San Juan de Énova, Spain
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Abello D.,Rovira i Virgili University | Sancho E.,Rovira i Virgili University | Camps J.,Rovira i Virgili University | Camps J.,Hospital Universitari Of Sant Joan | And 2 more authors.
International Journal of Molecular Sciences | Year: 2014

Paraoxonases (PON) are three enzymes (PON1, PON2 and PON3) that play a role in the organism’s antioxidant system; alterations in which are associated with diseases involving oxidative stress. In this review, we summarize the evidence of PON related to the pathogenesis of coronary artery disease (CAD) and atherosclerosis. We searched three electronic databases (PubMed, Scopus and Cochrane Database) with no date limit. All of the articles selected investigated PON enzymatic activity and/or PON gene polymorphisms. The selection focused on PON in relation to atherosclerosis, CAD and myocardial infarction. The exclusion criteria were a sample size <100 patients, non-human studies, editorials and systematic reviews without restrictions on the country of origin. With these criteria, we identified thirty-five prospective studies published between 1986 and 2014 with a total of 28,164 participants. The relationship between PON gene polymorphisms and CAD was not conclusive, but most studies support the concept that alterations in PON1 enzymatic activity levels do influence atheroma formation. Conversely, relationships between PON2 and PON3 vs. CAD have not been extensively investigated. Our review of the current data concludes that the bases of paraoxonases involvement in atherosclerosis are poorly understood and that this issue requires future comprehensive, multi-centered studies. © 2014 by the authors; licensee MDPI, Basel, Switzerland.


Lluch A.,Vitalinea Health Benefit Group | Hanet-Geisen N.,Vitalinea Health Benefit Group | Salah S.,Vitalinea Health Benefit Group | Salas-Salvado J.,Hospital Universitari Of Sant Joan | And 3 more authors.
Food Quality and Preference | Year: 2010

The objectives of this work were to investigate short-term appetite-reducing effects of an innovative low-fat yogurt enriched with protein (8 g/serving) and fibre (2.6-2.9 g/serving). Two studies were conducted using randomised cross-over designs. Healthy women consumed a mid-morning snack consisting of either the test or the control yogurt product (Study 1, n = 24: iso-energetic, not iso-weight conditions; Study 2, n = 121: iso-weight, not iso-energetic conditions) under laboratory conditions. Subjective appetite ratings (of hunger, fullness, desire to eat and prospective consumption) were recorded throughout the morning; sensory and hedonic ratings were also collected. In Study 2, two hours after consumption of the dairy snack, subsequent food intake at lunch was also measured. The test product reduced subjective appetite compared to the control (all ratings, P < 0.05). Energy intake at lunch was reduced by 274 kJ after the test compared to the control (P < 0.001). These two studies demonstrated that a low-fat dairy product enriched with protein and fibre can significantly reduce short-term appetite. © 2009 Elsevier Ltd. All rights reserved.


Parra S.,Rovira i Virgili University | Marsillach J.,Rovira i Virgili University | Aragones G.,Rovira i Virgili University | Beltran R.,Rovira i Virgili University | And 8 more authors.
Journal of Infectious Diseases | Year: 2010

Background. Oxidative stress is associated with human immunodeficiency virus (HIV) infection. Paraoxonase1 (PON1) is an antioxidant enzyme that is bound to high-density lipoproteins (HDLs). We evaluated whether PON1 gene haplotypes influence the metabolic disturbances, presence of subclinical atherosclerosis, and virologie outcome associated with the infection. Methods. DNA from blood samples collected from 234 HIV-infected patients and 633 healthy control subjects had single-nucleotide polymorphisms of PON1192, PON155, PON1-162, PON1-832, PON1 -909, PON1-1076, and PON1-1741 analyzed using the Iplex Gold MassArray method. Subsequently, the influence of these single-nucleotide polymorphisms on measured biochemical and clinical variables was assessed. Results. We observed significant differences in the haplotype distribution between the control subjects and the HIV-infected patients. Haplotype H10 (GTCCGTC) was more prevalent in the HIV-infected patients (6.41% vs 0.64%; P<.001), and haplotype H5 (GACCGTC) was less prevalent in HIV-infected patients (27.7% vs 42.9%; P = .001). In HIV-infected patients, haplotype H7 (AATTCCT) was associated with better CD4- cell count recovery, higher levels of HDL cholesterol (P = .048) and apolipoprotein A-I (P = .019), lower levels of triglycerides (P = .004), and lower rates of subclinical arteriosclerosis (P<.001). Conclusions. PON1 haplotypes segregate with HIV infection, HDL metabolism, the presence of subclinical atherosclerosis, and CD4+ cell recovery after treatment. © 2010 by the Infectious Diseases Society of America. All rights reserved.


Marsillach J.,Hospital Universitari Of Sant Joan | Checa M.A.,Hospital Del Mar | Pedro-Botet J.,Hospital Del Mar | Carreras R.,Hospital Del Mar | And 2 more authors.
Fertility and Sterility | Year: 2010

In this observational, case-control study in infertile women, we observed elevated serum oxidative stress that was significantly correlated with an increase in serum paraoxonase-1 activity and without any evidence of a proinflammatory reaction. These results suggest a protective role of paraoxonase-1 against inflammation in this clinical setting. © 2010 by American Society for Reproductive Medicine.


Mackness B.,Hospital Universitari Of Sant Joan | Beltran-Debon R.,Hospital Universitari Of Sant Joan | Aragones G.,Hospital Universitari Of Sant Joan | Joven J.,Hospital Universitari Of Sant Joan | And 2 more authors.
IUBMB Life | Year: 2010

We have studied the distribution of mRNA for paraoxonases (PON) 1 and 2 in 24 human tissues using Gene Expression Panels. PON1 mRNA was restricted to adult kidney, liver, and colon as well as fetal liver, whereas PON2 mRNA was more widely distributed in adult human brain, heart, kidney, spleen, liver, colon, lung, small intestine, muscle, stomach, testis, placenta, salivary, thyroid and adrenal glands, pancreas, skin, and bone marrow, as well as fetal brain and liver. PON2 mRNA was not found in ovary, uterus, or plasma leukocytes using the panels. However, using real time PCR, we found PON2 mRNA expression in human plasma leukocytes. There were differences between the tissue distribution of mRNAs found in this study and the immunohistochemical localization of the PON1 and PON2 proteins reported previously. In particular, PON1 protein is much more widely distributed than its mRNA, possibly indicating the delivery of PON1 to various tissues by HDL. In addition, differences between PON2 mRNA and protein distributions could be due to missence mutations in the PON2 gene, causing nontranslation of mRNA to protein in some tissues. © 2010 IUBMB.


Parra S.,Hospital Universitari Of Sant Joan | Coll B.,Hospital Universitari Of Sant Joan | Aragones G.,Hospital Universitari Of Sant Joan | Marsillach J.,Hospital Universitari Of Sant Joan | And 5 more authors.
HIV Medicine | Year: 2010

Objectives: HIV-infected patients show an increased cardiovascular disease (CVD) risk resulting, essentially, from metabolic disturbances related to chronic infection and antiretroviral treatments. The aims of this study were: (1) to evaluate the agreement between the CVD risk estimated using the Framingham risk score (FRS) and the observed presence of subclinical atherosclerosis in HIV-infected patients; (2) to investigate the relationships between CVD and plasma biomarkers of oxidation and inflammation. Methods: Atherosclerosis was evaluated in 187 HIV-infected patients by measuring the carotid intima-media thickness (CIMT). CVD risk was estimated using the FRS. We also measured the circulating levels of interleukin-6, monocyte chemoattractant protein-1 (MCP-1) and oxidized low-density lipoprotein (LDL), and paraoxonase-1 activity and concentration. Results: There was a weak, albeit statistically significant, agreement between FRS and CIMT (κ=0.229, P<0.001). A high proportion of patients with an estimated low risk had subclinical atherosclerosis (n=66; 56.4%). In a multivariate analysis, the presence of subclinical atherosclerosis in this subgroup of patients was associated with age [odds ratio (OR) 1.285; 95% confidence interval (CI) 1.084-1.524; P=0.004], body mass index (OR 0.799; 95% CI 0.642-0.994; P=0.044), MCP-1 (OR 1.027; 95% CI 1.004-1.050; P=0.020) and oxidized LDL (OR 1.026; 95% CI 1.001-1.051; P=0.041). Conclusion:FRS underestimated the presence of subclinical atherosclerosis in HIV-infected patients. The increased CVD risk was related, in part, to the chronic oxidative stress and inflammatory status associated with this patient population. © 2009 British HIV Association.


PubMed | Hospital Universitari Of Sant Joan
Type: Journal Article | Journal: Chemico-biological interactions | Year: 2016

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.


PubMed | Eurospital S.p.A, Leiden University, University of Groningen, Schneider Childrens Medical Center and 3 more.
Type: Journal Article | Journal: European journal of human genetics : EJHG | Year: 2015

Due to the association of coeliac disease and HLA-specificities DQ2 and DQ8, HLA-typing can be used for risk determination of the disease. This study was designed to evaluate the knowledge of parents from coeliac families regarding HLA-typing and the impact of HLA-typing on the perception of the health of their children. A structured questionnaire was sent to the Dutch, Spanish and German parents participating with their child in the European PreventCD study on disease prevention in high-risk families, addressing parents understanding of and attitude towards HLA-typing, distress related to HLA-typing and perceived health and health-related quality of life of their children. Sixty-eight percent of parents of 515 children returned the questionnaires, with 85% of children being DQ2/DQ8 positive. The majority of all parents answered the questions on knowledge correctly. Forty-eight percent of parents of DQ2/DQ8-negative children thought their child could develop coeliac disease. More distress was reported by parents of DQ2/DQ8-positive children (P<0.001). All parents showed few regrets and would repeat HLA-typing in future children. Perceived health and health-related quality of life were similar. In conclusion, we can say that misinterpretation of DQ2/DQ8-negative results by parents is frequent. DQ2/DQ8-positive results do not affect perceived health and health-related quality of life of children but may cause temporary negative feelings among parents. Parents of coeliac families seem to support HLA-typing.


PubMed | Hospital Universitari Of Sant Joan
Type: | Journal: Current clinical pharmacology | Year: 2016

Metformin is a biguanide used in the treatment of type 2 diabetes mellitus and obesity. The main mechanism of action is to decrease the intestinal glucose absorption and the hepatic glucose production. It does not influence insulin secretion. Metformin also increases the affinity of the insulin receptor, reduces high insulin levels and improves insulin resistance. Additionally, it promotes weight loss. Metformin is a pleiotropic compound but acts, largely, by activating 5 adenosine monophosphate (AMP)-activated protein kinase (AMPK). Data suggest that the therapeutic effects of this compound are mediated, at least in part, through an upregulation of paraoxonase-1 (PON1) synthesis. PON1 is a thiolactonase that degrades lipid peroxides, and downregulates the chemokine (C-C motif) ligand 2 (CCL2) which is a pro-inflammatory chemokine that stimulates the migration of monocytes to areas of inflammation where they differentiate into macrophages. Studies in PON1-deficient mice suggest that this enzyme is essential for the successful activation of AMPK in the liver and for facilitating metformins therapeutic function.


Bullo M.,Hospital Universitari Of Sant Joan | Bullo M.,CIBER ISCIII | Casas R.,CIBER ISCIII | Portillo M.P.,Polytechnic University of Valencia | And 9 more authors.
Nutrition, Metabolism and Cardiovascular Diseases | Year: 2013

Background and Aims: Epidemiological and clinical studies suggest that low-glycemic index diets could protect against weight gain. However, the relationship between these diets and adipokines or inflammatory markers is unclear. In the present study we examine how the dietary glycemic index (GI) and dietary glycemic load (GL) are associated with several adipokines and related metabolic risk markers of obesity and diabetes in a cross-sectional and longitudinal manner. Methods and Results: 511 elderly community-dwelling men and women at high cardiovascular risk were recruited for the PREDIMED trial. Dietary data were collected at baseline and after 1 year of follow-up. The GI and GL were calculated. Plasma leptin, adiponectin and other metabolic risk markers were measured at baseline and after 1 year. At baseline, subjects in the highest quartiles of GI showed significantly higher levels of TNF and IL-6 than those in the lowest quartiles. Dietary GI index was negatively related to plasma leptin and adiponectin levels. After 1 year of follow-up, subjects with a higher increase in dietary GI or GL showed a greater reduction in leptin and adiponectin plasma levels. There was no association between GI or GL and the other metabolic markers measured. Conclusion: Our results suggest that the consumption of high-GI or high-GL diets may modulate plasma concentrations of leptin and adiponectin, both adipostatic molecules implicated in energy balance and cardiometabolic risk. © 2011 Elsevier B.V.

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