Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The latent form of transforming growth factor-beta (TGF-beta) is a component of the extracellular matrix of bone. The active form, when locally injected in vivo, stimulates both inflammation and ectopic bone formation. The present study was undertaken to determine if TGF-beta also stimulated mineralization by isolated rat calvarial osteoblasts cultured in collagen gels. Gels were used because they should mimic in vivo conditions better than classical monolayer culture. Compared to cells in monolayers, osteoblasts cultured in collagen gels exhibited slower growth, but higher alkaline phosphatase activity and mineral deposition. Cultured cells also synthesized the osteoblast-specific marker, osteocalcin. The increase in osteocalcin in cell layers was parallel to the increase in mineral deposition. In the presence of TGF-beta, neither cell growth nor alkaline phosphatase activity increased. Instead, a small decrease occurred in both parameters when compared to untreated cultures. Accumulation of collagen, the major component of the extracellular matrix where mineralization occurs, was similar in untreated and TGF-beta 1-treated cultures. However, 8 pM TGF-beta 1 dramatically suppressed mineral deposition in both types of cultures. Despite TGF-beta 1 stimulating a fourfold increase in lactic acid, the consequent increase in culture medium acidity did not account for the inhibitory effects of TGF-beta 1 on mineralization. These results demonstrate that collagen gel culture is an improved technique over conventional monolayer culture for demonstrating differentiated osteoblast function and sensitivity to TGF-beta 1. TGF-beta 1, at a concentration that has little effect on cell growth, alkaline phosphatase activity, or collagen accumulation, is a potent inhibitor of mineralization.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transforming growth factor-beta inhibition of mineralization by neonatal rat osteoblasts in monolayer and collagen gel culture. 779 46

The buccal mucosa represents a potentially important topical route for delivery of peptide or protein drugs with some unique advantages such as the avoidance of hepatic first-pass metabolism and the acidity and protease activity encountered in the gastrointestinal tract. However, the bioavailabilities or relative potencies of intraorally administered peptides are usually quite low, unless permeabilizers are employed. Chitosan, a mucopolysaccharide of marine origin, has been claimed to act both as a bioadhesive and permeabilizer, making it a candidate system for mucosal drug delivery. In this study, the enhancement effect of chitosan in gel form for oral mucosa was investigated with a large bioactive peptide, transforming growth factor-beta (TGF-beta). Chitosan gel was prepared at 2% concentration in dilute lactic acid and TGF-beta was incorporated into the gel. The effect of chitosan as a permeabilizer was determined by measuring the flux of TGF-beta across porcine oral mucosa in an in vitro system. The localization of TGF-beta within the oral mucosa was determined by horizontal sectioning and counting. Chitosan was found to exert a marked permeabilizing effect on buccal mucosa for peptide drug.
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PMID:Enhancing effect of chitosan on peptide drug delivery across buccal mucosa. 1096 16

Calcium sulfate, plaster of Paris, has a long clinical history for use as a bone graft substitute in various skeletal sites. The current authors examined the in vivo response of calcium sulfate pellets alone or in combination with autogenous bone graft in a bilateral critical-size distal femoral cancellous defect in an adult sheep model. New thick bone formation was seen in defects filled with calcium sulfate pellets alone. Increased immunostaining for bone morphogenetic protein-2, bone morphogenetic protein-7, transforming growth factor-beta, and platelet derived growth factor was seen in defects filled with calcium sulfate pellets alone and in combination with autograft. The local acidity during calcium sulfate resorption is proposed as a possible in vivo mechanism for this type of material.
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PMID:Response of a calcium sulfate bone graft substitute in a confined cancellous defect. 1257 23