Monreal, J.I. (José Ignacio)

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    Evaluation of measured and calculated small dense low-density lipoprotein in capillary blood and association with the metabolic syndrome
    (Elsevier, 2024) Deza, S. (Sara); Beloqui, O. (Óscar); Colina, I. (Inmaculada); Varo, N. (Nerea); Maroto-García, J. (Julia); Gonzalez-Hernandez, A. (Alvaro); Mugueta, C. (Carmen); Martínez-Chávez, E. (Estéfani); Monreal, J.I. (José Ignacio)
    Background and aims: Small-dense-low-density-lipoprotein cholesterol (sdLDL-C) is proatherogenic and not commonly measured. The aims were to evaluate capillary blood and its stability for sdLDL-C measurement and measure sdLDL-C in patients with metabolic syndrome (MS). Methods: 182 patients were studied (49 with MS). sdLDL-C was measured by electrophoresis (LipoPrint®), direct measurement (Roche Diagnostics) and Sampson equation. Intima-media thickness (IMT) and presence of atheroma was evaluated. sdLDL-C was compared in paired venous and capillary blood according to CLSI-EP09c (n = 40). sdLDL-C stability was studied after 24 h at room temperature (RT). Results: sdLDL-C in capillary blood and venous blood showed agreement with the direct measurement (bias: 4.17 mg/dL, LOA 95 %:-5.66; 13.99) and estimation (bias:8.12 mg/dL, LOA 95 %:-8.59; 24.82). sdLDL-C is stable in capillary blood for 24 h at RT. The electrophoretic method yielded lower (p < 0.05) sdLDL-C than the equation or direct measurement. Patients with MS had (p < 0.05) higher sdLDL-C (%) than patients without MS. Patients with atheroma plaques had higher sdLDL-C (p < 0.05). Estimated sdLDL-C correlated with IMT (r = 0.259, p < 0.001). Conclusions: Capillary blood is an alternative to venous blood for sdLDL-C measurement and is stable for 24 h after collection. Estimated and directly measured sdLDL-C associate with the MS being accessible tools for cardiovascular risk assessment.
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    Estudio faunístico del macizo de Quinto Real. VI. Nematodos (Nematoda)
    (Servicio de Publicaciones de la Universidad de Navarra, 1982) Campoy, A. (A.); Monreal, J.I. (José Ignacio)
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    Association of the SH2B1 rs7359397 gene polymorphism with steatosis severity in subjects with obesity and non-alcoholic fatty liver disease
    (MDPI, 2020) Martinez, J.A. (José Alfredo); Riezu-Boj, J.I. (José Ignacio); Benito-Boíllos, A. (Alberto); Zulet, M.A. (María Ángeles); Tur, J.A. (Josep A.); Milagro-Yoldi, F.I. (Fermín Ignacio); Marin-Alejandre, B.A. (Bertha Araceli); Herrero, J.I. (José Ignacio); Monreal, J.I. (José Ignacio); Elorz, M. (Mariana); Abete, I. (Itziar); Cantero-González, I. (Irene); Pérez-Díaz-Campo, N. (Nuria) del
    Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver disease worldwide. Some genetic variants might be involved in the progression of this disease. The study hypothesized that individuals with the rs7359397 T allele have a higher risk of developing severe stages of NAFLD compared with non-carriers where dietary intake according to genotypes could have a key role on the pathogenesis of the disease. SH2B1 genetic variant was genotyped in 110 overweight/obese subjects with NAFLD. Imaging techniques, lipidomic analysis and blood liver biomarkers were performed. Body composition, general biochemical and dietary variables were also determined. The SH2B1 risk genotype was associated with higher HOMA-IR p equal 0.001; and Fatty Liver Index (FLI) p equal 0.032. Higher protein consumption (p equal 0.028), less mono-unsaturated fatty acid and fiber intake (p equal 0.045 and p equal 0.049, respectively), was also referred to in risk allele genotype. Lipidomic analysis showed that T allele carriers presented a higher frequency of non-alcoholic steatohepatitis (NASH) (69.1/100 vs. 44.4/100; p equal 0.006). In the genotype risk group, adjusted logistic regression models indicated a higher risk of developing an advanced stage of NAFLD measured by FLI (OR 2.91) and ultrasonography (OR 4.15). Multinomial logistic regression models showed that risk allele carriers had higher liver fat accumulation risk (RRR 3.93) and an increased risk of NASH (RRR 7.88). Consequently, subjects carrying the T allele were associated with a higher risk of developing a severe stage of NAFLD. These results support the importance of considering genetic predisposition in combination with a healthy dietary pattern in the personalized evaluation and management of NAFLD.
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    Changes in male rat urinary protein profile during puberty: a pilot study
    (BioMed Central, 2013) Wait, R. (Robin); Vettorazzi, A. (Ariane); Mantle, P. (Peter); Nagy, J. (Judit); Monreal, J.I. (José Ignacio)
    BACKGROUND: Androgen-dependent proteins (lipocalins) circulate in blood of male rats and mice and, being small (~ 18 kDa), pass freely into glomerular filtrate. Some are salvaged in proximal nephrons but some escape in urine. Several organic molecules can bind to these proteins causing, where salvage occurs, nephropathy including malignancy in renal cortex. In urine, both free lipocalins and ligands contribute to an increasingly-recognised vital biological role in social communication between adults, especially in the dark where reliance is on smell and taste. Crystal structure of the first-characterised lipocalin of male rats, alpha2u-globulin, has been determined and peptide sequences for others are available, but no study of occurrence during early puberty has been made. We have followed temporal occurrence in urine of juveniles (n = 3) for non-invasive pilot study by high resolution gradient mini-gel electrophoresis, tryptic digest of excised protein bands, and LC-MS/MS of digest to identify peptide fragments and assign to specific lipocalins. Study objective refers directly to external availability for social communication but also indirectly to indicate kinetics of circulating lipocalins to which some xenobiotics may bind and constitute determinants of renal disease. RESULTS: Mini-gels revealed greater lipocalin complexity than hitherto recognised, possibly reflecting post-translational modifications. Earliest patterns comprised rat urinary protein 1, already evident in Sprague-Dawley and Wistar strains at 36 and 52 days, respectively. By 44 and 57 days major rat protein (alpha2u-globulin) occurred as the progressively more dominant protein, though as two forms with different electrophoretic mobility, characterised by seven peptide sequences. No significant change in urinary testosterone had occurred in Wistars when major rat protein became evident, but testosterone surged by 107 days concomitant with the marked abundance of excreted lipocalins. CONCLUSIONS: Qualitative temporal changes in the composition of excreted lipocalins early in puberty, and apparent increase in major urinary protein as two resolvable forms, should catalyse systematic non-invasive study of urinary lipocalin and testosterone dynamics from early age, to illuminate this aspect of laboratory rodent social physiology. It could also define the potential temporal onset of nephrotoxic ligand risk, applicable to young animals used as toxicological models.
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    The Metabolic and Hepatic Impact of Two Personalized Dietary Strategies in Subjects with Obesity and Nonalcoholic Fatty Liver Disease: The Fatty Liver in Obesity (FLiO) Randomized Controlled Trial
    (MDPI AG, 2019) Huarte-Muniesa, M.P. (Maria Pilar); Benito-Boíllos, A. (Alberto); Zulet, M.A. (María Ángeles); Tur, J.A. (Josep A.); Marin-Alejandre, B.A. (Bertha Araceli); Martinez-Echeverria, A. (Ana); Uriz-Otano, J.I. (Juan Isidoro); Herrero, J.I. (José Ignacio); Martinez, A. (Alfredo); Monreal, J.I. (José Ignacio); Quiroga, J. (Jorge); Elorz, M. (Mariana); Abete, I. (Itziar); Cantero-González, I. (Irene)
    The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. NAFLD management is mainly focused on weight loss, but the optimal characteristics of the diet demand further investigation. This study aims to evaluate the effects of two personalized energy-restricted diets on the liver status in overweight or obese subjects with NAFLD after a 6 months follow-up. Ninety-eight individuals from the Fatty Liver in Obesity (FLiO) study were randomized into two groups and followed different energy-restricted diets. Subjects were evaluated at baseline and after 6 months. Diet, anthropometry, body composition, and biochemical parameters were evaluated. Liver assessment included ultrasonography, Magnetic Resonance Imaging, elastography, and determination of transaminases. Both dietary groups significantly improved their metabolic and hepatic markers after the intervention, with no significant differences between them. Multivariate regression models evidenced a relationship between weight loss, adherence to the Mediterranean Diet (MedDiet), and a decrease in liver fat content, predicting up to 40.9% of its variability after 6 months. Moreover, the antioxidant capacity of the diet was inversely associated with liver fat content. Participants in the group with a higher adherence to the MedDiet showed a greater reduction in body weight, total fat mass, and hepatic fat. These results support the benefit of energy-restricted diets, high adherence to the MedDiet, and high antioxidant capacity of the diet for the management of NAFLD in individuals with overweight or obesity.
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    Serum carboxy-terminal propeptide of procollagen type I is a marker of myocardial fibrosis in hypertensive heart disease
    (American Heart Association, 2000) Martinez-Ubago, J.L. (José L.); Gutierrez-Stampa, M. (M.); Querejeta, R. (Ramón); Lopez-Salazar, M.B. (María Begoña); Diez-Martinez, J. (Javier); Etayo, J.C. (Juan Carlos); Pardo-Mindan, F.J. (Francisco Javier); Larman, M. (Mariano); Gil, M.J. (María José); Monreal, J.I. (José Ignacio); Emparanza, J.I. (J. I.); Artiñano, E. (E.); Varo-Cenarruzabeitia, M.N. (Miren Nerea)
    BACKGROUND: This study was designed to investigate whether the serum concentration of the carboxy-terminal propeptide of procollagen type I (PIP), a marker of collagen type I synthesis, is related to myocardial fibrosis in hypertensive patients. METHODS AND RESULTS: The study was performed in 26 patients with essential hypertension in which ischemic cardiomyopathy was excluded after a complete medical workup. Right septal endomyocardial biopsies were performed in hypertensive patients to quantify collagen content. Collagen volume fraction (CVF) was determined on picrosirius red-stained sections with an automated image analysis system. The serum concentration of PIP was measured by specific radioimmunoassay. Compared with normotensives, both serum PIP and CVF were increased (P<0.001) in hypertensives. A direct correlation was found between CVF and serum PIP (r=0.471, P<0.02) in all hypertensives. Histological analysis revealed the presence of 2 subgroups of patients: 8 with severe fibrosis and 18 with nonsevere fibrosis. Serum PIP was higher (P<0.05) in patients with severe fibrosis than in patients with nonsevere fibrosis. Using receiver operating characteristic curves, we observed that a cutoff of 127 microg/L for PIP provided 78% specificity and 75% sensitivity for predicting severe fibrosis with a relative risk of 4.80 (95% CI, 1.19 to 19.30). CONCLUSIONS: These results show a strong correlation between myocardial collagen content and the serum concentration of PIP in essential hypertension. Although preliminary, these findings suggest that the determination of PIP may be an easy and reliable method for the screening and diagnosis of severe myocardial fibrosis associated with arterial hypertension.
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    Sex differences in ochratoxin a toxicity in F344 rats after 7 and 21 days of daily oral administration
    (Elsevier, 2018) Pastor, L. (Laura); García-Jalón, J.A. (José Antonio); Enciso-Gadea, J. M. (José Manuel); Lopez-de-Cerain, A. (Adela); Vettorazzi, A. (Ariane); Gonzalez-Peñas, E. (Elena); Monreal, J.I. (José Ignacio)
    Ochratoxin A (OTA) is a potent renal carcinogen in male rats but not in females. The mechanisms underlying these differences are unknown. The sex-dependent response of F344 rats after a repeated OTA oral administration for 7 (0.50 mg/kg bw) or 21 days (0.21 and 0.50 mg/kg bw) was evaluated. General toxicity, sex and thyroid hormones and histopathology were studied. OTA was quantified (HPLC-FLD) in plasma, kidney and liver and the expression of kidney transporters (RT-qPCR) was studied. After 7 days, kidney histopathology showed more pronounced signs of toxicity in males than in females. After 21 days, a higher toxicity was observed but sex differences disappeared. OTA concentration in plasma and tissues was similar in both sexes. Downregulation was the general OTA-induced effect. Oats' downregulation was slow in males and Oat3 did not change in females. Oatp1 was strongly downregulated in males after 21 days. An opposite effect was observed in Bcrp after 21 days: downregulation in males and upregulation in females. Females showed a dose- and time-dependent decrease of progesterone. Despite the sex differences, the final balance in OTA toxicokinetics at renal cell level does not seem to support a higher accumulation of OTA in male kidneys.
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    Independent association of fibrinogen with carotid intima-media thickness in asymptomatic subjects
    (Karger, 2003) Paramo, J.A. (José Antonio); Benito-Boilos, A. (Alberto); Irimia, P. (Pablo); Beloqui, O. (Óscar); Colina, I. (Inmaculada); Diez-Martinez, J. (Javier); Orbe, J. (Josune); Barba, J. (Joaquín); Zubieta, J.L. (José L.); Martinez-Vila, E. (Eduardo); Monreal, J.I. (José Ignacio)
    BACKGROUND: Fibrinogen has been found to be an independent risk factor for cardiovascular disease. Both genetic and environmental factors contribute to its variability in plasma. However, whether the relation between fibrinogen and carotid intima-media thickness (IMT) is independent of those factors has not been established. Therefore, the aim of this study was to investigate the relations of plasma fibrinogens and the -455 G/A Bbeta-fibrinogen polymorphism with the carotid IMT in a series of asymptomatic subjects. METHODS: Markers of inflammation, C-reactive protein (CRP) and leukocytes, and endothelial perturbation (von Willebrand factor, vWF) were measured in 135 subjects. All individuals underwent a complete clinical examination and lipid measurements (cholesterol and its fractions HDL and LDL and triglycerides). The carotid IMT was measured by B-mode ultrasound in the common carotid artery. RESULTS: Patients in the highest fibrinogen tertile had a significantly higher BMI (p < 0.01), LDL-cholesterol (p < 0.01), leukocyte count, CRP and vWF (p < 0.001). In the univariate model a strong positive relationship was found between plasma fibrinogen and carotid IMT (p < 0.01). Fibrinogen also correlated positively with age, BMI, arterial systolic pressure, cholesterol, cholesterol-LDL, smoking, CRP and vWF (p < 0.01). In the multivariate analysis, the association of fibrinogen with carotid IMT remained significant (p < 0.01) after adjustment for all the parameters analyzed. CONCLUSION: In a population sample of adults without clinically overt atherosclerotic disease, elevated fibrinogen was related to carotid IMT independent of a wide range of important confounding variables
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    Predictive value of serum ferritin in combination with alanine aminotransferase and glucose levels for noninvasive assessment of NAFLD: Fatty liver in obesity (FLiO) study
    (MDPI AG, 2020) Martinez, J.A. (José Alfredo); Benito-Boíllos, A. (Alberto); Zulet, M.A. (María Ángeles); Tur, J.A. (Josep A.); Marin-Alejandre, B.A. (Bertha Araceli); Galarregui-Miquelarena, C. (Cristina); Herrero, J.I. (José Ignacio); Monreal, J.I. (José Ignacio); Elorz, M. (Mariana); Abete, I. (Itziar); Cantero-González, I. (Irene); Pérez-Díaz-Campo, N. (Nuria) del
    The identification of affordable noninvasive biomarkers for the diagnosis and characterization of nonalcoholic fatty liver disease (NAFLD) is a major challenge for the research community. This study aimed to explore the usefulness of ferritin as a proxy biomarker of NAFLD condition, alone or in combination with other routine biochemical parameters. Subjects with overweight/obesity and ultrasound-confirmed liver steatosis (n = 112) from the Fatty Liver in Obesity (FLiO) study were assessed. The hepatic evaluation considered magnetic resonance imaging, ultrasonography, and credited routine blood liver biomarkers. Anthropometry and body composition, dietary intake (by means of a validated 137-item food frequency questionnaire), and specific biochemical markers were also determined. Serum ferritin levels were analyzed using a chemiluminescent microparticle immunoassay kit. Lower serum ferritin concentrations were associated with general better liver health and nutritional status. The evaluation of ferritin as a surrogate of liver damage by means of quantile regression analyses showed a positive association with alanine aminotransferase (ALT) (β = 19.21; p ≤ 0.001), liver fat content (β = 8.70; p = 0.008), and hepatic iron (β = 3.76; p ≤ 0.001), after adjusting for potential confounders. In receiver operating characteristic (ROC) analyses, the panel combination of blood ferritin, glucose, and ALT showed the best prediction for liver fat mass (area under the curve (AUC) 0.82). A combination of ferritin and ALT showed the higher predictive ability for estimating liver iron content (AUC 0.73). This investigation demonstrated the association of serum ferritin with liver health as well as with glucose and lipid metabolism markers in subjects with NAFLD. Current findings led to the identification of ferritin as a potential noninvasive predictive biomarker of NAFLD, whose surrogate value increased when combined with other routine biochemical measurements (glucose/ALT).
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    Tissue availability of insulin-like growth factor I is inversely related to insulin resistance in essential hypertension: effects of angiotensin converting enzyme inhibition
    (Lippincott williams and wilkins, 1998) Diez-Martinez, J. (Javier); Gonzalez, A. (Arantxa); Laviades, C. (Concepción); Gil, M.J. (María José); Monreal, J.I. (José Ignacio)
    Background: The insulin-like growth factor I possesses biologic actions that resemble those of insulin. Tissue access of the factor depends on the distribution of the circulating bound factor between its binding protein 3 that remains within the intravascular space and its binding protein I that is able to cross the endothelium. Preliminary results have shown that tissue availability of insulin-like growth factor I is a determinant of glucose regulation in essential hypertension Objective: To investigate whether the tissue availability of circulating insulin-like growth factor I in patients with essential hypertension is related to insulin resistance and whether chronic angiotensin converting enzyme inhibition influences tissue availability of the factor and insulin resistance in these patients. Design and methods: We studied 29 patients with essential hypertension and 20 age-matched and sex-matched normotensive subjects. The measurements were repeated for 25 patients after 12 months of treatment with lisinopril. Tissue availability of circulating insulin-like growth factor I was assessed by analyzing its distribution between its binding proteins 3 and 1. An insulin resistance index was estimated using the homeostasis model analysis of fasting insulin–glucose interactions. Levels of serum insulin-like growth factor I binding proteins 3 and 1, plasma insulin-like growth factor I, and insulin were determined by specific radioimmunoassays.