraf O. Abdel Aziz Copyright © 2014 Mostafa K. El Awady et al. All rights reserved. Severity of Hepatitis C Virus (Genotype-3) Infection Positively Correlates with Circulating MicroRNA-122 in Patients Sera Tue, 18 Feb 2014 06:31:28 +0000 http://www.hindawi.com/journals/dm/2014/435476/ Introduction. Hepatitis C virus (genotype-3) causes acute and chronic hepatitis infection predomination in India. The infectious phase of the virus requires various host factors for its survival and subsequent viral particle production. Small RNA molecules like microRNA-122 (miR-122) are one such factor mostly present in the liver and play a supportive role in viral replication. Objective. In this study, diagnostic potential of miR-122 is evaluated in the sera of chronic hepatitis C patients. Methods. miRNAs were isolated from the sera samples of patients as well as controls and miR-122 expression was quantified by real-time PCR. Results. A significant augmentation was observed in the level of circulating miR-122 (median level, 0.66 versus 0.29, ) in patients compared to controls with ROC value of (). Interestingly, miR-122 level also depicted a significant positive correlation with serum ALT (), AST (), and viral load (). Conclusion. The study thus unveiled the role of miR-122 as a plausible diagnostic biomarker during HCV genotype-3 infection in India. Subodh Kumar, Yogesh Kumar Chawla, Sujata Ghosh, and Anuradha Chakraborti Copyright © 2014 Subodh Kumar et al. All rights reserved. Breast Carcinoma Progression and Tumour Vascular Markers Related to Apoptotic Mechanisms Tue, 18 Feb 2014 06:28:28 +0000 http://www.hindawi.com/journals/dm/2014/156034/ Background. In the last few years, the cancer research had tried to identify and characterize new biochemical and molecular pathways in which the inhibition induces prosurvival mechanisms. Our work describes the expression of two different members of apoptotic regulatory pathway and their relationship with a progression of breast carcinoma. Materials and Methods. We compared expression of genes related to apoptosis (DR6 and Gpm6B) in the blood of patients suffering from stage I of breast cancer in different grades (I–IV), with healthy controls. After isolation of mRNA, transcription of mRNA into the cDNA was performed. The quantification of gene expression changes in DR6 and Gpm6B was detected by RT-PCR method. Analysis at the protein level was performed by the Western blot.Results. In statistical analysis of Dr6 mRNA level changes we detected significant increase starting in Grading 1 (G1) and reached maximal level in G3.This expression on mRNA levels was similar to protein levels, which copy rising tendency with maximal value in G3. The results of Gpm6B were significantly lower.Conclusion. This result showed that antiapoptotic signalling during neovascularization is increased significantly. It would be advisable in the future to study the influence of cytostatic treatment on the expression of genes related to apoptotic pathways and their relationship with progression of breast cancer tumours. Miroslava Bilecova-Rabajdova, Peter Urban, Kristina Gregova, Jan Varga, Viera Fialkovicová, Peter Kruzliak, and Maria Marekova Copyright © 2014 Miroslava Bilecova-Rabajdova et al. All rights reserved. Chemokines as Potential Markers in Pediatric Renal Diseases Mon, 17 Feb 2014 12:50:19 +0000 http://www.hindawi.com/journals/dm/2014/278715/ Glomerular diseases and obstructive uropathies are the two most frequent causes of chronic kidney disease (CKD) in children. Recently, biomarkers have become a focus of clinical research as potentially useful diagnostic tools in pediatric renal diseases. Among several putative biomarkers, chemokines emerge as promising molecules since they play relevant roles in the pathophysiology of pediatric renal diseases. The evaluation of these inflammatory mediators might help in the management of diverse renal diseases in children and the detection of patients at high risk to develop CKD. The aim of this paper is to revise general aspects of chemokines and the potential link between chemokines and the most common pediatric renal diseases by including experimental and clinical evidence. Ana Cristina Simões e Silva, André Barreto Pereira, Mauro Martins Teixeira, and Antônio Lúcio Teixeira Copyright © 2014 Ana Cristina Simões e Silva et al. All rights reserved. High Nuclear Expression of HDGF Correlates with Disease Progression and Poor Prognosis in Human Endometrial Carcinoma Mon, 17 Feb 2014 08:49:09 +0000 http://www.hindawi.com/journals/dm/2014/298795/ Aims. This study examined the correlation between high nuclear expression of hepatoma-derived growth factor (HDGF) and clinicopathologic data in endometrial carcinoma (EC), including patient survival. Methods. One hundred and twenty-two endometrial carcinoma (EC) patients from 2002 to 2008 were reviewed in the study. HDGF expression in tumor tissues was examined using immunohistochemistry (IHC), and its association with clinicopathological parameters was evaluated. Tumors with 80% or more nuclei staining were regarded as high expression and tumors with less than 80% nuclei staining considered as low expression. Results and Conclusions. Immunohistochemical analysis revealed that HDGF was expressed in both the nucleus and cytoplasm. High nuclear expression of HDGF was positively correlated with FIGO stage (), but not associated with other clinical features, such as histological grading or lymph node status. Patients with high expression of HDGF had poorer overall survival rates than those with low expression of HDGF (). However, multivariate analyses showed that high nuclear expression of HDGF protein was not an independent predictor of prognosis for EC patients (). Our results suggest that high nuclear expression of HDGF is a potential unfavorable factor for the progression and prognosis of EC. Lijing Wang, Qingping Jiang, Shengni Hua, Mengyang Zhao, Qiangyun Wu, Qiaofen Fu, Weiyi Fang, and Suiqun Guo Copyright © 2014 Lijing Wang et al. All rights reserved.