Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020500 (hyperoxaluria)
 912 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxalate degradation by the anaerobic bacterium Oxalobacter formigenes is important for human health, helping to prevent hyperoxaluria and disorders such as the development of kidney stones. Oxalate-degrading activity cannot be detected in the gut flora of some individuals, possibly because Oxalobacter is susceptible to commonly used antimicrobials. Here, clarithromycin, doxycycline, and some other antibiotics inhibited oxalate degradation by two human strains of O. formigenes. These strains varied in their response to gut environmental factors, including exposure to gastric acidity and bile salts. O. formigenes strains established oxalate breakdown in fermentors which were preinoculated with fecal bacteria from individuals lacking oxalate-degrading activity. Reducing the concentration of oxalate in the medium reduced the numbers of O. formigenes bacteria. Oxalate degradation was established and maintained at dilution rates comparable to colonic transit times in healthy individuals. A single oral ingestion of O. formigenes by adult volunteers was, for the first time, shown to result in (i) reduced urinary oxalate excretion following administration of an oxalate load, (ii) the recovery of oxalate-degrading activity in feces, and (iii) prolonged retention of colonization.
 ...
PMID:Oxalobacter formigenes and its potential role in human health. 1214 79

An early diagnostics of metabolism disorders by using different methods is still acute. In this respect, the crytstal-optic examination of the metabolism structures of blood serum, implemented in a polarized light (microscope MIN-8) is in the focus of attention. We studied the structure of blood serum of 160 patients with various metabolic disorders. The examinations were made through drying up, under control, the blood serum drops between two isotropic plates, the mentioned preparations were subsequently kept in the open air and examined under the microscope in polarized light. Simultaneously, the below substances were identified in the blood serum: oxalic acid, creatinines, total calcium, glycine, uric acid and cholesterol. In accordance with metabolic disorders, crystals were isolated, which characterize a type of a metabolic disorder. Thus, the fan-type dendrites are indicative of hyperoxaluria, druses and dendrite-like spherulites--hypercreatinemia; oolite spherulities are indicative of hypercalcemia, fine-grained particles are typical for hyperglycinemia, feather-like rays are typical for hyperuricemia and cross-like spherulites are typical of hypercholesterolemia. The suggested method improves the control over a type of metabolic disorder, and it can be used in the express diagnostics of a pre-pathology and pathology of metabolism.
 ...
PMID:[Polarization microscopy in diagnosis of metabolic disorders]. 1271 90

Proteins are thought to play a major role in stone formation. Oxalate binding protein plays a vital role in the transport of oxalate. This study was aimed at determining whether hyperoxaluria induces the expression of nuclear pore complex oxalate binding protein p62 which has the transport function. Hyperoxaluria was induced in male Wistar rats by feeding 0.75% ethylene glycol in water. The oxalate binding activity of the nuclear pore complex protein increased markedly during experimental hyperoxaluria, whereas nuclear lamina had no binding at all. There was an alteration in the elution profile of the nuclear pore complex oxalate binding protein during the hyperoxaluric condition. The protein was purified and had a molecular weight of 62 kDa (data not shown). The purified protein showed cross-reactivity with the monoclonal antibody (MAb 414) and it showed homogeneity. The expression of this protein (p62) during the hyperoxaluric condition was determined by ELISA and a 3-fold increase was observed when compared to control rats. The increased expression is further confirmed by Western blotting and immunohistochemistry. The increase in p62 protein expression may be either due to increased expression of certain genes or degradation of the cell membrane by oxalate-induced cell injury. Thus, the present study suggests that the increased expression of this protein (p62) may be due to the oxalate induction.
 ...
PMID:Expression of nuclear pore complex oxalate binding protein p62 in experimental hyperoxaluria. 1529 81

Oxalate induced renal calculi formation and the associated renal injury is thought to be caused by free radical mediated mechanisms. An in vivo model was used to investigate the effect of phycocyanin (from Spirulina platensis), a known antioxidant, against calcium oxalate urolithiasis. Male Wistar rats were divided into four groups. Hyperoxaluria was induced in two of these groups by intraperitoneal infusion of sodium oxalate (70 mg/kg) and a pretreatment of phycocyanin (100 mg/kg) as a single oral dosage was given, 1h prior to sodium oxalate infusion. An untreated control and drug control (phycocyanin alone) were also included in the study. We observed that phycocyanin significantly controlled the early biochemical changes in calcium oxalate stone formation. The antiurolithic nature of the drug was evaluated by the assessment of urinary risk factors and light microscopic observation of urinary crystals. Renal tubular damage as divulged by urinary marker enzymes (alkaline phosphatase, acid phosphatase and gamma-glutamyl transferase) and histopathological observations such as decreased tubulointerstitial, tubular dilatation and mononuclear inflammatory cells, indicated that renal damage was minimised in drug-pretreated group. Oxalate levels (P < 0.001) and lipid peroxidation (P < 0.001) in kidney tissue were significantly controlled by drug pretreatment, suggesting the ability of phycocyanin to quench the free radicals, thereby preventing the lipid peroxidation mediated tissue damage and oxalate entry. This accounts for the prevention of CaOx stones. Thus, the present analysis revealed the antioxidant and antiurolithic potential of phycocyanin thereby projecting it as a promising therapeutic agent against renal cell injury associated kidney stone formation.
 ...
PMID:Prophylactic role of phycocyanin: a study of oxalate mediated renal cell injury. 1529 40

Oxalate degrading enzymes have a number of potential applications, including medical diagnosis and treatments for hyperoxaluria and other oxalate-related diseases, the production of transgenic plants for human consumption, and bioremediation of the environment. This review seeks to provide a brief overview of current knowledge regarding the major classes of enzymes and related proteins that are employed in plants, fungi, and bacteria to convert oxalate into CO(2) and/or formate. Not only do these enzymes employ intriguing chemical strategies for cleaving the chemically unreactive C-C bond in oxalate, but they also offer the prospect of providing new insights into the molecular processes that underpin the evolution of biological catalysts.
 ...
PMID:The enzymes of oxalate metabolism: unexpected structures and mechanisms. 1558 76

Exposure to oxalate, a constituent of the most common form of kidney stones, generates toxic responses in renal epithelial cells, including altered membrane surface properties and cellular lipids, changes in gene expression, disruption of mitochondrial function, formation of reactive oxygen species and decreased cell viability. Oxalate exposure activates phospholipase A2 (PLA2), which increases two lipid signaling molecules, arachidonic acid and lysophosphatidylcholine (Lyso-PC). PLA2 inhibition blocks, whereas exogenous Lyso-PC or arachidonic acid reproduce many of the effects of oxalate on mitochondrial function, gene expression and cell viability, suggesting that PLA2 activation plays a role in mediating oxalate toxicity. Oxalate exposure also elicits potentially adaptive or protective changes that increase expression of proteins that may prevent crystal formation or attachment. Additional adaptive responses may facilitate removal and replacement of dead or damaged cells. The presence of different inflammatory cells and molecules in the kidneys of rats with hyperoxaluria and in stone patients suggests that inflammatory responses play roles in stone disease. Renal epithelial cells can synthesize a variety of cytokines, chemoattractants and other molecules with the potential to interface with inflammatory cells; moreover, oxalate exposure increases the synthesis of these molecules. The present studies demonstrate that oxalate exposure upregulates cyclooxygenase-2, which catalyzes the rate-limiting step in the synthesis of prostanoids, compounds derived from arachidonic acid that can modify crystal binding and may also influence inflammation. In addition, renal cell oxalate exposure promotes rapid degradation of IkappaBalpha, an endogenous inhibitor of the NF-kappaB transcription factor. A similar response is observed following renal cell exposure to lipopolysaccharide (LPS), a bacterial cell wall component that activates toll-like receptor 4 (TLR4). While TLRs are primarily associated with immune cells, they are also found on many other cell types, including renal epithelial cells, suggesting that TLR signaling could directly impact renal function. Prior exposure of renal epithelial cells to oxalate in vitro produces endotoxin tolerance, i.e. a loss of responsiveness to LPS and conversely, prior exposure to LPS elicits a similar heterologous desensitization to oxalate. Renal cell desensitization to oxalate stimulation may have profound effects on the outcome of renal stone disease by impairing protective responses.
 ...
PMID:Oxalate toxicity in renal cells. 1628 83

It is hypothesized that oxalate plays an active role in calcium oxalate (CaOx) nephrocalcinosis and oxalate driven nephrolithiasis by interacting with the kidney. We developed an adjustable, nonprecursor, continuous infusion model of hyperoxaluria and CaOx nephrocalcinosis to investigate this hypothesis. Minipumps containing PBS or KOx (60-360 micromol/day; n = 5-7/dose) were implanted subcutaneously in male Sprague-Dawley rats on D0 and D6. Rats were killed on D13. Oxalate excretion and CaOx crystalluria were monitored by 20+4 h urine collections. Localization and content of intrarenal crystals were determined on frozen sections using polarization and microFTIR. Oxalate excretion was significantly elevated in all KOx rats (P < or = 0.005). CaOx crystalluria was most persistent in the 240-360 micromol/day KOx rats, but even 60 micromol/day KOx rats showed sporadic crystalluria. One hundred percent of KOx rats had CaOx nephrocalcinosis as confirmed by microFTIR. Most crystals were localized to the lumens of the corticomedullary collecting ducts. A few crystals are localized just under the papillar urothelium. The minipump model is the first model of hyperoxaluria to provide continuous infusion of oxalate. It permits control of the levels of hyperoxaluria, crystalluria and CaOx nephrocalcinosis. The level of sustained hyperoxaluria and CaOx nephrocalcinosis induced by treatment with 360 micromol/day KOx for 13D models the conditions frequently observed in jejunoileal bypass patients. Adjustments in the length of treatment and level of hyperoxaluria may allow this model to also be used to study the oxalate driven CaOx-nephrolithiasis common in patients with hyperoxaluria due to other causes.
 ...
PMID:Continuous infusion of oxalate by minipumps induces calcium oxalate nephrocalcinosis. 1647 91

Of decisive importance for the many research groups all over Europe were the scientific symposia dealing with the theoretical foundations and clinical aspects of urinary stone disease. There were several sources from which today's European Urinary Stone meetings and the "Eurolithiasis Society" itself arose. It was a long way from Leeds in 1968 to Jena 1970, Bonn-Vienna in 1972 and to 11 European meetings from 1989 to 2005. Which developments in urinary stone disease research have been presented at our congresses during the past 40 years? The 1970s and 1980s are the years marked by efforts to measure the important lithogenic substances such as calcium, ionized calcium, uric acid, phosphate, oxalate with reliable methods. Hypercalciuria and specifically mild hyperoxaluria were the topics of numerous investigations in the 1970s, 1980s and 1990s. The calcium-loading test described by Pak has been discussed frequently since its application. It became apparent that oxalic acid is more important in urinary stone formation than hypercalciuria. Of importance were investigations done by Robertson and his colleagues on the influence of diet (in particular, an animal protein-rich diet) on urinary stone formation. Another emphasis of research was investigation of the crystallization process: supersaturation, crystal growth and aggregation are important steps in urinary stone formation. Of great importance in the formation of urinary stones are inhibitors (inhibitory activity): citrate, magnesium, pyrophosphate, macromolecules: GAGs, THP etc. and it became possible in the early 1970s to determine substances such as Tamm-Horsfall protein (THP) and GAGs. Much attention in the 1970s and 1980s was focused on urinary stone analysis (X-ray diffraction, infrared spectroscopy, polarization microscopy) and standardization of these methods. In the mid-1980s, a whole series of epidemiological studies were carried out, with data for the Federal Republic of Germany, East Germany, Czechoslovakia and Austria. The search for "stone-removing" medications, their description and clinical use was the subject of much clinical research and in vitro examinations. A definite advance occurred in the 1980s with the development of new instrumental technologies for the management of urinary stones such as shockwave ("Stosswelle") lithotripsy, percutaneous nephrolithotomy and ureterorenoscopy (" breakthrough innovations"). Since the 8th European Urolithiasis Symposium there have regularly been presentations pertaining to the topic of the molecular basis of inherited lithiasis. The last 10-15 years have shown an increasing turning toward the importance of cellular alterations and supersaturation and their relation to stone formation. In conclusion, I would like to note that it is of decisive importance for the research groups all over Europe to organize scientific symposia dealing with the theoretical foundations and clinical aspects of urinary stone disease under the protection of the European Urolithiasis Society.
 ...
PMID:Thirty-eight years of stone meetings in Europe. 1650 36

Oxalic acid is found in dietary sources (such as coffee, tea, and chocolate) or is produced by the intestinal microflora from metabolic precursors, like ascorbic acid. In the human intestine, oxalate may combine with calcium, sodium, magnesium, or potassium to form less soluble salts, which can cause pathological disorders such as hyperoxaluria, urolithiasis, and renal failure in humans. In this study, an operon containing genes homologous to a formyl coenzyme A transferase gene (frc) and an oxalyl coenzyme A decarboxylase gene (oxc) was identified in the genome of the probiotic bacterium Lactobacillus acidophilus. Physiological analysis of a mutant harboring a deleted version of the frc gene confirmed that frc expression specifically improves survival in the presence of oxalic acid at pH 3.5 compared with the survival of the wild-type strain. Moreover, the frc mutant was unable to degrade oxalate. These genes, which have not previously been described in lactobacilli, appear to be responsible for oxalate degradation in this organism. Transcriptional analysis using cDNA microarrays and reverse transcription-quantitative PCR revealed that mildly acidic conditions were a prerequisite for frc and oxc transcription. As a consequence, oxalate-dependent induction of these genes occurred only in cells first adapted to subinhibitory concentrations of oxalate and then exposed to pH 5.5. Where genome information was available, other lactic acid bacteria were screened for frc and oxc genes. With the exception of Lactobacillus gasseri and Bifidobacterium lactis, none of the other strains harbored genes for oxalate utilization.
 ...
PMID:Transcriptional and functional analysis of oxalyl-coenzyme A (CoA) decarboxylase and formyl-CoA transferase genes from Lactobacillus acidophilus. 1651 36

Hyperoxaluria is a risk factor for renal stones. It appears to be sustained by increased dietary load or increased intestinal absorption. The aim of this study was to evaluate whether oral administration of lactobacilli could prevent urolithiasis in stone-forming rats. Oxalate-degrading activities of lactobacilli were evaluated by measuring the oxalate level in a culture medium after inoculation with lactobacilli. Only the strains of Lactobacillus having oxalate-degrading activity were used. Sprague-Dawley rats were fed a powdered standard diet containing 3% sodium oxalate and/or received 100 mg/kg of celecoxib for the first 8 days by gavage, before or after the beginning of this experiment (groups with previous treatment or with co-treatment). Rats were sacrificed after 4 weeks and kidneys were harvested for the assay of crystal formation under a dissecting microscope. Twenty-four-hour urine collections were performed before kidney harvest. Only two strains, Lactobacillus casei HY2743 and L. casei HY7201 out of 31 strains of Lactobacillus were able to degrade oxalate. In both groups of co-treatment and previous treatment with L. casei HY2743 and L. casei HY7201, urine oxalate excretion decreased compared to the group without lactobacilli. The dissecting microscope examination of kidneys in the rats in two previous treatment groups and the co-treatment group with L. casei HY7201 showed less abundant crystals than control groups. Our results show that lactobacilli may be used as a potential therapeutic strategy in the prevention of urinary stones.
 ...
PMID:Prevention of nephrolithiasis by Lactobacillus in stone-forming rats: a preliminary study. 1663 9


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>