Servicio de Bioquimica Clinica

Majadahonda, Spain

Servicio de Bioquimica Clinica

Majadahonda, Spain
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Millan C.S.,Institute Investigaciones Biomedicas Alberto Sols | Soldevilla B.,Institute Investigaciones Biomedicas Alberto Sols | Martin P.,Servicio de Anatomia Patologica | Gil-Calderon B.,Grupo de senalizacion celular en cancer | And 4 more authors.
Clinical Cancer Research | Year: 2015

Background: The acquired resistance to chemotherapy represents the major limitation in the treatment of cancer. New strategies to solve this failure and improve patients' outcomes are necessary. The cancer preventive effect of β-cryptoxanthin has been widely described in population studies. Few reports support its putative use as an antitumoral compound. Here we focus on the therapeutic potential of β-cryptoxanthin individually or in combination with oxaliplatin in colon cancer and try to decipher the molecular basis underlying its effect. Methods: Apoptosis, viability and proliferation assays, mouse models, and an intervention study in 20 healthy subjects were performed. A PCR array was carried out to unravel the molecular putative basis of the β-cryptoxanthin effect, and further signaling experiments were conducted. Comet Assay was completed to evaluate the genotoxicity of the treatments. Results: β-Cryptoxanthin differentially regulates the expression of the P73 variants in vitro, in vivo, and in a human intervention study. This carotenoid decreases the proliferation of cancer cells and cooperates with oxaliplatin to induce apoptosis through the negative regulation of ΔNP73. The antitumoral concentrations of oxaliplatin decrease in the presence of β-cryptoxanthin to achieve same percentage of growth inhibition. The genotoxicity in peripheral blood mononuclear cells of mice decreased in the combined treatment. Conclusions: We propose a putative novel therapeutic strategy for the treatment of colon cancer based on the combination of β-cryptoxanthin and oxaliplatin. The combined regimen produced more benefit than either individual modality without increasing side effects. In addition, the concentration-limiting toxicity of oxaliplatin is reduced in the presence of the carotenoid. © 2015 American Association for Cancer Research.


PubMed | Grupo de senalizacion celular en cancer, Institute Investigaciones Biomedicas Alberto Sols, Servicio de Anatomia Patologica, Hospital Universitario Puerta Of Hierro Majadahonda and Servicio de Bioquimica Clinica
Type: Journal Article | Journal: Clinical cancer research : an official journal of the American Association for Cancer Research | Year: 2015

The acquired resistance to chemotherapy represents the major limitation in the treatment of cancer. New strategies to solve this failure and improve patients outcomes are necessary. The cancer preventive effect of -cryptoxanthin has been widely described in population studies. Few reports support its putative use as an antitumoral compound. Here we focus on the therapeutic potential of -cryptoxanthin individually or in combination with oxaliplatin in colon cancer and try to decipher the molecular basis underlying its effect.Apoptosis, viability and proliferation assays, mouse models, and an intervention study in 20 healthy subjects were performed. A PCR array was carried out to unravel the molecular putative basis of the -cryptoxanthin effect, and further signaling experiments were conducted. Comet Assay was completed to evaluate the genotoxicity of the treatments.-Cryptoxanthin differentially regulates the expression of the P73 variants in vitro, in vivo, and in a human intervention study. This carotenoid decreases the proliferation of cancer cells and cooperates with oxaliplatin to induce apoptosis through the negative regulation of NP73. The antitumoral concentrations of oxaliplatin decrease in the presence of -cryptoxanthin to achieve same percentage of growth inhibition. The genotoxicity in peripheral blood mononuclear cells of mice decreased in the combined treatment.We propose a putative novel therapeutic strategy for the treatment of colon cancer based on the combination of -cryptoxanthin and oxaliplatin. The combined regimen produced more benefit than either individual modality without increasing side effects. In addition, the concentration-limiting toxicity of oxaliplatin is reduced in the presence of the carotenoid.


Andres-Otero M.J.,Servicio de Bioquimica Clinica | De-Blas-Giral I.,University of Zaragoza | De-Blas-Giral I.,Instituto Agroalimentario Of Aragon | Puente-Lanzarote J.J.,Servicio de Bioquimica Clinica | And 11 more authors.
Clinical Biochemistry | Year: 2016

Background: The aim of this study was to compare fourteen non-invasive indexes/scores: AAR, APRI, Fibroindex, MODEL3, Forns index, FIB4, GUCI, FI, FCI, Pohl score, AP index, CDS, HGM-1 and HGM-2, in order to diagnose the hepatic fibrosis stage in a survey of patients with chronic hepatitis C. Methods: 84 patients with chronic hepatitis C were studied. Liver fibrosis was staged according to the Scheuer scoring system. The diagnostic accuracy of these indexes/scores was evaluated by AUROC, contingency tables and logistic regression analysis. Results: The best AUROCs (>. 0.9) to discriminate cirrhosis (F = 4), were observed for CDS, FI, AAR, MODEL3, FIB4, HGM-2 and FCI. To discriminate at least advance fibrosis (F. ≥. 3), the best AUROCs (>. 0.89) were for CDS, FI, FIB4, HGM2-2, MODEL3 and FCI. To discriminate at least significant fibrosis (F. ≥. 2), the best AUROCs (>. 0.8) were for FIB4, GUCI, APRI, FI, Forns index, HGM-2 and FCI. Contingency tables and logistic regression analysis supported the results obtained by AUROC. Conclusions: This study compares the diagnostic performance of fourteen indexes for the diagnosis of liver fibrosis stage in the same group of CHC patients. These results allow the selection of the best indexes for further studies in larger populations, in order to build diagnostic algorithms as an alternative to liver biopsy for fibrosis staging in patients with chronic HCV infection. These algorithms would allow to take therapeutical decisions and the continuous follow-up of hepatic fibrosis in these patients. © 2016.


Gutierrez-Mata A.P.,Servicio de Bioquimica Clinica | Antonia Vilaseca M.,Servicio de Radiologia | Capdevila-Cirera A.,Servicio de Oftalmologia | Vidal-Oller M.,Servicio de Gastroenterologia y Nutricion | And 10 more authors.
Revista de Neurologia | Year: 2012

Introduction. Phenylketonuria (PKU) is an autosomal recessive metabolic disease caused by a deficiency of phenylalanine hydroxylase. The dietary therapy for the effective management of PKU, in particular the restriction of high-protein foods of animal-origin, compromises patients' intake of fat and distorts the n-3:n-6 ratio of essential fatty acids in the diet. This deficiency can contribute to neurological and visual impairment. Aim. To evaluate changes in white matter alterations, visual evoked potential (VEP) latencies and performance in executive and motor functions in a group of early and continuously treated PKU patients after supplementation with docosahexaneoic acid (DHA). Patients and methods. We selected 21 PKU patients with early diagnosis (age range: 9-25 years), on a Phe-restricted diet and supplemented with PKU formula. Inclusion criteria were: low erythrocyte DHA values, prolonged P100 wave latencies in VEP and/or presence of white matter hyperintensities on brain magnetic resonance imaging (MRI), and intellectual quotient > 80. All patients were treated with DHA (10 mg/kg/day) for 12 months. Assessment was conducted at baseline and after 12 months of treatment, and included biochemical parameters, brain MRI, VEP, ophthalmologic evaluation and neuropsychological tests. Results and conclusion. All the patients normalized the DHA levels after supplementation. Improvement in the P100 wave latencies, and fine motor skills was significant. No significant improvement in the other explorations was evident after supplementation. Further investigations seem advisable to establish a cause-effect relationship between DHA treatment and the slight improvement observed in some neurological functions. © 2012 Revista de Neurología.


PubMed | Institute Investigacion Sanitaria Of Aragon, University of Zaragoza and Servicio de Bioquimica Clinica
Type: Journal Article | Journal: Clinical biochemistry | Year: 2016

The aim of this study was to compare fourteen non-invasive indexes/scores: AAR, APRI, Fibroindex, MODEL3, Forns index, FIB4, GUCI, FI, FCI, Pohl score, AP index, CDS, HGM-1 and HGM-2, in order to diagnose the hepatic fibrosis stage in a survey of patients with chronic hepatitis C.84 patients with chronic hepatitis C were studied. Liver fibrosis was staged according to the Scheuer scoring system. The diagnostic accuracy of these indexes/scores was evaluated by AUROC, contingency tables and logistic regression analysis.The best AUROCs (>0.9) to discriminate cirrhosis (F=4), were observed for CDS, FI, AAR, MODEL3, FIB4, HGM-2 and FCI. To discriminate at least advance fibrosis (F3), the best AUROCs (>0.89) were for CDS, FI, FIB4, HGM2-2, MODEL3 and FCI. To discriminate at least significant fibrosis (F2), the best AUROCs (>0.8) were for FIB4, GUCI, APRI, FI, Forns index, HGM-2 and FCI. Contingency tables and logistic regression analysis supported the results obtained by AUROC.This study compares the diagnostic performance of fourteen indexes for the diagnosis of liver fibrosis stage in the same group of CHC patients. These results allow the selection of the best indexes for further studies in larger populations, in order to build diagnostic algorithms as an alternative to liver biopsy for fibrosis staging in patients with chronic HCV infection. These algorithms would allow to take therapeutical decisions and the continuous follow-up of hepatic fibrosis in these patients.


San-Jose L.M.,CSIC - National Museum of Natural Sciences | San-Jose L.M.,CSIC - Pyrenean Institute of Ecology | Granado-Lorencio F.,Servicio de Bioquimica Clinica | Fitze P.S.,CSIC - National Museum of Natural Sciences | And 2 more authors.
Functional Ecology | Year: 2012

The importance of dietary lipids for carotenoid-based ornaments has rarely been investigated, although theory predicts that dietary lipids may control the development of these widespread animal signals. Dietary lipids have been suggested to enhance the expression of male carotenoid-based ornaments because they provide carotenoids with a hydrophobic domain that facilitates their absorption and transport. Dietary lipids may also enhance the uptake of tocopherols (vitamin E), which share common absorption and transport routes with carotenoids. Here, we test whether dietary lipids enhance carotenoid availability and male carotenoid-based colorations. We also explore the effects of dietary lipids on plasma tocopherol concentration, which allow disentangling between different pathways that may explain how dietary lipids affect ornamental expression. 2.Following a two-factorial design, we manipulated dietary access of naturally occurring fatty acids (oleic acid) and carotenoids (lutein and zeaxanthin) and measured its effects on the circulating concentrations of carotenoids (lutein and zeaxanthin) and vitamin E (α- and γ-(β-) tocopherols) and on the ventral, carotenoid-based coloration of male common lizards (Lacerta vivipara). 3.Lutein but not zeaxanthin plasma concentrations increased with carotenoid supplementation, which, however, did not affect coloration. Lipid intake negatively affected circulating concentrations of lutein and γ-(β-) tocopherol and led to significantly less orange colorations. The path analysis suggests that a relationship between the observed colour change and the change in plasma concentrations of γ-(β-) tocopherol may exist. 4.Our study shows for the first time that dietary lipids do not enhance but reduce the intensity of male carotenoid-based ornaments. Although dietary lipids affected plasma carotenoid concentration, its negative effect on coloration appeared to be linked to lower vitamin E plasma concentrations. These findings suggest that a conflict between dietary lipids and carotenoid and tocopherol uptake may arise if these nutrients are independently obtained from natural diets and that such conflict may reinforce signal honesty in carotenoid-based ornaments. They also suggest that, at least in the common lizard, sexual selection with respect to carotenoid-based coloration may select for males with low antioxidant capacity and thus for males of superior health. © 2012 The Authors. Functional Ecology © 2012 British Ecological Society.

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