Iván Hernández-Cañaveral

Association of the T54 allele of the FABP2 gene with cardiovascular risk factors in obese Mexican subjects

Genetic predisposition to cardiovascular risk may vary between different ethnic groups. We studied the effect of the FABP2 A54T polymorphism on biochemical and anthropometric cardiovascular risk factors in 114 obese Mexican subjects. The mean age of the patients studied was 36.8±13.3 years. Insulin resistance was present in 47%, hypercholesterolaemia in 49% and hyper-triglyceridaemia in 45%. Frequency of the FABP2 genotype was 39% AA, 54.8% AT and 6.2% TT. The AT/TT group showed an increase in body mass index (34±7.1 vs. 31±4.8 kg/m2), waist circumference (101±15.7 vs. 96.5±15.8 cm), triglycerides (145±60.8 vs. 127±79.4 mg/dL; 1.64±0.67 vs. 1.43±0.89 mmol/L), total cholesterol (176±39.4 vs. 164±38.2 mg/dL; 4.55±1.02 vs. 4.24±0.99 mmol/L), LDL (121±24.2 vs. 111±25.9 mg/dL; 3.13±0.62 vs. 2.88±0.67 mmol/L) and VLDL (28.8±12.1 vs. 25.1±16.1 mg/dL; 0.74±0.31 vs. 0.64±0.41 mmol/L) compared to the AA group (p<0.05). The AT/TT group had greatly increased cardiovascular risk, with an OR of 7.56 (95% CI, 1.82-36.24; p<0.001) compared to the AA group. Our results suggest that A54T polymorphism of the FABP2 gene is associated with cardiovascular disease risk in obese subjects.

Amplified expression of dominant‐negative transforming growth factor‐beta type II receptor inhibits collagen type I production via reduced Smad‐3 activity

Background and Aim:  As a pleiotropic protein, transforming growth factor (TGF)‐β induces its effects by binding to its Ser/Thr kinase receptor type II and then recruiting and activating receptor type I, which is phosphorylated and activates Smads that transduce the signal to the nucleus.

Effect of the ADIPOQ Gene -11391G/A Polymorphism Is Modulated by Lifestyle Factors in Mexican Subjects.

Background/Aims: Single nucleotide polymorphisms (SNPs) in the ADIPOQ gene could explain the adiponectin level. However, the knowledge about the influence of genetic and lifestyle factors is not sufficient. The aim was to analyze whether the effect of the -11391G/A SNP in the ADIPOQ gene is modulated by lifestyle factors in Mexican subjects. Methods: A cross-sectional study was performed in which 394 participants were analyzed. Genetic, anthropometric, biochemical, dietary, clinical and physical activity parameters were measured. Statistical analysis was performed with SPSSv19 software. Results: The distribution of the -11391G/A SNP genotypes was 55.6 and 44.4% for GG and AG, respectively. The adiponectin level was modulated by the -11391G/A SNP in response to the body mass index (BMI); A allele carriers showed a higher adiponectin level compared to G homozygous carriers but only in the minor BMI tertile group (p = 0.032). Adiponectin level variability was explained by gender [(r) = 1.5, 95% CI 1.1-1.9, p = 0.000], insulin resistance [(r) = -1.2, 95% CI -0.8 to -1.6, p = 0.000], physical activity [(r) = 0.6, 95% CI 0.2-0.9, p = 0.002] and monounsaturated fat intake [(r) = 0.5, 95% CI 0.38-1.0, p = 0.047]. Conclusions: The adiponectin level was modulated by the interaction between BMI and -11391G/A SNP; this suggests that the lifestyle rather than genetic factors modulates serum adiponectin.

Candida albicans isolated from human fungaemia induces apoptosis in an experimental endocarditis model

Candida albicans is the most common fungal pathogen known to cause endovascular infections, such as vascular catheter sepsis, infections of vascular prostheses and infective endocarditis. A C. albicans isolate was used to determine the apoptotic potential of the fungus in a rat endocarditis model. This study confirms the ability of C. albicans to induce apoptosis in myocardial tissue.

High Dietary ω-6:ω-3 PUFA Ratio Is Positively Associated with Excessive Adiposity and Waist Circumference

Objective: The aim of this study was to analyze dietary ω-6:ω-3 polyunsaturated fatty acid (PUFA) ratio and its association with adiposity and serum adiponectin levels in a Mexican population. Methods: In this cross-sectional study, individuals with a BMI ≥ 18.5 kg/m2, were classified using four methods to measure adiposity. Parameters of body composition were measured by InBody 3.0. Diet intake was evaluated prospectively using a 3-day written food record. Serum high-molecular weight adiponectin isoform was measured using an ELISA assay. Biochemical and adiposity variables were analyzed by tertiles of dietary ω-6:ω-3 PUFA ratio. Results: A total of 170 subjects were recruited with a mean age of 36.9 ± 11.8 years. The 73.5% of subjects were women. Subjects in the higher tertile of dietary ω-6:ω-3 PUFA ratio had more adiposity and higher levels of triglycerides, VLDL-c, glucose, insulin and HOMA-IR than those in the first tertile (p < 0.05). Adiponectin levels showed a trend according to dietary ω-6:ω-3 PUFA ratio (p = 0.06). A linear regression model showed that waist circumference, insulin, and HOMA-IR have positive associations with dietary ω-6:ω-3 PUFA ratio. Conclusion: This study suggests that high dietary ω-6:ω-3 PUFA ratio is positively associated with excessive adiposity and worse metabolic profile.

Cadmium and α-lipoic acid activate similar de novo synthesis and recycling pathways for glutathione balance

Glutathione (GSH) protects cells against oxidative stress. Redox modifiers induce GSH biosynthesis and recycling to maintain reduced environment inside cells. Cadmium (Cd2+) is a heavy metal that activates redox-sensitive transcriptional factors. The antioxidant α-lipoic acid (ALA) has shown to modulate GSH pathways. This study aimed to investigate de novo synthesis and recycling pathways for GSH balance by different Cd2+ concentrations and ALA in HepG2 cells. ALA activates Nrf2 pathway leading to GSH increment. Pre-treatment with 1μM Cd2+ or ALA produces tolerance to 5μM Cd2+ toxic effects. 5μM Cd2+ exposure significantly augmented nuclear Nrf2, GSH and GCLC, GCLM, HMOX1, TNFα and IL-6 mRNA expression but not GSR, however these upsurges were significantly abrogated by ALA or 1μM Cd2+ pre-treatments. Exposure to low Cd2+ concentration generate timely protective responses, similar to that elicited by ALA, maintaining a normal redox balance inside the cell due to GSH replenishment.

Waist Circumference Is an Anthropometric Parameter That Identifies Women with Metabolically Unhealthy Phenotypes

Metabolically healthy (MH) and metabolically unhealthy (MUH) phenotypes can be present in any subject independently of their body mass index (BMI). However, factors related to the presence of these phenotypes are poorly understood. Therefore, the aim of this cross-sectional study is to describe the prevalence and characteristics associated with the MH and MUH phenotypes in Mexican subjects with different BMI categories. Anthropometric and biochemical parameters were evaluated after 12 h of fasting. HMW (High Molecular Weight) adiponectin and insulin levels were measured by ELISA (enzyme-linked immunosorbent assay). A total of 345 subjects were included, of which, 73.9% were women. The prevalence of the MH phenotype was 69.9%, 46.7%, and 19% in normal weight, overweight, and obesity, respectively. ROC (receiver operating characteristic) curve analysis showed that the waist circumference demonstrated a statistical significance (p < 0.01) in detecting the MUH phenotype in each BMI group only in women. Furthermore, subjects with lower HMW adiponectin levels showed a 2.1 increased risk of presenting the MUH phenotype. In conclusion, in this Mexican population, waist circumference was an anthropometric parameter that identified women with the MUH phenotype in all BMI categories and hypoadiponectinemia was a risk factor for the presence of this phenotype.

Antifungal activity of caspofungin in experimental infective endocarditis caused by Candida albicans

BACKGROUND Infective endocarditis is a disease characterised by heart valve lesions, which exhibit extracellular matrix proteins that act as a physical barrier to prevent the passage of antimicrobial agents. The genus Candida has acquired clinical importance given that it is increasingly being isolated from cases of nosocomial infections. OBJECTIVE To evaluate the activity of caspofungin compared to that of liposomal amphotericin B against Candida albicans in experimental infective endocarditis. METHODS Wistar rats underwent surgical intervention and infection with strains of C. albicans to develop infective endocarditis. Three groups were formed: the first group was treated with caspofungin, the second with liposomal amphotericin B, and the third received a placebo. In vitro sensitivity was first determined to further evaluate the effect of these treatments on a rat experimental model of endocarditis by semiquantitative culture of fibrinous vegetations and histological analysis. FINDINGS Our semiquantitative culture of growing vegetation showed massive C. albicans colonisation in rats without treatment, whereas rats treated with caspofungin showed significantly reduced colonisation, which was similar to the results obtained with liposomal amphotericin B. CONCLUSIONS The antifungal activity of caspofungin is similar to that of liposomal amphotericin B in an experimental model of infective endocarditis caused by C. albicans.

Association of Paraoxonase-1 Q192R (rs662) Single Nucleotide Variation with Cardiovascular Risk in Coffee Harvesters of Central Colombia

Paraoxonase 1 (PON1), a high-density lipoprotein-associated antioxidant enzyme, hydrolyzes several organophosphate pesticides and oxidized lipids. The PON1 Q192R polymorphism affects the catalytic efficiency and is considered a risk factor for pesticide intoxication and cardiovascular disease (CVD) but the association is not consistent between individuals or populations. We aimed to study the association of PON1 Q192R polymorphism with CVD risk in coffee harvesters of central Colombia. Demographics were collected from 205 subjects via standardized questionnaires. Lipid profiles and serum butyrylcholinesterase (BChE) were measured by standard procedures. The calculated 10-year atherosclerotic CVD (ASCVD) risk was used as the cardiovascular risk estimate. Q192R genotype was determined by real-time PCR. Prevalence of hypertension, hypercholesterolemia, and the 10-year ASCVD risk was 33%, 62%, and 22%, respectively. BChE levels were no indicative of recent pesticide exposure, although a positive correlation was observed with BChE and hypercholesterolemia. The Q192R genotype frequencies were 38% (QQ), 44% (QR), and 18% (RR). We found an association of the 192Q genotype with hypertension. The results of this study signal the importance to evaluate the influence and potential interactions of BChE and PON1 192Q allele with known genetic and environmental factors implicated in the pathogenesis of CVD.

Acknowledgement to the Reviewers

Chris T. Bolliger, Tygerberg, South Africa Raphael Borie, Paris, France Piera Boschetto, Ferrara, Italy Gabriel T. Bosslet, Indianapolis, USA Louis-Philippe Boulet, Sainte-Foy, Canada A. Bourdin, Montpellier, France John Brannan, Sydney, Australia Joerg Brederlau, Berlin, Germany E.C. Breen, La Jolla, USA Fabienne Bregeon, Marseille, France Pilar Brito-Zeron, Barcelona, Spain Dunja Bruder, Braunschweig, Germany Guy G. Brusselle, Gent, Belgium Martin H. Brutsche, St. Gallen, Switzerland Antonio Bugalho, Lisbon, Portugal Janette Burgess, Camperdown, Australia Umberto Campia, Chicago, USA Giorgio Walter Canonica, Genova, Italy Andre Capderou, Le Plessis Robinson, France Gaetano Caramori, Ferrara, Italy Pierluigi Carratu, Bari, Italy Laura Carrozzi, Pisa, Italy C.R.F. Carvalho, Sao Paulo, Brazil Gian Luca Casoni, Forli, Italy Loris Ceron, Carbonera, Italy Stefania Cerri, Portland, USA Indranil Chakravorty, London, UK Rachel Chambers, London, UK Shi-Chuan Chang, Taipei, Taiwan Ling Chen, Baltimore, USA Alfredo Chetta, Parma, Italy Carlo Chezzi, Parma, Italy Prashant N. Chhajed, Mumbai, India Doo-Sup Choi, Rochester, USA Marco Matteo Ciccone, Bari, Italy Michal Ciurzynski, Warsaw, Poland Donald W. Cockcroft, Saskatoon, Canada Henri Colt, Irvine, USA Alison Condliffe, Cambridge, UK Marco Confalonieri, Trieste, Italy Claudius Conrad, Boston, USA Vittoria Conti, Rome, Italy Robalo Cordeiro, Coimbra, Portugal Massimo Corradi, Parma, Italy Raja Abboud, Vancouver, Canada Yossef Aelony, Rancho Palos Verdes, USA Michalis Agrafiotis, Magoula, Greece Khalid Al Shafi, London, UK Ghada Alsaleh, Illkirch, France Nicolino Ambrosino, Cisanello, Pisa, Italy Kayvan Amjadi, Ottawa, Canada Asha Anandiah, Boston, USA Stephan Andreas, Immenhausen, Germany Jouke T. Annema, Leiden, The Netherlands Katerina Antoniou, Heraklion, Greece Balazs Antus, Budapest, Hungary Juan Carlos Arevalo, Salamanca, Spain Christine Armbruster, Vienna, Austria Laurent Arnaud, Paris, France Hormoz Ashtyani, Hackensack, USA John D. Aubert, Lausanne, Switzerland Najib Ayas, Vancouver, Canada Imran Aziz, Wigan, UK Chung-Xue Bai, Shanghai, China Kristina Bailey, Omaha, USA Petros Bakakos, Athens, Greece Bruno Balbi, Veruno, Italy Ferran Barbe, Lleida, Spain Xavier Basagana Flores, Barcelona, Spain Sandip Basu, Bombay, India Salvatore Battaglia, Palermo, Italy Sevim Bavbek, Ankara, Turkey Gillian Beamer, Columbus, USA H.D. Becker, Heidelberg, Germany Jurgen Behr, Bochum, Germany Carolyn Behrendt, Duarte, USA Maria Belvisi, London, UK Norbert Berend, Glebe, Australia Gidon Berger, Haifa, Israel Robert Berkowitz, Hackensack, USA Nitin Bhatt, Columbus, USA Luca Bianchi, Lumezzane, Italy Andrea Bianco, Campobasso, Italy Semra Bilaceroglu, Izmir, Turkey Jose Blanquer, Valencia, Spain Alexander Blau, Berlin, Germany Konrad E. Bloch, Zurich, Switzerland