Is serum Osteopontin a predictor of carotid atherosclerosis severity among prevalent hemodialysis patients? / ¿Es la osteopontina sérica un factor predictivo de la gravedad de la aterosclerosis carotídea en los pacientes prevalentes en hemodiálisis?

BACKGROUND AND AIM: Chronic hemodialysis (HD) patients are among the highest population risk for accelerated atherosclerosis. Osteopontin (OPN) is a multifunctional protein that is increased in chronic kidney disease that may play a role in vascular remodelling and intimal proliferation. AIM: To assess the relation between OPN levels and severity of carotid atherosclerosis among prevalent HD patients. METHODS: Eighty chronic HD patients underwent serum OPN levels assessment and were further classified into 3 subgroups according to the OPN tertiles’ levels; sub-group 1 (lower tertile) subgroup 2 (middle tertile) and sub-group 3 (upper tertile), together with the carotid duplex and Transthoracic Doppler Echocardiography examination. RESULTS: The mean carotid intima-media thickness (CIMT) was 0.89±0.14mm. Out of the studied group, 50 (62.5%) patients had atheromatous plaques and 15 patients (18.8%). had significant stenosis. The 3rd group with the upper OPN tertile (78–270ng/dl) had the highest incidence of atherosclerosis. A significant correlation between the OPN levels and the CIMT (r=0.533, p=0.001). OPN values detect atherosclerosis with diagnostic sensitivity of 70%, specificity of 69%, positive predictive value (PPV) 73%, negative predictive value (NPV) 65% with area under the curve (AUC) 0.804 (95% CI: 0.711–0.897). Serum OPN detect carotid stenosis with sensitivity of 66%, specificity of 81%, PPV 45%, NPV 91% with AUC=0.769 and detect the presence of carotid atheroma with sensitivity 70%, specificity 66.67%, PPV 77.8%, NPV 57.1% and AUC=0.767 (p-value<0.001). Moreover, serum levels of OPN were significantly positively correlated with grade of diastolic dysfunction (r=0.312, p=0.005), E/A ratio (r=0.293, p=0.008) and inversely correlated with left ventricular ejection fraction (r=−0.304, p=0.006).

ANTECEDENTES Y OBJETIVO: Los pacientes de hemodiálisis crónica (HD) son una de las poblaciones de mayor riesgo de aterosclerosis acelerada. La osteopontina (OPN) es una proteína multifuncional que se incrementa en la enfermedad renal crónica, y que puede jugar un papel en la remodelación vascular y la proliferación de la íntima. OBJETIVO: Evaluar la relación entre los niveles de OPN y la gravedad de la aterosclerosis carotídea en los pacientes prevalentes en HD. MÉTODOS: Se evaluó el nivel sérico de OPN en 80 pacientes de HD crónica. Seguidamente, se clasificó a dichos pacientes en tres subgrupos con arreglo a los niveles de los terciles de OPN: subgrupo 1 (tercil inferior) subgrupo 2 (tercil medio) y subgrupo 3 (tercil superior), junto con dúplex carotídeo y ecocardiografía Doppler transtorácica. RESULTADOS: El espesor medio de la íntima-media carotídea (CIMT) fue de 0,89 ± 0,14 mm. En el grupo estudiado, 50 (62,5%) pacientes tenían placas ateromatosas y 15 pacientes (18,8%) tenían estenosis significativa. El tercer grupo, con tercil OPN (78-270 ng/dL) reflejó la mayor incidencia de aterosclerosis. Existió una correlación significativa entre los niveles de OPN y CIMT (r = 0,533, p = 0,001). Los valores de OPN detectaron aterosclerosis con una sensibilidad diagnóstica del 70%, especificidad del 69%, valor predictivo positivo (VPP) del 73%, valor predictivo negativo (VPN) del 65% y área bajo la curva (AUC) de 0,804 (intervalo de confianza [IC] 95%: 0,711-0,897). La OPN detectó estenosis carotídea con una sensibilidad del 66%, especificidad del 81%, VPP del 45%, VPN del 91%, y AUC = 0,769 y detectó la presencia de ateroma carotídeo con una sensibilidad del 70%, especificidad del 66,67%, VPP del 77,8%, VPN del 57,1% y AUC = 0,767 (valor p < 0,001). [...]

Cyclooxigenase-2 and osteopontin in gastric pre-neoplastic lesions in relation to H-pylori infection and grade of inflammation / Ciclooxigenasa-2 y osteopontina en lesiones pre-neoplásicas gástricas en relación con infección por H-pylori y grado de inflamación

The association between Helicobacter-pylori-induced inflammation and gastric adenocarcinoma is well documented and it has been suggested that the pro-mitotic and apoptotic effect of Cyclooxygenase-2 and Osteopontin on the epithelial cells of the gastric mucosa may have a role in carcinogenesis of the gastric mucosa. The aim of this study was to determine the expression of Cyclooxygenase-2 and Osteopontin in normal gastric mucosa, mucosa with gastritis and gastric mucosa with intestinal metaplasia, in relation to Helicobacter-pylori infection and grade of inflammation. Immunohistochemistry was performed on 108 gastric biopsies in order to detect Cyclooxygenase-2 and Osteopontin expression. The intensity and percentage of staining were evaluated using the H-Score, and its association with grade of inflammation, Helicobacter pylori infection and intestinal metaplasia was determined. Expression of Cyclooxygenase-2 and Osteopontin was higher in gastric biopsies (values shown respectively) with Helicobacter-pylori infection (179.9/142.3), intestinal metaplasia (208.8/179.3) or higher grades of inflammation (190/135.7) in comparison to normal gastric mucosa (100.7/80) or mild grade of inflammation (128.4/128.4), (p < 0.05).There is an overexpression of Cyclooxygenase-2 and Osteopontin in gastric mucosa with H. pylori infection, intestinal metaplasia and high grades of inflammation, suggesting a constant up-regulation of protein expression in response to the inflammatory process generated by a Helicobacter-pylori infection, leading to the development of intestinal metaplasia

Se ha documentado una asociación entre la inflamación inducida por Helicobacter-pylori y el adenocarcinoma gástrico, con posible participación del efecto pro-mitótico y anti-apoptótico inducido por Ciclo-oxigenasa-2 y Osteopontina en las células epiteliales gástricas. El objetivo de este estudio fue determinar la expresión de estas dos proteínas en mucosa gástrica normal, con gastritis, y, con metaplasia intestinal, en relación con infección por Helicobacter-pylori y el grado de inflamación. Se evaluó la intensidad y porcentaje de células con tinción inmunohistoquímica para Ciclo-oxigenasa-2 y Osteopontina en 108 biopsias gástricas. Se analizó la tinción de cada marcador y su asociación con: grado de inflamación, Helicobacter-pylori, y metaplasia intestinal. Los niveles de expresión de Ciclooxigenasa-2 y Osteopontina respectivamente, fueron superiores en las biopsias con Helicobacter-pylori (179.9, y 142.3), metaplasia intestinal (208.8, y 179.3), o, inflamación severa (190, y 135.7), comparados con la mucosa normal (100.7, y 80), o, la inflamación leve (128.4, y 128.4), (p <0.05). En conclusión, hay sobre-expresión de Ciclooxigenasa-2 y Osteopontina en la mucosa gástrica con Helicobacter-pylori, metaplasia intestinal, e inflamación severa. Esto sugiere sobre-regulación constante de la expresión de estas proteínas en la mucosa gástrica en respuesta al proceso inflamatorio generado por la infección por Helicobacter-pylori, llevando al desarrollo de metaplasia intestinal

Osteopontina láctea: nuevo ingrediente funcional en las fórmulas infantiles / Milk osteopontin: a new functional ingredient for infant formulas

La osteopontina (OPN) es una proteína bioactiva cuya ubicuidad y alta variabilidad molecular determinan que asuma funciones muy diversas por todo el organismo, aunque aún no están totalmente establecidas. La OPN está presente en la leche humana, donde es capaz de interaccionar favorablemente con otros componentes de la leche materna, como el calcio, y potenciar la actividad de proteínas como la lactoferrina y la lactoperoxidasa. Sin embargo, también desempeña un papel fundamental en el paso del estado prenatal al posnatal del sistema de respuesta inmunitaria-inflamatoria. La OPN láctea se perfila como un componente bioactivo capaz de emitir señales esenciales para la maduración del sistema inmunitario del lactante y la defensa frente a microorganismos patógenos. Por su similitud estructural y funcional, la adición de OPN de leche bovina a fórmulas infantiles puede promover una actividad fisiológica no nutritiva beneficiosa para el lactante. Se espera disponer de nuevos estudios que consoliden la evidencia y proporcionen datos cuantitativos de estos beneficios

Osteopontin (OPN) is a bioactive protein, whose ubiquity and high molecular variability makes it assume very different functions throughout the body, although they are not yet fully established. Milk OPN is present in human milk and is capable to interact favorably with other breast milk components as calcium, and enhance the activity of proteins such as lactoferrin and lactoperoxidase. But it plays a key role in the change from prenatal to postnatal state of the immune-inflammatory system response. Milk OPN is shaped up as a bioactive component able to send out essential signals for the maturation of the infant’s immune system and the defense against pathogenic organisms. Since their structural and functional similarity, the addition of bovine milk OPN to infant formulas could promote a non-nutritive physiologic activity beneficial to the infant. New studies are expected in order to gain solid evidence and provide quantitative data of these benefits

Tear osteopontin level and its relationship with local Th1/Th2/Th17/Treg cytokines in children with allergic conjunctivitis

Background: Allergic conjunctivitis (AC) is one of the most common allergic ocular diseases worldwide. Osteopontin (OPN), as a recently described Th2 inflammation related protein, may play a role in the pathogenesis of AC. The aim of this study was to identify the expression of OPN in children with AC. Methods: Eighty AC children (seasonal and perennial AC) and twenty controls were enrolled in this study. Serum and tears of different time points (during and out of the pollen season) were collected and used for enzyme-linked immunosorbent assay (ELISA) of OPN and T-help cell related cytokines, respectively. The relationship between serum and tears OPN and Th1/2/17Treg related cytokines as well as disease severity were analysed. Results: Our results showed that expression of tear OPN protein by perennial AC patients increased significantly compared with controls or seasonal AC patients out of the pollen season. Tear OPN expression was positively related to local Th2/17 cytokines and negatively related to IL-10 and TGF-Beta expression. The tear OPN expression was also significantly related to disease severity. Conclusion: Tear OPN reflects the local clinical status of ocular allergy and might play an important pathophysiological role in local Th2/17/Treg inflammation in children with AC (AU)

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Biomarkers of airway and systemic inflammation in obese asthmatic paediatric patients

Background: It is thought that airway inflammation is more common in obese asthmatic patients because inflammation is harder to control and does not respond well to glucocorticoid treatment. Objective: This study's aim was to investigate the effect of obesity on airway and systemic inflammation in children with asthma and to identify the biomarkers that play a role in this inflammation. Methods: The study included patients aged 6-16 years who were diagnosed with asthma in the paediatric allergy outpatient clinic of Bagcilar Training and Research Hospital in Turkey. Complete blood count parameters were compared between three groups: obese asthmatic (n = 43), obese non-asthmatic (n = 45), and non-obese non-asthmatic (control group, n = 30). Levels of high-sensitive CRP (hs-CRP), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN), and matrix metalloproteinase-9 (MMP-9), and 25(OH)-vitamin D were compared between the groups. Results: No statistically significant differences were observed in 25(OH)-vitamin D, NGAL, OPN, hs-CRP, and MMP-9 levels between groups. There was a statistically significant negative correlation between FEV1/FVC and NGAL and MMP-9. Conclusion: This is the first study to investigate levels of hs-CRP, NGAL, OPN, MMP-9, and 25(OH)-vitamin D in obese asthmatic children. Larger studies with sputum and BAL examinations are required to determine the potential of biomarkers for identifying inflammation in obese asthmatic children (AU)

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La osteopontina como biomarcador de riesgo neurológico en la enfermedad carotídea / Osteopontin as a neurological risk marker in carotid diseases

INTRODUCCIÓN: La osteopontina (OPN) incrementa el reclutamiento, migración y adhesión de los macrófagos y modula la expresión de citocinas proinflamatorias e interleucinas. Actualmente, no está definida su asociación con la inestabilidad de la placa de ateroma carotídea y la sintomatología clínica de los pacientes. OBJETIVOS: Estudiar los niveles en plasma de OPN de pacientes intervenidos quirúrgicamente de endarterectomía carotídea (ECA) y correlacionarlos con la sintomatología clínica preoperatoria, con el fin de valorar el riesgo neurológico y la inestabilidad de placa. MATERIAL Y MÉTODOS: Se diseñó un estudio prospectivo con una muestra de pacientes consecutivos intervenidos quirúrgicamente de ECA, previamente evaluados por el neurólogo o con la realización de una TAC o RMN cerebral. Los pacientes se dividieron en 2 grupos (sintomáticos y asintomáticos) y se compararon con un grupo control. Se excluyeron aquellos con enfermedades intercurrentes. La OPN se determinó mediante enzimoinmunoanálisis. Se utilizó para el análisis estadístico el programa SPSS V. 18.0. Las variables categóricas se describen como frecuencias y las cuantitativas como media y desviación estándar en el caso de utilizar pruebas paramétricas, y como mediana y rango intercuartil en el caso de utilizar pruebas no paramétricas. Se estableció que la relación fue estadísticamente significativa si p era inferior a 0,05. RESULTADOS: Durante el periodo de estudio, 44 pacientes (39 hombres, 5 mujeres), de edad media 75±6,62 años, fueron intervenidos de ECA por presentar una placa de ateroma que producía una estenosis significativa (>70% con ecodoppler). De acuerdo con sus antecedentes cerebrovasculares, 24 fueron sintomáticos y 20 asintomáticos. El grupo control fue de 25 sujetos sanos. La OPN en el grupo control fue de 60±6,62 ng/mL, de 74,3±60,8 ng/mL en asintomáticos y de 90,3±45,4 ng/mL en sintomáticos (p = 0,003). CONCLUSIONES: La (OPN) se comporta como un buen indicador de riesgo cerebrovascular en pacientes con placa carotídea, a pesar de que sus niveles y los mecanismos moleculares de expresión no están del todo aclarados

INTRODUCTION: Osteopontin (OPN) increases recruitment, migration and adhesion of macrophages and modulates the expression of proinflammatory cytokines and interleukins. Its association with the instability of carotid atheromatous plaque and the clinical symptoms of patients is currently not defined. AIMS: To study plasma levels of OPN in patients operated on by carotid endarterectomy (ECA) and correlate them with preoperative clinical symptoms, in order to assess the neurological risk and instability of plaque. MATERIAL AND METHODS: A prospective study was designed with a sample of consecutive patients who underwent surgery by ECA, and previously evaluated by a neurologist and/or by performing a CT or MRI brain scan. Patients were divided into 2 groups (symptomatic and asymptomatic) and compared with a control group. Those with intercurrent diseases were exclude. OPN was determined by enzyme immunoassay. Windows SPSS V. 18.0 program was used for statistical analysis. Categorical variables are described as frequencies, and quantitative variables as mean and standard deviation, in the case of using parametric tests, and median and interquartile range when using non-parametric tests. A P<.05 was established as a statistically significant relationship. RESULTS: During the study period, 44 patients (39 males, 5 females), mean age 75±6.62 years old, were operated on by ECA due to having a plaque that produced a significant stenosis (> 70% with echodoppler). According to their stroke history, 24 were symptomatic and 20 asymptomatic. The control group was 25 healthy subjects. The OPN in the control group was 60±6.62 ng/mL, 74.3±60.8 ng/mL in asymptomatic, and 45.4±90.3 ng/mL in symptomatic patients (P=.003). CONCLUSIONS: OPN behaves as a good indicator of stroke risk in patients with carotid plaque, even though its levels and molecular mechanisms of expression are not entirely clear

Is there any correlation between levels of serum ostepontin, CEA, and FDG uptake in lung cancer patients with bone metastasis? / ¿Existe correlación entre los niveles de osteopontina en suero sanguíneo, CEA y captación de 18F-FDG en pacientes con metástasis óseas por cáncer de pulmón?

Objective. In this study, an evaluation was made of the relationship between the serum levels of carcinoembryonic antigen (CEA), osteopontin (OPN), and the semi-quantitative parameters of 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in lung cancer patients with bone metastasis. Material and methods. The evaluation included 42 non-small cell lung cancer (NSCLC) and 31 small cell lung cancer (SCLC) patients who were referred to our institution for staging by 18F-FDG PET/CT. The biochemical parameters measured included CEA and OPN serum levels. Results. Serum levels of OPN in NSCLC patients with and without bone metastasis were 21.20 ± 4.97 ng/ml and 13.33 ± 4.53 ng/ml, respectively (p < 0.05). In SCLC patients with and without bone metastasis serum OPN levels were 23.95 ± 4.78 ng/ml and 17.30 ± 3.09 ng/ml, respectively (p < 0.05). Serum levels of CEA in NSCLC patients with and without bone metastasis were 33.79 ± 6.49 ng/ml and 11.74 ± 2.96 ng/ml, respectively (p < 0.05). In SCLC patients with and without bone metastasis serum levels of CEA were 28.93 ± 4.59 ng/ml and 13.88 ± 4.47 ng/ml, respectively (p < 0.05). There were no correlations between primary tumor SUVmax, and serum levels of CEA and OPN. Conclusions. Bone metastasis can be detected in patients with lung cancer by measuring CEA and OPN levels. Increased levels of CEA and OPN levels may be considered an early warning sign in patients needing accurate imaging, as they are at higher risk of bone metastasis (AU)

Objetivo. Evaluar la relación entre los niveles de antígeno carcinoembriionario (CEA), osteopontina (OPN) y los valores semicuantitativos (SUV) de la PET/TC con 18F-FDG en pacientes con metástasis óseas por cáncer de pulmón. Material y método. Se incluyeron 40 pacientes con cáncer de pulmón de células no pequeñas (NSCLC) y 31 pacientes con cáncer de pulmón de células pequeñas (SCLC) referidos a nuestro centro para la realización de un estudio PET/TC con 18F-FDG de estadificación. Se analizarón los niveles sanguíneos de OPN y CEA. Resultados. Los niveles de OPN en pacientes con NSCLC con y sin metástasis óseas fueron de 21.20 ± 4.97 ng/ml y 13.33 ± 4.53 ng/ml, respectivamente (p < 0.05). En pacientes con SCLC con y sin metástasis óseas fueron de 23.95 ± 4.78 ng/ml y 17.30 ± 3.09 ng/ml, respectivamente (p < 0.05). Los niveles sanguíneos de CEA en pacientes de NSCLC con y sin metástasis óseas fueron de 33.79 ± 6.49 ng/ml y 11.74 ± 2.96 ng/ml, respectivamente (p < 0.05). En pacientes con SCLC con y sin metástasis óseas fueron de 28.93 ± 4.59 ng/ml y 13.88 ± 4.47 ng/ml, respectivamente (p < 0.05). No hubo correlación entre el SUV máximo del tumor primario, los niveles OPN ni de CEA. Conclusiones. La metástasis ósea puede ser detectada en pacientes con cáncer de pulmón con la determinación de los niveles de OPN y CEA. Los niveles incrementados de CEA y OPN pueden ser considerados como una señal de advertencia temprana en pacientes que necesiten imágenes precisas, porque ellos están en mayor riesgo de metástasis en el hueso (AU)

Elevated level of serum osteopontin in school-age children with asthma

BACKGROUND: The role of osteopontin (OPN) has not been elucidated in childhood asthma. OBJECTIVE: Our purpose was to investigate whether OPN levels change due to allergic inflammation in pre-school and school-age children. METHODS: In this prospective, cross-sectional study, 42 healthy children and a total of 51 children with asthma were recruited. OPN levels and its association with clinical and laboratory parameters were investigated in the study population. The asthma group were divided into two groups with respect to age, ≤5-years (n = 23) and >5-years (n = 28), and labelled Asthma Group 1 and Asthma Group 2, respectively. OPN levels were compared between subgroups. RESULTS: Serum OPN levels were significantly higher in the asthma group when compared to the control group (p = 0.004). OPN levels were similar in Asthma Group 1 and control groups, whereas it was found to be higher in Asthma Group 2 (p > 0.025, p = 0.001, respectively). In the >5-years age asthmatic group, OPN levels of the patients with allergic rhinitis (n = 15) were higher than those of the patients (n = 13) without allergic rhinitis (p = 0.021). CONCLUSION: The study underscores the relationship between childhood asthma and OPN as the first study in the literature. In this study we found that OPN, which plays a role in Th2 mediated inflammation, may also play a role in childhood asthma. The fact that OPN levels do not increase in preschool-age children with asthma might be due to the transient wheezing in this group

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Effect of gingival application of melatonin on alkaline and acid phosphatase, osteopontin and osteocalcin in patients with diabetes and periodontal disease

Objectives: To assess the effect of topical application of melatonin to the gingiva on salivary fluid concentrations of acid phosphatase, alkaline phosphatase, osteopontin, and osteocalcin. Study Design: Cross-sectional study of 30 patients with diabetes and periodontal disease and 30 healthy subjects. Diabetic patients were treated with topical application of melatonin (1% orabase cream formula) once daily for 20 days and controls with a placebo formulation. Results: Before treatment with melatonin, diabetic patients showed significantly higher mean salivary levels of alkaline and acid phosphatase, osteopontin and osteocalcin than healthy subjects (P < 0.01). After treatment with melatonin, there was a statistically significant decrease of the gingival index (15.84± 10.3 vs 5.6 ± 5.1) and pocket depth (28.3 ± 19.5 vs 11.9 ± 9.0) (P < 0.001). Also, use of melatonin was associated with a significant reduction of the four biomarkers. Changes of salivary acid phosphatase and osteopontin correlated significantly with changes in the gingival index, whereas changes of alkaline phosphatase and osteopontin correlated significantly with changes in the pocket depth. Conclusions: Treatment with topical melatonin was associated with an improvement in the gingival index and pocket depth, a reduction in salivary concentrations of acid phosphatase, alkaline phosphatase, osteopontin and osteocalcin (AU)

EGFR expression is linked to osteopontin and Nf-kB signaling in clear cell renal cell carcinoma

AIM AND BACKGROUND: Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase involved in many important aspects of cell biology that are related to tumorigenesis. There are opposite evidences of the role of EGFR in renal cancer and the outcome of EGFR-targeted therapies, suggesting the complexity of EGFR signaling pathways. In vitro, osteopontin (OPN) and nuclear factor kappa B (NF-κB) are thought to be involved in specific ligand-independent EGFR activation that could have a role in resistance to EGFR mAb therapy. Aim of this study was to analyze the relationship between EGFR and OPN at the protein and mRNA level, as well as their relation to NF-κB in clear cell renal cell carcinoma (CCRCC). MATERIALS AND METHODS: Expression of EGFR, OPN, and p65 NF-κB protein was analyzed using immunohistochemistry and compared mutually in 88 CCRCC samples. Expression of EGFR and OPN mRNAs was analyzed using quantitative Real-time PCR in 22 CCRCC samples and compared mutually and with NF-κB protein expression. RESULTS: Epidermal growth factor receptor mRNA level was higher in CCRCC samples in comparison with normal renal tissue (p = 0.012) and was associated with high OPN mRNA level, and with NF-κB activation (p < 0.001 and p = 0.045, respectively). Immunohistochemical staining showed the inverse association; high EGFR protein expression was related with low OPN and NF-κB protein expression (p < 0.001 and p = 0.047, respectively). CONCLUSION: Epidermal growth factor receptor gene is upregulated in CRCC and associated with OPN gene expression and NF-kB signaling. The inverse relation between OPN and EGFR at the protein level could probably reflect dynamic changes that EGFR undergoes following activation (AU)