Biological Events in Periodontal Ligament and Alveolar Bone Associated with Application of Orthodontic Forces.

Orthodontic force-induced stresses cause dynamic alterations within the extracellular matrix and within the cytoskeleton of cells in the periodontal ligament and alveolar bone, mediating bone remodelling, ultimately enabling orthodontic tooth movement. In the periodontal ligament and alveolar bone, the mechanically induced tensile strains upregulate the expression of osteogenic genes resulting in bone formation, while mechanically induced compressive strains mediate predominantly catabolic tissue changes and bone resorption. In this review article we summarize some of the currently known biological events occurring in the periodontal ligament and in the alveolar bone in response to application of orthodontic forces and how these facilitate tooth movement.

Periodontal Biological Events Associated with Orthodontic Tooth Movement: The Biomechanics of the Cytoskeleton and the Extracellular Matrix.

The mechanical stimuli generated by orthodontic forces cause deformation of extracellular matrices and cells, vascular changes, inflammation, and the release of active biological agents generating a complex multifactorial sequence of biological events culminating in bone remodelling enabling orthodontic tooth movement. Orthodontic forces on the teeth generate stresses in periodontal tissues according to a number of variables including the type (continuous, interrupted, or intermittent), magnitude, direction, and frequency of the applied load. Whether the strain is compressive or tensile determines whether bone deposition or bone resorption will occur. The mechanically induced strains mediate structural changes in extracellular matrices and in cells, consequently affecting cellular gene expression and function. In the extracellular matrix, mechanosensing molecules integrated into the structure of various proteins can be activated upon load-induced protein unfolding. These specialized molecules have the capacity to sense and then to convert microenvironmental biomechanical stimuli into intracellular biochemical signals that interact to generate a coordinated tissue response. It is also possible that the applied force may directly cause nuclear deformation with configurational changes in chromatin, thus influencing gene expression. In this review article we summarize the current general concepts of mechanotransduction influencing the remodelling of periodontal tissues thus enabling tooth movement in response to applied orthodontic loads.

Oral candidosis in relation to oral immunity.

Symptomatic oral infection with Candida albicans is characterized by invasion of the oral epithelium by virulent hyphae that cause tissue damage releasing the inflammatory mediators that initiate and sustain local inflammation. Candida albicans triggers pattern-recognition receptors of keratinocytes, macrophages, monocytes and dendritic cells, stimulating the production of IL-1ß, IL-6 and IL-23. These cytokines induce the differentiation of Th17 cells and the generation of IL-17- and/or IL-22-mediated antifungal protective immuno-inflammatory responses in infected mucosa. Some immune cells including NKT cells, γδ T cells and lymphoid cells that are innate to the oral mucosa have the capacity to produce large quantities of IL-17 in response to C. albicans, sufficient to mediate effective protective immunity against C. albicans. On the other hand, molecular structures of commensal C. albicans blastoconidia, although detected by pattern-recognition receptors, are avirulent, do not invade the oral epithelium, do not elicit inflammatory responses in a healthy host, but induce regulatory immune responses that maintain tissue tolerance to the commensal fungi. The type, specificity and sensitivity of the protective immune response towards C. albicans is determined by the outcome of the integrated interactions between the intracellular signalling pathways of specific combinations of activated pattern-recognition receptors (TLR2, TLR4, Dectin-1 and Dectin-2). IL-17-mediated protective immune response is essential for oral mucosal immunity to C. albicans infection.

Noma (cancrum oris) in the South African context.

Noma (cancrum oris) is a destructive necrotising disease affecting orofacial tissues predominantly of malnourished young children. It is characterised by a rapid acute onset which usually starts in the mouth, spreads intra-orally destroying soft tissue and bone and progresses to perforate the facial skin, causing disfigurement. Polybacterial anaerobic infection is critical too, but is not alone sufficient for the initiation of noma. Cofactors, first and foremost malnutrition, but also systemic viral and bacterial infections are crucial to the development of noma. A patient with necrotising stomatitis or noma must be admitted to hospital for antibiotic treatment, fluid and electrolytes as well as nutritional supplementation and general supportive treatment. The epidemiology of noma in the South African population is unknown, and the clinicopathological features are poorly characterised. Although worldwide there is no evidence that HIV infection is a strong risk factor for noma, HIV infection may play a substantial role in the pathogenesis of noma in South Africa.

Race/ethnicity in biomedical research and clinical practice.

There is ongoing debate as to whether persons of different racial/ethnic groups are biologically significantly different, and, if such differences exist, whether they are relevant in relation to disease susceptibility and to treatment outcomes. There is also debate about the benefits of using race/ethnicity as a factor in clinical decision making, and as a variable in biomedical or public health research, because of the emotional sensitivities attached to race/ethnic categorisation. Such categorisation may also divert attention from underlying issues such as socioeconomic status and lack of access to modern health care. In this short article we will discuss these controversies, and will emphasize the importance of responsible and sensitive use of race/ethnicity as a variable in biomedical research and in clinical practice.

Oral medicine case book 64: Some aspects of the pathophysiology of angioedema with special reference to the upper aerodigestive tract.

Angioedema refers to a localized oedematous swelling of subcutaneous or submucosal tissues, caused by dilatation and increased permeability of blood vessels, usually mediated either by histamine or by bradykinin. Deficiency or loss of functional activity of the complement component C1 esterase inhibitor (C1-INH) affects multiple systems, including the kallikrein-kinin, complement, coagulation and fibrinolytic pathways, and in the context of angioedema, the result is increased production and release of bradykinin and other vasoactive substances such as C3a. Owing to impairment of C1-INH, factors Xlla and kallikrein, by a positive feedback mechanism, bring about persistent activation of the kallikrein-kinin pathway with amplification of production of bradykinin, resulting in angioedema. Histamine can cause histaminergic angioedema. As the name implies, this oedema is caused by degranulation of mast cells/basophils as a result of an IgE-dependant allergic reaction to extracts of food, drugs, infectious agents, or to physical stimulation; or as the result of direct degranulation of mast cells/basophils independently of IgE, caused by releasing agents such as opiates, antibiotics or radiocontrast media. As dental, oral and maxillofacial operative procedures may trigger the development of angioederria in susceptible individuals, the dental practitioner should be familiar with its

Oral medicine case book 65: Necrotising stomatitis.

Necrotising stomatitis is a fulminating anaerobic polybacterial infection affecting predominantly the oral mucosa of debilitated malnourished children or immunosuppressed HIV-seropositive subjects. It starts as necrotising gingivitis which progresses to necrotising periodontitis and subsequently to necrotising stomatitis. In order to prevent the progression of necrotising stomatitis to noma (cancrum oris), affected patients should be vigorously treated and may require admission to hospital. Healthcare personnel should therefore be familiar with the signs and symptoms of necrotising gingivitis/necrotising periodontitis, of their potential sequelae and of the need for immediate therapeutic intervention.

Osseointegration: biological events in relation to characteristics of the implant surface.

Osseointegration of titanium implants is a complex biological process involving interactions between immuno-inflammatory responses, angiogenesis and osteogenesis, all of which are influenced by the physical and chemical characteristics of the implant surface. An implant surface with moderately rough topography and high surface energy influences cellular activities, enhancing peri-implant bone wound healing. Primary mechanical stability of the implant is essential for osseointegration. In this article we review some of the more important biological events of peri-implant bone wound healing in the process of osseointegration, and discuss how the biophysical properties of implant surfaces influence cellular responses.

Oral HIV-associated Kaposi sarcoma.

Kaposi sarcoma (KS), an AIDS defining condition, remains one of the most commonly HIV-associated neoplasms. While the use of highly active antiretroviral therapy (HAART) has brought about a dramatic decrease in the prevalence and incidence of AIDS-KS worldwide, this has not been the case in resource-poor sub-Saharan African countries, where HIV has reached epidemic proportions and human herpesvirus-8 infection is endemic. Oral involvement is a common manifestation of AIDS-associated KS and may be an early presenting finding of HIV infection. The clinical manifestation of oral KS can vary and may have an unpredictable course ranging from mild to fulminant. Rapidly progressive facial lymphoedema associated with extensive advanced oral KS portends a poor prognosis. Oral KS may regress with antiretroviral therapy or may flare up as part of the immune reconstitution inflammatory syndrome. The oral lesions of AIDS-KS are best managed with HAART together with systemic chemotherapy. This article provides a review of contemporary knowledge of the biology, pathology, clinical features and management of oral AIDS-KS.

Oral leukoplakia in a South African sample: a clinicopathological study.

OBJECTIVE: This study analysed differences in clinicopathological features of oral leukoplakia in different racial groups in the greater Johannesburg area of South Africa, with emphasis on the black population. MATERIAL AND METHODS: The retrospective review included cases diagnosed clinically as oral leukoplakia and histologically as hyperkeratosis without dysplasia, hyperkeratosis with mild, moderate or severe dysplasia, and carcinoma in situ from 1990 to 2010. Age, gender, ethnicity, clinical appearance, site of lesion and tobacco smoking habit were recorded. RESULTS: Fourteen per cent of oral leukoplakia occurred in black South Africans compared with 80% in white South Africans. In contrast to whites, blacks were diagnosed with oral leukoplakia at a younger age; there were more men affected than women; and the proportion of idiopathic leukoplakia was greater. There were significantly more blacks (23%) than whites (13%) with non-homogenous leukoplakia and significantly more whites (51%) than blacks (23%) with dysplastic oral leukoplakia. CONCLUSION: This study suggests that oral leukoplakia, especially non-homogenous and idiopathic forms affects South African blacks less frequently than white South Africans; and in the former, it occurs more in men and at a younger age. These findings may provide some guidance in establishing screening policies for oral cancer, particularly suited for blacks.

Alveolar ridge preservation immediately after tooth extraction.

Ridge preservation procedures immediately after tooth extraction, are commonly used with a view to minimising remodelling and shrinkage of the alveolar ridge, associated with socket healing. These procedures may sometimes be effective, but they cannot completely prevent reduction in dimension of the ridge. Certain biomater als used may actually hamper normal deposition of bone within the healing socket, reducing bone trabeculae that can integrate with the implant surface. However, in extraction sockets in alveolar ridges of low bone density, particles of implanted bone substitute incorporated in the healing bone, may enhance the mechanical support for the implant, provided by normal healed bone of low trabecular density alone. This paper reviews biological rationales and procedures for ridge preservation immediately after extraction and comments on their clinical use.

Alcohol and oral squamous cell carcinoma.

Alcohol is a risk factor for oral squamous cell carcinoma. It enhances the permeability of the oral epithelium, acts as a solvent for tobacco carcinogens, induces basal-cell proliferation, and generates free radicals and acetaldehyde, which have the capacity to cause DNA damage. Alcohol-associated malnutrition and immune suppression may further promote carcinogenesis. However, acetaldehyde, the first metabolite of ethanol, is the critical agent by which prolonged and excessive consumption of alcoholic beverages increases the risk of oral squamous cell carcinoma. Alcohol also acts synergistically with the products of tobacco combustion in the pathogenesis of oral squamous cell carcinoma.

New 'second primary' cancers.

The term "second primary cancers" is applied to cancers that appear to be related to pre-existing treated or untreated cancers but that are in fact entities have arisen independently and not as a result of resurgence, nor as a result of metastasis of the original primary cancer. With respect to the original cancer, such cancers may justifiably be called second primary cancers. Most cancers develop in genetically susceptible persons exposed to exogenous carcinogens. Persons with rare inherited cancer susceptibility genes are at high risk of cancers, and those with genetic variants (genetic polymorphism) of specific genes encoding enzymes involved in breaking down common carcinogens, or in encoding DNA-repair proteins, though also at risk, are at significantly lower risk. Persons who have, or who have been treated for, primary carcinoma of the upper aerodigestive tract are at increased risk of developing second primary carcinomata in this region. This increased risk is most closely associated with tobacco smoking and with long-term excessive consumption of alcoholic beverages; and tobacco and alcohol used together have a synergistic effect. As primary oral squamous cell carcinoma usually develops within a field of pre-cancerised epithelium, and as treatment of the carcinoma does not necessarily eradicate the entire pre-cancerised field, because it is neither histologically detectable, nor is its extent determinable, additional cytogenetic alterations to the transformed keratinocytes in the field may give rise to second primary carcinomata in the upper-aero digestive tract.

Peri-implant mucositis and peri-implantitis: clinical and histopathological characteristics and treatment.

Osseointegrated dental implants are used routinely in dentistry in the confidence of predictable success. However, if the implant surfaces become colonised by pathogenic bacteria, the plaque-induced inflammation around the implants may cause peri-implant tissue destruction. Peri-implant mucositis is a reversible, plaque-induced inflammatory lesion confined to the peri-implant soft tissue unit and clinically is characterised by redness, swelling and bleeding on gentle probing. Peri-implantitis is an extension of peri-implant mucositis to involve the bone supporting the implant: it is characterised by loss of osseointegration of the coronal part of the implant, by increased probing depth and by bleeding and/or suppuration on probing. Established peri-implantitis does not respond predictably to treatment. The best management of plaque-induced peri-implant inflammatory diseases is prevention. Regular personal and professional cleaning of the implant is mandatory to minimise bacterial load. Despite our best efforts, plaque-induced peri-implant inflammatory diseases will occur frequently, and as these diseases respond best to early treatment, early detection of peri-implant mucositis by regular assessment will permit timely treatment. Peri-implant mucositis is readily treated non-surgically. Peri-implantitis is more difficult to treat largely because of the problem of decontamination of the roughened, threaded surfaces of exposed implants. As a rule, surgical treatment will be necessary, and even then success is not assured.

Peri-implant mucositis and peri-implantitis: bacterial infection.

Osseointegrated dental implants have a ong-term success rate of over 90%, but may be threatened by peri-implant mucostis and peri-implantitis, bacteria biofilm-induced inflammatory conditions. While peri-implant mucositis is a reversible inflammatory condition confined to the peri-implant soft-tissue unit, peri-implantitis is characterised by progressive inflammatory destruction of the crest of the alveolar bone supporting the implant, by increased peri-implant probing depths, and by bleeding and/or suppuration on probing. Effective treatment of peri-implant mucositis will prevent the development of peri-implantitis. Plaque accumulation on the implant/abutment surface juxtaposed to the junctional epithelium and to the connective tissue zone of the peri-implant soft-tissue unit induces the development of peri-implant mucositis which can subsequently progress to peri-implantitis. The aim of this paper is to review some aspects of bacterial infection of the tissue supporting dental implants, and to explore how to maintain the healthy peri-implant soft-tissue unit.

The peri-implant soft tissue unit: a literature review.

Restoration of the integrity of the dentition with endosseous implants is a treatment option made available to patients not only by specialists but increasingly also by non-specialist dental practitioners. Properly done implants at well-selected sites in suitable persons remain functionally and biologically sound for many years. An important factor n determining the success of implants s the integrity of the peri-implant soft tissue unit. Therefore, the implant placement protocol and the restorative protocol should be designed to favour the formation and maintenance of the peri-implant soft tissue unit. The purpose of this short review is to refresh the reader's knowledge of some important factors with regard to establishing and maintaining the integrity of the peri-implant soft tissue.

Cancer metastasis: a short account.

Tissue-specific cancer stem cells comprise a very small proportion of the cell population of a cancerous tumour. These cells have an undifferentiated phenotype, a relatively unlimited capacity for self renewal, and they divide slowly. Primary tumour cells with a stem cell phenotype are the driving force behind the uncontrolled proliferation of the cancerous tissue, and if they spread to distant sites, they can establish metastases. Cancer metastasis is a multistep process. The orderly sequence of events of the metastatic process comprises invasion of the surrounding normal stroma by cancer cells carrying a cancer stem cell phenotype, invasion of blood or lymphatic vessels, survival in the circulation during transport to a distant site, and establishment of micrometastases with subsequent metastatic growth. Microenvironment-specific chemokines secreted by cells at the candidate tissue site for metastasis attract type-specific tumour cells that express corresponding chemokine receptors. This is the critical mechanism determining the destination of metastatic cells. The subsequent paracrine interactions between the metastatic cells and their new microenvironment are essential for establishment of a metastatic cancer.

Lupus erythematosus: a short account.

Lupus erythematosus is a chronic autoimmune inflammatory disease with diverse clinical manifestations including arthritis, skin disorders and kidney disease. Pathologically it is characterised by complex interactions between multiple genetic, epigenetic and extraneous factors; and serologically by the presence of a variety of antibodies which are reactive to intracellular molecular constituents. Impaired clearance of apoptotic cells and of immune complexes, loss of immune tolerance to self-antigens and dysregulation of the cytokine network act synergistically with extraneous factors such as ultraviolet radiation, viruses and certain drugs to induce and sustain lupus erythematosus.

Bisphosphonate-related osteonecrosis of the jaw.

Bisphosphonates are agents commonly used in the treatment of osteoporosis, and in the management of metastatic bone disease, and of hypercalcaemia of malignancy. Any oral surgical procedure or traumatic event exposing bone to bacterial infection may precipitate osteonecrosis of the jaw in subjects who have been treated with bisphosphonates which suppress bone turnover and inhibit the angiogenesis associated with healing. New guidelines for the treatment of bisphosphonate-related osteonecrosis of the jaw are emerging, but hitherto treatment has been empirically conservative.

Discoid lupus erythematosus as it relates to cutaneous squamous cell carcinoma and to photosensitivity.

Lupus erythematosus is a chronic inflammatory autoimmune disease with diverse clinical manifestations ranging from an indolent chronic cutaneous form to a severe potentially life-threatening disease, systemic lupus erythematosus. Discoid lupus erythematosus is a subphenotype of chronic cutaneous lupus erythematosus, characterised by scaly disk-shaped plaques which may be localised or widespread, occurring predominantly on sun-exposed skin and which may rarely progress to squamous cell carcinoma. The pathogenesis of discoid LE comprises complex interactions between multiple susceptibility genes involved in immune responses and clearance of apoptotic cells on the one hand, and environmental factors on the other. Herein, we discuss some aspects of the pathogenesis of discoid lupus erythematosus in relation to ultraviolet radiation and malignant transformation.