Critical Reviews in Oral Biology & Medicine

The discovery of endogenous molecules involved in counterregulation of inflammatory responses that may lead to tissue injury provides an opportunity to explore new therapeutic approaches based on manipulation of new pathways. Natural counterregulatory pathways may reduce the possibility of unwanted toxic side-effects. Lipoxins are trihydroxytetraene-containing eicosanoids that are generated within the vascular lumen during platelet-leukocyte interactions and at mucosal surfaces via leukocyte-epithelial cell interactions. During cell-cell interactions, transcellular biosynthetic pathways are the major lipoxin biosynthetic routes, and thus, in humans, lipoxins are formed in vivo during multicellular responses, such as inflammation and asthma. This branch of the eicosanoid cascade generates specific tetraene-containing products that serve as "stop signals" for neutrophils that regulate key steps in leukocyte trafficking and prevent neutrophil-mediated tissue injury. These novel anti-inflammatory lipid mediators also appear to facilitate the resolution of the acute inflammatory response. In this review, recent findings and new concepts pertaining to the generation of lipoxins and their impact on the resolution of acute inflammation, and organ protection from leukocyte-mediated injury, are presented. The parallels and possible associations with periodontal diseases are discussed.

The past 50 years of research on the mechanical properties of human dentin are reviewed. Since the body of work in this field is highly inconsistent, it was often necessary to re-analyze prior studies, when possible, and to re-assess them within the framework of composite mechanics and dentin structure. A critical re-evaluation of the literature indicates that the magnitudes of the elastic constants of dentin must be revised considerably upward. The Young’s and shear moduli lie between 20-25 GPa and 7-10 GPa, respectively. Viscoelastic behavior (time-dependent stress relaxation) measurably reduces these values at strain rates of physiological relevance; the reduced modulus (infinite relaxation time) is about 12 GPa. Furthermore, it appears as if the elastic properties are anisotropic (not the same in all directions); sonic methods detect hexagonal anisotropy, although its magnitude appears to be small. Strength data are re-interpreted within the framework of the Weibull distribution function. The large coefficients of variation cited in all strength studies can then be understood in terms of a distribution of flaws within the dentin specimens. The apparent size-effect in the tensile and shear strength data has its origins in this flaw distribution, and can be quantified by the Weibull analysis. Finally, the relatively few fracture mechanics and fatigue studies are discussed. Dentin has a fatigue limit. For stresses smaller than the normal stresses of mastication, ∼ 30 MPa, a flaw-free dentin specimen apparently will not fail. However, a more conservative approach based on fatigue crack growth rates indicates that if there is a pre-existing flaw of sufficient size (∼ 0.3-1.0 mm), it can grow to catastrophic proportion with cyclic loading at stresses below 30 MPa.

Sleep bruxism (SB) is reported by 8% of the adult population and is mainly associated with rhythmic masticatory muscle activity (RMMA) characterized by repetitive jaw muscle contractions (3 bursts or more at a frequency of 1 Hz). The consequences of SB may include tooth destruction, jaw pain, headaches, or the limitation of mandibular movement, as well as tooth-grinding sounds that disrupt the sleep of bed partners. SB is probably an extreme manifestation of a masticatory muscle activity occurring during the sleep of most normal subjects, since RMMA is observed in 60% of normal sleepers in the absence of grinding sounds. The pathophysiology of SB is becoming clearer, and there is an abundance of evidence outlining the neurophysiology and neurochemistry of rhythmic jaw movements (RJM) in relation to chewing, swallowing, and breathing. The sleep literature provides much evidence describing the mechanisms involved in the reduction of muscle tone, from sleep onset to the atonia that characterizes rapid eye movement (REM) sleep. Several brainstem structures (e.g., reticular pontis oralis, pontis caudalis, parvocellularis) and neurochemicals (e.g., serotonin, dopamine, gamma aminobutyric acid [GABA], noradrenaline) are involved in both the genesis of RJM and the modulation of muscle tone during sleep. It remains unknown why a high percentage of normal subjects present RMMA during sleep and why this activity is three times more frequent and higher in amplitude in SB patients. It is also unclear why RMMA during sleep is characterized by co-activation of both jaw-opening and jaw-closing muscles instead of the alternating jaw-opening and jaw-closing muscle activity pattern typical of chewing. The final section of this review proposes that RMMA during sleep has a role in lubricating the upper alimentary tract and increasing airway patency. The review concludes with an outline of questions for future research.

The concept of a two-step process of cancer development in the oral mucosa, i.e., the initial presence of a precursor subsequently developing into cancer, is well-established. Oral leukoplakia is the best-known precursor lesion. The evidence that oral leukoplakias are pre-malignant is mainly derived from follow-up studies showing that between < 1 and 18% of oral pre-malignant lesions will develop into oral cancer; it has been shown that certain clinical sub-types of leukoplakia are at a higher risk for malignant transformation than others. The presence of epithelial dysplasia may be even more important in predicting malignant development than the clinical characteristics. Three major problems, however, are attached to the importance of epithelial dysplasia in predicting malignant development: (1) The diagnosis is essentially subjective, (2) it seems that not all lesions exhibiting dysplasia will eventually become malignant and some may even regress, and (3) carcinoma can develop from lesions in which epithelial dysplasia was not diagnosed in previous biopsies. There is, therefore, a substantial need to improve the histologic assessment of epithelial dysplasia or, since epithelial dysplasia does not seem to be invariably associated with or even a necessary prerequisite for malignant development, it may be necessary to develop other methods for predicting the malignant potential of pre-malignant lesions. As a consequence of these problems, numerous attempts have been made to relate biological characteristics to the malignant potential of leukoplakias. Molecular biological markers have been suggested to be of value in the diagnosis and prognostic evaluation of leukoplakias. Markers of epithelial differentiation and, more recently, genomic markers could potentially be good candidates for improving the prognostic evaluation of precursors of oral cancer. As yet, one or a panel of molecular markers has not been determined that allows for a prognostic prediction of oral pre-cancer which is any more reliable than dysplasia recording. However, these new markers could be considered complementary to conventional prognostic evaluation.

A substantial part of the maxillofacial surgery practice deals with maxillofacial bone healing. In the past decades, low-intensity ultrasound treatment has been shown to reduce the healing time of fresh fractures of the extremities up to 38%, and to heal delayed and non-unions up to 90% and 83%, respectively. Based on the assumption that the process of bone healing in the bones of the extremities and maxillofacial skeleton is essentially the same, the potential of ultrasound to stimulate maxillofacial bone healing was investigated. Although limited evidence is available to support the susceptibility of maxillofacial bone to the ultrasound signal, ultrasound may be of value in the treatment of delayed unions, in callus maturation after distraction, and in the treatment of osteoradionecrosis.