RESUMEN
OBJECTIVES: To assess the effect of the major efavirenz metabolizing enzyme (CYP2B6) genotype and the effects of rifampicin co-treatment on induction of CYP3A by efavirenz. PATIENTS AND METHODS: Two study arms (arm 1, n = 41 and arm 2, n = 21) were recruited into this study. In arm 1, cholesterol and 4ß-hydroxycholesterol were measured in HIV treatment-naive patients at baseline and then at 4 and 16 weeks after initiation of efavirenz-based antiretroviral therapy. In arm 2, cholesterol and 4ß-hydroxycholesterol were measured among patients taking efavirenz during rifampicin-based tuberculosis (TB) treatment (efavirenz/rifampicin) just before completion of TB treatment and then serially following completion of TB treatment (efavirenz alone). Non-linear mixed-effect modelling was performed. RESULTS: A one-compartment, enzyme turnover model described 4ß-hydroxycholesterol kinetics adequately. Efavirenz treatment in arm 1 resulted in 1.74 (relative standard error = 15%), 3.3 (relative standard error = 33.1%) and 4.0 (relative standard error = 37.1%) average fold induction of CYP3A for extensive (CYP2B6*1/*1), intermediate (CYP2B6*1/*6) and slow (CYP2B6*6/*6) efavirenz metabolizers, respectively. The rate constant of 4ß-hydroxycholesterol formation [mean (95% CI)] just before completion of TB treatment [efavirenz/rifampicin co-treatment, 7.40 × 10(-7) h(-1) (5.5 × 10(-7)-1.0 × 10(-6))] was significantly higher than that calculated 8 weeks after completion [efavirenz alone, 4.50 × 10(-7) h(-1) (4.40 × 10(-7)-4.52 × 10(-7))]. The CYP3A induction dropped to 62% of its maximum by week 8 of completion. CONCLUSIONS: Our results indicate that efavirenz induction of CYP3A is influenced by CYP2B6 genetic polymorphisms and that efavirenz/rifampicin co-treatment results in higher induction than efavirenz alone.
Asunto(s)
Fármacos Anti-VIH/farmacocinética , Antituberculosos/farmacocinética , Benzoxazinas/farmacocinética , Citocromo P-450 CYP2B6/genética , Citocromo P-450 CYP3A/metabolismo , Hidroxicolesteroles/análisis , Rifampin/farmacocinética , Adulto , Alquinos , Fármacos Anti-VIH/uso terapéutico , Antituberculosos/uso terapéutico , Benzoxazinas/uso terapéutico , Ciclopropanos , Femenino , Genotipo , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Rifampin/uso terapéutico , Tuberculosis/tratamiento farmacológicoRESUMEN
We investigated the effects of pharmacogenetic variations and efavirenz pharmacokinetics on inter-individual differences in the extent of CYP3A induction by efavirenz using 4ß-hydroxycholesterol/cholesterol (4ß-OHC/Chol) as a marker for CYP3A induction. Plasma 4ß-hydroxycholesterol and cholesterol concentrations were determined at baseline, and at the 4th, 16th and 48th week of efavirenz-based highly active antiretroviral therapy in antiretroviral therapy-naive HIV patients (n=77). Efavirenz plasma concentrations were quantified at weeks 4 and 16. CYP2B6, CYP3A5, ABCB1, UGT2B7 genotyping were done. Compared with baseline, the median plasma 4ß-OHC/Chol ratio increased at the 4th (257%), 16th (291%) and 48th (165%) week (P<0.0001). CYP2B6*6 genotype significantly influenced 4ß-OHC/Chol ratio at weeks 16 (P=0.02) and 48 (P=0.04) being highest in CYP2B6*6/*6>*1/*6>*1/*1. There were positive correlations between plasma efavirenz and 4ß-OHC/Chol ratios (week 4: P=0.02, week 16: P=0.001). CYP3A enzyme induction by efavirenz is pronounced in CYP2B6 slow metabolizers who have high efavirenz plasma exposure.
Asunto(s)
Benzoxazinas/uso terapéutico , Citocromo P-450 CYP3A/biosíntesis , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Alquinos , Ciclopropanos , Citocromo P-450 CYP3A/genética , Inducción Enzimática , Femenino , Infecciones por VIH/enzimología , Humanos , Masculino , Estudios ProspectivosRESUMEN
OBJECTIVE: Urinary caffeine metabolic ratios used to quantify the activity of numerous drug-metabolizing enzymes are an established component of cocktail approaches for metabolic phenotyping. Because in vitro evidence suggests that 1-methylxanthine (1-MX), a major caffeine metabolite, is actively secreted into urine by organic anion transporters (hOATs), coadministration of renal hOAT inhibitors like probenecid may impair these procedures. METHODS: In a randomized, placebo-controlled, double-blind crossover design, single oral doses of 300 mg caffeine with oral coadministration of placebo or 500 mg probenecid 3 times daily for 2 days were administered to 7 healthy men. The plasma and urine concentrations of caffeine and its major metabolites 1,7-dimethylxanthine (1,7-DMX) and 1-MX were determined by high-performance liquid chromatography. RESULTS: Coadministration of probenecid resulted in a 34% reduction of the renal clearance of 1-MX (mean +/- SD 190 +/- 42 versus 290 +/- 83 ml min(-1), 95% CI on difference 0.2, 200, p = 0.04) with a 41% reduction in its estimated non-glomerular clearance. The renal clearances of caffeine and 1,7-DMX and the area under the plasma concentration-time curves of all substances were not significantly changed. CONCLUSIONS: 1-MX undergoes renal tubular secretion which is substantially reduced by probenecid, possibly due to inhibition of renal hOATs. This inhibition may explain the influence of probenecid on urinary caffeine metabolic ratios and, thus, its impact on the assessment of enzyme activities. It also suggests that 1-MX might serve as a model substrate for the renal tubular transport of organic anions.
Asunto(s)
Cafeína/farmacocinética , Estimulantes del Sistema Nervioso Central/farmacocinética , Riñón/metabolismo , Probenecid/farmacología , Fármacos Renales/farmacología , Xantinas/metabolismo , Adulto , Área Bajo la Curva , Arilamina N-Acetiltransferasa/metabolismo , Cromatografía Líquida de Alta Presión , Creatinina/sangre , Creatinina/orina , Estudios Cruzados , Citocromo P-450 CYP1A2/metabolismo , Depresión Química , Método Doble Ciego , Femenino , Humanos , Masculino , Espectrofotometría Ultravioleta , Xantina Oxidasa/metabolismoRESUMEN
Foods containing soluble dietary fibers delay glucose absorption and lower postprandial plasma glucose. This effect of oat bran has been attributed to oat gum (80% beta-glucan). However, purified oat gum has previously not been available for human studies. In this study the glucose and insulin responses to consuming 14.5 g of specifically prepared oat gum with 50 g glucose were compared with the response to guar gum with glucose and to glucose alone in nine healthy, fasting subjects. Plasma glucose and insulin increases after the glucose drink were greater than after both gum meals between 20 and 60 min (P less than 0.01). The responses to the two gum meals were nearly identical. These results establish that the more palatable oat gum lowers postprandial plasma glucose and insulin concentrations in humans and may be comparable with or of greater benefit than guar gum.
Asunto(s)
Glucemia/metabolismo , Fibras de la Dieta/metabolismo , Grano Comestible , Glucosa/administración & dosificación , Insulina/sangre , Adulto , Femenino , Galactanos/metabolismo , Humanos , Masculino , Mananos/metabolismo , Gomas de PlantasRESUMEN
Ten patients with symptomatic coronary artery disease received oral azithromycin for 3 days and underwent directional atherectomy on the third day. Azithromycin was found in all plaque samples with a median concentration of 284 ng/ml (95% confidence interval 163 to 517 ng/ml).
Asunto(s)
Antibacterianos/farmacocinética , Azitromicina/farmacocinética , Enfermedad Coronaria/metabolismo , Antibacterianos/uso terapéutico , Aterectomía Coronaria , Azitromicina/uso terapéutico , Estudios de Casos y Controles , Chlamydophila pneumoniae/aislamiento & purificación , Enfermedad Coronaria/microbiología , Enfermedad Coronaria/terapia , Humanos , Estudios ProspectivosRESUMEN
The influence of gastrointestinal (GI) transit times on the pharmacokinetics (PK) of three calcium channel blockers (CCBs), recommended for once-daily dosing, was investigated. In a three-way crossover design, the single-dose PK of a controlled-delivery formulation of 240 mg diltiazem (DIL), an extended-release formulation of 10 mg felodipine (FEL), and 5 mg amlodipine (AML) were compared in two groups of healthy subjects, with either slow (> 35 h) or rapid (< 15 h) GI transit, as assessed by the metal detector method (EAS II). GI transit significantly affected the PK of DIL. Mean PK parameters in the rapid versus slow transit group were the following: trough levels (C24 h): 22.8 +/- 8.3 versus 49.5 +/- 35.7 ng/ml, p < 0.05; AUC 1134.4 +/- 512.7 versus 1704.7 +/- 1185.6 hng/ml, p < 0.05 (one-sided). Neither AUC nor trough levels of FEL and AML were significantly influenced by transit times, nor was Cmax after any of the three treatments. Variations in PK parameters, as indicated by coefficients of variation, were about twofold higher for both DIL and FEL, compared to AML. Variations in mean residence times were significantly lower for AML compared to DIL and FEL (7% vs. 30% and 17%, p < 0.001 and p < 0.002, respectively). Peak-to-trough ratios (Cmax/C24 h mean) were 1.8 +/- 0.9 for DIL, 7.6 +/- 3.5 for FEL, and 1.7 +/- 0.2 for AML. In conclusion, the predictability of pharmacokinetic behavior both in conditions of rapid or slow GI transit is optimized in drugs with intrinsically slow elimination such as amlodipine. The pharmacokinetics of the CCBs with formulation-based once-a-day characteristics are sensitive to GI transit if these processes are rapid enough to interfere with the formulation-specific release profile.
Asunto(s)
Amlodipino/farmacocinética , Bloqueadores de los Canales de Calcio/farmacocinética , Tránsito Gastrointestinal/fisiología , Adulto , Amlodipino/efectos adversos , Área Bajo la Curva , Disponibilidad Biológica , Bloqueadores de los Canales de Calcio/efectos adversos , Estudios Cruzados , Preparaciones de Acción Retardada , Diltiazem/efectos adversos , Diltiazem/farmacocinética , Felodipino/administración & dosificación , Felodipino/farmacocinética , Femenino , Enfermedades Gastrointestinales/inducido químicamente , Cefalea/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
AIDS patients may have achlorhydria, a condition that could result in drug malabsorption, especially of antifungals. The effect of a reduction in the production of gastric acid on the pharmacokinetics of the antimycotic fluconazole after a single 100 mg dose was investigated in a randomized two-way crossover study with 12 healthy volunteers. Gastric acid production was reduced by pretreatment with 20 mg omeprazole/day over a period of 7 days; pH and gastric emptying times were measured by a radiotelemetering pH capsule. Omeprazole pretreatment significantly raised the median gastric pH (from pH 1.1 to pH 4.7, p < 0.0001), but had no significant influence on gastric emptying time of the pH capsule (median = 4.3 vs 4.9 hours). The pharmacokinetics of fluconazole were unchanged; plasma parameters were Cmax = 2.04 micrograms/ml, tmax = 4.08 h and AUC = 98.91 h micrograms/ml after the omeprazole treatment, compared to 2.06 microliters/ml, 3.92 hours and 97.29 h micrograms/ml, respectively. The median bioavailability ratio of fluconazole before and after omeprazole treatment was 1.00. It is inferred that there is no interference of omeprazole with the plasma pharmacokinetics of fluconazole. The findings suggest that changes in gastric pH, as in patients with AIDS or those being treated with anti-ulcer drugs, should not influence the pharmacokinetics of fluconazole.
Asunto(s)
Fluconazol/farmacocinética , Omeprazol/farmacología , Estómago/química , Administración Oral , Adulto , Análisis de Varianza , Disponibilidad Biológica , Cromatografía Líquida de Alta Presión , Estudios Cruzados , Interacciones Farmacológicas , Femenino , Fluconazol/administración & dosificación , Fluconazol/sangre , Ácido Gástrico/metabolismo , Vaciamiento Gástrico/efectos de los fármacos , Gastrinas/sangre , Humanos , Concentración de Iones de Hidrógeno , Masculino , Persona de Mediana Edad , Omeprazol/administración & dosificaciónRESUMEN
We established a new limited sampling strategy to assess CYP3A activity and evaluated the time course of reversible (voriconazole) and irreversible (ritonavir) CYP3A inhibition. In this randomized trial, two groups, each with eight healthy participants, received CYP3A inhibitors voriconazole or ritonavir orally for 9 days, with 3 mg midazolam (MDZ) administered before the inhibitor treatment, on days 1, 2, 3, 5, 8, and 9 during inhibitor treatment, and on days 10, 11, and 12 (3 days) after discontinuation. Plasma MDZ area under the curve (AUC) between 2 and 4 h after oral administration in the form of a solution strongly correlated with MDZ clearance. Using this parameter, maximum inhibition of voriconazole and ritonavir was calculated to have occurred only 48 h after starting of the inhibitor (percentage of baseline MDZ clearance, voriconazole: 10.6%; ritonavir: 8.4%). Recovery of CYP3A activity occurred with a half-life of 24 h after voriconazole, whereas ritonavir inhibition was still strong 3 days after discontinuation. These findings underscore the substantial and gradual alterations in dose requirements in the first days of and after such combination therapies.
Asunto(s)
Inhibidores del Citocromo P-450 CYP3A , Inhibidores Enzimáticos/farmacología , Pirimidinas/farmacología , Ritonavir/farmacología , Triazoles/farmacología , Administración Oral , Adolescente , Adulto , Área Bajo la Curva , Citocromo P-450 CYP3A/metabolismo , Interacciones Farmacológicas , Femenino , Semivida , Humanos , Masculino , Midazolam/administración & dosificación , Midazolam/farmacocinética , Persona de Mediana Edad , Factores de Tiempo , Voriconazol , Adulto JovenRESUMEN
We performed a prospective comparative study to examine, from a pharmacogenetics perspective, the effect of rifampicin (RIF) on long-term efavirenz (EFV) autoinduction and kinetics. In a study population of patients with HIV receiving EFV with RIF (arm 2, n = 54) or without RIF (arm 1, n = 128 controls), intraindividual and interindividual plasma EFV and 8-hydroxyefavirenz levels were compared at weeks 4 and 16 of EFV therapy. In arm 2, RIF was initiated 4 weeks before starting EFV. In controls (arm 1), the plasma EFV was significantly lower whereas 8-hydroxyefavirenz was higher at week 16 as compared to week 4. By contrast, there were no significant differences in plasma EFV and 8-hydroxyefavirenz concentrations over time in arm 2. At week 4, the plasma EFV concentration was significantly lower in arm 2 as compared to arm 1, but no significant differences were observed by week 16. When stratified by CYP2B6 genotype, significant differences were observed only with respect to CYP2B6*1/*1 genotypes. Ours is the first report of the CYP2B6 genotype-dependent effect of RIF on long-term EFV autoinduction.
Asunto(s)
Antibióticos Antituberculosos/uso terapéutico , Hidrocarburo de Aril Hidroxilasas/genética , Benzoxazinas/sangre , Oxidorreductasas N-Desmetilantes/genética , Inhibidores de la Transcriptasa Inversa/sangre , Rifampin/uso terapéutico , Subfamilia B de Transportador de Casetes de Unión a ATP , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Alquinos , Alelos , Fármacos Anti-VIH/sangre , Fármacos Anti-VIH/metabolismo , Fármacos Anti-VIH/uso terapéutico , Antibióticos Antituberculosos/sangre , Terapia Antirretroviral Altamente Activa , Benzoxazinas/metabolismo , Benzoxazinas/uso terapéutico , Ciclopropanos , Citocromo P-450 CYP2B6 , Citocromo P-450 CYP3A/genética , Interacciones Farmacológicas , Inducción Enzimática , Femenino , Genotipo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , VIH-1/efectos de los fármacos , VIH-1/genética , Humanos , Masculino , Polimorfismo de Nucleótido Simple , Inhibidores de la Transcriptasa Inversa/metabolismo , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Rifampin/sangre , Tuberculosis/tratamiento farmacológico , Tuberculosis/genéticaRESUMEN
We investigated the influence of gender and pharmacogenetic variations on long-term efavirenz autoinduction and disposition among patients with HIV in Tanzania (N = 129). Plasma concentrations (at 16 h) of efavirenz and 8-hydroxyefavirenz were quantified at weeks 4 and 16 of therapy. Genotyping was performed to identify cytochrome P450 (CYP) 2B6*6, CYP3A5*3, *6, and *7, and ABCB1-3435 C/T genotypes. There were reductions in the median efavirenz concentration (Wilcoxon matched-pair test P < 0.001) and efavirenz/8-hydroxyefavirenz ratio (P < 0.001) by 19 and 32%, respectively, at week 16 as compared with week 4. The proportion of patients with efavirenz concentration <1 µg/ml at week 16 was higher by 67, 25, and 5% in CYP2B6*1/*1, *1/*6, and *6/*6 genotypes, respectively. The defined therapeutic range based on observed plasma concentrations is affected by the time point of sampling and the CYP2B6 genotype. The effect of efavirenz autoinduction on reducing plasma exposure continues up to week 16 and predominantly affects CYP2B6 extensive metabolizers. Among CYP2B6 slow metabolizers, the presence of a CYP3A5 genotype allele is associated with greater effects of efavirenz autoinduction on plasma concentrations of the drug. The cumulative induction may influence the long-term antiretroviral therapy outcome, particularly in CYP2B6*1 carriers.
Asunto(s)
Benzoxazinas/farmacocinética , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Transcriptasa Inversa/farmacocinética , Subfamilia B de Transportador de Casetes de Unión a ATP , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Adulto , Alquinos , Terapia Antirretroviral Altamente Activa , Hidrocarburo de Aril Hidroxilasas/genética , Hidrocarburo de Aril Hidroxilasas/metabolismo , Benzoxazinas/administración & dosificación , Benzoxazinas/sangre , Biotransformación , Ciclopropanos , Citocromo P-450 CYP2B6 , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Esquema de Medicación , Femenino , Genotipo , Infecciones por VIH/sangre , Humanos , Hidroxilación , Masculino , Persona de Mediana Edad , Oxidorreductasas N-Desmetilantes/genética , Oxidorreductasas N-Desmetilantes/metabolismo , Fenotipo , Estudios Prospectivos , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Inhibidores de la Transcriptasa Inversa/sangre , Factores Sexuales , TanzaníaRESUMEN
A sensitive enantioselective gas chromatographic assay has been developed for amlodipine, 2-[(2-aminoethoxy)-methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5- methoxycarbonyl-6-methyl-1,4-dihydropyridine, a calcium channel blocking therapeutic agent. The assay involves conversion of the (+)-(R)- and (-)-(S)-enantiomers of amlodipine into their acyl derivatives with the chiral reagent (+)-(S)-alpha-methoxy-alpha-trifluoromethylphenylacetyl chloride (Mosher's reagent). Peak separation after chromatography of the diastereomers was larger than 85%, and the lower limit of detection in blood plasma was 0.02 ng/ml for each enantiomer. The method has been used for the measurement of amlodipine enantiomers in human, rat and dog plasma, and in various organs of the rat.
Asunto(s)
Amlodipino/análisis , Cromatografía de Gases/métodos , Adulto , Amlodipino/sangre , Amlodipino/química , Animales , Química Encefálica , Cromatografía de Gases/estadística & datos numéricos , Perros , Humanos , Pulmón/química , Masculino , Músculos/química , Miocardio/química , Ratas , Sensibilidad y Especificidad , EstereoisomerismoRESUMEN
Two sensitive methods for the determination of the azalide antibiotic azithromycin in human serum were compared. High-performance liquid chromatography (HPLC) and a microbiological assay were simultaneously applied to 768 serum samples obtained in a clinical study. There was excellent agreement between the azithromycin concentrations measured by HPLC and by the bioassay. The correlation coefficient for the two methods was r2 = 0.96. The precision and the sensitivity of the methods were found to be very similar.
Asunto(s)
Eritromicina/análogos & derivados , Azitromicina , Bioensayo , Cromatografía Líquida de Alta Presión , Eritromicina/sangre , Eritromicina/farmacocinética , HumanosRESUMEN
Various doses of cadmium chloride were injected to chick embryos between the seventh and 14th day of incubation. Doses over 15 micrograms/egg produced high mortality and, when injected between the tenth and 11th day, widespread curling of the feathers in the surviving embryos. A different type of malformation, consisting of hemorrhagic atrophy of the distal part of the feathers, was observed in the embryos injected with similar doses during the 12th day. No feather malformations were observed in embryos injected before the ninth or after the 12th day of incubation. The simultaneous injection of an equimolar amount of zinc sulfate prevented the feather malformations.
Asunto(s)
Cadmio/toxicidad , Plumas/anomalías , Zinc/uso terapéutico , Anomalías Inducidas por Medicamentos/prevención & control , Animales , Cadmio/antagonistas & inhibidores , Embrión de Pollo , Plumas/efectos de los fármacosRESUMEN
The enantiomers of glyceryl-1-nitrate, a metabolite of glyceryl trinitrate, were pharmacologically characterized in vitro and in animals. In the Langendorff heart (l) G-1-N was double as potent as (d) G-1-N with respect to the enhancement of coronary flow. The two enantiomers showed almost the same dose-response curves in rabbit aortic strips contracted with phenylephrine. In the same model there were no enantiospecific differences in the development of cross-tolerance to glyceryl-trinitrate. In anaesthetized rabbits, intravenous (l) G-1-N reduced the blood pressure slightly more than (d) G-1-N, while in the conscious dog the blood pressure lowering effect of (d) G-1-N was greater and had a much longer duration (4-6 versus 2 h) than that of (l)G-1-N. The differences in dogs are probably explained by enantiospecific pharmacokinetics: (d) G-1-N had higher plasma levels and showed a longer half-life of elimination than (l) G-1-N (more than 5 h versus 2.7 h). Both enantiomers enhanced the rate of survival after acute coronary ligature in rats with a tendency to higher long-term survival rates after the (d) form.
Asunto(s)
Nitroglicerina/análogos & derivados , Administración Oral , Animales , Presión Sanguínea/efectos de los fármacos , Chinchilla , Circulación Coronaria/efectos de los fármacos , Perros , Tolerancia a Medicamentos , Femenino , Cobayas , Semivida , Corazón/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Técnicas In Vitro , Masculino , Contracción Miocárdica/efectos de los fármacos , Nitroglicerina/farmacocinética , Nitroglicerina/farmacología , Conejos , Ratas , Ratas Sprague-Dawley , EstereoisomerismoRESUMEN
An extract from oats known as oat gum (OG) is composed mainly of the polysaccharide (1-->3) (1-->4)-beta-D-glucan, which is highly viscous in aqueous solution. Viscous polysaccharides are known to attenuate postprandial plasma glucose and insulin responses. The purposes of this study were to determine the dose-response to OG and establish quantitatively the effect of viscosity on plasma glucose and insulin levels of healthy humans consuming 50 g glucose. Increasing the dose of OG successively reduced the plasma glucose and insulin responses relative to a control without gum. Reduction of the viscosity of OG by acid hydrolysis reduced or eliminated the capacity to decrease postprandial glucose and insulin levels. The ability of OG to modify glycaemic response was unchanged following agglomeration in the presence of maltodextrin. Agglomerated gum dispersed smoothly in a drink without formation of lumps, and development of maximum viscosity was delayed. These properties improve palatability. There was a highly significant linear relationship between log[viscosity] of the mixtures consumed and the glucose and insulin responses. The relationship shows that 79-96% of the changes in plasma glucose and insulin are attributable to viscosity, and that changes occur at relatively low doses and viscosities.
Asunto(s)
Avena , Glucemia/metabolismo , Glucanos/administración & dosificación , Glucosa/administración & dosificación , Insulina/sangre , Extractos Vegetales/administración & dosificación , Adulto , Avena/química , Relación Dosis-Respuesta a Droga , Femenino , Alimentos , Glucanos/metabolismo , Humanos , Masculino , Factores de Tiempo , ViscosidadRESUMEN
The aim of the current study was to characterize the effects of isolated and native sources of beta-glucan, oat gum, and oat bran, respectively, when incorporated into a complete meal. Fasting control subjects and subjects with Type 2 diabetes were fed porridge meals containing either wheat farina, wheat farina plus oat gum or oat bran. Blood samples were collected for 3 h after the test meals and plasma glucose and insulin were measured. Oat bran and wheat farina plus oat gum meals reduced the postprandial plasma glucose excursions and insulin levels when compared with the control wheat farina meal in both control and Type 2 diabetic subjects. This study shows that both the native cell wall fibre of oat bran and isolated oat gum, when incorporated into a meal, act similarly by lowering postprandial plasma glucose and insulin levels. A diet rich in beta-glucan may therefore be of benefit in the regulation of postprandial plasma glucose levels in subjects with Type 2 diabetes.
Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Fibras de la Dieta , Ingestión de Alimentos , Grano Comestible , Glucanos , Insulina/sangre , Adulto , Pan , Carbohidratos de la Dieta , Femenino , Hemoglobina Glucada/análisis , Humanos , Insulina/metabolismo , Secreción de Insulina , Masculino , Persona de Mediana Edad , Valores de Referencia , Factores Sexuales , Factores de Tiempo , TriticumRESUMEN
Although three germ cell-specific transcripts of type 1 hexokinase exist in murine male germ cells, only one form, HK1-sc, is found at the protein level. This single isoform localizes to three distinct structures in mouse spermatozoa: the membranes of the head, the mitochondria in the midpiece, and the fibrous sheath in the flagellum (Travis, A. J., Foster, J. A., Rosenbaum, N. A., Visconti, P. E., Gerton, G. L., Kopf, G. S., and Moss, S. B. (1998) Mol. Biol. Cell 9, 263-276). The mechanism by which one protein is targeted to multiple sites within this highly polarized cell poses important questions of protein targeting. Because the study of protein targeting in germ cells is hampered by the lack of established cell lines in culture, constructs containing different domains of the germ cell-specific hexokinase transcripts were linked to a green fluorescent protein and transfected into hexokinase-deficient M+R42 cells. Constructs containing a nonhydrophobic, germ cell-specific domain, present at the amino terminus of the HK1-SC protein, were targeted to the endoplasmic reticulum and the plasma membrane. Mutational analysis of this domain demonstrated that a complex motif, PKIRPPLTE (with essential residues italicized), represented a novel endoplasmic reticulum-targeting motif. Constructs based on another germ cell-specific hexokinase transcript, HK1-sa, demonstrated the specific proteolytic removal of an amino-terminal domain, resulting in a protein product identical to HK1-SC. Such processing might constitute a regulatory mechanism governing the spatial and/or temporal expression of the protein.