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BACKGROUNDS AND AIMS: Insulin resistance is a common feature of metabolic syndrome that may be influenced by genetic risk factors. We hypothesized that genetic risk scores (GRS) of SNPs that influence insulin resistance and signaling interact with lifestyles to modulate insulin resistance in Korean adults. METHODS AND RESULTS: Genome-wide association studies (GWAS) of subjects aged 40-65 years who participated in the Ansung/Ansan cohorts (8842 adults) in Korea revealed 52 genetic variants that influence insulin resistance. The best gene-gene interaction model was explored using the generalized multifactor dimensionality reduction (GMDR) method. GRS from the best model were calculated and the GRS were divided into low, medium and high groups. The best model for representing insulin resistance included SLIT3_rs2974430, PLEKHA5_rs1077044, and PPP2R2C_rs16838853. The odds ratios for insulin resistance were increased by 150% in the High-GRS group compared to the Low-GRS group. However, ORs for insulin secretion capacity, measured by HOMA-B, were not associated with GRS. Coffee and caffeine intake and GRS had an interaction with insulin resistance: In subjects with high coffee (≥10 cups/week) or caffeine intake (≥220 mg caffeine/day), insulin resistance was significantly elevated in the High-GRS group, but not in the Low-GRS. However, alcohol intake, smoking and physical activity did not have an interaction with GRS. Insulin secretion capacity was not significantly influenced by GRS when evaluating the adjusted odds ratios. CONCLUSIONS: Subjects with High-GRS may be susceptible to increased insulin resistance by 50% and its risk may be exacerbated by consuming more than 10 cups coffee/week or 220 mg caffeine/day.
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Cafeína/administración & dosificación , Estimulantes del Sistema Nervioso Central/administración & dosificación , Café , Resistencia a la Insulina/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Estilo de Vida , Proteínas de la Membrana/genética , Polimorfismo de Nucleótido Simple , Proteína Fosfatasa 2/genética , Adulto , Glucemia/metabolismo , Femenino , Interacción Gen-Ambiente , Estudio de Asociación del Genoma Completo , Humanos , Insulina/sangre , Masculino , Persona de Mediana Edad , República de Corea , Medición de Riesgo , Factores de RiesgoRESUMEN
It is important to understand what genetic risk factors lead to hypertension and how genotype-specific dietary and lifestyle modification can mitigate the risk of developing hypertension. The ATP2B1 rs17249754 gene, which encodes a calcium pump expressed in vascular smooth muscle was identified as having variants that conferred higher or lower risk of hypertension-with the major allele carriers being increased at risk. However, the effects of dietary intakes on risk of hypertension among carriers of the different alleles have not been fully elucidated. Therefore, we evaluated ATP2B1 rs17249754 and its interaction with dietary intakes of sodium (Na), potassium (K) and calcium (Ca) on the risk of developing hypertension using the Ansan/Ansung (n=8842) and City-Rural (n=5512) cohorts from the Korean Genome and Epidemiology Study. Carriers of the major allele of ATP2B1 rs17249754 were at greater risk of developing hypertension and high Na intake and low Ca increased the risk more in major allele than among minor allele carriers. High potassium intake was more protective against hypertension in the subjects expressing minor alleles and a low Na/K intake ratio was the most consistently beneficial to the subjects expressing the minor allele. When controlling for Na and K, low Ca intake was associated with a substantially higher risk for high systolic blood pressure in the major allele carriers compared with minor allele, suggesting good calcium status is especially important for the major allele carriers. In conclusion, people with the major allele of ATP2B1 rs17249754 are susceptible to hypertension especially in low intake of Ca and high ratio of Na and K.
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Calcio de la Dieta , Hipertensión/etiología , ATPasas Transportadoras de Calcio de la Membrana Plasmática/genética , Potasio en la Dieta , Sodio en la Dieta/efectos adversos , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
We report an optically accessible pyrolysis micro-reactor suitable for in situ laser spectroscopic measurements. A radiative heating design allows for completely unobstructed views of the micro-reactor along two axes. The maximum temperature demonstrated here is only 1300 K (as opposed to 1700 K for the usual SiC micro-reactor) because of the melting point of fused silica, but alternative transparent materials will allow for higher temperatures. Laser induced fluorescence measurements on nitric oxide are presented as a proof of principle for spectroscopic characterization of pyrolysis conditions.
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Transient carotid artery occlusion causes ischemia/reperfusion (I/R) injury resulting in neuron and pancreatic ß-cell death with consequential post-stroke hyperglycemia, which can lead to diabetes and may accelerate the development of Alzheimer's disease. Antioxidants have been shown to protect against the I/R injury and destruction of neurons. However, it is unknown whether the protection against I/R injury extends to the pancreatic ß-cells. Therefore, we investigated whether treatment with ebselen, a glutathione peroxidase mimic, prevents neuronal and ß-cell death following I/R in gerbils susceptible to stroke. After 28 days post artery occlusion, there was widespread neuronal cell death in the CA1 of the hippocampus and elevated IL-1ß and TNF-α levels. Pretreatment with ebselen prevented the death by 56% and attenuated neurological damage (abnormal eyelid drooping, hair bristling, muscle tone, flexor reflex, posture, and walking patterns). Ischemic gerbils also exhibited impaired glucose tolerance and insulin sensitivity which induced post-stroke hyperglycemia associated with decreased ß-cell mass due to increased ß-cell apoptosis. Ebselen prevented the increased ß-cell apoptosis, possibly by decreasing IL-1ß and TNF-α in islets. Ischemia also attenuated hepatic insulin signaling, and expression of GLUT2 and glucokinase, whereas ebselen prevented the attenuation and suppressed gluconeogenesis by decreasing PEPCK expression. In conclusion, antioxidant protection by ebselen attenuated I/R injury of neurons and pancreatic ß-cells and prevented subsequent impairment of glucose regulation that could lead to diabetes and Alzheimer's disease.
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Antiinflamatorios no Esteroideos/farmacología , Azoles/farmacología , Isquemia Encefálica/tratamiento farmacológico , Células Secretoras de Insulina/efectos de los fármacos , Insulina/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Compuestos de Organoselenio/farmacología , Animales , Supervivencia Celular , Citocinas/metabolismo , Gerbillinae , Glucógeno/metabolismo , Hiperglucemia/tratamiento farmacológico , Insulina/farmacología , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patología , Isoindoles , Masculino , Distribución Aleatoria , Daño por Reperfusión/metabolismo , Transducción de SeñalRESUMEN
BACKGROUND/OBJECTIVES: Gestational diabetes mellitus (GDM) risk factors are well established for Caucasians, but not for Asians. We hypothesized that nutrient intakes, plasma adipokines and/or gestational hormones might be linked to GDM development among pregnant Korean women. This study sought to identify new risk factors for GDM and adverse pregnancy outcomes according to body weight at prepregnancy. SUBJECTS/METHODS: All subjects were pregnant women visiting the Cheil General Hospital and Women's Healthcare Center between June 2006 and March 2009. Non-GDM (n=531) and GDM (n=215) participants were divided into normal-weight and overweight groups according to prepregnancy body mass index (BMI) above or below 23 kg/m(2) at 24-28th week of gestation. At that time, glucose tolerance, insulin resistance as homeostatic model assessment for insulin resistance, insulin secretory capacity as homeostatic model assessment for ß-cell function, anthropometric measurement, nutrient intakes, and plasma levels of adipokines and gestational hormones were determined. RESULTS: GDM women gained more weight in early pregnancy than non-GDM among normal-weight women. GDM was mainly associated with increased insulin resistance in overweight women and decreased insulin secretory capacity in normal-weight women. Plasma visfatin and adiponectin were lower and progesterone levels higher in GDM than non-GDM independent of BMI while plasma resistin levels were higher in non-GDM, but not GDM, overweight women. Energy and saturated fat intakes were higher in GDM independent of body weight, whereas taurine intakes were lower in GDM than non-GDM only in normal-weight women. CONCLUSIONS: Low visfatin and adiponectin and high progesterone levels in the circulation and high energy and saturated fat intakes were common risk factors for GDM and pregnancy outcome such as large for gestational age. Daily reference intakes for energy and fat during pregnancy need to be re-evaluated according to prepregnancy BMI.
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Adiponectina/sangre , Índice de Masa Corporal , Diabetes Gestacional/etiología , Grasas de la Dieta/efectos adversos , Ingestión de Energía , Ácidos Grasos/efectos adversos , Nicotinamida Fosforribosiltransferasa/sangre , Diabetes Gestacional/sangre , Dieta/efectos adversos , Femenino , Humanos , Insulina/metabolismo , Resistencia a la Insulina , Secreción de Insulina , Sobrepeso , Embarazo , Progesterona/sangre , Valores de Referencia , Factores de Riesgo , Taurina/farmacología , Aumento de PesoRESUMEN
AIMS: In this study, we investigated the anti-obesity effects of kimchi (Korean traditional fermented vegetable) fermented either without starter culture or with a specific starter culture, Weissella koreensis OK1-6. METHODS AND RESULTS: C57BL/6J mice were divided into four groups (n = 7); normal diet, HF (high-fat diet), HF-KC (high-fat diet containing 3% kimchi manufactured without starter) and HF-KCO (high-fat diet containing 3% kimchi manufactured with the starter culture W. koreensis OK1-6). After 12 weeks of dietary intervention, the mice were killed, and serum and tissue samples were examined. Serum and hepatic lipid profile, insulin, leptin concentration and expression level of lipid anabolic genes like peroxisome proliferator-activated receptor γ, stearoyl-CoA desaturase-1, liver X receptor α and SREBP2 were significantly decreased (<0.05) along with body and epididymal fat pad weight in the HF-KCO group compared with the HF-KC and HF group. CONCLUSIONS: These results suggested that kimchi fermented with the starter W. koreensis OK1-6 has anti-obesity effects in HF-induced obese mice. SIGNIFICANCE AND IMPACT OF THE STUDY: These results may contribute to nutraceutical and food industries in developing functional food and probiotics based therapies for the treatment and prevention of obesity.
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Brassica/microbiología , Microbiología de Alimentos , Obesidad/prevención & control , Weissella/fisiología , Tejido Adiposo/efectos de los fármacos , Animales , Peso Corporal/efectos de los fármacos , Dieta Alta en Grasa , Grasas de la Dieta/metabolismo , Modelos Animales de Enfermedad , Fermentación , Insulina/sangre , Insulina/metabolismo , Leptina/sangre , Leptina/metabolismo , Lípidos/sangre , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/metabolismo , PPAR gamma/metabolismoRESUMEN
A single photon ionization, molecular beam sampling, reflectron time-of-flight mass spectrometer (SPI/MBTOFMS) has been developed and used to study pyrolysis products from a selection of biomass materials. Spectra are characterized by high resolution and decreased fragmentation compared to electron-impact ionization mass spectra from related molecular beam mass spectrometer systems equipped with quadrupole mass analyzers.
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Biomasa , Espectrometría de Masas/métodosRESUMEN
Excitation scans of the MgO B(1)?(+)-A(1)? transition were made in a seeded acetylene-air flame. The combustion of magnesium in oxygen and carbon dioxide is well known and is of significant interest for fire safety, solid propellant applications, and recently for use as an in situ resource propellant for planetary exploration of Mars. This spectroscopic study expands the available data on this electronic transition, particularly data at high rotational states that are lacking in the literature. Rotational parameters of the v = 0, 1, and 2 states of B(1)?(+) are derived.
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We have previously shown that supplementary choline causes significant decreases in urinary excretion of carnitine in humans. The objectives of the present work were to study this interaction in a different human population and on other body pools of carnitine in an animal model. In young adult women, daily choline supplementation (20 mg/kg body wt) resulted in a 75% lower urinary carnitine excretion than in controls, without significantly altering plasma carnitine concentrations. Supplementary choline was added to the ground diet of Sprague-Dawley rats (2.5 g/kg diet) and guinea pigs (3 g/kg diet). Choline supplementation had no effect on plasma concentrations or urinary excretion of carnitine in the rats. In guinea pigs, however, choline supplementation resulted in a significantly lower urinary excretion and higher plasma total carnitine concentrations. The skeletal muscle carnitine concentration was higher in the choline-supplemented guinea pigs, but not significantly higher in other tissues. These studies demonstrated that choline supplementation results in decreased urinary excretion of carnitine in young adult women, that guinea pigs are a suitable animal model for studying the effect of choline supplementation on carnitine status in humans, and that choline results in a conservation of carnitine in guinea pigs and perhaps in humans.
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Carnitina/metabolismo , Colina/farmacología , Ácido 3-Hidroxibutírico , Adulto , Animales , Carnitina/sangre , Carnitina/orina , Colina/administración & dosificación , Creatinina/orina , Femenino , Alimentos Fortificados , Cobayas , Homeostasis/efectos de los fármacos , Homeostasis/fisiología , Humanos , Hidroxibutiratos/sangre , Masculino , Músculo Esquelético/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
The use of two-line atomic fluorescence (TLF) as a diagnostic tool in combustion research offers a number of advantages over other temperature measurement techniques. The most important is its potential to take data at rates high enough (10 kHz) to follow turbulent flow. An experimental investigation of the feasibility of constructing a TLF system with these capabilities has been carried out. To meet the high data rate requirements, dye-laser excitation sources and a computer data acquisition system were incorporated in a system that utilized the 410- and 451-nm transitions of indium seeded into a flat-flame methane burner. Preliminary one-shot results exhibited a precision of approximately 13% and 350 K accuracy and served to allow the identification of the major sources of experimental error associated with a TLF system of this type. Recommendations are made for eliminating these error sources, and it is expected that at high data rates precision and accuracy of better than 2% can be attained.
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The response of OH in flames to laser excitation is studied in some detail. The population balance equations are solved numerically using an empirical model for the rotational relaxation rates. The empirical model parameters are fit to experimental spectra using a linear regression procedure and the resulting description of OH behavior is shown to be satisfactory to within the precision of the data. The model is then used to recover branching ratios for a number of flame conditions.
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A technique for measuring translational flame temperature utilizing the laser induced fluorescence spectrum of OH is demonstrated. The method is based on matching the observed spectrum to a numerical model in which the detailed balance temperature is a parameter. The precision of the method exceeds that of the line reversal technique. Accuracy is limited by the calibration source and the validity of the numerical rotational relaxation rate model.
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The use of coherent optical transient spectroscopy to study collisional processes in flames has been considered. A short discussion of the density matrix equations is used to illustrate transient phenomena of possible interest. Characteristic times that arise for such phenomena are calculated for a variety of flame conditions, and it is concluded that both dephasing and energy decay rates for electronic and ir transitions in selected species may be measured. Available excitation sources and transient measurement techniques are examined and found suitable for making such measurements.
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The method of saturated fluorescence for measuring species concentrations in flames is usually performed with laser beams that do not provide a constant intensity distribution across the focal volume. Because of the intensity distribution across the beam, the fluorescence signal does not depend on laser power or intensity in the same manner as for uniform illumination. This leads to anomolous apparent saturation intensities. In the following, the effect is considered for atomic fluorescence. Relations for the fluorescence signal under two common excitation geometries are derived and uncertainty relations used to consider the benefits of high laser intenstiy.
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Uncertainty relations are derived for fluorescence caused by laser excitation in flames. The effect of statistical and systematic uncertainties on the detectability limits for excited states are examined. Fluorescence trapping is discussed and shown to establish an upper limit on the number density that can be measured. Methods for minimizing the trapping effect are discussed.
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Laser based spectroscopic diagnostic tools offer the possibility of spatially and temporally resolved measurements of species concentrations in complex reacting gas flows of engineering interest. The major problem associated with such measurements is the effect of quenching reactions on the fluorescence signal. To overcome this difficulty operating in the saturation mode is proposed. For suitable systems the fluorescence signal is then no longer a function of quenching rates or laser power. Very low detectability limits appear possible.
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In describing the excitation of atomic and molecular species with lasers in spectroscopic applications, only the density matrix formulation is exactly correct. Many workers, however, have used the conventional rate equation formulation. The range of application of the conventional rate equations is examined and, for flames, shown to be valid for sufficiently slow laser pulse rise times under single-mode excitation and for certain special cases of multimode excitation.
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The application of pulsed resonance spectroscopy to the measurement of species concentrations in chemically reacting turbulent flows is discussed. The theory of such measurements is developed. An uncertainty analysis is performed and the results applied to typical combustion conditions. Experimental aspects are discussed. The method shows a significant theoretical improvement in accuracy over Raman and Rayleigh scattering techniques, and no significant barriers appear to block its development.