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)

We have studied a large Mennonite kindred in which 20 members were affected with Hirschsprung disease (HSCR), 5 of whom had one or more manifestations of Waardenburg syndrome (WS) type II (WS2). Eleven additional relatives had signs of WS2 without HSCR. Since HSCR and WS2 each represent perturbations of neural crest migration/differentiation, this large pedigree with apparent cosegregation of HSCR and WS2 offered an opportunity to search for linkage between these loci, candidate genes, and random DNA markers, particularly in view of recent discoveries of genes for Waardenburg syndrome type I (WS1) and Hirschsprung disease (c-ret). We have examined the following possible linked markers in 69 relatives in this family: the c-ret gene (HSCR); the human PAX3 gene (HuP2) on chromosome 2q (WS1) and placental alkaline phosphatase (ALPP) on chromosome 2q (linked to WS1); argininosuccinate synthetase (ASS) on chromosome 9q, close to ABO blood groups which have shown weak linkage to WS; and the beta 1 GABA receptor gene (GABARB1) on chromosome 4q13-11, close to c-kit, deletions of which cause piebaldism. Linkage between any of these loci and HSCR/WS in this kindred was excluded, demonstrating that there is at least one further locus for HSCR other than c-ret.
 ...
PMID:Second locus for Hirschsprung disease/Waardenburg syndrome in a large Mennonite kindred. 780 41

The aim of this study was to evaluate two biodegradable polymeric systems as scaffolds for bone tissue engineering. Rat bone marrow cells were seeded and cultured for 1 week on two biodegradable porous polymeric systems, one composed of poly(ethylene glycol)-terephthalate/poly(butylene terephthalate) (PEGT/PBT) and the other composed of cornstarch blended with poly(epsilon-caprolactone) (SPCL). Porous hydroxyapatite granules were used as controls. The ability of cells to proliferate and form extracellular matrix on these scaffolds was assessed by a DNA quantification assay and by scanning electron microscopy examination; their osteogenic differentiation was screened by the expression of alkaline phosphatase. In addition, the in vivo osteogenic potential of the engineered constructs was evaluated through ectopic implantation in a nude mouse model. Results revealed that cells were able to proliferate, differentiate, and form extracellular matrix on all materials tested. Moreover, all constructs induced abundant formation of bone and bone marrow after 4 weeks of implantation. The extent of osteogenesis (approximately 30% of void volume) was similar in all types of implants. However, the amount of bone marrow and the degree of bone contact were higher on HA scaffolds, indicating that the polymers still need to be modulated for higher osteoconductive capacity. Nevertheless, the findings suggest that both PEGT/PBT and SPCL systems are excellent candidates to be used as scaffolds for a cell therapy approach in the treatment of bone defects.
 ...
PMID:Evaluation of two biodegradable polymeric systems as substrates for bone tissue engineering. 1451 73

Native extracellular matrix (ECM) is a complex fibrous structure loaded with bioactive cues that affects the surrounding cells. A promising strategy to mimicking native tissue architecture for tissue engineering applications is to engineer fibrous scaffolds using electrospinning. By loading appropriate bioactive cues within these fibrous scaffolds, various cellular functions such as cell adhesion, proliferation and differentiation can be regulated. Here, we report on the encapsulation and sustained release of a model hydrophobic drug (dexamethasone (Dex)) within beaded fibrillar scaffold of poly(ethylene oxide terephthalate)-poly(butylene terephthalate) (PEOT/PBT), a polyether-ester multiblock copolymer to direct differentiation of human mesenchymal stem cells (hMSCs). The amphiphilic beads act as depots for sustained drug release that is integrated into the fibrillar scaffolds. The entrapment of Dex within the beaded structure results in sustained release of the drug over the period of 28days. This is mainly attributed to the diffusion driven release of Dex from the amphiphilic electrospun scaffolds. In vitro results indicate that hMSCs cultured on Dex containing beaded fibrillar scaffolds exhibit an increase in osteogenic differentiation potential, as evidenced by increased alkaline phosphatase (ALP) activity, compared to the direct infusion of Dex in the culture medium. The formation of a mineralized matrix is also significantly enhanced due to the controlled Dex release from the fibrous scaffolds. This approach can be used to engineer scaffolds with appropriate chemical cues to direct tissue regeneration.
...
PMID:Amphiphilic beads as depots for sustained drug release integrated into fibrillar scaffolds. 2479 94

Additive manufactured scaffolds are fabricated from three commonly used biomaterials, polycaprolactone (PCL), poly (L\DL) lactic acid (P(L\DL)LA), and poly(ethylene oxide terephthalate)/poly(butylene terephthalate) (PEOT/PBT). Scaffolds are compared biologically and tribologically. Cell-seeded PEOT/PBT scaffolds cultured in osteogenic and chondrogenic differentiation media show statistical significantly higher alkaline phosphatase (ALP) activity/DNA and glycosaminoglycans (GAG)/DNA ratios, followed by PCL and P(L\DL)LA scaffolds, respectively. The tribological performance is assessed by determining the friction coefficients of the scaffolds at different loads and sliding velocities. With increasing load or decreasing sliding velocity, the friction coefficient value decreases. PEOT/PBT show to have the lowest friction coefficient value, followed by PCL and P(L\DL)LA. The influence of the scaffold architecture is further determined with PEOT/PBT. Reducing of the fiber spacing results in a lower friction coefficient value. The best and the worst performing scaffold architecture are chosen to investigate the effect of cell culture on the friction coefficient. Matrix deposition is low in the cell-seeded scaffolds and the effect is, therefore, undetermined. Taken together, our studies show that PEOT/PBT scaffolds support better skeletal differentiation of seeded stromal cells and lower friction coefficient compared to PCL and P(L/DL)A scaffolds.
...
PMID:Biological and Tribological Assessment of Poly(Ethylene Oxide Terephthalate)/Poly(Butylene Terephthalate), Polycaprolactone, and Poly (L\DL) Lactic Acid Plotted Scaffolds for Skeletal Tissue Regeneration. 2677 15

Swift progress in biofabrication technologies has enabled unprecedented advances in the application of developmental biology design criteria in three-dimensional scaffolds for regenerative medicine. Considering that tissues and organs in the human body develop following specific physico-chemical gradients, in this study, we hypothesized that additive manufacturing (AM) technologies would significantly aid in the construction of 3D scaffolds encompassing such gradients. Specifically, we considered surface energy and stiffness gradients and analyzed their effect on adult bone marrow derived mesenchymal stem cell differentiation into skeletal lineages. Discrete step-wise macroscopic gradients were obtained by sequentially depositing different biodegradable biomaterials in the AM process, namely poly(lactic acid) (PLA), polycaprolactone (PCL), and poly(ethylene oxide terephthalate)/poly(butylene terephthalate) (PEOT/PBT) copolymers. At the bulk level, PEOT/PBT homogeneous scaffolds supported a higher alkaline phosphatase (ALP) activity compared to PCL, PLA, and gradient scaffolds, respectively. All homogeneous biomaterial scaffolds supported also a significantly higher amount of glycosaminoglycans (GAGs) production compared to discrete gradient scaffolds. Interestingly, the analysis of the different material compartments revealed a specific contribution of PCL, PLA, and PEOT/PBT to surface energy gradients. Whereas PEOT/PBT regions were associated to significantly higher ALP activity, PLA regions correlated with significantly higher GAG production. These results show that cell activity could be influenced by the specific spatial distribution of different biomaterial chemistries in a 3D scaffold and that engineering surface energy discrete gradients could be considered as an appealing criterion to design scaffolds for osteochondral regeneration.
...
PMID:Surface energy and stiffness discrete gradients in additive manufactured scaffolds for osteochondral regeneration. 2692 24

Materials based on biodegradable polyesters, such as poly(butylene terephthalate) (PBT) or poly(butylene terephthalate-co-poly(alkylene glycol) terephthalate) (PBTAT), have potential application as pro-regenerative scaffolds for bone tissue engineering. Herein, the preparation of films composed of PBT or PBTAT and an engineered spider silk protein, (eADF4(C16)), that displays multiple carboxylic acid moieties capable of binding calcium ions and facilitating their biomineralization with calcium carbonate or calcium phosphate is reported. Human mesenchymal stem cells cultured on films mineralized with calcium phosphate show enhanced levels of alkaline phosphatase activity suggesting that such composites have potential use for bone tissue engineering.
 ...
PMID:Biomineralization of Engineered Spider Silk Protein-Based Composite Materials for Bone Tissue Engineering. 2877 81