ABSTRACT
BACKGROUND: To evaluate bone regenerative capacity of cryoprotected corticocancellous allogeneic bone graft performed in type II and III post-extraction sockets for ridge preservation after twelve weeks in-vivo. MATERIAL AND METHODS: Twenty-seven type II or III bony-walled extraction sockets (mandible and maxilla) were selected for this study. Following atraumatic tooth-extraction a cryoprotected corticocancellous allogeneic bone graft material and a resorbable porcine-derived collagen membrane were used for ridge preservation. During re-entry surgery at approximately 12 weeks, bone core biopsies were obtained using a 3.2 mm trephine drill and samples were histologically processed and subjected to qualitative and quantitative histomorphometric analysis. Quantitative data was analyzed using a general linear mixed model with results presented as mean values with the corresponding 95% confidence interval values. RESULTS: Healing without incident and ridge preservation allowed for the placement of dental implants after 12 weeks in 25 out of the 27 treated socket sites. Analyses yielded an average of ~21.0±7% of old/native bone, ~17±5.5% of newly regenerated bone (total of ~38±12.8% for all bone), 0.23±0.14% of new bone presenting with nucleating sites within the matrix, ~52±5.12% of soft tissue, and 3.6±2.09% of damaged bone. The average regenerated bone was statistically analogous to that of old/native bone (p=0.355). Furthermore, an atypical histological pattern of bone regeneration was observed, with newly formed bone exhibiting "infiltration-like" behavior and with new bone nucleating sites observed within the demineralized bone matrix. CONCLUSIONS: Cryoprotected corticocancellous allogeneic bone-graft demonstrated osteoconductive, osteoinductive, and osteogenic properties, yielding unique healing patterns which does warrant further investigation.
Subject(s)
Alveolar Bone Loss , Alveolar Ridge Augmentation , Hematopoietic Stem Cell Transplantation , Animals , Swine , Tooth Socket/surgery , Alveolar Ridge Augmentation/methods , Bone Regeneration , Wound Healing , Tooth Extraction , Bone Transplantation/methods , Alveolar Bone Loss/surgeryABSTRACT
Macrocyclic compounds are an attractive modality for drug development, but the limited availability of large, structurally diverse macrocyclic libraries hampers the discovery of leads. Here, we describe the discovery of efficient macrocyclization reactions based on thiol-to-amine ligations using bis-electrophiles, their application to synthesize and screen large libraries of macrocyclic compounds, and the identification of potent small macrocyclic ligands. The thiol-to-amine cyclization reactions showed unexpectedly high yields for a wide substrate range, which obviated product purification and enabled the generation and screening of an 8988 macrocycle library with a comparatively small effort. X-ray structure analysis of an identified thrombin inhibitor (K i = 42 ± 5 nM) revealed a snug fit with the target, validating the strategy of screening large libraries with a high skeletal diversity. The approach provides a route for screening large sub-kilodalton macrocyclic libraries and may be applied to many challenging drug targets.
Subject(s)
Amines/chemistry , Macrocyclic Compounds/chemistry , Small Molecule Libraries , Sulfhydryl Compounds/chemistry , Antithrombins/chemistry , Antithrombins/pharmacology , Cyclization , Drug Discovery , Humans , Ligands , Macrocyclic Compounds/chemical synthesis , Macrocyclic Compounds/pharmacology , Models, Molecular , Molecular Conformation , Molecular Structure , Trypsin Inhibitors/chemistry , Trypsin Inhibitors/pharmacologyABSTRACT
AIM: To determine if women with diabetes in pregnancy have a delayed onset of lactation through a systematic review of the literature. METHODS: We searched databases including MEDLINE, Web of Science, PubMed, CINAHL Plus and PsychINFO for articles assessing diabetes in pregnancy and lactogenesis. Thirty-one articles were screened and 10 articles were included in the systematic review. We extracted data on diabetes in pregnancy and onset of lactation (secretory activation or lactogenesis II). RESULTS: The 10 studies examining the association between women with diabetes in pregnancy and delayed onset of lactation reported a significant delay in women with diabetes compared with women without diabetes. Two studies assessed the impact of metabolic control on lactogenesis, and found an association between poorer metabolic control and delayed onset of lactation. CONCLUSIONS: Although this review has found evidence of an association between women experiencing diabetes during pregnancy and delayed onset of lactation, the presence of many potential confounding factors need to be acknowledged.
