RESUMEN
OBJECTIVE: The aim of our study was to determine whether eating behaviors and/or physical activity level may explain contradicting results in adipocytokines levels in anorexia nervosa (AN). SUBJECTS/METHODS: Fasting levels of circulating adipocytokines (adiponectin, resistin and leptin), insulin, glucose, C-reactive protein, cytokines (tumor necrosis factor-alpha and interleukin (IL)-1beta), body composition and resting energy expenditure were measured in 24 women AN patients and 14 women controls. These parameters were compared according to AN subtypes: 15 patients with restrictive (R-AN) form versus 9 patients with binge/purge (BP-AN) form; 15 patients with hyperactive (H-AN) form versus 9 patients with nonhyperactive (NH-AN) form. RESULTS: BP-AN patients had significantly higher serum adiponectin levels compared with R-AN patients (P<0.05), and H-AN patients had higher serum leptin and lower serum resistin levels compared with NH-AN patients (P<0.05 for both). CONCLUSIONS: Our study shows specific adipocytokines profiles depending on the subtype of AN: restrictive versus binge/purge and hyperactive versus Nonhyperactive forms. We suggest that these biological signatures could interfere with the outcome of the disease.
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Adiponectina/sangre , Anorexia Nerviosa/sangre , Bulimia Nerviosa/sangre , Hipercinesia/sangre , Leptina/sangre , Resistina/sangre , Adolescente , Adulto , Femenino , Humanos , Actividad Motora , Adulto JovenRESUMEN
2nd generation assays are currently available to determine the concentration of thyrotropin receptor antibody (TRAb) present in Graves' disease. The aim of this study was to evaluate the analytical performance of TRAb assay on Elecsys 2010 and Cobas(R)e of Roche Diagnostics, a new test using electrochemiluminescence immunoassay (ECLIA). The analytical performance observed with this assay is accurate (repetability and reproductibility, analytical and functional sensitivities). Comparing this method with Brahms' assay (TRAK human RIA), the correlation observed can be put in the equation: y = 1.013 x + 1.381; r = 0.92. With a positive value in ECLIA at 0.9 UI/L and at 1 UI/L in RIA (functional sensitivity fixed by manufacturers), concordance study shows a false negative and two false positive. With a positive value at 0.8 UI/L with ECLIA (functional sensitivity calculated from precision's profile for a CV inferior to 10%), there is no false negative and two false-positive results, this value seems to give a better sensitivity.
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Anticuerpos/sangre , Enfermedad de Graves/diagnóstico , Inmunoensayo/métodos , Receptores de Tirotropina/inmunología , Enfermedad de Graves/sangre , Enfermedad de Graves/inmunología , Humanos , Valor Predictivo de las Pruebas , Sensibilidad y EspecificidadRESUMEN
AIMS: To determine plasma levels of apoprotein (apo) C-II and apoprotein C-III in Type 2 diabetic patients and to examine the clinical and biological factors that are associated with elevated apoC concentrations. METHODS: We measured apoC-II and apoC-III in total plasma and in non-high-density lipoprotein fractions by an immunoturbidimetric assay in 88 Caucasian Type 2 diabetic patients and in 138 healthy control subjects. RESULTS: Plasma levels of both apoC-II and apoC-III were increased in Type 2 diabetic patients. The clinical conditions associated with an increase of plasma apoC-II and apoC-III were abdominal obesity, body mass index, poor glycaemic control and lack of insulin treatment. However, when multivariate analysis was used, plasma apoCs levels correlated with triglyceride levels only. The apoC-III/apoC-II ratio was similar in the Type 2 diabetic and control subjects. CONCLUSIONS: Our study shows the parallel increase of apoC-II and C-III in Type 2 diabetic patients. This parallel increase is related to hypertriglyceridaemia only.
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Apolipoproteínas C/sangre , Diabetes Mellitus Tipo 2/sangre , Hipertrigliceridemia/sangre , Anciano , Índice de Masa Corporal , Estudios de Casos y Controles , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Diabetes Mellitus Tipo 2/terapia , Femenino , Humanos , Lipoproteína Lipasa/metabolismo , Masculino , Persona de Mediana Edad , ObesidadRESUMEN
The medical commission of the International Olympic Committee forbids the use of anabolic androgenic steroids to improve sporting performances. Nine anabolic steroids (androsterone (A), nandrolone, estradiol, testosterone propionate, nandrolone-17 propionate, dydrogesterone, testosterone, epitestosterone, boldenone) and alpha-cholestane as internal standard were studied by gas chromatography coupled with mass spectrometry (GC/MS). The derivatisation reagent employed for the derivatisation of anabolic steroids was a mixture of N-methyl-N-trimethylsilyltrifluoroacetamide (MSTFA), ammonium iodide and 2-mercaptoethanol (1000:2:6, v/w/v). Trimethylsilyl (TMS) derivatives were obtained. Anabolic steroids can be derivatised into one or two forms, mainly for androsterone into A-monoTMS and A-diTMS. The aim of this study was to research the optimization conditions of the derivatisation process (maximum yield of silylation reaction) of each anabolic steroid into only one form. A two-level factorial Doelhert design was used to determine the influence of different parameters and their interactions on each compound, thanks to response surface methodology. The parameters to be optimized were the reaction time and the temperature. The interaction "temperature-reaction time" is significant and has a positive effect on the improvement of the effectiveness of the derivatisation. Considering the large amount of information, often not convergent, a global desirability function was applied for multi-responses optimization. Thus, the optimized temperature and the reaction time of silylation were 85 degrees C and 24 min, respectively. Several GC/MS analytical parameters were also studied: linearity (regression coefficient upper than 0.99 for each compound, sensibility (range of concentration 0.05-0.30 microg/ml). Confirmatory experiments were applied to check the predicted values and to validate the model. The confirmatory assay responses are relatively close to the responses predicted. We observed satisfactory resolutions by GC/MS and a run lower than 12 min.
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Anabolizantes/análisis , Cromatografía de Gases y Espectrometría de Masas/métodos , Esteroides/análisis , Análisis Multivariante , Estándares de ReferenciaRESUMEN
We have developed a validated gas chromatography/mass spectrometry (GC/MS) method with two labelled cholesterol tracers, i.e. (2)H(4) ([2H4]-Chol) and (2)H(7) ([2H7]-Chol) enriched moieties, with a new way of calculating the abundance of labelled cholesterol in plasma without natural cholesterol interference. The isotopomers of the analytes could interfere during analysis. Elimination of these interferences can be performed by the blank or mathematical subtraction method. Validation was performed with the two interference elimination methods. For both methods, linearity was obtained in the range 5 x 10(-4) to 10(-2) mM for both labelled cholesterol moieties. In the same range, repeatability and reproducibility were less than 6.5% and 7.5% for [2H4]-Chol and [2H7]-Chol, respectively. Accuracy was about 100% and recoveries always included 100% for the two labelled cholesterols. We demonstrate that measurement of blank plasma is not necessary when using the validated abundance isotope calculation method. This saves time, reagent and samples. This calculation strategy can be extrapolated to comparable tracer approaches.
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Artefactos , Análisis Químico de la Sangre/métodos , Colesterol/sangre , Cromatografía de Gases y Espectrometría de Masas/métodos , Humanos , Marcaje Isotópico/métodos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
The antifungal activity of the essential oil from Cinnamomum cassia, alone or combined with amphotericin B, a drug widely used for most indications despite side-effects was investigated. The composition of the oil was analysed by GC/MS and characterized by its very high content of cinnamaldehyde (92.2%). The minimal inhibitory concentration (MIC 80%), used to evaluate the antifungal activity against Candida albicans, was determined by a macrobroth dilution method followed by a modelling of fungal growth. The essential oil of Cinnamomum cassia exhibited strong antifungal effect (MIC 80% = 0.169 microL/mL and K(aff) = 18,544 microL/mL). A decrease of the MIC 80% of amphotericin B was obtained when the culture medium contained essential oil concentrations ranging from 0.08 to 0.1 microL/mL. The strongest decrease (70%) was obtained when the medium contained 0.1 microL/mL of essential oil. This potentiation of amphotericin B obtained in vitro may show promise for the development of less toxic and more effective therapies especially for the treatment of HIV infection.
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Anfotericina B/farmacología , Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , Cinnamomum aromaticum/química , Aceites Volátiles/química , Aceites Volátiles/farmacología , Acroleína/análogos & derivados , Acroleína/aislamiento & purificación , Acroleína/farmacología , Candida albicans/crecimiento & desarrollo , Candidiasis/tratamiento farmacológico , Cinamatos/aislamiento & purificación , Sinergismo Farmacológico , Cromatografía de Gases y Espectrometría de Masas/métodos , Pruebas de Sensibilidad Microbiana , Fitoterapia , Extractos Vegetales/farmacología , Análisis de RegresiónRESUMEN
In traditional medicine in Mali, extracts derived from Mitragyna inermis (Willd.) O. Kuntze (Family: Rubiaceae) are commonly used to treat malaria. The antimalarial activity and the lack of genotoxicity in vitro and in vivo have been demonstrated in previous studies. Acute and chronic evaluation of the toxicity of the hydroethanolic extract of Mitragyna inermis leaves was performed in this study, according to the recommendations (cahier de l'Agence no. 3) of the French Drug Office. Two dosages (300 mg/kg and 3 g/kg) were given in one single administration by gavage to male and female rats. No animal died and no behavioral signs of acute toxicity were observed. Chronic toxicity studies over 28 days showed no changes in body weight and no macroscopic abnormality in the 14 organs examined after the animals were sacrificed. With the 3 g/kg/d drug dosage (100-fold higher than those proposed in man), only slight histological abnormalities were observed. Statistically significant differences, compared to control animals, in the weight of some organs and the values of some haematological or biochemical parameters were observed. However, these values always remained in the range given by the breeder for naive animals of the same strain. These investigations thus seemed to indicate the safety of repeated oral administration (up to 3 g/kg/d) of the hydroethanolic extract of Mitragyna inermis leaves, which can therefore be continuously used with safety by the African population in traditional treatment of malaria.
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Antimaláricos/farmacología , Medicinas Tradicionales Africanas , Mitragyna , Extractos Vegetales/farmacología , Animales , Antimaláricos/administración & dosificación , Antimaláricos/toxicidad , Femenino , Intubación Gastrointestinal , Masculino , Malí , Extractos Vegetales/administración & dosificación , Extractos Vegetales/toxicidad , Hojas de la Planta , Ratas , Ratas WistarRESUMEN
OBJECTIVE: The study aimed to characterize the lipid and apolipoprotein profile and the prevalence of cardiovascular risk factors in a population of urban adult women of Morocco. DESIGN: A total of 213 women 25-55 y old were sampled from an agricultural province of Morocco: El Jadida. The following parameters of lipid and apolipoprotein profile were measured: plasma triglycerides (TG), plasma cholesterol (TC), triglyceride-rich lipoprotein triglycerides (TRL-TG), TRL-cholesterol (TRL-C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and apolipoproteins A1, B, B48, CIII and E. Waist circumference (WC), body mass index (BMI) and blood pressure (BP) were also determined. RESULTS: The women studied showed the following pattern: elevated TC, LDL-C levels and TC/HDL-C in 10, 19.4 and in 43.8%, respectively; low HDL-C levels in 45.3% (<0.9 mmol/l) or in 95% (when the cutoff <1.3 mmol/l is used), elevated TG levels in 11.8%. Elevated TRL-C (>0.6 mmol/l) and TRL-TG (>0.8 mmol/l) were observed in 13.4%. Obesity and hypertension were highly prevalent in 23.9 and 16.5%, respectively. Plasma triglyceride concentrations were closely correlated with plasma concentrations of TRL-TG (R = 0.86, P = 0.0001), apoB (R = 0.50, P = 0.0001) and apoCIII (R = 0.52, P = 0.0001) and moderately correlated with HDL-C levels (R = -0.3, P = 0.0001) and BMI (R = 0.4, P = 0.0001). The association between BMI and systolic blood pressure was statistically significant (R = 0.3, P = 0.0001). Obesity, BP, TRL-C, TRL-TG, TG, apoB and apoCIII increased with age. CONCLUSION: There is a high prevalence of some risk factors for cardiovascular disease including altered lipid and lipoprotein profiles in the Moroccan urban women studied, some of these risk factors are associated with age.
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Envejecimiento/sangre , Enfermedades Cardiovasculares/epidemiología , Colesterol/sangre , Triglicéridos/sangre , Adulto , Apolipoproteínas/sangre , Biomarcadores/sangre , Presión Sanguínea , Índice de Masa Corporal , Enfermedades Cardiovasculares/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Marruecos , Prevalencia , Factores de Riesgo , Población Urbana , Relación Cintura-CaderaRESUMEN
We investigated lithium-induced changes in norepinephrine (NE) catabolism. NE and its major metabolites 3-methoxy-4-hydroxyphenylglycol (MHPG) and 3,4-dihydroxyphenyl glycol (DHPG), ions such as lithium (Li(+)), magnesium (Mg(2+)), and potassium (K(+)) were measured in rat plasma and cerebral cortex using an HPLC method with electrochemical detection for amines. The results obtained with a group of rats treated by lithium chloride (2 mmol/kg/IP) were compared with a control group receiving sodium chloride (2 mmol/kg/IP). Animals were killed at different times over a period of six hours in the morning following salt administration to minimize possible chronobiological effects. There are two pathways leading to MHPG formation: way A, without DHPG, and way B, with DHPG. In plasma and cerebral cortex of lithium treated rats, way A catabolism seems to be preferential. Lithium increases Mg(2+) and K(+) plasma levels. These results suggest that lithium may increase inactivation of NE and decrease NE available for adrenergic receptors.
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Corteza Cerebral/metabolismo , Cloruro de Litio/farmacología , Metoxihidroxifenilglicol/análogos & derivados , Modelos Biológicos , Norepinefrina/metabolismo , Animales , Área Bajo la Curva , Cromatografía Líquida de Alta Presión , Electroquímica , Femenino , Litio/sangre , Litio/metabolismo , Magnesio/sangre , Magnesio/metabolismo , Metoxihidroxifenilglicol/sangre , Metoxihidroxifenilglicol/metabolismo , Potasio/sangre , Potasio/metabolismo , Ratas , Ratas Wistar , Cloruro de Sodio , EspectrofotometríaRESUMEN
OBJECTIVE: To report the rationale, recruitment, design, dietary intervention and baseline characteristics of participants in the Medi-RIVAGE study (Mediterranean Diet, Cardiovascular Risks and Gene Polymorphisms). DESIGN: A randomised, parallel trial comparing a new nutritional programme with a conventional programme. SETTING: Centre for Detection and Prevention of Arteriosclerosis, Timone University Hospital, Marseille, France, and collaborating teams. SUBJECTS: Two hundred and twelve male and female volunteers with at least one cardiovascular risk factor. INTERVENTION: A Mediterranean-type diet characterised mainly by the quality of fatty acids, amount of fish, vegetable foodstuffs and fibre was proposed and compared with a usually prescribed, low-fat/cholesterol diet. Body mass index, fasting lipids and lipoproteins, apolipoproteins, glucose, insulin and homocysteine were the main outcome measures. Gene polymorphisms of interest were determined. RESULTS: Characteristics of men in the two arms were comparable with regard to sociodemographic variables, and clinical and biological cardiovascular risk factors. There were few differences between the groups of women (cholesterol-related parameters, P<0.05). There was no difference between arms in allelic distribution of the gene polymorphisms studied. Saturated fat and protein intakes were high while carbohydrate and fibre intakes were low, but with no difference between arms. Overall, the nutritional markers were comparable in both arms with few exceptions. Correlations between nutritional intakes and plasma nutrient levels ranged from 0.19 (beta-carotene) to 0.47 (folate). CONCLUSIONS: The comparability of the two arms is notable and warrants a low risk of biases. Current diet departs from the traditional Mediterranean one. The assessment of nutritional intake is validated by correlations obtained between dietary intake and relevant biomarkers. This will be important to estimate participant compliance and to analyse intervention data.
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Arteriosclerosis/prevención & control , Dieta con Restricción de Grasas , Dieta Mediterránea , Adulto , American Heart Association , Arteriosclerosis/etiología , Biomarcadores/sangre , Índice de Masa Corporal , Colesterol/efectos adversos , Colesterol/sangre , Grasas de la Dieta/administración & dosificación , Grasas de la Dieta/efectos adversos , Femenino , Francia , Humanos , Metabolismo de los Lípidos , Lípidos/genética , Masculino , Persona de Mediana Edad , Evaluación Nutricional , Polimorfismo Genético , Prevención Primaria/métodos , Factores de RiesgoRESUMEN
The antifungal effect of the essential oil from Satureja montana L., Lavandula angustifolia Mill., Lavandula hybrida Reverchon, Syzygium aromaticum (L.) Merril and Perry, Origanum vulgare L., Rosmarinus officinalis L. and six chemotypes of Thymus vulgaris L. on Candida albicans growth were studied. The most efficiency was obtained with the essential oil from Thymus vulgaris thymol chemotype (MIC 80% = 0.016 microL/mL and Kaff = 296 microL/mL). The presence in the culture medium of essential oil from Thymus vulgaris thymol chemotype (0.01, 0.1, 0.2, 0.3 microg/mL) and amphotericin B involved a decrease of the MIC 80% of amphotericin B. In contrast, the combination of amphotericin B and low concentrations (0.00031-0.0025 microg/mL) of essential oil was antagonistic. The strongest decrease (48%) of the MIC 80% was obtained with medium containing 0.2 microL/mL of essential oil. These results signify that the essential oil of Thymus vulgaris thymol chemotype potentiates the antifungal action of amphotericin B suggesting a possible utilization of this essential oil in addition to antifungal drugs for the treatment of mycoses.
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Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , Fitoterapia , Aceites de Plantas/farmacología , Thymus (Planta) , Anfotericina B/administración & dosificación , Anfotericina B/farmacología , Anfotericina B/uso terapéutico , Antifúngicos/administración & dosificación , Antifúngicos/uso terapéutico , Combinación de Medicamentos , Sinergismo Farmacológico , Humanos , Pruebas de Sensibilidad Microbiana , Aceites de Plantas/administración & dosificación , Aceites de Plantas/uso terapéuticoRESUMEN
Daphnetoxin, a mezerein derivative, was isolated from the stem bark of Daphne gnidium. Mezerein is a PKC activator that exhibits antileukemic properties. However, daphnetoxin and its analogue 12-hydroxydaphnetoxin were described as being devoid of this effect. In the present study daphnetoxin and mezerein were compared as PKC activators on classical (alpha and beta I), novel (delta) and atypical (zeta) isoforms, using an alternative in vivo yeast phenotypic assay. The aim was to clarify if daphnetoxin is a PKC activator and if the differences between the antiproliferative effect of mezerein and of its analogue daphnetoxin may be ascribed to differences on their potency or selectivity as PKC activators. Yeast samples expressing each of the mammalian PKC isoforms tested were incubated with daphnetoxin or mezerein. Growth inhibition caused by these drugs was assumed to be due to PKC activation since it did not occur when expression was not induced. Mezerein inhibited the growth of yeast expressing PKC alpha (IC(50) = 1190 +/- 237 nM; n = 20), PKC beta I (IC(50) = 908 +/- 46 nM; n = 20), and PKC delta (IC(50) = 141 +/- 25 nM; n = 20) but not of yeast expressing PKC zeta. Daphnetoxin also inhibited the growth of yeast expressing isoforms alpha, beta I and delta, being more potent than mezerein on PKC alpha (IC(50) = 536 +/- 183 nM; n = 20; P < 0.05), as potent as mezerein on PKC beta I (IC(50) = 902 +/- 129 nM; n = 20) and less potent than mezerein upon PKC delta (IC(50) = 3370 +/- 492 nM; n = 20; P < 0.05). These results show that daphnetoxin is a potent PKC activator but with a selectivity different from that of mezerein. It is suggested that the lack of antileukemic and antiproliferative effects of daphnetoxin may be due to its lower potency to activate PKC delta.
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Antineoplásicos Fitogénicos/farmacología , Diterpenos , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Proteína Quinasa C/metabolismo , Terpenos/farmacología , Thymelaeaceae , Antineoplásicos Fitogénicos/química , Relación Dosis-Respuesta a Droga , Regulación de la Expresión Génica/efectos de los fármacos , Compuestos Heterocíclicos de 4 o más Anillos/química , Isoenzimas/genética , Isoenzimas/metabolismo , Corteza de la Planta/química , Extractos Vegetales/farmacología , Proteína Quinasa C/genética , Proteína Quinasa C beta , Proteína Quinasa C-alfa , Proteína Quinasa C-delta , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crecimiento & desarrollo , Terpenos/químicaRESUMEN
OBJECTIVE: To determine if fructosamine can be used as a surrogate for HbA(1c) to monitor whether therapeutic goals in diabetes mellitus are achieved when HbA(1c) cannot be used for this purpose (hemoglobinopathies, anemia...). MATERIAL AND METHODS: Blood samples of 76 diabetic patients and 30 healthy subjects characterized by the absence of any risk of interference in the interpretations of HbA(1c) and fructosamine were studied in order to, first, deduce from the correlation a prediction of HbA(1c) from the fructosamine values, second, to evaluate the predictive value of such predicted HbA(1c) in the determination of poor metabolic control as defined by UKPDS and DCCT studies. RESULTS: The correlation between predicted HbA(1c) and actual fructosamine was fair (r=0.88) in diabetic patients but not in control subjects (r=0.01). It was therefore only possible to estimate HbA(1c) from fructosamine in diabetic patients. Nevertheless, the range of positive and negative predictive values of estimated HbA(1c) to detect a poor metabolic control defined by two thresholds of HbA(1c) (7%, 7.5%) was 91-93% and 86-87%, respectively. Then, even in this highly selected population, the risk of misclassification was around 10% when fructosamine was used to estimate HbA(1c). These results were unchanged when fructosamine was corrected by plasma protein level. CONCLUSIONS: This study shows the limitations to use fructosamine in place of HbA(1c) to evaluate the efficacy of antidiabetic treatments, even in a selected population.
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Biomarcadores/sangre , Glucemia/análisis , Diabetes Mellitus/sangre , Fructosamina/sangre , Hemoglobina Glucada/análisis , Adulto , Anciano , Índice de Masa Corporal , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Ayuno , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
This study evaluated serum cystatin C as a potential new marker of glomerular filtration rate (GFR) in 49 patients who had steady-state diabetes with early renal impairment. We determined the correlation between GFR measured by chromium 51-labeled EDTA and levels of serum cystatin C, serum creatinine, serum beta(2)-microglobulin, endogenous creatinine clearance, and Cockcroft formula. Sensitivity and specificity for the diagnosis of renal failure, defined as a GFR less than either 80 or 60 mL/min/1.73 m(2), were calculated by receiver operating characteristic (ROC) curves for creatinine, cystatin C, and beta(2)-microglobulin. Finally, we compared mean values of these three serum parameters in patients grouped according to GFR using the two definitions of renal failure. Correlation coefficients with GFR were -0.77 for serum creatinine level, -0.65 for serum cystatin C level, -0.71 for serum beta(2)-microglobulin level, +0.56 for endogenous creatinine clearance, and +0.69 for Cockcroft formula (all P < 0.001). With a cutoff value of 60 mL/min/1.73 m(2), areas under the ROC curve were 0.972 for beta(2)-microglobulin, 0.925 for cystatin C, and 0.916 for creatinine levels. With a cutoff value of 80 mL/min/1.73 m(2), these were 0.838 for beta(2)-microglobulin, 0.780 for cystatin C, and 0.905 for creatinine levels (P = not significant between parameters). These results were not altered after the exclusion of patients (n = 8) with a serum creatinine level greater than 1.41 mg/dL. When patients were classified into three groups according to GFR (group 1, >80 mL/min/1.73 m(2); group 2, 60 to 80 mL/min/1.73 m(2); group 3, <60 mL/min/1.73 m(2)), mean values of serum parameters in the three groups were statistically different (P < 0.0001) except between groups 1 and 2 for cystatin C and beta(2)-microglobulin. With patients classified into two groups (GFR > or < 80 mL/min/1.73 m(2)), mean values for each parameter were statistically different (P < 0.001). Sensitivity, specificity, and positive and negative predictive values for serum creatinine and serum cystatin C levels were very close for both definitions of renal failure. Serum cystatin C is not better than serum creatinine or serum beta(2)-microglobulin levels for estimating GFR in patients with steady-state diabetes using ROC curves or other validation tests.
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Creatinina/sangre , Cistatinas/sangre , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/diagnóstico , Adulto , Anciano , Biomarcadores/sangre , Cistatina C , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/etiología , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Sensibilidad y Especificidad , Microglobulina beta-2/sangreRESUMEN
BACKGROUND: The process of intestinal absorption and chylomicron resecretion of dietary cholesterol in humans is poorly understood. OBJECTIVE: The present study aimed to test the hypothesis that dietary cholesterol ingested during a given meal is resecreted into chylomicrons (and plasma) during several subsequent postprandial periods. DESIGN: Seven healthy subjects ingested 3 comparable mixed test meals (at 0, 8, and 24 h) containing a given amount of fat (49 g) and cholesterol (157 mg); blood samples were taken 3 and 6 h after each test meal and 48 and 72 h after the beginning of the experiment. Heptadeuterated dietary cholesterol was present in the first test meal only, enabling its specific determination with use of gas chromatography-mass spectrometry. Chylomicrons, LDL, and HDL were isolated and lipids were quantified. RESULTS: In apolipoprotein B-48-containing chylomicrons, deuterated cholesterol concentrations were moderate after the first meal (1.3 x 10(-4) mmol/L), reached a maximum after the second meal (2.4 x 10(-4) mmol/L), and were still elevated after the third meal (1.7 x 10(-4) mmol/L). In plasma, LDL and HDL cholesterol enrichment in deuterated cholesterol was lower than in chylomicrons and plateaued after 24--48 h. Estimates of newly secreted exogenous deuterated cholesterol in chylomicrons indicate that 30.7%, 55.2%, and 14.1% of the total was secreted after the first, second, and third meals, respectively. CONCLUSION: Ingested dietary cholesterol is secreted by the small intestine in chylomicrons into the circulation during > or =3 subsequent postprandial periods in healthy humans. This likely results from a complex multistep intestinal processing of cholesterol with dietary fat as a driving force.
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Colesterol en la Dieta/farmacocinética , Quilomicrones/metabolismo , Periodo Posprandial/fisiología , Adulto , Apolipoproteína B-48 , Apolipoproteínas B/sangre , Colesterol/sangre , Quilomicrones/sangre , Deuterio , Cromatografía de Gases y Espectrometría de Masas , Humanos , Absorción Intestinal , Intestino Delgado/fisiología , Lipoproteínas HDL/sangre , Lipoproteínas LDL/sangre , Masculino , Valores de Referencia , Triglicéridos/sangreRESUMEN
Ursodeoxycholic acid is a protective agent against liver toxicity caused by some drugs. In the present pilot study, we assessed the effect of this bile acid on tacrine-induced hepatotoxicity. Fourteen patients with a diagnosis of Alzheimer's disease received tacrine and ursodeoxycholic acid (13 mg/kg/day) for 105 days. Serum ALAT was the main evaluation criterion. Serum levels of ALAT were compared with those of 100 patients who had been treated with tacrine in the same centre. In patients receiving ursodeoxycholic acid, ALAT serum levels were normal in 93 per cent of cases vs. 69 per cent in control patients and moderate hepatotoxicity (ULN < ALAT < 3 ULN) did not occur while it was present in 25 per cent of controls (p = 0.036). In contrast, the percentage of patients with ALAT > 3 ULN was similar in the two groups (7 per cent vs. 6 per cent). These present findings suggest that UDC could prevent moderate tacrine-induced hepatotoxicity. These results should be confirmed in a controlled therapeutical trial.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Nootrópicos/efectos adversos , Tacrina/efectos adversos , Ácido Ursodesoxicólico/uso terapéutico , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/tratamiento farmacológico , Femenino , Humanos , Pruebas de Función Hepática , Masculino , Nootrópicos/uso terapéutico , Tacrina/uso terapéuticoRESUMEN
The role of postprandial insulin in the regulation of postprandial lipid metabolism is still poorly understood. The roles of hyperinsulinemia and insulin resistance in the alteration of postprandial lipid metabolism are not clear either. To improve knowledge in this area, we submitted healthy men to acute hyperinsulinemia in two different ways. In the first study, we compared in 10 men the effects of four isolipidic test meals that induce different degrees of hyperinsulinemia on postprandial lipid metabolism. Three different carbohydrate sources were compared according to their glycemic indexes (GIs; 35, 75, and 100 for white kidney bean, spaghetti, and white bread test meals, respectively); the fourth test meal did not contain any carbohydrates. Postprandial plasma insulin levels were proportional to the GIs (maximal plasma insulin concentrations: 113 +/- 16 to 266 +/- 36 pmol/l). We found a strong positive correlation during the 6-h postprandial period between apolipoprotein (apo) B-48 plasma concentration and insulin plasma concentration (r2 = 0.70; P = 0.0001). In a second study, 5 of the 10 subjects again ingested the carbohydrate-free meal, but during a 3-h hyperinsulinemic- (550 +/- 145 pmol/l plasma insulin) euglycemic (5.5 +/- 0.8 mmol/l plasma glucose) clamp. A biphasic response was observed with markedly reduced levels of plasma apoB-48 during insulin infusion, followed by a late accumulation of plasma apoB-48 and triglycerides. Overall, the data obtained showed that portal and peripheral hyperinsulinism delays and exacerbates postprandial accumulation of intestinally derived chylomicrons in plasma and thus is involved in the regulation of apoB-48-triglyceride-rich lipoprotein metabolism, in the absence of insulin-resistance syndrome.
Asunto(s)
Apolipoproteínas B/sangre , Hiperinsulinismo/sangre , Lipoproteínas/sangre , Triglicéridos/sangre , Enfermedad Aguda , Adulto , Apolipoproteína B-48 , Glucemia/análisis , Alimentos , Humanos , Insulina/sangre , Lípidos/sangre , Masculino , Periodo Posprandial/fisiología , Valores de ReferenciaRESUMEN
The aim of this work was to study the cholesterol-lowering mechanisms induced by dietary soybean lecithin in hypercholesterolemic rabbits. Male New Zealand white rabbits (n = 6 in each group) were fed for 10 weeks either a low-fat control C diet, containing 27 g fat/kg, or high-fat diets enriched with 2 g cholesterol/kg and 77 g fat/kg. The high-fat diets contained 50 g lard (L), 50 g soybean triacylglycerol (SO), or 50 g pure soybean phosphatidylcholine (PLE). PLE diet decreased by 30% beta-VLDL-cholesterol, compared with SO diet. HDL2-, HDL3- and LDL-lipid contents were unchanged in the L, SO and PLE groups. In gallbladder bile, amounts of phospholipids, bile salts and cholesterol were significantly increased in PLE group by respectively 45%, 11% and 44%, in comparison with SO group. Intestinal and hepatic Hydroxy Methyl Glutaryl Coenzyme A reductase activities were not increased by PLE diet. Triacylglycerol hepatic content was lower in PLE group than in L or SO groups. Compared with triacylglycerol enriched diet, phosphatidylcholine enriched diet developed significant higher cholesterol- and triacylglycerol-lowering effects by a two-step mechanism: i) by reducing the beta-VLDLs, ii) by enhancing the secretion of bile cholesterol. Such results constitute promising effects of soybean phosphatidylcholine at the hepato-biliary level, in the treatment or prevention of hyperlipidemia and related atherosclerosis.
Asunto(s)
Colesterol/sangre , Dieta , Vesícula Biliar/metabolismo , Hipercolesterolemia/dietoterapia , Hígado/metabolismo , Fosfatidilcolinas/administración & dosificación , Animales , Ácidos y Sales Biliares/metabolismo , Colesterol en la Dieta/administración & dosificación , Vesícula Biliar/patología , Hidroximetilglutaril-CoA Reductasas/metabolismo , Hipercolesterolemia/sangre , Hipercolesterolemia/patología , Hígado/patología , Masculino , Microsomas Hepáticos/enzimología , Fosfolípidos/metabolismo , ConejosRESUMEN
The beneficial metabolic effects of dietary soybean lecithin on lipid metabolism are now more clearly established. The intestinal absorption of cholesterol is decreased by soybean phosphatidylcholine-enriched diet and results in a cholesterol-lowering effect. There is an enhancement of the cholesterol efflux by endothelial cells incubated with soybean phosphatidylcholines, and a stimulation of the reverse cholesterol transport by high density lipoprotein-phosphatidylcholines. As a result of all these processes, phosphatidylcholines provided by the soybean lecithin metabolism appear to be key molecules controlling the biodynamic exchanges of lipids. They regulate homeostasis of cholesterol and fatty acids by decreasing their synthesis and promoting cholesterol oxidation into bile salts. Finally, the outcome is the increase in bile secretion of these lipids and/or their metabolite forms. Such findings constitute promising goals in the field of nutritional effects of soybean lecithin in the treatment or prevention of hyperlipidemia and related atherosclerosis.