RESUMEN
The influence of the polymorphism of the estrogen receptor-beta gene, cytosine-adenine (CA) dinucleotide repeat in intron 6, in the occurrence of rheumatoid arthritis (RA) was investigated. Forty-seven RA patients and 36 control subjects with osteoarthritis (OA) were recruited. CA repeat polymorphism was examined using denaturing high-performance liquid chromatography (WAVE DNA Fragment Analysis System). The mean number of CA repeats was significantly higher in RA than in OA patients. Two groups were established: Asunto(s)
Artritis Reumatoide/genética
, Repeticiones de Dinucleótido/genética
, Receptor beta de Estrógeno/genética
, Polimorfismo Genético
, Adenina
, Adulto
, Anciano
, Alelos
, Estudios de Casos y Controles
, Citosina
, Femenino
, Frecuencia de los Genes
, Genotipo
, Humanos
, Intrones
, Masculino
, Persona de Mediana Edad
, Factores de Riesgo
Asunto(s)
Artritis Reumatoide/genética , Autoanticuerpos/sangre , Hidrolasas/genética , Péptidos Cíclicos/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico/genética , Femenino , Frecuencia de los Genes , Humanos , Japón , Masculino , Persona de Mediana Edad , Arginina Deiminasa Proteína-Tipo 4 , Desiminasas de la Arginina ProteicaRESUMEN
[reaction: see text]. A convenient and asymmetric protocol for the synthesis of chiral oligoisoprenoids is described. Typically, a C14 vitamin E side chain 5 was synthesized in 47% yield over four steps. Isomeric purity of 5 was upgraded to >99% R at C-2 and 97% R at C-6 by the statistical formation of stereoisomeric p-phenylenebisurethanes and their diastereomeric separation. In addition, phytol and vitamin K were synthesized in 21% and 28% overall yields, respectively, over five steps from 1.
Asunto(s)
Fitol/síntesis química , Vitamina E/síntesis química , Vitamina K/síntesis química , Alquenos/química , Alquilación , Aluminio/química , Productos Biológicos/síntesis química , Catálisis , Compuestos Organometálicos/química , Estereoisomerismo , Circonio/químicaRESUMEN
Antipyrine is a useful probe to evaluate variation of in vivo activities of oxidative hepatic drug-metabolizing enzymes. Here we describe an approach using (13)C labeling and NMR spectroscopy for the direct and simultaneous analysis of major metabolites of antipyrine in human urine. [C-Methyl-(13)C]antipyrine (500 mg) was dosed orally to human volunteers, and the post-dose urine was analyzed by 100-MHz (13)C NMR spectroscopy under the conditions of distortionless enhancement by polarization transfer (DEPT) without any pretreatments such as deconjugation, chromatographic separation, or solvent extraction. Consequently, all the major metabolites in urine were successfully detected with favorable signal-to-noise ratios in the limited acquisition time (30 min). The reproducibility of the NMR detection was sufficient for the quantitative evaluation of the metabolic profile. A quantitative method is proposed using a combination of inverse gated decoupling and DEPT experiments with [2-(13)C]sodium acetate as an internal standard. The present approach is useful and practical to evaluate variation of in vivo activities of the conjugation enzymes as well as oxidative enzymes responsible for the formation of antipyrine metabolites in humans. This direct approach would enhance the value of the antipyrine test because of its simplicity and convenience.
Asunto(s)
Antipirina/orina , Espectroscopía de Resonancia Magnética/métodos , Adulto , Isótopos de Carbono , Humanos , MasculinoRESUMEN
A strictly "pair"-selective synthesis of conjugated diynes via Pd-catalyzed cross coupling of 1,3-diynylzincs is described. This method, like the Cadiot-Chodkiewicz reaction, requires three steps for the synthesis of R(1)Ctbd1;CCtbd1;CR(2) from R(1)Ctbd1;CH, R(2)X, and HCtbd1;CH. However, the high "pair"-selectivity permitting high-yield production of the desired conjugated diynes without separation of symmetrical diynes promises to make the present protocol superior to the Cadiot-Chodkiewicz reaction in many cases.
Asunto(s)
Alquinos/síntesis química , Compuestos Organometálicos/síntesis química , Zinc , Alquinos/química , Catálisis , Indicadores y Reactivos , Compuestos Organometálicos/química , PaladioRESUMEN
[structure: see text] Xerulin, an inhibitor of cholesterol biosynthesis, has been synthesized from commercially available (E)-1-bromopropene, acetylene, and propynoic acid in five steps (longest linear sequence) in 30% overall yield and >96% stereoselectivity. The preparation of (E)-iodobromoethylene and its use in the Pd-catalyzed cross coupling are two of the novel aspects of the synthesis reported herein.
Asunto(s)
Anticolesterolemiantes/síntesis química , Lactonas/síntesis química , Lactonas/farmacología , Estructura Molecular , EstereoisomerismoRESUMEN
Antipyrine is a useful probe to evaluate variation of in vivo activities of oxidative hepatic drug-metabolizing enzymes. Here we describe a new approach using (13)C labeling and NMR spectroscopy for the direct and simultaneous detection of all phase I and phase II metabolites of antipyrine in rat urine. [C-methyl-(13)C]Antipyrine was synthesized and administered orally to rats (100 mg/kg), and the 0- to 24-h postdose urine was analyzed by 100-MHz (13)C NMR spectroscopy under the conditions of distortionless enhancement by polarization transfer without any pretreatments such as deconjugation, chromatographic separation, and solvent extraction. Consequently, all the major metabolites in urine were successfully detected with favorable signal-to-noise ratios in the limited acquisition time (30 min). The assignments of the resonances were performed by enzymic modification and spiking authentic samples. The reproducibility of the NMR detection was sufficient for the quantitative evaluation of the metabolic profile. Effects of 3-methylcholanthrene on antipyrine metabolism were examined by this approach to evaluate variation of in vivo phase I and phase II metabolism of antipyrine in rats. The present approach is useful and practical to evaluate variation of in vivo activities of conjugation enzymes as well as oxidation enzymes responsible for the formation of antipyrine metabolites in rats. This direct approach would enhance the value of the antipyrine test because of the simplicity and convenience.
Asunto(s)
Antiinflamatorios no Esteroideos/orina , Antipirina/orina , Espectroscopía de Resonancia Magnética/métodos , Animales , Isótopos de Carbono , Marcaje Isotópico , Masculino , Ratas , Ratas Wistar , Sensibilidad y EspecificidadRESUMEN
[formula: see text] Pd-catalyzed reaction of iododienes and iodoarylalkenes represented by 1, 8, and 10 under 1 atm of CO and a small amount of O2 in the presence of a base, e.g., NEt3, as well as MeOH and H2O in DMF can undergo a highly diastereoselective cyclic carbopalladation-carbonylative esterification tandem process (Type II C-Pd process) to give in high yields the corresponding ester-containing cyclization products, e.g., 2, 9, and 11, in as high as 98% diastereoselectivity.
Asunto(s)
Alquenos/síntesis química , Yodobencenos/síntesis química , Paladio/química , Compuestos de Aluminio , Catálisis , Ciclización , Ésteres/síntesis química , Indicadores y Reactivos , Compuestos de Litio , Sustancias Reductoras , EstereoisomerismoRESUMEN
The amount of hippuric acid synthesized and excreted in the urine after benzoic acid loading (hippuric acid test) is a useful index of liver function. However, the hippuric acid test gives erroneous results in the event of failure of renal excretory function. A new stable isotope co-administration methodology using nuclear magnetic resonance (NMR) spectroscopy has been developed to overcome this defect. [7-(13)C]Benzoic acid and [glycine carbonyl-13C]hippuric acid ([gly-13C]hippuric acid), each 0.4-0.6 mmol kg(-1) were simultaneously administered intravenously as probes to normal or liver-injured rats and the urine was analysed by 100 MHz 13C NMR spectroscopy. Consequently, urinary excretion of [7-(13)C]hippuric acid formed from [7-(13)C]benzoic acid and [gly-13C]hippuric acid was successfully traced with very simple and convenient procedures. The urinary excretion of [7-(13)C]hippuric acid indicated the combined functions of hippuric acid synthesis and renal excretion, whereas that of [gly-13C]hippuric acid was indicative of renal excretion of hippuric acid only. The heights of resonances for C7 of [7-(13)C]hippuric acid and the glycine carbonyl carbon of [gly-13C]hippuric acid were used to calculate the concentrations of labelled hippuric acids. [7-(13)C]Hippuric acid was excreted more slowly than [gly-13C]hippuric acid by both normal and liver-injured rats. The liver-injured rats excreted the labelled hippuric acids more slowly than the normal rats. The kinetic parameters were computed for the individual rats on the basis of Michaelis-Menten elimination for benzoic acid and first-order elimination for hippuric acid. The maximum rates of metabolism (Vmax) (4.8-5.8 micromol min(-1) kg(-1)) and the renal elimination rate constants of hippuric acid (Kre) (0.010-0.021 min(-1)) in the liver-injured rats were lower than those (Vmax 6.7-11.8 micromol min(-1) kg(-1); Kre 0.026-0.045 min(-1)) in the normal rats. These results have demonstrated that liver function can be evaluated from the Vmax value even though the renal function of hippuric acid excretion (Kre) is impaired. Thus the co-administration methodology is feasible and can remove the defect of the previous hippuric acid test. These results could form the basis for a more convenient and reliable hippuric acid test in man.