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)

A sensitive nonradioactive northern blotting for the detection of acetylcholinesterase mRNA in mammalian tissues is described and compared to its radioactive version. Best results were obtained if digoxigenin labeled RNA probe was used for hybridization and CDP-Star, a chemiluminescent alkaline phosphatase substrate, for detection. The described nonradioactive technique for acetylcholinesterase mRNA determination is as sensitive as the radioactive one, but requires no protection against radiation and is less time consuming. Because of higher stability of the labeled probe, nonradioactive technique is also more convenient from the standpoint of experimental planning.
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PMID:Nonradioactive northern blotting for the determination of acetylcholinesterase mRNA. Comparison to the radioactive technique. 1065 46

Dosing convenience is a key element in the effective management of any chronic disease, and is particularly important in the long-term management of osteoporosis. Less frequent dosing with any medication may enhance compliance, thereby maximizing the effectiveness of therapy. Animal data support the rationale that once-weekly dosing with alendronate 70 mg (7 times the daily oral treatment dose) could provide similar efficacy to daily dosing with alendronate 10 mg due to its long duration of effect in bone. In addition, dog studies suggest that the potential for esophageal irritation, observed with daily oral bisphosphonates, may be substantially reduced with once-weekly dosing. This dosing regimen would provide patients with increased convenience and would be likely to enhance patient compliance. We compared the efficacy and safety of treatment with oral once-weekly alendronate 70 mg (N=519), twice-weekly alendronate 35 mg (N=369), and daily alendronate 10 mg (N=370) in a one-year, double-blind, multicenter study of postmenopausal women (ages 42 to 95) with osteoporosis (bone mineral density [BMD] of either lumbar spine or femoral neck at least 2.5 SDs below peak premenopausal mean, or prior vertebral or hip fracture). The primary efficacy endpoint was the comparability of increases in lumbar spine BMD, using strict pre-defined equivalence criteria. Secondary endpoints included changes in BMD at the hip and total body and rate of bone turnover, as assessed by biochemical markers. Both of the new regimens fully satisfied the equivalence criteria relative to daily therapy. Mean increases in lumbar spine BMD at 12 months were: 5.1% (95% CI 4.8, 5.4) in the 70 mg once-weekly group, 5.2% (4.9, 5.6) in the 35 mg twice-weekly group, and 5.4% (5.0, 5.8) in the 10 mg daily treatment group. Increases in BMD at the total hip, femoral neck, trochanter, and total body were similar for the three dosing regimens. All three treatment groups similarly reduced biochemical markers of bone resorption (urinary N-telopeptides of type I collagen) and bone formation (serum bone-specific alkaline phosphatase) into the middle of the premenopausal reference range. All treatment regimens were well tolerated with a similar incidence of upper GI adverse experiences. There were fewer serious upper GI adverse experiences and a trend toward a lower incidence of esophageal events in the once-weekly dosing group compared to the daily dosing group. These data are consistent with preclinical animal models, and suggest that once-weekly dosing has the potential for improved upper GI tolerability. Clinical fractures, captured as adverse experiences, were similar among the groups. We conclude that the alendronate 70 mg once-weekly dosing regimen will provide patients with a more convenient, therapeutically equivalent alternative to daily dosing, and may enhance compliance and long-term persistence with therapy.
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PMID:Therapeutic equivalence of alendronate 70 mg once-weekly and alendronate 10 mg daily in the treatment of osteoporosis. Alendronate Once-Weekly Study Group. 1074 26

A major challenge in the management of primary hyperparathyroidism (pHPT) is the decision regarding which patients should undergo parathyroidectomy (PTX). although the Consensus Development Conference of the National Institutes of Health (NIH) has proposed guidelines for the indication of surgery. We found that PTX brings about increases in radial and lumbar BMD values as high as 10% in virtually all pHPT patients including postmenopausal women and those without an indication for surgery based on NIH criteria. Serum alkaline phosphatase (ALP) level and the severity of cortical bone mass reduction are clinically useful for predicting the changes in lumbar BMD after PTX. The present findings provide a useful clue for the indication of surgery in pHPT, and seem to warrant a more extended indication than that of the NIH. We also described the recent progress in studies on calcium-sensing receptor (CaR), and discussed the possibility of bone mass recovery by medical treatment of pHPT with a newly introduced CaR agonist ('calcimimetics').
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PMID:Treatment of osteopenia secondary to primary hyperparathyroidism. 1091 4

We conducted a cross-sectional study of the effects of soybean protein intake on bone mineral density and biochemical markers in 85 postmenopausal Japanese women. Nutrients in the diet of postmenopausal Japanese women visiting the osteoporosis unit, including subjects with normal lumbar spine bone mineral density (L2-4 BMD), were investigated by questionnaire, and the calculated daily energy, protein, soy protein and calcium intake were obtained. L2-4 BMD was measured with dual-energy X-ray absorptiometry, and assays done of serum alkaline phosphatase (ALP) and serum intact osteocalcin (IOC) as bone formation markers and urinary pyridinoline (UPYR) and urinary deoxypyridinoline (UDPYR) as bone resorption markers. Soy protein intake was significantly associated with the Z-score for L2-4 BMD (r = 0.23,p = 0.038) and UDPYR (r = -0.23, p = 0.034). Stepwise multiple regression analyses showed that soy protein intake is significantly associated with the Z-score for L2-4 BMD (beta = 0.225, p = 0.04) and UDPYR (beta = -0.08, p = 0.03) among four nutritional factors. These results suggest that high soy protein intake is associated with a higher bone mineral density and a lower level of bone resorption, but further studies are needed to confirm the causal dynamic mechanisms.
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PMID:Effect of soy protein on bone metabolism in postmenopausal Japanese women. 1109 77

The aim of a study was to estimate the renal osteodystrophy status using bone densitometry in relation to selected biochemical parameters of calcium-phosphate metabolism. The study population consisted of 123 patients with end-stage renal disease, including 24 patients treated with continuous ambulatory peritoneal dialysis (CAPD), aged between 22 and 73 years (mean 49.9 years), on dialysis program for mean period of 14.9 months and 99 patients on maintenance hemodialysis for mean period of 58.8 months, aged between 19 and 72 years (mean 46.6 years). Densitometric measurements using DEXA technique were performed in three different skeletal points: distal ends of both radial bones, lumbar spinal region and femoral neck. Concomitantly, serum concentrations of total and ionized calcium, phosphates and parathormone as well as alkaline phosphatase serum activity were measured. Among male patients treated with CAPD significantly higher BMD values in right forearm were found as compared to women treated with this method (0.769 vs. 0.616; p < 0.001). Higher values of BMD were also found in both forearms in whole CAPD population as compared to those on hemodialysis. However, there was no difference in densitometry results between CAPD and HD patients as well as between men and women within these groups, when measured in femoral neck and lumbar spinal region. Among hemodialysis patients higher levels of phosphates and PTH were found as compared to CAPD, doses of drugs used for treatment of osteodystrophy--calcium carbonate, aluminum hydroxide and active vitamin D were also higher in individuals on HD. In addition, in CAPD patients statistically significant, positive correlations were found between BMD value in lumbar spinal area as well as in femoral neck and amount of ingested calcium carbonate, between BMD in lumbar spinal area and aluminum hydroxide dose taken by patients and between BMD in both forearms and dose of active vitamin D. We failed to demonstrate any relationship between obtained densitometric results as well as biochemical markers of calcium-phosphate metabolism and quantitative parameters of dialysis adequacy in both treatment modes. Obtained results let us to conclude that renal osteodystrophy is less advanced in patients treated with peritoneal dialysis, however this may be related only to markedly shorter renal replacement therapy period in this group. Lack of significant abnormalities in densitometry measurements taken in lumbar spinal area and femoral neck, while they are present in forearms, may suggest that the latter point of skeleton may be most useful for identification of bone mass deficiency in dialyzed patients.
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PMID:[Renal osteodystrophy in dialysis patients as estimated by three-point bone densitometry]. 1110 68

Bone Sialoprotein (BSP), synthesized by osteoblasts and osteoclasts, is a highly glycosylated and phosphorylated protein, accounting for approximately 5-10% of noncollagenous proteins of bone extracellular matrix. The present study investigates possible correlations between serum values of immunoreactive Bone Sialoprotein in relation to established bone turnover markers like osteocalcin (OC), bone alkaline phosphatase (B-ALP) and the c-terminal extension peptide of type-I-Procollagen (PICP) in 170 osteoporosis patients (female n = 144, male n = 26) in order to evaluate the usefulness of BSP in the diagnosis of bone disease. Fasting venous blood samples were collected from our osteoporosis outpatients in the morning and stored at -80 degrees C until processing. Serum levels of BSP were determined by RIA, OC and B-ALP were measured by IRMA, and PICP was assessed employing an ELISA technique. A significant correlation was found between BSP serum values and B-ALP (r = 0.532, p = 0.0001). Median serum BSP levels were 8.0 micrograms/l, median B-ALP values were 22.39 U/ml in these patients. Also a significant correlation was observed between BSP and OC (r = 0.588, p = 0.0001), more pronounced in the female patient group (r = 0.632, p < 0.0001). A weak association between BSP and PICP in the female group was detected (r = 0.398, p = 0.0001). In the female group BSP was inversely related to serum estradiol levels (r = -0.274, p = 0.002) as to BMD (DEXA) at the lumbar spine and femoral neck. In conclusion, BSP might be a useful marker of non-collagenous organic bone matrix in laboratory assessment of bone turnover, being inversely related to BMD at lumbar spine and femoral neck and showing significant correlations to established markers of bone turnover like B-ALP and OC.
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PMID:Serum levels of immunoreactive bone sialoprotein in osteoporosis: positive relations to established biochemical parameters of bone turnover. 1112 46

Hyperthyroidism is associated with enhanced osteoblastic and osteoclastic activity, and patients frequently have low bone mineral density and high bone turnover. The aim of this study was to examine the bone formation and resorption markers trend in 12 female patients, before and after normalization of thyroid activity. The following measurements were made at baseline and 1 and 6 months after hormone normalization induced by methimazole treatment: total alkaline phosphatase (ALP), bone alkaline phosphatase (BALP), collagen type C-terminal propeptide (PICP), osteocalcin (BGP), telopeptide (ICTP), urinary-hydroxyproline/urinary creatinine (uOHP/uCreat), urinary calcium/urinary creatinine (uCa/uCreat) and deoxypyridinoline crosslinks (D-Pyr). Compared with controls, all of these parameters were significantly increased (ALP p = 0.014; BALP p = 0.0001; PICP p = 0.013; BGP p = 0.009; ICTP p = 0.0001; uOHP/uCreat p = 0.002; uCa/uCreat p = 0.044; crosslinks p = 0.0001). After treatment the values of ALP, BALP and PICP in hyperthyroid patients showed an initial slight increase and then a significant downwards trend (ALP p = 0.008, BAP p = 0.001, PICP p = 0.026). Furthermore, resorption markers showed a significant decrease (uOHP/ uCreat p < 0.005 and D-Pyr p < 0.008). As regards lumbar BMD patients, measurements were significantly reduced in comparison with the control group (p = 0.005). Six months after serum thyroid hormones level normalization, we observed a significant increase (p=0.014 vs baseline). Both neoformation and resorption markers are useful to assess pathological bone turnover and bone involvement in hyperthyroidism. They could also be employed to monitor the effect of antithyroid treatment on bone and to indicate if bone antiresorption therapy should be considered.
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PMID:Bone turnover in hyperthyroidism before and after thyrostatic management. 1119 5

Serum bone-Gla protein (BGP), bone alkaline phosphatase (B-AP), and C-terminal cross-linked telopeptide of type I collagen (ICTP) levels were evaluated in 18 adults with acquired GH deficiency (GHD, 14 males and 4 females, age range: 25-59 yr) before, at 3, 6, 9 and 12 months of rec-GH treatment (0.125 IU/kg/week for the first month, followed by 0.25 IU/kg/week for 11 months) and 6 months after the withdrawal of therapy. Total body bone mineral density (BMD, g/cm2) was measured with dual energy X-ray absorptiometry (Hologic QDR 1000/W) before, at 12 months of GH treatment and 6 months after its withdrawal. Before treatment, BGP (mean+/-SE: 5.1+/-0.4 ng/ml), B-AP (59.4+/-6.5 IU/l), ICTP (3.1+/-0.3 ng/ml) levels of patients were similar to in healthy controls (BGP: 5.4+/-0.1 ng/ml; B-AP: 58.2+/-2.0 IU/l; ICTP: 4.1+/-0.3 ng/ml). GH treatment caused a significant increase of BGP, B-AP, ICTP levels, the maximal stimulation of bone resorption, occurring after 3 months of GH treatment, while the maximal effect on bone formation being evident later (at 6th month). A slight decline in BGP, B-AP, T-AP and ICTP levels occurred at 9-12 months of therapy, although the values remained significantly higher than in basal conditions and with respect to healthy controls. Before treatment, mean total body BMD of patients (1.110+/-0.027 g/cm2, range: 0.944-1.350 g/cm2) was not significantly different (z-score: +0.47+/-0.31, NS) from that observed in healthy controls (1.065+/-0.008 g/cm2, range: 1.008-1.121 g/cm2). GH therapy was associated with a significant reduction of mean total body BMD values (6th month: -1.8+/-0.5%, p<0.01; 12th month: -2.1+/-1.0%, p<0.05 vs baseline), particularly evident in the first six months of treatment. Six months after the withdrawal of GH therapy, BGP (5.9+/-0.5 ng/ml), B-AP (57.3+/-7.0 IU/l) and ICTP (3.2+/-0.1 ng/ml) levels returned similar to those recorded before treatment, while total BMD increased (+1.5+/-0.7, p<0.05), remaining however slightly lower than in basal conditions (-0.6+/-1.2, NS). In conclusion, our study shows that: a) acquired GHD in adulthood is associated with both normal bone formation/resorption indexes and normal total body BMD; b) GH therapy causes a significant rise of bone formation/resorption markers (earlier and greater for bone resorption); c) one-year GH therapy is associated with a reduction of total body BMD values, particularly evident in the first 6 months of treatment; d) the effects of GH therapy on bone turnover are transient, being completely reverted six months after the withdrawal of GH therapy; e) the increase of total body BMD (up to baseline values) after GH withdrawal might be explained as consequence of persisting effects of previous GH stimulation on bone remodeling.
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PMID:Effects of 12-month GH treatment on bone metabolism and bone mineral density in adults with adult-onset GH deficiency. 1138 8

Over the past decade, the outcome of liver transplantation in primary sclerosing cholangitis (PSC) patients with end-stage liver disease has improved significantly with many centres reporting 1-year patient and graft survival of 90-97% and 85-88%, respectively. Based on these results, liver transplantation has emerged as the treatment of choice for PSC patients. Specific complications related to PSC remain problematical. Inflammatory bowel disease (IBD) occurs in 70% of patients, and there is a distinctly increased risk of colorectal neoplasia both pre- and post-transplantation. Furthermore, symptoms related to IBD post-transplantation can become severe and lead to the need for proctocolectomy. Cholangiocarcinoma remains a major risk facing the PSC patient and develops in 15-30% of patients. Markers to detect the early neoplastic changes of cholangiocarcinoma are not available. To date, outcome following liver transplantation in PSC patients who have associated cholangiocarcinoma has been dismal. However, those patients who are found to have an incidental cholangiocarcinoma have an acceptable low incidence of recurrence of disease. To assess optimal timing of liver transplantation, natural history risk scores have been developed and utilized. Utilizing such risk scores, estimated survival for the individual PSC patient can be obtained. Finally, there is an increased incidence of both acute and chronic rejection, hepatic artery thrombosis and biliary stricturing in PSC patients undergoing liver transplantation. A late rise in serum alkaline phosphatase level is almost always indicative of biliary stricturing and recurrence of disease. Approximately 20% of patients followed for 5 years or more will have recurrence of PSC documented both on cholangiography and histology.
Best Pract Res Clin Gastroenterol 2001 Aug
PMID:Liver transplantation for primary sclerosing cholangitis: timing, outcome, impact of inflammatory bowel disease and recurrence of disease. 1149 75

Bone loss is accelerated in elderly men. Little is known about the pathophysiology of senile bone loss or about the role played by relative sex steroid deficiency in the determination of bone turnover in elderly men. In a population-based sample of 283 healthy, ambulatory men, aged 71-86 years, we sought to determine whether lower bone mineral density (BMD; using dual-energy X ray absorptiometry at the hip and the forearm) is associated with higher bone turnover, and we assessed the impact of sex steroid status on bone turnover. Indices of bone formation, serum osteocalcin (s-Oc), and bone-specific alkaline phosphatase (s-bAP) and indices of bone resorption, serum and urinary telopeptide of type I collagen (s-CTx and u-CTx), and urinary free deoxypyridinoline (u-Dpd) were intercorrelated (r = 0.29-0.76, p < 0.001). Bone turnover indices were negatively associated with BMD (r = -0.17 to -0.34, p < 0.01). In univariate analyses, there was a trend toward weak negative associations of bone turnover markers with serum free testosterone (FT), significant only for s-Oc and s-CTx (r = -0.16 and -0.14, p < 0.01), and with serum free estradiol (FE(2)), significant only for u-CTx and s-CTx (r = -0.18 and -0.19; p < 0.01). The lower quartile for FE(2) was associated with higher values of u-CTx (p = 0.003) and s-CTx (p < 0.001). However, in multivariate models, for the individual markers of bone turnover a negative association between estradiol (E(2)) or FE(2) and s-CTx was the only remaining (marginally) significant association (p < 0.05) for the relationship between sex steroids and any of the bone turnover indices assessed. In community-dwelling men age >70 years, bone turnover rate, as determined by biochemical markers, is a significant negative determinant of prevalent BMD. However, the findings do not support the view that relative differences in sex steroid status, as observed among healthy elderly men, have a major impact on bone turnover.
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PMID:Inverse association between bone turnover rate and bone mineral density in community-dwelling men >70 years of age: no major role of sex steroid status. 1155 74


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