Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0451641 (urolithiasis)
 3,973 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence of urolithiasis has increased in the industrialized nations. However, both the pathogenesis and methods for its prevention remain to be clarified. We demonstrate that the antioxidative effect of green tea decreases the formation of calcium oxalate stones, OPN (osteopontin) expression, and apoptosis, and increases SOD (superoxide dismutase) activity in rat kidney tissues. The inhibitory effect of green tea on calcium oxalate urolithiasis is most likely due to its antioxidative effects. Therefore, we examined oxidative stress in vivo applied to Madin-Darby canine kidney (MDCK) cells, to which catechin, an antioxidant, was added. To evaluate the effects of oxidative stress on MDCK cells, we use a hypoxic condition because hypoxia is known to lead to oxidative stress. Confluent cultures of MDCK cells were exposed to (-)epigallocatechin 3 gallate (EGCG) (0, 0.1, 0.5, 5.0 mg/ml) for 2, 4, 8 or 16 h to determine changes in protein secretion and apoptosis. OPN protein expression was observed in MDCK cells of all 16 groups. The levels of expression of OPN protein were the same among all groups. In all groups, SOD protein expression was observed. In the groups exposed to EGCG 0.5, 5.0 mg/ml, SOD staining was more enhanced than in the EGCG 0 and 0.1 mg/ml groups. No deposits were detected in any of the 16 groups. RT-PCR was performed to detect sequences from OPN (979 bp) and SOD (447 bp). Quantitative analyses showed that SOD activity decreased gradually in all groups. Only in the EGCG 0 mg/ml 16 h group were TUNEL-positive cells observed. In the other groups, TUNEL-positive cells were not detected. EGCG used as an antioxidant protects renal tubular cell from cellular injury caused by oxidative stress through SOD protein expression.
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PMID:Examination of the anti-oxidative effect in renal tubular cells and apoptosis by oxidative stress. 1604 15

Urolithiasis is a common complication in patients with hypouricemia. Using a microarea x-ray diffractometer and nanoflow liquid chromatography-mass spectrometry (LC-MS) following SDS-polyacrylamide gel electrophoresis (PAGE), recurrent urinary calculi complicating a hypouricemic patient were analyzed. Analysis with the microarea x-ray diffractometer showed that one of the calculi was composed of calcium oxalate monohydrate and hydroxyapatite. The other was found to be formed from calcium oxalate dihydrate. After determination with LC-MS, both were found to contain uromodulin, albumin, osteopontin, protein Z, and defensins. Lysozyme and calgranulin A were also identified in these calculi. Defensins, which were antimicrobial peptides, and lysozyme, a mucopeptide glycohydrolase, were identified as new organic components of urinary stones. The role of these proteins in the process of urolithiasis is of particular interest.
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PMID:Analysis of urinary calculi obtained from a patient with idiopathic hypouricemia using micro area x-ray diffractometry and LC-MS. 1613 78

This study was undertaken to determine whether the use of different washing procedures could explain dissident findings in published studies examining the role of urinary macromolecules in urolithiasis. Calcium oxalate monohydrate (COM) crystals were deposited from or added to the same sieved urine, washed with copious or limited amounts of distilled water, or with methanol, and examined by field emission scanning electron microscopy (FESEM). Demineralized extracts were analysed by SDS-PAGE and Western blotting for Tamm-Horsfall glycoprotein (THG), human serum albumin (HSA), osteopontin (OPN) and prothrombin fragment 1 (PTF1). Synchrotron X-ray diffraction (SXRD) with Rietveld whole-pattern peak fitting and profile analysis was used to determine non-uniform crystal strain and crystallite size in crystals generated from inorganic solutions in the presence of increasing concentrations of THG and prothrombin (PT). HSA and PTF1 were present in all demineralized crystal extracts, confirming their inclusion within COM. OPN was present in all extracts except those derived from pure inorganic COM crystals, because of its occlusion within small numbers of calcium oxalate dihydrate (COD) crystals contaminating the COM population. THG was absent from the demineralized extracts of all crystals washed copiously with water, but present in those washed with methanol or limited amounts of water. FESEM showed extraneous organic material associated only with crystals whose extracts contained THG, confirming that the protein does not bind permanently to the COM crystal surface and is not occluded within the mineral bulk. This was confirmed by SXRD, which showed that non-uniform strain and crystallite size remained unaltered in crystals grown in the presence of increasing THG concentrations. However, non-uniform strain increased and crystallite size decreased with increasing PT concentrations, demonstrating unambiguously that PT is included in COM crystals. It was concluded that scrupulous care must be taken to ensure the complete removal of extraneous THG adventitiously associated with CaOx crystals in order to avoid inaccurate analysis of crystal matrix protein content and possible misinterpretation of experimental data.
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PMID:The importance of a clean face: the effect of different washing procedures on the association of Tamm-Horsfall glycoprotein and other urinary proteins with calcium oxalate crystals. 1727 22

Strong evidence that osteopontin (OPN) is a determinant of urolithiasis has prompted studies comparing the protein's urinary excretion in healthy subjects and stone formers. However, reported mean urinary values have varied widely, from <1 microg/mL to more than 20 times that value. Since OPN binds to CaOx crystals, the presence of crystals in urine may cause underestimation of its urinary levels. Using a commercial ELISA, we measured urinary OPN levels in the presence of endogenous or exogenous CaOx monohydrate (COM) and dihydrate (COD) crystals. OPN concentrations decreased in the presence of endogenous and exogenous CaOx crystals, but never below 2 microg/mL. Increasing the urinary calcium concentration decreased detectable OPN levels, possibly as a result of changes in the three-dimensional conformation of the protein. Because calcium concentration and the formation of CaOx crystals cannot be controlled in urine, the use of urinary OPN levels as a biomarker for any human pathology must be seriously questioned, but particularly for the investigation of stone formers in whom hypercalciuria and crystalluria are more common than in healthy subjects.
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PMID:High calcium concentration and calcium oxalate crystals cause significant inaccuracies in the measurement of urinary osteopontin by enzyme linked immunosorbent assay. 1847 19

Several clinical and epidemiological studies revealed increased bone turnover and lower bone mass in patients with urolithiasis. Bone mass loss is particularly evident in idiopathic calcium stone formers. However, pathogenetic mechanisms and factors implicated in bone loss in these patients are still unknown. Dietary calcium restriction, increased intake of salt and animal proteins, vitamin D receptor polymorphisms are likely risk factors, while role of inflammatory cytokines, osteopontin and prostaglandin mediated bone resorption is yet to be determined. Regarding treatment and prevention, it has been proven that calcium supplements and high calcium diet with the addition of potassium alkali have an important role in prevention and treatment of both, urolithiasis and osteoporosis. Thiazide diuretics reduce hypercalciuria in renal tubules, and in addition promote osteoblast differentiation. Finally, bisphosphonates, a commonly used drugs in treatment of osteoporosis, show the potential to inhibit calcium stone formation, whereas a possible protective effect of antioxidants in bone loss and renal injurie needs to be investigated further.
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PMID:Urolithiasis and osteoporosis: clinical relevance and therapeutic implications. 2012 Apr 12

Our aim was to examine the attachment to, and incorporation of intact, highly phosphorylated osteopontin (OPN) into inorganic (i) and urinary (u) calcium oxalate monohydrate (COM) and dihydrate (COD) crystals. uCOM and uCOD crystals were precipitated from ultrafiltered (UF) urine containing human milk OPN (mOPN) labelled with Alexa Fluor 647 fluorescent dye at concentrations of 0.1-5.0 mg/L. iCOM and iCOD crystals were generated in aqueous solutions at concentrations of 0.01-0.5 mg/L. Crystals were demineralised with EDTA and the resulting extracts analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis and western blotting, or examined by fluorescent confocal microscopy and field emission scanning electron microscopy before and after washing to remove proteins bound reversibly to the crystal surfaces. Binding of mOPN to pre-formed iCOM crystals was also studied in phosphate-buffered saline (PBS) and ultrafiltered (UF) urine. mOPN attached to the {100} faces and to the {010} sides of the {100}/{010} edges of iCOM crystals was removed by washing, indicating that it was not incorporated into the mineral bulk. In both PBS and urine, mOPN was attached to the {021} faces of pre-formed iCOM crystals as well as to the {100}/{010} edges, but was concentrated at the intersection points of the {100} and {121} faces at the crystal tips. Attachment in UF urine appeared to be greater than in PBS and stronger at higher calcium concentrations than lower calcium concentrations. In uCOM crystals, the distribution of fluorescence and patterns of erosion after washing suggested attachment of mOPN to the four end faces, followed by interment within the mineral phase. Fluorescence distributions of mOPN associated with both iCOD and uCOD crystals were consistent with uniform binding of the protein to all equivalent {101} faces and concentration along the intersections between them. Persistence of fluorescence after washing indicated that most mOPN was incarcerated within the mineral phase. We concluded that attachment of mOPN to calcium oxalate crystals is face-specific and depends upon the anatomical and genetic source of the protein and whether the crystals are (1) COM or COD; (2) pre-formed or precipitated from solution, and (3) precipitated from urine or aqueous solutions. Our findings emphasise the need for caution when drawing conclusions about possible roles of OPN or other proteins in urolithiasis from experimental data obtained under inorganic conditions.
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PMID:Face-specific incorporation of osteopontin into urinary and inorganic calcium oxalate monohydrate and dihydrate crystals. 2065 61

The aim of this study was to compare the comprehensive intracrystalline protein profiles of calcium oxalate monohydrate (COM) and dihydrate (COD) crystals precipitated from the same human urine samples. Three separate batches of COM and COD crystals were precipitated from pooled healthy human urine by the addition of sodium oxalate at calcium concentrations of 2 and 8 mM, respectively. Proteins in whole extracts of demineralised COM and COD crystals, as well as in spots excised from 2D-PAGE gels of the extracts, were identified using liquid chromatography and tandem mass spectrometry (LC-MS/MS). The number and type of individual proteins differed between COM and COD: 14 substantive proteins were found inside COM crystal extracts and 34 inside COD, with 9 proteins occurring in both crystal types. Numerous keratins were detected. However, in line with consensus in the proteomics literature, as well as a lack of published evidence linking them to urolithiasis, they were excluded as contaminants, leaving very few consistently detected proteins. On the basis of their known association with stone disease or identification in multiple runs, the principal proteins in COM crystal extracts were prothrombin fragment 1, protein S100A9, and IGkappaV1-5, while those in extracts of COD crystals included osteopontin, IGkappaV1-5, protein S100A9, annexin A1, HMW kininogen-1, and inter-alpha-inhibitor (IalphaI). In general, proteins incorporated into both hydromorphs were acidic (pI<6), smaller than 55 kDa, and calcium binders. We concluded that the incorporation of proteins into urinary COM and COD crystals is selective and that only a few of the urinary proteins associated with the two hydromorphs are likely to play any significant role in stone pathogenesis.
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PMID:Comparison of the specific incorporation of intracrystalline proteins into urinary calcium oxalate monohydrate and dihydrate crystals. 2067 53

A nationwide survey of urolithiasis in Japan conducted in 2005 disclosed its steady increase in incidence and the life-long risk was estimated to be 15% in men and 6% in women. The recurrence rate has also increased, to 70 -80% in the extracorporeal shock wave lithotripsy (ESWL) era from around 50% previously. Although urolithiasis is very common and highly recurrent, the impact and concern of stone disease are not necessarily as high as expected either medically or socially, because of its benign nature and easy accessibility to treatments by ESWL and/or endourological procedures. Dramatic progress is taking place both experimentally and clinically in this field, such as development of a simple method of measuring metastable limits using a microplate, clarifying altered oxalate metabolism due to insulin resistance and close relationship between stone disease and metabolic syndrome, elucidating the exact role of osteopontin in an experimental model at a molecular level, prophylaxis of stone disease by angiotensin II type I receptor blocker, and addition of a new modality of fiberscopic transurethral lithotripsy (f-TUL) to the conventional endourological treatments. We hope that "change and future perspective" in the field of urolithiasis will be discussed and clarified in this symposium.
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PMID:[Change in concepts of urolithiasis: recent advances in pathogenesis, assessment, treatment and prophylaxis]. 2130 58

Chinese herbs Desmodium styracifolium (Ds) and Pyrrosiae petiolosa (Pp) have been widely used to treat urolithiasis with few side effects in traditional Chinese medicine (TCM). In vitro crystallization study has confirmed their prophylaxis of Calcium oxalate (CaO( x )) stones formation. However, little is known on their possible mechanisms in vivo. In the present study, we proposed to systematically evaluate their antilithic effects and clarify the underlying mechanism of Ds and Pp using a rat nephrolithiasis model and administering the aqueous extracts. Adult male Wistar rats were fed with 5% ammonium oxalate (AmO( x )) forage to induce nephrolithiasis. After 1 week, the rats were randomly divided into eight groups, and given low, medium, and high dose of each herb treatments (275, 550 and 1,100 mg/kg for Ds and 150, 300 and 600 mg/kg for Pp) by gavage for 3 weeks. In contrast to urolithic rats, urinary oxalate significantly reduced, and urinary calcium increased in medium and high dose Ds groups. Few depositions were observed in kidney with slight dilation of tubules and inflammatory infiltration. Osteopontin (OPN), nitric oxide (NO), and malondialdehyde (MDA) levels significantly decreased, but Superoxide dismutase (SOD) activities were enhanced in kidneys. In high dose Pp group, crystals were found in the dilation of tubules with slight inflammatory infiltration. Partial serum and urinary variables returned to the normal range. In conclusion, medium and high dose Ds has beneficial effect in preventing CaO( x ) stone formation by rising urinary Citrate excretion, decreasing urinary calcium, diuresis, and antioxidative effects. Although high dose Pp has relatively weak prophylaxis, it indicates significant anti-inflammatory and antioxidant effects.
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PMID:Evaluation of antiurolithic effect and the possible mechanisms of Desmodium styracifolium and Pyrrosiae petiolosa in rats. 2182 40

In vivo, urinary crystals are associated with proteins located within the mineral bulk as well as upon their surfaces. Proteins incarcerated within the mineral phase of retained crystals could act as a defence against urolithiasis by rendering them more vulnerable to destruction by intracellular and interstitial proteases. The aim of this study was to examine the effects of intracrystalline and surface-bound osteopontin (OPN) on the degradation and dissolution of urinary calcium oxalate dihydrate (COD) crystals in cultured Madin Darby canine kidney (MDCK) cells. [(14)C]-oxalate-labelled COD crystals with intracrystalline (IC), surface-bound (SB) and IC + SB OPN, were generated from ultrafiltered (UF) urine containing 0, 1 and 5 mg/L human milk OPN and incubated with MDCKII cells, using UF urine as the binding medium. Crystal size and degradation were assessed using field emission scanning electron microscopy (FESEM) and dissolution was quantified by the release of radioactivity into the culture medium. Crystal size decreased directly with OPN concentration. FESEM examination indicated that crystals covered with SB OPN were more resistant to cellular degradation than those containing IC OPN, whose degree of disruption appeared to be related to OPN concentration. Whether bound to the crystal surface or incarcerated within the mineral interior, OPN inhibited crystal dissolution in direct proportion to its concentration. Under physiological conditions OPN may routinely protect against stone formation by inhibiting the growth of COD crystals, which would encourage their excretion in urine and thereby perhaps partly explain why, compared with calcium oxalate monohydrate crystals, COD crystals are more prevalent in urine, but less common in kidney stones.
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PMID:The effect of intracrystalline and surface-bound osteopontin on the degradation and dissolution of calcium oxalate dihydrate crystals in MDCKII cells. 2193 31


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