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OBJECTIVE: To analyze the nutritional status and plasma levels of vitamins and minerals in a cohort of Chilean children between 4 and 14 years old from three cities in Chile (Santiago, Antofagasta, and Concepcion). DESIGN: This is a descriptive analysis of micronutrient levels in Chilean children as it relates to obesity and food consumption. SETTING: This study included 1235 children from schools in Santiago (central area), Antofagasta (northern area), and Concepcion (southern area) in Chile. RESULTS: Plasma levels of micronutrients revealed deficiencies in children from all these cities. Copper (26.4%) and calcium (33.0%) deficiencies were found in the children from Antofagasta, whereas iron (26.7%) and zinc (20.8%) deficiencies were found in the children from Concepcion and Santiago, respectively. The percentage of children with vitamin D deficiencies was exceptionally high in all cities (over 78%). The analysis of micronutrients and nutritional status revealed that vitamin D deficiencies were significantly higher (p = 0.02) in overweight children, particularly in Antofagasta. In the analysis of the nutritional status of children and their food consumption habits, the proportion of overweight and obesity was significantly higher (p = 0.001) in children that skipped breakfast compared to children that did not. Finally, children from low socioeconomic levels were significantly more overweight and obese compared to children from high socioeconomic levels (p < 0.05). CONCLUSIONS: this is the first study to describe plasma levels of micronutrients in Chilean children and adolescents. High percentages of obesity, overweight, and vitamin D deficiency were detected in children. These results are of significant relevance to future public health policies in Chile.
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Obesidade Infantil , Oligoelementos , Deficiência de Vitamina D , Adolescente , Humanos , Criança , Pré-Escolar , Micronutrientes , Chile/epidemiologia , Obesidade Infantil/epidemiologia , Sobrepeso , Estado Nutricional , Deficiência de Vitamina D/epidemiologia , PrevalênciaRESUMO
Improvements in computing capacity have allowed computers today to execute increasingly complex tasks. One of the main benefits of these improvements is the possibility of developing machine learning algorithms, of which the fields of application are extensive and varied. However, an area in which this type of algorithms acquires an increasing relevance is structural health monitoring (SHM), where inspection strategies and guided wave-based approaches make the evaluation of the structural conditions of an aircraft, vessel or building among others possible, by detecting and classifying existing damages. The use of sensors, data acquisition systems (DAQ) and computation has also allowed these damage detection and classification tasks to be carried out automatically. Despite today's advances, it is still necessary to continue with the development of more robust, reliable, and low-cost structural health monitoring systems. For this reason, this work contemplates three key points: (i) the configuration of a data acquisition system for signal gathering from an an active piezoelectric (PZT) sensor network; (ii) the development of a damage classification methodology based on signal processing techniques (normalization and PCA), from which the models that describe the structural conditions of the plate are built; and (iii) the use of machine learning algorithms, more specifically, three variants of the self-organizing maps called CPANN (counterpropagation artificial neural network), SKN (supervised Kohonen) and XYF (X-Y fused Kohonen). The data obtained allowed one to carry out an experimental validation of the damage classification methodology, to determine the presence of damages in two aluminum plates of different sizes, where masses were added to change the vibrational responses captured by the sensor network and a composite (CFRP) plate with real damages, such as delamination and cracks. This classification methodology allowed one to obtain excellent results by validating the usefulness of the SKN and XYF networks in damage classification tasks, showing overall accuracies of 73.75% and 72.5%, respectively, according to the cross-validation process. These percentages are higher than those obtained in comparison with other neural networks such as: kNN, discriminant analysis, classification trees, partial least square discriminant analysis, and backpropagation neural networks, when the cross-validation process was applied.
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Algoritmos , Redes Neurais de Computação , Análise Discriminante , Análise dos Mínimos Quadrados , Aprendizado de MáquinaRESUMO
The aim of this work was to determine in an exploratory manner the effect of excessive iron supplementation on iron, zinc, and copper contents in pork and pork offal. Pigs averaging 50 days in age and 15 ± 1.3 kg body weight were allocated to a control group (500 ppm dietary Fe) and a supplemental group (3000 ppm dietary Fe). After an iron supplementation period of 60 days, blood samples were analyzed to determine iron biomarkers, serum copper, and zinc contents. Animals were slaughtered to assess total iron, non-heme iron, heme iron, zinc, and copper contents in samples of nine meat cuts and some offal. Iron supplementation improved the iron status in pigs with increased hemoglobin and hematocrit, but did not affect serum levels of iron, zinc, and copper. Iron supplementation did not affect the heme and non-heme iron contents of the different meat cuts. Zinc contents decreased by 32-55% in meat cuts, where iron content increased in the liver, spleen, kidneys, and pancreas. No differences of zinc and copper were observed in offal samples. High concentrations of iron supplementation reduce zinc content in pork.
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Type 2 diabetes mellitus (T2D) is a metabolic disorder caused by chronic hyperglycemia due to a deficiency in the secretion and/or action of insulin. Zinc (Zn) supplementation and strength exercise increases insulin signaling. We evaluate the effect of Zn supplementation and strength exercise on insulin resistance in the liver of rats with diet-induced T2D through the study of phosphorylation of Akt and protein tyrosine phosphatase 1B (PTP1B). Rats were fed with a high-fat diet (HFD) for 18 weeks to induce T2D and then assigned in four experimental groups: HFD, HFD-Zn (Zn), HFD-strength exercise (Ex), and HFD-Zn/strength exercise (ZnEx) and treated during 12 weeks. Serum Zn, lipid profile, transaminases, glucose, and insulin were measured. In the liver with/without insulin stimuli, total and phosphorylated Akt (pAktSer473) and PTP1B (pPTP1BSer50) were determined by western blot. Hepatic steatosis was evaluated by histological staining with red oil and intrahepatic triglyceride (IHTG) content. There were no differences in biochemical and body-related variables. The ZnEx group showed a higher level of pAkt, both with/without insulin. The ZnEx group also showed higher levels of pPTP1B with respect to HFD and Zn groups. The ZnEx group had higher levels of pPTP1B than groups treated with insulin. Liver histology showed a better integrity and less IHTG in Ex and ZnEx with respect to the HFD group. The Ex and ZnEx groups had lower IHTG with respect to the HFD group. Our results showed that Zn supplementation and strength exercise together improved insulin signaling and attenuated nonalcoholic liver disease in a T2D rat model.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Condicionamento Físico Animal , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Zinco/farmacologia , Animais , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica , Suplementos Nutricionais , Insulina/metabolismo , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fosforilação , Ratos , Zinco/metabolismoRESUMO
Obesity is characterized by mild chronic inflammation that is linked with impaired iron homeostasis. Studies in human and murine show that there is a transgenerational epigenetic inheritance via the gametes in obesity; however, there is little information on changes in the expression of microRNAs related to inflammation and iron homeostasis in spermatozoa from obese subjects. The present study investigated the expression of microRNAs related to inflammation (miR-21 y miR-155) and iron nutrition (miR-122 and miR-200b) in plasma, peripheral blood mononuclear cells (PBMC) and spermatozoa from normozoospermic controls (Cn; n = 17; BMI: 24.6 ± 2.0) and obese (Ob; n = 17; BMI: 32.6 ± 4.4) men. To determine the inflammation levels, we measured IL-6, TNF-α, and monocyte chemoattractant protein-1 (MCP1) by Magnetic Luminex® Assay. mRNA expression of IL6, TNF-α, and hepcidin (HAMP) in PBMC were evaluated by RT-qPCR. The analysis of microRNAs was performed using the Taqman® assays. The iron content in PBMC, seminal plasma, and spermatozoa was determined by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). High serum IL6, TNF-α, and MCP1 levels were observed in Ob group (p < 0.05). Gene expression analysis showed an increased abundance relative of TNF-α (p = 0.018), HAMP (p = 0.03), and IL6 (p = 0.02) in PBMC from obese subjects. Also, we observed high levels of serum ferritin (p = 0.03), iron content in seminal plasma (p = 0.04), and spermatozoa (p = 0.002), but lower serum Fe (p = 0.007) in obese subjects. In the Ob group, a high expression of miR-155 (p = 0.02) and miR-21 (p = 0.03) was observed in PBMC and miR-122 (p = 0.03) in plasma. In sperm, both miR-155 (p = 0.004) and miR-122 (p = 0.028) were high in the Ob group. Our results showed that obese subjects have increased expressions of miR-155 and miR-122, two microRNAs that were previously related with inflammation and iron metabolism, respectively, at both the systemic and sperm levels.
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La anemia por deficiencia de hierro continúa siendo la deficiencia nutricional más abundante en el mundo, y son los lactantes, preescolares, mujeres en edad fértil y embarazadas los grupos de mayor susceptibilidad. Debido a esto es que se hace necesario el conocer los mecanismos de regulación de captación, transporte y absorción del metal a nivel celular, principalmente a nivel del enterocito y, una vez que el hierro entra a la circulación, conocer cuáles son los biomarcadores que permiten realizar un seguimiento del estatus del hierro corporal. En esta revisión mostramos, en primer lugar, cómo se regula la entrada de hierro a nivel de la célula del epitelio intestinal, mostrando las principales proteínas involucradas (transportadores de entrada y salida de hierro, oxido-reductasas, proteína de almacenamiento) y, para finalizar, hacemos un recuento de los principales biomarcadores del metabolismo de hierro una vez que este ha entrado y circula por el organismo.
Iron deficiency anemia is the most common nutritional deficiency worldwide, and the most susceptible groups are infants, preschoolers, women of childbearing age, and pregnant women. It is therefore essential to understand the mechanisms of regulation of iron uptake, transport, and absorption at the cellular level, particularly in enterocytes, and to identify blood biomarkers that allow the evaluation of iron status. This review describes how iron absorption is regulated by intestinal epithelial cells, the main proteins involved (iron transporters, oxidoreductases, storage proteins), and the main blood biomarkers of iron metabolism.
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Humanos , Ferro/metabolismo , Fenômenos Fisiológicos da Nutrição , Biomarcadores/sangue , Inflamação/metabolismo , Ferro/sangueRESUMO
Although there is evidence of the benefits of propolis on human health, the vast majority of studies have been conducted using animal models. The present study includes the chemical characterization and clinical evaluation of the effects of the oral administration of propolis solution on the oxidative status and modulation of lipids in a human population in Talca, Chile. Chemical characterization of propolis, total phenol, flavonoids, and total antioxidant capacity were determined by ORAC. Identification of phenols and flavonoids in propolis was assessed by HPLC-DAD. A double-blind, placebo-controlled clinical trial was conducted. Subjects provided informed consent form and the Bioethics Committee of the Universidad de Talca approved protocol. Eligible subjects (n = 67) were randomized in two groups: propolis (n = 35) and placebo (n = 32). All subjects were evaluated at 0 (baseline), 45, and 90 days. In the propolis group, we observed that increases in HDL-c went from 53.9 ± 11.9 to 65.8 ± 16.7 mg/dL (p < 0.001) from baseline to 90 days. Compared to placebo subjects, consumption of propolis induced a net increase in GSH levels (p < 0.0001) and a decrease (p < 0.001) in TBARS levels for the propolis group. Our findings indicate potential benefits of propolis use in human health. The use of propolis appears to have positive effects on oxidative status and improvement of HDL-c, both of which contribute to a reduced risk of cardiovascular disease.
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INTRODUCTION: Tyrosinemia Type 1 (HT1) is an autosomal recessive disorder caused by a defect in the enzyme fumarylacetoacetate hydroxylase in the tyrosine pathway. Implementation of nitisinone (NTBC) treatment has dramatically improved survival rate of individuals with HT1, yet recent reports on cognitive impairment in treated patients exist. AIMS: Describe long-term neurocognitive outcome individuals with HT1 treated with nitisinone and protein restricted diet. METHODOLOGY: Twelve individuals with HT1 were analyzed with respect to psychomotor development and cognitive functioning using standardized psychometric tests. Plasma tyrosine and phenylalanine concentrations were also collected and analyzed, as part of the regular HT1 follow up program in our clinic. RESULTS: Delayed performance in Bayley scale mental developmental index (MDI) was identified in 29% to 38% of the patients assessed at different ages. At preschool age, mean full scale IQ (FSIQ) was 88 ± 16; six out of nine assessed children preformed within normal range, and one child presented with intellectual disability. At school age mean FSIQ was 79 ± 18, three out of nine children preformed within normal range and two showed intellectual disability. Repeated measures showed IQ decline over time in four out of eight patients, all of whom presented with symptoms in their first months of life. Patients that showed no progressive IQ decline were 8 months or older at diagnosis, with a mean age of 17 months. Significant correlation between Phe/Tyr ratio and FSIQ at school age was identified (r = - 0.689; p < 0.044). CONCLUSION: Some patients with HT1 treated with nitisinone and protein restricted diet are at risk of presenting developmental delay and impaired cognitive functioning. Patients with early onset of symptoms could be at risk for progressive cognitive functioning decline over time.
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Iron deficiency anemia is the most common nutritional deficiency worldwide, and the most susceptible groups are infants, preschoolers, women of childbearing age, and pregnant women. It is therefore essential to understand the mechanisms of regulation of iron uptake, transport, and absorption at the cellular level, particularly in enterocytes, and to identify blood biomarkers that allow the evaluation of iron status. This review describes how iron absorption is regulated by intestinal epithelial cells, the main proteins involved (iron transporters, oxidoreductases, storage proteins), and the main blood biomarkers of iron metabolism.
La anemia por deficiencia de hierro continúa siendo la deficiencia nutricional más abundante en el mundo, y son los lactantes, preescolares, mujeres en edad fértil y embarazadas los grupos de mayor susceptibilidad. Debido a esto es que se hace necesario el conocer los mecanismos de regulación de captación, transporte y absorción del metal a nivel celular, principalmente a nivel del enterocito y, una vez que el hierro entra a la circulación, conocer cuáles son los biomarcadores que permiten realizar un seguimiento del estatus del hierro corporal. En esta revisión mostramos, en primer lugar, cómo se regula la entrada de hierro a nivel de la célula del epitelio intestinal, mostrando las principales proteínas involucradas (transportadores de entrada y salida de hierro, oxido-reductasas, proteína de almacenamiento) y, para finalizar, hacemos un recuento de los principales biomarcadores del metabolismo de hierro una vez que este ha entrado y circula por el organismo.
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Ferro/metabolismo , Fenômenos Fisiológicos da Nutrição , Biomarcadores/sangue , Humanos , Inflamação/metabolismo , Ferro/sangueRESUMO
OBJECTIVE: To determine the effect of phytic acid, tannic acid and pectin on fasting non-heme iron bioavailability in both the presence and absence of calcium. RESEARCH METHODS: Twenty-eight apparently healthy adult females participated in two iron absorption studies using radioactive iron isotopes ((59)Fe and (55)Fe). One group received 5mg of iron (as FeSO4) alone (control), together with 10mg of phytic acid, 100mg of tannic acid and 250mg of pectin (study A), on different days. The second group received the same iron doses and compounds as the other group, plus 800mg of calcium (CaCl2) (study B). The compounds were administered after an overnight fast, and no food or beverages were consumed for the following 3h. Iron status and circulating radioactivity were measured in venous blood samples. RESULTS: The geometric means of iron bioavailability (range±1SD) for iron alone, iron with phytic acid, iron with tannic acid, and iron with citrus pectin were 25.0% (11.9-52.0); 18.9% (9.9-35.8); 16.8% (8.7-32.3); and 21.1% (10.2-43.9), respectively (repeated-measures ANOVA, p<0.02 (Dunnett's post hoc: control vs tannic acid p<0.05). When 800mg of calcium was added (study B), iron bioavailability was 16.7% (10.1-27.5); 13.2% (7.1-24.6); 14.8% (8.8-25.1); and 12.6% (5.5-28.8), respectively (repeated-measures ANOVA, NS). CONCLUSIONS: Tannic acid decreases the fasting bioavailability of non-heme iron, however this effect did not exist in the presence of calcium. No effect was observed by phytic acid or citrus pectin on fasting non-heme iron bioavailability in both the presence and absence of calcium.
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Cálcio/farmacologia , Jejum/metabolismo , Ferro/metabolismo , Pectinas/farmacologia , Ácido Fítico/farmacologia , Taninos/farmacologia , Adulto , Disponibilidade Biológica , Feminino , Heme/metabolismo , HumanosRESUMO
UNLABELLED: It is not clear how frequent is copper deficiency in humans. Current copper markers are not sensitive enough to detect early copper deficiency and new markers are needed. CCS is a candidate to become a copper biomarker. OBJECTIVE: Measuring CCS mRNA relative expression in malnourished children and compare results (a) with those of the same children after nutritional recovery and (b) with well-nourished children. METHOD: On admission to the protocol and after 15 day nutritional treatment, severely (G1=18) and moderately (G2=10) malnourished children were compared with well-nourished healthy controls (G3=15), measuring anthropometric indicators, blood biochemistry, Cu, Fe and Zn serum concentrations, ceruloplasmin, C Reactive protein and mRNA abundance of CCS, SOD and MT2 in peripheral mononuclear cells. RESULT: In malnourished groups, mean serum copper concentration was below the cut-off on admission to hospital and increased after 15 days (t-test, p<0.01). On admission to protocol, CCS mRNA abundance in G1 and G2 was higher than in G3 (one way ANOVA, p<0.001). After 15 days, CCS expression decreased as expected (t-test, p<0.001). Initial SOD mRNA relative abundance was higher in study groups than controls and also between G1 and G2 (One way ANOVA, both p<0.01); after 15 days, G1 and G2 were not different (t-test, NS). MT2A abundance of transcripts did not follow a clear change pattern. CONCLUSION: CCS mRNA abundance responded as expected, being higher in malnourished children than in controls; nutritional recovery in these latter resulted in decreasing expression of the chaperone, supporting the hypothesis that CCS may be a copper biomarker.
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Transtornos da Nutrição Infantil/sangue , Transtornos da Nutrição Infantil/enzimologia , Cobre/deficiência , Superóxido Dismutase/metabolismo , Pré-Escolar , Cobre/sangue , Feminino , Humanos , Lactente , Masculino , Superóxido Dismutase/análiseRESUMO
BACKGROUND: Type 2 diabetes is highly prevalent in populations having high rates of overweight and obesity. It is a chronic condition responsible for long-term severe dysfunction of several organs, including the kidneys, heart, blood vessels, and eyes. Although there are a number of pharmacologic products in the market to treat insulin resistance and impaired insulin secretion--the most prominent features of this disease--interventions directed at preserving the integrity and function of beta-cells in the long term are less available. The use of some nutrients with important cellular protective roles that may lead to a preservation of beta-cells has not been fully tested; among these, zinc may be an interesting candidate. OBJECTIVE: To assess the potential of zinc supplementation as coadjuvant to diabetes therapy. METHODS: This article reviews the available information on the use of zinc as part of diabetes therapy. RESULTS: Cellular and animal models provide information on the insulin mimetic action of zinc, as well as its role as a regulator of oxidative stress, inflammation, apoptosis, and insulin secretion. Zinc supplementation studies in humans are limited, although some positive effects have been reported; mainly, a modest but significant reduction in fasting glucose and a trend to decreased glycated hemoglobin (HbA1c). CONCLUSIONS: Zinc supplementation may have beneficial effects on glycemic control. Nevertheless, among the studies considered, the vast majority lasted for 6 months or less, suggesting the importance of conducting long-duration studies given the characteristics of type 2 diabetes as a chronic disease.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Zinco/uso terapêutico , Animais , Apoptose , Glicemia/análise , Diabetes Mellitus Tipo 2/complicações , Suplementos Nutricionais , Humanos , Inflamação , Insulina/metabolismo , Resistência à Insulina , Secreção de Insulina , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/fisiologia , Estresse Oxidativo , Zinco/administração & dosagem , Zinco/fisiologiaRESUMO
Inflammation and iron accumulation are present in a variety of neurodegenerative diseases that include Alzheimer's disease and Parkinson's disease. The study of the putative association between inflammation and iron accumulation in central nervous system cells is relevant to understand the contribution of these processes to the progression of neuronal death. In this study, we analyzed the effects of the inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) and of lipopolysaccharide on total cell iron content and on the expression and abundance of the iron transporters divalent metal transporter 1 (DMT1) and Ferroportin 1 (FPN1) in neurons, astrocytes and microglia obtained from rat brain. Considering previous reports indicating that inflammatory stimuli induce the systemic synthesis of the master iron regulator hepcidin, we identified brain cells that produce hepcidin in response to inflammatory stimuli, as well as hepcidin-target cells. We found that inflammatory stimuli increased the expression of DMT1 in neurons, astrocytes, and microglia. Inflammatory stimuli also induced the expression of hepcidin in astrocytes and microglia, but not in neurons. Incubation with hepcidin decreased the expression of FPN1 in the three cell types. The net result of these changes was increased iron accumulation in neurons and microglia but not in astrocytes. The data presented here establish for the first time a causal association between inflammation and iron accumulation in brain cells, probably promoted by changes in DMT1 and FPN1 expression and mediated in part by hepcidin. This connection may potentially contribute to the progression of neurodegenerative diseases by enhancing iron-induced oxidative damage.
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Peptídeos Catiônicos Antimicrobianos/genética , Proteínas de Transporte de Cátions/genética , Encefalite/imunologia , Encefalite/metabolismo , Ferro/metabolismo , Animais , Peptídeos Catiônicos Antimicrobianos/imunologia , Peptídeos Catiônicos Antimicrobianos/metabolismo , Astrócitos/citologia , Astrócitos/imunologia , Astrócitos/metabolismo , Encéfalo/citologia , Encéfalo/imunologia , Proteínas de Transporte de Cátions/imunologia , Proteínas de Transporte de Cátions/metabolismo , Encefalite/genética , Feminino , Feto/citologia , Hepcidinas , Interleucina-6/imunologia , Interleucina-6/farmacologia , Lipopolissacarídeos/farmacologia , Masculino , Microglia/citologia , Microglia/imunologia , Microglia/metabolismo , Degeneração Neural/genética , Degeneração Neural/imunologia , Degeneração Neural/metabolismo , Neurônios/citologia , Neurônios/imunologia , Neurônios/metabolismo , Cultura Primária de Células , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
Studies concerning oxidative stress (OxE) parameters have increased, mainly because of its important role in cardiovascular diseases and diabetes complications. The main objective of this study was to evaluate iron nutrition status and oxidative stress parameters in subjects that had developed metabolic syndrome (MetS). Subjects from the Research Program of Risk Factors for Cardiovascular Disease (n = 155) were studied (ages ranging from 45 to 65 years old) and classified according to the Adult Treatment Panel III criterion. A blood sample was taken after a 12-h fasting period, and basal glucose, insulin, thiobarbituric acid reactive substances (TBARS), oxidized LDL (oxLDL), heme oxygenase (HO) activity, lipid profile, and iron nutrition status were determined. Eighty-five subjects were classified as MetS, and 70 non-MetS. Individuals with MetS showed higher Fe storage (high levels of ferritin, total body iron and low transferrin receptor), oxLDL, TBARS, and homeostatic model assessment for insulin resistance levels. The MetS group showed high levels of oxidative stress parameters (HO activity, oxLDL, and TBARS). The presence of MetS showed an association with LDL oxidation risk (multiple lineal regression according to sex and age, p < 0.001). High levels of triglycerides (p < 0.001) and waist circumference (p < 0.012) were associated with oxLDL levels, as well as an association between TBARS and oxLDL with ferritin levels. Through logistic regression analyses, the highest quartile of ferritin was associated with a threefold risk of developing MetS compared to the lowest quartile; also, TBARS showed a 21-fold risk for the development of MetS. Finally, elevated levels of oxidative stress parameters such us oxLDL, TBARS, HO, and Fe storage were associated to MetS.
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Ferro/sangue , Síndrome Metabólica/sangue , Síndrome Metabólica/fisiopatologia , Estresse Oxidativo/fisiologia , Idoso , Glicemia/metabolismo , Índice de Massa Corporal , Jejum/sangue , Feminino , Ferritinas/sangue , Heme Oxigenase (Desciclizante)/sangue , Heme Oxigenase (Desciclizante)/metabolismo , Humanos , Insulina/sangue , Resistência à Insulina/fisiologia , Lipídeos/sangue , Lipoproteínas LDL/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Substâncias Reativas com Ácido Tiobarbitúrico/análiseRESUMO
Background: The pharmacological action of metformin goes beyond mere glycemic control, decreasing markers of inflammation and contributing to the reduction of oxidative stress. Aim: To evaluate biochemical, anthropometric and pro-inflammatory markers in obese type 2 diabetic patients treated or not with metformin. Patients and Methods: Obese patients with type 2 diabetes were invited to participate in the study if they were aged more than 40 years, were not receiving insulin, did not have cardiovascular diseases and were not taking anti-inflammatory drugs. A pharmacological history was taken and patients were stratified in two groups whether they were using metformin or not. A fasting blood sample was obtained to measure blood glucose, insulin, lipid levels, C reactive protein (hsCRP) and to isolate peripheral blood mononuclear cells. RNA was isolated from these cells to measure expression of tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), Toll-Like Receptor 2/4 (TLR 2/4) and beta-2-microglobulin (B2M). Results: Thirty participants were studied. Of these, 16 subjects aged 54.4 ± 5.5years were treated with metformin and 14 subjects aged 54.9 ± 6.4 years did not receive the drug. Participants receiving metformin had lower levels of hsCRP and lower mRNA relative abundance of TNF-α and TLR 2/4. There were no differences in glucose levels or lipid profile between both groups. Conclusions: Obese diabetic patients treated with metformin had lower levels of hsCRP expression of TNF-α and TLR 2/4, than their counterparts not receiving the drug.
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Humanos , Masculino , Pessoa de Meia-Idade , Proteína C-Reativa/análise , /tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Obesidade/sangue , Receptores Toll-Like/sangue , Fator de Necrose Tumoral alfa/sangue , Biomarcadores/análise , Índice de Massa Corporal , Estudos de Casos e Controles , /sangue , Hipoglicemiantes/farmacologia , Inflamação/genética , /sangue , /genética , Leucócitos Mononucleares/efeitos dos fármacos , Metformina/farmacologia , Obesidade/complicações , Obesidade/fisiopatologia , Reação em Cadeia da Polimerase em Tempo Real , Receptores Toll-Like/genética , Fator de Necrose Tumoral alfa/genéticaRESUMO
UNLABELLED: Type 1 diabetes mellitus (T1D) is an autoimmune disease characterized by a progressive destruction of pancreatic ß cells. It has been reported that patients with autoimmune diseases exhibit decreased expression of caspase 3 and other pro-apoptotic markers in peripheral blood mononuclear cells (PBMC). AIM: To estimate the expression of apoptosis markers in PBMC from T1D patients cultured with high glucose concentration. RESULTS: At 11 mM of glucose, the pro-apoptotic gene fas showed a 7-fold decreased expression in the T1D group compared to controls, while bax showed a 50-fold decreased expression (medians 0.14 and 0.02, respectively, considering patients as 1). At 44 mM of glucose, there is a decreased expression of the same genes, but less abrupt (medians 0.75 and 0.47). Only the anti-apoptotic gene xiap showed a 2-fold increased expression at 11 mM of glucose (median 2.3). Regarding the clinical history, no relationships were observed with age of diagnosis, ketoacidosis, glucose at debut or GAD-65 and IA-2 titles. CONCLUSION: We can conclude that the apoptotic mechanisms in PBMC of T1D patients under high glucose conditions are altered, and this is proved by the decreased expression of the pro-apoptotic genes fas and bax and by the increased expression of the anti-apoptotic gene xiap.
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Diabetes Mellitus Tipo 1/genética , Glucose/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Proteína X Associada a bcl-2/genética , Receptor fas/genética , Adolescente , Adulto , Apoptose/efeitos dos fármacos , Biomarcadores/metabolismo , Células Cultivadas , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patologia , Regulação para Baixo , Feminino , Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Humanos , Lactente , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/patologia , Masculino , Pessoa de Meia-Idade , Regulação para Cima , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo , Proteína X Associada a bcl-2/metabolismo , Receptor fas/metabolismoRESUMO
Heme-Fe is an important source of dietary iron in humans; however, the mechanism for heme-Fe uptake by enterocytes is poorly understood. Heme carrier protein 1 (HCP1) was originally identified as mediating heme-Fe transport although it later emerged that it was a folate transporter. We asked what happened to heme-Fe and folate uptake and the relative abundance of hcp1 and ho1 mRNA in Caco-2 cells after knockdown by transfection with HCP1-directed short hairpin (sh)RNA. Control Caco-2 cells were cultured in bicameral chambers with 0-80 µM heme-Fe for selected times. Intracellular Fe and heme concentration increased in Caco-2 cells reflecting higher external heme-Fe concentrations. Maximum Fe, heme, and heme oxygenase 1 (HO1) expression and activity were observed between 12 and 24 h of incubation. Quantitative RT-PCR for hcp1 revealed that its mRNA decreased at 20 µM heme-Fe while ho1 mRNA and activity increased. When shRNA knocked down hcp1 mRNA, heme-(55)Fe uptake and [(3)H]folate transport mirrored the mRNA decrease, ho1 mRNA increased, and flvcr mRNA was unchanged. These data argue that HCP1 is involved in low-affinity heme-Fe uptake not just in folate transport.
Assuntos
Enterócitos/metabolismo , Heme/metabolismo , Ferro/metabolismo , Transportador de Folato Acoplado a Próton/metabolismo , Animais , Células CACO-2 , Compostos Férricos/administração & dosagem , Compostos Férricos/sangue , Heme Oxigenase-1/metabolismo , Humanos , Injeções Intravenosas , Radioisótopos de Ferro , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Reação em Cadeia da Polimerase , Transportador de Folato Acoplado a Próton/genética , Interferência de RNA , RNA Mensageiro/metabolismo , Coelhos , Receptores Virais/genética , Receptores Virais/metabolismo , Fatores de Tempo , TransfecçãoRESUMO
Type 2 diabetes (T2D) is directly related to alterations in iron status, oxidative stress and decreased mitochondrial activity, but the possible interaction of these parameters among T2D patients and their offspring is unclear. The whole study included 301 subjects: 77 T2D patients and one of their offspring and 51 control subjects with one of their offspring. The offspring were older than 20 years old. We measured parameters of iron status (serum iron, ferritin and transferrin receptor), diabetes (pre and post-prandial glucose, insulin, lipids), oxidative stress (Heme oxygenase activity, TBARS, SOD, GSH, Vitamin E), as well as the expression of genes in blood leukocytes related to mitochondrial apopotosis (mitofusin and Bcl/Bax ratios). The offspring of T2D patients had increased levels of serum ferritin (P < 0.01) and lower transferrin receptor (P < 0.008); higher insulin (P < 0.03) and total and LDL cholesterol; higher heme oxygenase and SOD activities increased TBARS and lower GSH; decreased mitofusin and Bcl/Bax expression ratios compared to offspring of normal subjects. These results suggest that the offspring of T2D patients could have an increased metabolic risk of develop a cardiovascular disease mediated by oxidative stress and iron status.
Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Ferro/metabolismo , Mitocôndrias/metabolismo , Estresse Oxidativo/fisiologia , Adulto , Células Cultivadas , Feminino , Ferritinas/sangue , Glutationa/sangue , Heme Oxigenase (Desciclizante)/metabolismo , Humanos , Insulina/sangue , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Estresse Oxidativo/genética , Receptores da Transferrina/sangue , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Vitamina E/sangueRESUMO
Liver cells respond to copper loading upregulating protective mechanisms. However, to date, except for liver content, there are no good indicators that identify individuals with excess liver copper. We hypothesized that administering high doses of copper to young (5.5 mg Cu · kg⻹ . d⻹) and adult (7.5 mg Cu · kg⻹ . d⻹) capuchin monkeys would induce detectable liver damage. Study groups included adult monkeys (2 females, 2 males) 3-3.5 y old at enrollment treated with copper for 36 mo (ACu); age-matched controls (1 female, 3 males) that did not receive additional copper (AC); young monkeys (2 female, 2 males) treated from birth with copper for 36 mo (YCu); and young age-matched controls (2 female, 2 males) that did not receive additional copper (YC). We periodically assessed clinical, blood biochemical, and liver histological indicators and at 36 mo the hepatic mRNA abundance of MT2a, APP, DMT1, CTR1, HGF, TGFß, and NFκΒ only in adult monkeys. After 36 mo, the liver copper concentration was 4-5 times greater in treated monkeys relative to controls. All monkeys remained healthy with normal routine serum biochemical indices and there was no evidence of liver tissue damage. Relative mRNA abundance of HGF, TGFß and NFκB was significantly greater in ACu than in AC monkeys. In conclusion, capuchin monkeys exposed to copper at doses up to 50 times the current upper level enhanced expression of genes related to inflammation and injury without clinical, blood biochemical, or histological evidence of liver damage.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/patologia , Gluconatos/administração & dosagem , Gluconatos/toxicidade , Fígado/metabolismo , Transcrição Gênica/fisiologia , Administração Oral , Envelhecimento , Animais , Biomarcadores/metabolismo , Cebus , Relação Dose-Resposta a Droga , Feminino , Gluconatos/análise , Cabelo/química , Fígado/citologia , Fígado/efeitos dos fármacos , Testes de Função Hepática , Masculino , Modelos Animais , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcrição Gênica/efeitos dos fármacosRESUMO
Assessment of proteins in blood and other tissues has failed to identify markers of early copper effects on health. Studies in animal models show that chaperone of SOD (CCS) respond to changes of copper status. Evidence about other copper chaperones (COXIV, ATOX) is not clear. The aim of this study was to assess by means of an in vitro challenge the mRNA relative abundance of ccs, sod1, coxIV, mtIIa and atox in peripheral mononuclear cells (PMNCs) obtained from healthy individuals, acutely and chronically supplemented with small-to-moderate amounts of copper. Healthy participants received 8 mg Cu/d (supplemented group, SG) or placebo, (placebo group, PG) for 2 months. Biochemical indicators were assessed at basal (T0) and after 2 (T2) and 60 days (T60). At these times PMNCs were obtained, challenged with 1, 5 or 20 µM Cu-histidine for 20 h and the mRNA relative abundance of the selected genes assessed by real time PCR. The results showed that at T0, intracellular copper was not different between experimental and control groups. This increased at T2 and T60 when the copper in the media increased (two-way ANOVA, P < 0.001). In PG, CCS mRNA transcripts showed no significant changes (two-way ANOVA) at T2 and T60. In SG, CCS changed by treatment, time and interaction (two-way ANOVA, all P < 0.001). SOD, ATOX and COXIV expressions changed in both PG and SG showing various patterns of response, requiring further study. MTII responded as expected. We conclude that using healthy individuals as a human model, CCS but not SOD, ATOX or COXIV responded consistently to controlled changes of copper availability in an in vitro copper challenge.