Enhancement of experimental fracture healing with parathyroid hormone (1-34)

PLEASE NOTE: This work is protected by copyright. Downloading is restricted to the BU community: please click Download and log in with a valid BU account to access. If you are the author of this work and would like to make it publicly available, please contact [email protected] (D.Sc.D)--Boston University, Henry M. Goldman School of Dental Medicine, 2004 (Prothodontics).Includes bibliographic references (leaves 76-87).Substantial progress has been made in the use of surgically implanted recombinant proteins to enhance fracture healing where there is nonunion or substantial loss of bone. However, a systemically administered therapy that could promote fracture healing would be desirable. We therefore tested the hypothesis that a once-daily subcutaneous injection of Parathyroid hormone (1-34) (PTH (1-34)) could enhance fracture healing. Two hundred seventy male Sprague Dawley rats underwent standard, closed mid diaphyseal femoral fractures. Immediately post fractures, animals were divided into three groups and administered daily injections of 5[Mu]g PTH (1-34)Kg, 30[Mu]g PTH (1-34)/Kg, or aqueous vehicle alone (control) for a maximum of 35 days treatment. Each group was further divided into three subgroups, which were euthanized on day 21 , 35, or 84 post fractures respectively. At necropsy, bones were harvested and the calluses subjected to quantitative micro computerized tomography (QCT) scan and mechanical torsion testing to failure. Additionally, calluses from three animals in each group were analyzed by histomorphometry. The 30[Mu]gPTH (1 -34)[Mu]g/day dose produced significant increases on day 21 post fracture for bone mineral content (BMC; P=.008), bone mineral density (BMD; P=.001), and percent cartilage in the callus approaching the significant level (P=.061) relative to controls. On day 35, the 30[Mu]g PTH (1-34)/Kg/day group (p[less than].000) showed increases in BMC and BMD. At this time, the 30[Mu]g PTH (1-34)Kg/day group also showed a significant increase in torque strength (p=.006). While dosing was discontinued after day 35, analyses performed after 84 days in rats previously treated with 30[Mu]g PTH (1-34)/Kg/day showed sustained increases over control for BMC (p=.017) and BMD (P=.041). Histological analysis and geometric measurements of the calluses further showed that there was no change in osteoclast number, while overall cortical diameters in the PTH (1-34) treated animals were greatest at 84 days. These data show that daily subcutaneous administration of low-dose PTH (1 -34), enhances fracture healing by increasing BMD, BMC, and strength, and produces a sustained anabolic effect throughout the remodeling phase of fracture repair

Effects of acid hydrolysis and mechanical polishing on surface residual stresses of low-fusing dental ceramics

PLEASE NOTE: This work is protected by copyright. Downloading is restricted to the BU community: please click Download and log in with a valid BU account to access. If you are the author of this work and would like to make it publicly available, please contact [email protected] (M.Sc.D.)--Boston University, Henry M. Goldman School of Dental Medicine, 2001 (Prosthodontics).Includes bibliographical references (leaves 63-65).The purpose of this study was to evaluate by means of indentation technique the effects of acid hydrolysis and mechanical polishing on the surface residual stresses of two low-fusing ceramic materials: Duceram-LFC (Dentin and Enamel) and Finesse (Dentin and Enamel) porcelains. Sixteen sample bars (25.O mm x 3.5 mm x 2.5 mm) were fabricated for each material, and assigned to 4 surface-treatment groups (4 bars for each group): control, hydrolysis, glazed then polished, and polished then glazed. Surface residual stresses were determined by conventional micro indentation crack technique. A Buehler Vickers indenter contacted the Duceram samples with a 500-gram load for 10 seconds, and the Finesse samples with a 300-gram load for the same time period. A scanning electron microscope (SEM) was used to study surface texture before and after hydrolysis and polishing. Mean crack length values created from the Vickers indenter are shown in (Table l and Table 2). [TRUNCATED

Whole-exome sequencing reveals a recurrent mutation in the cathepsin C gene that causes Papillon–Lefevre syndrome in a Saudi family

Papillon–Lefevre syndrome (PALS) is a rare, autosomal recessive disorder characterized by periodontitis and hyperkeratosis over the palms and soles. Mutations in the cathepsin C gene (CTSC) have been recognized as the cause of PALS since the late 1990s. More than 75 mutations in CTSC have been identified, and phenotypic variability between different mutations has been described. Next generation sequencing is widely used for efficient molecular diagnostics in various clinical practices. Here we investigated a large consanguineous Saudi family with four affected and four unaffected individuals. All of the affected individuals suffered from hyperkeratosis over the palms and soles and had anomalies of both primary and secondary dentition. For molecular diagnostics, we combined whole-exome sequencing and genome-wide homozygosity mapping procedures, and identified a recurrent homozygous missense mutation (c.899G>A; p.Gly300Asp) in exon 7 of CTSC. Validation of all eight family members by Sanger sequencing confirmed co-segregation of the pathogenic variant (c.899G>A) with the disease phenotype. This is the first report of whole-exome sequencing performed for molecular diagnosis of PALS in Saudi Arabia. Our findings provide further insights into the genotype–phenotype correlation of CTSC pathogenicity in PALS