W Harvey

Bio: W Harvey is an academic researcher from University College London. The author has contributed to research in topics: Oral submucous fibrosis & Areca. The author has an hindex of 10, co-authored 15 publications receiving 703 citations.

The stimulation of bone formation in vitro by therapeutic ultrasound

Abstract: A controlled study was performed to evaluate the effects of different ultrasound (US) intensities on 5-day-old mouse calvaria bone in tissue culture. A special technique to apply the US was developed, and the following parameters were measured: collagen and noncollagenous protein (NCP) synthesis (bone formation), and temperature change. It was found that ultrasound at 0.1 W/cm2 (SATA), pulsed 1:4, 3 MHz, 5 min, significantly stimulates bone formation (i.e., the synthesis of collagen and NCP) (p < 0.001 and p < 0.01). However, pulsed ultrasound at higher doses (1.0-2.0 W/cm2 (SATA), pulsed 1:4, 3 MHz, 5 min) significantly inhibited the synthesis of both collagen and NCP (p < 0.05). The temperature measurements showed a maximum rise of 1.8 degrees C [at 2.0 W/cm2 (SATA)] and no detected rise at 0.1 W/cm2 (SATA), suggesting that the effects in this study were primarily nonthermal. These results may reflect the healing effect of US on fractures and osteoradionecrosis and reinforces the use of low intensity US regimens [0.1 W/cm2 (SATA)] in clinical practice.

Stabilisation of collagen by betel nut polyphenols as a mechanism in oral submucous fibrosis.

Abstract: Treatment of reconstituted collagen fibrils and pieces of rat dermis with the crude extract, purified tannins or (+)-catechin from betel nut (Areca catechu) increases their resistance to both human and bacterial collagenases in a concentration-dependent manner. These tanning agents may stabilise collagen in vivo following damage to the oral epithelium and promote the sub-epithelial fibrosis which occurs in betel nut chewers.

Therapeutic applications of ultrasound.

Abstract: Therapeutic applications of ultrasound predate its use in imaging. A range of biological effects can be induced by ultrasound, depending on the exposure levels used. At low levels, beneficial, reversible cellular effects may be produced, whereas at high intensities instantaneous cell death is sought. Therapy ultrasound can therefore be broadly divided into "low power" and "high power" applications. The "low power" group includes physiotherapy, fracture repair, sonophoresis, sonoporation and gene therapy, whereas the most common use of "high power" ultrasound in medicine is probably now high intensity focused ultrasound. Therapeutic effect through the intensity spectrum is obtained by both thermal and non-thermal interaction mechanisms. At low intensities, acoustic streaming is likely to be significant, but at higher levels, heating and acoustic cavitation will predominate. While useful therapeutic effects are now being demonstrated clinically, the mechanisms by which they occur are often not well understood.

Bacterially induced bone destruction: mechanisms and misconceptions.

Abstract: Normal bone remodelling requires the coordinated regulation of the genesis and activity of osteoblast and osteoclast lineages. Any interference with these integrated cellular systems can result in dysregulation of remodelling with the consequent loss of bone matrix. Bacteria are important causes of bone pathology in common conditions such as periodontitis, dental cysts, bacterial arthritis, and osteomyelitis. It is now established that many of the bacteria implicated in bone diseases contain or produce molecules with potent effects on bone cells. Some of these molecules, such as components of the gram-positive cell walls (lipoteichoic acids), are weak stimulators of bone resorption in vitro, while others (PMT, cpn60) are as active as the most active mammalian osteolytic factors such as cytokines like IL-1 and TNF. The complexity of the integration of bone cell lineage development means that there are still question marks over the mechanism of action of many well-known bone-modulatory molecules such as parathyroid hormone. The key questions which must be asked of the now-recognized bacterial bone-modulatory molecules are as follows: (i) what cell population do they bind to, (ii) what is the nature of the receptor and postreceptor events, and (iii) is their action direct or dependent on the induction of secondary extracellular bone-modulating factors such as cytokines, eicosanoids, etc. In the case of LPS, this ubiquitous gram-negative polymer probably binds to osteoblasts or other cells in bone through the CD14 receptor and stimulates them to release cytokines and eicosanoids which then induce the recruitment and activation of osteoclasts. This explains the inhibitor effects of nonsteroidal and anticytokine agents on LPS-induced bone resorption. However, other bacterial factors such as the potent toxin PMT may act by blocking the normal maturation pathway of the osteoblast lineage, thus inducing dysregulation in the tightly regulated process of resorption and replacement of bone matrix. At the present time, it is not possible to define a general mechanism by which bacteria promote loss of bone matrix. Many bacteria are capable of stimulating bone matrix loss, and the information available would suggest that each organism possesses different factors which interact with bone in different ways. With the rapid increase in antibiotic resistance, particularly with Staphylococcus aureus and M. tuberculosis, organisms responsible for much bone pathology in developed countries only two generations ago, we would urge that much greater attention should be focused on the problem of bacterially induced bone remodelling in order to define pathogenetic mechanisms which could be therapeutic targets for the development of new treatment modalities.

The tissue, cellular, and molecular regulation of orthodontic tooth movement: 100 years after Carl Sandstedt.

Abstract: The first experimental investigation of orthodontic tooth movement was published by Sandstedt in 1904-1905. After 100 years, there is a good understanding of the sequence of events at both tissue and cellular levels and now the current focus of research is at the molecular level. The techniques of reverse transcription-polymerase chain reaction and in situ hybridization to detect mRNAs of interest have revolutionized tooth movement studies and an expanding list of antibodies and enzyme-linked immunosorbent assays directed against human and animal proteins will facilitate their identification in tissue sections and/or culture supernatants. Nevertheless, although this technology has greatly simplified research for the clinical and laboratory investigator, message is not always translated into protein, and the presence of a protein does not necessarily mean it is biologically active. In vivo and in vitro methods have been widely used in tooth movement studies. However, data from in vitro models, in which the mechanical stimulus can be carefully controlled (tension versus compression; intermittent versus continuous), should be correlated with in vivo data from animal models. The current evidence suggests that downstream from the initial mechanotransduction event at focal adhesions which link the extracellular matrix to the cytoskeleton, mechanically induced remodelling is mediated by a complex feedback mechanism involving the synthesis of cytokines such as interleukin-1 (IL-1), IL-6, and receptor activator of nuclear factor k B ligand by cells of the osteoblast and/or fibroblast lineages. These in turn act in an autocrine/paracrine fashion to regulate the expression of transcription factors, cytokines, growth factors, enzymes, and structural molecules involved in the differentiation, proliferation, and function of mesenchymal and other cell types. Contrary to the impression gained from the literature, tooth movement is not confined to events within the periodontal ligament. Orthodontic tooth movement involves two interrelated processes: (1) deflection or bending of the alveolar bone and (2) remodelling of the periodontal tissues.