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)

Urinary excretion of oxalate is one of risk factors in urinary stone formation. Prevention of undesirable overflow into the production of oxalate definitely leads to a decrease of urolithiasis. The activity of serine : pyruvate/alanine : glyoxylate aminotransferase (SPT/AGT) or glyoxylate reductase/hydroxypyruvate reductase (GRHPR), the key enzyme of primary hyperoxlauria type 1 and 2, respectively, and their subcellular distribution highly affects the oxalate production. On the other hand, urolithiasis is tightly related to lifestyle disease, such as diabetes mellitus and insulin resistance. The hypothesis that insulin resistance induces mitochondria dysfunction, resulting in the decrease of mitochondria-related enzyme activity is a very attractive new treatment strategy of urolithiasis. Namely, the improvement of insulin resistance might prevent stone formation.
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PMID:[Future perspective in the treatment of urolithiasis based on oxalate metabolism]. 2130 60

Primary hyperoxalurias (PH) are inborn errors in the metabolism of glyoxylate and oxalate. PH type 1, the most common form, is an autosomal recessive disorder caused by a deficiency of the liver-specific enzyme alanine, glyoxylate aminotransferase (AGT) resulting in overproduction and excessive urinary excretion of oxalate. Recurrent urolithiasis and nephrocalcinosis are the hallmarks of the disease. As glomerular filtration rate decreases due to progressive renal damage, oxalate accumulates leading to systemic oxalosis. Diagnosis is often delayed and is based on clinical and sonographic findings, urinary oxalate assessment, DNA analysis, and, if necessary, direct AGT activity measurement in liver biopsy tissue. Early initiation of conservative treatment, including high fluid intake, inhibitors of calcium oxalate crystallization, and pyridoxine in responsive cases, can help to maintain renal function in compliant subjects. In end-stage renal disease patients, the best outcomes have been achieved with combined liver-kidney transplantation which corrects the enzyme defect.
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PMID:Primary hyperoxaluria. 2174 1

The ethanolic extract of Acalypha indica was tested for its biopotency on membrane bound enzymes and marker enzymes in urolithiasis in male wistar albino rats. Calcium oxalate urolithiasis was induced by 0.75% ethylene glycol in drinking water for 30 days. There was a significant decrease in membrane bound enzymes such as Ca(2+) ATPase, Mg(2+) ATPase, Na(+)K(+) ATPase and marker enzymes Aspartate Transaminase (AST), Alanine Transaminase (ALT), Acid phosphatase (ACP) and Alkaline Phosphatase (ALP) in liver and kidney. The AST, ALT, ACP and ALP were increased in serum and urine of rats. Therapeutic treatment with plant extract (200mg/kg b.wt.dose(-1) day(-1) oral(-1)) has significantly ameliorated to near normalcy in the curative group. These results of the present study concluded that A. indica can play an important role in the prevention of disorders associated with kidney stone formation.
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PMID:Biopotency of Acalypha indica Linn on Membrane Bound ATPases and Marker Enzymes urolithic Rats. 2273 83

In July 2009, a 14-yr-old male caracal (Caracal caracal) at the National Zoological Gardens of South Africa was found, on abdominal ultrasound, to have a single large cystolith. The cystolith was removed, and the composition was determined to be 100% cystine. Blood and urine samples were also collected from three other apparently healthy caracals at the zoo and were submitted, together with the samples from the affected animal, for analysis using gas chromatograph mass spectrometry for cystine, lysine, alanine, and ornithine levels. The cystine levels in the urine, the fractional excretion of cystine, and the normalized excretion of cystine (micromol/g of creatinine) were all higher in the affected caracal than in the healthy animals. Only a single other case of cystine urolithiasis has been previously reported in any wild felid in the literature.
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PMID:Cystine urolithiasis in a caracal (Caracal caracal). 2308 35

Primary hyperoxaluria type 1 (PH1) is a rare metabolic disorder characterized by a defect in the liver-specific peroxisomal enzyme alanine-glyoxylate and serine-pyruvate aminotransferase (AGT). This disorder results in hyperoxaluria, recurrent urolithiasis, and nephrocalcinosis. Three forms of PH1 have been reported. Data on the infantile form of PH1 are currently limited in literature. Despite the fact that China is the most populated country in the world, only a few AGXT mutations have been reported in several Chinese PH1 patients. In the present study, we investigated a Chinese family in which two siblings are affected by the infantile form of PH1. Sanger sequencing was carried out on the proband, but the results were misleading. Two novel missense mutations (c.517T > C/p.Cys173Arg and c.667A > C/p.Ser223Arg) of the AGXT gene were successfully detected through whole-exome sequencing. These two mutations occurred in the highly conserved residues of the AGT. Four software programs predicted both mutations as the cause of the disease. A postmortem examination was performed and revealed the occurrence of global nephrocalcinosis on both kidneys. The crystals were collected and analyzed as calcium oxalate monohydrate. This study extends the knowledge on the clinical phenotype-genotype correlation of the AGXT mutation. That is, (i) two novel missense mutations were identified for the infantile form of PH1 and (ii) the same AGXT genotype caused the same infantile form of PH1 within the family.
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PMID:Two Novel AGXT Mutations Cause the Infantile Form of Primary Hyperoxaluria Type I in a Chinese Family: Research on Missed Mutation. 3078 79

Primary hyperoxaluria type I is caused by mutations in the alanine glyoxylate aminotransferase gene (AGXT), leading to accumulation of glyoxylate and subsequent production of oxalate and urolithiasis. Here, we generated a novel rat model of primary hyperoxaluria type I that carries a D205N mutation in the partially humanized Agxt gene through the CRISPR/Cas9 system. The AgxtD205N mutant rats showed undetectable alanine glyoxylate aminotransferase protein expression, developed hyperoxaluria at 1 month of age and exhibited severe renal calcium oxalate deposition after ethylene glycol challenge. This suggests our novel model is more relevant to the human disease than existing animal models. To test whether this model could be used for the development of innovative therapeutics, SaCas9 targeting hydroxyacid oxidase 1, responsible for metabolizing glycolate into glyoxylate, was delivered via adeno-associated viral vectors into newborn rats with primary hyperoxaluria type 1. This approach generated nearly 30% indels in the Hao1 gene in the liver, leading to 42% lower urine oxalate levels in the treated group than in the control group and preventing the rats with primary hyperoxaluria type 1 from undergoing severe nephrocalcinosis for at least 12 months. Thus, our results demonstrate that this partially humanized AgxtD205N rat strain is a high-performing model of primary hyperoxaluria type 1 for understanding pathology, and the development of novel therapeutics, such as reprogramming of the metabolic pathway through genome editing.
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PMID:CRISPR/Cas9-mediated metabolic pathway reprogramming in a novel humanized rat model ameliorates primary hyperoxaluria type 1. 3282 Oct 3


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