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

---

Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dichloromethylene diphosphonate (Cl2MDP, or clodronate disodium) is one of the most potent of the known diphosphonates as an inhibitor of bone resorption and differs from EHDP in that it does not inhibit skeletal mineralization. It is one of the second generation diphosphonates now undergoing clinical evaluation. In the study described here Cl2MDP was given by mouth (800-1600 mg/day for 6 months) to 35 patients with symptomatic Paget's disease of bone. Cl2MDP induced a marked fall in serum alkaline phosphatase and urinary hydroxyproline to normal or near normal values in all patients. This was accompanied by clinical improvement in all but 4 patients. Cl2MDP appears to be another effective oral drug for the treatment of Paget's disease of bone and compares favorably with the calcitonins and EHDP.
...
PMID:Biochemical and clinical responses to dichloromethylene diphosphonate (Cl2MDP) in Paget's disease of bone. 644 4

The effects on serum uric acid (SUA) of two diphosphonates (EHDP at 5 and 20 mg/kg/day and Cl2MDP at 400 and 1600 mg/day) were studied in 49 pagetic patients treated for 6 months. Patients were divided into two groups: group I, initially normouricemic (SUA less than 385 mumol/l); group II, initially hyperuricemic (SUA greater than or equal to 385 mumol/l). SUA was significantly decreased (P less than 0.01) after 6 months of diphosphonate therapy in all group II patients. However, 3 months after withdrawal of therapy, SUA returned to values not significantly different from those initially recorded in this group. SUA did not change during or after treatment in the group I patients. Groups I and II could not be differentiated on the basis of initial serum alkaline phosphatase or urinary hydroxyproline values. In response to therapy, both groups showed the same reduction in these parameters. These results suggest that diphosphonates have no effect at a single level in uric acid metabolism. They certainly reduce the part of the urate pool coming from the nucleic acids of the increased bone cell population by reducing the number of osteoclasts and osteoblasts, which is extremely high in pagetic bone. They also must act on uric acid metabolism through other mechanisms which need to be investigated in further studies.
...
PMID:Effects of two diphosphonates (EHDP and Cl2MDP) on serum uric acid in pagetic patients. 645 54

Etidronate used in recommended doses (usually 5 mg/kg/day for 6 months) produces symptomatic improvement in approximately 60% of patients. The serum alkaline phosphatase and urinary hydroxyproline are reduced to about 50% of initial values. A sustained remission occurs in many patients and retreatment is usually effective upon relapse. The abnormally elevated osteoclast count and resorption surfaces are reduced, and at the low dose there is no accumulation of osteoid. The medication is generally well tolerated and at the recommended dosage there is no evidence of increased fracture rate.
...
PMID:Use of etidronate (EHDP) in Paget's disease of bone. 677 43

Forty patients with Paget's disease of bone were treated with intermittent courses of the diphosphonate, EHDP. Seven individuals had prolonged remissions after their initial course of therapy, nineteen responded to retreatment with 5 mg/kg of EHDP for 6 months of each year, while 14 patients required cycles of 20 mg/kg for 1 month of every 4. Improvement was indicated by alleviation of symptoms and reduction in serum alkaline phosphatase and urinary hydroxyproline. Data suggesting a possible role for parathyroid hormone in the expression of Paget's disease are also discussed.
...
PMID:Long-term therapy of Paget's disease of bone with EHDP. 677 44

Fifty-one patients with Paget's disease were treated during 6 months with ethane-01 hydroxy-1, 1 diphosphonate (EHDP, etidronate) in doses of 5 mg/kg/day. The drug was most effective in relieving pain, at the same time diminishing the uptake of pagetic lesions on quantitative bone scans and lowering by almost 70% the abnormally high serum alkaline phosphatase levels and 24-hour hydroxyproline urinary levels. Histologically, the resorption surfaces and the number of osteoclasts per mm2 of bone tissue were significantly reduced. On follow-up, the improvement persisted for at least one year after treatment was discontinued. EHDP was well tolerated clinically and biologically, and on histological sections no accumulation of osteoid tissue due to impaired mineralization was seen. EHDP at the 5 mg/kg/day dose appears to be effective in the treatment of Paget's disease.
...
PMID:[Treatment of Paget's disease of bone with ethane-1 hydroxy-1, 1 diphosphonate at low dosage (author's transl)]. 677 52

During the past 6 years 16 patients suffering from Paget's disease of bone have been treated and regularly followed up in our department. 10 of these patients have received etidronate (ethane-hydroxy-diphosphonate), 4 others have received synthetic human calcitonin and the last 2 have received both treatments, first successively then simultaneously. Under either therapy satisfactory clinical and biological results have been observed (diminution of pain and decreased levels of serum alkaline phosphatase and hydroxyprolinuria). Etidronate has been more efficient in reducing biological parameters, whereas calcitonin has produced a faster symptomatic response. On the basis of these observations the present principles for treatment of Paget's disease are discussed.
...
PMID:[Treatment of Paget's disease of bone: diphosphonates or calcitonin?]. 678 79

Studies regarding the efficacy of EHDP in the treatment of Paget's disease of bone conducted at our institution are described. An initial placebo-controlled clinical trial established that doses of 5 mg/kg/day for 6 months produced symptomatic improvement and a 50% lowering of serum alkaline phosphatase and urinary hydroxyproline. A subsequent study indicated that the biochemical suppression was maintained during the ensuing 6 months without therapy. Current results of long-term intermittent EHDP treatment in 40 patients studied for 5-8 years demonstrate that a small minority of individuals experience a sustained remission after a single six-month course of therapy, while a majority require repeated courses of 5 mg/kg/day for 6 of every 12 months to maintain their initial improvement. Data are also presented describing the successful use of EHDP at a dose of 20 mg/kg/day for 1 of every 4 months in patients refractory to conventional low doses of therapy. The possible role of parathyroid hormone in the expression of Paget's disease is also discussed, and recommendations regarding the pharmacologic management of patients with this disorder are provided.
...
PMID:Clinical and biochemical effects of EHDP in Paget's disease of bone: patterns of response to initial treatment and to long-term therapy. 682 Jan 11

The effects of long-term treatment with 25-hydroxycholecalciferol (25OHD3) and disodium ethane-1-hydroxydiphosphonate, or 25OHD3 alone on biochemical parameters, and radiographic and quantitative histomorphometry of bone tissue were evaluated in 17 dialysis patients. They all displayed evidence of bone disease consisting of osteitis fibrosa and defective mineralization of varying degree and predominance. 100 micrograms/day of 25OHD3 significantly improved the state of bone mineralization in many patients with a pronounced fall in the osteoid volume and surface and produced a small reduction in the active resorption surface. Serum parathyroid hormone (iPTH) and alkaline phosphatase levels decreased in some patients. The combination of 25OHD3 with EHDP caused the healing of bone mineralization as did 25OHD3 alone and produced a significant fall in serum alkaline phosphatase and iPTH. The mean magnitude of the reduction in iPTH was higher in patients treated with 25OHD3 and EHDP than with 25OHD3 alone. Treatment with 25OHD3 and EHDP seems more effective for the improvement of osteitis fibrosa than is 25OHD3 alone.
...
PMID:Therapeutic effects of 25-hydroxycholecalciferol and sodium etidronate on renal osteodystrophy. 682 Apr 73

Rhenium-186 hydroxyethylidene diphosphonate (186Re-HEDP) has been used for the palliative treatment of metastatic bone pain. A phase 1 dose escalation study was performed using 186Re-HEDP. Twenty-four patients with hormone-resistant prostate cancer entered the study. Each patient had at least four bone metastases and adequate haematological function. Groups of at least three consecutive patients were treated with doses starting at 1295 MBq and increasing to 3515 MBq (escalated in increments of 555 MBq). Thrombocytopenia proved to be the dose-limiting toxicity, while leucopenia played a minor role. Early death occurred in one patient (10 days after administration) without clear relationship to the 186Re-HEDP therapy. Transient neurological dysfunction was seen in two cases. Two patients who received 3515 MBq 186Re-HEDP showed grade 3 toxicity (thrombocytes 25-50 x 10(9)/l), defined as unacceptable toxicity. After treatment alkaline phosphatase levels showed a transient decrease in all patients (mean: 26% +/- 10% IU/l; range: 11%-44%). Prostate-specific antigen values showed a decline in eight patients, preceded by a temporary increase in three patients. From this study we conclude that the maximally tolerated dose of 186Re-HEDP is 2960 MBq. A placebo-controlled comparative study on the efficacy of 186Re-HEDP has been initiated.
...
PMID:Dose escalation study of rhenium-186 hydroxyethylidene diphosphonate in patients with metastatic prostate cancer. 753 Jan 99

We demonstrated that polyamines, such as spermine and spermidine, can enhance the pyrophosphatase (PPase) activity of alkaline phosphatase (ALP). Bisphosphonates such as disodium-1-hydroxy-1-aminopropylidine-1,1-diphosphonate (APD) and ethane-1-hydroxy-1,1'-diphosphonate (HEDP) inhibited ALP phosphate ester hydrolysis activity more than PPase activity at the same concentrations. This indicated that PPase activity of ALP was available in the presence of pyrophosphate analogues and possibly organic pyrophosphates as well. Vanadate and cadmium inhibited ALP and PPase activity more than ALP phosphate ester hydrolysis activity at the same concentrations. Calcium inhibited ALP PPase activity, though it did not inhibit ALP phosphate ester hydrolysis activity. At high concentrations, ascorbic acid slightly inhibited ALP PPase activity, though it did not inhibit ALP phosphate ester hydrolysis activity. ALP PPase activity appeared to have ubiquitous intracellular existence, broad substrate specificity and extensive interaction with calcium, vanadium and polyamines-substances which are important for cell metabolism and cell growth. These findings suggested that intracellular ALP modulated cell metabolism and cell growth by its PPase activity.
...
PMID:[Implications of alkaline phosphatase pyrophosphatase activity: intracellular functions of alkaline phosphatase]. 807 80


<< Previous 1 2 3 4 5 6 Next >>

---