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)

The effect of magnesium deficiency on bone cell differentiation and bone formation was investigated using in vivo matrix-induced endochondral ossification as a test system. Demineralized bone matrix was implanted subcutaneously in young (35-day-old) male Long-Evans rats that had been fed a semisynthetic Mg-deficient diet (50 ppm Mg) for 7 days. Plasma Mg levels were reduced to 25-30% of control values at that time. Control rats were paired the same diet, supplemented to contain 1000 ppm Mg. The implants were harvested 7, 9, 11, 15, and 20 days after implantation and analyzed for Mg and Ca content, 45Ca incorporation, and alkaline phosphatase levels. At each stage, plaques (implants) removed from Mg-deficient rats showed retardation in cartilage and bone differentiation and matrix calcification. Magnesium content was markedly reduced when compared to the control plaques. Histological appearance of the matrix-induced plaques confirmed the retardation in bone development and mineralization suggested by the chemical indicators. Most marked was the virtual absence of bone marrow in 20-day-old plaques in Mg-depleted rats. These data show that bone cell differentiation can occur in a severely Mg-depleted environment, although the onset of mineralization and bone remodeling was delayed and bone marrow differentiation was impaired.
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PMID:Influence of magnesium depletion on matrix-induced endochondral bone formation. 11 39

The collagenous extracellular matrix of bone obtained after dissociative extraction with 4 M guanidine-HCl is an optimal substratum for bone induction by osteogenin, a bone morphogenetic protein. As a proteinaceous substratum, this matrix and other collagen-based materials may be immunogenic. Thus, the search and discovery of a non-immunogenic substratum is a necessary prerequisite for the therapeutic application of the principle of bone induction to skeletal repair. Bovine osteogenin, purified greater than 50,000-fold and with an apparent molecular mass of 28-42 kilodaltons, was delivered into nonresorbable porous hydroxyapatite in granular and disc configuration. A total of 328 preparations were bioassayed for osteogenic activity by subcutaneous implantation into 164 Long-Evans rats. Specimens were harvested at day 7, 11 and 21 after implantation and subjected to alkaline phosphatase activity determination and histologic analysis. Osteogenin combined with discs of porous hydroxyapatite induced in vivo differentiation of the osteogenic phenotype in mesenchymal cells invading the three-dimensional porous space of the inorganic substratum. The geometry of the substratum had a profound influence on bone induction, since the expression of the osteogenic phenotype was solely confined in porous hydroxyapatite with disc configuration. Osteogenin did not induce bone differentiation when combined with granules of porous hydroxyapatite with identical pore dimensions. The finding that the biological activity of osteogenin can be restored and delivered by a substratum with defined geometry other than the insoluble collagenous matrix may form the basis of the potential therapeutic application of bone morphogenetic proteins.
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PMID:The critical role of geometry of porous hydroxyapatite delivery system in induction of bone by osteogenin, a bone morphogenetic protein. 132 28

Plasmodium yoelii nigeriensis infection in mice caused an increase in uptake of 125I-labeled bovine serum albumin, 51Cr-labeled erythrocytes and Evans blue dye from peripheral circulation into the brain. Isolated cerebral microvessels which were characterized in terms of their morphology under scanning electron microscope and enhancement of the specific activities of biochemical markers, viz. alkaline phosphatase, gamma-glutamyl transpeptidase, and monoamine oxidase, showed significant decrease in these activities due to P. yoelii nigeriensis infection. On the other hand, relatively minor (statistically insignificant) changes occurred in the first two enzyme specific activities in the cerebral cortex and monoamine oxidase registered an increase in this tissue due to infection. Histological examination of the cerebral tissue of infected animals by light and electron microscopy showed broken blood vessel walls and leakage of erythrocytes into extravascular space, some of which contained intraerythrocytic malarial parasite in a state of cell division.
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PMID:Aberrations in cerebral vascular functions due to Plasmodium yoelii nigeriensis infection in mice. 135 26

In awake normocapnic rats, the density of the total and of the perfused capillary network was determined in 10 brain areas. The density of perfused capillaries was measured by using fluorescein isothiocyanate (FITC) globulin or Evans blue as intravenous marker and by fluorescent microscopy. The density of morphologically existing capillaries was determined according to either the histochemical alkaline phosphatase method or a newly developed immunohistochemical fluorescent method that allows marking of the capillary wall constituent fibronectin with a primary antibody directed against fibronectin. This antibody is made visible by a second FITC-coupled antibody (indirect immunofluorescence). Comparison of perfused and existing capillary counts revealed high congruence when fluorescent results were compared. In contrast, the alkaline phosphatase technique yielded capillary counts that were consistently 30% lower than the fibronectin and the FITC globulin counts. The identity of the perfused and the morphologically existing capillary network could be confirmed by a newly developed double-staining technique. First, the perfused capillaries were quantified by intravascular Evans blue. Then, the existing capillaries were relocated in the same measuring field by the fibronectin technique. Such double staining resulted in identical capillary counts in 97% of all cases. The following conclusions have been reached: 1) Fluorescent methods show a perfusion of virtually all capillaries in the brain of the awake normocapnic rat. 2) The alkaline phosphatase technique appears to underestimate the capillary density in the rat brain.
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PMID:Congruence of total and perfused capillary network in rat brains. 168 41

Experiments were performed to investigate the effects of lindane and linuron on calcium metabolism, femur morphometry and nephrotoxicity. Long-Evans hooded rats were dosed daily for 10 weeks with 0, 10 or 20 mg lindane or 10, 20 or 40 mg linuron/kg body weight beginning at weaning. Lindane significantly decreased urinary calcium concentration, serum alkaline phosphatase concentration and the cross-sectional medullary area of the bone. Lindane was nephrotoxic at both dose levels as demonstrated by elevated kidney weights, kidney-to-body-weight ratios, urinary LDH, tubule regeneration and hyaline droplet degeneration. Linuron significantly reduced medullary cross-sectional area at the 2 higher dose levels and decreased the total femur cross-sectional area at the highest dose level in the absence of effects on calcium excretion. Femur density and strength were also significantly reduced at the highest dose level of linuron. Neither compound affected the serum concentrations of parathyroid hormone or 1,25-dihydroxy Vitamin D-3. Both linuron and lindane exposure significantly increased serum cholesterol concentrations and reduced serum triglyceride concentrations. Both compounds affected calcium metabolism and/or bone morphometry but possibly by different mechanisms since the effects were not the same.
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PMID:The effects of lindane and linuron on calcium metabolism, bone morphometry and the kidney in rats. 169 Apr 64

Alterations in regional cerebral blood flow (rCBF) and percent perfused capillaries (indicative of functional intercapillary distance) were determined in conscious male Long-Evans rats after reducing their blood O2-carrying capacity by exposing them to 1% CO for 12 min. rCBF was determined by the iodoantipyrine method. rCBF increased from a mean of 106 +/- 8 (SE) ml.min-1.100 g-1 before CO exposure to 173 +/- 14 ml.min-1.100 g-1 after CO exposure. There was a greater flow increase (126%) in the cerebral cortex than in the lower brain stem [pons (45%), medulla (39%)]. Presence of fluorescein isothiocyanate-labeled dextran identified the perfused capillaries before and after CO exposure. The volume fraction (Vv) and number/mm2 (Na) of all capillaries (perfused and nonperfused) in a given area of brain were determined after staining for alkaline phosphatase. The percent Vv and percent Na of perfused capillaries increased uniformly (from approximately 50% to approximately 80%) in all parts of the brain after CO exposure. In the presence of tissue hypoxia with undiminished plasma PO2, the brain vasculature allowed greater flow of blood while the microvasculature adjusted to reduce the diffusion distance for O2.
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PMID:Cerebral regional capillary perfusion and blood flow after carbon monoxide exposure. 175 41

The susceptibility to lipid peroxidation (LPO) of liver, kidneys, brains, lungs, heart, and testes was assessed in rats administered intraperitoneally with various doses of cadmium (Cd). Dose-response studies were carried out with male Long Evans rats (12-week-old; 300 +/- 33 g) injected with 25, 125, 500, and 1250 micrograms Cd/kg as CdCl2 and sacrificed after 24 h. In time-response studies, animals were administered with 25 and 500 micrograms Cd/kg as CdCl2 and sacrificed after 2, 6, 12, 24, and 72 h. Exposure of rats to low and moderate doses of Cd by the intraperitoneal route stimulated LPO in all the tissues investigated as assessed by the measurement of thiobarbituric acid reactive substances (TBARS). Lungs and brain were the most responsive, and these tissues and liver displayed early responses following Cd exposure. Comparison of LPO to various tissue indicators (for liver: alanine aminotransferase (ALT), sorbitol dehydrogenase (SDH), alkaline phosphatase (ALP); for lungs: ALP, gamma-glutamyl transpeptidase (GGT] suggested that low doses of Cd stimulated LPO without any evidence of acute damages. These results suggest that LPO is an early and sensitive consequence of Cd exposure as determined in various organs. Investigation of liver, lungs, and heart antioxidant defense system components (glutathione peroxidase (GPX), glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PDH), superoxide dismutase (SOD] revealed that GPX might be considered as a potential modulator of the Cd-induced LPO reaction in lungs and heart tissues.
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PMID:Studies on lipid peroxidation in rat tissues following administration of low and moderate doses of cadmium chloride. 182 34

The purpose of this study was to determine the cerebral regional microvascular and vascular responses to amphetamine sulfate at a dose (5 mg/kg) known to affect neuronal function. Cerebral blood flow (14C-iodoantipyrine method) and percent of perfused capillaries (fluorescein isothiocyanate-dextran and alkaline phosphatase staining method) were determined during control and after intravenous administration of amphetamine in conscious Long-Evans rats. Amphetamine caused an increase in blood pressure (34%) and heart rate (31%). There was a significant increase in averaged cerebral blood flow from 98 +/- 8 to 166 +/- 9 ml/min/100 g after amphetamine. This flow increase was significant in the cortex, basal ganglia, pons and medulla, however the increase was not significant in the hypothalamus. In control rats, there were approximately 325 +/- 17 capillaries/mm2 of brain tissue and 52 +/- 1% of them were perfused. Amphetamine increased the percent perfused significantly to 72 +/- 1% in all examined regions. There was a similar significant increase in the percent of perfused cerebral capillary volume fraction. There were both vascular and microvascular responses to amphetamine, increasing cerebral blood flow as well as reducing the diffusion distance for oxygen.
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PMID:Effect of amphetamine on cerebral blood flow and capillary perfusion. 190 79

Subcutaneous implantation of demineralized bone matrix (DBM) from rat initiates a sequence of developmental events that results in endochondral bone formation. This investigation examined the modification of the osteoinductive potential of DBM during the initial stages of this developmental cascade. Diffusion chambers (DC), constructed with filters of known pore size, permitting or excluding cells from entering the chambers, and containing DBM were subcutaneously implanted into Long-Evans male rats for specific time periods (1-7 days). DC were recovered and the osteoinductive potential of the matrix from these chambers was then tested by subcutaneous implantation and assaying the resulting day 11 plaque tissue enzymatically for alkaline phosphatase activity, and histologically for evidence of chondrogenesis and osteogenesis. The possible modification of DBM by local systemic factors (enzymatic degradation) or contact by polymorphonuclear leukocytes (PMNs) was also investigated. We have concluded from this study that the osteoinductive potential of DBM has a half-life of 5-7 days following implantation and although the enzymes collagenase, elastase, and trypsin abolished this activity, pepsin significantly enhanced it. Culture of PMNs with matrix prior to its implantation appeared to have little effect. Furthermore, during the initial stages of matrix-induced endochondral bone formation, DBM serves as both the instructive inducer and permissive substratum required in this process.
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PMID:In vivo analysis of the half-life of the osteoinductive potential of demineralized bone matrix using diffusion chambers. 250 25

Hydroxyapatite (HA) and Demineralized Bone Matrix (DBM) are being investigated as potential osteogenic agents with hopes that these substances can be used to induce bone formation in non-union fractures. This study was done to determine the relative effects of HA and DBM implanted as moldable phospholipid composites in bone defects that result in non-unions. We studied 22 ten-month-old Long-Evans male rats with 5.0 mm unilateral radial defects implanted with HA, DBM, and a combination of both substances. Control defects were left unfilled. Eight weeks after implantation, the histological sections demonstrated a decrease in bone formation with HA relative to controls. The HA crystals were encapsulated by connective tissue stroma made up of collagenous elements, fibroblasts, and blood vessels. There were no indications of bone formation within the fibrous stroma. 45Calcium, alkaline phosphatase, and bone gla protein (BGP) assays demonstrated a 16% increase in bone formation in rats implanted with DBM, an 80% decrease in groups implanted with HA (p = 0.01) and an 80% decrease with DBM plus HA (p = 0.01). Radiologic analysis corresponds well with histological and biochemical results. We conclude that osteogenesis in non-union defects is enhanced by the implantation of DBM, while HA interferes with bone formation in the rat model. In the presence of both substances, HA appears to impede new bone growth, negating any positive effects seen with DBM.
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PMID:Osteogenesis in bone defects in rats: the effects of hydroxyapatite and demineralized bone matrix. 255 16


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