Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:025734 (ANOVA)
 22,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum TSH levels are moderately but significantly (P ANOVA: 0.05) decreased by troleandomycin (T; 1 g bid over a 10-day period) compared with josamycin (J) (same doses) and placebo (P) in healthy volunteers. T also significantly increases serum estradiol concentration (P ANOVA: 0.03). This effect may be related to a T-induced inhibition of some P450 monooxygenase isoenzymes and more specifically P 450 NF, determined in our study by a decrease in urinary excretion of 6-beta-hydroxy-cortisol. Troleandomycin and josamycin both show poor upper GI tolerance. Liver enzymes (SGOT, SGPT, alkaline phosphatase and gGT) are significantly altered by T compared with J and P (P ANOVA: 0.007, 0.001, 0.09 and 0.04 respectively). After J, liver function tests are very close to control values (placebo). Liver enzymes are significantly more altered by T than by J (P 0.004, 0.001 and 0.06 for SGOT, SGPT and gGT respectively). Using 6 volunteers in a latin-square designed study, some established effects of oral macrolides were confirmed (poor upper GI tolerance; liver toxicity of T). Some other effects of T were also elicited, which were either unknown (decrease in serum TSH) or expected but which had not previously been assessed in man (increase in serum estradiol; decreased urinary excretion of 6-beta-hydroxy-cortisol).
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PMID:Effects of troleandomycin and josamycin on thyroid hormone and steroid serum levels, liver function tests and microsomal monooxygenases in healthy volunteers: a double blind placebo-controlled study. 195 96

The diagnostic efficacy of five serum liver function tests (aspartate and alanine aminotransferase, alkaline phosphatase, 5' nucleotidase, and bilirubin) was investigated in 95 bone marrow transplant recipients in whom acute graft-vs-host disease was graded by the Seattle criteria. The patient population included a control group of 22 autologous transplant recipients (group I), 33 patients with no GVHD (group II), 21 patients with grades 1 and 2 GVHD (group III), 12 patients with grade 3 GVHD (group IV), and 7 patients with grade 4 GVHD (group V). Student t test analysis of the analytes among the five groups of patients showed that 5' nucleotidase and alkaline phosphatase were the best discriminants among all the possible combinations of group pairs. Peak levels of 5' nucleotidase within each group of patients correlated well with those of alkaline phosphatase in all the allogeneic transplant groups (II-V; r = 0.59), but the correlation of these with bilirubin was less frequent. Also, 5' nucleotidase and alkaline phosphatase showed significant discrimination (P less than 0.05) even between groups I and II, suggesting that they are more sensitive than the Seattle criteria in the diagnosis of GVHD. They also showed the best overall discriminatory ability by one-factor analysis of variance (ANOVA; P = 0.0001 as compared with 0.002, 0.009, and 0.04 for aspartate aminotransferase, alanine aminotransferase, and bilirubin, respectively). Receiver-operating curves of the five analytes again revealed that 5' nucleotidase and alkaline phosphatase were by far the best discriminators among the five groups of patients. Bilirubin was relatively insensitive because it was a good discriminator only between the control group and groups IV and V. The hepatocellular enzymes, alanine and aspartate aminotransferase, correlated well (r = 0.80) but discriminated poorly among the four groups of allogeneic transplant recipients (II-V), suggesting that all four groups had some measure of hepatocellular damage that was independent of the severity of GVHD.
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PMID:Serum 5'nucleotidase and alkaline phosphatase--highly predictive liver function tests for the diagnosis of graft-versus-host disease in bone marrow transplant recipients. 255 45

The aim of this study was to assess the effect of a long-term course of high-dose i.v. pulses of calcitriol (CLT) on hyperparathyroid bone disease (HBD) and functional mass of parathyroid glands of chronically hemodialyzed uremic (CHU) patients. We prospectively studied nine CHU patients treated with CLT, 30 ng/kg/body wt, i.v., thrice weekly over a period of eight months. Plasma concentrations of intact parathyroid hormone (iPTH), bone GLA protein (bGLA) and bone isoenzyme of alkaline phosphatase (biALP) were sampled throughout. Transiliac bone biopsies were made before and after the start of CLT therapy. Double scanning scintigraphy of the neck with 201Tl-99Tc was made before, during and eight months after the start of the treatment. All patients but one, who later responded to higher than planned CLT doses, had significant decreases of plasma iPTH (F = 76; P < 0.0001; ANOVA). The mean pretreatment value of PTH was 966 +/- 160 (mean +/- SE) pg/ml and it had decreased significantly by the first week (T = 2.4, P < 0.04), and had fallen an average of 80% by the 35th week. Ionized plasma calcium concentration was 1.19 +/- .01 mmol/liter which rose significantly (F = 13.5; P < 0.0001) by the 14th week to maximal peak levels, averaging 1.34 +/- .02 mmol/liter. Changes in biALP were parallel to those of iPTH, while bGLA tended to increase immediately after the start of the therapy and to significantly decrease thereafter (T = 3.2; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evidence of healing of secondary hyperparathyroidism in chronically hemodialyzed uremic patients treated with long-term intravenous calcitriol. 786 7

Previous findings in our laboratory have shown that hPTH-(53-84) stimulates alkaline phosphatase activity in dexamethasone-treated ROS 17/2.8 cells. In the present study, we examined the effects of hPTH-(53-84) and hPTH-(1-34) on the expressions of alkaline phosphatase, osteocalcin, and collagen type I mRNA levels in the human osteosarcoma cell line SaOS-2. The effect of hPTH-(53-84) on alkaline phosphatase and osteocalcin message levels was dose dependent (ANOVA, p < 0.005 and p < 0.001, respectively), with significant stimulation observed at 10 nM. Treatment with 10 nM hPTH-(53-84) for 24 h resulted in significant 2- and 1.4-fold increases in mRNA levels for alkaline phosphatase and osteocalcin, respectively (p < 0.05), but had no effect on collagen type I expression. The increased alkaline phosphatase mRNA levels was associated with a 1.5-fold increase in enzyme activity (p < 0.05). In contrast, under similar incubation conditions, hPTH-(1-34) had no significant effects on alkaline phosphatase or osteocalcin mRNA levels. On the other hand, hPTH-(1-34) had dose-dependent stimulatory effects on collagen type I mRNA levels (ANOVA, p < 0.001), 10 nM hPTH-(1-34) stimulating collagen type I expression 1.6-fold (p < 0.05). The results indicate that carboxyl-terminal hPTH-(53-84) has direct and unique biologic effects in human osteoblast-like cells in culture.
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PMID:Carboxyl-terminal parathyroid hormone peptide (53-84) elevates alkaline phosphatase and osteocalcin mRNA levels in SaOS-2 cells. 803 Apr 32

We sought to assess efficacy and safety of a new oral formulation (tablet) of tiludronate in Paget's disease of bone. We studied 128 patients with Paget's disease in an open-label uncontrolled trial. Patients received a daily dose of 400 mg oral tiludronate (two tablets). Treatment was for 6 months. Serum alkaline phosphatase activity (SAP) and fasting urinary excretion of hydroxyproline/creatine (OH/Cr) were measured every 3 months, as were biochemical parameters reflecting renal, hepatic, and hematologic functions. Analgesic efficacy was self-evaluated from a visual analog scale (VAS). Statistical analysis revealed a significant reduction from baseline in SAP and OH/Cr levels, as well as VAS scores. In the whole population with evaluation under treatment, there was a reduction in initial SAP activity after 3 months (47.2 +/- 2.2%, mean +/- SEM) and 6 months (58.3 +/- 2.3%). In the population with SAP levels above twice the upper limit at inclusion and with evaluation at month 3 and month 6 (n = 96), the reduction in SAP levels was 49.3 +/- 2.4% after 3 months and of 59.5 +/- 2.6% after 6 months (ANOVA time effect, p = 0.0001). Aside from mild gastrointestinal disturbances, as experienced with other oral bisphosphonates, clinical tolerance was good. Exhaustive biochemical investigation failed to reveal significant toxicity of tiludronate tablets at the dose of 400 mg/day. The dose of 400 mg daily of this new formulation appears to be a satisfactory tiludronate regimen for the treatment of Paget's disease of bone.
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PMID:Efficacy and tolerability of a new formulation of oral tiludronate (tablet) in the treatment of Paget's disease of bone. 805 89

Phospholipase A2 (PLA2) modifications were investigated in patients with acute and chronic liver diseases, PLA2 variations were related to indices of liver function as well as to parameters of the acute phase response. Serum PLA2 activity modifications were fluorimetrically measured in 105 patients affected by acute and chronic liver diseases or extra-hepatic diseases. One-way ANOVA demonstrated a significant difference among groups (F = 4.53, P < 0.001); Bonferroni's test for pairwise comparisons showed that patients with hepatocellular carcinoma had higher mean values than subjects with benign extra-hepatic diseases (P < 0.01) and mild chronic liver disease (P < 0.05). Multiple regression analysis, performed choosing PLA2 as the dependent variable and blood urea nitrogen, C-reactive protein, alkaline phosphatase and alpha 1-fetoprotein as predictor variables was significant (multiple R = 0.7056, multiple R2 = 0.4978, F = 15.36, P = < 0.0001). The standardized regression coefficients found to be significant were those of C-reactive protein, blood urea nitrogen and alpha 1-fetoprotein. In conclusion, in patients with chronic liver disease, serum PLA2 activity increases parallel to disease severity and accompanies the expression of proteins of the acute phase response that, like PLA2 activity, increase in serum while liver synthesis declines.
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PMID:Increased serum phospholipase A2 activity in advanced chronic liver disease as an expression of the acute phase response. 826 31

Patients with primary hyperparathyroidism have increased bone turnover, but it is less well documented how brief periods of excess parathyroid hormone (PTH) (endogenous or exogenous) affect bone metabolism. In the present double blind study, we examined the effect of either ethylenediaminetetraacetatic acid (EDTA) or placebo on serum levels of PTH and biochemical markers of bone turnover in 15 women and 39 men (aged 41 to 81 years) suffering intermittent claudication due to atherosclerosis. Disodium EDTA was administered as 20 repeated infusions of 3 grams during a period of 5-9 weeks. Serum calcium and serum phosphate decreased following treatment (p < 0.001) and remained unchanged in the placebo group. However, the differences between the groups were insignificant (ANOVA p = 0.13 and p < 0.10, respectively). PTH increased 2 1/2 fold following EDTA treatment (p < 0.001, ANOVA). The change in serum PTH was inversely correlated with the change in serum calcium (r = -0.53, p < 0.01). In the EDTA group, urinary hydroxyproline/creatinine and calcium/creatinine increased after treatment (ANOVA p < 0.001 and p < 0.05, respectively). Serum bone alkaline phosphatase decreased significantly in the EDTA group immediately after treatment (p < 0.001, ANOVA) and returned to baseline level at three months while only an insignificant decrease in serum osteocalcin was seen following treatment. We conclude that EDTA treatment increases endogenous PTH secretion considerably and leads to increased bone resorption. However, no changes in osteoblastic markers indicating increased activation of bone remodeling could be demonstrated. Our findings support that chelation therapy with EDTA is accompanied by bone loss.
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PMID:Effects of intravenous EDTA treatment on serum parathyroid hormone (1-84) and biochemical markers of bone turnover. 829 6

We tested the effect of osteoblastic differentiation on the interactive effects of 17 beta-oestradiol (E2) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on alkaline phosphatase activity. As cell models we utilized the more differentiated human osteosarcoma (SaOS) cells that had been cultured for 6 days in medium containing 10 nM dexamethasone (Dex) (SaOS+Dex cells) and the less differentiated cells cultured in the absence of Dex (SaOS-Dex cells). The cells were challenged with 1,25(OH)2D3 in the presence or absence of Dex for 24 h and then with E2 for an additional 24 h. In SaOS-Dex cells, alkaline phosphatase activity remained constant over the 48-h period and was not significantly affected by E2, 1,25(OH)2D3 or 1,25(OH)2D3+E2 treatment. On the other hand, in SaOS+Dex cells, 1,25(OH)2D3 and E2+1,25(OH)2D3 stimulated alkaline phosphatase activity (ANOVA, F = 154.2, P < 0.0001) with the maximal response at 48 h (P < 0.01). In SaOS+Dex cells, 1,25(OH)2D3 had dose-dependent stimulatory effects which were strongly enhanced by 10 nM E2 (ANOVA, F = 46.0, P < 0.001). Studies on dose-dependent effects of E2, in the presence or absence of 100 nM 1,25(OH)2D3, revealed that in the presence of 1,25(OH)2D3, the E2 dose-response curve was biphasic in SaOS+Dex cells (ANOVA, F = 3.40, P < 0.005), with maximum stimulation at 10 nM E2 (P < 0.01). The specificity of E2 was verified using the inactive 17 alpha-oestradiol and the oestrogen antagonist, tamoxifen. These data indicate that E2 and 1,25(OH)2D3 have positive interactive effects on alkaline phosphatase activity in human osteoblasts, and suggest that the expression of this interaction is dependent on the stage of differentiation of the cells.
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PMID:17 beta-oestradiol enhances the stimulatory effect of 1,25-dihydroxyvitamin D3 on alkaline phosphatase activity in human osteosarcoma SaOS-2 cells in a differentiation-dependent manner. 856 66

The efficacy of bone alkaline phosphatase (ALP) isoenzyme measurement, using a lectin precipitation method, in confirming metastatic sites was assessed in 65 patients with cancer and skeletal (n = 44), hepatic (n = 15) or lymph node (n = 6) metastases; the control group consisted of 33 healthy adults. In all subjects, total ALP activity and osteocalcin were also assayed. Our results confirm that isoenzyme analysis is more specific than total enzymatic activity measurement in the identification of bone metastases: the mean for total ALP values was increased in all patients, while significantly high mean values of bone fraction (p < 0.05 by ANOVA) were observed only in patients with bone secondaries. In the serial monitoring of 9 patients with skeletal metastases, bone ALP values correlate with pain symptomatology: a progressive decrease in bone isoenzyme activity was observed in patients with a complete remission of pain after radiotherapy, while a progressive increase in activity was observed in the presence of increased bone pain. The measurement of bone isoenzyme activity is useful in screening for skeletal metastases; levels appear to correlate with the course of bone symptomatology, thus providing useful objective evidence of response to treatment.
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PMID:Serum bone alkaline phosphatase in the follow-up of skeletal metastases. 857 29

We previously developed two models of human osteoblasts with distinct differentiation stages using cells derived from iliac crest trabecular bone explants cultured long term in the presence (HOB + DEX) and absence (HOB - DEX) of 10 nM dexamethasone (DEX) (Wong et al., J Bone Miner Res 1990;5:803). Using these models from 36 subjects aged 41-80 years, we examined the effects of 17 beta-estradiol (E2) on cell proliferation, osteocalcin (OC) production, alkaline phosphatase (ALP) and basal and parathyroid hormone (PTH)-stimulated adenylate cyclase activities, as well as the steady-state mRNA levels of ALP, collagen type I(COLL), OC, and receptors for E2 (ER) and PTH (PTHr). E2 alone had no effect on [3H]thymidine uptake in (HOB - DEX) cells but appeared to stimulate the uptake in (HOB + DEX) cells in a dose-dependent manner, with maximum effect at 10(-10)M (p < 0.05). However, in the presence of 10(-6)M PTH, E2 inhibited the uptake in (HOB - DEX) cells (ANOVA, KW = 18.95, p < 0.005) but stimulated the uptake in (HOB + DEX) cells (KW = 13.52, p < 0.025). E2 decreased the amount of osteocalcin in culture media from both (HOB - DEX) and (HOB + DEX) cells (p < 0.05). PTH alone or E2, alone or in combination with 10(-9)M PTH, had no effect on ALP activity in (HOB - DEX) cells. In contrast, in (HOB + DEX) cells, E2 + PTH but not E2 alone, had biphasic effects on ALP activity, with maximum stimulation observed at 10(-11) and 10(-10)M E2, and a return to basal levels at 10(-9)M E2. E2 decreased basal adenylate cyclase activities in a dose-dependent manner in (HOB + DEX) but not (HOB - DEX) cells (KW = 13.48, p < 0.05). In (HOB + DEX) cells, E2 had biphasic effects on PTH-stimulated adenylate cyclase activity, with significant stimulation observed at 10(-10)M (p < 0.05). While E2 had no significant effect on osteoblastic marker mRNA levels in (HOB - DEX) cells, it decreased osteocalcin and stimulated PTHr mRNA levels in (HOB + DEX) cells. Thus, in our human osteoblastic cell models, estrogen regulated metabolic function largely in the more differentiated cells, by modifying the effects of PTH.
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PMID:Positive interaction between 17 beta-Estradiol and parathyroid hormone in normal human osteoblasts cultured long term in the presence of dexamethasone. 870 48


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