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)

It has been suggested that docosahexaenoic acid (DHA) or other n-3 polyunsaturated fatty acids (PUFAs) may prevent or ameliorate methyl mercury's neurotoxicity. To examine interactions between PUFAs and methyl mercury exposure, sixty-six female Long-Evans rats were exposed to methyl mercury continuously via drinking water from fifteen weeks of age. Water included methyl mercury concentrations of 0, 0.5, and 5.0 ppm, creating estimated intakes of about 0, 40, and 400 microg/kg/day across exposure groups. An additional fifty-eight female offspring were exposed to methyl mercury only during gestation. Rats consumed one of two diets, each based on AIN-93 formulation, providing a 2 (generation) X 2 (diet) X 3 (methyl mercury exposure) factorial experimental design. A "coconut oil" diet (1/3 of fats were provided by coconut oil) was marginally adequate in n-3 PUFAs and contained no DHA. A "fish oil" diet was rich in n-3 fatty acids, including DHA. The diets were approximately equal in n-6 fatty acids. Forelimb grip strength declined with age for all groups, but the decline was greatest for those exposed chronically to 400 microg/kg/day of methyl mercury. This high-dose group also displayed hind limb crossing, gait disorders, and diminished running wheel activity. Dietary n-3 fatty acids did not influence these effects. Chronic exposure to 400 microg/kg/day of methyl mercury resulted in blood and brain concentrations of about 70 and 10 ppm, respectively, approximately 50-fold higher than concentrations seen in rats exposed to 40 microg/kg/day. Rats that became ill and died before the experiment ended had higher concentrations of mercury than their cohorts who survived to the end. Organic mercury was highly correlated with total mercury in these rats but inorganic mercury remained approximately constant. Some deaths were due to urolithiasis (kidney or bladder stones) associated with a dietary contaminant and that was eventually fatal to 22% of the females in the colony. Neurobehavioral effects are reported on rats that did not become ill.
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PMID:Neuromotor deficits and mercury concentrations in rats exposed to methyl mercury and fish oil. 1602 22

We have previously proposed that intracrystalline proteins would increase intracellular proteolytic disruption and dissolution of calcium oxalate (CaOx) crystals. Chauvet MC, Ryall RL. J Struct Biol 151: 12-17, 2005; Fleming DE, van Riessen A, Chauvet MC, Grover PK, Hunter B, van Bronswijk W, Ryall RL. J Bone Miner Res 18: 1282-1291, 2003; Ryall RL, Fleming DE, Doyle IR, Evans NA, Dean CJ, Marshall VR. J Struct Biol 134: 5-14, 2001. The aim of this investigation was to determine the effect of increasing concentrations of intracrystalline protein on the rate of CaOx crystal dissolution in Madin-Darby canine kidney (MDCKII) cells. Crystal matrix extract (CME) was isolated from urinary CaOx monohydrate (COM) crystals. Cold and [14C]oxalate-labeled COM crystals were precipitated from ultrafiltered urine containing 0-5 mg/l CME. Crystal surface area was estimated from scanning electron micrographs, and synchrotron X-ray diffraction was used to determine nonuniform strain and crystallite size. Radiolabeled crystals were added to MDCKII cells and crystal dissolution, expressed as radioactive label released into the medium, was measured. Increasing CME content did not significantly alter crystal surface area. However, nonuniform strain increased and crystallite size decreased in a dose-response manner, both reaching saturation at a CME concentration of 3 mg/ and demonstrating unequivocally the inclusion of increasing quantities of proteins in the crystals. This was confirmed by Western blotting. Crystal dissolution also followed saturation kinetics, increasing proportionally with final CME concentration and reaching a plateau at a concentration of approximately 2 mg/l. These findings were complemented by field emission scanning electron microscopy, which showed that crystal degradation also increased relative to CME concentration. Intracrystalline proteins enhance degradation and dissolution of CaOx crystals and thus may constitute a natural defense against urolithiasis. The findings have significant ramifications in biomineral metabolism and pathogenesis of renal stones.
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PMID:Intracrystalline urinary proteins facilitate degradation and dissolution of calcium oxalate crystals in cultured renal cells. 1807 96