Disease Markers - Volume 34, issue 5

Authors: Jiang, Zhu-Ling | Cui, Yu-Qiong | Gao, Rui | Li, Ying | Fu, Zhao-Chen | Zhang, Bin | Guan, Cheng-Chao

Article Type: Research Article

Abstract: OBJECTIVE: In this study, we sought to investigate the dynamic changes in the levels of TNF-α, IL-1β and LPS in the gingival crevicular fluid (GCF) in a rat model of diabetes mellitus (DM) and periodontitis (PD). Additionally, we evaluated alveolar bone loss and the histopathological response associated with experimental diabetes mellitus and experimental periodontitis. METHODS: DM and PD were induced together in 15 rats (group 1) by streptozotocin injection and ligature induction. Periodontitis alone …was produced by ligature induction in 15 rats (group 2), diabetes alone was produced by streptozotocin injection in 15 rats (group 3), and fifteen systemically and periodontally healthy rats were used as controls (group 4). The gingival TNF-α, IL-1β and LPS levels were measured by using ELISA method. Periodontal destruction was assessed by measuring the alveolar bone loss. Periodontal inflammation was quantified by histopathological grading in H&E stained samples. RESULTS: Higher levels of TNF-α, IL1-β and LPS, increased alveolar bone loss and more serve histopathology were found in group 1 compared with group 2, group 3 and group 4 (p< 0.05). The quantities of TNF-α, IL1-β and LPS, the amount of alveolar bone loss and the severity of the histopathological finding were greater in group 2 than group 3 and group 4 (p< 0.05). Group 3 demonstrated higher levels of TNF-α, IL1-β and LPS, increased alveolar bone loss and more serve histopathology than group 4 (p< 0.05). Statistically significant differences were noted between all of the groups. CONCLUSIONS: These data indicate that DM may lead to enhanced TNF-α, IL1-β and LPS production in the periodontal tissues. The resorption values of alveolar bone and the histological inflammation were more severe in rats with periodontitis and diabetes mellitus than in those with periodontitis alone, diabetes mellitus alone and control rats. Our findings are consistent with the hypothesis that hyperglycemia contributes to the heightened inflammatory response associated with periodontitis. Show more

Keywords: TNF-α, IL-1β, LPS, GCF, diabetes mellitus, periodontitis, alveolar bone loss, histopathology

DOI: 10.3233/DMA-130974

Citation: Disease Markers, vol. 34, no. 5, pp. 295-304, 2013

Authors: Sukhtankar, Laxmi | Kulloli, Anita | Kathariya, Rahul | Shetty, Sharad

Article Type: Research Article

Abstract: BACKGROUND: Superoxide dismutase (SOD), an antioxidant acting against superoxide (oxygen radical, O_{2}^{.-} ), it is released in inflammatory pathways and causes connective tissue breakdown. Increased SOD activity in inflamed gingiva may indicate increased O_{2}^{.-} radical generation by neutrophils and other inflammatory cells at the diseased site. The aim of the study was to evaluate the effects of non-surgical periodontal therapy (NSPT) on SOD levels in gingival tissues of chronic …periodontitis patients. METHODS: Forty subjects: 20 periodontally healthy (Control) and 20 chronic periodontitis (Test); age range 24–55 years were recruited. Gingival tissue samples were collected by excising the inner lining of the periodontal pocket at baseline (prior to non-surgical periodontal therapy) and 2 months post therapy. In controls, tissue samples were obtained immediately after tooth extraction scheduled for orthodontic reasons. Clinical parameters included probing depth, clinical attachment level, gingival index, bleeding index, plaque index. SOD activities were assessed spectrophotometrically at baseline and 2 months post NSPT, results were analysed statistically. RESULTS: At baseline, patients with chronic periodontitis had higher mean SOD activity (2.73 ± 1.36) than the control subjects (1.12 ± 1.13) with p=0.00003 (p< 0.05). At 2 months post NSPT median SOD level (1.00) had come close to median SOD value of control group (0.85); p=0.99 (p> 0.05). The resolution of inflammation with successful NSPT resulted in decreased SOD levels as in control group. Clinical parameters in patients with chronic periodontitis showed a significant improvement 2 months post NSPT (p< 0.05). CONCLUSION: Non-surgical periodontal therapy significantly improves the clinical parameters and restores previously increased SOD levels to normal in chronic periodontitis patients. Show more

Keywords: Non-surgical periodontal therapy, superoxide dismutase, chronic periodontitis, gingiva, neutrophils

DOI: 10.3233/DMA-130978

Citation: Disease Markers, vol. 34, no. 5, pp. 305-311, 2013

Authors: Kamodyová, Natália | Tóthová, L'ubomíra | Celec, Peter

Article Type: Research Article

Abstract: BACKGROUND: Salivary markers of oxidative stress and antioxidant status represent promising tool for the research of oral diseases. One of the criteria is the validation of these biomarkers from the perspective of the confounding and modifying factors. AIM: To examine the effect of circadian rhythm, tooth-brushing and ascorbic acid treatment on selected salivary markers of oxidative and carbonyl stress, and antioxidant status. SUBJECTS AND METHODS: Whole unstimulated saliva samples were collected from …19 healthy participants three times during a day, before and after tooth-brushing, and before and after the administration of vitamin C (250 mg). Advanced oxidation protein products (AOPP), thiobarbituric acid reactive substances (TBARS), advanced glycation end products (AGEs), ferric reducing antioxidant power (FRAP) and total antioxidant capacity (TAC) were measured. RESULTS: Salivary AGEs levels varied significantly during the day (p< 0.05) with the highest concentrations in the morning. FRAP levels varied during the day (p < 0.01) with the highest concentrations in the afternoon. Tooth-brushing decreased AGEs (p< 0.05) and TBARS levels (p< 0.01) and increased FRAP levels (p< 0.05). Single intake of vitamin C significantly decreased AGEs (p < 0.001) and increased both FRAP (p< 0.01) and TAC (p< 0.01) concentrations. CONCLUSION: Significant daily variations were observed in salivary AGEs and FRAP levels. Tooth-brushing and treatment with vitamin C decreased carbonyl stress and increased the antioxidant status. These results are important from the perspective of using saliva for the research of oral diseases. Show more

Keywords: Oxidative stress, saliva, antioxidant status, circadian rhythm, tooth-brushing, ascorbic acid

DOI: 10.3233/DMA-130975

Citation: Disease Markers, vol. 34, no. 5, pp. 313-321, 2013

Authors: Cai, Anping | Zheng, Dongdan | Qiu, Ruofeng | Mai, Weiyi | Zhou, Yingling

Article Type: Research Article

Abstract: Atherosclerosis and its manifestations namely cardiovascular diseases (CVD) are still the leading cause of morbidity and mortality worldwide. Although intensified interventions have been applied, the residual cardiovascular (CV) risks are still very high. Lipoprotein-associated phospholipase A2 (Lp-PLA_2 ) is a novel and unique biomarker highly specific for vascular inflammation and atherosclerosis. Both pro-atherogenic property of Lp-PLA_2 and positive correlation with CV events have already been demonstrated by a large …number of scientific and clinical studies. Currently, in the Adult Treatment Panel III (ATP III) guideline, Lp-PLA_2 has been recommended as an adjunct to traditional risk factors in assessing future CV risks. Encouragingly, darapladib, an orally Lp-PLA_2 specific inhibitor, has been tested in basic research and preclinical trials and the outcomes are quite striking. Additionally, there are two phase III ongoing clinical trials in evaluating the efficacy and safety of darapladib on cardiovascular outcomes. With regard to the potential values of Lp-PLA_2 in risk stratification, therapeutic regimen establishment and prognosis evaluation in patients with moderate or high risk, our present review is going to summarize the relevant data about the bio-chemical characteristics of Lp-PLA_2 , the actions of Lp-PLA_2 on atherosclerosis and the results of Lp-PLA_2 in scientific research and clinical studies. Show more

Keywords: Lipoprotein-associated phospholipase A2, cardiovascular diseases, inflammatory biomarker

DOI: 10.3233/DMA-130976

Citation: Disease Markers, vol. 34, no. 5, pp. 323-331, 2013

Authors: Qing, Ping | Luo, Song-Hui | Guo, Yuan-Lin | Liu, Jun | Xu, Rui-Xia | Zhu, Cheng-Gang | Jia, Yan-Jun | Ma, Feng-Lian | Wu, Na-Qiong | Jiang, Li-Xin | Li, Jian-Jun

Article Type: Research Article

Abstract: BACKGROUND: Cardiac syndrome X (CSX) is a condition characterized by chest pain with normal coronary arteries. However, its pathogenesis has not fully been understood yet. Red blood cell distribution width (RDW) has recently been suggested as a marker of acute and chronic cardiovascular diseases, while no data is available in patients with CSX. METHODS: One hundred and twenty consecutive patients with CSX and 102 normal controls were prospectively enrolled in this study. Blood samples …were drawn from all individuals for measuring RDW and high-sensitivity C-reactive protein (CRP). The baseline data were compared between patients with CSX and normal controls. RESULTS: The RDW levels were significantly higher in patients with CSX than that in those with normal controls (13.1 ± 2.1 versus 12.3 ± 1.8, p=0.011). Moreover, the data showed that the levels of plasma CRP were marked higher in patients with CSX than those that were observed in normal controls (CRP: 2.8 ± 2.2 mg/L versus 2.0 ± 1.7 mg/dl, p=0.014). In addition, the multivariate analysis indicated that peripheral monocyte cell, CRP and RDW were the independent variables most strongly associated with CSX. In a receiver operating characteristic (ROC) curve analysis, we found that an RDW value of 12.8% was used as an effective cut-point in the segregation of the presence or absence of cardiac syndrome X, a sensitivity of 52.0% and a specificity of 65.4% were obtained. Finally, correlation analysis suggested that there was positive correlation between plasma levels of CRP and RDW levels (n=120, γ =0.381, P=0.013). CONCLUSIONS: The present study, for the first time, demonstrated that elevated RDW and CRP levels were independently associated with the presence of CSX. Show more

Keywords: Cardiac syndrome X, Red cell distribution width, C-reactive protein, complete blood count

DOI: 10.3233/DMA-130977

Citation: Disease Markers, vol. 34, no. 5, pp. 333-339, 2013

Authors: Palavra, Filipe | Marado, Daniela | Mascarenhas-Melo, Filipa | Sereno, José | Teixeira-Lemos, Edite | Nunes, Carla Cecília | Gonçalves, Grilo | Teixeira, Frederico | Reis, Flávio

Article Type: Research Article

Abstract: OBJECTIVES: This study aimed to characterize a population of multiple sclerosis (MS) patients in terms of traditional and new cardiovascular risk factors and assess their putative correlation with clinical disease activity (evaluated by the Expanded Disability Status Scale [EDSS]). METHODS: Thirty relapsing MS patients and 66 subjects, matched by age and sex, were enrolled in this cross-sectional study. For each subject, anthropometric data were collected and classical biochemical (including lipid profile, glucose and C …reactive protein [CRP] levels) and novel markers (paraoxonase 1 [PON1] enzyme activity and contents of high-density lipoprotein [HDL] cholesterol, oxidized low-density lipoprotein [Ox-LDL], tumor necrosis factor [TNF]-alfa, vascular endothelial growth factor [VEGF] and adiponectin) were studied. RESULTS: In patients group, 23 women and 7 men were included, aged 35.00 (28.25–40.25) years and scoring a median of 2.00 (1.50–3.13) in EDSS. Comparing with controls, the most relevant differences encountered were: increased serum triglycerides (P< 0.001), Ox-LDL (P< 0.001) as well as Ox-LDL/LDL ratio and reduced small HDL (P=0.040), accompanied by a trend to increased VEGF concentration. LDL content, especially Ox-LDL, showed positive and significant correlation with EDSS (r=0.458; P=0.011) and VEGF (r=0.453; P=0.014). CONCLUSIONS: MS patients presented a profile of early CV risk, being Ox-LDL contents a putative good marker and having correlation with the clinical activity of the disease. Show more

Keywords: Multiple sclerosis, early cardiovascular risk, EDSS, oxidized-LDL, small HDL, VEGF

DOI: 10.3233/DMA-130979

Citation: Disease Markers, vol. 34, no. 5, pp. 341-348, 2013

Authors: AlFadhli, Suad

Article Type: Research Article

Abstract: The purpose of this study was to analyse the effect of the T-786C polymorphism and intron 4 27 bp variable number tandem repeat(VNTR) eNOS markers for their potential association with Systemic Lupus Erythematosus(SLE), Hashimotos thyroiditis(HT) and Rheumatoid arthritis(RA) as well as to explore their effect on eNOS mRNA expression and nitrate production(NOx). Kuwaitis (n=383) matched by age, gender and ethnicity were genotyped by fluorescent-labelled-restriction fragment length polymorphism (RFLP) and fragment analysis. Expression …of eNOS mRNA was analysed using RT-PCR and sera from subjects were screened for NOx using ELISA. Analysis of the allelic frequency revealed a significant association of the 4b allele with susceptibility to SLE (p=0.0092, OR=1.76). The 4bb genotype was found to be associated with SLE (p=0.0076, OR=1.97) and HT (p=0.05, OR=1.81). Allelic and genotypic distribution did not differ between RA patients and healthy control subjects. The 4bb genotype resulted in reduced expression of eNOS mRNA in SLE, RA and HT, but only the reduction in HT was significant (p=0.05). The 4ab genotype revealed a significant association with increased eNOS expression in HT (p=0.03) and RA (p=0.014) patients, and elevated NOx levels were detected in the autoimmune disease cohorts (p< 0.05) when compared to healthy control subjects. The T-786C SNP failed to show a significant association (p> 0.05) with SLE, HT, and RA patients. This study is the first to reveal a significant association between the 4bb genotype of the 27 bp VNTR and susceptibility to HT. The expression of eNOS is related to the number of 27 bp repeats, with heterozygous 4bb repeats showing a decrease in eNOS expression. eNOS – endothelial nitric oxide synthase. Show more

Keywords: eNOS, SLE, RA, HT

DOI: 10.3233/DMA-130983

Citation: Disease Markers, vol. 34, no. 5, pp. 349-359, 2013

Authors: Korzeniecka-Kozerska, Agata | Wasilewska, Anna | Tenderenda, Edyta | Sulik, Agnieszka | Cybulski, Kamil

Article Type: Research Article

Abstract: BACKGROUND: The study was undertaken to develop a potential new markers for distinguishing minimal change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS) in children. We hypothesized that matrix metalloproteinase-9/neutrophil gelatinase-associated lipocalin (MMP-9/NGAL) is a better marker of focal sclerosis in the glomerulus then matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 (MMP-9/TIMP-1) and matrix metalloproteinase-2/tissue inhibitor of metalloproteinase-2 MMP2/TIMP-2. METHODS: The present study used a sample of 36 children and …adolescents subdivided into two groups: I – 20 children with MCNS, subjected to examination twice: A – in relapse of nephrotic syndrome, before treatment and B – after regression of proteinuria; II – 16 children with FSGS. MMPs and TIMPs and NGAL levels were measured in the urine using ELISA kit. MMP-9/TIMP-1, MMP-2/TIMP-2 and MMP-9/NGAL ratios were calculated. RESULTS: Median NGAL/cr. was significantly higher in MCNS and FSGS patients when compared to healthy controls. Both, NGAL and MMP-9 urinary levels were significantly elevated in FSGS subjects, as compared with control subjects. Contrary to FSGS children, in MCNS group, before treatment only NGAL/cr., but not MMP-9/cr. was increased. Urinary concentrations of NGAL and MMP-9 were highly associated with each other (NGAL/cr. vs. MMP-9/cr., r=0.485, p<0.01). Median urine MMP-9/NGAL ratio in FSGS patients was significantly higher than in patients with MCNS. We also found that significant increase in MMP-9/NGAL was associated with FSGS [odds ratio (OR) – 9.0; confidence interval (CI) 1.97–41.07]. CONCLUSION: MMP-9/NGAL ratio may serve as differentiation marker between MCNS and FSGS in nephrotic children. Show more

Keywords: MMP-9, NGAL, focal glomerulosclerosis, nephrotic syndrom

DOI: 10.3233/DMA-130980

Citation: Disease Markers, vol. 34, no. 5, pp. 357-362, 2013

Authors: Baccar, Amal | Ferchichi, Imen | Troudi, Wafa | Marrakchi, Raja | Ben Hmida, Naziha | Jebini, Sondes | Mrad, Karima | Ben Romdhane, Khaled | Benammar Elgaaied, Amel

Article Type: Research Article

Abstract: In an attempt to better unfold the antitumor immune response and invasion strategies perused by tumor cells, markers such as CD99 and HLA-II have been stained in breast tumors, some of them turned out to be important for prognosis and its outcome. CD99 is involved in the intracellular transport of HLA-II proteins. The expression of HLA-II and CD99 molecules has been demonstrated in a broader range of neoplastic tissues, including some epithelial tumors. In the present …work, we stained CD99 and HLA-II in breast malignant and non-malignant tissues sections obtained from biopsies resected surgically from 80 Tunisian women. Data implied that CD99 marks malignant tissue significantly as compared to non-malignant breast tissue. HLA-II staining allowed determining the correlation between breast cancer and HLA-II with cytoplasmic localization. CD99 and HLA-II immunostaining was also examined in correlation with two of the most important breast cancer prognostication in routine clinical practice, the lymph node stage and the histological assessment. Results let suggest that CD99^+ HLA-II^- is a marker of worst prognostic since this phenotype is strongly linked to lymph node metastasis in breast cancer. Show more

Keywords: CD99, HLA-II, breast cancer, histological grade, lymph node metastasis

DOI: 10.3233/DMA-130982

Citation: Disease Markers, vol. 34, no. 5, pp. 363-371, 2013

Authors: de Melo Rêgo, Moacyr Jesus Barreto | Cordeiro, Marina Ferraz | de Lima Bezerra Cavalcanti, Carmelita | de Carvalho Junior, Luiz Bezerra | Beltrão, Eduardo Isidoro Carneiro

Article Type: Research Article

Abstract: Her-2 status evaluation in breast cancer has prognostic and treatment response value but its interobserver variation among pathologists is a problem since it is not quantitatively assayed. This study presents an immunohistochemiluminescence method to quantify Her-2 in breast cancer. Anti-Her-2 antibody was conjugated to acridinium ester (AE) and used to evaluate/quantify Her-2 status in breast Invasive Ductal Carcinoma (IDC, n=50) comparing with traditional immunohistochemistry. Anti-HER-2-AE results were expressed in Relative Lights Units …(RLU) and showed to be able to distinguish and quantify the differences between the three groups of Her-2 status. 3+ Her-2 status presented the highest RLU (246,982 × 10^{3} ± 2.061 × 10^{3} ) compared to 2+ (76,146 × 10^{3} ± 0.290 × 10^{3} ), negative (27,415 × 10^{3} ± 1.445 × 10^{3} ) and normal tissues (27,064 × 10^{3} ± 2.060). Status differences were significant between 3+ and 2+ (p=0.0025); 2+ and negative (p=0.0003), and +3 and +1 (p=0.0001) beside this, normal breast control RLU was 27,064 × 10^{3} ± 2,060 × 10^{3} , similar to negative cases. Results showed that anti-HER-2-AE conjugate was effective in breast tumors Her-2 status evaluation, allowing its quantitative establishment to consequently decrease the subjectivity in prognostic and predictive information intrinsic to this test. Show more

Keywords: Immunochemiluminescence, HER-2, invasive ductal carcinoma

DOI: 10.3233/DMA-130981

Citation: Disease Markers, vol. 34, no. 5, pp. 373-377, 2013