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)

Twenty-seven patients with mild to moderate essential hypertension were randomized to receive therapy with either hydrochlorothiazide or diltiazem. After a placebo run-in period of 2 weeks, patients received increasing doses of either drug for 14 weeks. Those in whom hypertension was effectively controlled continued for 26 weeks of total treatment. Those not controlled, i.e. blood pressure greater than 140/90 mm Hg or less than 10 mm Hg reduction of pressure, were unblinded and crossed over to therapy with both drugs. Eleven of 14 patients (79%) were effectively treated with diltiazem alone, and 8 of 13 patients (62%) were effectively treated with hydrochlorothiazide alone. Supine blood pressures fell from 152 +/- 5/97 +/- 1 to 142 +/- 4/87 +/- 3 mm Hg in the 11 patients treated with diltiazem, from 152 +/- 2/99 +/- 1 to 134 +/- 3/88 +/- 2 mm Hg in the 8 patients treated with hydrochlorothiazide, and from 151 +/- 4/104 +/- 3 to 140 +/- 5/92 +/- 1 mm Hg in the 8 patients who received both drugs (p less than 0.01 for each group). Diltiazem patients had significant increases in alkaline phosphatase and urinary magnesium. Hydrochlorothiazide patients had increases in serum uric acid, serum globulin, CO2 content, and plasma renin activity. Serum potassium, serum chloride, urinary osmolality, and urinary calcium decreased after treatment with hydrochlorothiazide. Patients receiving both drugs had increases in serum glucose, serum BUN, serum uric acid, serum globulin, and CO2 content. These patients had decreased serum chloride and urinary calcium. Diltiazem monotherapy was comparable to hydrochlorothiazide in efficacy of lowering blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal-metabolic consequences of antihypertensive therapy with diltiazem versus hydrochlorothiazide. 332 Jul 20

Thiazide diuretics have been shown to decrease bone-loss rate and to improve bone mineral density in patients using this medication. However, the exact role of thiazides on bone cells is still debated. In the present work, we studied whether thiazides could affect the normal features of osteoblasts using the human model cell line MG-63. Hydrochlorothiazide (HCTZ) did not affect cell growth nor DNA synthesis in these cells, yet slightly increased alkaline phosphatase activity in these cells at pharmacologically relevant concentrations. Under similar conditions, HCTZ dose-dependently inhibited 1,25(OH)2D3-induced osteocalcin secretion by these cells (maximal effect, -40 to 50%, P < 0.005). However, HCTZ did not inhibit the basal production of osteocalcin in MG-63 cells (without 1,25(OH)2D3 induction), which was very low to undectable. Two different thiazide derivatives, chlorothiazide and cyclothiazide, and two structurally related sulfonamides with selective inhibition of carbonic anhydrase (Acetazolamide) or hyperglycemic effects (Diazoxide) were also tested. Chlorothiazide (1000 microM) inhibited osteocalcin secretion (-42 +/- 12.7%) at doses 10-fold higher than HCTZ (100 microM) while cyclothiazide was effective at doses of 1 microM (-27 +/- 3.6%), and hence 100-fold lower than HCTZ, compatible with the relative natriuretic effect in vivo of these compounds. Acetazolamide (10 microM) poorly affected osteocalcin secretion at doses 100-fold higher than those needed in vivo to inhibit carbonic anhydrase. Likewise, Diazoxide (100 microM) poorly affected osteocalcin secretion at doses known to promote its biological effect. Higher doses of acetazolamide and diazoxide induced cell death. Neither Acetazolamide nor Diazoxide affected alkaline phosphatase, whereas chlorothiazide had a weak positive effect on this enzymatic activity. The production of macrophage colony-stimulating factor (M-CSF) was stimulated in the presence of 1,25(OH)2D3 (50 nM), TNF-alpha (2 ng/ml) or both in MG-63 cells. HCTZ (25 microM, 24 hr of preincubation) did not modify basal M-CSF production and did not reduce the response to 1,25(OH)2D3 alone. In contrast, HCTZ inhibited the response to TNF-alpha alone (P < 0.05), and also reduced the response to a combination of 1,25(OH)2D3 and TNF-alpha (P < 0.01). In conclusion, these results indicate that thiazide diuretics show a selective inhibition of osteocalcin secretion and M-CSF production by MG-63 cells unlike structurally related drugs. Therefore, these features may explain, in part, the positive effect of thiazides on bone mineral density.
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PMID:Selective effect of thiazides on the human osteoblast-like cell line MG-63. 891 12