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

Six patients with extensive polyostotic Paget's disease were treated for 3 months with dichloromethane diphosphonate (CL2MDP; 1600 mg/day, orally). Serum alkaline phosphatase and urinary hydroxyproline excretion decreased 60-80% in each patient. Blood ionized calcium (ca++) and immunoreactive PTH (iPTH) were measured weekly during the first month of therapy and monthly thereafter. As an index of parathyroid function, PTH secretory reserve was assessed by EDTA infusions before treatment, at the end of treatment, and 3 months after Cl2 MDP therapy was stopped. Before therapy, iPTH and Ca++ were normal in all patients. During treatment, Ca++ decreased and iPTH increased in all patients; mean iPTH approximately doubled (95% confidence limits, 1.5- to 2.7-fold increase). At the end of 3 months of treatment, EDTA infusion raised iPTH in each patient to a level higher than that in the control infusion, indicating augmented PTH secretory reserve. Ca++, iPTH, and the iPTH response to EDTA-induced hypocalcemia returned toward baseline by 3 months after the end of CL2MDP treatment. The results indicate that secondary hyperparathyroidism developed as a result of Cl2MDP therapy. The cause of the parathyroid-gland adaptation is not known; the hyperparathyroidism is, however, at least partly reversible. Cl2MDP inhibits bone resorption while allowing bone mineralization to continue; this differential effect could lead to the hypocalcemia and parathyroid hyperfunction.
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PMID:Secondary hyperparathyroidism associated with dichloromethane diphosphonate treatment of Paget's disease. 621 19

Twenty-four symptomatic patients with symptoms of active Paget's disease of bone were evaluated, during the course of their therapy, a total of 71 times (24 baseline and 47 follow-up examinations) by serial alkaline phosphatase levels (AP), Tc-99m MDP bone scans, and radionuclide blood-flow studies. The flow study correlated with disease activity in all of the baseline studies and in at least 85% of the follow-up studies. In five patients (seven follow-up studies) the changes in local blood flow correctly anticipated the eventual rise or fall of AP. In comparison with the bone scan, the changes in blood flow preceded the bone-scan alterations or were more reliable indicators of disease activity in 12 of the 13 follow-up studies in which the results of the two examinations disagreed. We conclude that the radionuclide flow study provides useful additional clinical information in the management of Paget's disease.
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PMID:Observations on serial radionuclide blood-flow studies in Paget's disease: concise communication. 622 40

After twenty weeks of continuous dosing with Trichostrongylus colubriformis larvae substantial, but declining, numbers of worms had persisted in most of the lambs examined, although there were wide inter-individual variations. Mucosal lesions were found in the proximal small intestines of all the infected animals, their severity being directly related to worm burden. Representative brush border enzyme activities analysed in intestinal mucosal extracts from the same lambs showed differing responses. Alkaline phosphatase and glycyl-L-leucine dipeptidase were significantly depleted, whereas maltase activity was only marginally reduced, and leucine aminopeptidase activity was normal. Mucosal acetylcholinesterase activity was significantly elevated in the parasitised animals and, interestingly in view of the postulated role of this enzyme in nematode pathogenicity, the level of activity was directly correlated with individual worm burdens. Intestinal trypsin and chymotrypsin activities were unaffected and the level of superoxide dismutase, an enzyme associated with the inflammatory response, was normal. There were also no consistent changes in the mucosal activities of several enzymes including lactic dehydrogenase, creatine phosphokinase, aldolase, and glutamic oxaloacetate transaminase, whose leakage from damaged or necrotic tissues has been well defined in terms of the concomitant increase in their activity in the circulation. Lambs treated orally with fenbendazole five and/or ten weeks before slaughter either in the presence or absence of continued larval intake, had negligible worm burdens, and showed little evidence of intestinal damage at post mortem. Brush border enzyme levels, with the exception of alkaline phosphatase and, in two cases dipeptidase, were normal in these animals. The activity of alkaline phosphatase was approximately double that in the continuously infected, untreated lambs, but remained markedly lower than in the uninfected controls. The activities of the other enzymes studied, including acetylcholinesterase, were within the control range. In summary, in chronic trichostrongylosis even relatively low nematode burdens were associated with marked pathological and biochemical damage in the intestine with both lesion severity and mucosal acetylcholinesterase activity being directly related to worm numbers. Although morphological integrity was completely restored after anthelmintic treatment, the persistent low activity of brush border alkaline phosphatase coupled with the enzymological findings in untreated, infected animals suggests that recovery of the full functional capability of the intestinal mucosa may take longer.
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PMID:Intestinal enzyme activity in lambs chronically infected with Trichostrongylus colubriformis: effect of anthelmintic treatment. 634 11

Ten patients with severe Paget's disease of bone and serum alkaline phosphatase (sAP) greater than 900 IU/l were treated for six months with the oral diphosphonate APD, (3-amino-1-hydroxypropylidene-1, 1-bisphosphonate). By the end of the treatment period there was a reduction in the log mean urine hydroxyproline (uHP) and the log mean sAP of 92% and 87% respectively. In four patients both sAP and uHP fell to within the normal range and remained normal for at least six months after therapy was stopped. Bone scintigraphy showed a fall in 99mTc-MDP uptake in sites of active Paget's disease in all patients and histomorphometry showed no increase in osteoid. Repair of radiological osteolytic lesions was observed in 6/6 patients and progression of tibial osteolytic wedges was arrested in 5/5 patients and reversed in four. This improvement persisted six months after completion of therapy but further wedge progression occurred in one patient whose urine HP remained elevated. There were no serious effects though five patients complained of nausea. The clinical and biochemical responses to APD were equivalent to those observed in the same patients during a previous six month course of combined therapy with human calcitonin (CT) + EHDP except that there was additional biochemical and radiological evidence of bone healing. This study confirms PAD as an effective treatment of severe Paget's disease of bone.
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PMID:Effective oral treatment of severe Paget's disease of bone with APD (3-amino-1-hydroxypropylidene-1,1-bisphosphonate); a comparison with combined calcitonin + EHDP (1-hydroxyethylidene-1,1-bisphosphonate). 644 63

The distribution and localization of Tc-99m methylene diphosphonate (Tc-MDP) in the epiphyseal growth plates of the rat were elucidated by contact and microautoradiography. The uptake of the tracer was found to be especially high in the calcified cartilage bars at the end of the vascular loops. In addition to areas of mineralization, increased uptake was found in the Howship's lacunae on the resorbing surfaces. This labeling corresponded with the fluorescence of tetracycline, which labeled both forming and resorbing surfaces, when given with short labeling interval. Distribution of Tc-MDP did not coincide with new production of collagen, as judged by H-3 proline labeling; nor was the uptake localized within cells with high alkaline phosphatase activity. The affinity of the tracer for the mineral phase was confirmed by decalcification of in vivo labeled sections with EDTA, which showed loss of radioactivity in contrast to sections incubated in water. By chromatography the activity in the decalcification medium could not be distinguished from that of Tc-MDP.
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PMID:Localization of Tc-99m MDP in epiphyseal growth plates of rats. 645 74

Measurements of 24-h whole body retention of 99m-Tc-MDP (WBR) has been performed in 125 normal volunteers, together with determinations of serum alkaline phosphatase, urinary hydroxyproline excretion and creatinine clearance. WBR decreased slightly from the 3rd to the 4th decade, after which it increased gradually in the older age-groups. Serum alkaline phosphatase followed an identical pattern, while the urinary hydroxyproline excretion demonstrated a marked but temporary rise in the post-menopausal age-groups. Finally, the creatinine clearance decreased gradually in the older age groups. Analysis of variance demonstrated that WBR varied independently with serum alkaline phosphatase and creatinine clearance, while no relationship between WBR and the hydroxyproline excretion was found. It seems likely that the increasing retention of diphosphonate in elderly persons reflects rising osteoblastic activity as well as decreasing glomerular filtration.
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PMID:Measurements of whole body retention of diphosphonate and other indices of bone metabolism in 125 normals: dependency on age, sex and glomerular filtration. 652 12

Two hundred cancer patients with bone metastases were studied by gammagraphy employing 555 MBq of 99mTc-MDP. The results were compared with those obtained by radiology and alkaline phosphatase determination, showing that gammagraphy is positive in 93 per 100 of the cases and is more useful than the other procedures to make a pre-radiologic diagnosis of bone metastases (27 per 100).
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PMID:[Value of studying oncologic patients using bone gammagraphy for the diagnosis of skeletal metastasis. Review of 200 cases]. 654 32

The therapy of Paget's bone disease is essentially based on the use of calcitonin and diphosphonates: both drugs, if used in large doses for long periods, have shown themselves able to provoke particular side-effects. It was, therefore, decided to study the therapeutic efficacy of combined low-dosage treatment using synthetic salmon calcitonin and sodium-etidronate on a group of patients with Paget's osteodystrophy. A clear evident diminution in plasma alkaline phosphatase, hydroxyprolinuria and whole body retention (WBR) of MDP-Tc99m was observed, demonstrating a reduction of metabolic turnover in the bone. No changes in the bone mass (BMC), evaluated by bone mineral detector, were observed at the end of treatment. With this treatment the plateau effect was shown to be appreciably less than normally occurs when either calcitonin or sodium etidronate are used alone.
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PMID:[Effects of the combined calcitonin and sodium etidronate therapy in Paget's disease of bone]. 680 55

In 27 patients on periodic haemodialysis, serum levels of alkaline phosphatase (ALP), osteocalcin (BGP), intact parathyroid hormone (PTHi) and its two fragments, terminal COOH (PTH-Cter) and middle molecule (PTH-MM), and procollagen type 1 carboxy-terminal extension peptide (P1CP) were measured. The same patients underwent radiography of the skull and of the hands, ultrasonography of the parathyroids and scintigraphy of the skeleton with 99mTc-MDP. The study was completed by the measurement of aluminium (Al) in the blood and the deferoxamine test (DFO). Two groups of patients emerged, one (group A, n = 14) with PTHi greatly increased (201.07 +/- 109.72 pg/mL) and the other (group B, n = 13) with values within the normal range (32.69 +/- 17.06 pg/mL) (p < 0.001). In group A, ALP, BGP and particularly P1CP were increased with a statistically significant difference compared to group B. Specific radiographic alterations were found in 12 patients of group A; 7 patients also had hypertrophy of the parathyroids. There was no difference in the scintigraphic alterations of the skeleton between the two groups. The authors conclude that it is the association of the high values of PTHi with those of the markers of bone metabolism, the normal level of Al, the negativity of the DFO test and the radiological alterations which together allow the diagnosis of renal osteodystrophy with hyperparathyroidism.
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PMID:Renal osteodystrophy with hyperparathyroidism: the diagnostic value of intact parathormone, alkaline phosphatase, osteocalcin and procollagen. 786 45

Incubation of pig kidney microvillar membranes with Bacillus thuringiensis or Staphylococcus aureus phosphatidylinositol-specific phospholipase C (PI-PLC) resulted in the release of a number of glycosyl-phosphatidylinositol (GPI)-anchored hydrolases, including alkaline phosphatase (EC 3.1.3.1), amino-peptidase P (EC 3.4.11.9), membrane dipeptidase (EC 3.4.13.19), 5'-nucleotidase (EC 3.1.3.5) and trehalase (EC 3.2.1.28). Of these five ectoenzymes only for membrane dipeptidase was there a significant (approx. 100%) increase in enzymic activity upon release from the membrane. Maximal activation occurred at a PI-PLC concentration 10-fold less than that required for maximal release. In contrast solubilization of the membranes with n-octyl beta-D-glucopyranoside had no effect on the enzymic activity of membrane dipeptidase. A competitive e.l.i.s.a. with a polyclonal antiserum to membrane dipeptidase indicated that the increase in enzymic activity was not due to an increase in the amount of membrane dipeptidase protein. Although PI-PLC cleaved the GPI anchor of the affinity-purified amphipathic form of pig membrane dipeptidase there was no concurrent increase in enzymic activity. In the absence of PI-PLC, membrane dipeptidase in the microvillar membranes hydrolysed Gly-D-Phe with a Km of 0.77 mM and a Vmax. of 602 nmol/min per mg of protein. However, in the presence of a concentration of PI-PLC which caused maximal release from the membrane and maximal activation of membrane dipeptidase the Km was decreased to 0.07 mM while the Vmax. remained essentially unchanged at 624 nmol/min per mg of protein. Overall these results suggest that cleavage by PI-PLC of the GPI anchor on membrane dipeptidase may relax conformational constraints on the active site of the enzyme which exist when it is anchored in the lipid bilayer, thus resulting in an increase in the affinity of the active site for substrate.
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PMID:Activation of the glycosyl-phosphatidylinositol-anchored membrane dipeptidase upon release from pig kidney membranes by phospholipase C. 798 Apr 26


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