Recent determinations of serum phosphatase activity in patients with cancer (1, 2, 3) suggest that values obtained in cases with widespread osteoplastic metastases are, in general, significantly higher than those found in association with osteolytic metastases. In the series reported by Gutman, Tyson and Gutman (1), for example, the serum phosphatase activity exceeded 10 Bodansky units per 100 c.c. in 6 of 10 cases with osteoplastic metastases but in only 3 of 19 patients with osteolytic metastases. In 2 patients with very extensive osteoplastic skeletal lesions, values exceeding 100 Bodansky units per 100 c.c. of serum were obtained, as contrasted with the normal maximum of 4.0 Bodansky units. It has been assumed (1, 3) that the rise in phosphatase activity of the serum in such cases is the result of increased elaboration of phosphatase, which is subsequently released into the circulating fluids. Direct evidence in support of this assumption is afforded by the present investigation, which disclosed strikingly increased phosphatase activity of bone at the site of osteoplastic skeletal metastases in a patient with carcinoma of the prostate gland.

Conclusions The best base for alloys, wear resistant against abrasive action, is unstable residual austenite in combination with certain quantities of martensite. The wear resistance of material with this base is higher the higher the concentration of carbide phase. However, the use of plates made from highly alloyed irons possessing high resistance to wearing is not at present possible because of their brittleness.

The effect of allopurinol on the metabolism of pro benecid was evaluated in patients for two reasons: allopurinol was re ported to inhibit drug metabolism, and combined therapy (allopurinol and probenecid) is occasionally employed in the treatment of gout. Metabolism of probenecid was estimated by the determination of probenecid plasma level decay (T½). ln 8 of 14 subjects, a prolongation of T½ was found during concurrent allopurinol treatment. Allopurinol isboth a substrate and an inhibitor of xanthine oxidase and thus it can inhibit its own metabolism. It had also been shown that probenecid influences the fate of alloxanthine, the major metabolite of allopurinol. The present studies illustrate an additional complex feature of interactions between allopurinol and probenecid in man.

AbstractDie Metaboliten (II) des Probenecids (I) werden synthetisiert und ihre UV‐ Spektren, pKa‐Werte und Verteilungskoeffizienten bestimmt.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMetabolites of probenecid. Chemical, physical, and pharmacological studiesZ. H. Israili, J. M. Perel, R. F. Cunningham, P. G. Dayton, T. F. Yu, A. B. Gutman, K. R. Long, R. C. Long Jr., and J. H. GoldsteinCite this: J. Med. Chem. 1972, 15, 7, 709–713Publication Date (Print):July 1, 1972Publication History Published online1 May 2002Published inissue 1 July 1972https://pubs.acs.org/doi/10.1021/jm00277a004https://doi.org/10.1021/jm00277a004research-articleACS PublicationsRequest reuse permissionsArticle Views319Altmetric-Citations33LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts

In a survey of 425 cases of hyperuricemia with gouty arthritis or uric acid stone, or both, we found partial deficiency of H-G PRTase, a newly recognized cause of these manifestations, in only 7 subjects, of whom 5 were members of one family. The prevalence in this series was thus 1.6%, which is probably higher than in the gouty population at large because this study included a disproportionately large number of severely afflicted patients. Transmission was through heterozygous, asymptomatic mothers and was expressed only in sons, consistent with X-linkage. Six of the seven hemizygotes detected conformed to previous reports in having very low erythrocyte H-G PRTase activity (about 0.1% to 1% of normal) and increased urinary hypoxanthine to xanthine ratios, usually with relatively early onset of severe symptoms. In the seventh case erythrocyte H-G PRTase activity was about 30% of normal, with an accompanying increase in the urinary hypoxanthine to xanthine ratio. This patient had late onset of moderately severe recurrent gouty arthritis.

The metabolism of probenecid has been investigated in both normal and gouty subjects. To carry out these studies, specific spectrophotometric methods were developed for the measurement of a major metabolite of probenecid, the acyl glucuronide. This conjugate was isolated in semi-pure state and its identity as a mono acyl glucuronide established. Our experiments indicate that about 25% of probenecid is converted to its acyl glucuronide and that only a small amount of the drug is excreted unchanged. About 80% of orally administered14C probenecid could be accounted for in urine, and about half of this was found to consist of metabolites more polar than the parent drug. The renal clearance of probenecid acyl glucuronide was shown to be about 1/3 that of creatinine clearance, whereas the clearance of probenecid was lower. The present findings in man and those of other workers in animals, raise the important question of the possible contribution of these metabolites to the overall pharmacological effects resulting from the administration of probenecid.

ARTICLESLow uricase activity in the Dalmatian dog simulated in mongrels given oxonic acidTF Yu, AB Gutman, L Berger, and C KaungTF Yu, AB Gutman, L Berger, and C KaungPublished Online:01 Apr 1971https://doi.org/10.1152/ajplegacy.1971.220.4.973MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByGrain free diets for utility dogs during training work: Evaluation of the nutrient digestibility and faecal characteristicsAnimal Nutrition, Vol. 5, No. 3Uricosuric and Hypo-Uricemic ActivityUricosuric and Hypo-Uricemic Activity21 April 2015Renal System in Safety PharmacologyActivity on Urinary TractSafety Pharmacology of Drugs for the Urinary TractThe dalmatian defect: A hepatic endocrinopathy of urate transport1 January 2005 | Arthritis & Rheumatism, Vol. 52, No. 8Evaluation of the association between sex and risk of forming urate uroliths in DalmatiansJournal of the American Veterinary Medical Association, Vol. 227, No. 4Activity on urinary tract1Multiple intrasplenic hepatocyte transplantations in the dalmatian dogSurgery, Vol. 127, No. 2Renal activityFanconi Syndrome in a Labrador RetrieverJournal of Veterinary Internal Medicine, Vol. 8, No. 6Uric acid degrading enzymes, urate oxidase and allantoinase, are associated with different subcellular organelles in frog liver and kidneyJournal of Cell Science, Vol. 107, No. 4The fate of administered purines in the Dalmatian Coach HoundJournal of Comparative Pathology, Vol. 96, No. 3Uric acid uptake in erythrocytes of Beagle and Dalmatian dogsComparative Biochemistry and Physiology Part A: Physiology, Vol. 85, No. 3Etiopathogenesis of Uric Acid and Ammonium Urate Uroliths in Non-Dalmatian DogsVeterinary Clinics of North America: Small Animal Practice, Vol. 16, No. 1Serum urate concentrations in the Dalmatian Coach HoundJournal of Comparative Pathology, Vol. 95, No. 2Urolithiasis in Hereditary Renal HypouricemiaDefect of uric acid uptake in Dalmatian dog liverExperientia, Vol. 40, No. 12Renal Handling of UrateGoutUrate CalculiSpontaneous Fanconi syndrome in the dogMetabolism, Vol. 27, No. 1Use of the Uricase-Inhibited Rat as an Animal Model in Toxicology25 September 2008 | Clinical Toxicology, Vol. 13, No. 1Tubular Handling of Allantoin in the Rat KidneyDrugs Affecting the Renal Handling of Uric AcidHypouricemiaArthritis & Rheumatism, Vol. 18, No. S1Handling of allantoin by the rat kidneyPfl�gers Archiv European Journal of Physiology, Vol. 357, No. 3-4Supplement: 21st rheumatism reviewArthritis & Rheumatism, Vol. 17, No. 5Action of 4-prenyl-1,2-diphenyl-3,5-pyrazolidinedione (DA 2370) on an experimental hyperuricosuria in the ratPharmacological Research Communications, Vol. 5, No. 2Hypouricemia due to isolated renal tubular defectThe American Journal of Medicine, Vol. 53, No. 3Renal mechanisms for regulation of uric acid excretion, with special reference to normal and gouty manSeminars in Arthritis and Rheumatism, Vol. 2, No. 1 More from this issue > Volume 220Issue 4April 1971Pages 973-979 Copyright & PermissionsCopyright © 1971 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1971.220.4.973PubMed5551153History Published online 1 April 1971 Published in print 1 April 1971 Metrics

The interactions between the uricosuric agents probenecid and sulfinpyrazone were studied in subjects with gout by means of renal clearance experiments. It was found that in both acid and alkaline urine, probenecid markedly inhibited renal tubular secretion of sulfinpyrazone without significantly altering the maximal uric acid clearance observed with each drug alone. It was also observed that probenecid inhibits the tubular secretion of the p‐hydroxy metabolite of sulfinpyrazone. The implications of these findings are discussed in terms of multiple "cascade" renal interactions among administered drugs and their respective metabolites.

Ir is an honor indeed to have your Section on Urology take notice of certain studies made by my late wife, Ethel Benedict Gutman, and myself at the Columbia-Presbyterian Medical Center about 30 years ago. To acknowledge your generous Ferdinand C. Valentine Award for these studies I have been advised that it would be appropriate to review the circumstances of the work then accomplished, with such intimate details as are usually omitted from formal publications. You are therefore invited to embark upon a sentimental journey, less engaging than that of Lawrence Sterne through France and Italy, but somewhat more urologically oriented. Our initial interest was in serum alkaline phosphatase and its relationship to bone formation in disorders affecting the skeleton, an interest inspired by the pioneer investigations in this field by Dr. Aaron Bodansky, my erstwhile instructor in physiological chemistry at the Ithaca branch of Cornell Medical College, and later a close neighbor at the Hospital for Joint Diseases. In the course of these earlier studies1 we had found, as had Woodard, Twombly, and Coley,2 that the serum alkaline phosphatase was usually substantially higher in the presence of widespread osteoplastic metastases, notably secondary to prostatic carcinoma, than in association with osteolytic metastases due, for example, to breast carcinoma. This increase in serum alkaline phosphatase was generally assumed to arise from augmented osteoblastic activity, with consequently increased elaboration of the enzyme. To put this hypothesis to the test we began in I935 to examine the alkaline phosphatase activity of bone at the site of osteoplastic metastases sec-

Available estimates indicate that about 10 per cent of all renal calculi encountered in the U.S.A. as a whole are composed of uric acid and that the prevalence of uric acid nephrolithiasis in the population at large is of the order of 0.01 per cent. In pathogenesis the critical factors are those that lead to supersaturation of the urine with respect to undissociated (free) uric acid, which is more sparingly soluble than urates, and the factors that lead to separation of solid phase uric acid from its saturated solution in the urine, with organized crystal overgrowth. In regard to the first, the importance of persistent undue acidity of the urine, hyperuricosuria and contraction of the urine volume is stressed; the controversial role of deficient urinary ammonium excretion in undue acidity of the urine is discussed. In regard to the second, it is concluded that initiating uric acid crystals probably form the nidus in most cases, seeds of calcium oxalates in some.