Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

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

This study was designed to test the hypothesis that formulation of hepatitis B vaccine with tetradecyl-beta-maltoside (TDM) enhances the immune response after pulmonary administration in a rodent model. Commercially available recombinant hepatitis B vaccine (rHBV) was formulated with varying concentrations of TDM and administered intratracheally to anesthetized male Sprague-Dawley rats. rHBV administered intramuscularly at doses of 2 and 4 microg served as positive controls. All formulations were administered on days 0 and 14 and the immune response was evaluated for 28 days. Specific antibodies generated to HBsAg were analyzed by ELISA. Safety studies were carried out by measuring the levels of alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and tumor necrosis factor alpha (TNF-alpha) in bronchoalveolar lavage (BAL) fluid. There was a significant increase in the immune response when the vaccine was administered intramuscularly at a dose of 4 microg. Only a modest increase in the immune response was observed when plain rHBV was administered intratracheally at the same dose. However, a pulmonary formulation of 4 microg rHBV plus 0.5% TDM produced a fourfold increase in the immune response compared to plain rHBV administered via the pulmonary route. No increase in immune response was observed for formulations containing rHBV plus 0.125% or 0.25% TDM. The levels of ALP and LDH in the BAL fluid suggest that the hepatitis B vaccine plus TDM formulations cause some injury to the lungs after the first intratracheal instillation of the formulation; however, the enzyme levels tended to be lower after the second instillation. The level of TNF-alpha in the BAL fluid of TDM-treated rats was substantially lower than that in rats treated with the positive control substance, sodium dodecyl sulfate. Overall, rHBV formulated with TDM increases the immune response after pulmonary administration, and pulmonary formulation of rHBV plus TDM could be used as an alternative to needle-based delivery of hepatitis B vaccine.
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PMID:Feasibility study of inhaled hepatitis B vaccine formulated with tetradecylmaltoside. 1782 46

The proinflammatory cytokine tumor necrosis factor alpha seems to play a major role in the pathogenesis of both rheumatoid arthritis and primary biliary cirrhosis. We describe the case of a 46-year-old female patient with rheumatoid arthritis and concomitant primary biliary cirrhosis treated with anti-tumor necrosis factor alpha agents. During infliximab treatment we observed a poor clinical response and persistence of liver function test abnormalities. After infliximab interruption the levels of alkaline phosphatase dropped and had nearly reached normal values when etanercept was started. This new therapeutic regimen was well tolerated with joint clinical improvement and normalization of alkaline phosphatase. This single case shows that etanercept therapy maintained liver enzymes within the normal range and controlled the arthritis with a 30-month follow-up whereas infliximab did not account for similar results.
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PMID:Effect of tumor necrosis factor alpha antagonists in a patient with rheumatoid arthritis and primary biliary cirrhosis. 1789 Jan 33

The aim of this study was to investigate the effects of combinations of pegilated-interferon (PEG-IFN), ribavirin, and danazol on thrombocytopenia and liver injury in rats with fibrosis. Male adult Wistar rats were treated with either mineral oil, danazol (0.83 mg/kg per day), PEG-interferon alpha-2a (PEG-IFN, 0.3 microg/ week) + ribavirin (12 mg/kg per day), PEG-IFN + ribavirin + danazol, CCl(4) (4 g/kg for eight weeks), CCl(4) + PEG-IFN + ribavirin, or CCl(4) + PEG-IFN + ribavirin+ danazol. The following assays were conducted: hematology, clinical chemistry, liver function, liver fibrosis, lymphocyte cytokine mRNA expression, and bone-marrow DNA content. Platelet counts were low in sham-treated animals and animals treated with PEG- IFN + ribavirin (30% and 25% respectively; P < 0.05). PEG-IFN + ribavirin + danazol reduced platelet counts of fibrotic animals by only 9% (P < 0.05). PEG- IFN + ribavirin reduced hepatic collagen content by 50%, whereas danazol + PEG-IFN + ribavirin reduced hepatic collagen content by 60% (P < 0.05). PEG-IFN + ribavirin reduced the total bilirubin concentration by 27%, alanine amino transferase (ALT) activity by 75% and gamma-glutamyl transpeptidase (gamma-GTP) activity by 74% (P < 0.05). In contrast, danazol + PEG-IFN + ribavirin reduced total bilirubin levels by 61%, alkaline phosphatase activity by 45%, ALT activity by 76%, and gamma-GTP activity by 74% (P < 0.05). The only treatment that increased interleukin 10 (IL-10) mRNA in fibrotic rats was PEG-IFN + ribavirin. However, danazol + PEG-IFN + ribavirin reduced the expression of IL-6, IL-10, tumor necrosis factor alpha and transforming growth factor ss. Bone-marrow DNA content was not altered by any treatment. In conclusion, PEG-IFN + ribavirin + danazol could be a new therapeutic option for patients with liver injury, fibrosis, and thrombocytopenia.
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PMID:Combined therapy with danazol, pegilated interferon, and ribavirin improves thrombocytopenia and liver injury in rats with fibrosis. 1800 53

Mercuric chloride (HgCl(2)) is a widespread environmental toxin that affects mainly liver and kidney. The present study has been carried out to investigate the protective action of a protein (the CI protein) isolated from the herb, Cajanus indicus Spreng against HgCl(2) induced renal and hepatic toxicities in mice. Intraperitoneal administration of HgCl(2) at a dose of 5 mg/kg body weight for 1 d significantly reduced the activities of antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Moreover, it also depleted the glutathione to oxidized glutathione (GSH/GSSG) ratio. In addition, HgCl(2) increased the activities of serum marker enzymes (namely, glutamate pyruvate transaminase, GPT and alkaline phosphatase, ALP), creatinine, blood urea nitrogen and serum tumor necrosis factor alpha (TNF-alpha) level along with hepatic and renal lipid peroxidation. Besides, application of HgCl(2) to hepatocytes increased reactive oxygen species production and reduced the total antioxidant activity of the treated hepatocytes. Treatment with the CI protein intraperitoneally at a dose of 2 mg/kg body weight before or after HgCl(2) administration showed that it could scavenge free radicals in vitro and protect the alterations of the antioxidant molecules and the other parameters used in this particular study. Histological studies also revealed a milder lesion in kidney and liver samples of the CI protein treated mice compared to mice treated with HgCl(2) alone. Effects of a known antioxidant N-acetylcysteine have been used to compare its action to that of the CI protein.
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PMID:A protein from Cajanus indicus Spreng protects liver and kidney against mercuric chloride-induced oxidative stress. 1875 54

The purpose of this study was to investigate possible beneficial effects of morin on CCl(4)-induced acute hepatotoxicity in rats. Rats received a single dose of CCl(4) (150 microL/100 g 1:1 in corn oil). Morin treatment (20 mg/kg) was given at 48, 24, and 2 h before CCl(4) administration. CCl(4) challenge elevated serum alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) levels, but these effects were prevented by the pretreatment of rats with morin. To identify the mechanism of protective activity of morin in CCl(4)-induced hepatotoxicity in rats, we investigated expressions of tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and inducible nitric oxide (iNOS). The expressions of TNF-alpha, IL-1beta, IL-6, and iNOS were increased by CCl(4) treatment and increased expressions of those were decreased by morin. These findings suggest that morin prevents acute liver damage by inhibiting the production of TNF-alpha, IL-1beta, IL-6, and iNOS.
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PMID:Morin protects acute liver damage by carbon tetrachloride (CCl(4)) in rat. 1880 59

Nonalcoholic steatohepatitis (NASH) comprises dysregulation of lipid metabolism and inflammation. Identification of the various genetic and environmental susceptibility factors for NASH may provide novel treatments to limit inflammation and fibrosis in patients. This study utilized a mouse model of hypercholesterolemia, low-density lipoprotein receptor knockout (LDLr(-/-)) mice fed a high-fat diet for 5 months, to test the hypothesis that farnesoid X receptor (FXR) deficiency contributed to NASH development. Either the high-fat diet or FXR deficiency increased serum alanine aminotransferase activity, whereas only FXR deficiency increased bile acid and alkaline phosphatase levels. FXR deficiency and high-fat feeding increased serum cholesterol and triglycerides. Although high fat led to macrosteatosis and hepatocyte ballooning in livers of mice regardless of genotype, no inflammatory infiltrate was observed in the livers of LDLr(-/-) mice. In contrast, in the livers of LDLr(-/-)/FXR(-/-) mice, foci of inflammatory cells were observed occasionally when fed the control diet and were greatly increased when fed the high-fat diet. Consistent with enhanced inflammatory cells, hepatic levels of tumor necrosis factor alpha and intercellular adhesion molecule-1 mRNA were increased by the high-fat diet in LDLr(-/-)/FXR(-/-) mice. In agreement with elevated levels of procollagen 1 alpha 1 and TGF-beta mRNA, type 1 collagen protein levels were increased in livers of LDLr(-/-)/FXR(-/-) mice fed a high-fat diet. In conclusion, FXR deficiency induces pathologic manifestations required for NASH diagnosis in a mouse model of hypercholesterolemia, including macrosteatosis, hepatocyte ballooning, and inflammation, which suggest a combination of FXR deficiency and high-fat diet is a risk factor for NASH development, and activation of FXR may be a therapeutic intervention in the treatment of NASH.
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PMID:Farnesoid X receptor deficiency induces nonalcoholic steatohepatitis in low-density lipoprotein receptor-knockout mice fed a high-fat diet. 1894 97

Electrochemical assay using HeLa cell lines transfected with various plasmid vectors encoding SEAP (secreted alkaline phosphatase) as the reporter has been performed by using SECM (scanning electrochemical microscopy). The plasmid vector contains different responsive elements that include GRE (glucocorticoid response elements), CRE (cAMP responsive elements), or kappaB (binding site for NFkappaB (nuclear factor kappa B)) upstream of the SEAP sequence. The transfected HeLa cells were patterned on a culture dish in a 4x4 array of circles of diameter 300 microm by using the PDMS (poly(dimethylsiloxane)) stencil technique. The cellular array was first exposed to 100 ng mL(-1) dexamethasone, 10 ng mL(-1) forskolin, or 100 ng mL(-1) TNF-alpha (tumor necrosis factor alpha) after which it was further cultured in an RPMI culture medium for 6 h. After incubation, the cellular array was soaked in a measuring solution containing 4.7 mM PAPP (p-aminophenylphosphate) at pH 9.5, following which electrochemical measurements were performed immediately within 40 min. The SECM method allows parallel evaluation of different cell lines transfected with pGRE-SEAP, pCRE-SEAP, and pNFkappaB-SEAP patterned on the same solid support for detection of the oxidation current of PAP (p-aminophenol) flux produced from only 300 HeLa cells in each stencil pattern. The results of the SECM method were highly sensitive as compared to those obtained from the conventional CL (chemiluminescence) protocol with at least 5x10(4) cells per well.
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PMID:Development of electrochemical reporter assay using HeLa cells transfected with vector plasmids encoding various responsive elements. 1936 25

Scanning electrochemical microscopy (SECM) was used for the analysis of single-cell gene-expression signals on the basis of a reporter system. We microfabricated a single-cell array on an Indium tin oxide (ITO) electrode comprising 4 x 4 SU-8 microwells with a diameter of 30microm and a depth of 25microm. HeLa cells transfected with plasmid vectors encoding the secreted alkaline phosphatase (SEAP) were seeded in the microwell at a concentration of 1 cell per well by positive-dielectrophoresis (pDEP). A pDEP pulse of 3.0Vpp and 1MHz was applied between the microwell array/ITO electrode and an ITO counter electrode located on the top of the flow-cell assembly of the microdevice. The electrochemical responses of the individual HeLa cells transfected with SEAP were significantly larger than those of the wild-type HeLa cells. The electrochemical response of the transfected single cells was statistically distinguishable from that of wild-type HeLa cells. The size of the wells and the material of the single-cell array were optimized in order to evaluate the tumor necrosis factor alpha (TNF-alpha)-induced activation process of nuclear factor kappa B (NFkappaB) that was used as the model for on-chip monitoring of cellular signal transduction.
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PMID:Electrochemical single-cell gene-expression assay combining dielectrophoretic manipulation with secreted alkaline phosphatase reporter system. 1977 81

Intimal calcification is a feature of advanced atherosclerotic disease that predicts a two- to eightfold increase in the risk of coronary events. Type I collagen promotes vascular smooth muscle cell-mediated calcification, although the mechanism by which this occurs is unknown. The discoidin domain receptor 1 (DDR1) is a collagen receptor that is emerging as a critical mediator of atherosclerosis. To determine whether DDR1 is involved in intimal calcification, we fed male Ddr1(-/-);Ldlr(-/-) and Ddr1(+/+);Ldlr(-/-) mice an atherogenic diet for 6, 12, or 24 weeks. DDR1 deficiency significantly reduced the calcium content of the aortic arch, and microcomputed tomography demonstrated a significant decrease in hydroxyapatite deposition after 24 weeks of atherogenic diet. Reduced calcification was correlated with decreases in macrophage accumulation and tumor necrosis factor alpha staining, suggesting that the reduction in calcification was in part due to decreased inflammation. The chondrogenic markers type II collagen, type X collagen, and Sox-9 were expressed within the mineralized foci. An in vitro assay performed with vascular smooth muscle cells revealed that DDR1 was required for cell-mediated calcification of the matrix, and Ddr1(+/+) smooth muscle cells expressed more alkaline phosphatase activity, whereas Ddr1(-/-) smooth muscle cells expressed elevated levels of mRNA for nucleotide pyrophosphatase phosphodiesterase 1, an inhibitor of tissue mineralization. Taken together, our results demonstrate that DDR1 mediates an important mechanism for atherosclerotic calcification.
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PMID:Discoidin domain receptor-1 deficiency attenuates atherosclerotic calcification and smooth muscle cell-mediated mineralization. 1989 47


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