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Desaturase enzyme activities (DEA) are associated with several metabolic diseases. The aim of the present study was to assess the relationship between estimated plasma DEA and the metabolic syndrome (MetS), as well as their relationship with individual components of the MetS. We conducted a longitudinal study of 148 participants recruited at random from the PREDIMED trial (Hospital Clinic site). At baseline and after 1 year of follow-up, DEA were estimated from product/precursor ratios of individual plasma fatty acids. Logistic regressions were used to assess the relationship of estimated DEA MetS, adjusted for potential cofounders. Estimated Δ5 desaturase (D5D) activity was associated with lower risk of MetS, whereas stearoyl-CoA (SCD)-16 and SCD-18 were negatively associated with MetS status. SCD-16, SCD-18, and Δ6 desaturase (D6D) were positively associated with triglycerides, SCD-18 was inversely associated with HDL-cholesterol. Estimated D6D activity was found to be associated with increases in diastolic blood pressure. In contrast, D5D was negatively associated with triglycerides, diastolic blood pressure and waist circumference. The present longitudinal study suggests that estimated SCD-16, SCD-18, and D6D have a negative impact in MetS and its components, whereas D5D may have beneficial effects for metabolic health.
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Systemic inflammation is associated with an increased risk of non-communicable diseases, such as cardiovascular diseases and diabetes. Circulating fatty acids (FA) are known to be related to these conditions, possibly through their role in inflammation, although different types of FAs can have opposite effects on inflammatory mediators. The aim of the present study was to analyze the association of plasma FAs with inflammatory biomarkers in a PREDIMED trial subsample after one year of intervention. In a one-year longitudinal study of 91 participants of the PREDIMED trial (Barcelona-Clinic center), plasma FAs and inflammatory biomarkers were analyzed using gas chromatography and ELISA, respectively. In baseline plasma, a multivariable-adjusted ordinary least squares regression model showed that n-3 polyunsaturated FAs concentrations were inversely associated with concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and E-selectin, whereas the level of the most abundant saturated FA, palmitic acid, was directly associated with concentrations of interleukin-6 (IL-6) (ß = 0.48 pg/mL, 95% CI: 0.03, 0.93 per 1-SD increase, p-value = 0.037). After one year of nutritional intervention, changes of plasma diet-derived total saturated FAs and palmitic acid were directly associated with changes in IL-6 (ß = 0.59 pg/mL [95% CI: 0.28, 0.89] per 1-SD, p-value = 0.001; ß = 0.64 pg/mL, 95% CI: 0.31, 0.98, p-value = 0.001), respectively, after correction for multiple testing. Our findings suggest that saturated FAs of dietary origin, especially palmitic acid, are directly involved in the increase of IL-6 in plasma.
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Ácidos Graxos , Interleucina-6 , Biomarcadores , Humanos , Inflamação , Estudos Longitudinais , Ácido PalmíticoRESUMO
Background: Adequate nutrient intake during the first few months of life plays a critical role on brain structure and function development. Objectives: To analyze the long-term effects of an experimental infant formula (EF) on neurocognitive function and brain structure in healthy children aged 6 years compared to those fed with a standard infant formula or breastfed. Methods: The current study involved 108 healthy children aged 6 years and participating in the COGNIS Study. At 0-2 months, infants were randomized to receive up to 18 months of life a standard infant formula (SF) or EF enriched with milk fat globule membrane (MFGM), long-chain polyunsaturated fatty acids (LC-PUFAs) and synbiotics. Furthermore, a reference group of breastfed (BF) infants were also recruited. Children were assessed using neurocognitive tests and structural Magnetic Resonance Imaging (MRI) at 6 years old. Results: Experimental infant formula (EF) children showed greater volumes in the left orbital cortex, higher vocabulary scores and IQ, and better performance in an attention task than BF children. EF children also presented greater volumes in parietal regions than SF kids. Additionally, greater cortical thickness in the insular, parietal, and temporal areas were found in children from the EF group than those fed with SF or BF groups. Further correlation analyses suggest that higher volumes and cortical thickness of different parietal and frontal regions are associated with better cognitive development in terms of language (verbal comprehension) and executive function (working memory). Finally, arachidonic acid (ARA), adrenic acid (AdA), docosahexaenoic acid (DHA) levels in cheek cell glycerophospholipids, ARA/DHA ratio, and protein, fatty acid, and mineral intake during the first 18 months of life seem to be associated with changes in the brain structures at 6 years old. Conclusions: Supplemented infant formula with MFGM components, LC-PUFAs, and synbiotics seems to be associated to long-term effects on neurocognitive development and brain structure in children at 6 years old. Clinical Trial Registration: https://www.clinicaltrials.gov/, identifier: NCT02094547.
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Ochronosis is a rare genetic disease of phenylamine and tyrosine metabolism in which an accumulation of homogentisic acid occurs. The accumulation of HGA causes alkaptonuria and deposition in the connective tissue causing a dark colouring of the tissue. In the joints, it can lead to early and very disabling arthropathy, known as ochronotic arthropathy. We present the case of a patient diagnosed with ochronosis and ochronotic arthropathy of the left knee, in which we describe the intraoperative process with the macroscopic and microscopic anatomopathological findings. The patient made good progress after implantation of a total knee prosthesis (TKP), PS type, and was able to follow the same rehabilitation protocol used in patients without ochronotic arthropathy undergoing TKP. The patient showed improvement in the different functional scales, as well as disappearance of pain.
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INTRODUCTION: Cerebral palsy is considered to be the main cause of physical disability in childhood. General movements are an assessment tool in order to predict the neurological and long-term outcome of the newborn. AIM: To analyze the current evidence on the general movements assessment in preterm infants as cerebral palsy prognostic tool. SUBJECTS AND METHODS: Systematic review following PRISMA statements. Databases consulted were: PubMed/Medline, Lilacs, IBECS, Cochrane, PEDro, Cinhal, Sport Discuss, Phyinfo, Academic Search Complete, Web of Science, and SciELO. We included studies that evaluated general movements in the first 20 weeks premature newborns. We excluded studies where the sample submit other pathologies or medication was administered. Newcastle-Ottawa Scale was used to assessment the risk of bias. RESULTS: Ten cohort studies form this review. 2243 premature, with an average of 30.9 weeks of gestation, were analyzed. General movements recording was carried out between 5 and 30 minutes. When there are abnormal general movements, the chances of neurological involvement increase during development, whereas when normal general movements are evaluated, there will rarely be a subsequent cerebral palsy diagnosis. CONCLUSIONS: The predictive validity of the preterm general movements assessment is confirmed as a tool to predict cerebral palsy early. Since preterm infants are more likely to trigger abnormal general movements, it is interesting to promote this type of assessment.
TITLE: Valoración de movimientos generales como herramienta pronóstica de parálisis cerebral infantil en prematuros: revisión sistemática.Introducción. La parálisis cerebral infantil se considera la principal causa de discapacidad física en la infancia. La valoración de los movimientos generales es una herramienta de evaluación con el fin de pronosticar la afectación neurológica y el desenlace a largo plazo del recién nacido. Objetivo. Analizar la evidencia científica sobre la valoración de los movimientos generales en recién nacidos prematuros como medida pronóstica de parálisis cerebral infantil. Sujetos y métodos. Revisión sistemática siguiendo la normativa PRISMA. Se consultaron las bases de datos PubMed/Medline, Lilacs, IBECS, Cochrane, PEDro, Cinhal, Sport Discuss, Phyinfo, Academic Search Complete, Web of Science y SciELO. Se incluyeron estudios donde se valoraban movimientos generales en las primeras 20 semanas de recién nacidos prematuros y se excluyeron aquellos donde la muestra presentaba otras patologías o administraba medicación. Se utilizó la Newcastle-Ottawa Scale para valorar el riesgo de sesgo. Resultados. Se seleccionaron 10 estudios de cohortes para esta revisión y se analizaron un total de 2.243 prematuros, con una media de 30,9 semanas de gestación. Se llevó a cabo la grabación de movimientos generales entre 5 y 30 minutos. Cuando se observan movimientos generales anormales, aumentan las posibilidades de afectación neurológica durante el desarrollo, mientras que cuando se valoran movimientos generales normales, raramente habrá un posterior diagnóstico de parálisis cerebral. Conclusiones. Se confirma la validez predictiva de la valoración de los movimientos generales en prematuros para pronosticar parálisis cerebral de forma precoz. Como los recién nacidos prematuros tienen mayor posibilidad de desencadenar movimientos generales anormales, es interesante promover este tipo de valoración.
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Paralisia Cerebral/complicações , Paralisia Cerebral/fisiopatologia , Discinesias/etiologia , Movimento , Criança , Humanos , PrognósticoRESUMO
This study analyzed how maternal obesity affected fatty acids (FAs) in breast milk and their association with infant growth and cognition to raise awareness about the programming effect of maternal health and to promote a healthy prenatal weight. Mother-child pairs (n = 78) were grouped per maternal pre-pregnancy body mass index (BMI): normal-weight (BMI = 18.5-24.99), overweight (BMI = 25-29.99) and obese (BMI > 30). Colostrum and mature milk FAs were determined. Infant anthropometry at 6, 18 and 36 months of age and cognition at 18 were analyzed. Mature milk exhibited lower arachidonic acid (AA) and docosahexaenoic acid (DHA), among others, than colostrum. Breast milk of non-normal weight mothers presented increased saturated FAs and n6:n3 ratio and decreased α-linolenic acid (ALA), DHA and monounsaturated FAs. Infant BMI-for-age at 6 months of age was inversely associated with colostrum n6 (e.g., AA) and n3 (e.g., DHA) FAs and positively associated with n6:n3 ratio. Depending on the maternal weight, infant cognition was positively influenced by breast milk linoleic acid, n6 PUFAs, ALA, DHA and n3 LC-PUFAs, and negatively affected by n6:n3 ratio. In conclusion, this study shows that maternal pre-pregnancy BMI can influence breast milk FAs and infant growth and cognition, endorsing the importance of a healthy weight in future generations.
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Desenvolvimento Infantil/efeitos dos fármacos , Cognição/efeitos dos fármacos , Ácidos Graxos/análise , Leite Humano/química , Obesidade/metabolismo , Índice de Massa Corporal , Pré-Escolar , Colostro/química , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Fenômenos Fisiológicos da Nutrição Materna , Gravidez , Complicações na Gravidez/metabolismo , Efeitos Tardios da Exposição Pré-Natal/etiologiaRESUMO
An adult female Eastern Grey kangaroo (Macropus giganteus) was examined for lameness due to a mass located at the right tibiotarsal joint. Radiographs revealed a metal arrowhead-shaped foreign body within the mass alongside a pathologic fracture. Grossly, at necropsy, there was a multilobulated and haemorrhagic mass with intralesional metal fragments, associated osteolysis of the tibiotarsus and pulmonary metastatic nodules. Histologically the neoplasm was composed of plump elongated and fusiform cells that often formed concentrically around small vessels. The pulmonary nodules were composed of similar neoplastic cells, necrosis and haemorrhage. Neoplastic cells were positive immunohistochemically for vimentin and smooth muscle actin. The histological features, immunohistochemical profiles and behaviour of this tumour support a diagnosis of a primary angioleiomyosarcoma with lung metastasis associated with a metal foreign body.
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Angiomioma/veterinária , Corpos Estranhos/veterinária , Leiomiossarcoma/veterinária , Macropodidae , Angiomioma/etiologia , Angiomioma/patologia , Animais , Autopsia/veterinária , Feminino , Corpos Estranhos/complicações , Coxeadura Animal/etiologia , Leiomiossarcoma/etiologia , Leiomiossarcoma/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/veterinária , New South Wales , Osteólise/etiologia , Osteólise/patologia , Osteólise/veterinária , Tíbia/patologiaRESUMO
OBJECTIVE: To evaluate whether higher omega-6:omega-3 (n-6:n-3) long-chain polyunsaturated fatty acid ratio in cord plasma is associated with more symptoms of attention deficit and hyperactivity disorder (ADHD) at 4 and 7 years of age. STUDY DESIGN: This study was based on a population-based birth cohort in Spain. N-6 arachidonic acid and n-3 eicosapentaenoic and docosahexaenoic acid concentrations were measured in cord plasma. At 4 years old, ADHD symptoms were reported by teachers through the ADHD Diagnostic and Statistical Manual of Mental Disorders, 4th ed checklist (n = 580). At 7 years old, ADHD symptoms were reported by parents through the Conners' Rating Scale-Revised (short form; n = 642). The ADHD variable was treated as continuous (score) and as dichotomous (symptom diagnostic criteria). Child and family general characteristics were prospectively collected through questionnaires. We applied pooled zero-inflated negative binomial and logistic regressions adjusted for covariates. RESULTS: A higher omega-6:omega-3 long-chain polyunsaturated fatty acid ratio in cord plasma was associated with a higher ADHD index (incidence rate ratio, 1.13; 95% CI, 1.03, 1.23) at 7 years old. The association was not observed at 4 years old (incidence rate ratio, 1.04; 95% CI, 0.92-1.18). No associations were found using ADHD symptom diagnostic criteria. CONCLUSIONS: High prenatal omega-6:omega-3 long-chain polyunsaturated fatty acid ratio preceded the appearance of subclinical ADHD symptoms during mid-childhood. Our findings suggest that maternal diet during pregnancy may modulate the risk to develop long-term ADHD symptoms in the offspring.
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Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Sangue Fetal/química , Fenômenos Fisiológicos da Nutrição Pré-Natal , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Gravidez , Estudos ProspectivosRESUMO
Polymorphisms in the fatty acid desaturase (FADS) genes influence the arachidonic (AA) and docosahexaenoic (DHA) acid concentrations (crucial in early life). Infants with specific genotypes may require different amounts of these fatty acids (FAs) to maintain an adequate status. The aim of this study was to determine the effect of an infant formula supplemented with AA and DHA on FAs of infants with different FADS genotypes. In total, 176 infants from the COGNIS study were randomly allocated to the Standard Formula (SF; n = 61) or the Experimental Formula (EF; n = 70) group, the latter supplemented with AA and DHA. Breastfed infants were added as a reference group (BF; n = 45). FAs and FADS polymorphisms were analyzed from cheek cells collected at 3 months of age. FADS minor allele carriership in formula fed infants, especially those supplemented, was associated with a declined desaturase activity and lower AA and DHA levels. Breastfed infants were not affected, possibly to the high content of AA and DHA in breast milk. The supplementation increased AA and DHA levels, but mostly in major allele carriers. In conclusion, infant FADS genotype could contribute to narrow the gap of AA and DHA concentrations between breastfed and formula fed infants.
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Ácido Araquidônico/administração & dosagem , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Graxos Dessaturases/genética , Genótipo , Fórmulas Infantis/análise , Adulto , Suplementos Nutricionais , Ácidos Graxos/administração & dosagem , Ácidos Graxos/sangue , Feminino , Humanos , Lactente , Masculino , Polimorfismo Genético , Adulto JovemRESUMO
BACKGROUND & AIMS: In recent years, obesity has reached alarming levels among children and adolescents. The study of plasma fatty acid (FA) composition, as a reflection of diet, and its associations with other parameters, that are closely linked to obesity and the cardiometabolic profile, may be useful for setting nutritional goals for obesity treatment and prevention. This study explored the relationship between plasma FA levels and body fat and cardiometabolic risk markers, in overweight adolescents. METHODS: A multidisciplinary weight loss program was followed by 127 overweight and obese adolescents aged 12-17 years old. Plasma FA composition, anthropometric indicators of adiposity and biochemical parameters were analyzed at baseline, two months (the end of the intensive intervention phase) and six months (the end of the extensive phase). RESULTS: While saturated fatty acid (SFA) and n-6 polyunsaturated fatty acid (PUFA) levels decreased significantly during the intervention, monounsaturated fatty acid (MUFA) and n-3 PUFA showed the opposite trend. The decrease in SFA C14:0 was associated with a reduction in total and LDL cholesterol, apolipoprotein B and insulin. The increase in MUFAs, especially C18:1n-9, was related to a reduction in weight, fat mass, fat mass index and glucose. Regarding PUFAs, changes in the n-3 series were not associated with any of the parameters studied, whereas the reduction in n-6 PUFAs was directly related to weight, fat mass, total and HDL cholesterol, apolipoprotein A1, glucose and insulin, and inversely associated with diastolic blood pressure. The adolescents with greater weight loss presented significant changes in MUFAs, n-6 PUFAs and C14:0. CONCLUSIONS: Modifications in plasma FA composition were associated with adiposity reduction and cardiometabolic profile improvement in an anti-obesity program aimed at adolescents. The changes observed in FA composition were related to the success of the treatment, since the individuals most affected by these variations were those who presented the greatest weight loss.
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Ácidos Graxos/sangue , Obesidade , Adolescente , Criança , Feminino , Humanos , Masculino , Obesidade/sangue , Obesidade/epidemiologia , Obesidade/terapia , Redução de Peso/fisiologia , Programas de Redução de PesoRESUMO
Single nucleotide polymorphisms (SNPs) in the genes encoding the fatty acid desaturase (FADS) and elongase (ELOVL) enzymes affect long-chain polyunsaturated fatty acid (LC-PUFA) production. We aimed to determine if these SNPs are associated with body mass index (BMI) or affect fatty acids (FAs) in pregnant women. Participants (n = 180) from the PREOBE cohort were grouped according to pre-pregnancy BMI: normal-weight (BMI = 18.5-24.9, n = 88) and overweight/obese (BMI≥25, n = 92). Plasma samples were analyzed at 24 weeks of gestation to measure FA levels in the phospholipid fraction. Selected SNPs were genotyped (7 in FADS1, 5 in FADS2, 3 in ELOVL2 and 2 in ELOVL5). Minor allele carriers of rs174545, rs174546, rs174548 and rs174553 (FADS1), and rs1535 and rs174583 (FADS2) were nominally associated with an increased risk of having a BMI≥25. Only for the normal-weight group, minor allele carriers of rs174537, rs174545, rs174546, and rs174553 (FADS1) were negatively associated with AA:DGLA index. Normal-weight women who were minor allele carriers of FADS SNPs had lower levels of AA, AA:DGLA and AA:LA indexes, and higher levels of DGLA, compared to major homozygotes. Among minor allele carriers of FADS2 and ELOVL2 SNPs, overweight/obese women showed higher DHA:EPA index than the normal-weight group; however, they did not present higher DHA concentrations than the normal-weight women. In conclusion, minor allele carriers of FADS SNPs have an increased risk of obesity. Maternal weight changes the effect of genotype on FA levels. Only in the normal-weight group, minor allele carriers of FADS SNPs displayed reduced enzymatic activity and FA levels. This suggests that women with a BMI≥25 are less affected by FADS genetic variants in this regard. In the presence of FADS2 and ELOVL2 SNPs, overweight/obese women showed higher n-3 LC-PUFA production indexes than women with normal weight, but this was not enough to obtain a higher n-3 LC-PUFA concentration.
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Acetiltransferases/genética , Peso Corporal , Ácidos Graxos Dessaturases/genética , Ácidos Graxos/sangue , Estudos de Associação Genética , Variação Genética , Mães , Alelos , Índice de Massa Corporal , Dessaturase de Ácido Graxo Delta-5 , Diabetes Gestacional , Elongases de Ácidos Graxos , Ácidos Graxos Insaturados/sangue , Feminino , Seguimentos , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Gravidez , EspanhaRESUMO
SCOPE: Traditional Mediterranean diet (TMD) protects against cardiovascular disease through several mechanisms such as decreasing LDL cholesterol levels. However, evidence regarding TMD effects on LDL atherogenic traits (resistance against oxidation, size, composition, cytotoxicity) is scarce. METHODS AND RESULTS: We assessed the effects of a 1-year intervention with a TMD on LDL atherogenic traits in a random sub-sample of individuals from the PREDIMED study (N = 210). We compared two TMDs: one enriched with virgin olive oil (TMD-VOO, N = 71) and another with nuts (TMD-Nuts, N = 68), versus a low-fat control diet (N = 71). After the TMD-VOO intervention, LDL resistance against oxidation increased (+6.46%, p = 0.007), the degree of LDL oxidative modifications decreased (-36.3%, p<0.05), estimated LDL particle size augmented (+3.06%, p = 0.021), and LDL particles became cholesterol-rich (+2.41% p = 0.013) relative to the low-fat control diet. LDL lipoproteins became less cytotoxic for macrophages only relative to baseline (-13.4%, p = 0.019). No significant effects of the TMD-Nuts intervention on LDL traits were observed versus the control diet. CONCLUSION: Adherence to a TMD, particularly when enriched with virgin olive oil, decreased LDL atherogenicity in high cardiovascular risk individuals. The development of less atherogenic LDLs could contribute to explaining some of the cardioprotective benefits of this dietary pattern.
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Aterosclerose/prevenção & controle , Doenças Cardiovasculares/prevenção & controle , Dieta Mediterrânea , Lipoproteínas LDL/metabolismo , Idoso , Células Cultivadas , Feminino , Humanos , Lipoproteínas LDL/toxicidade , Masculino , Pessoa de Meia-Idade , Nozes , Tamanho da Partícula , RiscoRESUMO
BACKGROUND: The biological functions of high-density lipoproteins (HDLs) contribute to explaining the cardioprotective role of the lipoprotein beyond quantitative HDL cholesterol levels. A few small-scale interventions with a single antioxidant have improved some HDL functions. However, to date, no long-term, large-scale, randomized controlled trial has been conducted to assess the effects of an antioxidant-rich dietary pattern (such as a traditional Mediterranean diet [TMD]) on HDL function in humans. METHODS: This study was performed in a random subsample of volunteers from the PREDIMED Study (Prevención con Dieta Mediterránea; n=296) after a 1-year intervention. We compared the effects of 2 TMDs, one enriched with virgin olive oil (TMD-VOO; n=100) and the other enriched with nuts (TMD-Nuts; n=100), with respect to a low-fat control diet (n=96). We assessed the effects of both TMDs on the role of HDL particles on reverse cholesterol transport (cholesterol efflux capacity, HDL ability to esterify cholesterol, and cholesteryl ester transfer protein activity), HDL antioxidant properties (paraoxonase-1 arylesterase activity and total HDL antioxidant capacity on low-density lipoproteins), and HDL vasodilatory capacity (HDL ability to induce the release of nitric oxide in endothelial cells). We also studied the effects of a TMD on several HDL quality-related characteristics (HDL particle oxidation, resistance against oxidative modification, main lipid and protein composition, and size distribution). RESULTS: Both TMDs increased cholesterol efflux capacity relative to baseline (P=0.018 and P=0.013 for TMD-VOO and TMD-Nuts, respectively). The TMD-VOO intervention decreased cholesteryl ester transfer protein activity (relative to baseline, P=0.028) and increased HDL ability to esterify cholesterol, paraoxonase-1 arylesterase activity, and HDL vasodilatory capacity (relative to control, P=0.039, P=0.012, and P=0.026, respectively). Adherence to a TMD induced these beneficial changes by improving HDL oxidative status and composition. The 3 diets increased the percentage of large HDL particles (relative to baseline, P<0.001). CONCLUSIONS: The TMD, especially when enriched with virgin olive oil, improved HDL atheroprotective functions in humans. CLINICAL TRIAL REGISTRATION: URL: http://www.controlled-trials.com. Unique identifier: ISRCTN35739639.
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Doenças Cardiovasculares/dietoterapia , Dieta Mediterrânea , Lipídeos/imunologia , Lipoproteínas HDL/metabolismo , Humanos , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
BACKGROUND/OBJECTIVE: Many controversies regarding the association of liver miRNAs with obesity and nonalcoholic fatty liver diseases (NAFLD) call for additional validations. This study sought to investigate variations in genes and hepatic miRNAs in a sample of obese patients with or without NAFLD and human hepatocytes (HH). SUBJECTS/METHODS: A total of 60 non-consecutive obese women following bariatric surgery were recruited. Subjects were classified as NAFLD (n=17), borderline (n=24) and controls (n=19) with normal enzymatic profile, liver histology and ultrasound assessments. Profiling of 744 miRNAs was performed in 8 obese women with no sign of hepatic disease and 11 NAFLD patients. Additional validation and expression of genes related to de novo fatty acid (FA) biosynthesis, uptake, transport and ß-oxidation; glucose metabolism, and inflammation was tested in the extended sample. Induction of NAFLD-related genes and miRNAs was examined in HepG2 cells and primary HH treated with palmitic acid (PA), a combination of palmitate and oleic acid, or high glucose, and insulin (HG) mimicking insulin resistance in NAFLD. RESULTS: In the discovery sample, 14 miRNAs were associated with NAFLD. Analyses in the extended sample confirmed decreased miR-139-5p, miR-30b-5p, miR-122-5p and miR-422a, and increased miR-146b-5p in obese subjects with NAFLD. Multiple linear regression analyses disclosed that NAFLD contributed independently to explain miR-139-5p (P=0.005), miR-30b-5p (P=0.005), miR-122-5p (P=0.021), miR-422a (P=0.007) and miR-146a (P=0.033) expression variance after controlling for confounders. Decreased miR-122-5p in liver was associated with impaired FA usage. Expression of inflammatory and macrophage-related genes was opposite to decreased miR-30b-5p, miR-139-5p and miR-422a, whereas increased miR-146b-5p was associated with FABP4 and decreased glucose metabolism and FA mobilization. In partial agreement, PA (but not HG) led to decreased miR-139-5p, miR-30b-5p, miR-422a and miR-146a in vitro, in parallel with increased lipogenesis and FA transport, decreased glucose metabolism and diminished FA oxidation. CONCLUSION: This study confirms decreased liver glucose and lipid metabolism but increased FA biosynthesis coupled with changes in five unique miRNAs in obese patients with NAFLD.
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Ácidos Graxos/biossíntese , Fígado/metabolismo , MicroRNAs/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/metabolismo , Células Cultivadas , Estudos Transversais , Feminino , Regulação Enzimológica da Expressão Gênica/fisiologia , Células Hep G2 , Hepatócitos/metabolismo , Humanos , Metabolismo dos Lipídeos , Lipogênese , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Obesidade/complicações , Obesidade/fisiopatologiaRESUMO
BACKGROUND & AIMS: In vivo and in vitro evidence suggests that antioxidant vitamins and carotenoids may be key factors in the treatment and prevention of obesity and obesity-associated disorders. Hence, the objective of the present study was to determine the relationship between plasma lipid-soluble antioxidant vitamin and carotenoid levels and adiposity and cardio-metabolic risk markers in overweight and obese adolescents participating in a multidisciplinary weight loss programme. METHODS: A therapeutic programme was conducted with 103 adolescents aged 12-17 years old and diagnosed with overweight or obesity. Plasma concentrations of α-tocopherol, retinol, ß-carotene and lycopene, anthropometric indicators of general and central adiposity, blood pressure and biochemical parameters were analysed at baseline and at 2 and 6 months of treatment. RESULTS: Lipid-corrected retinol (P < 0.05), ß-carotene (P = 0.001) and α-tocopherol (P < 0.001) plasma levels increased significantly, whereas lipid-corrected lycopene levels remained unaltered during the treatment. Anthropometric indicators of adiposity (P < 0.001), blood pressure (P < 0.01) and biochemical parameters (P < 0.05) decreased significantly, whereas fat free mass increased significantly (P < 0.001). These clinical and biochemical improvements were related to changes in plasma lipid-corrected antioxidant vitamin and carotenoid levels. The adolescents who experienced the greatest weight loss also showed the largest decrease in anthropometric indicators of adiposity and biochemical parameters and the highest increase in fat free mass. Weight loss in these adolescents was related to an increase in plasma levels of lipid-corrected α-tocopherol (P = 0.001), ß-carotene (P = 0.034) and lycopene (P = 0.019). CONCLUSIONS: Plasma lipid-soluble antioxidant vitamin and carotenoid levels are associated with reduced adiposity, greater weight loss and an improved cardio-metabolic profile in overweight and obese adolescents.
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Adiposidade , Antioxidantes/análise , Doenças Cardiovasculares/sangue , Síndrome Metabólica/sangue , Obesidade Infantil/sangue , Vitaminas/sangue , Adolescente , Antropometria , Apolipoproteínas/sangue , Doenças Cardiovasculares/prevenção & controle , Carotenoides/sangue , Criança , Colesterol/sangue , Estudos de Coortes , Dieta , Feminino , Seguimentos , Humanos , Licopeno , Masculino , Síndrome Metabólica/prevenção & controle , Avaliação Nutricional , Sobrepeso/sangue , Obesidade Infantil/diagnóstico , Obesidade Infantil/terapia , Fatores de Risco , Triglicerídeos/sangue , Vitamina A/sangue , alfa-Tocoferol/sangue , beta Caroteno/sangueRESUMO
BACKGROUND: Maternal overweight, obesity, and gestational diabetes (GD) have been negatively associated with offspring development. Further knowledge regarding metabolic and nutritional alterations in these mother and their offspring are warranted. METHODS: In an observational cohort study we included 331 pregnant women from Granada, Spain. The mothers were categorized into four groups according to BMI and their GD status; overweight (n:56), obese (n:64), GD (n:79), and healthy normal weight controls (n:132). We assessed maternal growth and nutritional biomarkers at 24 weeks (n = 269), 34 weeks (n = 310) and at delivery (n = 310) and the perinatal characteristics including cord blood biomarkers. RESULTS: Obese and GD mothers had significantly lower weight gain during pregnancy and infant birth weight, waist circumference, and placental weight were higher in the obese group, including a significantly increased prevalence of macrosomia. Except for differences in markers of glucose metabolism (glucose, HbA1c, insulin and uric acid) we found at some measures that overweight and/or obese mothers had lower levels of transferrin saturation, hemoglobin, Vitamin B12 and folate and higher levels of C-reactive protein, erythrocyte sedimentation rate, ferritin, and cortisol. GD mothers had similar differences in hemoglobin and C-reactive protein but higher levels of folate. The latter was seen also in cord blood. CONCLUSIONS: We identified several metabolic alterations in overweight, obese and GD mothers compared to controls. Together with the observed differences in infant anthropometrics, these may be important biomarkers in future research regarding the programming of health and disease in children. TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov, identifier ( NCT01634464 ).
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Diabetes Gestacional/fisiopatologia , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Adulto , Biomarcadores/sangue , Peso ao Nascer/fisiologia , Estudos de Coortes , Feminino , Macrossomia Fetal/epidemiologia , Humanos , Lactente , Masculino , Gravidez , Fenômenos Fisiológicos da Nutrição Pré-Natal/fisiologia , Espanha/epidemiologia , Aumento de Peso/fisiologia , Adulto JovemRESUMO
PURPOSE: To investigate the association between carbohydrate quality, fat quality or adherence to the Mediterranean diet and intake adequacy of 19 micronutrients in the PREDIMED (PREvención con DIeta MEDiterránea) trial, a multicenter, randomized, controlled, parallel group and primary prevention trial conducted in Spain. METHODS: We assessed baseline dietary intake of 6,542 elderly subjects at high cardiovascular risk through a validated food frequency questionnaire (FFQ) and a validated 14-item Mediterranean diet (Med-diet) score. We used a multidimensional carbohydrate quality index (CQI) using four criteria and a fat quality index (FQI) according to the ratio (MUFA + PUFA)/(SFA + TFA). The probability of intake adequacy was calculated comparing the intakes to DRI, and also using the probabilistic approach. Absolute and adjusted probability of having inadequate intake for either ≥6 DRI or ≥8 DRI were estimated to assess nutritional adequacy according to quintiles of each index. RESULTS: The lowest prevalence of inadequate micronutrient intake (≥8 DRI) was found in the highest quintile of CQI or Med-diet score, and in the lowest quintile of FQI (adjusted fold risk: 1.4, 3.4 and 10.2 respectively in comparison with the lowest quintile). P for trend <0.001 in three multivariable models. A higher CQI or Med-Diet score and a lower FQI were significantly associated with a lower fold risk of unmet EAR values. CONCLUSIONS: A multidimensional assessment of CQI can be a useful tool to evaluate the quality of carbohydrates. This score and a 14-item Med-diet score were positively related to overall micronutrient adequacy in elderly participants.
Assuntos
Dieta Mediterrânea , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Valor Nutritivo , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Doenças Cardiovasculares/prevenção & controle , Fibras na Dieta/administração & dosagem , Ingestão de Energia , Ácidos Graxos/administração & dosagem , Ácidos Graxos Monoinsaturados/administração & dosagem , Ácidos Graxos Insaturados/administração & dosagem , Feminino , Humanos , Modelos Logísticos , Masculino , Micronutrientes/administração & dosagem , Pessoa de Meia-Idade , Cooperação do Paciente , Reprodutibilidade dos Testes , Fatores de Risco , Espanha , Inquéritos e Questionários , Ácidos Graxos trans/administração & dosagemRESUMO
Plasma is the most commonly employed matrix for analyzing fatty acids (FAs), but its extraction is not well accepted in the infant population. The objectives of this study were to evaluate cheek cells and capillary blood as alternatives to plasma sampling for FA analysis and to standardize the methodology. Samples were obtained from 20 children who underwent lipid extraction, phospholipid isolation by Solid Phase Extraction (SPE) in a 96-well plate, methylation, and analysis by fast gas chromatography (GC). A positive correlation was found for most of the FAs, especially long-chain polyunsaturated fatty acids (LC-PUFAs), in cheek cells and capillary blood versus plasma samples (r = 0.32-0.99). No differences were found in the levels of n-6: n-3 PUFA and n-6: n-3 LC-PUFA ratios between cheek cells and capillary blood. These two proposed samples can therefore be used as alternatives to plasma sampling for phospholipid FA analysis, especially LC-PUFAs.
Assuntos
Bochecha , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Fosfolipídeos/análise , Criança , Cromatografia Gasosa , Humanos , Plasma/química , Reprodutibilidade dos Testes , Extração em Fase SólidaRESUMO
BACKGROUND: Peroxisome proliferator activated receptors (PPARs) are ligand activated transcription factors with crucial functions in lipid homeostasis, glucose metabolism, anti-inflammatory processes, placental development, and are involved in cognitive functions and neurodegenerative diseases. Polymorphisms in PPAR genes are shown to influence the activity of these receptors. AIMS: 1) To examine the association of PPARG Pro12Ala polymorphism in pregnant women and their offspring on infant's neurodevelopmental outcomes during the first 18 months of life; 2) to determine the influence of Pro12Ala polymorphism on fatty acid concentrations in plasma phospholipids and placental tissue. STUDY DESIGN: 138 mother-infant pairs from the PREOBE observational study were genotyped for PPARG Pro12Ala. Plasma phospholipids and placental fatty acid concentrations were measured at delivery. Infants' neuropsychological assessment at 6 and 18 months of age was performed using Bayley III. RESULTS: The effect of Pro12Ala on infant's neurodevelopmental outcomes was detected at 18 months, but not at 6 months of age. 18 months old infants born to mothers with wild-type Pro12 genotype had better cognitive (OR=5.11, 95% CI: 1.379-18.96, p=0.015), language (OR=3.41, 95% CI: 1.35-11.24, p=0.044), and motor development scores (OR=4.77, 95% CI: 1.243-18.33, p=0.023) than the Ala allele carriers. Pro12Ala variants did not seem to affect fatty acids concentrations in blood nor in placenta at delivery. CONCLUSIONS: Infants born to mothers with Pro12 genotype have better neurodevelopmental outcomes at 18 months of age than Ala allele carriers, indicating a long-term transplacental action of PPARγ variants on foetal brain development.
Assuntos
Desenvolvimento Infantil , PPAR gama/genética , Polimorfismo de Nucleotídeo Único , Adulto , Cognição , Feminino , Heterozigoto , Humanos , Lactente , Masculino , Troca Materno-Fetal/genética , Mutação de Sentido Incorreto , GravidezRESUMO
For the first time, a procedure for the simultaneous determination of the iodinated drug amiodarone and its major metabolite, N-desethylamiodarone, in sludge from urban sewage treatment plants (STPs) is proposed. Matrix solid-phase dispersion (MSPD) followed by on-line cationic exchange clean-up, in modular configuration, was used as sample preparation technique. Liquid chromatography with tandem mass spectrometry (LC-MS/MS), based on a hybrid quadrupole time-of-flight (QTOF) system, was employed for the selective determination of target compounds. The optimized procedure provided exhaustive recoveries with little effect of the sample matrix in the efficiency of electrospray ionization (ESI). The overall recoveries of the method ranged between 95 and 111%, for samples spiked at different concentration levels. The achieved limits of quantification (LOQs) remained below 10ngg(-1) for both compounds, and the linear response range extended up to 2500ngg(-1). Amiodarone and N-desethylamiodarone were ubiquitous in sludge samples, from different STPs located in the Northwest of Spain, with maximum concentrations above 300ngg(-1) referred to the freeze-dried matrix. They were also present in stabilized sludge (mixed with lime and thermally dehydrated), which is mostly disposed in agriculture fields as fertilizer. Furthermore, mono-iodinated analogues of amiodarone and N-desethylamiodarone were also tentatively identified in some samples from their accurate MS and MS/MS spectra.