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Biomedical subjects

J R Sandy

Publications and source records attributed to J R Sandy.

88 records · Page 5Linked to original sources

Tooth eruption and orthodontic movement.

Teeth have been moved in man for centuries and the process of tooth eruption has occurred presumably since he evolved. The cellular and molecular mechanisms which are involved in these two phenomena are amongst the most intriguing questions in dental research today. The aim of this paper is to review some of the theories which have been proposed to explain the two processes. It is also intended to place in context the contribution being made by biological sciences, which might explain tooth eruption and tooth movement. It is not the intention to describe morphologic observations which are well documented and illustrated in more elaborate texts.

Bone Remodeling↗

Stimulation of bone collagen and non-collagenous protein synthesis by products of 5- and 12-lipoxygenase: determination by use of a simple quantitative assay.

The influence of 5- and 12-lipoxygenase products on the rate of collagen and non-collagenous protein (NCP) synthesis by murine calvarial explants has been investigated using a new assay based on the resistance of native collagen to degradation by pepsin. The reproducibility and simplicity of this assay allows the quantitative estimation of the rate of bone formation in large numbers of cultures. Hydroxyeicosatetraenoic acids (HETEs) stimulated both the rate of collagen and NCP synthesis with maximal stimulation occurring at 10-100 pM. All leukotrienes stimulated collagen synthesis. LTB4, C4 and D4 showed similar dose-responses with maximal activity occurring at 100 pM. LTE4 was less potent only showing activity at 1-10 nM. Only LTD4 demonstrated the capacity to stimulate NCP synthesis with significant stimulation being seen at 10 nM. The extreme sensitivity of bone collagen and NCP synthesis to lipoxygenase products suggests that these mediators may play a physiological role in bone remodelling.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Repair of cleft lip and palate: 1. Surgical techniques.

Studies in Sri Lanka have demonstrated that in the absence of surgery, growth of the facial skeleton is normal. In developed countries, however, it is considered unacceptable to leave a child with an unrepaired cleft. The aim of surgery being to produce a near normal face. Part 1 provides an overview of the surgical repair of clefts and outline the general principles, as well as the most common surgical procedures. Part 2 will evaluate the surgical techniques and discuss the clinical research methodology involved.

Alveolar Process↗

Second messengers: regulators of mechanically-induced tissue remodelling.

One of the most intriguing aspects of tissue reaction to mechanical forces such as in orthodontic tooth movement is the transduction of force into a meaningful cellular response. The behaviour of all eukaryotic cells is modulated by internal signalling systems which translate a wide array of external stimuli such as hormones or mechanical forces, into a very narrow range of internal signals (second messengers). Classically, the second messenger associated with mechanical force transduction is adenosine 3'5' cyclic monophosphate (cAMP); since it was virtually the only second messenger understood in any detail from 1960 to the late 1970s this is hardly surprising. A great deal more is now known about cell signalling mechanisms and for various reasons outlined in this review, the assumption that cyclic AMP is the sole messenger system in the transduction of mechanical forces is no longer tenable.

Animals↗

Leukotriene B4 increases intracellular calcium concentration and phosphoinositide metabolism in mouse osteoblasts via cyclic adenosine 3',5'-monophosphate-independent pathways.

Leukotriene B4 is one of a number of agents which stimulate bone resorption by acting on osteoblasts. Some agonists, such as PTH or prostaglandins, are known to activate adenylate cyclase in osteoblasts, whereas others, such as vitamin D3, have no effect on adenylate cyclase. Recent evidence suggests that both classes of agonist may raise the intracellular calcium concentration, although the relative importance for bone resorption of calcium mobilization and adenylate cyclase activity in the osteoblast is not clear. Here it is shown 1) that leukotriene B4 does not activate but may be inhibitory toward adenylate cyclase in intact osteoblasts or membrane preparations, 2) that leukotriene B4 causes an elevation of intracellular calcium levels in osteoblast monolayers, 3) leukotriene B4 rapidly activates phosphatidylinositol bisphosphate breakdown in osteoblast membranes and intact osteoblasts, and 4) that leukotriene B4 stimulates phosphatidylinositol kinase activity concurrently with phosphoinositidase C in intact osteoblasts over a similar timescale. These results suggest that leukotriene B4 may increase the concentration of intracellular calcium in osteoblasts by stimulating phosphoinositide turnover, and support the proposal that calcium signaling rather than activation of adenylate cyclase in osteoblasts may be of overriding importance in the regulation of bone resorption.

1-Methyl-3-isobutylxanthine↗

Dual elevation of cyclic AMP and inositol phosphates in response to mechanical deformation of murine osteoblasts.

Mechanical deformation of bone cells was thought to be mediated via prostaglandin production and the cyclic AMP pathway. We present evidence that the phosphoinositide pathway is also activated by mechanical stress. We find that inositol phosphate production, but not glycerophosphoinositol production, is elevated, and the activation of adenylate cyclase is relatively small. These results are not compatible with the proposal that mechanical deformation of bone cells acts solely via prostaglandin synthesis.

Animals↗

Murine osteoblasts release bone-resorbing factors of high and low molecular weights: stimulation by mechanical deformation.

Murine calvarial osteoblasts in monolayer culture were found to constitutively produce bone-resorbing factors; mechanical deformation significantly increased the synthesis and/or release of these factors. In short-term cultures (2 h) the resorptive activity was largely dialysable, indicating a relative molecular mass (Mr) less than 2000. Intermittent mechanical deformation stimulated the synthesis of these low Mr factors irrespective of serum conditions. Continuous deformation, however, was without effect. When the culture period was extended to 24 h, bone resorptive activity was stimulated by both intermittent and continuous deformation in the presence of 10% serum. This activity was dialysable. Over this same period in cultures with 2% serum, intermittent deformation also produced a non-dialysable bone-resorbing factor. We also cultured osteoblasts for 72 h in serum-free conditions and deformed the cells intermittently. Fractionation of the medium by high pressure liquid chromatography (HPLC) resolved three peaks of bone resorptive activity: peak I (Mr 50-60,000); peak II (Mr 5-20,000); and peak III (Mr less than 1000). Only peaks II and III were stimulated by mechanical deformation. These bone-resorbing factors remain as yet poorly characterized, but none of the activity in the HPLC fractions was attributable to interleukin-1 or prostaglandin E2.

Animals↗

Magnets and orthodontics.

The first part of this paper is a literature review of magnets and their uses in orthodontics. The biological safety of magnets is considered and a report is given of experiments carried out on rat osteosarcoma cell line UMR-106. The second part of the paper describes a case where neodynium-iron-boron magnets were used to assist eruption of an unerupted, vertically impacted upper right canine. Previously, space was available for this tooth, but it failed to show signs of eruption. Following surgical attachment of a magnet, and the use of a second magnet attached to an upper removable appliance, rapid eruption occurred producing a favourable position for bonding.

Animals↗

Parathyroid hormone and prostaglandin E2 stimulate both inositol phosphates and cyclic AMP accumulation in mouse osteoblast cultures.

Parathyroid hormone (PTH) and prostaglandin E2 (PGE2) are physiological agonists which stimulate bone cells to resorb bone, a process by which the mineralized extracellular bone matrix is dissolved. Bone resorption has a key role in the maintenance of plasma calcium levels. It has been established that both PTH and PGE2 activate adenylate cyclase in osteoblasts, but it is apparent that (1) the two agents have qualitatively different effects on osteoblasts, and (2) the generation of cyclic AMP cannot account for all the effects of PTH on bone cell metabolism. Others have demonstrated that PTH and PGE2 may also elevate intracellular calcium levels, but the mechanism by which this is achieved has not been fully defined. Here we have investigated the effects of PTH on neonatal mouse osteoblasts in culture and shown that physiological concentrations of the hormone (50 nM) caused a small increase (22%) in total inositol phosphates accumulation, with a larger increase (40%) in inositol trisphosphate. We found that this activation occurred at lower concentration than was necessary to activate adenylate cyclase. PGE2 was a more effective activator of inositol phosphates accumulation than PTH, causing up to 300% increase in the total inositol phosphates after 30 min. Both PTH and PGE2 stimulated cyclic AMP accumulation, but the activation of adenylate cyclase by forskolin did not enhance inositol phosphates production. We conclude that both PTH and PGE2 stimulate phosphoinositide turnover in mouse osteoblasts and suggest that this mechanism may contribute to their elevation of intracellular calcium in bone cells.

Animals↗

Heterogeneity of bone resorbing factors produced by unstimulated murine osteoblasts in vitro and in response to stimulation by parathyroid hormone and mononuclear cell factors.

The bone resorbing activity of factors released from monolayer cultures of osteoblasts (OB) was examined by measurement of calcium released by neonatal mouse calvaria in vitro. Unstimulated conditioned media (CM) were found to contain significant bone resorbing activity, which was partially inhibited by indomethacin, dexamethasone and nordihydroguaiaretic acid. Ultrafiltration of CM (molecular weight cut-off of 5000) revealed bone resorbing activity in the filtrate and retentate. Fractionation of the CM by high-performance liquid chromatography revealed four major peaks of bone resorbing activity. Stimulation of the OB by mononuclear cell factor and parathyroid hormone significantly increased the synthesis and/or release of these factors with a relatively greater increase of lipid-soluble, low molecular-weight activity. These results suggested an important role for relatively small non-popular mediators in hormonally stimulated bone resorption.

Animals↗

Stimulation of bone resorption by lipoxygenase metabolites of arachidonic acid.

We have studied the effect of leukotrienes, (LT): B4, C4, D4 and E4 and the hydroxyeicosatetraenoic acids (HETEs) 5-HETE and 12-HETE on bone resorption in vitro. Resorption was measured by colorimetric assay of calcium released from neonatal mouse calvaria maintained in organ culture for 72h. All the LTs and HETEs stimulated bone resorption, with optimum responses at picomolar or nanomolar concentrations. The responses were biphasic, with a decreasing effect at higher concentrations. In contrast, prostaglandin E2 (PGE2) stimulated resorption only at 10nM and above. Indomethacin partially inhibited resorption by LTB4, LTC4 and LTD4, but did not affect resorption stimulated by LTE4, 5-HETE and 12-HETE. These results indicate that lipoxygenase products of arachidonic acid are highly potent bone resorbing factors and may play an important role in the localised bone loss associated with inflammatory lesions.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Macromolecular osteolytic factor synthesised by squamous carcinoma cell lines from the head and neck in vitro is interleukin 1.

Three human cell lines derived from oro-pharyngeal squamous cell carcinomas of the head were investigated for bone-resorbing activity in vitro. Culture media from all three spontaneously produced a non-dialysable osteolytic factor with activity in three in vitro assays for interleukin 1 (IL1), viz. the lymphocyte activating factor (LAF) assay, stimulation of collagenase synthesis by articular chondrocytes, and stimulation of prostaglandin E2 synthesis by fibroblasts. Addition of anti-human IL1 antibody to the culture media abolished all the bone-resorbing activity. Fractionation of the cell culture media by high performance liquid chromatography (HPLC) showed a single peak of activity in the chondrocyte assay with an apparent mol.wt of 15-17,000. This co-eluted with activity in a preparation of IL1 from rat peritoneal macrophage cultures. These results indicate that IL1 is responsible for the prostaglandin-independent bone resorbing activity synthesised by these cells in vitro, and may contribute to the bone destruction associated with the tumour.

Bone Resorption↗

Anterior salivary gland inclusion in the mandible: pathological entity or anatomical variant?

A case of anterior salivary gland inclusion of the mandible is reported and the literature reviewed. It is suggested that these inclusions arise in the same way as the more common examples from the angle of the mandible, by progressive resorption of the lingual cortex in response to pressure exerted by the adjacent salivary glands. It is likely that these lesions become evident on radiographs only when the resorption is marked, and they may, therefore, be more widespread than reported figures indicate. Supportive evidence for this hypothesis is provided by the observations that the lesions usually present in middle age and, on histological examination, exhibit evidence of resorption.

Bone Resorption↗

The use of osseointegrated implants in orthodontic patients: 2. Absolute anchorage.

Following the first article which explored the use of restorative implants in orthodontic patients which are later used to replace missing teeth, such as in hypodontia patients, this second paper examines the use of implants in orthodontics to provide 'Absolute Anchorage' after highlighting the standard orthodontic approaches to anchorage. It explains the advantages and disadvantages such methods give the specialist in treating full arch orthodontic patients over standard techniques used in modern orthodontics. Three different types of implant used in full arch orthodontic treatment are described in detail; the mid palatal implant, the OnPlant and the mini screw. The methods used in placing the implants and the techniques employed to gain the anchorage required are highlighted.

Alveolar Process↗

Repair of cleft lip and palate: 2. Evaluation of surgical techniques.

Currently there is no consensus on which surgical technique, timing or sequence produces optimal results. In addition, there are now good indications that strategies adopted by some centres produce consistently superior results compared with other centres. Part 1 provided an overview of the surgical repair of clefts and outlined the general principles, as well as the most common surgical procedures. Part 2 evaluates the surgical techniques and discusses the clinical research methodology involved.

Cleft Lip↗