Indiana University-Purdue University Indianapolis (IUPUI) / Fluoride has been used in the treatment of osteoporosis because of its apparent ability to directly initiate bone formation. However, fluoride's therapeutic efficacy is controversial. Clinical trials in the range of 50 to 75 mg/day demonstrated severe side effects and a lack of consistent therapeutic benefits. Animal studies have not fully proven a positive effect of fluoride on bone strength. The objective of this study was to determine the histomorphometric changes in the cortical bone of rabbits caused by high doses of fluoride. The hypothesis was that high-dose fluoride intake enhances bone modeling and inhibits bone remodeling. Twenty-four young adult (four months old) female, Dutch Belted rabbits were randomly divided in two groups. The control group received no fluoride in their drinking water, while the experimental group received 100-ppm fluoride. Both groups received approximately 12-ppm fluoride in their food. A pair of tetracycline labels was given two weeks apart before initiation of the experiment. Fluoride treatment was given for six months. A terminal pair of calcein green labels was given before the animals were euthanized. Histomorphometric measurements were made using stereological point-hit and linear-intercept methods. The histomorphometric findings were correlated with fluoride serum and bone levels and also with strength tests. The study demonstrated that fluoride increases bone modeling by increasing periosteal bone apposition and endosteal bone resorption. The net effect of fluoride was an enlargement of the cortical bone and bone marrow and, therefore, the total tissue cross-section. However, the observed increase in bone mass produced by fluoride did not have a positive effect on the mechanical properties of bone. Fluoride did not produce a change in the primary histomorphometric parameters of osteoid surface (OS/BS%) or mineralizing surface (MS/BS%). Fluoride treatment produced an increase in the cortical periosteal modified mineral apposition rate (CPMAR). The remaining dynamic indices (i.e. endosteal MAR, remodeling MAR, cortical endosteal BFR and total BFR, activation frequency and formation period) were not affected by fluoride. The study failed to show an inhibitory effect of fluoride on bone remodeling.

Indiana University-Purdue University Indianapolis (IUPUI) / The bisphosphonate etidronate, a drug commonly used to treat osteolytic bone disorders, produces a long lasting inhibition of bone resorption. Since continual bone remodeling appears crucial for the long-term success of endosseous implants, the effects of this drug on the bone surrounding implants were investigated. The specific objective was to quantify the static and dynamic histomorphometric properties of bone surrounding implants placed in 12 beagle dogs treated with this drug. The dogs were divided into three groups (4 dogs/group) based on the bisphosphonate treatment dose: 0, 0.5 and 5.0 mg/kg/day. Since remodeling is different at distinct sites around implants, we analyzed bone at different distances (<1, 1-2 and 2-3 mm from the implant) and in different regions (periosteal and endosteal calluses and intracortical bone). Factorial ANOVA with repeated measures was used to compare site and regional differences in the dose groups. Results show that etidronate treatment produced a decrease in remodeling activity in the treated groups. The high dose group had impaired bone formation and a complete inhibition of remodeling. Low dose produced the same trend, but was not statistically different from controls. The significant differences (p < 0.05) were shown by the high dose group compared to controls for Mineralizing Surface (MS/BS), Activation Frequency (AcF), Mineral Apposition Rate (MAR), Bone Formation Rate (BFR), Formation Period (FP), Mineralization Lag Time (MLT), Adjusted Apposition Rate (AjAr) and Bone Volume (BV/TV), while Osteoid Volume (OV/TV) and Osteoid Thickness (OTh) were higher (p < 0.05) in the high dose group. Since it has been suggested that a remodeling rate of 500 percent per year is achieved in the first millimeter around an implant in successful osseointegration, the area within the first millimeter, as expected, was more affected by all the parameters than further away. These results agree with earlier studies in which areas of high remodeling were shown to be more affected by bisphosphonate therapy than areas of low remodeling. The area closest to the implant showed significantly greater BV/TV, Void Volume (VV/TV), Osetoid Volume over Bone volume (OV/BV), Osteoid Surface (OS/BS), MS/BS, BFR, FP, AcF and MLT while OV/TV was significantly increased in the area most distant from the implant. It was found that etidronate interfered with normal bone mineralization, since there was a decrease in MLT and an accumulation of osteoid. If remodeling is high around implants so as to repair or prevent microdamage, then etidronate could impair this from happening, thereby resulting in eventual implant failure. Though these high doses are not ordinarily used for the clinical treatment of osteoporosis, a low dose might still be harmful if given long-term. These data confirm our hypothesis that etidronate affects bone resorption and mineralization around an implant, when given at the high dose. Two hypotheses were rejected, since in this study, the effect of etidronate was not dose-dependent. This study was supported by NIH 2PO1AG05793, Merck and CO., and Procter and Gamble Pharmaceuticals.

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Purpose: In response to resistance exercise training, it has been shown that individuals with a previous training history acquire muscle volume at an accelerated rate. This phenomenon may be attributed, in part, to the myonuclear enrichment resulting from the proliferation of muscle progenitor cells, which promotes essential protein synthesis following subsequent muscle training. As a highly energy demand tissue, the successful hypertrophy of muscle fiber depends on mitochondrial biogenic progression. Moreover, the majority of genes that encode mitochondrial proteins are within nuclear genome. Therefore, in this study, we investigated the effect of increased number of myonuclei in response to the previous resistance exercise preconditioning on mitochondrial adaptations to subsequent resistance training. Our central hypothesis was that pre-trained muscles would show an accelerated acquisition of training-induced mitochondrial function leading to a greater skeletal muscle hypertrophy compared to previously non-trained muscles and this may be associated with increased number of myonuclei in the pre trained muscles. Methods: Thirty-two Sprague-Dawley rats were randomly assigned to four groups (n=8 per group) which include control, pre-training, training, and retraining group. Resistance exercise training was carried out by ladder climbing with weights attached to the tail at ages of either 8- (pre-training) and 36-week-old (training), or both (retraining). Each training session consisted of 3 sets of 5 repetitions, and the training protocol was performed every third day for 8 weeks. At 44 weeks of age, specific muscle groups were carefully collected and stored at -80 °C until further analyses. 4', 6-Diamidino-2-phenylindole staining, hematoxylin & eosin staining, cytochrome c oxidase and succinate dehydrogenase staining were performed. Western blotting and immunohistochemstry were performed to assess the abundance of mitochondrial regulatory proteins and the mitochondrial content. In complementary in vitro studies, confluent L6 myoblast cells were further grown in differentiation media for 4 days with or without insulin-like growth factor 1 (50 ng/ml) supplementation. Mitochondrial gene expression levels and mitochondrial respiratory function were assessed after 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR, 1 mM), a 5' AMP-activated protein kinase activator, treatment. Results: Myonuclei numbers were higher in training and retraining groups than control group (all, p &lt; 0.05), suggesting that ladder climbing training protocol increased myonuclei number. There was a significantly higher level of myonuclei number in pretraining group compared to the control group indicating that the acquired myonuclei during exercise preconditioning were retained over the 20-week detraining period. Muscle cross-sectional area, mitochondrial content and mitochondrial enzymatic activities (COX and SDH) were significantly greater in retraining group compared to training group (p &lt; 0.01, p &lt; 0.01 and p &lt; 0.05, respectively). In in vitro study, L6 myotubes preconditioned with IGF-1 showed increased myonuclei numbers within each myotube and presented a higher level of mitochondrial gene expression and oxygen consumption rate under AICAR treatment condition. Conclusions: These data provide physiological evidence that pre-trained muscle with more myonuclei make the muscles more responsive to subsequent training in terms of muscle hypertrophy and mitochondrial remodeling. Furthermore, this study provides a proof-of-concept of biological processes underlying potential nuclear-mitochondrial interplay during muscle hypertrophy. These findings warrant future studies to identify a novel target for mitochondrial medicine to treat muscle atrophy. / Kinesiology

Thesis (M. Arch.)--Massachusetts Institute of Technology, Dept. of Architecture, 1981. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND ROTCH. / Includes bibliographical references (leaves 72-73). / This thesis explores the processes of building evolution and the methods in which old buildings are recycled for continued use. Reuse is the process in which a building's life is extended through a preservation or alteration of its existing morphology. It is a process in which memories are both extended and interpreted; designers try to renovate outdated structures into rich and diverse environments in which people can once again live and work. This thesis is a case study in reuse, in which I study the process of recycling several old industrial buildings. The Walter Baker Chocolate Factory sits on the boundary line between the Massachusetts towns of Milton and Dorchester, straddling the Neponset River. I discuss the morphology of the existing buildings, and I explore their conversion into an artists' colony. Reuse makes sense economically and environmentally, and also helps us preserve a connection to our ancestry, our cultural heritage, and our collective memory. In Working Places: the Adaptive Use of Industrial Buildings, Walter C. Kidney says: "America, at least in its attitude toward material wealth, may be undergoing a major psychological change. In the recent past, anything made the day before yesterday, whether it was a building, a car or a saucepan, was liable to be scrapped." Today, this trend is beginning to reverse, and architects are looking to explore the potential for reuse of outdated buildings. As a guide for my exploration, I have selected the program that the architectural team of Gelardin, Bruner, and Cutt used to create the "Piano Craft Guild", an artists' colony in the South End of Boston. I have, however, taken the freedom to tailor the program to fit the specific conditions extant at the east complex of the Walter Baker Chocolate Factory. / by Fernando D. Castro. / M.Arch.

Thesis. 1978. M.Arch--Massachusetts Institute of Technology. Dept. of Architecture. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND ROTCH. / Bibliography: leaves 60-63. / M.Arch

Thesis. 1978. M.Arch.A.S.--Massachusetts Institute of Technology. Dept. of Architecture. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND ROTCH. / Bibliography: leaves 109-110. / by Hazel W.S. Wong. / M.Arch.A.S.

Fan Hong Ki. / "Architecture Department, Chinese University of Hong Kong, Master of Architecture Programme 2004-2005, design report." / Chapter 1.0 --- Foreword / Chapter 1.0.1 --- Synopsis / Chapter 1.0.2 --- Thesis Statement / Chapter 2.0 --- Research Studies / Chapter 2.0.1 --- City Level Study / Chapter 2.0.2 --- Preliminary Site Selection / Chapter 2.0.3 --- District Level Study / Chapter 2.0.4 --- Building Level Study / Chapter 2.0.5 --- Program and Target Group Study / Chapter 3.0 --- Site / Chapter 3.0.1 --- Site Analysis / Chapter 3.0.2 --- Site Strategies / Chapter 4.0 --- Design Development / Chapter 4.0.1 --- Conceptual Urban Design / Chapter 4.0.2 --- Design Intentions / Chapter 4.0.3 --- Preliminary Design / Chapter 4.0.4 --- Modified Design / Chapter 4.0.5 --- Final Design