Anabel García-heredia - Academia.edu (original) (raw)

Papers by Anabel García-heredia

Research paper thumbnail of Adherence to Mediterranean diet and its association with multiple colonic polyps of unknown origin: a case-control study

Frontiers in Nutrition, Jun 22, 2023

Introduction: Multiple colonic polyps do not have a genetic origin in most patients, and the caus... more Introduction: Multiple colonic polyps do not have a genetic origin in most patients, and the cause of this phenotype remains elusive. Environmental factors, such as diet, could be related to this phenotype. Our aim was to investigate the relationship between the adherence to Mediterranean diet and multiple colonic polyps of unknown origin. Methods: A case-control pilot study was carried out with a sample of 38 individuals, including 23 cases with more than 10 adenomatous or serrated polyps from the national multicenter project EPIPOLIP and 15 healthy controls with normal colonoscopy. A validated Spanish version of the MEDAS questionnaire was administered to cases and controls. Results: Adherence to Mediterranean diet was higher in controls than in patients with multiple colonic polyps (MEDAS score: 8.6 ± 1.4 vs. 7.0 ± 1.6; p = 0.01). Optimal overall adherence to the Mediterranean diet pattern was significantly higher among the controls than among cases (MEDAS score >9: 46% vs. 13%; OR 0.17; 95% CI 0.03-0.83). Non-optimal adherence to the Mediterranean diet acts as a risk factor for developing colorectal cancer derived from colorectal polyps. Conclusion: Our results suggest that environmental factors play a role in the pathogenesis of this phenotype.

Research paper thumbnail of Paraoxonases and infectious diseases

Clinical Biochemistry, Sep 1, 2017

Research paper thumbnail of The Role of chemokine (C-C motif) ligand 2 and the diet influence in the energy metabolism

Journal of Hepatology, 2017

Research paper thumbnail of A novel non-invasive colorectal cancer diagnostic method: Volatile organic compounds as biomarkers

Research paper thumbnail of Lynch-like Syndrome: Potential Mechanisms and Management

Cancers, 2022

Lynch syndrome is an autosomal dominant disorder caused by germline mutations in DNA mismatch rep... more Lynch syndrome is an autosomal dominant disorder caused by germline mutations in DNA mismatch repair (MMR) system genes, such as MLH1, MSH2, MSH6, or PMS2. It is the most common hereditary colorectal cancer syndrome. Screening is regularly performed by using microsatellite instability (MSI) or immunohistochemistry for the MMR proteins in tumor samples. However, in a proportion of cases, MSI is found or MMR immunohistochemistry is impaired in the absence of a germline mutation in MMR genes, BRAF mutation, or MLH1 hypermethylation. These cases are defined as Lynch-like syndrome. Patients with Lynch-like syndrome represent a mixture of truly hereditary and sporadic cases, with a risk of colorectal cancer in first-degree relatives that is between the risk of Lynch syndrome in families and relatives of sporadic colon cancer cases. Although multiple approaches have been suggested to distinguish between hereditary and sporadic cases, a homogeneous testing protocol and consensus on the adeq...

Research paper thumbnail of Research Article Ubiquitous Transgenic Overexpression of C-C Chemokine Ligand 2: A Model to Assess the Combined Effect of High Energy Intake and Continuous Low-Grade Inflammation

Copyright © 2013 Esther Rodŕıguez-Gallego et al. This is an open access article distributed unde... more Copyright © 2013 Esther Rodŕıguez-Gallego et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Excessive energymanagement leads to low-grade, chronic inflammation, which is a significant factor predicting noncommunicable diseases. In turn, inflammation, oxidation, and metabolism are associated with the course of these diseases; mitochondrial dysfunction seems to be at the crossroads of mutual relationships.Themigration of immune cells during inflammation is governed

Research paper thumbnail of Role of α-ketoglutarate and β-hydroxybutyrate in morbid obesity-associated non-alcoholic fatty liver disease: metabolomic approach

Journal of Hepatology, 2017

Research paper thumbnail of Phenol-enriched olive oils modify paraoxonase-related variables: A randomized, crossover, controlled trial

Molecular nutrition & food research, Oct 25, 2017

Low paraoxonase (PON)1 activities, and high PON1 and low PON3 protein levels are characteristic o... more Low paraoxonase (PON)1 activities, and high PON1 and low PON3 protein levels are characteristic of cardiovascular disease. Our aim was to assess short- and long-term effects of virgin olive oils (VOO), enriched with their own phenolic compounds (PC; FVOO) or with them plus complementary PC from thyme (FVOOT), on PON-related variables and the mechanisms involved. Two randomized, controlled, double-blind, and crossover interventions were conducted. In an acute intake study, participants ingested three FVOOs differing in PC content. In a sustained intake study, participants ingested a control VOO and two different FVOOs with the same PC content but differing in PC source. Acute and sustained intake of VOO and FVOO decreased PON1 protein and increased PON1-associated specific activities, while FVOOT yielded opposite results. PON3 protein levels increased only after sustained consumption of VOO. Mechanistic studies performed in rat livers showed that intake of isolated PC from VOO and fr...

Research paper thumbnail of Preliminary study on serum paraoxonase-1 status and chemokine (C-C motif) ligand 2 in hospitalized elderly patients with catheter-associated asymptomatic bacteriuria

European Journal of Clinical Microbiology & Infectious Diseases, 2016

Urinary tract infections (UTI) are common among elderly patients in residential care facilities, ... more Urinary tract infections (UTI) are common among elderly patients in residential care facilities, as well as in the hospital setting. Identifying new biochemical markers of UTI is an active line of research since UTI management is resource intensive. Paraoxonase-1 (PON1) forms part of the patient's immune system, the response-to-injury and inflammation. Our study sought to evaluate alterations in inflammation-related paraoxonase-1 (PON1) and chemokine (C-C motif) ligand 2 (CCL2) in patients with an indwelling catheter to assess their potential usefulness as biomarkers of infection. Patients (n = 142) who had had the urinary catheter removed and 100 healthy volunteers were recruited. In all participants we measured serum PON1 activity, PON1 concentration, CCL2, procalcitonin and C-reactive protein (CRP). Results indicated that patients had higher CCL2, CRP and procalcitonin concentrations than the control group, and lower paraoxonase activity. There were no significant differences in PON1 concentrations. When comparing the diagnostic accuracy of CRP, procalcitonin, CCL2 and the PON1-related variables in discriminating between patients with and those without UTI, we found a considerable degree of overlap between groups, i.e., a low diagnostic accuracy. However, there were significant inverse logarithmic correlations between serum paraoxonase activity and the number of days the urinary catheter had been in situ. Our results suggest that measurement of these biochemical variables may be useful in investigating complications of long-term use of these devices and help to improve the economic and clinical investment required in the management of the often-associated infection.

Research paper thumbnail of Erratum to: Preliminary study on serum paraoxonase-1 status and chemokine (C-C motif) ligand 2 in hospitalized elderly patients with catheter-associated asymptomatic bacteriuria

European Journal of Clinical Microbiology & Infectious Diseases, 2016

Research paper thumbnail of Biochemical indices of oxidative stress and inflammation in the evaluation of peripheral artery disease

Free Radical Biology and Medicine, 2016

Background: The aims of this study were: (1) to investigate changes in indices of oxidative stres... more Background: The aims of this study were: (1) to investigate changes in indices of oxidative stress and inflammation in the evaluation of peripheral artery disease (PAD); (2) to compare the diagnostic efficacy of these parameters with that of classical clinical laboratory routine parameters. Design and methods: We studied 115 patients with PAD and 300 healthy volunteers. Results: PAD patients had significantly increased circulating concentrations of F 2-isoprostanes, protein carbonyls, chemokine (C-C motif) ligand 2 (CCL2), high-sensitivity C-reactive protein (hs-CRP), β-2-microglobulin (B2M), and decreased paraoxonase-1 (PON1) levels. When patients were classified according to the Fontaine score, we observed important increases in plasma F 2-isoprostanes and CCL2 that appeared in milder stages of the disease, and remained so at similar levels in more advanced stages; almost no overlapping with the control group was noted. Receiver operating characteristics analysis comparing patients and controls revealed that the areas under the curve for F 2-isoprostanes and CCL2 approached unity [0.999 (0.998-1.000) and 0.993 (0.985-1.000)], respectively, and significantly higher to those of the other measured parameters. Conclusion: Our data suggest that F 2-isoprostanes and CCL2 measurements may be useful tools for the diagnosis of PAD.

Research paper thumbnail of Paraoxonases, mitochondrial dysfunction and non-communicable diseases

Chemico-Biological Interactions, 2016

The most common non-communicable diseases (NCD) are obesity, cardiovascular disease, diabetes, ca... more The most common non-communicable diseases (NCD) are obesity, cardiovascular disease, diabetes, cancer, chronic respiratory diseases, and neurological diseases. Together, they constitute the commonest cause of death and disability worldwide. Mitochondrial alterations, oxidative stress and inflammation underpin NCD and are molecular mechanisms playing major roles in the disease onset and natural history. Interrelations between the mechanisms of oxidative stress, inflammation and metabolism are, in the broadest sense of energy transformations, being increasingly recognized as part of the problem in NCD. Whether or not oxidative stress and inflammation are the causes or the consequences of cellular disturbances, they do significantly contribute to NCD. Paraoxonases are associated with mitochondria and mitochondria-associated membranes. They modulate mitochondria-dependent superoxide production, and prevent apoptosis. Their overexpression protects mitochondria from endoplasmic reticulum stress and subsequent mitochondrial dysfunction; highlighting that the anti-inflammatory effects of paraoxonases may be mediated, at least in part, by their protective role in mitochondria and associated organelle function. Since oxidative stress is implicated in the development of NCD (as a result of mitochondrial dysfunction), these data suggest that understanding the role and the molecular targets of paraoxonases may provide novel strategies of intervention in the treatment of these important diseases.

Research paper thumbnail of Metformin administration induces hepatotoxic effects in paraoxonase-1-deficient mice

Chemico-Biological Interactions, 2016

Metformin is the first-line pharmacological treatment of diabetes. In these patients, metformin r... more Metformin is the first-line pharmacological treatment of diabetes. In these patients, metformin reduces body weight and decreases the risk of diabetes-related complications such as cardiovascular disease. However, whether metformin elicits beneficial effects on liver histology is a controversial issue and, as yet, there is no consensus. Paraoxonase-1 (PON1), an enzyme synthesized mainly by the liver, degrades lipid peroxides and reduces oxidative stress. PON1 activities are decreased in chronic liver diseases. We evaluated the effects of metformin in the liver of PON1-deficient mice which, untreated, present a mild degree of liver steatosis. Metformin administration aggravated inflammation in animals given a standard mouse chow and in those fed a high-fat diet. Also, it was associated with a higher degree of steatosis in animals fed a standard chow diet. This report is a cautionary note regarding the prescription of metformin for the treatment of diabetes in patients with concomitant liver impairment.

Research paper thumbnail of Paraoxonase-1 Activity and Concentration After Radiation Therapy Treatment in Patients With Breast Cancer: Can Be a Useful Marker to Predict the Radiation Therapy Toxicity and Breast Cancer Prognosis?

International Journal of Radiation Oncology*Biology*Physics, 2015

Sixty-eight patients were identified as having radiation therapy fields within the region of the ... more Sixty-eight patients were identified as having radiation therapy fields within the region of the thoracolumbar spinal cord, defined as extending inferiorly down to L2. Pathological diagnosis for patients in this review included chordoma (29 patients, 42.7%), chondrosarcoma (25 patients, 36.8%), osteosarcoma (2 patients, 2.9%), other sarcoma (10 patients, 14.7%), and other (2 patients, 2.1%). Patient data was reviewed retrospectively. Composite plans and DVH were constructed for both pre-operative and post-operative radiation therapy courses in MIM-Vista software, as available. Dose constraints to the center and surface of the cord were 5400 cGy (RBE), and 6300 cGy (RBE) respectively; patients receiving concurrent chemotherapy had the radiation dose reduced by 8%. Spinal cord toxicity was recorded using the RTOG/EORTC late effects scoring system Results: Clinical and dosimetric data for each patient were analyzed. Median prescription dose to the tumor bed was 7020 cGy (RBE), (range, 5940-7820 cGy (RBE)) in conventional fractionation. For all patients, median follow-up all patients was 12.9 months (range, 0-116 months). Forty patients had follow-up available after the completion of treatment, for which median-follow-up was 49.6 months, (range, 1.5-116 months). Five-year overall survival for all patients in this group was 86.9% (95%CI 68.4 e 94.9). No grade 2 or higher toxicities to the spinal cord attributed to radiation therapy were noted. Reasons for spinal cord toxicity following treatment included: local disease progression, noted in 5 patients (10.9%), and direct surgical complications, noted in 4 patients (8.7%). 5 years life without neurological injury is 92.7% (95%CI: 78.8-97.6). Conclusion: Our clinical and dosimetric data suggest that the noted dose constraints are safe and acceptable with regard to spinal cord complications. Pre-existing disease characteristics, surgical complications, as well as tumor progression, appear to be greater factors when it comes to spinal cord toxicity.

Research paper thumbnail of PPARS in regulation of paraoxonases

Research paper thumbnail of PPARs in Regulation of Paraoxonases: Control of Oxidative Stress and Inflammation Pathways

PPAR Research, 2012

The paraoxonase (PON) group of enzymes, composed of PON1, PON2, and PON3, play an important role ... more The paraoxonase (PON) group of enzymes, composed of PON1, PON2, and PON3, play an important role in decreasing oxidative stress by degrading lipid peroxides. PON1 synthesis is upregulated by PPAR. Several pharmacological compounds (acting as antioxidants and, hence, atheroprotective) stimulate both PPAR activity and PON1 expression. Recent evidence suggests that PON1 and the monocyte chemoattractant protein-1 (MCP-1) are involved in coordinating the inflammatory response in damaged tissues; PPAR may be central in the regulation of these biochemical pathways. This article reviews the state of knowledge on PON1 biochemistry and function, the influence of genetic variation, and the regulation of PON1 expression by pharmaceutical compounds that increase PPAR activity. We also describe recent lines of evidence suggesting links between PON1 and MCP-1 and how their production may be regulated by PPAR.

Research paper thumbnail of The Level of DING Proteins Is Increased in HIV-Infected Patients: In Vitro and In Vivo Studies

PLoS ONE, 2012

DING proteins constitute an interesting family, owing to their intriguing and important activitie... more DING proteins constitute an interesting family, owing to their intriguing and important activities. However, after a decade of research, little is known about these proteins. In humans, at least five different DING proteins have been identified, which were implicated in important biological processes and diseases, including HIV. Indeed, recent data from different research groups have highlighted the anti-HIV activity of some DING representatives. These proteins share the ability to inhibit the transcriptional step of HIV-1, a key step of the viral cycle that is not yet targeted by the current therapies. Since such proteins have been isolated from humans, we undertook a comprehensive study that focuses on the relationship between these proteins and HIV-infection in an infectious context. Hence, we developed a home-made ELISA for the quantification of the concentration of DING proteins in human serum. Using this method, we were able to determine the concentration of DING proteins in healthy and HIV-infected patients. Interestingly, we observed a significant increase of the concentration of DING proteins in non treated and treated HIV-infected patients compared to controls. In addition, cell cultures infected with HIV also show an increased expression of DING proteins, ruling out the possible role of antiretroviral treatment in the increase of the expression of DING proteins. In conclusion, results from this study show that the organism reacts to HIVinfection by an overexpression of DING proteins.

Research paper thumbnail of Ubiquitous Transgenic Overexpression of C-C Chemokine Ligand 2: A Model to Assess the Combined Effect of High Energy Intake and Continuous Low-Grade Inflammation

Mediators of Inflammation, 2013

Excessive energy management leads to low-grade, chronic inflammation, which is a significant fact... more Excessive energy management leads to low-grade, chronic inflammation, which is a significant factor predicting noncommunicable diseases. In turn, inflammation, oxidation, and metabolism are associated with the course of these diseases; mitochondrial dysfunction seems to be at the crossroads of mutual relationships. The migration of immune cells during inflammation is governed by the interaction between chemokines and chemokine receptors. Chemokines, especially C-C-chemokine ligand 2 (CCL2), have a variety of additional functions that are involved in the maintenance of normal metabolism. It is our hypothesis that a ubiquitous and continuous secretion of CCL2 may represent an animal model of low-grade chronic inflammation that, in the presence of an energy surplus, could help to ascertain the afore-mentioned relationships and/or to search for specific therapeutic approaches. Here, we present preliminary data on a mouse model created by using targeted gene knock-in technology to integr...

Research paper thumbnail of Paraoxonase-1 Inhibits Oxidized Low-Density Lipoprotein-Induced Metabolic Alterations and Apoptosis in Endothelial Cells: A Nondirected Metabolomic Study

Mediators of Inflammation, 2013

We studied the influence of PON1 on metabolic alterations induced by oxidized LDL when incubated ... more We studied the influence of PON1 on metabolic alterations induced by oxidized LDL when incubated with endothelial cells. HUVEC cells were incubated with native LDL, oxidized LDL, oxidized LDL plus HDL from wild type mice, and oxidized LDL plus HDL from PON1-deficient mice. Results showed alterations in carbohydrate and phospholipid metabolism and increased apoptosis in cells incubated with oxidized LDL. These changes were partially prevented by wild type mouse HDL, but the effects were less effective with HDL from PON1-deficient mice. Our results suggest that PON1 may play a significant role in endothelial cell survival by protecting cells from alterations in the respiratory chain induced by oxidized LDL. These results extend current knowledge on the protective role of HDL and PON1 against oxidation and apoptosis in endothelial cells.

Research paper thumbnail of Rosiglitazone and Fenofibrate Exacerbate Liver Steatosis in a Mouse Model of Obesity and Hyperlipidemia. A Transcriptomic and Metabolomic Study

Journal of Proteome Research, 2014

Peroxisome proliferator-activated receptors (PPAR) play an important role in the regulation of li... more Peroxisome proliferator-activated receptors (PPAR) play an important role in the regulation of lipid and glucose metabolism, inflammatory, and vascular responses. We show the effect of treatment with two PPAR agonists, fenofibrate (FF) and rosiglitazone (RSG), on ob/ob and LDLR-double deficient mice, by combined gene-expression and metabolomic analyses. Male mice were daily treated for 12 weeks with RSG (10 mg·kg(1-)·day(-1) per os (p.o.), n = 8) and FF (50 mg·kg(1-)·day(-1) p.o., n = 8). Twelve untreated ob/ob and LDLR-double deficient mice were used as controls. To integrate the transcriptomic and metabolomic results, we designed a hierarchical algorithm, based on the average linkage method in clustering. Data were also interpreted with the Ingenuity Pathway Analysis program. FF and RSG treatments significantly increased the hepatic triglyceride content in the liver when compared with the control group, and the treatments induced an increase in the number and size of hepatic lipid droplets. Both drugs simultaneously activate pro-steatotic and antisteatotic metabolic pathways with a well-ordered result of aggravation of the hepatic lipid accumulation. The present study is a cautionary note not only to researchers on the basic mechanism of the action of PPAR activators but also to the use of these compounds in clinical practice.

Research paper thumbnail of Adherence to Mediterranean diet and its association with multiple colonic polyps of unknown origin: a case-control study

Frontiers in Nutrition, Jun 22, 2023

Introduction: Multiple colonic polyps do not have a genetic origin in most patients, and the caus... more Introduction: Multiple colonic polyps do not have a genetic origin in most patients, and the cause of this phenotype remains elusive. Environmental factors, such as diet, could be related to this phenotype. Our aim was to investigate the relationship between the adherence to Mediterranean diet and multiple colonic polyps of unknown origin. Methods: A case-control pilot study was carried out with a sample of 38 individuals, including 23 cases with more than 10 adenomatous or serrated polyps from the national multicenter project EPIPOLIP and 15 healthy controls with normal colonoscopy. A validated Spanish version of the MEDAS questionnaire was administered to cases and controls. Results: Adherence to Mediterranean diet was higher in controls than in patients with multiple colonic polyps (MEDAS score: 8.6 ± 1.4 vs. 7.0 ± 1.6; p = 0.01). Optimal overall adherence to the Mediterranean diet pattern was significantly higher among the controls than among cases (MEDAS score >9: 46% vs. 13%; OR 0.17; 95% CI 0.03-0.83). Non-optimal adherence to the Mediterranean diet acts as a risk factor for developing colorectal cancer derived from colorectal polyps. Conclusion: Our results suggest that environmental factors play a role in the pathogenesis of this phenotype.

Research paper thumbnail of Paraoxonases and infectious diseases

Clinical Biochemistry, Sep 1, 2017

Research paper thumbnail of The Role of chemokine (C-C motif) ligand 2 and the diet influence in the energy metabolism

Journal of Hepatology, 2017

Research paper thumbnail of A novel non-invasive colorectal cancer diagnostic method: Volatile organic compounds as biomarkers

Research paper thumbnail of Lynch-like Syndrome: Potential Mechanisms and Management

Cancers, 2022

Lynch syndrome is an autosomal dominant disorder caused by germline mutations in DNA mismatch rep... more Lynch syndrome is an autosomal dominant disorder caused by germline mutations in DNA mismatch repair (MMR) system genes, such as MLH1, MSH2, MSH6, or PMS2. It is the most common hereditary colorectal cancer syndrome. Screening is regularly performed by using microsatellite instability (MSI) or immunohistochemistry for the MMR proteins in tumor samples. However, in a proportion of cases, MSI is found or MMR immunohistochemistry is impaired in the absence of a germline mutation in MMR genes, BRAF mutation, or MLH1 hypermethylation. These cases are defined as Lynch-like syndrome. Patients with Lynch-like syndrome represent a mixture of truly hereditary and sporadic cases, with a risk of colorectal cancer in first-degree relatives that is between the risk of Lynch syndrome in families and relatives of sporadic colon cancer cases. Although multiple approaches have been suggested to distinguish between hereditary and sporadic cases, a homogeneous testing protocol and consensus on the adeq...

Research paper thumbnail of Research Article Ubiquitous Transgenic Overexpression of C-C Chemokine Ligand 2: A Model to Assess the Combined Effect of High Energy Intake and Continuous Low-Grade Inflammation

Copyright © 2013 Esther Rodŕıguez-Gallego et al. This is an open access article distributed unde... more Copyright © 2013 Esther Rodŕıguez-Gallego et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Excessive energymanagement leads to low-grade, chronic inflammation, which is a significant factor predicting noncommunicable diseases. In turn, inflammation, oxidation, and metabolism are associated with the course of these diseases; mitochondrial dysfunction seems to be at the crossroads of mutual relationships.Themigration of immune cells during inflammation is governed

Research paper thumbnail of Role of α-ketoglutarate and β-hydroxybutyrate in morbid obesity-associated non-alcoholic fatty liver disease: metabolomic approach

Journal of Hepatology, 2017

Research paper thumbnail of Phenol-enriched olive oils modify paraoxonase-related variables: A randomized, crossover, controlled trial

Molecular nutrition & food research, Oct 25, 2017

Low paraoxonase (PON)1 activities, and high PON1 and low PON3 protein levels are characteristic o... more Low paraoxonase (PON)1 activities, and high PON1 and low PON3 protein levels are characteristic of cardiovascular disease. Our aim was to assess short- and long-term effects of virgin olive oils (VOO), enriched with their own phenolic compounds (PC; FVOO) or with them plus complementary PC from thyme (FVOOT), on PON-related variables and the mechanisms involved. Two randomized, controlled, double-blind, and crossover interventions were conducted. In an acute intake study, participants ingested three FVOOs differing in PC content. In a sustained intake study, participants ingested a control VOO and two different FVOOs with the same PC content but differing in PC source. Acute and sustained intake of VOO and FVOO decreased PON1 protein and increased PON1-associated specific activities, while FVOOT yielded opposite results. PON3 protein levels increased only after sustained consumption of VOO. Mechanistic studies performed in rat livers showed that intake of isolated PC from VOO and fr...

Research paper thumbnail of Preliminary study on serum paraoxonase-1 status and chemokine (C-C motif) ligand 2 in hospitalized elderly patients with catheter-associated asymptomatic bacteriuria

European Journal of Clinical Microbiology & Infectious Diseases, 2016

Urinary tract infections (UTI) are common among elderly patients in residential care facilities, ... more Urinary tract infections (UTI) are common among elderly patients in residential care facilities, as well as in the hospital setting. Identifying new biochemical markers of UTI is an active line of research since UTI management is resource intensive. Paraoxonase-1 (PON1) forms part of the patient's immune system, the response-to-injury and inflammation. Our study sought to evaluate alterations in inflammation-related paraoxonase-1 (PON1) and chemokine (C-C motif) ligand 2 (CCL2) in patients with an indwelling catheter to assess their potential usefulness as biomarkers of infection. Patients (n = 142) who had had the urinary catheter removed and 100 healthy volunteers were recruited. In all participants we measured serum PON1 activity, PON1 concentration, CCL2, procalcitonin and C-reactive protein (CRP). Results indicated that patients had higher CCL2, CRP and procalcitonin concentrations than the control group, and lower paraoxonase activity. There were no significant differences in PON1 concentrations. When comparing the diagnostic accuracy of CRP, procalcitonin, CCL2 and the PON1-related variables in discriminating between patients with and those without UTI, we found a considerable degree of overlap between groups, i.e., a low diagnostic accuracy. However, there were significant inverse logarithmic correlations between serum paraoxonase activity and the number of days the urinary catheter had been in situ. Our results suggest that measurement of these biochemical variables may be useful in investigating complications of long-term use of these devices and help to improve the economic and clinical investment required in the management of the often-associated infection.

Research paper thumbnail of Erratum to: Preliminary study on serum paraoxonase-1 status and chemokine (C-C motif) ligand 2 in hospitalized elderly patients with catheter-associated asymptomatic bacteriuria

European Journal of Clinical Microbiology & Infectious Diseases, 2016

Research paper thumbnail of Biochemical indices of oxidative stress and inflammation in the evaluation of peripheral artery disease

Free Radical Biology and Medicine, 2016

Background: The aims of this study were: (1) to investigate changes in indices of oxidative stres... more Background: The aims of this study were: (1) to investigate changes in indices of oxidative stress and inflammation in the evaluation of peripheral artery disease (PAD); (2) to compare the diagnostic efficacy of these parameters with that of classical clinical laboratory routine parameters. Design and methods: We studied 115 patients with PAD and 300 healthy volunteers. Results: PAD patients had significantly increased circulating concentrations of F 2-isoprostanes, protein carbonyls, chemokine (C-C motif) ligand 2 (CCL2), high-sensitivity C-reactive protein (hs-CRP), β-2-microglobulin (B2M), and decreased paraoxonase-1 (PON1) levels. When patients were classified according to the Fontaine score, we observed important increases in plasma F 2-isoprostanes and CCL2 that appeared in milder stages of the disease, and remained so at similar levels in more advanced stages; almost no overlapping with the control group was noted. Receiver operating characteristics analysis comparing patients and controls revealed that the areas under the curve for F 2-isoprostanes and CCL2 approached unity [0.999 (0.998-1.000) and 0.993 (0.985-1.000)], respectively, and significantly higher to those of the other measured parameters. Conclusion: Our data suggest that F 2-isoprostanes and CCL2 measurements may be useful tools for the diagnosis of PAD.

Research paper thumbnail of Paraoxonases, mitochondrial dysfunction and non-communicable diseases

Chemico-Biological Interactions, 2016

The most common non-communicable diseases (NCD) are obesity, cardiovascular disease, diabetes, ca... more The most common non-communicable diseases (NCD) are obesity, cardiovascular disease, diabetes, cancer, chronic respiratory diseases, and neurological diseases. Together, they constitute the commonest cause of death and disability worldwide. Mitochondrial alterations, oxidative stress and inflammation underpin NCD and are molecular mechanisms playing major roles in the disease onset and natural history. Interrelations between the mechanisms of oxidative stress, inflammation and metabolism are, in the broadest sense of energy transformations, being increasingly recognized as part of the problem in NCD. Whether or not oxidative stress and inflammation are the causes or the consequences of cellular disturbances, they do significantly contribute to NCD. Paraoxonases are associated with mitochondria and mitochondria-associated membranes. They modulate mitochondria-dependent superoxide production, and prevent apoptosis. Their overexpression protects mitochondria from endoplasmic reticulum stress and subsequent mitochondrial dysfunction; highlighting that the anti-inflammatory effects of paraoxonases may be mediated, at least in part, by their protective role in mitochondria and associated organelle function. Since oxidative stress is implicated in the development of NCD (as a result of mitochondrial dysfunction), these data suggest that understanding the role and the molecular targets of paraoxonases may provide novel strategies of intervention in the treatment of these important diseases.

Research paper thumbnail of Metformin administration induces hepatotoxic effects in paraoxonase-1-deficient mice

Chemico-Biological Interactions, 2016

Metformin is the first-line pharmacological treatment of diabetes. In these patients, metformin r... more Metformin is the first-line pharmacological treatment of diabetes. In these patients, metformin reduces body weight and decreases the risk of diabetes-related complications such as cardiovascular disease. However, whether metformin elicits beneficial effects on liver histology is a controversial issue and, as yet, there is no consensus. Paraoxonase-1 (PON1), an enzyme synthesized mainly by the liver, degrades lipid peroxides and reduces oxidative stress. PON1 activities are decreased in chronic liver diseases. We evaluated the effects of metformin in the liver of PON1-deficient mice which, untreated, present a mild degree of liver steatosis. Metformin administration aggravated inflammation in animals given a standard mouse chow and in those fed a high-fat diet. Also, it was associated with a higher degree of steatosis in animals fed a standard chow diet. This report is a cautionary note regarding the prescription of metformin for the treatment of diabetes in patients with concomitant liver impairment.

Research paper thumbnail of Paraoxonase-1 Activity and Concentration After Radiation Therapy Treatment in Patients With Breast Cancer: Can Be a Useful Marker to Predict the Radiation Therapy Toxicity and Breast Cancer Prognosis?

International Journal of Radiation Oncology*Biology*Physics, 2015

Sixty-eight patients were identified as having radiation therapy fields within the region of the ... more Sixty-eight patients were identified as having radiation therapy fields within the region of the thoracolumbar spinal cord, defined as extending inferiorly down to L2. Pathological diagnosis for patients in this review included chordoma (29 patients, 42.7%), chondrosarcoma (25 patients, 36.8%), osteosarcoma (2 patients, 2.9%), other sarcoma (10 patients, 14.7%), and other (2 patients, 2.1%). Patient data was reviewed retrospectively. Composite plans and DVH were constructed for both pre-operative and post-operative radiation therapy courses in MIM-Vista software, as available. Dose constraints to the center and surface of the cord were 5400 cGy (RBE), and 6300 cGy (RBE) respectively; patients receiving concurrent chemotherapy had the radiation dose reduced by 8%. Spinal cord toxicity was recorded using the RTOG/EORTC late effects scoring system Results: Clinical and dosimetric data for each patient were analyzed. Median prescription dose to the tumor bed was 7020 cGy (RBE), (range, 5940-7820 cGy (RBE)) in conventional fractionation. For all patients, median follow-up all patients was 12.9 months (range, 0-116 months). Forty patients had follow-up available after the completion of treatment, for which median-follow-up was 49.6 months, (range, 1.5-116 months). Five-year overall survival for all patients in this group was 86.9% (95%CI 68.4 e 94.9). No grade 2 or higher toxicities to the spinal cord attributed to radiation therapy were noted. Reasons for spinal cord toxicity following treatment included: local disease progression, noted in 5 patients (10.9%), and direct surgical complications, noted in 4 patients (8.7%). 5 years life without neurological injury is 92.7% (95%CI: 78.8-97.6). Conclusion: Our clinical and dosimetric data suggest that the noted dose constraints are safe and acceptable with regard to spinal cord complications. Pre-existing disease characteristics, surgical complications, as well as tumor progression, appear to be greater factors when it comes to spinal cord toxicity.

Research paper thumbnail of PPARS in regulation of paraoxonases

Research paper thumbnail of PPARs in Regulation of Paraoxonases: Control of Oxidative Stress and Inflammation Pathways

PPAR Research, 2012

The paraoxonase (PON) group of enzymes, composed of PON1, PON2, and PON3, play an important role ... more The paraoxonase (PON) group of enzymes, composed of PON1, PON2, and PON3, play an important role in decreasing oxidative stress by degrading lipid peroxides. PON1 synthesis is upregulated by PPAR. Several pharmacological compounds (acting as antioxidants and, hence, atheroprotective) stimulate both PPAR activity and PON1 expression. Recent evidence suggests that PON1 and the monocyte chemoattractant protein-1 (MCP-1) are involved in coordinating the inflammatory response in damaged tissues; PPAR may be central in the regulation of these biochemical pathways. This article reviews the state of knowledge on PON1 biochemistry and function, the influence of genetic variation, and the regulation of PON1 expression by pharmaceutical compounds that increase PPAR activity. We also describe recent lines of evidence suggesting links between PON1 and MCP-1 and how their production may be regulated by PPAR.

Research paper thumbnail of The Level of DING Proteins Is Increased in HIV-Infected Patients: In Vitro and In Vivo Studies

PLoS ONE, 2012

DING proteins constitute an interesting family, owing to their intriguing and important activitie... more DING proteins constitute an interesting family, owing to their intriguing and important activities. However, after a decade of research, little is known about these proteins. In humans, at least five different DING proteins have been identified, which were implicated in important biological processes and diseases, including HIV. Indeed, recent data from different research groups have highlighted the anti-HIV activity of some DING representatives. These proteins share the ability to inhibit the transcriptional step of HIV-1, a key step of the viral cycle that is not yet targeted by the current therapies. Since such proteins have been isolated from humans, we undertook a comprehensive study that focuses on the relationship between these proteins and HIV-infection in an infectious context. Hence, we developed a home-made ELISA for the quantification of the concentration of DING proteins in human serum. Using this method, we were able to determine the concentration of DING proteins in healthy and HIV-infected patients. Interestingly, we observed a significant increase of the concentration of DING proteins in non treated and treated HIV-infected patients compared to controls. In addition, cell cultures infected with HIV also show an increased expression of DING proteins, ruling out the possible role of antiretroviral treatment in the increase of the expression of DING proteins. In conclusion, results from this study show that the organism reacts to HIVinfection by an overexpression of DING proteins.

Research paper thumbnail of Ubiquitous Transgenic Overexpression of C-C Chemokine Ligand 2: A Model to Assess the Combined Effect of High Energy Intake and Continuous Low-Grade Inflammation

Mediators of Inflammation, 2013

Excessive energy management leads to low-grade, chronic inflammation, which is a significant fact... more Excessive energy management leads to low-grade, chronic inflammation, which is a significant factor predicting noncommunicable diseases. In turn, inflammation, oxidation, and metabolism are associated with the course of these diseases; mitochondrial dysfunction seems to be at the crossroads of mutual relationships. The migration of immune cells during inflammation is governed by the interaction between chemokines and chemokine receptors. Chemokines, especially C-C-chemokine ligand 2 (CCL2), have a variety of additional functions that are involved in the maintenance of normal metabolism. It is our hypothesis that a ubiquitous and continuous secretion of CCL2 may represent an animal model of low-grade chronic inflammation that, in the presence of an energy surplus, could help to ascertain the afore-mentioned relationships and/or to search for specific therapeutic approaches. Here, we present preliminary data on a mouse model created by using targeted gene knock-in technology to integr...

Research paper thumbnail of Paraoxonase-1 Inhibits Oxidized Low-Density Lipoprotein-Induced Metabolic Alterations and Apoptosis in Endothelial Cells: A Nondirected Metabolomic Study

Mediators of Inflammation, 2013

We studied the influence of PON1 on metabolic alterations induced by oxidized LDL when incubated ... more We studied the influence of PON1 on metabolic alterations induced by oxidized LDL when incubated with endothelial cells. HUVEC cells were incubated with native LDL, oxidized LDL, oxidized LDL plus HDL from wild type mice, and oxidized LDL plus HDL from PON1-deficient mice. Results showed alterations in carbohydrate and phospholipid metabolism and increased apoptosis in cells incubated with oxidized LDL. These changes were partially prevented by wild type mouse HDL, but the effects were less effective with HDL from PON1-deficient mice. Our results suggest that PON1 may play a significant role in endothelial cell survival by protecting cells from alterations in the respiratory chain induced by oxidized LDL. These results extend current knowledge on the protective role of HDL and PON1 against oxidation and apoptosis in endothelial cells.

Research paper thumbnail of Rosiglitazone and Fenofibrate Exacerbate Liver Steatosis in a Mouse Model of Obesity and Hyperlipidemia. A Transcriptomic and Metabolomic Study

Journal of Proteome Research, 2014

Peroxisome proliferator-activated receptors (PPAR) play an important role in the regulation of li... more Peroxisome proliferator-activated receptors (PPAR) play an important role in the regulation of lipid and glucose metabolism, inflammatory, and vascular responses. We show the effect of treatment with two PPAR agonists, fenofibrate (FF) and rosiglitazone (RSG), on ob/ob and LDLR-double deficient mice, by combined gene-expression and metabolomic analyses. Male mice were daily treated for 12 weeks with RSG (10 mg·kg(1-)·day(-1) per os (p.o.), n = 8) and FF (50 mg·kg(1-)·day(-1) p.o., n = 8). Twelve untreated ob/ob and LDLR-double deficient mice were used as controls. To integrate the transcriptomic and metabolomic results, we designed a hierarchical algorithm, based on the average linkage method in clustering. Data were also interpreted with the Ingenuity Pathway Analysis program. FF and RSG treatments significantly increased the hepatic triglyceride content in the liver when compared with the control group, and the treatments induced an increase in the number and size of hepatic lipid droplets. Both drugs simultaneously activate pro-steatotic and antisteatotic metabolic pathways with a well-ordered result of aggravation of the hepatic lipid accumulation. The present study is a cautionary note not only to researchers on the basic mechanism of the action of PPAR activators but also to the use of these compounds in clinical practice.