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 early acute pulmonary response of Wistar rats exposed nose-only to respirable polymeric diphenylmethane 4,4'-diisocyanate (MDI) aerosol was examined. This study investigated the time course of the relationship between acute pulmonary irritation and ensuing disturbances of the air/blood barrier in rats exposed to concentrations of 0.7, 2.4, 8, or 20 mg MDI/m3. The duration of exposure was 6 h. The time-response relationship of MDI-induced acute lung injury was examined 0 h (directly after cessation of exposure), 3 h, 1 day, 3 days, and 7 days after exposure. Bronchoalveolar lavage (BAL) fluid was analyzed for markers indicative of injury of the bronchoalveolar region, i.e., angiotensin-converting enzyme, protein, alkaline phosphatase, lactate dehydrogenase, gamma-glutamyltranspeptidase, and sialic acid. Phosphatidylcholine and acid phosphatase were determined in BAL fluid and cells. Glutathione was determined in BAL fluid and lung tissue. This analysis revealed no latent period of effects except a transiently delayed influx of cells and increased lung weights on postexposure days 1 and 3. Markedly loaded BAL cells with phosphatidylcholine were observed on day 1 only. In most instances, changes returned to the level of the air exposed control on day 7, except increased glutathione in lung tissue. The findings suggest that the most sensitive markers of dysfunction of the air/blood barrier are angiotensin-converting enzyme and protein, including alkaline phosphatase. The statistically significant increase in intracellular phosphatidylcholine and decreased intracellular acid phosphatase on the exposure day suggest that increased amounts of phospholipids are phagocytized by alveolar macrophages, associated with protracted lysosomal catabolism. Partially glutathione-depleted rats exposed to 20 mg/m3 experienced a more pronounced increase in BAL protein than normal rats. In summary, this study suggests that respirable polymeric MDI aerosol interacts directly with the air/blood barrier causing increased extravasation of plasma constituents as a result of increased permeability of capillary endothelial cells. Overall, a transient dysfunction of the pulmonary epithelial barrier occurred at level as low as 0.7 mg/m3 and appears to be related a dysfunction of pulmonary surfactant. Nonprotein sulfhydryl constituents appear to play a role as portal-of-entry specific modifying factors.
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PMID:Acute inhalation toxicity of polymeric diphenyl-methane 4,4'-diisocyanate in rats: time course of changes in bronchoalveolar lavage. 1095 1

This study was performed to verify the response of human bone-derived cells (HBDCs) to moisture-cured silicone-urethanes (mcSUUs) in vitro, as the first step toward using them as scaffolds for bone tissue engineering. Good surgical handling, tissue cavity filling, stable mechanical properties, and potentially improved oxygen supply to cells after implantation justify the investigation of these nondegradable elastomers. A set of various mcSUUs were obtained by moisture-curing NCO-terminated prepolymers, synthesized from oligomeric siloxane diols of two different oligosiloxane chain lengths, and two different diisocyanates (MDI and IPDI), using two different NCO/OH molar ratios. Dibutyltindilaurate (DBTL) or N-dimethylethanolamine (N-met) served as catalysts. After 7 days of culture, cell number, viability, and alkaline phosphatase (ALP) activity were determined, and after 21 days, cell viability and collagen production were determined. Material characteristics significantly influenced the cell response. The mcSUUs prepared with DBTL (widely used in the syntheses of biomaterials) were cytotoxic. The MDI-based mcSUUs were significantly more favored by HBDCs than the IPDI-based ones in all performed tests. MDI-based material with low 2/1 NCO/OH and short chain length was the best support for cells, comparable with tissue-culture polystyrene (with ALP activity even higher). HBDCs cultured on porous scaffolds from this mcSUU produced a tissue-like structure in culture. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.
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PMID:Moisture-cured silicone-urethanes-candidate materials for tissue engineering: a biocompatibility study in vitro. 2009 5

This work reports preliminary results on the development of biointegrable scaffolds, composed of biostable 3D polymer matrices and bioabsorbable inorganic salts, to be used for cell anchorage in bone regeneration. Three crosslinked polyurethane foams (PUFs), prepared by one-step bulk polymerisation from a polyether-polyol mixture, polymeric MDI and water as expanding agent, were tested for their ability to promote adhesion and growth of bone-derived cells. The open porosity of these foams ranged from 16 to 31% with an average pore size of 470 /600 microm, compressive strength (at 10% ε ) of 0.28/0.38 MPa and elastic moduli of 4.88/6.61 MPa. The human osteosarcoma line Saos-2, and primary cultures of normal human articular chondrocytes and bone marrow-derived (HBM) stromal cells were used for in vitro cytocompatibility tests. For cell adhesion and proliferation analysis, DNA synthesis was evaluated by 3 H-thymidine uptake. Osteoblastic differentiation of Saos-2 adherent cells was determined by measuring the enzymatic activity of alkaline phosphatase (ALP). All cell types were able to adhere to all tested PUFs and to synthesize DNA. At 48 hr culture, HBM stromal cells showed the maximal rate of adhesion with the highest rate of proliferation onto PUFs with the largest pore size, whereas both chondrocytes and Saos-2 appeared to adhere preferentially onto foams exhibiting the highest percentage of open porosity. Up to 8 days in culture Saos-2 cells were able to proliferate into all PUFs, with a time-dependent increase of DNA synthesis and ALP activity. At SEM, the morphology of cells adherent to PUF pores was spread with cytoplasmatic extroflessions, indicating a good metabolic activation. These results demonstrate a good cytocompatibility of the proposed 3D matrices, suggesting that their use in the preparation of composite scaffolds is worth further investigation. (Journal of Applied Biomaterials & Biomechanics 2003; 1: 58-66)ABSTRACT: This work reports preliminary results on the development of biointegrable scaffolds, composed of biostable 3D polymer matrices and bioabsorbable inorganic salts, to be used for cell anchorage in bone regeneration. Three crosslinked polyurethane foams (PUFs), prepared by one-step bulk polymerisation from a polyether-polyol mixture, polymeric MDI and water as expanding agent, were tested for their ability to promote adhesion and growth of bone-derived cells. The open porosity of these foams ranged from 16 to 31% with an average pore size of 470 /600 microm, compressive strength (at 10% ε ) of 0.28/0.38 MPa and elastic moduli of 4.88/6.61 MPa. The human osteosarcoma line Saos-2, and primary cultures of normal human articular chondrocytes and bone marrow-derived (HBM) stromal cells were used for in vitro cytocompatibility tests. For cell adhesion and proliferation analysis, DNA synthesis was evaluated by 3 H-thymidine uptake. Osteoblastic differentiation of Saos-2 adherent cells was determined by measuring the enzymatic activity of alkaline phosphatase (ALP). All cell types were able to adhere to all tested PUFs and to synthesize DNA. At 48 hr culture, HBM stromal cells showed the maximal rate of adhesion with the highest rate of proliferation onto PUFs with the largest pore size, whereas both chondrocytes and Saos-2 appeared to adhere preferentially onto foams exhibiting the highest percentage of open porosity. Up to 8 days in culture Saos-2 cells were able to proliferate into all PUFs, with a time-dependent increase of DNA synthesis and ALP activity. At SEM, the morphology of cells adherent to PUF pores was spread with cytoplasmatic extroflessions, indicating a good metabolic activation. These results demonstrate a good cytocompatibility of the proposed 3D matrices, suggesting that their use in the preparation of composite scaffolds is worth further investigation. (Journal of Applied Biomaterials & Biomechanics 2003; 1: 58-66).
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PMID:Cytocompatibility of polyurethane foams as biointegrable matrices for the preparation of scaffolds for bone reconstruction. 2080 73

Mechanical loading represents a crucial factor in the regulation of skeletal homeostasis. Its reduction causes loss of bone mass, eventually leading to osteoporosis. In a previous global transcriptome analysis performed in mouse calvarial osteoblasts subjected to simulated microgravity, the most upregulated gene compared to unit gravity condition was Lcn2, encoding the adipokine Lipocalin 2 (LCN2), whose function in bone metabolism is poorly known. To investigate the mechanoresponding properties of LCN2, we evaluated LCN2 levels in sera of healthy volunteers subjected to bed rest, and found a significant time-dependent increase of this adipokine compared to time 0. We then evaluated the in vivo LCN2 regulation in mice subjected to experimentally-induced mechanical unloading by (1) tail suspension, (2) muscle paralysis by botulin toxin A (Botox), or (3) genetically-induced muscular dystrophy (MDX mice), and observed that Lcn2 expression was upregulated in the long bones of all of them, whereas physical exercise counteracted this increase. Mechanistically, in primary osteoblasts transfected with LCN2-expression-vector (OBs-Lcn2) we observed that Runx2 and its downstream genes, Osterix and Alp, were transcriptionally downregulated, and alkaline phosphatase (ALP) activity was less prominent versus empty-vector transduced osteoblasts (OBs-empty). OBs-Lcn2 also exhibited an increase of the Rankl/Opg ratio and IL-6 mRNA, suggesting that LCN2 could link poor differentiation of osteoblasts to enhanced osteoclast stimulation. In fact, incubation of purified mouse bone marrow mononuclear cells with conditioned media from OBs-Lcn2 cultures, or their coculture with OBs-Lcn2, improved osteoclastogenesis compared to OBs-empty, whereas treatment with recombinant LCN2 had no effect. In conclusion, our data indicate that LCN2 is a novel osteoblast mechanoresponding gene and that its regulation could be central to the pathological response of the bone tissue to low mechanical forces.
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PMID:Lipocalin 2: a new mechanoresponding gene regulating bone homeostasis. 2511 32