Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A variety of analogs of 1,25-(OH)2D3 with less calcemic activity and lower receptor binding affinity than 1,25-(OH)2D3 have been developed. However, these compounds have equal or greater ability to differentiate leukemia cells and psoriatic fibroblasts and to suppress PTH synthesis and secretion. The mechanism for this selectivity has not been elucidated. Because the lower potency of ergocalciferol compared to cholecalciferol in preventing or curing rickets in chicks was associated with a lower affinity of the avian vitamin D binding protein (DBP) for vitamin D2, we tested five analogs with low calcemic activity including 22-oxa-1,25-(OH)2D3 (OCT), MC903, 1,25-(OH)2-16 ene-23-yne D3, 1,25-(OH)2-26,27 dihomo-22-ene-D3, and 1,25-(OH)2-24-trihomo-22-ene-D3 for their affinity for rat serum DBP. All analogs had a low affinity for DBP, ranging from 50-3000 times less than that of 1,25-(OH)2D3. OCT also bound with low affinity to dog and human serum DBP. We tested with OCT the possible consequences of its low affinity for serum DBP. One of the functions of DBP is to prolong the lifetime of 1,25-(OH)2D3 in circulation. Quantification of the metabolic clearance rate (MCR) of OCT in 8 normal dogs using a single bolus injection technique showed that OCT was cleared at a rate of 48.2 +/- 7.5 ml/min, approximately 6-7 times more rapidly than 1,25-(OH)2D3 (6.8 +/- 0.4 ml/min). The estimated half-life of OCT in the circulation was 2.5 +/- 0.3 h compared to 7.0 +/- 0.6; n = 7 for 1,25-(OH)2D3. As our primary interest is the potential of OCT in treating the secondary hyperparathyroidism of CRF, we also measured the MCR of OCT in 5/6 nephrectomized dogs. Uremia does not affect the rate of clearance of OCT from the circulation (MCR: 56.8 +/- 4.5; t1/2 = 2.1 +/- 0.2 n = 4). Despite its shorter half-life, OCT suppressed PTH secretion in vivo in uremic dogs. The effects of low binding to DBP on the percentage uremic dogs. The effects of low binding to DBP on the percentage of free sterol were determined using an ultrafiltration procedure. We compared the proportion of free (unbound) OCT and 1,25-(OH)2D3 in 0.1% BSA-PBS with concentrations of human serum ranging from 0-25%. The proportion of OCT in the free form was significantly higher than that of 1,25-(OH)2D3 for every serum concentration tested. The physiological relevance of a higher percentage of free OCT was tested in normal human macrophages.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:On the mechanisms for the selective action of vitamin D analogs. 200 95

The removal of protein-bound substances of pathogenetic relevance from blood is of therapeutic interest for drug intoxications, renal and liver failure, and metabolic disorders. Current methods using adsorbents are effective but often not specific enough. This work presents an alternative method that enables the dialyzability of albumin-bound toxins from plasma by the use of a high-flux dialyzer (F 60 Fresenius) and an albumin solution circulating on the dialysate side to increase selectively the affinity for albumin-bound toxins. This method resulted in effective removal of unconjugated bilirubin, drugs with a high protein-binding ratio (sulfobromophthalein, theophylline), and a protein-bound toxin (phenol). The additional removal of PBS could extend the applicability of dialysis, for example, to drug intoxications and liver failure or could improve the elimination of protein-bound uremic toxins in chronic renal failure.
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PMID:Dialysis against a recycled albumin solution enables the removal of albumin-bound toxins. 824 75

Carbazate groups were grafted on the commercial cellulose membrane (CM) to specifically scavenge the carbonylated proteins for hemodialysis. It confirmed that carbazate groups were successfully covalently attached on the CMs by XPS and EDS, and the modified CMs still saved their original morphology and crystalline structures by SEM and XRD. Furthermore, the modified CMs presented favorable physicochemical stability at wide pH range from 2.5 to 7.4. It was also found that the carbazate modified CMs could selectively remove carbonylated proteins from acrolein treated bovine serum albumin (BSA) or ESRD patient's blood serum in PBS buffer. The modified CMs showed the potential to be utilized as the substitute of dialysis membranes in hemodialysis.
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PMID:Weak acidic stable carbazate modified cellulose membranes target for scavenging carbonylated proteins in hemodialysis. 3188 49