Revistas
Autores:
Midya, V.; Colicino, E.; Conti, D. V.; et al.
Revista:
JAMA NETWORK OPEN
ISSN:
2574-3805
Año:
2022
Vol.:
5
N°:
7
Págs.:
e2220176
IMPORTANCE Prenatal exposures to endocrine-disrupting chemicals (EDCs) may increase the risk for liver injury in children; however, human evidence is scarce, and previous studies have not considered potential EDC-mixture effects. Furthermore, the association between prenatal EDC exposure and hepatocellular apoptosis in children has not been studied previously. OBJECTIVE To investigate associations of prenatal exposure to EDC mixtures with liver injury risk and hepatocellular apoptosis in childhood. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study used data collected from April 1, 2003, to February 26, 2016, from mother-child pairs from the Human Early-Life Exposome project, a collaborative network of 6 ongoing, population-based prospective birth cohort studies from 6 European countries (France, Greece, Lithuania, Norway, Spain, and the UK). Data were analyzed from April 1, 2021, to January 31, 2022. EXPOSURES Three organochlorine pesticides, 5 polychlorinated biphenyls, 2 polybrominated diphenyl ethers (PBDEs), 3 phenols, 4 parabens, 10 phthalates, 4 organophosphate pesticides, 5 perfluoroalkyl substances, and 9 metals. MAIN OUTCOMES AND MEASURES Child serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), and CK-18 were measured at 6 to 11 years of age. Risk for liver injury was defined as having ALT, AST, and/or GGT levels above the 90th percentile. Associations of liver injury or cytokeratin 18 (CK-18) levels with each chemical group among the 45 EDCs measured in maternal blood or urine samples collected in pregnancy were estimated using 2 complimentary exposure-mixture methods: bayesian weighted quantile sum (BWQS) and bayesian kernel machine regression. RESULTS The study included 1108 mothers (mean [SD] age at birth, 31.0 [4.7] years) and their singleton children (mean [SD] age at liver assessment, 8.2 [1.6] years; 598 [54.0%] boys). Results of the BWQS method indicated increased odds of liver injury per exposure-mixture quartile increase for organochlorine pesticides (odds ratio [OR], 1.44 [95% credible interval (CrI), 1.21-1.71]), PBDEs (OR, 1.57 [95% CrI, 1.34-1.84]), perfluoroalkyl substances (OR, 1.73 [95% CrI, 1.45-2.09]), and metals (OR, 2.21 [95% CrI, 1.65-3.02]). Decreased odds of liver injury were associated with high-molecular-weight phthalates (OR, 0.74 [95% CrI, 0.60-0.91]) and phenols (OR, 0.66 [95% CrI, 0.54-0.78]). Higher CK-18 levels were associated with a 1-quartile increase in polychlorinated biphenyls (beta, 5.84 [95% CrI, 1.69-10.08] IU/L) and PBDEs (beta, 6.46 [95% CrI, 3.09-9.92] IU/L). Bayesian kernel machine regression showed associations in a similar direction as BWQS for all EDCs and a nonlinear association between phenols and CK-18 levels. CONCLUSIONS AND RELEVANCE With a combination of 2 state-of-the-art exposure-mixture approaches, consistent evidence suggests that prenatal exposures to EDCs are associated with higher risk for liver injury and CK-18 levels and constitute a potential risk factor for pediatric nonalcoholic fatty liver disease.
Revista:
ADVANCES IN LABORATORY MEDICINE / AVANCES EN MEDICINA DE LABORATORIO
ISSN:
2628-491X
Año:
2022
Vol.:
3
N°:
4
Págs.:
317 - 318
Revista:
CLINICAL CHEMISTRY AND LABORATORY MEDICINE
ISSN:
1434-6621
Año:
2022
Vol.:
60
N°:
7
Págs.:
1003 - 1010
Objectives Retrospective studies frequently assume analytes long-term stability at ultra-low temperatures. However, these storage conditions, common among biobanks and research, may increase the preanalytical variability, adding a potential uncertainty to the measurements. This study is aimed to evaluate long-term storage stability of different analytes at Methods Twenty-one analytes commonly measured in clinical laboratories were quantified in 60 serum samples. Samples were immediately aliquoted and frozen at <-70 degrees C, and reanalyzed after 11 +/- 3.9 years of storage. A change in concentration after storage was considered relevant if the percent deviation from the baseline measurement was significant and higher than the analytical performance specifications. Results Preanalytical variability (CVP) due to storage, determined by the percentage deviation, showed a noticeable dispersion. Changes were relevant for alanine aminotransferase, creatinine, glucose, magnesium, potassium, sodium, total bilirubin and urate. No significant differences were found in aspartate aminotransferase, calcium, carcinoembryonic antigen, cholesterol, C-reactive protein, direct bilirubin, free thryroxine, gamma-glutamyltransferase, lactate dehydrogenase, prostate-specific antigen, triglycerides, thyrotropin, and urea. As nonnegligible, CVP must remain included in reference change value formula, which was modified to consider whether one or two samples were frozen. Conclusions After long-term storage at ultra-low temperatures, there was a significant variation in some analytes that should be considered. We propose that reference change value formula should include the CVP when analyzing samples stored in these conditions.
Revista:
ONCOIMMUNOLOGY
ISSN:
2162-402X
Año:
2022
Vol.:
11
N°:
1
Págs.:
2070337
The high metabolic activity and insufficient perfusion of tumors leads to the acidification of the tumor microenvironment (TME) that may inhibit the antitumor T cell activity. We found that pharmacological inhibition of the acid loader chloride/bicarbonate anion exchanger 2 (Ae2), with 4,4'-diisothiocyanatostilbene-2,2'-disulfonicacid (DIDS) enhancedCD4(+) andCD8(+) T cell function upon TCR activation in vitro, especially under low pH conditions. In vivo, DIDS administration delayed B16OVA tumor growth in immunocompetent mice as monotherapy or when combined with adoptive T cell transfer of OVA-specificT cells. Notably, genetic Ae2 silencing in OVA-specificT cells improvedCD4(+)/CD8(+) T cell function in vitro as well as their antitumor activity in vivo. Similarly, genetic modification of OVA-specificT cells to overexpress Hvcn1, a selectiveH(+) outward current mediator that prevents cell acidification, significantly improved T cell function in vitro, even at low pH conditions. The adoptive transfer of OVA-specificT cells overexpressing Hvcn1 exerted a better antitumor activity in B16OVA tumor-bearingmice. Hvcn1 overexpression also improved the antitumor activity of CAR T cells specific for Glypican 3 (GPC3) in mice bearing PM299L-GPC3tumors. Our results suggest that preventing intracellular acidification by regulating the expression of acidifier ion channels such as Ae2 or alkalinizer channels like Hvcn1 in tumor-specificlymphocytes enhances their antitumor response by making them more resistant to the acidic TME.
Revista:
TRANSLATIONAL RESEARCH
ISSN:
1931-5244
Año:
2021
Vol.:
233
Págs.:
77 - 91
Lung cancer screening detects early-stage cancers, but also a large number of benign nodules. Molecular markers can help in the lung cancer screening process by refining inclusion criteria or guiding the management of indeterminate pulmonary nodules. In this study, we developed a diagnostic model based on the quantification in plasma of complement-derived fragment C4c, cytokeratin fragment 21-1 (CYFRA 21-1) and C-reactive protein (CRP). The model was first validated in two independent cohorts, and showed a good diagnostic performance across a range of lung tumor types, emphasizing its high specificity and positive predictive value. We next tested its utility in two clinically relevant contexts: assessment of lung cancer risk and nodule malignancy. The scores derived from the model were associated with a significantly higher risk of having lung cancer in asymptomatic individuals enrolled in a computed tomography (CT)-screening program (OR = 1.89; 95% CI = 1.20-2.97). Our model also served to discriminate between benign and malignant pulmonary nodules (AUC: 0.86; 95% CI = 0.80-0.92) with very good specificity (92%). Moreover, the model performed better in combination with clinical factors, and may be used to reclassify patients with intermediate-risk indeterminate pulmonary nodules into patients who require a more aggressive work-up. In conclusion, we propose a new diagnostic biomarker panel that may dictate which incidental or screening-detected pulmonary nodules require a more active work-up. (Translational Research 2021; 233:77-91)
Autores:
Stratakis, N. (Autor de correspondencia); Golden-Mason, L.; Margetaki, K.; et al.
Revista:
HEPATOLOGY
ISSN:
0270-9139
Año:
2021
Vol.:
74
N°:
3
Págs.:
1546 - 1559
Background and Aims Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of liver disease in children. Mercury (Hg), a ubiquitous toxic metal, has been proposed as an environmental factor contributing to toxicant-associated fatty liver disease. Approach and Results We investigated the effect of prenatal exposure to Hg on childhood liver injury by combining epidemiological results from a multicenter mother-child cohort with complementary in vitro experiments on monocyte cells that are known to play a key role in liver immune homeostasis and NAFLD. We used data from 872 mothers and their children (median age, 8.1 years; interquartile range [IQR], 6.5-8.7) from the European Human Early-Life Exposome cohort. We measured Hg concentration in maternal blood during pregnancy (median, 2.0 mu g/L; IQR, 1.1-3.6). We also assessed serum levels of alanine aminotransferase (ALT), a common screening tool for pediatric NAFLD, and plasma concentrations of inflammation-related cytokines in children. We found that prenatal Hg exposure was associated with a phenotype in children that was characterized by elevated ALT (>= 22.1 U/L for females and >= 25.8 U/L for males) and increased concentrations of circulating IL-1 beta, IL-6, IL-8, and TNF-alpha.
Autores:
García, E. (Autor de correspondencia); Stratakis, N.; Valvi, D.; et al.
Revista:
ENVIRONMENTAL EPIDEMIOLOGY
ISSN:
2474-7882
Año:
2021
Vol.:
5
N°:
3
Págs.:
e153
Background: Nonalcoholic fatty liver disease is the most prevalent pediatric chronic liver disease. Experimental studies suggest effects of air pollution and traffic exposure on liver injury. We present the first large-scale human study to evaluate associations of prenatal and childhood air pollution and traffic exposure with liver injury. Methods: Study population included 1,102 children from the Human Early Life Exposome project. Established liver injury biomarkers, including alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and cytokeratin-18, were measured in serum between ages 6-10 years. Air pollutant exposures included nitrogen dioxide, particulate matter <10 <mu>m (PM10), and <2.5 <mu>m. Traffic measures included traffic density on nearest road, traffic load in 100-m buffer, and inverse distance to nearest road. Exposure assignments were made to residential address during pregnancy (prenatal) and residential and school addresses in year preceding follow-up (childhood). Childhood indoor air pollutant exposures were also examined. Generalized additive models were fitted adjusting for confounders. Interactions by sex and overweight/obese status were examined. Results: Prenatal and childhood exposures to air pollution and traffic were not associated with child liver injury biomarkers. There was a significant interaction between prenatal ambient PM10 and overweight/obese status for alanine aminotransferase, with stronger associations among children who were overweight/obese. There was no evidence of interaction with sex. Conclusion: This study found no evidence for associations between prenatal or childhood air pollution or traffic exposure with liver injury biomarkers in children. Findings suggest PM10 associations maybe higher in children who are overweight/obese, consistent with the multiple-hits hypothesis for nonalcoholic fatty liver disease pathogenesis.
Autores:
Pujol, C.; Varo, N; Manero, M. R.; et al.
Revista:
ANALES DEL SISTEMA SANITARIO DE NAVARRA
ISSN:
1137-6627
Año:
2021
Vol.:
44
N°:
2
Págs.:
205 - 214
Background. The aim of this paper is to analyze the role of the biomarkers Interleukin 6, Tumoral Necrosis Factor a, sCD40L, high sensitive Troponin T, high sensitive C-Reactive Protein and Galectin-3 in predicting super response (SR) to Cardiac Resynchronization Therapy (CRT), as they have not been studied in this field before. Methods. Clinical, electrocardiographic and echocardiographic data was obtained preimplant and after one year. SR was defined as reduction in LVESV = 30% at one year follow-up. Blood samples were extracted preimplant. Multivariate logistic regression and ROC curves were performed. Results. 50 patients were included, 23 (46%) were SR. Characteristics related to SR were: female (35 vs. 11%, p = 0.04), suffering from less ischemic cardiomyopathy (13 vs. 63%, p < 0.0001) and lateral (0 vs. 18%, p = 0.03), inferior (4 vs. 33%, p = 0.01) and posterior infarction (0 vs. 22%, p =0.01); absence of mitral regurgitation (47% vs. 22%, p = 0.04), wider QRS width (157.7 +/- 22.9 vs. 140.8 +/- 19.2 ms, p =0.01), higher concentrations of sCD40L (6.9 +/- 5.1 vs. 4.4 +/- 3.3 ng/mL, p= 0.02), and left ventricular lead more frequent in lateral medial position (69 vs. 26%, p = 0.002). QRS width, lateral medial position of the lead and absence of mitral regurgitation were independent predictors of SR. sCD40L showed a moderate direct correlation with SR (r = 0.39, p = 0.02) and with the reduction of LVESV (r = 0.44, p = 0.02). Conclusion. sCD40L correlates significantly with SR to CRT. QRS width, absence of mitral regurgitation and lateral medial position of the lead are independent predictors of SR in this cohort.
Revista:
THE INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (PRINT)
ISSN:
1176-9106
Año:
2020
Vol.:
15
Págs.:
1823 - 1829
Rationale: Emphysema and osteoporosis are tobacco-related diseases. Many studies have shown that emphysema is a strong and independent predictor of low bone mineral density (BMD) in smokers; however, none of them explored its association with different emphysema subtypes.
Objective: To explore the association between the different emphysema subtypes and the presence of low bone mineral density in a population of active or former smokers with and without chronic obstructive pulmonary disease (COPD).
Methods: One hundred and fifty-three active and former smokers from a pulmonary clinic completed clinical questionnaires, pulmonary function tests, a low-dose chest computed tomography (LDCT) and a dual-energy absorptiometry (DXA) scans. Subjects were classified as having normal BMD or low BMD (osteopenia or osteoporosis). Emphysema was classified visually for its subtype and severity. Logistic regression analysis explored the relationship between the different emphysema subtypes and the presence of low BMD adjusting for other important factors.
Results: Seventy-five percent of the patients had low BMD (78 had osteopenia and 37 had osteoporosis). Emphysema was more frequent (66.1 vs 26.3%, p=<0.001) and severe in those with low BMD. Multivariable analysis adjusting for other significant cofactors (age, sex, FEVi, and severity of emphysema) showed that BMI (OR=0.91, 95% CI: 0.76-0.92) and centrilobular emphysema (OR=26.19, 95% CI: 1.71 to 399.44) were associated with low BMD.
Conclusion: Low BMD is highly prevalent in current and former smokers. BMI and centrilobular emphysema are strong and independent predictors of its presence, which suggests that they should be considered when evaluating smokers at risk for low BMD.
Revista:
THE INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (ONLINE)
ISSN:
1178-2005
Año:
2020
Vol.:
15
Págs.:
1823 - 1829
Rationale: Emphysema and osteoporosis are tobacco-related diseases. Many studies have shown that emphysema is a strong and independent predictor of low bone mineral density (BMD) in smokers; however, none of them explored its association with different emphysema subtypes.
Objective: To explore the association between the different emphysema subtypes and the presence of low bone mineral density in a population of active or former smokers with and without chronic obstructive pulmonary disease (COPD).
Methods: One hundred and fifty-three active and former smokers from a pulmonary clinic completed clinical questionnaires, pulmonary function tests, a low-dose chest computed tomography (LDCT) and a dual-energy absorptiometry (DXA) scans. Subjects were classified as having normal BMD or low BMD (osteopenia or osteoporosis). Emphysema was classified visually for its subtype and severity. Logistic regression analysis explored the relationship between the different emphysema subtypes and the presence of low BMD adjusting for other important factors.
Results: Seventy-five percent of the patients had low BMD (78 had osteopenia and 37 had osteoporosis). Emphysema was more frequent (66.1 vs 26.3%, p=<0.001) and severe in those with low BMD. Multivariable analysis adjusting for other significant cofactors (age, sex, FEVi, and severity of emphysema) showed that BMI (OR=0.91, 95% CI: 0.76-0.92) and centrilobular emphysema (OR=26.19, 95% CI: 1.71 to 399.44) were associated with low BMD...
Autores:
Stratakis, N.; Conti, D. V. ; Jin, R.; et al.
Revista:
HEPATOLOGY
ISSN:
0270-9139
Año:
2020
Vol.:
72
N°:
5
Págs.:
1758 - 1770
Background and Aims Per- and polyfluoroalkyl substances (PFAS) are widespread and persistent pollutants that have been shown to have hepatotoxic effects in animal models. However, human evidence is scarce. We evaluated how prenatal exposure to PFAS associates with established serum biomarkers of liver injury and alterations in serum metabolome in children. Approach and Results We used data from 1,105 mothers and their children (median age, 8.2 years; interquartile range, 6.6-9.1) from the European Human Early-Life Exposome cohort (consisting of six existing population-based birth cohorts in France, Greece, Lithuania, Norway, Spain, and the United Kingdom). We measured concentrations of perfluorooctane sulfonate, perfluorooctanoate, perfluorononanoate, perfluorohexane sulfonate, and perfluoroundecanoate in maternal blood. We assessed concentrations of alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase in child serum. Using Bayesian kernel machine regression, we found that higher exposure to PFAS during pregnancy was associated with higher liver enzyme levels in children. We also measured child serum metabolomics through a targeted assay and found significant perturbations in amino acid and glycerophospholipid metabolism associated with prenatal PFAS. A latent variable analysis identified a profile of children at high risk of liver injury (odds ratio, 1.56; 95% confidence interval, 1.21-1.92) that was characterized by high prenatal exposure to P
Revista:
CLINICAL CHEMISTRY AND LABORATORY MEDICINE
ISSN:
1434-6621
Año:
2019
Vol.:
57
N°:
10
Págs.:
1539 - 1545
Background: Exosomes are nanovesicles released by cells that can be detected in blood. Exosomes contain several molecules, such as cytokines that have potential utility as disease biomarkers. The aim of the present work is to compare six different commercial kits suitable for the clinical laboratory in relation to the efficiency and purity of exosome isolation, and their effect in subsequent cytokines analysis. Methods: Serum exosomes were obtained from 10 volunteers using six commercial kits: exoEasy, ExoQuick, Exo-spin, ME kit, ExoQuick Plus and Exo-Flow. Exosome concentrations and size distributions were quantified by nanoparticle tracking analysis. Exosome markers CD63, CD9 and TSG101 were determined by Western blot. ApoB and albumin were measured using nephelometry. S100A9, CXCL5 and CXCL12 were measured using a Luminex assay. Results: The concentration of particles obtained between different kits varied by a factor of 100. There was no correlation in particle concentrations extracted between different kits, except between ExoQuick and Exo-Flow. The highest exosome purity was achieved with ExoQuick Plus and exoEasy, while the lowest were achieved with ME and ExoQuick. Albumin was present in all exosome extracts analyzed and ApoB in all except those extracted with Exo-Flow and ME. Cytokine detection varied depending on the purification kit used and there was no correlation in cytokine concentrations between samples obtained with different kits. Conclusions: Both the sample and the type of commercial kit used affect the efficiency and purity of exosome isolation. In addition, the exosome purification method deeply affects the capability to detect and quantify cytokines.
Revista:
CLINICAL ENDOCRINOLOGY
ISSN:
0300-0664
Año:
2019
Vol.:
91
N°:
3
Págs.:
391 - 399
Context Bone loss is accelerated in the late perimenopause and early menopause. The date of the final menstrual period cannot be stated until 1 year after it has ended, and at that time, most of the rapid bone loss phase will have elapsed. Therefore, early detection of bone loss is crucial. Objectives To evaluate the utility of bone turnover markers (BTM) to identify the women who are more likely to lose more bone mass during the transition to menopause and quantify the loss of bone quality measured by trabecular bone score (TBS). Design, patients and setting Sixty-four healthy premenopausal women, mean age between 44 and 57 years old, were enrolled and followed up for 5 years. Clinical features, lifestyle, bone densitometry, TBS and BTM (CTX, P1NP and osteocalcin) were measured at baseline and follow-up. Results All women had densitometrically normal bone at the time of enrolment. After 5 years, 48.4% had normal bone mineral density, 45.8% low bone mass and 6.3% osteoporosis. Women with osteopenia/osteoporosis at follow-up had higher CTX and P1NP at enrolment compared with women with densitometrically normal bone. The areas under the curve for the prediction of low bone mass or osteoporosis were 0.69 (P = 0.011) for P1NP, 0.69 for CTX (P = 0.013) and 0.77 (P 0.001) for OC. A significant correlation was found between P1NP increase after 5 years and the decrease in lumbar bone density (r = -0.383, P = 0.002). At baseline, 7 (10.9%) women had deteriorated microarchitecture (TBS < 1.3). Three of these women developed osteoporosis and four osteopenia at follow-up. Conclusions Women with higher P1NP and CTX and lower TBS at baseline had lower BMD in the transition to menopause suggesting these novel tools could have potential use in identifying women at high risk of rapidly decreasing bone mass.
Revista:
PLOS ONE
ISSN:
1932-6203
Año:
2019
Vol.:
14
N°:
2
Págs.:
e0209777
BACKGROUND: Smoking is a recognized risk factor for osteoporosis. Trabecular bone score (TBS) is a novel texture parameter to evaluate bone microarchitecture. TBS and their main determinants are unknown in active and former smokers.
OBJECTIVE: To assess TBS in a population of active or former smokers with and without Chronic Obstructive Pulmonary Disease (COPD) and to determine its predictive factors.
METHODS: Active and former smokers from a pulmonary clinic were invited to participate. Clinical features were recorded and bone turnover markers (BTMs) measured. Lung function, low dose chest Computed Tomography scans (LDCT), dual energy absorptiometry (DXA) scans were performed and TBS measured. Logistic regression analysis explored the relationship between measured parameters and TBS.
RESULTS: One hundred and forty five patients were included in the analysis, 97 (67.8%) with COPD. TBS was lower in COPD patients (median 1.323; IQR: 0.13 vs 1.48; IQR: 0.16, p = 0.003). Regression analysis showed that a higher body mass index (BMI), younger age, less number of exacerbations and a higher forced expiratory volume-one second (FEV1%) was associated with better TBS (ß = 0.005, 95% CI:0.000-0.011, p = 0.032; ß = -0.003, 95% CI:-0.007(-)-0.000, p = 0.008; ß = -0.019, 95% CI:-0.034(-)-0.004, p = 0.015; ß = 0.001, 95% CI:0.000-0.002, p = 0.012 respectively). The same factors with similar results were found in COPD patients.
Revista:
ANNALES D ENDOCRINOLOGIE
ISSN:
0003-4266
Año:
2018
Vol.:
79
N°:
2
Págs.:
85 - 86
Revista:
ENDOCRINE PATHOLOGY
ISSN:
1046-3976
Año:
2016
Vol.:
27
N°:
1
Págs.:
50 - 54
The most common cause of organic fasting hypoglycemia in adults is the presence of an insulin-producing pancreatic adenoma, but when high insulin levels are not found, the differential diagnosis is challenging. Misdiagnosis can lead to an unnecessary pancreatectomy. Insulin concentrations may be low in some cases despite a clinical history suggestive of insulinoma. In these cases, a proinsulinoma should be suspected, although the rarity of this condition requires an extensive workup before reaching a final diagnosis. We describe an unusual case of a 38-year-old man with a severe hypoglycemic syndrome due to a proinsulin-secreting pancreatic adenoma. Insulin was measured by the specific assay and suppressed under the lower detection limit during fasting hypoglycemia. Serum proinsulin and C-peptide levels were abnormally elevated, and further tests revealed an islet cell tumor. The tumor was surgically removed, relieving the fasting hypoglycemia. Histopathological study showed a conventional well-differentiated neuroendocrine tumor with high immunoreactivity against proinsulin and with lesser intensity against insulin. Interestingly, GS-9A8 antibody clone used for immunostaining proinsulin did not cross-react with human insulin or C-peptide, providing an unbiased picture of proinsulin secretion. The resolution of symptoms, the fall of proinsulin concentrations after tumor removal and the histopathology study confirmed the diagnosis of proinsulinoma
Autores:
Baz-Davila, R. (Autor de correspondencia); Espinoza-Jimenez, A.; Rodriguez-Perez, M.C.; et al.
Revista:
PLOS ONE
ISSN:
1932-6203
Año:
2016
Vol.:
11
N°:
5
Págs.:
e0154998
Hypoxia is involved in the development of chronic inflammatory processes. Under hypoxic conditions HIF1A, VEGF and VEGFR2 are expressed and mediate the course of the resultant disease. The aim of the present study was to define the associations between tSNPs in these genes and COPD susceptibility and progression in a Spanish cohort. The T alleles in rs3025020 and rs833070 SNPs (VEGFA gene) were less frequent in the group of COPD cases and were associated with a lower risk of developing the disease (OR = 0.60; 95% CI = 0. 39-0.93; p = 0.023 and OR = 0.60; 95% CI = 0.38-0.96; p = 0.034, respectively) under a dominant model of inheritance. The haplotype in which both SNPs presented the T allele confirmed the association found (OR = 0.02; 95% CI = 0.00 to 0.66; p = 0.03). Moreover, patients with COPD carrying the T allele in homozygosis in rs3025020 SNP showed higher lung function values and this association remained constant during 3 years of follow-up. In conclusion, T allele in rs833070 and rs3025020 may confer a protective effect to COPD susceptibility in a Spanish population and the association of the SNP rs3025020 with lung function may be suggesting a role for VEGF in the progression of the disease.
Revista:
INTERNATIONAL JOURNAL OF CARDIOLOGY
ISSN:
0167-5273
Año:
2015
Vol.:
185
Págs.:
177 - 185
BACKGROUND/OBJECTIVES:
The validation of effective screening tools for the identification of patients with subclinical myocardial remodelling is a major clinical need. Thus, we explored the associations of circulating biomarkers of cardiomyocyte injury and stress with subclinical cardiac remodelling and dysfunction, and with biomarkers reflecting collagen turnover.
METHODS:
We randomly recruited 727 subjects from a general population (51.2% women; mean age 51.3 years). Measurements included echocardiographic left atrial (LA) and left ventricular (LV) structure and function, quantification of high sensitivity cardiac Troponin T (hs-cTnT), NT-proBNP, and biomarkers of collagen types I and III turnover.
RESULTS:
In unadjusted and adjusted analyses, the prevalence of LA enlargement (LAE), LV hypertrophy (LVH) and LV diastolic dysfunction (LVDD) increased with higher hs-cTnT (P ¿ 0.031). NT-proBNP was independently associated with LVDD (P=0.009). Both biomarkers combined yielded significant integrated discrimination and net reclassification improvements (P ¿ 0.014 and P ¿ 0.009, respectively) for LAE, LVH and LVDD, over the conventional risk factors, and were independently and positively associated with biomarkers of collagen type I turnover. In a sensitivity analysis, after excluding participants with previous cardiac diseases, our findings remained consistent.
CONCLUSIONS:
Our population-based study suggested that subclinical LV and LA remodelling were associated with hs-cTnT, and that, in combination with NT-proBNP, hs-cTnT showed incremental diagnostic utility over the conventional risk factors. Both biomarkers were associated with biomarkers of collagen type I turnover. Thus, biomarkers of cardiomyocyte microinjury and hemodynamic stress may stimulate fibrosis-related mechanisms and facilitate the diagnosis of subclinical LA and LV remodelling and dysfunction in the general population.
Revista:
THE NEPHRON JOURNALS
ISSN:
1660-8151
Año:
2015
Vol.:
131
N°:
1
Págs.:
51 - 58
We evaluated the effectiveness of oral sodium citrate versus intravenous (IV) sodium bicarbonate for CI-AKI prophylaxis as well as their influence on kidney injury biomarkers. Material and Methods: A randomized, controlled, single-center study including 130 hospitalized patients (62.3% men), who were randomized to receive sodium bicarbonate (1/6 men, 3 ml/kg/h for 1 h; n = 43), oral sodium citrate (75 ml/10 kg divided into 4 doses; n = 43) or nonspecific hydration (n = 44) before contrast administration, was conducted. Serum creatinine and kidney injury biomarkers (cystatin C, neutrophil gelatinase-associated lipocalin, interleukin-8, F2-isoprostanes and cardiotrophin-1 [CT-1]) were assessed. Results: Incidence of CI-AKI was 9.2% with no differences found between hydration groups: 7.0% in sodium bicarbonate group, 11.6% in oral sodium citrate group and 9.1% in the nonspecific hydration group. Urinary creatinine and urinary CT-1/creatinine ratio decreased 4 h after contrast infusion (p < 0.001), but none of the biomarkers assessed were affected by the treatments. Conclusions: There were no differences in hydration with oral sodium citrate and IV sodium bicarbonate for the prophylaxis of CI-AKI. Therefore, oral hydration represents a safe, inexpensive and practical method for preventing CI-AKI in low-risk patients. No effect on biomarkers for kidney injury could be demonstrated.
Revista:
LIVER INTERNATIONAL
ISSN:
1478-3223
Año:
2015
Vol.:
35
N°:
5
Págs.:
1590 - 96
BACKGROUND & AIMS:
Radioembolization may rarely induce liver disease resulting in a syndrome that is similar to veno-occlusive disease complicating bone marrow transplantation where inflammation, endothelial cell activation and thrombosis are likely involved. We hypothesized that similar mechanisms could be implicated in radioembolization-induced liver disease (REILD). Moreover, lobar radioembolization may induce hypertrophy of the non-treated hemiliver most probably by inducing liver regeneration.
METHODS:
In patients with hepatocellular carcinoma, we prospectively studied serum levels of markers of liver regeneration, oxidative stress, pro-inflammatory pathways, endothelial activation and coagulation parameters over 2 months after radioembolization.
RESULTS:
Although REILD did not occur among 14 treated patients, a decrease in effective liver blood flow was observed. Radioembolization was followed by a persistent increase in pro-inflammatory (interleukin 6 and 8) and oxidative stress (malondyaldehide) markers, an induction of endothelial injury markers (vW factor and PAI-1) and an activation of the coagulation cascade (factor VIII, PAI-1, D-Dimer) as well as a significant increase in factors related to liver regeneration (FGF-19 and HGF).
CONCLUSION:
Radioembolization activates liver regeneration, produces oxidative stress, activates inflammatory cytokines and induces endothelial injury with partial activation of the coagulation cascade. These findings may have implicati
Revista:
CLINICAL BIOCHEMISTRY
ISSN:
0009-9120
Año:
2014
Vol.:
47
N°:
18
Págs.:
272-8
This study shows that OPG may potentially be a biomarker for cardiovascular risk/damage in the MS and identifies adipose tissue as a potential source of OPG.
Revista:
JOURNAL OF HYPERTENSION
ISSN:
0263-6352
Año:
2013
Vol.:
31
N°:
3
Págs.:
587 - 594
Objectives: Cardiotrophin-1 (CT-1) induces hypertrophic growth and contractile dysfunction in cardiomyocytes. This cross-sectional study was aimed to analyze CT-1 associations with echocardiographically assessed left ventricular systolic properties taking into account the influence of left ventricular growth [i.e. left ventricular hypertrophy (LVH) and inappropriate left ventricular mass (iLVM)] in asymptomatic hypertensive patients. Methods: Serum CT-1 was measured by ELISA in 278 asymptomatic hypertensive patients with a left ventricular ejection fraction more than 50% and in 25 age and sex-matched normotensive patients. Results: Serum CT-1 was increased in hypertensive patients as compared to normotensive patients. CT-1 was directly correlated with parameters of left ventricular mass (LVM) and inversely correlated with parameters assessing myocardial systolic function and left ventricular chamber contractility in hypertensive patients, these associations being independent of a number of potential confounding factors. Interestingly, the associations of CT-1 with myocardial systolic function were independent of LVM even in patients with LVH or iLVM. In addition, there was a significant increment of serum CT-1 in hypertensive patients with LVH or iLVM, especially in those in whom LVH or iLVM were accompanied by impaired myocardial systolic function, as compared to the remaining hypertensive patients and normotensive patients. Plasma amino-terminal pro-brain natriuretic peptide was not correlated with any of the assessed left ventricular systolic parameters in either group of patients. Conclusion: These findings suggest that serum CT-1 is associated with myocardial systolic dysfunction in asymptomatic hypertensive patients, independently of LVM, even in those patients with pathologic left ventricular growth.
Revista:
JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
ISSN:
0021-972X
Año:
2013
Vol.:
98
N°:
11
Págs.:
E1740 - E1748
Context: Bone turnover markers (BTMs) may identify changes in bone remodeling within a relatively short time interval before changes in bone mineral density can be detected. New markers such as osteoprotegerin, receptor activator of nuclear factor-B ligand, and sclerostin have emerged, but there is little information about their potential use in clinical practice.
Design, Patients, and Setting: We performed an observational prospective study in pre-and postmenopausal ambulatory women (n =72 and n =152, respectively).
Intervention: Postmenopausal women with osteoporosis (n =18) were treated with risedronate and calcium. Womenfilled out a questionnaire and underwent bone mineral density measurement using dual-energy x-ray absorptiometry at the time of enrollment and after 1 year of follow-up. BTMs were measured at baseline, at 6 months, and after 1 year.
Results: Increased levels of N-terminal propeptide of type 1 procollagen (P1NP) and beta-type I collagen telopeptides (CTXs) were associated with low bone mineral density in the premenopausal (P =.02 and P =.04, respectively) and postmenopausal (P =.03 and P =.02) groups. The best analytical performance to diagnose osteoporosis was for = -CTX, osteocalcin, and P1NP, with areas under the curve of 0.70 (P =.005), 0.64 (P =.048), and 0.71 (P =.003). A significant decrease was found in P1NP, osteocalcin, tartrate-resistant acid phosphatase-5b, =-CTX, and bone alkaline phosphatase after 1 year of treatment (all P =.05).
Conclusions: Our data suggest that measurement of beta beta-CTX and P1NP shows adequate analytical performance and could potentially be included in algorithms for the screening of osteoporosis. Furthermore, these two markers, along with osteocalcin and tartrate-resistant acid phosphatase5b, are useful to monitor the response to risedronate.
Autores:
Pinto, Victor; Casanova, Ciro; Müllerova, Hana; et al.
Revista:
RESPIRATORY RESEARCH
ISSN:
1465-993X
Año:
2012
Vol.:
13
N°:
1
Págs.:
71
Background: The relationship between serum biomarkers and clinical expressions of COPD is limited. We planned to further describe this association using markers of inflammation and injury and repair.
Methods: We studied lung function, comorbidities, exercise tolerance, BODE index, and quality of life in 253 COPD patients and recorded mortality over three years. Serum levels of Interleukins 6,8 and 16, tumor necrosis factor alpha (TNF alpha) [inflammatory panel], vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP-9)[injury and repair panel] and pulmonary and activation-regulated chemokine (PARC/CCL-18) and monocyte chemotactic protein 1 (MCP-1/CCL2) [chemoattractant panel] were measured. We related the pattern of the biomarker levels to minimal clinically important differences (MCID) using a novel visualization method [ObServed Clinical Association
Results (OSCAR) plot]. Results: Levels of the inflammatory markers IL-6, TNF alpha were higher and those of injury and repair lower (p < 0.01) with more advanced disease (GOLD 1 vs. 4). Using the OSCAR plot, we found that patients in the highest quartile of inflammatory and lowest quartile of injury and repair biomarkers level were more clinically compromised and had higher mortality (p < 0.05).
Conclusions: In COPD, serum biomarkers of inflammation and repair are distinctly associated with important clinical parameters and survival.
Revista:
Arteriosclerosis, thrombosis and vascular biology (Print)
ISSN:
1079-5642
Año:
2012
Vol.:
32
N°:
6
Págs.:
1477 - 1487
Revista:
JOURNAL OF CLINICAL ULTRASOUND
ISSN:
0091-2751
Año:
2012
Vol.:
40
N°:
8
Págs.:
479 - 485
Background. The assessment of carotid intima-media thickness (CIMT) may improve cardiovascular risk prediction. The optimal protocol for CIMT measurement is unclear. CIMT may be measured in the common carotid artery (CCA), carotid bifurcation (CB), and internal carotid artery (ICA), but measurements from CB and ICA are more difficult to obtain. We studied the influence of body mass index (BMI) and atheroma plaques on the capacity to obtain CIMT measurements at different carotid sites. Methods. Using an automatic system, CIMT was measured in 700 subjects aged 4575, in the near and far walls of CCA, CB, and ICA bilaterally. The presence of atheroma plaques, BMI and vascular risk factors were recorded. Results. CIMT measurements in CCA were possible in all except one subject. It was not possible to obtain CIMT measurements at CB or ICA in 24.1% of normal weight and 58.8% of obese subjects. The likelihood of obtaining CIMT measurement at all carotid sites decreased as the BMI increased. Atheroma plaques in a carotid segment did not preclude CIMT measurement at this site. Conclusions. CIMT measurements in distal carotid segments are more challenging in obese subjects. Measuring CIMT at CCA remains feasible in obese subjects and should be the primary endpoint in these subjects. Nevertheless, CB and ICA measurements, when feasible, would improve risk classification.
Autores:
Lorente, L; Martin, M; Varo, N; et al.
Revista:
Critical care medicine
ISSN:
0090-3493
Año:
2011
Vol.:
15
N°:
2
Págs.:
1 - 8
Revista:
Nutricion Hospitalaria
ISSN:
0212-1611
Año:
2011
Vol.:
26
N°:
1
Págs.:
144 - 151
Revista:
PLoS One
ISSN:
1932-6203
Año:
2011
Vol.:
6
N°:
1
Págs.:
e1602
Autores:
Córdoba, Elizabeth; Baz, Rebeca; De Torres, Juan P; et al.
Revista:
B M C Medical Genetics-(BioMed Central Ltd.)
ISSN:
1471-2350
Año:
2011
Vol.:
12
Págs.:
132
Revista:
American journal of physiology: endocrinology and metabolism
ISSN:
0193-1849
Año:
2010
Vol.:
298
N°:
5
Págs.:
1072 - 1077
Autores:
Missiou, A; Wolf, D; Platzer, I; et al.
Revista:
Thrombosis and haemostasis
ISSN:
0340-6245
Año:
2010
Vol.:
103
N°:
4
Págs.:
788 - 796
Revista:
JOURNAL OF HYPERTENSION
ISSN:
0263-6352
Año:
2010
Vol.:
28
N°:
11
Págs.:
2219 - 2226
Autores:
Missiou, A; Rudolf, P; Stachon, P; et al.
Revista:
Circulation Research
ISSN:
0009-7330
Año:
2010
Vol.:
107
N°:
6
Págs.:
757 - 766
Autores:
Stachon, P; Missiou, A; Walter, C; et al.
Revista:
PLoS One
ISSN:
1932-6203
Año:
2010
Vol.:
5
N°:
7
Págs.:
e11589
Autores:
Missiou, A; Köstlin, K; Varo, N; et al.
Revista:
Circulation
ISSN:
0009-7322
Año:
2010
Vol.:
121
N°:
18
Págs.:
2033 - 2044
Nacionales y Regionales
Título:
Caracterización de PRDM1 como diana terapéutica para la obesidad y la diabetes: desde el desarrollo de adipocitos hasta la regulación nutricional/farmacológica.
Código de expediente:
PID2019-106982RB-I00
Financiador:
MINISTERIO DE CIENCIA E INNOVACIÓN
Convocatoria:
2019 AEI PROYECTOS I+D+i (incluye Generación del conocimiento y Retos investigación)
Fecha de inicio:
01/06/2020
Fecha fin:
31/05/2024
Importe concedido:
181.500,00€
Otros fondos:
Fondos FEDER
Título:
Estudio genómico para la personalización del diagnóstico y el tratamiento de los pacientes con insuficiencia cardiaca crónica y enfermedad renal crónica (Medicina cardIoreNal pERsonalizada en NaVArra) (MINERVA)
Código de expediente:
0011-1411-2018-000036
Investigador principal:
Juan José Gavira Gómez
Financiador:
GOBIERNO DE NAVARRA
Convocatoria:
2018 GN PROYECTOS ESTRATEGICOS DE I+D 2018-2020
Fecha de inicio:
01/04/2018
Fecha fin:
30/11/2020
Importe concedido:
97.237,60€
Otros fondos:
-
Título:
Caracterización del estrés oxidativo vascular en la fisiopatología de la diabetes: NADPH oxidasa 5 como potencial diana terapéutica
Código de expediente:
PI22/01450
Investigador principal:
Guillermo Zalba Goñi
Financiador:
INSTITUTO DE SALUD CARLOS III
Convocatoria:
2022 AES Proyectos de investigación
Fecha de inicio:
01/01/2023
Fecha fin:
31/12/2025
Importe concedido:
183.920,00€
Otros fondos:
Fondos FEDER
Título:
Papel de la MMP-10 y la perfusión tisular en el diagnóstico y seguimiento de la nefropatía y patología cardiovascular de pacientes con diabetes mellitus tipo 2.
Código de expediente:
PI20/01678
Investigador principal:
Nuria García Fernández
Financiador:
INSTITUTO DE SALUD CARLOS III
Convocatoria:
2020 AES Proyectos de investigación
Fecha de inicio:
01/01/2021
Fecha fin:
31/12/2023
Importe concedido:
102.608,00€
Otros fondos:
Fondos FEDER
Título:
Estudio clínico y experimental del papel de la MMP-10 en la nefropatía diabética tipo 2
Código de expediente:
PI15/02111
Investigador principal:
Nuria García Fernández
Financiador:
INSTITUTO DE SALUD CARLOS III
Convocatoria:
2015 AES PROYECTOS DE INVESTIGACIÓN
Fecha de inicio:
01/01/2016
Fecha fin:
30/11/2020
Importe concedido:
116.765,00€
Otros fondos:
Fondos FEDER
Título:
Estudio de exosomas tumorales como inductores de células mieloides supresoras y mensajeros transportadores de moléculas inmunosupresoras.
Código de expediente:
PI14/00274
Investigador principal:
Álvaro González Hernández
Financiador:
INSTITUTO DE SALUD CARLOS III
Convocatoria:
2014 ISCIII Proyectos de I+D
Fecha de inicio:
01/01/2015
Fecha fin:
31/12/2018
Importe concedido:
55.055,00€
Otros fondos:
-