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RESUMEN Introducción. El síndrome post COVID (SPC), que se caracteriza por síntomas que se extienden superando las 4 semanas post-infección, podría desencadenar aumento en el riesgo cardiovascular. Las lipoproteínas de alta densidad (HDL) presentan funciones antiaterogénicas, como su capacidad para promover el transporte inverso del colesterol (TIC) y su actividad antioxidante, en la que es clave la enzima paraoxonasa 1 (PON 1). Objetivo. Evaluar funcionalidad de HDL en pacientes con SPC comparados con pacientes asintomáticos (PA) y controles. Material y métodos. Se incluyeron 9 individuos con SPC, 18 PA y 10 controles. Se midieron el hemograma, el perfil lipoproteico básico, las apolipoproteínas A-I y B, y marcadores inflamatorios por métodos automatizados. La actividad de PON 1 se evaluó empleando un método espectrofotométrico y los 3 pasos del TIC, eflujo de colesterol (ECC), y actividades de lecitina:colesterol aciltransferasa (LCAT) y proteína transportadora de colesterol esterificado (CETP), por métodos radiométricos. Resultados. No se observaron diferencias en sexo, edad, ni parámetros generales. El grupo PA presentó mayor actividad PON que los controles (94±76 vs. 183±111 vs. 148±58 nmol/mL.min, en controles, PA y SPC, respectivamente; p=0,049). No se observaron diferencias en el TIC. El ECC (r=-0,45; p=0,049) y CETP (r=-0,38; p=0,028) correlacionaron negativamente con el índice neutrófilos/linfocitos. LCAT correlacionó inversamente con la ferritina (r=-0,34; p=0,046). Conclusiones. El incremento de PON 1 en el grupo PA representaría un mecanismo de defensa frente al estrés oxidativo post-infección. Todos los pasos del TIC mostraron una correlación negativa con marcadores inflamatorios. Nuestros resultados podrían explicar, en parte, el vínculo entre COVID y ateroesclerosis.

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ABSTRACT Background. Post-COVID syndrome (PCS), characterized by symptoms that persist for more than 4 weeks after initial infection, could increase cardiovascular risk. High-density lipoproteins (HDL) have antiatherogenic functions, such as the ability to promote reverse cholesterol transport (RCT) and antioxidant activity. In this regard, paraoxonase 1 (PON 1) plays a key role. Objective. The aim of this study was to evaluate HDL functions in patients with PCS and compare them with asymptomatic patients (AP) and controls. Methods. The study included 9 patients with PCS, 18 AP and 10 controls. Complete blood count, basic lipoprotein profile, apolipoproteins A-I and B, and inflammatory markers were measured using automated methods. PON 1 activity was evaluated by a spectrophotometric assay, and the 3 steps of RCT, cellular cholesterol (efflux CCE), lecithin-cholesterol acyltransferase (LCAT) activity and cholesteryl ester transfer protein (CETP) activity were evaluated by radiometric assays. Results. There were no differences in sex, age, or general parameters. The AP group had higher PON activity than the control group (94±76 vs. 183±111 vs. 148±58 nmol/mL.min, in controls, AP and PCS, respectively; p=0.049). There were no differences in RCT. Cellular cholesterol efflux (r=-0.45; p=0.049) and CETP (r=- 0.38; p=0.028) had a negative correlation with neutrophil-to-lymphocyte ratio. LCAT had an inverse correlation with ferritin (r=-0.34; p=0.046). Conclusions . Increased antioxidant activity of PON 1 would represent a defensive mechanism against oxidative stress after infection. All the RCT steps had a negative correlation with inflammatory markers. Our findings may explain, at least in part, the link between COVID-19 and atherosclerosis.

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The aim of this work was to analyze the effects of long-term exposure to titanium dioxide (TiO2) micro- (MPs) and nanoparticles (NPs) (six and 12 months) on the biochemical and histopathological response of target organs using a murine model. Male Wistar rats were intraperitoneally injected with a suspension of TiO2 NPs (5 nm; TiO2-NP5 group) or MPs (45 µm; TiO2-NP5 group); the control group was injected with saline solution. Six and 12 months post-injection, titanium (Ti) concentration in plasma and target organs was determined spectrometrically (ICP-MS). Blood smears and organ tissue samples were evaluated by light microscopy. Liver and kidney function was evaluated using serum biochemical parameters. Oxidative metabolism was assessed 6 months post-injection (determination of superoxide anion by nitroblue tetrazolium (NBT) test, superoxide dismutase (SOD) and catalase (CAT), lipid peroxidation, and paraoxonase 1). Titanium (Ti) concentration in target organs and plasma was significantly higher in the TiO2-exposed groups than in the control group. Histological evaluation showed the presence of titanium-based particles in the target organs, which displayed no structural alterations, and in blood monocytes. Oxidative metabolism analysis showed that TiO2 NPs were more reactive over time than MPs (p < .05) and mobilization of antioxidant enzymes and membrane damage varied among the studied organs. Clearance of TiO2 micro and nanoparticles differed among the target organs, and lung clearance was more rapid than clearance from the lungs and kidneys (p < .05). Conversely, Ti concentration in plasma increased with time (p < .05). In conclusion, neither serum biochemical parameters nor oxidative metabolism markers appear to be useful as biomarkers of tissue damage in response to TiO2 micro- and nanoparticle deposits at chronic time points.

Asunto(s)

Ratas Wistar , Titanio , Titanio/química , Animales , Masculino , Ratas , Nanopartículas del Metal/química , Riñón/metabolismo , Riñón/patología , Riñón/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Nanopartículas/química , Hígado/metabolismo , Hígado/patología

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The surface of a biomedical implant can be a potential endogenous source of release of microparticles (MPs) and nanoparticles (NPs) into the biological environment. In addition, titanium particles from exogenous sources can enter the body through inhalation, ingestion, or dermal contact. The aim of this work was to evaluate the biological response of the lung, liver, and kidneys to acute exposure to titanium dioxide (TiO2 ). Male Wistar rats were intraperitoneally injected with a suspension of 45 µm or 5 nm TiO2 particles. One month post-exposure, titanium concentration was determined spectrometrically (ICP-MS) in plasma and target organs. Blood smears and organ tissue samples were examined histopathologically, and oxidative metabolism was analyzed (superoxide anion by nitro blue tetrazolium (NBT) test; superoxide dismutase (SOD) and catalase (CAT); lipid peroxidation; paraoxonase 1). Liver (aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase) and kidney (urea, creatinine) function was evaluated using serum biochemical markers. Microchemical and histological analysis revealed the presence of particles, though no structural alterations, in TiO2 -exposed groups. NBT test showed an increase in the percentage of reactive cells and antioxidant enzyme consumption in lung samples in the 45 µm and 5 nm TiO2 -exposed groups. Only the 5 nm particles caused a decrease in SOD and CAT activity in the liver. No changes in renal oxidative metabolism were observed in either of the TiO2 -exposed groups. Determination of serum biochemical markers and analysis of oxidative metabolism are not early bioindicators of tissue damage caused by TiO2 MPs and NPs.

Asunto(s)

Nanopartículas , Titanio , Animales , Antioxidantes/farmacología , Biomarcadores/metabolismo , Modelos Animales de Enfermedad , Masculino , Ratones , Estrés Oxidativo , Ratas , Ratas Wistar , Superóxido Dismutasa , Titanio/química , Titanio/farmacología

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OBJECTIVE: To explore the association between Triglyceride/High-density lipoprotein cholesterol (TG/HDL-C) index and these enzymes and proteins in a pediatric population. METHODS: Children and adolescents (7-14 y old) were recruited (n = 150) and anthropometric data were registered. Glucose, TG, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), HDL-C plus cholesteryl ester transfer protein (CETP), lipoprotein-associated phospholipase A2 (Lp-PLA2) and paraoxonase 1 (PON1) activities were determined. RESULTS: Twenty-five individuals presented TG/HDL-C ratio ≥ 3.0. These individuals exhibited higher TG [164 (126-186) vs. 65 (48-72) mg/dL; p < 0.01] CETP [250 (232-263) vs. 223 (193-237)% mL/min; p < 0.01] and Lp-PLA2 (4.5 ± 1.9 vs. 3.5 ± 1.3; p < 0.05) plus lower HDL-C [41 (37-49) vs. 52 (48-62) mg/dL; p < 0.01] compared to an age-matched group with TG/HDL-C < 3.0. TG/HDL-C ratio was associated to CETP (p < 0.01) and Lp-PLA2 (p < 0.05). Multiple lineal regression analyses showed TG/HDL-C index as an independent predictor of CETP (r2 = 0.29; beta = 0.49; p < 0.01) and Lp-PLA2 (r2 = 0.21; beta = 0.32; p < 0.05) activities. CONCLUSION: Children and adolescents with TG/HDL-C ≥ 3.0 presented a more atherogenic lipid profile and higher CETP and Lp-PLA2 activities, which would indicate alterations in lipoprotein metabolism and quality.

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1-Alquil-2-acetilglicerofosfocolina Esterasa , Proteínas de Transferencia de Ésteres de Colesterol , 1-Alquil-2-acetilglicerofosfocolina Esterasa/metabolismo , Adolescente , Arildialquilfosfatasa , Niño , Proteínas de Transferencia de Ésteres de Colesterol/metabolismo , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Humanos , Triglicéridos/sangre

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BACKGROUND: In patients with rheumatoid arthritis (RA), qualitative alterations of low and high-density lipoproteins (LDL and HDL, respectively) might partially explain their increased cardiovascular risk. Tocilizumab has been associated with an increase in lipids, including triglyceride (TG) and cholesterol levels. The aim of this study is to evaluate the effect of tocilizumab on certain LDL and HDL characteristics (oxidized LDL levels, HDL-associated enzymes, chemical composition of both total HDL and HDL3c subpopulation, and their capacity to promote cellular cholesterol efflux) at baseline and 3 months after the start of treatment in patients with RA. METHODS: Twenty-eight RA patients (ACR/EULAR 2010 criteria) with indication of treatment with tocilizumab were included in the present study. Clinical assessment [Health assessment questionnaire (HAQ)], disease activity score 28 (DAS28), high-sensitivity C reactive protein (hsCRP) concentration, lipid profile, and lipoprotein (a) [Lp(a)] levels were evaluated in all patients at baseline and after 3 months of treatment with tocilizumab. Lipoprotein characteristics were evaluated through the levels of oxidized LDL (OxLDL), the activity of paraoxonase (PON) 1, the composition of total HDL and small, dense HDL3c subpopulation, and their ability to promote cellular cholesterol efflux. RESULTS: After 3 months of treatment with tocilizumab, HAQ (- 23%, p < 0.05), DAS28 (- 49%, p < 0.001), and hsCRP (- 94%, p < 0.01) levels decreased significantly. Total cholesterol (TC), LDL-C, non-HDL-C, and apo B levels showed a significant increase after treatment (TC: + 7.0%, p < 0.01; LDL-C: + 10%, p < 0.01; non-HDL-C: + 9.9%, p < 0.01; and apo B: + 9.6%, p < 0.05). Decreases in Lp(a) and OxLDL levels were also observed after treatment [Lp(a): - 50%, p < 0.01; and oxLDL: - 5.4%, p < 0.05]. The latter was in accordance with the increment detected in PON activity. No changes were observed in HDL capacity to promote cholesterol efflux (p > 0.05) in the whole group. CONCLUSIONS: Treatment with tocilizumab reduced hsCRP levels and displayed positive effects on certain lipoprotein-related parameters, such as a potent decrease inLp(a) and a reduction in OxLDL levels. Moreover, HDL capacity to promote cellular cholesterol efflux was maintained after 3 months of treatment.

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PURPOSE: Morbid obesity represents the most severe form of obesity and surgical intervention would be its only successful treatment. Bariatric surgery could generate modifications in carbohydrate metabolism and in lipid profile plus lipoprotein-associated proteins and enzymes, such as lipoprotein-associated phoslipase A2 (Lp-PLA2), cholesteryl ester transfer protein (CETP), and paraoxonase (PON) 1. The aim of the present study was to analyze changes in inflammation markers, carbohydrate metabolism, and lipid parameters in patients who underwent bariatric surgery. METHODS: Thirty-seven patients with morbid obesity were recruited. Evaluations were performed before (T0) and 1 (T1) and 6 (T2) months after surgery. Glucose, insulin, high-sensitivity C-reactive protein (hsCRP), triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, apolipoproteins (apo) A-I, and B plus Interleukin 1ß and 6 levels in addition to CETP, Lp-PLA2, and PON 1 activities were determined. RESULTS: Body mass index decreased at T1 and T2 (p < 0.01). An improvement in all markers of insulin resistance (p < 0.05) was observed at T1. hsCRP levels diminished at T2 (p < 0.05). Triglyceride levels decreased at T1 and T2 (p < 0.05). HDL-C and apo A-I showed a decrease at T1 which was completely reversed at T2 (p < 0.05). Lp-PLA2 activity increased at T1, which was reversed at T2 (p < 0.05), and CETP activity was diminished at T2 (p < 0.05). PON and ARE activities decreased at T1 and partially recovered at T2 (p < 0.05). CONCLUSIONS: These results would be indicative of a favorable effect of bariatric surgery on markers of carbohydrate metabolism and cardiovascular disease lipid risk factors.

Asunto(s)

Derivación Gástrica , Obesidad Mórbida , Proteínas de Transferencia de Ésteres de Colesterol , HDL-Colesterol , LDL-Colesterol , Humanos , Lipoproteínas , Obesidad Mórbida/cirugía

RESUMEN

INTRODUCCIÓN Los pacientes pediátricos con enfermedad celíaca (EC) y diabetes mellitus tipo 1 (DM1) pueden presentan un riesgo mayor de enfermedad cardiovascular (ECV) en la vida adulta. Las HDL constituyen las únicas lipoproteínas con capacidad ateroprotectora. La dieta libre de gluten (DLG) es el único tratamiento en la EC. Objetivo Evaluar factores de riesgo de ECV tradicionales y emergentes en niños con DM1, EC y con DM1+EC. MÉTODOS 86 niños <18 años, pareados por sexo y z-IMC (52 con DM1, 34 con EC y 16 con DM1+EC). La edad fue menor en la EC; la estadística se ajustó por edad. Triglicéridos (TG),colesterol total (CT), colesterol de LDL (C-LDL) y de HDL (C-HDL), apo B y apo A-I (métodos estandarizados); actividades enzimáticas asociadas a la función de las HDL (CETP, PON-1, LCAT y Lp-PLA2), y el eflujo de colesterol (técnicas desarrolladas). Diecisiete niños con EC se revaloraron a los 6 meses de una DLG. Test de Kruskal Wallis; Wilcoxon test. Expresión de los datos mediana (Q1-Q3). RESULTADOS El grupo DM1+EC presentó mayor concentración (mg/dL) de TG: 87 (55-185), CT 183 (141-213), C-no HDL 135 (85-172) y de apo B 93 (57-122) y mayor actividad de CETP 167 (109-207) %/ml.min respecto de los niños con EC [63 (50-85), 163 (130-180), 113 (93-135), 74 (64- 84) y 112 (104-124), respectivamente], p< 0,05. La concentración (mg/dL) de C-HDL: 41 (34-48) y de apo A-I (106-136) fue menor en la EC comparado con DM1 49 (43-54) y 136 (126-150), respectivamente, y DM1+EC 46 (40-56) y 145 (136-161), respectivamente (p< 0,01). El eflujo de colesterol aumentó a 6 meses de DLG [4,8 (3,7-5,5) vs. 7,3 (6,4-8,7) %; p<0,01, basal y 6 meses de DLG, respectivamente]. DISCUSIÓN La coexistencia de DM1 y de EC en niños se asoció una disminución en la funcionalidad de las HDL (mayor CETP), incrementando el riesgo de ECV en ellos respecto de niños con EC. La DLG mejoró el perfil ateroprotector de las HDL, reflejado en parte, por una mayor capacidad de eflujo de colesterol.

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Enfermedad Celíaca , Diabetes Mellitus Tipo 1 , Factores de Riesgo de Enfermedad Cardiaca

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BACKGROUND: Hereditary hemochromatosis (HH) is a primary iron overload (IO) condition. Absolute telomere length (ATL) is a marker of cellular aging and DNA damage associated with chronic diseases and mortality. AIM: To evaluate the relationship between ATL and IO in patients with HH. METHODS: Cross-sectional study including 25 patients with HH: 8 with IO and 17 without IO (ferritin < 300 ng/ml) and 25 healthy controls. Inclusion criteria were: age > 18 years, male sex and HH diagnosis. Patients with diabetes or other endocrine and autoimmune diseases were excluded. ATL was measured by real-time PCR. RESULTS: HH patients with IO were older (P<0.001) and showed higher ferritin concentration (P<0.001). Patients with HH, disregarding the iron status, showed higher glucose and body mass index (BMI) than controls (both P<0.01). ATL was shorter in patients with IO than controls [with IO: 8 (6-14), without IO: 13 (9-20), and controls: 19 (15-25) kilobase pairs, P<0.01]; with a linear trend within groups (P for trend <0.01). Differences in ATL remained statistically significant after adjusting by age, BMI and glucose (P<0.05). DISCUSSION: Patients with IO featured shorter ATL while patients without IO showed only mild alterations vs. controls. Screening for IO is encouraged to prevent iron-associated cellular damage and early telomere attrition.

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Hemocromatosis/inmunología , Hierro/metabolismo , Leucocitos/inmunología , Homeostasis del Telómero/inmunología , Telómero/metabolismo , Adulto , Anciano , Envejecimiento/inmunología , Estudios Transversales , Ferritinas/sangre , Hemocromatosis/sangre , Hemocromatosis/diagnóstico , Hemocromatosis/genética , Proteína de la Hemocromatosis/genética , Humanos , Hierro/sangre , Leucocitos/metabolismo , Masculino , Persona de Mediana Edad , Mutación , Estrés Oxidativo/inmunología

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Urban air pollution is a serious environmental problem in developing countries worldwide, and health is a pressing issue in the megacities in Latin America. Buenos Aires is a megacity with an estimated moderate Air Quality Index ranging from 42 to 74 µg/m3. Exposure to Urban Air Particles from Buenos Aires (UAP-BA) induces morphological and physiological respiratory alterations; nevertheless, no studies on extrapulmonary organs have been performed. The aim of the present study was to explore the health effects of chronic exposure to UAP-BA (1, 6, 9, and 12 months) on the liver, heart, and serum risk biomarkers. BALB/c mice were exposed to UAP-BA or filtered air (FA) in inhalation chambers, and liver and heart histopathology, oxidative metabolism (superoxide dismutase, SOD; catalase, CAT; lipoperoxidation, TBARS), amino transaminases (AST, ALT) as serum risk biomarkers, alkaline phosphatase (ALP), paraxonase-1 (PON-1), and lipoprotein-associated phospholipase A2 (Lp-PLA2) were evaluated. Chronic exposure to real levels of UAP in Buenos Aires led to alterations in extrapulmonary organs associated with inflammation and oxidative imbalance and to changes in liver and heart risk biomarkers. Our results may reflect the impact of the persistent air pollution in Buenos Aires on individuals living in this Latin American megacity.

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Contaminantes Atmosféricos/análisis , Contaminación del Aire , Animales , Biomarcadores , Ratones , Ratones Endogámicos BALB C , Material Particulado/análisis

RESUMEN

BACKGROUND: High altitude is associated with hypobaric hypoxia, and metabolic modifications. In particular, alterations to lipoprotein-associated enzymes have been reported under hypoxia. OBJECTIVE: To determine the association between paraoxonase 1 (PON-1) and Cholesteryl-ester transfer protein (CETP) activities and altitude in two groups of Argentinean Indigenous schoolchildren living at different altitudes. METHODS: A cross-sectional study compared 151 schoolchildren from San Antonio de los Cobres (SAC), 3,750 m, with 175 schoolchildren from Chicoana (CH), 1,400 m. Anthropometric data, lipids, apolipoprotein (apo) A-I, apo B, plus PON-1 and CETP activities were determined. RESULTS: The prevalence of overweight/obesity was significantly lower in SAC than in CH. Z- BMI (0.3 vs 0.7), Apo A-I/Apo B (1.67 vs. 1.85) and PON-1 (170 vs. 243 nmol/mL.min) were significantly lower in SAC than in CH, respectively. Total cholesterol (156 vs 144 mg/dL), triglycerides (TG) (119 vs. 94 mg/dL), apo A-I (133 vs. 128 mg/dL), apo B (84 vs. 73 mg/dL), hematocrit (48 vs. 41%), transferrin (295 vs. 260 mg/dL) and CETP (181 vs. 150%/mL.h) were significantly higher in SAC than in CH. There was a significant univariate association between altitude and transferrin (r0.38), hematocrit (r0.75), TG (r0.24), apo B (r0.29), PON-1 (r-0.40), and CETP (r0.37). Multiple linear regression analyses showed that altitude was significantly associated with children's TG (ß = 0.28, R2 = 0.14), HDL-C (ß = â€’0.27; R2 = 0.23), apo B (ß = 0.32; R2 = 0.14), CETP (ß = 0.38; R2 = 0.15) and PON-1 (ß = â€’0.36; R2 = 0.16), adjusted for age, gender and BMI. CONCLUSION: SAC children presented a more atherogenic lipid profile, plus lower PON1 and higher CETP activities, than CH children.

Asunto(s)

Altitud , Arildialquilfosfatasa/metabolismo , Proteínas de Transferencia de Ésteres de Colesterol/metabolismo , Antropometría , Apolipoproteína A-I/análisis , Apolipoproteínas B/análisis , Argentina/epidemiología , Aterosclerosis/diagnóstico , Niño , Colesterol/sangre , Estudios Transversales , Femenino , Hematócrito , Humanos , Masculino , Obesidad/epidemiología , Prevalencia , Factores de Riesgo , Transferrina/análisis , Triglicéridos/sangre

RESUMEN

Primary iron overload (IO) is commonly associated with mutations in the hereditary hemochromatosis gene (HFE). Nonetheless, other genetic variants may influence the development of IO beyond HFE mutations. There is a single nucleotide polymorphism (SNP) at - 174 G>C of the interleukin (IL)-6 gene which might be associated with primary IO. Our aim was to study the association between the SNP - 174 G>C gene promoter of IL-6 and primary IO in middle-aged male patients. We studied 37 men with primary IO diagnosed by liver histology. Controls were age-matched male volunteers (n = 37). HFE mutations and the SNP - 174 G>C gene promoter of IL-6 were evaluated by PCR-RFLP. Logistic regression was used to evaluate the association between primary IO and SNP - 174 G>C gene promoter of IL-6. Patients and control subjects were in Hardy-Weinberg equilibrium for the SNP - 174 G>C gene promoter of IL-6 (p = 0.17). Significantly different genotype frequencies were observed between patients (43% CC, 43% CG, and 14% GG) and control subjects (10% CC, 41% CG, and 49% GG) (OR = 4.09, 95% CI = 2.06-8.13; p < 0.0001). The multiple logistic regression analysis showed that IO was significantly associated with CC homozygosis in the SNP - 174 G>C gene promoter of IL-6 (OR = 6.3, 95% CI = 1.9-21.4; p < 0.005) in a model adjusted by age and body mass index. In conclusion, CC homozygosis in the SNP - 174 G>C gene promoter of IL-6 can be proposed as one of the gene variants influencing iron accumulation in male adults with HFE mutations. Studies in larger cohorts are warranted.

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Hemocromatosis/genética , Interleucina-6/genética , Sobrecarga de Hierro/genética , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas/genética , Adulto , Estudios de Casos y Controles , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Hemocromatosis/diagnóstico , Proteína de la Hemocromatosis/genética , Homocigoto , Humanos , Sobrecarga de Hierro/diagnóstico , Masculino , Persona de Mediana Edad , Polimorfismo de Longitud del Fragmento de Restricción

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Uptake of low-density lipoprotein (LDL) particles by macrophages represents a key step in the development of atherosclerotic plaques, leading to the foam cell formation. Chemical modification of LDL is however necessary to induce this process. Proatherogenic LDL modifications include aggregation, enzymatic digestion and oxidation. LDL oxidation by one-electron (free radicals) and two-electron oxidants dramatically increases LDL affinity to macrophage scavenger receptors, leading to rapid LDL uptake and fatty streak formation. Circulating high-density lipoprotein (HDL) particles, primarily small, dense, protein-rich HDL3, provide potent protection of LDL from oxidative damage by free radicals, resulting in the inhibition of the generation of pro-inflammatory oxidized lipids. HDL-mediated inactivation of lipid hydroperoxides involves their initial transfer from LDL to HDL and subsequent reduction to inactive hydroxides by redox-active Met residues of apolipoprotein A-I. Several HDL-associated enzymes are present at elevated concentrations in HDL3 relative to large, light HDL2 and can be involved in the inactivation of short-chain oxidized phospholipids. Therefore, HDL represents a multimolecular complex capable of acquiring and inactivating proatherogenic lipids. Antioxidative function of HDL can be impaired in several metabolic and inflammatory diseases. Structural and compositional anomalies in the HDL proteome and lipidome underlie such functional deficiency. Concomitant normalization of the metabolism, circulating levels, composition and biological activities of HDL particles, primarily those of small, dense HDL3, can constitute future therapeutic target.

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OBJECTIVE: The study aims to determine the association between apo B levels in mothers and their pre-school offspring. METHODS: Anthropometric measurement (e.g. BMI), lipids, lipoproteins, and apolipoproteins (e.g. apo B) levels in mothers and their children were obtained in November 2015 in Buenos Aires. RESULTS: Eighty-four children (42M) aged 5.3±1.6 years and their mothers aged 33.8±7.2 years were examined. The prevalence of overweight was 39.2 % (33) in mothers and 22.6 % (19) in children, and the prevalence of obesity was 38.1% (32) in mothers and 10.7% (9) in children. Multiple linear regression analysis showed that maternal apo B levels were associated with apo B levels in their offspring, adjusted for confounding variables (Beta=0.29; p=0.03; R2=0.25). Furthermore, offspring born to mothers with high apo B levels were six times likelier to have high apo B levels (OR), 5.7; (95% CI 1.3-25.5). CONCLUSION: This study suggests that maternal apo B levels were significantly associated with apo B concentration in their pre-school age children.

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Apolipoproteína B-100/sangre , Sobrepeso/sangre , Sobrepeso/epidemiología , Adulto , Argentina/epidemiología , Enfermedades Cardiovasculares/epidemiología , Niño , Preescolar , Estudios Transversales , Dislipidemias/sangre , Dislipidemias/epidemiología , Femenino , Humanos , Masculino , Obesidad/sangre , Obesidad/epidemiología , Linaje , Factores de Riesgo

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AIM: To evaluate novel risk factors and biomarkers of cardiovascular disease in celiac disease (CD) patients compared with healthy controls. METHODS: Twenty adult patients with recent diagnosis of CD and 20 sex, age and body mass index-matched healthy controls were recruited during a period of 12 mo. Indicators of carbohydrate metabolism, hematological parameters and high sensitive C reactive protein were determined. Moreover, lipoprotein metabolism was also explored through evaluation of the lipid profile and the activity of cholesteryl ester transfer protein and lipoprotein associated phospholipase A2, which is also considered a specific marker of vascular inflammation. The protocol was approved by the Ethic Committee from School of Pharmacy and Biochemistry, University of Buenos Aires and from Buenos Aires Italian Hospital, Buenos Aires, Argentina. RESULTS: Regarding the indicators of insulin resistance, CD patients showed higher plasma insulin levels [7.2 (5.0-11.3) mU/L vs 4.6 (2.6-6.7) mU/L, P < 0.05], increased Homeostasis Model Assessment-Insulin Resistance [1.45 (1.04-2.24) vs 1.00 (0.51-1.45), P < 0.05] and lower Quantitative Sensitive Check index [0.33 (0.28-0.40) vs 0.42 (0.34-0.65), P < 0.05] indexes. Folic acid concentration [5.4 (4.4-7.9) ng/mL vs 12.2 (8.0-14.2) ng/mL, P < 0.01] resulted to be lower and High-sensitivity C reactive protein levels higher (4.21 ± 6.47 mg/L vs 0.98 ± 1.13 mg/L, P < 0.01) in the patient group. With respect to the lipoprotein profile, CD patients showed lower high density lipoprotein-cholesterol (HDL-C) (45 ± 15 mg/dL vs 57 ± 17 mg/dL, P < 0.05) and apo A-I (130 ± 31 mg/dL vs 155 ± 29 mg/dL, P < 0.05) levels, as well as higher total cholesterol/HDL-C [4.19 (3.11-5.00) vs 3.52 (2.84-4.08), P < 0.05] and apo B/apo A-I (0.75 ± 0.25 vs 0.55 ± 0.16, P < 0.05) ratios in comparison with control subjects. No statistically significant differences were detected in lipoprotein-associated lipid transfer protein and enzymes. CONCLUSION: The presence and interaction of the detected alterations in patients with CD, would constitute a risk factor for the development of atherosclerotic cardiovascular disease.

RESUMEN

The incidence of metabolic disorders including obesity, type 2 diabetes and metabolic syndrome have seriously increased in the last decades. These diseases - with growing impact in modern societies - constitute major risk factors for neurodegenerative disorders such as Alzheimer's disease (AD), sharing insulin resistance, inflammation and associated cognitive impairment. However, cerebral cellular and molecular pathways involved are not yet clearly understood. Thus, our aim was to study the impact of a non-severe high fat diet (HFD) that resembles western-like alimentary habits, particularly involving juvenile stages where the brain physiology and connectivity are in plain maturation. To this end, one-month-old C57BL/6J male mice were given either a control diet or HFD during 4 months. Exposure to HFD produced metabolic alterations along with changes in behavioral and central parameters, in the absence of obesity. Two-month-old HFD mice showed increased glycemia and plasmatic IL1ß but these values normalized at the end of the HFD protocol at 5 months of age, probably representing an acute response that is compensated at later stages. After four months of HFD exposure, mice presented dyslipidemia, increased Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity, hepatic insulin resistance and inflammation. Alterations in the behavioral profile of the HFD group were shown by the impediment in nest building behavior, deficiencies in short and mid-term spatial memories, anxious and depressive- like behavior. Regarding the latter disruptions in emotional processing, we found an increased neural activity in the amygdala, shown by a greater number of c-Fos+ nuclei. We found that hippocampal adult neurogenesis was decreased in HFD mice, showing diminished cell proliferation measured as Ki67+ cells and neuronal differentiation in SGZ by doublecortin labeling. These phenomena were accompanied by a neuroinflammatory and insulin-resistant state in the hippocampus, depicted by a reactive phenotype in Iba1+ microglia cells (increased in number and soma size) and an impaired response to insulin given by decreased phosphorylated Akt levels and increased levels of inhibitory phosphorylation of IRS1. Our data portray a set of alterations in behavioral and neural parameters as a consequence of an early-life exposure to a quite moderate high fat diet, many of which can resemble AD-related features. These results highly emphasize the need to study how metabolic and neurodegenerative disorders are interrelated in deep, thus allowing the finding of successful preventive and therapeutic approaches.

Asunto(s)

Amígdala del Cerebelo , Conducta Animal/fisiología , Disfunción Cognitiva/etiología , Dieta Alta en Grasa/efectos adversos , Dislipidemias/etiología , Hipocampo , Inflamación/etiología , Neurogénesis/fisiología , Amígdala del Cerebelo/metabolismo , Amígdala del Cerebelo/patología , Amígdala del Cerebelo/fisiopatología , Animales , Hipocampo/metabolismo , Hipocampo/patología , Hipocampo/fisiopatología , Hiperinsulinismo/etiología , Masculino , Ratones , Ratones Endogámicos C57BL

RESUMEN

BACKGROUND AND AIMS: Rheumatoid arthritis (RA) is a chronic, inflammatory disease associated with increased risk of cardiovascular disease (CVD). Measures of HDL metabolism/function were shown to be altered in RA patients with high disease activity. We aimed at evaluating the effect of HDL characteristics on arterial stiffness in RA patients classified according to the inflammatory disease activity. METHODS: RA patients were classified according to disease activity (DAS-28) into active RA (n = 27; DAS-28 > 3.2) and inactive RA patients (n = 17; DAS-28 < 3.2). A control group of healthy individuals was also studied (n = 33). Clinical and biochemical characteristics, cholesteryl ester transfer protein (CETP) and paraoxonase 1 (phenylacetate and paraoxonase) activities and carotid-femoral pulse wave velocity (cf-PWV) were determined. RESULTS: Anthropometric characteristics were similar in all groups. In accordance with the inflammatory status, active RA patients presented elevated hsCRP levels (p < 0.001). There were no differences in the lipid profile between groups. Similarly, features of insulin resistance were absent in RA patients (p = non-significant). Active RA patients presented higher CETP activity than the other two groups (p = 0.026). Phenylacetate and paraoxonase activities were altered in active RA patients in comparison with the other groups (p = 0.034 and p = 0.041, respectively). Cf-PWV was significantly higher in active RA patients in comparison with controls, following adjustment by age (p = 0.030). Age (ßst = 0.468, p = 0.013) and apo A-I levels (ßst = -0.405, p = 0.029) were independent predictors of cf-PWV in a model including hsCRP, HOMA-IR, and phenylacetate activity (r(2) = 0.42). CONCLUSIONS: High DAS-28 identifies patients with alterations in HDL characteristics. Plasma levels of apo A-I can be used as a marker of arterial stiffness in RA.

Asunto(s)

Apolipoproteína A-I/metabolismo , Arterias/patología , Artritis Reumatoide/fisiopatología , Lipoproteínas HDL/sangre , Rigidez Vascular , Anciano , Antropometría , Antioxidantes/química , Artritis Reumatoide/metabolismo , Arildialquilfosfatasa/sangre , Biomarcadores/sangre , Enfermedades Cardiovasculares/metabolismo , Proteínas de Transferencia de Ésteres de Colesterol/sangre , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Análisis de la Onda del Pulso , Índice de Severidad de la Enfermedad

RESUMEN

Exposure to air particulate matter (PM) is associated with increased cardiovascular morbimortality. However, PM doesn't affect equally to all people, being the old cohort the most susceptible and studied. We hypothesized that another specific life phase, the middle-aged subpopulation, may be negatively affected. Therefore, the aim of this study was to analyze in vivo the acute biological impact of two environmental particles, Urban Air Particles from Buenos Aires and Residual Oil Fly Ash, on the cardiorespiratory system of middle-aged mice, evaluating oxidative metabolism and inflammation. Both PM provoked a local and systemic inflammatory response, leading to a reduced alveolar area in the lung, an epicard inflammation in the heart, an increment of IL-6, and a reduction on PON 1 activity in serum of middle-aged animals. The positive correlation of local parameters with systemic markers of oxidative stress and inflammation could be responsible for associations of cardiovascular morbimortality in this subpopulation.

Asunto(s)

Contaminantes Atmosféricos/toxicidad , Enfermedades Cardiovasculares/inducido químicamente , Exposición por Inhalación/efectos adversos , Pulmón/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Material Particulado/toxicidad , Contaminantes Atmosféricos/análisis , Animales , Argentina , Biomarcadores/sangre , Líquido del Lavado Bronquioalveolar/inmunología , Enfermedades Cardiovasculares/inmunología , Ceniza del Carbón/análisis , Ceniza del Carbón/toxicidad , Corazón/efectos de los fármacos , Inflamación , Exposición por Inhalación/análisis , Interleucina-6/sangre , Interleucina-6/inmunología , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Miocardio/inmunología , Miocardio/patología , Estrés Oxidativo/inmunología , Material Particulado/análisis

RESUMEN

AIMS: The aim of this study was to evaluate the effects of acute hypobaric hypoxia (HH) on vascular reactivity and biochemical markers associated with endothelial function (EF). MAIN METHODS: Ten healthy subjects were exposed to a simulated altitude of 4,000 meters above sea level for 4 hours in a hypobaric chamber. Vascular reactivity was measured by the flow-mediated vasodilatation (FMVD) test. Endothelin-1, high sensitive-C reactive protein (hsCRP), vascular cell adhesion molecule 1, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), paraoxonase and adiponectin levels, and FMVD were evaluated before and after the exposure. KEY FINDINGS: Subjects were young (age: 32±6 years), lean [body mass index: 23.9±2.0kg/m(2), waist circumference: 77(IQR: 72-80) cm], and presented normal clinical and biochemical parameters. No significant changes were evidenced in FMVD in response to HH (pre: 0.45 (0.20-0.70) vs. during: 0.50 (0.20-1.22) mm; p=0.594). On the other hand, endothelin-1 (+54%, p<0.05), hsCRP (+37%, p<0.001), IL-6 (+75%, p<0.05), TNF-α (+75%, p<0.05), and adiponectin (-39%, p<0.01) levels were significantly altered post-HH. FMVD was increased in 7 subjects, and it was decreased in 3 individuals during HH exposure. Interestingly, when EF biomarkers were compared between these two subgroups of subjects, only post exposure-adiponectin levels were significantly different (49±5 vs. 38±6µg/ml, respectively, p<0.05). SIGNIFICANCE: HH exposure had an effect on endothelin-1, adiponectin, hsCRP, IL-6, and TNF-α concentration. However, adiponectin was the only biomarker associated with an altered vascular reactivity.

Asunto(s)

Biomarcadores/metabolismo , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiología , Hipoxia/metabolismo , Hipoxia/fisiopatología , Adiponectina/metabolismo , Adulto , Arildialquilfosfatasa/metabolismo , Proteína C-Reactiva/metabolismo , Endotelina-1/metabolismo , Voluntarios Sanos , Humanos , Interleucina-6/metabolismo , Masculino , Factor de Necrosis Tumoral alfa/metabolismo , Molécula 1 de Adhesión Celular Vascular/metabolismo , Vasodilatación/fisiología , Adulto Joven

RESUMEN

Iron overload (IO) has been associated with glucose metabolism alterations and increased risk of cardiovascular disease (CVD). Primary IO is associated with mutations in the HFE gene. To which extent HFE gene mutations and metabolic alterations contribute to the presence of atherogenic lipoprotein modifications in primary IO remains undetermined. The present study aimed to assess small, dense low-density lipoprotein (LDL) levels, chemical composition of LDL and high-density lipoprotein (HDL) particles, and HDL functionality in IO patients. Eighteen male patients with primary IO and 16 sex- and age-matched controls were recruited. HFE mutations (C282Y, H63D and S65C), measures of insulin sensitivity and secretion (calculated from the oral glucose tolerance test), chemical composition and distribution profile of LDL and HDL subfractions (isolated by gradient density ultracentrifugation) and HDL functionality (as cholesterol efflux and antioxidative activity) were studied. IO patients compared with controls exhibited insulin resistance (HOMA-IR (homoeostasis model assessment-estimated insulin resistance): +93%, P< 0.001). Metabolic profiles differed across HFE genotypes. C282Y homozygotes (n=7) presented a reduced ß-cell function and insulin secretion compared with non-C282Y patients (n=11) (-58% and -73%, respectively, P< 0.05). In addition, C282Y homozygotes featured a predominance of large, buoyant LDL particles (C282Y: 43±5; non-C282Y: 25±8; controls: 32±7%; P< 0.001), whereas non-C282Y patients presented higher amounts of small, dense LDL (C282Y: 23±5; non-C282Y: 39±10; controls: 26±4%; P< 0.01). HDL particles were altered in C282Y homozygotes. However, HDL functionality was conserved. In conclusion, metabolic alterations and HFE gene mutations are involved in the presence of atherogenic lipoprotein modifications in primary IO. To what extent such alterations could account for an increase in CVD risk remains to be determined.

Asunto(s)

Aterosclerosis/etiología , Glucemia/metabolismo , HDL-Colesterol/sangre , Antígenos de Histocompatibilidad Clase I/genética , Insulina/sangre , Sobrecarga de Hierro/sangre , Sobrecarga de Hierro/genética , Proteínas de la Membrana/genética , Mutación , Adulto , Anciano , Aterosclerosis/sangre , Aterosclerosis/genética , Biomarcadores/sangre , Estudios de Casos y Controles , Línea Celular , LDL-Colesterol/sangre , Análisis Mutacional de ADN , Predisposición Genética a la Enfermedad , Prueba de Tolerancia a la Glucosa , Proteína de la Hemocromatosis , Heterocigoto , Homocigoto , Humanos , Resistencia a la Insulina , Células Secretoras de Insulina/metabolismo , Sobrecarga de Hierro/complicaciones , Sobrecarga de Hierro/diagnóstico , Masculino , Persona de Mediana Edad , Fenotipo , Factores de Riesgo

RESUMEN

Objective. Ultrasonographic characteristics are associated with thyroid malignancy. Our aim was to compare the diagnostic value of ultrasound features in the detection of thyroid malignancy in both solid and mixed nodules. Methods. We prospectively studied female patients (≥50 years) referred to ultrasound-guided fine needle aspiration biopsy. Ultrasound features considered suspicious were hypoechogenicity, microcalcifications, irregular margins, high anteroposterior (AP)/axial-ratio, and absent halo. Associations were separately assessed in mixed and solid nodules. Results. In a group of 504 elderly female patients (age = 69 ± 8 years), the frequency of malignant cytology was 6%. Thirty-one percent of nodules were mixed and 60% were solid. The rate of malignant cytology was similar for mixed and solid nodules (7.4 versus 5.8%, P: 0.56). While in mixed nodules none of the ultrasound characteristics were associated with malignant cytology, in solid nodules irregular margins and microcalcifications were significant (all P < 0.05). The combination of irregular margins and/or microcalcifications significantly increased the association with malignant cytology only in solid nodules (OR: 2.76 (95% CI: 1.25-6.10), P: 0.012). Conclusions. Ultrasound features were of poor diagnostic value in mixed nodules, which harbored malignant lesions as often as solid nodules. Our findings challenge the recommended minimal size for ultrasound-guided fine needle aspiration biopsy in mixed nodules.