Med.Ctr., Rockefeller Univ. NY, Lava1 Univ. Quebec Extensive metabolic and enzymatic studies i n a patient with hereditary hepatorenal tyrosinemia demonstrated f o r the f i r s t time a deficiency of red c e l l and hepatic glutathione (GSH). Markedly decreased hepatic fumarylacetoacetate hydrolase a c t i v i t y was measured i n t h i s patient (1-16% of normal). The a c t i v i t y of enzymes not involved i n tyrosine metabolism were a l s o measured i n l i v e r tissue. Assay of mixed function oxidase a c t i v i t y demonstrated low levels of arylhydrocarbon hydroxylase and 7-ethoxycoumarindeethylase. This depression of mixed function oxidase activity'may r e s u l t i n a decreased detoxification capacity of t h e l i v e r . Delta-amino levulinic acid dehydratase (ALAD) a c t i v i t y was undetectable. Succinyl acetone (4,6 dioxoheptanoic a c i d ) , an abnormal metabolic product secondary t o the fumarylacetoacetate hydrolase deficiency, was measurable i n serum and urine. Succinyl acetone was demonstrated t o i n h i b i t ALAD _In_ v i t r o , as did the urine, plasma and red c e l l l y s a t e s of t h e -p a t i e n t . The decreased GSH observed i n t h i s condition may play a r o l e i n the hepatic pathology and increased malignant p o t e n t i a l i n t h i s disorder. Therefore, the decrease i n GSH demonstrated i n our patient suggests the p o s s i b i l i t y of a new mode of therapy. W e studied t h e e f f e c t of 1,25(OH)2D3 on phosphate (Pi) homeos t a s i s i n the H mouse, a homologue of X-linked hypophosphatemia i n man. 1 ,25($2D3 (83 pg/g.day, infused subcut. x 10 days) produced s i g n i f i c a n t hypercalcemia in normal mice (1 1 .34+0.07 vs . W e conclude t h a t 1,25(OH)2D3 does not correct the renal BBM transport defect in rn mice, a t t h e supraphysiologic dose t h a t improves Pi homeostas i s . On t h e other hand, 1,25(OH)2~3 enhances ( p < 0 . 0 2 ) . i n t e s t inal absorption of Pi i n t h e m m o u s e , thus explaining i t s e f f e c t on Pi homeostasis i n t h e mutant phenotype of mouse and man. PERSISTANCE OF THE DEFECT IN RENAL BRUSH-BORDER MEM- 1184 PHARMACOKINETICS AND BIOAVAILABILITY OF A SUSTAINED-RELEASE THEOPHYLLINE PREPARATION (THEODUR) IN CYSTIC'Ig5 FIBROSIS (CF). Scott 8. Valet, Robert H. Schwartr, and John G. Brooks, University of R o c h e s t e r m o T of Medicine and m i r t r -t . Ped. Rochester, New York. Theophyll ine (theoph,) improves lung function in some CF pat i e n t s . Pharmacoki netics and bi oavai l abi l i t y of oral theoph, a r e not defined f o r these patients. W e studied the elimination of theoph. a f t e r IV Aminophylline,andabsorption of sustainedrelease oral theoph.(Theodur) in 10 CF patients (age 10-48 y r s ) . Each received a bolus of aminophyll i n e (4 mg/kg anhydrous theoph. ) and 10 plasma theophs.levels were measured over 8 hrs.El imination h a l f -l i f e (Tlg), t o t a l body clearance (Cl), volume of distribution (Vd) and area under the concentration curve (AUCiv) were determined.Two days l a t e r each pa...
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