Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the liver that is characterized by progressive cholestasis and the development of secondary biliary cirrhosis. There is no widely recognized therapy for this disease, although anti-inflammatory agents (steroids), immunosuppressive agents (methotrexate), anti-fibrotics (colchicine), and choleretic agents (ursodeoxycholic acid) have been used in various small series. In the present study, Tacrolimus (FK 506), a new and powerful immunosuppressive macrolide antibiotic, has been used to treat 10 patients with PSC. Each subject had a liver biopsy, ERCP with visualization of the intra- and extrahepatic biliary tree, and a panel of hematological, serological, and biochemical laboratory tests before the initiation of the FK 506 therapy. The FK 506 was administered orally at 12-h intervals and was monitored by serial plasma FK 506 trough levels. After 360 days of treatment, the median serum bilirubin level was reduced by 75%, and the serum alkaline phosphatase was reduced by 70%. Moreover, the serum ALT and AST levels were reduced by 80 and 86%, respectively. No change in the serum level of BUN and creatinine levels occurred as a consequence of the FK 506 treatment. These data demonstrate that: 1) FK 506 can be used to treat PSC; 2) the response to FK 506 by patients with PSC is rapid; and, 3) no adverse effect on the serum BUN and creatinine levels was observed. It is anticipated that FK 506 will become an important agent for the treatment of patients with PSC because of its powerful immunosuppressive activity.
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PMID:Tacrolimus (FK 506), a treatment for primary sclerosing cholangitis: results of an open-label preliminary trial. 753 12

The authors studied the effect of hematocrit, bilirubin, and alkaline phosphatase on microparticle enzyme immunoassay for tacrolimus II (MEIA II) using specimens of whole blood obtained from 33 patients undergoing cyclosporine treatment. Tacrolimus was added to these samples at a final concentration of 7.5 microg/L and 15 microg/L. Both coefficients of variation were over 20% (21% at 7.5 macrog/L of tacrolimus and 22% at 15 microg/L of tacrolimus). No correlation was found between bilirubin and tacrolimus concentrations or between alkaline phosphatase and tacrolimus concentrations. On the other hand, negative correlations were found between hematocrit values and tacrolimus concentrations (r2 = 0.47; P < 0.0001 at 7.5 microg/L tacrolimus, r2 = 0.54; P < 0.0001 at 15 microg/L tacrolimus). Negative correlations were also found between hematocrit and the tacrolimus concentration using normal human red blood cells diluted with physiological saline solution (r2 = 0.93; P < 0.0001 at 7.5 microg/L tacrolimus, r2 = 0.91; P < 0.0001 at 15 microg/L tacrolimus). The results showed that the hematocrit interferes with the MEIA II for tacrolimus, and the magnitude of the interference is clinically significant. Beyond the normal range of hematocrit values, caution should be exercised in interpreting results as one may need to compensate for the levels of tacrolimus.
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PMID:Interference of hematocrit in the tacrolimus II microparticle enzyme immunoassay. 1276 49

Topical tacrolimus represents an effective and well-tolerated treatment for atopic dermatitis (AD). Its known effects include reduced production of proinflammatory cytokines and reduced chemokine gradient. We performed lesional skin biopsies on adult patients affected by moderate-to-severe AD. Then, patients were randomized to receive local treatment with tacrolimus ointment 0.1% and hydrocortisone butyrate ointment 1%. On the 21st day of treatment, another skin specimen was taken. Nine patients treated with tacrolimus and seven treated with hydrocortisone successfully concluded the trial. By immunohistochemistry (alkaline phosphatase/antialkaline phosphatase method), we demonstrated that endothelial leucocyte adhesion molecule (ELAM)-1, vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 showed different intensities and patterns of expression in untreated AD lesions. Tacrolimus-treated specimens featured a significant reduction of the expression of ELAM-1, VCAM-1 and ICAM-1, while hydrocortisone-treated lesions did not. Inhibition of adhesion molecule expression may represent another selective mechanism of action of topical tacrolimus in AD.
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PMID:Expression of adhesion molecules in atopic dermatitis is reduced by tacrolimus, but not by hydrocortisone butyrate: a randomized immunohistochemical study. 1704 Feb 64

Tacrolimus is used for transplant patients with refractory graft rejection and those with intolerance to cyclosporin (CsA), without the disfiguring adverse effects frequently attributed to CsA therapy. Since we have shown that CsA-associated bone loss can also affect alveolar bone, the purpose of this study was to evaluate the effects of conversion of monotherapy from CsA to tacrolimus on alveolar bone loss in rats. Groups of rats were treated with either CsA (10 mg/kg/day, s.c.), tacrolimus (1 mg/kg/day, s.c.), or drug vehicle for 60 and 120 days, and an additional group received CsA for 60 days followed by conversion to tacrolimus for a further 60-day period. Bone-specific alkaline phosphatase (BALP), tartrate-resistent acid phosphatase (TRAP-5b), calcium (Ca(2+)), interleukin (IL)-1beta, IL-6, and tumor necrosis factor alpha (TNF-alpha) concentrations were evaluated in the serum. Analyses of bone volume, bone surface, number of osteblasts, and osteoclasts were performed. Treatment with CsA for either 60 or 120 days was associated with bone resorption, represented by lower bone volume and increased number of osteoclasts; serum BALP, TRAP-5b, IL-1beta, IL-6, and TNF-alpha were also higher in these animals. After conversion from CsA to tacrolimus, all the altered serum markers returned to control values in addition to a significant increase of bone volume and a lower number of osteoclasts. This study shows that conversion from CsA to tacrolimus therapy leads to a reversal of the CsA-induced bone loss, which can probably be mediated by downregulation of IL-1beta, IL-6, and TNF-alpha production.
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PMID:Conversion of immunosuppressive monotherapy from cyclosporin a to tacrolimus reverses bone loss in rats. 1761 78

Tacrolimus (FK506) has been used as a therapeutic drug beneficial for the treatment of rheumatoid arthritis in humans. In this study, we investigated the effects of FK506 on cellular differentiation in cultured chondrogenic cells. Culture with FK506 led to a significant and concentration-dependent increase in Alcian blue staining for matrix proteoglycan at 0.1 to 1,000 ng/ml, but not in alkaline phosphatase (ALP) activity, in ATDC5 cells, a mouse pre-chondrogenic cell line, cultured for 7 to 28 days, while the non-steroidal anti-inflammatory drug indomethacin significantly decreased Alcian blue staining in a concentration-dependent manner, without altering ALP activity. FK506 significantly increased the expression of mRNA for both type II and type X collagen, but not for osteopontin, in ATDC5 cells. Similar promotion was seen in chondrogenic differentiation in both mouse metatarsals and chondrocytes cultured with FK506. However, FK506 failed to significantly affect transcriptional activity of the reporter construct for either sry-type HMG box 9 (Sox9) or runt-related transcription factor-2 (Runx2), which are both transcription factors responsible for chondrocytic maturation as a master regulator. These results suggest that FK506 may predominantly promote cellular differentiation into proliferating chondrocytes through a mechanism not relevant to the transactivation by either Sox9 or Runx2 in chondrogenic cells.
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PMID:Predominant promotion by tacrolimus of chondrogenic differentiation to proliferating chondrocytes. 1927 Apr 31