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)

Improved histochemical techniques for the demonstration of NADP+-specific isocitrate dehydrogenase and malate dehydrogenase in tissue sections are described. With these techniques a semipermeable membrane is interposed between the incubating solutions and the tissue sections preventing diffusion of enzymes into the medium during incubation. In the histochemical system the NADP+-dependent enzymes catalyze the electron transfer from threo-Ds-isocitrate or L-malate into NADP+. Phenazine methosulphate and menadione serve as intermediate electron acceptors between reduced coenzyme and nitro-BT. Sodium-azide and amytal are incorporated into the incubating-medium to block electron transfer to the cytochromes. For demonstrating enzyme activities in sections containing non-specific alkaline phosphatase, a phosphatase inhibitor is added into the incubation media. Problems involved in the histochemical demonstration of both enzymes are discussed.
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PMID:Semipermeable membranes for improving the histochemical demonstration of enzyme activities in tissue sections. V. Isocitrate: NADP+ oxidoreductase (decarboxylating) and malate: NADP+ oxidoreductase (decarboxylating). 23 22

The regenerating forelimb of the adult newt, Notophthalmus viridescens was investigated for 5'-nucleotidase (5' ribonucleotide phosphohydrolase, 3.1.3.5) acitivity. The newt's humeri were surgically removed, and after a twenty-one-day recovery period, the forelimbs amputated above the elbows. Regenerates were sampled at predetermined times for specific phases in the progress of regeneration, frozen, sectioned in a cryostat, and the sections fixed in 10% cold formol calcium. The Wachstein and Meisel [25] lead procedure at neutral pH was used predominately in these experiments, although tests were also conducted with Gomori's [14] calcium, Allen's [21] highly alkaline procedures. The substrates used to obtain specific enzyme reactions were adenine, cytosine, guanine, uracil and inosine 5'-monophosphate nucleotides. Sodium beta-glycerophosphate served as a non-specific phosphomonoesterase substrate, distilled water replaced substrate, and inhibitors such as zinc and cyanide ions were used as control measures to assist in increasing the precision in interpreting the results obtained. The most reactive 5'-nucleotidase (5'-Nase) loci were in the walls of the blood vascular system, mysial and neural sheaths, dermis, and periosteum: the principal cells involved were macrophages, endothelium of blood vessels, and fibrocytes of connective tissues. A moderate enzyme response was elicited from secretory cells of some of the subcutaneous glands, hypertrophied chondrocytes and osteogenic centers, chondrocytes in the articular regions and within red blood cells and leucocytes. Normal, injured and degenerating, or regenerating striated muscle and nerve fibers were judged unreactive for 5'-Nase. The epidermis and wound epithelium displayed negative responses for 5'-Nase. Cells forming the regeneration blastema were 5'-Nase reactive during the early formative phase, but with growth and development of the blastema into bulb and conic forms, these cells did not respond for this enzyme-activity. One suggestion offered is that the absence of 5'-Nase in cells of the blastema may be related to the lack of an adequate blood-vascular supply. Several functions of 5'-Nase in normal and regenerating tissues are discussed. A basic conclusion reached is that 5'-nucleotidase hydrolyses may be more involved in fundamental anabolic than in catabolic metabolism.
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PMID:Localization of 5'-ribonucleotide phosphohydrolase in regenerating (and normal) limb tissues of the adult newt Notophthalmus viridescens. 24 77

Thirteen cases of advanced Paget's Disease of bone were treated with Sodium Etidronate (EHDP) at 20 mg/kg/day for 6 months and followed at 2 to 3-month intervals for 20 months with serum alkaline phosphatase, 24-hour urinary hydroxyproline, radiographic skeletal survey, whole-body scanning with Tc-99m-Sn-EHDP and F-18, external body counting with the same radiopharmaceuticals over preselected areas, skin temperature, densitometry of normal phalanges and bone biopsies. Sodium etidronate had a marked effect on Pagetoid bone in all cases with reduction of bone turnover demonstrated by the chemistries, scanning, external counting, skin temperature and X-ray diffraction studies of the bone biopsies. Normal bone did not appear to be materially affected by the drug. Complications drug dose-related included new pain in 6 cases, two fractures in Pagetoid areas and one case of severe demineralization. There was one case of spinal cord compression unlikely to be drug related. All complications cleared or were successfully treated by the end of the study. Some patients continued to show reduction in bone turnover to the end of the study, as long as 14 months after stopping EHDP. Long-term follow-up is needed for final evaluation of the efficacy of the drug. Sodium etidronate shows promise as an agent in the treatment of Paget's Disease. Smaller doses or shorter courses of therapy or combination of EHDP and calcitonin may be just as efficacious and may avoid complications.
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PMID:Evaluation of sodium etidronate in the treatment of Paget's disease of bone. Osteitis deformans. 40 46

The dog jejunum is a much denser tissue than the ileum, with a greater weight per unit length and higher proportion of mucosal tissue. Morphometric analysis reveals longer and wider villi, deeper crypts and larger enterocytes in the jejunal mucosa. Uptake of phenylalanine or beta-methyl-glucoside by tissue slices in vitro is slightly greater in jejunal than in ileal tissue. The levels of acid phosphatase and alkaline phosphatase in the individual enterocytes are significantly greater in the jejunum, according to quantitative histochemical analysis. The absorption of water, sodium, potassium, chloride and glucose in vivo is significantly smaller in the jejunal than in ileal loops, particularly when expressed in terms of unit mucosal weight. Sodium and water absorptions are stimulated by glucose at both sites, but the stimulation is significantly greater in the ileum. Opposite results have been obtained in rats where the transport of phenylalannie in vitro is greater in the ileum, but water, electrolyte and glucose absorption in vivo is greater in the jejunum.
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PMID:Functional and structural characteristics of the jejunum and ileum in the dog and the rat. 84 73

Dexamethasone (4-8 mg/m2 body surface area) was given orally or intravenously to six normal volunteers. The maximum neutrophil count occurred 4-6 h after oral or intravenous administration of dexamethasone and was due almost entirely to an increase in mature neutrophils; concomitantly there was a lymphocytopenia. A second rise in the neutrophil count occurred 24 h after oral ingestion of dexamethasone, coinciding with a lymphocytosis. Neutrophil alkaline phosphatase (NAP) activity during development fell as the neutrophil count rose. Other haematological values were unchanged except for small increments in erythrocyte sedimentation rate (ESR). Sodium concentration in serum and urine remained normal but urinary potassium excretion and urine volume increased after the intravenous dose. There was a direct relationship between plasma concentration of dexamethasone and the rise in neutrophil count following intravenous but not oral administration. The concentration of dexamethasone in plasma fell to half its peak value in 2-6 h. Dexamethasone-induced neutrophilia was similar to that induced by other corticosteroids. Dexamethasone in a dose of 6 mg/m2 produced minimal discomfort while inducing an adequate neutrophilia in the volunteers.
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PMID:Development of Neutrophilia by serially increasing doses of dexamethasone. 87 36

In the serum of 40 male and 40 female rats the following parameters were determined: Sodium, potassium, creatinine, chloride, calcium, inorganic phosphorus, glucose, urea, protein, cholesterol, bilirubin, lipids, alanine amino-transferase, alkaline phosphatase and leucine arylamidase. The analyses were carried out in the same rats both after continuous feeding, and after a 24-hour fasting periods spaced at intervals of 3- to 4-weeks. The concentration of glucose and the activities of alanine aminotransferase and alkaline phosphatase were higher after feeding than after fasting, and in most cases these differences were statistically significant. The concentration of lipids tended towards increased values. The other parameters examined were slightly or not influenced by the time of the foregoing feeding.
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PMID:[The influence of feeding on clinical-chemical parameters in the serum of rats (author's transl)]. 119 11

Ifosfamide (IF) is an alkylating cytostatic derived from nitrogen mustard. In addition to its well-known urotoxic effects (hemorrhagic cystitis), several cases of Fanconi syndrome following IF therapy have been reported. No information is available concerning the pathomechanisms of this tubulotoxicity. We used the permanent renal epithelial cell line LLC-PK1 in order to investigate whether major metabolites of IF (i.e. 4-OH-IF, acrolein and chloracetyldehyde) induced the transport defects most frequently detected after IF therapy in vivo. LLC-PK1 cells of passages 162-177, grown in plastic culture dishes, were used in a confluent state. Sodium-dependent and independent fluxes of l-[3H]alanine and of D-[3H]glucose were determined by standard techniques. Activities of marker enzymes of apical and basolateral membranes, of mitochondria and of endoplasmic reticulum were determined in cell homogenates. IF itself has no detectable effect on fluxes of l-alanine and D-glucose in LLC-PK1 cells. The IF metabolite 4-OOH-IF induces a clear inhibition of sodium-dependent fluxes of both substrates after a 24-hour exposure of cells to 100 mumol/l of 4-OOH-IF. Chloracetaldehyde induces a biphasic response of sodium-dependent fluxes of l-alanine with increased uptake rates at low concentrations (< 200 mumol/l) and with a short incubation time, while higher concentrations and long exposure of the cells leads to a reduction in sodium coupled transport. Glucose transport is affected in a comparable way, however, in contrast to alanine transport, chloracetaldehyde also stimulates sodium-independent fluxes of glucose. Acrolein is the most toxic substance tested. It severely damages cell monolayers at concentrations beyond 75 mumol/l. Sodium-coupled glucose and alanine transport is inhibited by acrolein at concentrations higher than 50 mumol/l. Sodium-coupled glucose transport is more sensitive to all metabolites tested than alanine transport. While acrolein strongly affects both transport systems, marker enzymes of the apical plasma membrane, i.e. alkaline phosphatase and leucine amino-peptidase, are not significantly inhibited, suggesting a specificity of the toxic effect for the transport proteins. We conclude that LLC-PK1 cells represent a good model for further investigation of the pathogenesis of Fanconi syndrome after IF therapy. Sodium-dependent transport systems are more sensitive to acrolein than other cell surface proteins.
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PMID:Inhibition of sodium-dependent transport systems in LLC-PK1 cells by metabolites of ifosfamide. 128 22

Sodium zeolite A (SZA), a synthetic sodium aluminosilicate having a high ion exchange capacity, has been shown to influence Ca and P utilization in chickens. A 3 x 2 x 2 factorial arrangement of treatments was used to investigate the effect of dietary P (.41, .55, and .69% total P), Ca (.6 and 1%), and SZA (0 and .75%) on growth, plasma, and tibia characteristics of chicks from 5 to 15 days of age. Growth, feed intake, gain:feed ratio, and tibia characteristics were influenced by dietary Ca and P in a manner consistent with dietary recommendations for these macro minerals. The addition of Ca, SZA, or both exacerbated the adverse effects of feeding low-P diets, yet alleviated the adverse effects of feeding a low-Ca, high-P diet. Dietary SZA had no effect (P greater than .5) on plasma Ca or alkaline phosphatase; however, SZA reduced (P less than .01) plasma P. Dietary SZA increased (P less than .02) tibia Mn, Zn, Cu, and Al. The SZA-induced increase in tibia Al was most evident in chicks fed low levels of P (SZA by P interaction, P less than .02). The overall response to dietary SZA addition paralleled the response observed from Ca supplementation, indicating that SZA increased Ca utilization, reduced P utilization, or contributed to both of these effects. These data demonstrate that the effects of SZA are influenced by the dietary concentration of Ca and P and that the addition of SZA to diets low in P results in bone Al accumulation.
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PMID:Effect of dietary sodium zeolite A and graded levels of calcium and phosphorus on growth, plasma, and tibia characteristics of chicks. 131 80

Metacyclogenesis of Trypanosoma cruzi epimastigotes was evaluated in a medium supplemented with Triatoma infestans intestinal homogenate in the presence of sugars and derivates as are mannose, galactose, fucose, N-acetylglucosamine, mannose 6-P, and fructose 1,6-P at a concentration of 25 mM. Only mannose significantly inhibited metacyclogenesis. Sodium metaperiodate and trypsin treatment of the intestinal homogenate also inhibited differentiation. In our opinion there exists a proteinic factor in the intestine of the vector that promotes metacyclogenesis and is incorporated by the parasite. Treatment of the intestinal homogenate with alkaline phosphatase had no effect. Instead, high ionic strength in the medium (0.4 M NaCl) strongly inhibited metacyclogenesis indicating that, in these conditions, the possible binding of the differentiation factor to the parasite surface was inhibited.
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PMID:Trypanosoma cruzi: inhibition of metacyclogenesis by mannose. 132 84

Sodium zeolite A (SZA), a synthetic sodium aluminosilicate having high ion-exchange capacity, has been shown to increase eggshell specific gravity in laying hens and to improve Ca utilization in chickens. A 4 x 2 factorial arrangement of treatments was used to investigate the effect of dietary Ca (.6, .8, 1.0, and 1.2%) and SZA (0 and .75%) on growth, plasma, and tibia characteristics of chicks from 5 to 15 days of age. Increasing dietary Ca linearly increased (P less than .05) Ca and alkaline phosphatase (AP) in plasma and increased tibia shearing force and percentage ash, Ca, and P in tibiae. However, dietary Ca linearly decreased (P less than .05) inorganic P and Mg in plasma and Mg and Mn in tibiae. Sodium zeolite A decreased (P less than .05) plasma P and AP and tibia Mg but increased (P less than .05) tibia Ca, Zn, Al, and Mn concentrations. Tibia ash and shearing force were increased in chicks fed SZA receiving inadequate dietary Ca, but they were decreased in chicks fed SZA and excess Ca (Ca by SZA interaction, P less than .05). Tibia density showed a similar trend, but the effect was not significant (Ca by SZA interaction, P less than .12). The addition of SZA enhanced tibia ash, density, and shearing force when dietary Ca was low; however, when added to diets containing 1.2% Ca, SZA reduced many bone mineralization indices with the exception of tibia Ca.
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PMID:Effect of dietary sodium zeolite A and graded levels of calcium on growth, plasma, and tibia characteristics of chicks. 166 18


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