Urine concentrations of xanthine, hypoxanthine and uric acid in<scp>UK</scp>Cavalier King Charles spaniels

Jacinto, A M L; Mellanby, Richard J.; Chandler, Marge; Bommer, Nick; Carruthers, Harvey; Fairbanks, Lynette D.; Gow, Adam

doi:10.1111/jsap.12106

Cited by 11 publications

(9 citation statements)

References 25 publications

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“…Human mutations in xanthine dehydrogenase activity result in the disorder xanthinuria type I. An equivalent disease also occurs in dogs, most notably the Cavalier King Charles spaniel breed [ 18 ]. Patients with xanthinuria type I, one of the few single gene disorders known to result in nephrolithiasis in humans, form debilitating, recurrent kidney stones [ 19 ].…”

Section: Resultsmentioning

confidence: 99%

“…Ectopic calcification was studied in the Drosophila Malpighian tubule utilizing a background of inhibition of Xdh [ 53 ]. Xanthine dehydrogenase is deficient in a subset of patients with nephrolithiasis [ 19 ] and some dog species [ 18 ]. The demonstration of ectopic calcifications in Drosophila deficient in Xdh reflects a conserved role for xanthine dehydrogenase in ectopic calcification.…”

Section: Discussionmentioning

confidence: 99%

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A Drosophila Model Identifies a Critical Role for Zinc in Mineralization for Kidney Stone Disease

et al. 2015

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Ectopic calcification is a driving force for a variety of diseases, including kidney stones and atherosclerosis, but initiating factors remain largely unknown. Given its importance in seemingly divergent disease processes, identifying fundamental principal actors for ectopic calcification may have broad translational significance. Here we establish a Drosophila melanogaster model for ectopic calcification by inhibiting xanthine dehydrogenase whose deficiency leads to kidney stones in humans and dogs. Micro X-ray absorption near edge spectroscopy (μXANES) synchrotron analyses revealed high enrichment of zinc in the Drosophila equivalent of kidney stones, which was also observed in human kidney stones and Randall’s plaques (early calcifications seen in human kidneys thought to be the precursor for renal stones). To further test the role of zinc in driving mineralization, we inhibited zinc transporter genes in the ZnT family and observed suppression of Drosophila stone formation. Taken together, genetic, dietary, and pharmacologic interventions to lower zinc confirm a critical role for zinc in driving the process of heterogeneous nucleation that eventually leads to stone formation. Our findings open a novel perspective on the etiology of urinary stones and related diseases, which may lead to the identification of new preventive and therapeutic approaches.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A Drosophila Model Identifies a Critical Role for Zinc in Mineralization for Kidney Stone Disease

et al. 2015

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“…Their concentration levels are sensitive indicators of certain diseases, including perinatal asphyxia, cerebral ischemia, hyperuricemia, gout CONTACT Junwei Yang yangjw@sdju.edu.cn [6][7][8], and positive effect on cardiovascular system [9][10][11][12][13]. Therefore, the accurate measurement of HX, XA, and UA is very important in food, biochemical, and clinical diagnosis [14][15][16][17][18]. Various techniques have been developed for the simultaneous determination of HX, XA, and UA, such as enzymatic methods [19][20][21], as well as a highperformance liquid chromatographic method [22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Density functional theory study of interaction of graphene with hypoxanthine, xanthine, and uric acid

2016

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Hypoxanthine (HX), xanthine (XA), and uric acid (UA) are important molecules in human beings. However, the physics underlying the interaction between these molecules and carbon nanomaterials is still unclear. In this study, we theoretically anlaysed the interaction of the graphene with HX, XA, and UA via the LDA, Perdew-Burke-Ernzerhof, and a second version of van der Waals (vdW)-DF2 exchange-correlation functionals of density functional theory. It was observed that these molecules could be adsorbed on the surface of the graphene steadily. The adsorption energies of these molecules on the graphene for the same site in vdW-DF2 functional show the following ordering: UA > XA > HX, the adsorption distances the following ordering: UA < XA < HX. The mechanism of this stable adsorption was revealed to be π -π and O-π interactions between these molecules and the graphene. Simulated scanning tunnelling microscopy (STM) images of HX, XA, and UA on the surface of the graphene layer as application, HX can be distinguished from XA and UA via the STM technique as a result of the interaction between the graphene and these molecules. The findings of this study provide a theoretical reference in the development and design of highly accurate biodevices and biosensors.

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“…Defects in purine metabolism can result in tissue accumulation and excessive renal excretion of xanthine, with increased hypoxanthine and decreased uric acid concentrations. Xanthine is moderately insoluble at any urine pH and therefore can lead to the formation of xanthine crystals and urolithiasis (Osborne 2010; Jacinto 2013; Raivio 2014). …”

Section: Introductionmentioning

confidence: 99%

Hereditary xanthinuria and urolithiasis in a domestic shorthair cat

Furman¹,

Hooijberg²,

Leidinger³

et al. 2015

Comp Clin Pathol

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A 2-year-old domestic shorthair cat was presented with a history of hematuria, stranguria and intermittent urethral obstruction. Urine sediment showed hematuria, pyuria, and yellow-brown, amorphous and spherical crystals. Upon surgical correction of the obstructed urethra by perineal urethrostomy, many dark yellow to grey, irregular, gravel-like to millet grain-sized uroliths, consisting of 100% xanthine by crystallography were found. The urinary xanthine concentration was high. The cat subsequently developed bilateral nephroliths, recurrent urinary tract infection, and chronic kidney failure. Dietary management with a low-purine diet failed in part due to poor compliance, and the cat was euthanized at 6 years of age. Xanthinuria is rare inborn error of metabolism in cats and other species but should be considered as a differential diagnosis in cases of feline urolithiasis. No associated molecular genetic defect has been elucidated, and management of these cases is difficult. In the absence of calculi for analysis, measuring urinary xanthine concentration can help in diagnosing this metabolic defect.

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Urine concentrations of xanthine, hypoxanthine and uric acid inUKCavalier King Charles spaniels

Abstract: Asymptomatic xanthinuria was not detected in this UK Cavalier King Charles spaniel population. This data may be used as a reference for urinary purine metabolite concentrations in the dog.

Cited by 11 publications

References 25 publications

A Drosophila Model Identifies a Critical Role for Zinc in Mineralization for Kidney Stone Disease

A Drosophila Model Identifies a Critical Role for Zinc in Mineralization for Kidney Stone Disease

Density functional theory study of interaction of graphene with hypoxanthine, xanthine, and uric acid

Hereditary xanthinuria and urolithiasis in a domestic shorthair cat

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