Urinary macromolecules deposit on the plaque surface

Urinary macromolecules deposit on the plaque surface. matrix-gla-protein), and creation of matrix vesicles, which support nucleation of CaP crystals. These small deposits promote aggregation and calcification of surrounding collagen. Mineralization continues by calcification of membranous cellular degradation products and other fibers until the Cefpodoxime proxetil plaque reaches the papillary epithelium. Through the activity of matrix metalloproteinases or perhaps by brute physical force produced by the large subepithelial crystalline mass, the surface is breached and further stone growth occurs by organic matrix-associated nucleation of CaOx or by the transformation of the outer layer of CaP crystals into CaOx crystals. Should this theory hold true, developing an understanding of the cellular mechanisms involved in Cefpodoxime proxetil progression of a small, basic interstitial plaque to that of an expanding, penetrating plaque could assist in the development of new therapies for stone prevention. animal models as well as studies have provided the evidence that transition from one crystal type to another depends upon the urinary environment.[48,58C60] Hydroxyapatite and struvite (St) crystals coated the surface of the foreign body implanted into the bladder of a rat on a normal diet. Induction of hyperoxaluria in these rats, which was associated with lower urinary pH, generated a layer of CaOx crystals growing over the CaP/St. Reversing the hyperoxaluria led to the deposition of a layer of CaP/St over CaOx.[55,60] Both, the pH and supersaturation /activity product with respect to CaOx and CaP change as tubular fluid courses through the renal tubules. [61C64] A driving force for CaP precipitation is present in the thin loops of Henle while that for CaOx exists in the collecting ducts and the pelvic urine. Precipitation of CaP within the interstitium would require medullary alkalinization involving K+ depletion and activation of H+/K+ ATPase.[65] Dissolution of HA of the plaque at lower urinary pH that exists in the calyceal and pelvic urine would create localized areas of higher calcium concentration and therefore CaOx supersaturation promoting CaOx growing over CaP.[63] CaOx and CaP crystals found in both urine and kidney stones are coated with phospholipids, Tamm Horsfall Protein, albumin and a mix of organic matrix macromolecules such as osteopontin, inter–inhibitor, Cefpodoxime proxetil and urinary prothrombin fragment-1.[66C68] These macromolecule are present on mineral externally as well as internally, existing within stones as concentric tree-ring like layers of crystalline deposits[55] and within Randalls plaque at the sites of stone attachment, making epitaxial nucleation of one crystal over another unlikely[20]. Despite their production by epithelial cells to aid in crystal clearance, these macromolecules may by themselves promote the nucleation of CaOx as has been shown studies were performed to determine the possibility of HA replacement by CaOx monohydrate.[72] Large single HA crystals as well as bone pieces (mimic for Randalls plaque) were incubated in 0.25 mM, 0.5 mM and 1.00 mM oxalate solution with pH between 4.5 to 7.5 with the hypothesis that dissolution of HA will release calcium which will bind with the available oxalate to form CaOx crystals. Precipitation of CaOx monohydrate on HA crystals required very acidic pH and or high oxalate. CaOx precipitation on bone was seen even at a physiological oxalate concentration of 0.25 mM oxalate and pH of 5.0. Higher oxalate concentration of 0.5 mM was required for precipitation at pH of 6.00. Demineralization of bone produced a gel like layer on the surface. This layer may have produced physical hindrance for diffusion of calcium resulting in its accumulation near the bone surface and increasing local supersaturation and precipitation of CaOx as has previously been suggested.[63] Vascular Calcification Years ago, vascular calcification, or the deposition of apatite in the medial or intimal layers of the vessel walls, was considered as Rabbit Polyclonal to Collagen XI alpha2 an irreversible degenerative process that occurred by a passive, unregulated, physicochemical mechanism. Over the last 10C15 years, a large body of literature has replaced this passive theory to a central theory that describes vascular calcification as an active, regulated process in Cefpodoxime proxetil which vascular smooth cells (VSMC) acquire osteogenic phenotype.[73C75] Exposure of VSMC to elevated levels of calcium and phosphate triggers osteogenic transformation of VSMC, [76C79] which involves an.