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)

Activities of glutamic-oxalacetic transaminase, glutamate dehydrogenase, gamma-glutamyl transferase were reduced in unstimulated pooled saliva of 15-year-old adolescents with endemic fluorosis, vs. those without fluorosis. This point to reduced production of glutamate which is indispensable for bacterial growth. The activity of acid phosphatase in pooled stimulated with 1% pilocarpin saliva of rats fed a water ration with 5 and 20 mg/liter fluorine in comparison with control rats fed water with fluorine concentration of 0.21 mg/liter. Noteworthy that alkaline phosphatase activity was virtually unchanged at fluorine concentrations 5 and 20 mg/liter in the water. The significance of the results as far as it regards the pathogenesis of caries and fluorosis is discussed.
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PMID:[The enzymes of glutamate and organic phosphate metabolism in the saliva in fluorosis (clinical and experimental research)]. 748 2

We have recently demonstrated that phenytoin is an osteogenic agent at low doses. The present paper describes observations that a mitogenic dose (i.e., 20 microM in BGJb medium) of fluoride significantly augments the phenytoin-dependent stimulation of normal human bone cell proliferation and alkaline phosphatase (ALP) activity in cell culture. Additionally, the present study was designed to investigate whether fluoride and phenytoin would interact to increase bone formation in rats in vivo. Four groups of weight-matched adult male rats received daily I.P. injection of (1) vehicle (10% DMSO), (2) 5 mg/kg/day phenytoin, (3) 5 mg/kg/day phenytoin and 50 ppm NaF, and (4) 50 ppm NaF and vehicle, respectively, for 36 days. Sodium fluoride (NaF) was delivered in drinking water. Blood samples were drawn weekly and analyzed for serum osteocalcin, ALP, calcium, phosphorus, and 25(OH)D3. Rats were labeled with tetracycline at day 21 and 30 and histomorphometric analysis was carried out on the tibia at the end of the experiment. Neither agent by itself or together affected the serum calcium, phosphorus, or 25(OH)D3 levels. All measures of bone formation, i.e., serum osteocalcin level and ALP activity, bone ALP specific activity, mineral apposition rate, bone formation rate, and % bone formation surface, were increased by each agent. Fluoride and phenytoin together produced bigger increases in each parameter than did each agent alone. Trabecular bone volume was increased in the tibial metaphysis by fluoride or phenytoin alone; and when administered together, the two agents produced a greater increase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phenytoin and fluoride act in concert to stimulate bone formation and to increase bone volume in adult male rats. 762 47

The osteoporotic syndrome is characterized by a reduction in quantity (osteopenia) and damage of the quality (microarchitecture) of bone mineralization. These are heterogeneous disturbances caused by multiple not well known metabolic causes. It is diagnosed by the presence of bone deformations or non-traumatic fractures. The early detection of osteopenia is important and it is considered that individuals whose bone mineral density (BMD) is lower than 80% of the normal value, are more exposed to fractures. Serum alkaline phosphatase, hydroxyproline and urinary pyridolines are biochemical markers. Nutritional aspects and physical movements are emphasized to obtain a larger bone mass, specially during the growing period. It is absolutely necessary to ingest enough quantity of calcium and in the southern regions of the country consumption of Vitamin D must be increased. Therapeutical resources tend to prevent osteopenia more effectively. Estrogens are greatly used in postmenopausic women for the prevention but not for the treatment of osteoporosis once established. They are effective but there still exist some doubts about the innocuousness of long term treatments. Calcitonines increase vertebral mineralization temporarily and may be used as alternatives of replacement hormonal therapies. Bisphosponates present different mechanisms, for example, pamidronate is not cytotoxic and for this reason does not interfere in the remodelling process, which is absolutely necessary to maintain or improve the architectural quality of the bone. The effect of bisphosphonates on mineralization is lasting. As they are new drugs, they have not yet been definitely approved in every country. Fluorine salts have always produced controversial results, some favourable initial effects do not prevent adverse consequences in a long treatment. Vitamin D, gallium nitrate and ipriflavone produce fairly good results, which must still be compared with those of the more active agents. The use of other drugs (tamoxifeno, parathormone, growth factors, thiazide and inhibitors of the proton pump) is still under development. It is concluded that osteoporosis is a pathologic process of ageing, for which there are pharmaceutical products available, specially to prevent osteopenia and bone damage.
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PMID:[Osteoporosis. Detection, prevention, and treatment]. 824 34

The in vitro osteogenic effects of fluoride have not always been consistently observed in human bone cells. The present study sought to test if dexamethasone (Dex) could potentiate the action of fluoride to increase the detectability of the stimulatory effects of fluoride on [3H]thymidine incorporation, alkaline phosphatase (ALP) specific activity, collagen synthesis, and osteocalcin secretion in human TE85 osteosarcoma cells. Neither Dex at 10(-10)-10(-6) M or fluoride at a mitogenic dose (100 microM) had any consistent stimulatory effects on thymidine incorporation. When the cells were treated with both agents simultaneously, significant and highly reproducible stimulations were observed. The mitogenic effects of the two agents were confirmed with cell number counting. Analysis of variance (ANOVA) revealed a significant interaction (P < 0.001) between fluoride and Dex on cell proliferation. The enhancing effect of Dex on [3H]thymidine incorporation was not due to a shift of the optimal dose response of fluoride. Though fluoride alone or Dex alone also had no consistent effect on ALP specific activity, the co-treatment with fluoride and Dex for 24 hours produced significant (P < 0.001, ANOVA) stimulation in ALP specific activity. Fluoride alone had no consistent effect on collagen synthesis and on 1, 25(OH)2D3-dependent osteocalcin secretion, whereas Dex treatment consistently inhibited these two osteoblastic parameters in a dose-dependent manner. However, both the collagen synthesis and osteocalcin secretion rates were significantly higher (P < 0.001 ANOVA for each) when the cells were co-treated with Dex and fluoride (100 microM) than when they were treated with Dex alone. Thus, these data indicate that the response in collagen synthesis and osteocalcin secretion to fluoride stimulation was more readily observed in the presence of Dex than in its absence. ANOVA analysis revealed that the interaction between fluoride and Dex on collagen synthesis, but not the 1,25(OH)2D3-dependent osteocalcin secretion, was significant (P < 0.02). In summary, we have demonstrated for the first time that in TE85 cells (1) Dex potentiated the effects of fluoride on cell proliferation, ALP specific activity, and collagen synthesis; (2) while Dex at 10(-7)-10(-6) M alone inhibited the collagen synthesis and at 10(-9)-10(-6) M reduced osteocalcin secretion, Dex at 10(-8)-10(-6) M significantly stimulated the proliferation of TE85 cells; and (3) Dex interacted with fluoride to increase the percentage of experiments showing an osteogenic action of fluoride. In conclusion, the in vitro osteogenic actions of fluoride in human TE85 cells are more consistently observed in the presence than in the absence of Dex.
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PMID:Dexamethasone enhances the osteogenic effects of fluoride in human TE85 osteosarcoma cells in vitro. 866 71

The aim of the present study was to assess the effects of the new fluorine pro-drug monofluorophosphate (MFP) in postmenopausal women with vertebral osteopenia and high bone turnover. We enrolled postmenopausal women (PMW, 43-59 years) who had had a natural menopause 2-5 years before the study, had vertebral bone mineral density (BMD) < 1 SD from the premenopausal mean, and had at least one of the biochemical markers of bone remodeling > 1 SD over the mean for premenopausal women. Patients were randomly divided into two treatment groups (group 1, 500 mg/day of oral calcium; group 2, MFP at the dose of 20 mg F-equivalents + 600 mg calcium/day) for 2 years (n = 21 in each group). The lumbar vertebral (L2-4) BMD and total body bone mineral (TBBM) were measured by dual-energy X-ray absorptiometry (Lunar DPX, Lunar Corporation, USA). Urinary hydroxyproline excretion (OH-P/Cr), plasma bone Gla protein (BGP) and serum alkaline phosphatase (AP) were assayed. In group 1 the markers of bone turnover and vertebral BMD did not show any significant modification, while TBBM showed a significant (p < 0.05) decrease after 24 months. In group 2 a significant (p < 0.05) decrease in OH-P/Cr (-23.9 +/- 2.0%), and an increase in both BGP (+19.4 +/- 2.6%) and AP (+10.3 +/- 2.6%) levels were observed after 24 months of MFP administration. In this group, both vertebral BMD (+5.01 +/- 0.9%, p < 0.01) and TBBM (+4.0 +/- 0.6%, p < 0.05) showed a significant increase after 24 months. Present results suggest that, in osteopenic PMW, MFP administration induces a significant increase in vertebral BMD without impairment of cortical bone, with a reduction in bone resorption and an increase in bone formation rate.
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PMID:Treatment of postmenopausal vertebral osteopenia with monofluorophospate: a long-term calcium-controlled study. 869 70

Cortical and trabecular bone loss can lead to osteoporosis in chronic forms of anorexia nervosa (AN). As there is some debate about the reversibility of this condition, we performed a longitudinal follow-up study of 27 cases in which clinical, biological, X-ray and lumbar and femoral neck dual photon absorptiometry examinations were conducted every 6 months for up to 30 months. Three groups were distinguished: G1, untreated amenorrheic AN (N = 14, total follow-up 126 months); G2, effectively treated AN (N = 11, total follow-up 192 months), with two subgroups: fluoride (N = 5) and estrogen (N = 6); and G3, remitting AN with normalization of the gonadic function (N = 2, total follow-up 36 months). Results were adjusted for each patient to a 6-month variation. Semestrial variations in lumbar bone mineral density (BMD) were -2.1 +/- 1.3%, +2.8 +/- 1.5%, and -0.3 +/- 1.3% (mean +/- SEM), respectively for G1, G2 and G3; those for femoral neck BMD semestrial variations were -5.9 +/- 2.1%, -3.8 +/- 1.2% and -1.0 +/- 0.6%. Femoral neck and lumbar BMD variations for G1 were mainly correlated positively with bone-forming markers (serum osteocalcin, alkaline phosphatase) and negatively with initial lumbar BMD. Estrogen alone increased lumbar BMD by +1.4 +/- 2.3% every 6 months but did not stabilize femoral neck BMD (-3.5 +/- 1.4%). Fluoride increased lumbar BMD by 4.8 +/- 1.8%. Both lumbar and femoral neck BMD were stabilized in the remission group (-0.3 +/- 1.3% and -1.0 +/- 0.6%), despite half of the follow-up time with amenorrhea. In conclusion, untreated AN is associated with a marked trabecular and cortical bone loss (4-10% per year), which can lead to osteoporotic fractures. In prevention of bone loss, the efficacy of estrogen is difficult to investigate in AN, even with a well-controlled trial. Our study could provide argument that, when the observance of this preventive treatment is assessed, lumbar BMD can be stabilized in chronic forms of AN.
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PMID:Follow-up of bone mineral density in 27 cases of anorexia nervosa. 898 Jan 62

We hypothesized that fluoride partly acts by changing the levels of circulating calcium-regulating hormones and skeletal growth factors. The effects of oral fluoride on 24 female, Dutch-Belted, young adult rabbits were studied. The rabbits were divided into two study groups, one control and the other receiving about 16 mg fluoride/rabbit/day in their drinking water. After 6 months of fluoride dosing, all rabbits were euthanized and bone and blood samples were taken for analyses. Fluoride treatment increased serum and bone fluoride levels by over an order of magnitude (P < 0.001), but did not affect body weight or the following serum biochemical variables: urea, creatinine, phosphorus, total protein, albumin, bilirubin, SGOT, or total alkaline phosphatase. No skeletal fluorosis or osteomalacia was observed histologically, nor did fluoride affect serum PTH or Vitamin D metabolites (P > 0.4). BAP was increased 37% (P < 0.05) by fluoride; serum TRAP was increased 42% (P < 0.05); serum IGF-1 was increased 40% (P < 0.05). Fluoride increased the vertebral BV/TV by 35% (P < 0.05) and tibial ash weight by 10% (P < 0.05). However, the increases in bone mass and bone formation were not reflected in improved bone strength. Fluoride decreased bone strength by about 19% in the L5 vertebra (P < 0.01) and 25% in the femoral neck (P < 0. 05). X-ray diffraction showed altered mineral crystal thickness in fluoride-treated bones (P < 0.001), and there was a negative association between crystal width and fracture stress of the femur (P < 0.02). In conclusion, fluoride's effects on bone mass and bone turnover were not mediated by PTH. IGF-1 was increased by fluoride and was associated with increased bone turnover, but was not correlated with bone formation markers. High-dose fluoride treatment did not improve, but decreased, bone strength in rabbits, even in the absence of impaired mineralization.
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PMID:Fluoride treatment increased serum IGF-1, bone turnover, and bone mass, but not bone strength, in rabbits. 919 19

Gemcitabine is a novel fluorine-substituted cytarabine (Ara-C) analogue with activity against a range of solid tumours. Besides dose-limiting haematological toxicity, renal side-effects were observed from phase I and II studies concerning elevations of serum creatinine, proteinuria and erythrocyturia. The aim of this study was to investigate the effect of gemcitabine on renal function in 11 untreated patients with non-small cell lung cancer (NSCLC). Gemcitabine was given as weekly infusions of 1250 mg/m2 for 3 weeks, followed by 1 week rest. This comprised one cycle (maximum of six cycles). The glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured simultaneously with a constant infusion of 125I-iothalamate and 131I-hippuran, respectively. Tubular damage was monitored by excretion of tubular enzymes (lactic dehydrogenase (LDH), alkaline phosphatase (ALP), gamma-glutamyltransferase (GT) and beta 2-microglobulin); glomerular damage was monitored by excretion of albumin in the urine. In 9 patients, the effect of the first infusion was evaluated. After the first infusion of gemcitabine, no change was observed in renal function. After two, three, and six cycles of treatment, no significant changes in GFR and ERPF were noticed in 9 evaluable patients. However, in 3 patients, a decrease in GFR of > 10% was observed after multiple cycles. In one of them this was accompanied with albuminuria (360 mg/24 h) and erythrocyturia. There were no significant changes in urinary excretion of tubular enzymes or albumin. In conclusion, we did not observe acute renal toxicity with gemcitabine. No significant cumulative effects of gemcitabine on renal function could be detected, although 3 patients, treated with multiple cycles of gemcitabine, showed a moderate decrease in renal function. Glomerular damage might play a role in the development of renal function loss.
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PMID:Effects of gemcitabine on renal function in patients with non-small cell lung cancer. 962 59

This study investigated the biochemical structure of proteoglycans synthesized during matrix maturation by mineralizing bone cells in vitro, in the presence and absence of fluoride. Bone cells were obtained from rat femur washes and cultured in alpha MEM media supplemented with fetal calf serum, ascorbic acid, beta-glycerophosphate and dexamethasone. Cells were characterized as osteoblast-like by the expression of alkaline phosphatase activity and the synthesis of collagen type I and osteocalcin. Fluoride, present in the culture media at concentrations of 10(-5) M or 10(-7) M, had negligible effect on cell viability. However, calcium deposition was increased in cell cultures incubated in the presence of fluoride. Proteoglycans were extracted from the extracellular matrix with 4 M guanidinium chloride and purified by anion exchange chromatography. Biochemical analysis identified the presence of the small leucine rich proteoglycan, decorin and biglycan, in addition to degradation products relating to the larger chondroitin sulphate protoeglycan, versican. Fluoride had little effect on the size or amino acid composition of the protein core, but resulted in significant alterations to the GAG chains, including a dramatic reduction in chain length, reduction in sulphation and decrease in the proportion of dermatan sulphate compared to chondroitin sulphate. The influence of fluoride on proteoglycan structure synthesized by mineralizing bone cells provides valuable information, indicating specific roles for dermatan sulphate and chondroitin sulphate proteoglycans. The results suggested that fluoride affected the post-translational assembly of the GAG chains which may be an influential factor in the mineralization process.
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PMID:Structural analysis of proteoglycans synthesized by mineralizing bone cells in vitro in the presence of fluoride. 974 42

1. We investigated the effect of protein kinases and phosphatases on murine cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels, expressed in Chinese hamster ovary (CHO) cells, using iodide efflux and the excised inside-out configuration of the patch-clamp technique. 2. The protein kinase C (PKC) activator, phorbol dibutyrate, enhanced cAMP-stimulated iodide efflux. However, PKC did not augment the single-channel activity of either human or murine CFTR Cl- channels that had previously been activated by protein kinase A. 3. Fluoride, a non-specific inhibitor of protein phosphatases, stimulated both human and murine CFTR Cl- channels. However, calyculin A, a potent inhibitor of protein phosphatases 1 and 2A, did not enhance cAMP-stimulated iodide efflux. 4. The alkaline phosphatase inhibitor, (-)-bromotetramisole augmented cAMP-stimulated iodide efflux and, by itself, stimulated a larger efflux than that evoked by cAMP agonists. However, (+)-bromotetramisole, the inactive enantiomer, had the same effect. For murine CFTR, neither enantiomer enhanced single-channel activity. In contrast, both enantiomers increased the open probability (Po) of human CFTR, suggesting that bromotetramisole may promote the opening of human CFTR. 5. As murine CFTR had a low Po and was refractory to stimulation by activators of human CFTR, we investigated whether murine CFTR may open to a subconductance state. When single-channel records were filtered at 50 Hz, a very small subconductance state of murine CFTR was observed that had a Po greater than that of human CFTR. The occupancy of this subconductance state may explain the differences in channel regulation observed between human and murine CFTR.
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PMID:Regulation of murine cystic fibrosis transmembrane conductance regulator Cl- channels expressed in Chinese hamster ovary cells. 976 19


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