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)

Raloxifene is a selective estrogen receptor modulator that in experimental animals acts as an estrogen receptor antagonist in breast and endometrium but as an estrogen receptor agonist in the skeletal and cardiovascular systems. We conducted a 1-year prospective, randomized, double-blind trial in 143 postmenopausal osteoporotic women (mean +/- SD age, 68.4+/-5.0 years) with at least one prevalent vertebral fractures and low bone mineral density (BMD), comparing groups receiving raloxifene at 60 mg/day (RLX60) or 120 mg/day (RLX120) and a control group receiving supplements of 750 mg/day of calcium and 400 IU/day of vitamin D. There were no differences among groups in the occurrence of uterine bleeding, thrombophlebitis, breast abnormalities, or increased endometrial thickness (assessed by ultrasonography). As compared with controls, the changes in values over 1 year for RLX60 and RLX120, respectively, were significant for serum bone alkaline phosphatase (-14.9%, -8.87%), serum osteocalcin (-20.7%, -17.0%), and urinary C-telopeptide fragment of type I collagen/creatinine (-24.9%, -30.8%), markers of bone turnover; for serum total cholesterol (-7.0% for RLX60) and low density lipoprotein cholesterol (LDL) (-11.4% for RLX60) and for the LDL/HDL cholesterol ratio (-13.2%, -8.3%). BMD increased significantly in the total hip (1.66% for RLX60) and ultradistal radius (2.92%, 2.50%). There were nonsignificant trends toward increases over controls in BMD for lumbar spine, total body, and total hip (for RLX120). Using a >15% cutoff definition, raloxifene had no effect on incident fractures, but using a >30% cutoff, there was a dose-related reduction (p = 0.047). We conclude that raloxifene therapy is well tolerated, reduces serum lipids, and does not stimulate the uterus or breasts. It has beneficial effects on bone, although, under the conditions of this study, these appear to be of a smaller magnitude than have been reported with estrogen therapy.
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PMID:Treatment of established postmenopausal osteoporosis with raloxifene: a randomized trial. 979 84

About 50 mg of silver leaf (metallic silver) was given daily by mouth to 30 healthy volunteers for 20 days. A statistically significant hypophospholipidemic, hypotriglyceridemic, hypocholesterolemic and hypoglycemic effect was observed. This was accompanied by a less marked fall in total lipids and significant rise in HDL-cholesterol. In addition, a decrease in plasma enzymes - alkaline phosphatase (ALP), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), creatine phosphokinase (CPK), gamma glutamyl transpeptidase (GGT) and lactate dehydrogenase (LDH) was noted. This was statistically significant for all enzymes except CPK. The safety of ingested silver foil is indicated by absence of pathology in urine and unaltered levels of protein and albumin in the plasma. These observations suggest that silver could be beneficial in conditions like diabetes mellitus, obesity and atherosclerosis.
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PMID:Effect of silver leaf on circulating lipids and cardiac and hepatic enzymes. 1023 75

The results of the determination of 24 basic blood chemistry variables from 262 men and 239 women, half of each group 44.4 +/- 0.9 and 63.0 +/- 0.9 (men) and 44.4 +/- 0.9 and 62.8 +/- 0.8 years old (women), resp., are compared. In men, only 6 analytes show significant differences between the age groups: Alanine aminotransferase decreases, aspartate aminotransferase decreases, iron decreases with p < 0.05; sodium increases, calcium decreases, protein (serum) decreases with p < 0.001. In women, 16 analytes, compared between both groups, are significantly different: Urea, uric acid, creatinine, triglycerides, total cholesterol, LDL cholesterol, LDL-C/HDL-C ratio, alanine aminotransferase, alkaline phosphatase, gamma-glutamyltransferase, sodium and ferritin are increased in the older group, whereas HDL cholesterol, iron, transferrin, and total protein are decreased. The sex differences are more distinct in the group of 44 years old persons than in the 63 years old one. These results will be completed by the comparison with the evaluation of the stored laboratory values of 9923 patients between 20 and 89 years old.
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PMID:[Clinical laboratory diagnosis and aging. 1: Results of data evaluation of clinico-chemical laboratory values in a study of aging]. 1040 12

In 262 men (about half of them 44.4 +/- 0.9 and 63.0 +/- 0.9 years old, resp.) and 239 women (about half of them 44.4 +/- 0.9 and 62.8 +/- 0.8 years old, resp.) the results of 12 clinical chemical analytes were used to calculate laboratory indices which were compared with the biological age in accordance with Ries. The indices were calculated by using concentrations of alkaline phosphatase, iron, total protein, total cholesterol, glucose, uric acid, urea, HDL cholesterol, creatinine, LDL cholesterol, transferrin, and triglycerides. Only in the younger group of women are the correlations between laboratory indices and biological age significant. In the same group, several single parameters also significantly correlate with pre-aging. Among them are alkaline phosphatase, the LDL-C/HDL-C ratio, bilirubin, triglycerides, and glucose.
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PMID:[Clinical laboratory diagnosis and aging. 2: Suitability of clinico-chemical basic parameters as markers ob biological aging]. 1040 13

A new class of compounds known as selective estrogen receptor modulators (SERMs) may possess the optimal combination of characteristics desirable in a drug designed for use in postmenopausal women. Among this class of compounds, raloxifene is the most studied and is currently available for clinical use in some countries for the prevention of osteoporosis in post-menopausal women. Raloxifene is a non-steroidal benzotiophene derivative shown to prevent bone loss at axial and appendicular sites and reduce serum cholesterol, like estrogen, in oophorectomized rats and in postmenopausal women. In animal models, unlike estrogen, raloxifene does not stimulate breast or uterine tissues. These appealing attributes make raloxifene a potential treatment for osteoporosis and other menopause related risks in middle aged and elderly women. Multicenter studies have been performed in early postmenopausal women, randomly assigned to receive raloxifene 30, 60, or 150 mg/day or placebo. All subjects received a calcium supplement. Bone mineral density, which was measured twice a year over 24 months by dual X-ray absorptiometry, decreased significantly at all skeletal sites with placebo, and significantly increased with raloxifene at the spine, hip, and total body at the three doses. At 24 months, the mean increase with raloxifene 60 mg compared with placebo was 2.4% at the lumbar spine and at the total hip, and 2% at the total body. Markers of bone formation (serum osteocalcin and bone specific alkaline phosphatase) and of resorption (urinary CrossLaps) decreased significantly to the premenopausal range within 3-6 months of treatment with raloxifene. In addition, total serum and low-density lipoprotein cholesterol decreased significantly in all raloxifene therapy groups in a dose-related fashion. Serum HDL-cholesterol and triglycerides were not significantly changed by therapy. The most commonly observed side-effect was hot flushes, with patients taking raloxifene reporting a slightly higher rate of flushes (25%) than those on placebo (18%). This adverse event usually occurred within the first few months of therapy, was generally mild, and did not result in excess study dropout (raloxifene 1.5%, placebo 2.1%). Preliminary 2-year data indicated that raloxifene is not associated with an increased risk of breast cancer. In summary, the clinical efficacy and safety of raloxifene is very promising and this compound will offer a particularly attractive choice for postmenopausal women.
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PMID:Clinical efficacy of raloxifene in postmenopausal women. 1042 20

The proposed laboratory investigation was designed to evaluate the effects of acute exposure to both continuous and intermittent magnetic fields (MFs) (50 Hz-10 microT) on the circadian rhythm of clinical chemistry variables in humans: electrolytes (magnesium, calcium, phosphorus, sodium, potassium, and chloride), enzymes (amylase, lipase, aldolase, gamma glutamyl-transferase [GGT], lactate dehydrogenase [LDH], aspartate aminotransferase [ASAT], and alkaline phosphatase [ALP]), lipids (cholesterol, high-density lipoprotein [HDL], apolipoprotein A1 [ApoA1], and ApoB), proteins (total proteins and albumin), nitrogen substances (uric acid, urea, and creatinine), iron, glycemia, and transferrin. Young volunteers (32 subjects; 16 exposed and 16 sham exposed) were selected according to the screening criteria. Each subject participated in two sessions held within a 4-week period. In the first session, one group of volunteers (16 subjects) was exposed to a continuous MF and then, in the second session, to an intermittent MF. The second group (16 subjects) served as a control for both sessions. At each session, blood samples were collected at 3 h intervals from 11:00 to 20:00 and hourly from 22:00 to 08:00. The results indicate that both continuous and intermittent 50-Hz linearly polarized MFs of 10 microT intensity have no effects on the circadian rhythms or on the levels of the variables studied here.
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PMID:Assessment of the effects of nocturnal exposure to 50-Hz magnetic fields on the human circadian system. A comprehensive study of biochemical variables. 1058 79

Norethisterone 2.5 mg/day was administered to 26 postmenopausal women (aged 54-79 years) with varying degrees of osteoporosis and with a forearm bone mineral density value more than 2 SD below the young normal mean. Fasting blood and urine samples were collected and radiocalcium absorption measured at baseline and after treatment for a median period of 4 months. There were significant falls in serum calcium and its fractions, phosphate, alkaline phosphatase and cholesterol (HDL and LDL), and significant rises in serum chloride and parathyroid hormone. In the urine, there were significant falls in calcium, sodium and hydroxyproline. These changes were in close agreement with our previously reported responses to norethisterone 5 mg/day. We conclude that norethisterone in a dose of 2.5 mg/day is probably as effective as 5 mg/day in reducing bone resorption in postmenopausal women with low bone density.
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PMID:The effects of low dose norethisterone on biochemical variables in postmenopausal women. 1062 56

The present study was designed to evaluate the effects of long-term administration of testosterone enanthate (TE) on lipid and liver function parameters in rhesus monkeys (n = 9) maintained under controlled dietary conditions. Bimonthly administration of 50 mg of TE increased serum testosterone into the supraphysiological range one day after injection and peak levels were seen on day 3, followed by a decrease to above baseline values by day 14. High density lipoprotein cholesterol (HDL-C) levels decreased gradually; compared to baseline values, the decline was significant from the 19th month of injection until the first month of recovery. The increase in low density lipoprotein cholesterol (LDL-C) levels and the LDL-C/HDL-C ratio during the treatment period was not significant compared to baseline values; however, when compared to control animals, HDL-C and LDL-C levels and the LDL-C/HDL-C ratio were significantly elevated from the 12th month until the end of the treatment period. All lipid parameters recovered by the end of the treatment period. Control animals (n = 9) did not show significant changes in HDL-C and LDL-C levels and the LDL-C/HDL-C ratio during the study period. Total cholesterol levels decreased in control (n = 9) and treated animals from 6 to 15th months of the treatment period, coinciding with the feeding of sprouted grams to animals. TE injections did not change the levels of triglycerides, alkaline phosphatase or bilirubin in control and treated animals. However, transaminase (SGOT and SGPT) levels increased following TE injections and remained elevated until the end of injections followed by a return to baseline values or below during the recovery period. These effects could be due to the pharmacokinetic profile of TE in which testosterone levels were elevated to supraphysiological values after injections. The recovery of the TE-induced changes in lipid parameters and liver transminases is reassuring but the changes in these parameters during TE injections indicate the need for long-acting androgens with better pharmacokinetic properties.
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PMID:Effects of long-term use of testosterone enanthate. II. Effects on lipids, high and low density lipoprotein cholesterol and liver function parameters. 1062 3

Hormone replacement therapy is well known for its beneficial effects on climacteric symptoms and is also used for the prevention of osteoporosis. In a prospective open label study we evaluated the efficacy and safety of hormone replacement therapy with 17 beta estradiol dydrogesterone (Femoston, 17 beta estradiol/continuously and dydrogesterone/sequentially). We observed 704 women who were treated with 17 beta estradiol-dydrogesterone over three months. 448 of the women previously had not used hormone replacement therapy, 224 women had been treated with a different hormone replacement therapy before they were entered into the study; for 20 women this information was not available. The physicians were asked to assess the severity of climacteric symptoms at baseline and after three months of hormone replacement therapy. In addition, the following parameters were evaluated before and at the end of the study: blood pressure, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, blood glucose, alkaline phosphatase and gamma glutamyltransferase. Twelve women did not tolerate 17 beta estradiol-dydrogesterone and therefore dropped out of the study. Climacteric symptoms clearly improved after treatment with 17 beta estradiol-dydrogesterone. During our open label prospective study, a significant decrease in blood pressure and serum levels of total cholesterol, LDL cholesterol and the LDL/HDL ratio were observed, whereas serum levels of HDL cholesterol increased significantly. Surprisingly, triglyceride levels also decreased significantly. Serum levels of alkaline phosphatase decreased significantly in women who had received a different hormone replacement therapy before they took 17 beta estradiol-dydrogesterone. We conclude that hormone replacement therapy with 17 beta estradiol-dydrogesterone is highly effective and well tolerated. Hormone replacement therapy with 17 beta estradiol-dydrogesterone appears to have a positive effect on blood pressure and the serum lipid profile. We therefore hypothesise that prolonged treatment with 17 beta estradiol-dydrogesterone may reduce morbidity and mortality secondary to cardiovascular diseases.
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PMID:[Hormone replacement therapy with 17 beta-estradiol dydrogesterone: results of a 3-month open-label study]. 1067 91

Nowadays, bisphosphonates are considered the drugs of choice for the treatment of several bone disorders. Their exact mechanism of action is not clear but recently it has been reported that the aminobisphosphonates inhibit cholesterol biosynthesis and that this might be relevant for their actions on bone osteoclasts. The study includes 87 postmenopausal women with moderate to severe osteoporosis. The patients were randomly assigned to intravenous (iv) infusion of 50 mg of the aminobisphosphonate Neridronate dissolved in 100 ml of saline solution every 2 months for a year (44 patients). The remaining 43 served as controls. At the time of each infusion blood samples were obtained for the evaluation of total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-I (Apo A-I), apolipoprotein B (Apo B), and total and bone alkaline phosphatase (AP). Free deoxypyridinoline (f-DPD) was measured in fasting urine specimens. In the control group no significant changes were observed throughout the study period for any of the biochemical variables. In the Neridronate-treated patients both bone AP and f-DPD excretion fell significantly by 15-20%. In these patients serum total cholesterol and serum triglycerides showed marginal decreases, which were occasionally significant. LDL-C and Apo B fell by 5-6% and these changes were statistically significant at most time points. Apo A-I and HDL-C rose progressively with time. At the 12th month, HDL-C rose 17-18% (p < 0.0001) above the baseline values. Similar findings were obtained in four postmenopausal women given high iv doses of Pamidronate or Alendronate. In conclusion aminobisphophonates, at least when given iv, induce remarkable and unexpected effects on lipid metabolism with a final profile that might be clinically relevant.
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PMID:Chronic intravenous aminobisphosphonate therapy increases high-density lipoprotein cholesterol and decreases low-density lipoprotein cholesterol. 1075 May 76


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