bluuebunny/crossref_metadata_2025 huggingface dataset:
Phospholipids in Amelogenesis and Dentinogenesis
Authors: Goldberg M. , Septier D.
Published: January 2009

Phospholipids have been identified in enamel and dentin. Before demineralization, a group of phospholipids extracted by lipid solvents was associated with cell membranes and is therefore closely related to cell growth and intracellular regulations. After demineralization, a second group of phospholipids, associated with the extracellular matrix, was extracted; this group is probably linked to the mineralized phase. Using imidazole-osmium tetroxide fixation of rat incisors, we stained cellular unsaturated fatty acids, so that we could visualize the membrane domains, coated pits, and endocytic inclusions. Filipin, a probe for cholesterol, varied in density along the plasma membrane of secretory ameloblasts, and allowed us to visualize membrane remnants inside the forming enamel. With respect to phospholipids located in the extracellular matrix, the malachite-green–glutaraldehyde (MGA) method or iodoplatinate (IP) reaction retains and visualizes enamel and dentin phospholipids. In predentin, aggregates appearing as granules and filaments, or liposome-like structures, were located in the spaces between collagen fibrils. In dentin, organic envelopes coating the crystals, also named “crystal-ghost” structures, outlined groups of collagen fibrils. Histochemical data provided evidence that phospholipids are co-distributed or interact with proteoglycans. Radioautography after IP reaction established that [3H] choline was detected in dentin as early as 30 min after the intravenous injection of the labeled precursor, before any labeling was seen in odontoblasts and predentin. This suggests that blood-serum-labeled phospholipids pass between odontoblasts, cross the distal permeable junctional complex, and diffuse in dentin prior to any cellular uptake and phospholipid synthesis. Pharmacologically and genetically induced pathology also supports the suggestion that phospholipids play an important role in the formation and mineralization of dental tissues.
Molecular Dissection of Craniofacial Development Using Zebrafish
Authors: Yelick Pamela C. , Schilling Thomas F.
Published: January 2009

The zebrafish, Danio rerio, is a small, freshwater teleost that only began to be used as a vertebrate genetic model by the late George Streisinger in the early 1980s. The strengths of the zebrafish complement genetic studies in mice and embryological studies in avians. Its advantages include high fecundity, externally fertilized eggs and transparent embryos that can be easily manipulated, inexpensive maintenance, and the fact that large-scale mutagenesis screens can be performed. Here we review studies that have used the zebrafish as a model for craniofacial development. Lineage studies in zebrafish have defined the origins of the cranial skeleton at the single-cell level and followed the morphogenetic behaviors of these cells in skeletal condensations. Furthermore, genes identified by random mutational screening have now revealed genetic pathways controlling patterning of the jaw and other pharyngeal arches, as well as the midline of the skull, that are conserved between fish and humans. We discuss the potential impact of specialized mutagenesis screens and the future applications of this versatile, vertebrate developmental model system in the molecular dissection of craniofacial development.
Dental Caries Vaccines: Prospects and Concerns
Authors: Smith D.J.
Published: January 2009

Dental caries remains one of the most common infectious diseases of mankind. Cariogenic micro-organisms enter the dental biofilm early in life and can subsequently emerge, under favorable environmental conditions, to cause disease. In oral fluids, adaptive host defenses aroused by these infections are expressed in the saliva and gingival crevicular fluid. This review will focus on methods by which mucosal host defenses can be induced by immunization to interfere with dental caries caused by mutans streptococci. The natural history of mutans streptococcal colonization is described in the context of the ontogeny of mucosal immunity to these and other indigenous oral streptococci. Molecular targets for dental caries vaccines are explored for their effectiveness in intact protein and subunit (synthetic peptide, recombinant and conjugate) vaccines in pre-clinical studies. Recent progress in the development of mucosal adjuvants and viable and non-viable delivery systems for dental caries vaccines is described. Finally, the results of clinical trials are reviewed, followed by a discussion of the prospects and concerns of human application of the principles presented.
Dynamics of the Human Masticatory System
Authors: Koolstra J.H.
Published: January 2009

In this review, the movement characteristics of the human masticatory system are discussed from a biomechanical perspective. The discussion is based upon the three fundamental laws of mechanics applied to the various anatomical structures that are part of the masticatory system. An analysis of the forces and torques applied to the mandible by muscles, joints, articular capsules, and teeth is used to assess the determinants of jaw movement. The principle of relating the interplay of forces to the center of gravity of the lower jaw, in contrast to a hinge axis near its joints, is introduced. It is evident that the muscles are the dominant determinants of jaw movement. The contributions of the individual muscles to jaw movements can be derived from the orientation of their lines of action with respect to the center of gravity of the lower jaw. They cause the jaw to accelerate with six degrees of freedom. The ratio between linear and angular accelerations is subtly dependent on the mass and moments of inertia of the jaw, and the structures that are more or less rigidly attached to it. The effects of articular forces must be taken into account, especially if the joints are loaded asymmetrically. The muscles not only move the jaw but also maintain articular stability during midline movements. Passive structures, such as the ligaments, become dominant only when the jaw reaches its movement boundaries. These ligaments are assumed to prevent joint dislocation during non-midline movements.
The Biologic Role for Nuclear Factor-KappaB in Disease and its Potential Involvement in Mucosal Injury Associated with Anti-neoplastic Therapy
Authors: Sonis Stephen T.
Published: January 2009

Oral mucosal barrier injury (mucositis) is a frequent, painful, serious, dose-limiting toxicity associated with many anti-neoplastic drugs and radiation to the head and neck. Results of recent studies suggest that mucositis is the result of a complex series of interactive biological events that take place in the submucosa and epithelium. The nuclear transcription factor NF-κB has been implicated in the control of a broad range of biological responses, the activation of a large number of specific cellular genes, and the determination of the fate of cells exposed to ionizing radiation and anti-neoplastic drugs. Of particular importance to mucositis is the fact that NF-κB regulates key elements in the apparent sequence that leads to normal tissue toxicity. Not the least of these is the effect that NF-κB activation has on apoptosis. In particular, a paradox exists between the potential pro-apoptotic effect NF-κB exerts on normal cells, and the anti-apoptotic and cytoprotective effect it causes in tumor cells. This paper provides a review of the structure and function of NF-κB and speculates how its apparent enigmatic effect on normal and tumor cells may occur.
Oral Lichen Planus and Malignant Transformation: Is a Recall of Patients Justified?
Authors: Mattsson Ulf , Jontell Mats , Holmstrup Palle
Published: January 2009

There has been a continuous debate regarding the possible malignant potential of oral lichen planus (OLP). Based on the results from follow-up studies, OLP is regarded by several authors as a pre-malignant condition, and patients with OLP have been recommended to have their lesions monitored two to four times annually. This recommendation needs reconsideration, because a recall system of all patients with OLP requires substantial economic resources. In a reality where such resources are limited, a recall system must be weighed against other benefits and the fact that the malignant potential of OLP is most likely very low. The present review focuses on the diagnostic criteria for OLP, the pre-malignant potential of OLP, and the extent to which the available information can be used to reduce morbidity and mortality of oral cancer related to OLP.
Lipoxins in Chronic Inflammation
Authors: Kantarci Alpdogan , Van Dyke Thomas E.
Published: January 2009

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 Mechanical Properties of Human Dentin: a Critical Review and Re-evaluation of the Dental Literature
Authors: Kinney J.H. , Marshall S.J. , Marshall G.W.
Published: January 2009

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.
Prognosis of Oral Pre-malignant Lesions: Significance of Clinical, Histopathological, and Molecular Biological Characteristics
Authors: Reibel Jesper
Published: January 2009

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.
Genetically Altered Mouse Models: the Good, the Bad, and the Ugly
Authors: Thyagarajan Tamizchelvi , Totey Satish , Danton Mary Jo S. , Kulkarni Ashok B.
Published: January 2009

Targeted gene disruption in mice is a powerful tool for generating murine models for human development and disease. While the human genome program has helped to generate numerous candidate genes, few genes have been characterized for their precise in vivo functions. Gene targeting has had an enormous impact on our ability to delineate the functional roles of these genes. Many gene knockout mouse models faithfully mimic the phenotypes of the human diseases. Because some models display an unexpected or no phenotype, controversy has arisen about the value of gene-targeting strategies. We argue in favor of gene-targeting strategies, provided they are used with caution, particularly in interpreting phenotypes in craniofacial and oral biology, where many genes have pleiotropic roles. The potential pitfalls are outweighed by the unique opportunities for developing and testing different therapeutic strategies before they are introduced into the clinic. In the future, we believe that genetically engineered animal models will be indispensable for gaining important insights into the molecular mechanisms underlying development, as well as disease pathogenesis, diagnosis, prevention, and treatment.
Mast Cells and Oral Inflammation
Authors: Walsh Laurence J.
Published: January 2009

Mast cells are mobile granule-containing secretory cells that are distributed preferentially about the microvascular endothelium in oral mucosa and dental pulp. The enzyme profile of mast cells in oral tissues resembles that of skin, with most mast cells expressing the serine proteases tryptase and chymase. Mast cells in oral tissues contain the pro-inflammatory cytokine tumour necrosis factor-α in their granules, and release of this promotes leukocyte infiltration during evolving inflammation in several conditions, including lichen planus, gingivitis, pulpitis, and periapical inflammation, through induction of endothelial-leukocyte adhesion molecules. Mast cell synthesis and release of other mediators exerts potent immunoregulatory effects on other cell types, while several T-lymphocyte-derived cytokines influence mast cell migration and mediator release. Mast cell proteases may contribute to alterations in basement membranes in inflammation in the oral cavity, such as the disruptions that allow cytotoxic lymphocytes to enter the epithelium in oral lichen planus. A close relationship exists among mast cells, neural elements, and laminin, and this explains the preferential distribution of mast cells in tissues. Mast cells are responsive to neuropeptides and, through their interaction with neural elements, form a neural immune network with Langerhans cells in mucosal tissues. This facilitates mast cell degranulation in response to a range of immunological and non-immunological stimuli. Because mast cells play a pivotal role in inflammation, therapies that target mast cell functions could have value in the treatment of chronic inflammatory disorders in the oral cavity.
Oral Sequelae of Head and Neck Radiotherapy
Authors: Vissink A. , Jansma J. , Spijkervet F.K.L. , Burlage F.R. , Coppes R.P.
Published: January 2009

In addition to anti-tumor effects, ionizing radiation causes damage in normal tissues located in the radiation portals. Oral complications of radiotherapy in the head and neck region are the result of the deleterious effects of radiation on, e.g., salivary glands, oral mucosa, bone, dentition, masticatory musculature, and temporomandibular joints. The clinical consequences of radiotherapy include mucositis, hyposalivation, taste loss, osteoradionecrosis, radiation caries, and trismus. Mucositis and taste loss are reversible consequences that usually subside early post-irradiation, while hyposalivation is normally irreversible. Furthermore, the risk of developing radiation caries and osteoradionecrosis is a life-long threat. All these consequences form a heavy burden for the patients and have a tremendous impact on their quality of life during and after radiotherapy. In this review, the radiation-induced changes in healthy oral tissues and the resulting clinical consequences are discussed.
Prevention and Treatment of the Consequences of Head and Neck Radiotherapy
Authors: Vissink A. , Burlage F.R. , Spijkervet F.K.L. , Jansma J. , Coppes R.P.
Published: January 2009

The location of the primary tumor or lymph node metastases dictates the inclusion of the oral cavity, salivary glands, and jaws in the radiation treatment portals for patients who have head and neck cancer. The clinical sequelae of the radiation treatment include mucositis, hyposalivation, loss of taste, osteoradionecrosis, radiation caries, and trismus. These sequelae may be dose-limiting and have a tremendous effect on the patient’s quality of life. Most treatment protocols to prevent these sequelae are still based on clinical experience, but alternatives based on fundamental basic and clinical research are becoming more and more available. Many of these alternatives either need further study before they can be incorporated into the protocols commonly used to prevent and treat the radiation-related oral sequelae or await implementation of these protocols. In this review, the various possibilities for prevention and/or treatment of radiation-induced changes in healthy oral tissues and their consequences are discussed.
The Role of Acquired Immunity and Periodontal Disease Progression
Authors: Teng Yen-Tung A.
Published: January 2009

Our understanding of the pathogenesis in human periodontal diseases is limited by the lack of specific and sensitive tools or models to study the complex microbial challenges and their interactions with the host’s immune system. Recent advances in cellular and molecular biology research have demonstrated the importance of the acquired immune system not only in fighting the virulent periodontal pathogens but also in protecting the host from developing further devastating conditions in periodontal infections. The use of genetic knockout and immunodeficient mouse strains has shown that the acquired immune response—in particular, CD4+ T-cells—plays a pivotal role in controlling the ongoing infection, the immune/inflammatory responses, and the subsequent host’s tissue destruction. In particular, studies of the pathogen-specific CD4+ T-cell-mediated immunity have clarified the roles of: (i) the relative diverse immune repertoire involved in periodontal pathogenesis, (ii) the contribution of pathogen-associated Th1-Th2 cytokine expressions in periodontal disease progression, and (iii) micro-organism-triggered periodontal CD4+ T-cell-mediated osteoclastogenic factor, ‘RANK-L’, which is linked to the induction of alveolar bone destruction in situ. The present review will focus on some recent advances in the acquired immune responses involving B-cells, CD8+ T-cells, and CD4+ T-cells in the context of periodontal disease progression. New approaches will further facilitate our understanding of their underlying molecular mechanisms that may lead to the development of new treatment modalities for periodontal diseases and their associated complications.

Abbreviations used in the paper are as follows: Antibody, Ab; antigen, Ag; antigen-presenting cells, APC; Actinobacillus actinomycetemcomitans, A. actinomycetemcomitans or Aa; β2-microglobulin, β2m; cytotoxic CD8+ αβ T-lymphocytes, CTL; dendritic cells, DC; delayed-type hypersensitivity, DTH; immunoglobulin, Ig; Fc receptor, Fc-R; interferon-γ, IFN-γ; receptor activator of NF-κB ligand, RANK-L; molecular weight, MW; Porphyromonas gingivalis, P. gingivalis or Pg; localized juvenile periodontitis, LJP; lipopolysaccharide, LPS; mouse mammalian tumor virus, MMTV; non-obese diabetic and severe combined immunodeficiency mice, NOD/SCID mice; osteoclast, OC; T-helper cells, Th; superantigen, SAg; transforming growth factor-β, TGF-β; secretory-IgA, s-IgA; T-cell receptor, TCR; T cytotoxic-1 cells, Tc1; and T cytotoxic-2 cells, Tc2.
Paracoccidioidomycosis of the Mouth: an Emerging Deep Mycosis
Authors: Almeida Oslei Paes , Jorge Junior Jacks , Scully Crispian
Published: January 2009

Oral fungal infections (mycoses) have come into particular prominence since the advent of infection with Human Immunodeficiency Virus (HIV), and recognition of the Acquired Immune Deficiency Syndrome (AIDS), as well as the phenomenal increase in world travel with increased exposure to infections endemic in the tropics. Paracoccidioidomycosis is a rare mycosis worldwide but common in Brazil and some other areas in Latin America. It can be life-threatening and can manifest with a spectrum of clinical presentations, including frequent oral lesions. This paper reviews the more recent information on Paracoccidioidomycosis, emphasizing those areas most relevant in dental science.
Tooth Bleaching—a Critical Review of the Biological Aspects
Authors: Dahl J.E. , Pallesen U.
Published: January 2009

Present tooth-bleaching techniques are based upon hydrogen peroxide as the active agent. It is applied directly, or produced in a chemical reaction from sodium perborate or carbamide peroxide. More than 90% immediate success has been reported for intracoronal bleaching of non-vital teeth, and in the period of 1–8 years’ observation time, from 10 to 40% of the initially successfully treated teeth needed re-treatment. Cervical root resorption is a possible consequence of internal bleaching and is more frequently observed in teeth treated with the thermo-catalytic procedure. When the external tooth-bleaching technique is used, the first subjective change in tooth color may be observed after 2–4 nights of tooth bleaching, and more than 90% satisfactory results have been reported. Tooth sensitivity is a common side-effect of external tooth bleaching observed in 15%-78% of the patients, but clinical studies addressing the risk of other adverse effects are lacking. Direct contact with hydrogen peroxide induced genotoxic effects in bacteria and cultured cells, whereas the effect was reduced or abolished in the presence of metabolizing enzymes. Several tumor-promoting studies, including the hamster cheek pouch model, indicated that hydrogen peroxide might act as a promoter. Multiple exposures of hydrogen peroxide have resulted in localized effects on the gastric mucosa, decreased food consumption, reduced weight gain, and blood chemistry changes in mice and rats. Our risk assessment revealed that a sufficient safety level was not reached in certain clinical situations of external tooth bleaching, such as bleaching one tooth arch with 35% carbamide peroxide, using several applications per day of 22% carbamide peroxide, and bleaching both arches simultaneously with 22% carbamide peroxide. The recommendation is to avoid using concentrations higher than 10% carbamide peroxide when one performs external bleaching. We advocate a selective use of external tooth bleaching based on high ethical standards and professional judgment.
Molecular Genetic Analysis of the Virulence of Oral Bacterial Pathogens: An Historical Perspective
Authors: Kuramitsu Howard K.
Published: January 2009

This review will focus on the impact of molecular genetic approaches on elucidating the bacterial etiology of oral diseases from an historical perspective. Relevant results from the pre- and post-recombinant DNA periods will be highlighted, including the roles of gene cloning, mutagenesis, and nucleotide sequencing in this area of research. Finally, the impact of whole-genome sequencing on deciphering the virulence mechanisms of oral pathogens, along with new approaches to control these organisms, will be discussed.
The Molecular Biology of Mucosal Field Cancerization of the Head and Neck
Authors: Ha Patrick K. , Califano Joseph A.
Published: January 2009

Field cancerization was first described in 1953 as histologically altered epithelium surrounding tumor samples taken from the upper aerodigestive tract. Since then, the term has been used to describe multiple patches of pre-malignant disease, a higher-than-expected prevalence of multiple local second primary tumors, and the presence of synchronous distant tumors within the upper aerodigestive tract. Molecular techniques such as karyotype analysis, microsatellite analysis, p53 mutation screening, and X-chromosome inactivation studies have further refined the relationship among these lesions. While there are differences in the techniques used to identify the clonal origins of the lesions, these studies indicate that there is often lateral clonal spread of pre-malignant or malignant disease, and a significant portion of local second primary tumors are in fact genetically related. Distant second primary tumors found in the esophagus are often not related to concurrent head and neck cancer, whereas synchronous squamous lung tumors with a head and neck primary are often, in fact, metastases, rather than independently arising malignancies. These observations help to explain the high incidence of recurrent disease, despite excision or other therapy—pre-malignant or malignant clones often have the ability to migrate and persist outside of the field of treatment. Therefore, alternative means of prevention or therapy that can affect the entire head and neck region may be of benefit to such patients. Future studies will further refine the relationship among these lesions and perhaps identify key molecular alterations to be used as targets for gene therapy.
Tongue Movements in Feeding and Speech
Authors: Hiiemae Karen M. , Palmer Jeffrey B.
Published: January 2009

The position of the tongue relative to the upper and lower jaws is regulated in part by the position of the hyoid bone, which, with the anterior and posterior suprahyoid muscles, controls the angulation and length of the floor of the mouth on which the tongue body ‘rides’. The instantaneous shape of the tongue is controlled by the ‘extrinsic muscles’ acting in concert with the ‘intrinsic’ muscles. Recent anatomical research in non-human mammals has shown that the intrinsic muscles can best be regarded as a ‘laminated segmental system’ with tightly packed layers of the ‘transverse’, ‘longitudinal’, and ‘vertical’ muscle fibers. Each segment receives separate innervation from branches of the hypoglosssal nerve. These new anatomical findings are contributing to the development of functional models of the tongue, many based on increasingly refined finite element modeling techniques. They also begin to explain the observed behavior of the jaw-hyoid-tongue complex, or the hyomandibular ‘kinetic chain’, in feeding and consecutive speech. Similarly, major efforts, involving many imaging techniques (cinefluorography, ultrasound, electro-palatography, NMRI, and others), have examined the spatial and temporal relationships of the tongue surface in sound production. The feeding literature shows localized tongue-surface change as the process progresses. The speech literature shows extensive change in tongue shape between classes of vowels and consonants. Although there is a fundamental dichotomy between the referential framework and the methodological approach to studies of the orofacial complex in feeding and speech, it is clear that many of the shapes adopted by the tongue in speaking are seen in feeding. It is suggested that the range of shapes used in feeding is the matrix for both behaviors.
Cells and Extracellular Matrices of Dentin and Pulp: A Biological Basis for Repair and Tissue Engineering
Authors: Goldberg Michel , Smith Anthony J.
Published: January 2009

Odontoblasts produce most of the extracellular matrix (ECM) components found in dentin and implicated in dentin mineralization. Major differences in the pulp ECM explain why pulp is normally a non-mineralized tissue. In vitro or in vivo, some dentin ECM molecules act as crystal nucleators and contribute to crystal growth, whereas others are mineralization inhibitors. After treatment of caries lesions of moderate progression, odontoblasts and cells from the sub-odontoblastic Höhl’s layer are implicated in the formation of reactionary dentin. Healing of deeper lesions in contact with the pulp results in the formation of reparative dentin by pulp cells. The response to direct pulp-capping with materials such as calcium hydroxide is the formation of a dentinal bridge, resulting from the recruitment and proliferation of undifferentiated cells, which may be either stem cells or dedifferentiated and transdifferentiated mature cells. Once differentiated, the cells synthesize a matrix that undergoes mineralization. Animal models have been used to test the capacity of potentially bioactive molecules to promote pulp repair following their implantation into the pulp. ECM molecules induce either the formation of dentinal bridges or large areas of mineralization in the coronal pulp. They may also stimulate the total closure of the pulp in the root canal. In conclusion, some molecules found in dentin extracellular matrix may have potential in dental therapy as bioactive agents for pulp repair or tissue engineering.
Biological Risks of Resin-based Materials to the Dentin-Pulp Complex
Authors: Bouillaguet Serge
Published: January 2009

Over the past 30 years, restorative dentistry has seen a revolution in materials, restorative techniques, and patient priorities. This revolution has been made possible with the development of new resin-based materials which can be bonded to the tooth structure. Not all of these changes have been without controversy or concern, and some have raised questions about the biological safety of these new materials and techniques. It is the purpose of this review to present recent and relevant information about the biological risks and consequences of resin-tooth bonding and how these risks are affected by the material, its clinical properties, and its manipulation by the practitioner. These biological risks are complex and interactive, and are still incompletely defined. In broad terms, these risks can be divided into those stemming from the toxicological properties of the materials themselves (direct biological risks) and those stemming from microbiological leakage (indirect biological risks).
Post-translational Modifications of SIBLING Proteins and Their Roles in Osteogenesis and Dentinogenesis
Authors: Qin C. , Baba O. , Butler W.T.
Published: January 2009

The extracellular matrix (ECM) of bone and dentin contains several non-collagenous proteins. One category of non-collagenous protein is termed the SIBLING (Small Integrin-Binding LIgand, N-linked Glycoprotein) family, that includes osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), and matrix extracellular phosphoglycoprotein (MEPE). These polyanionic SIBLING proteins are believed to play key biological roles in the mineralization of bone and dentin. Although the specific mechanisms involved in controlling bone and dentin formation are still unknown, it is clear that some functions of the SIBLING family members are dependent on the nature and extent of post-translational modifications (PTMs), such as phosphorylation, glycosylation, and proteolytic processing, since these PTMs would have significant effects on their structure. OPN and BSP are present in the ECM of bone and dentin as full-length forms, whereas amino acid sequencing indicates that DMP1 and DSPP exist as proteolytically processed fragments that result from scission of X-Asp bonds. We hypothesized that the processing of DMP1 and DSPP is catalyzed by the PHEX enzyme, since this protein, an endopeptidase that is predominantly expressed in bone and tooth, has a strong preference for cleavage at the NH2-terminus of aspartyl residue. We envision that the proteolytic processing of DMP1 and DSPP may be an activation process that plays a significant, crucial role in osteogenesis and dentinogenesis, and that a failure in this processing would cause defective mineralization in bone and dentin, as observed in X-linked hypophosphatemic rickets.
The Embryonic Origins of Left-Right Asymmetry
Authors: Levin Michael
Published: January 2009

The bilaterally symmetric body plan of vertebrates features several consistent asymmetries in the placement, structure, and function of organs such as the heart, intestine, and brain. Deviations from the normal pattern result in situs inversus, isomerisms, or heterotaxia (independent randomization), which have significant clinical implications. The invariance of the left-right (LR) asymmetry of normal morphology, neuronal function, and phenotype of several syndromes raises fascinating and fundamental questions in cell, developmental, evolutionary, and neurobiology. While a pathway of asymmetrically expressed signaling factors has been well-characterized in several model systems, very early steps in the establishment of LR asymmetry remain poorly understood. In particular, the origin of consistently oriented asymmetry is unknown. Recently, a candidate for the origins of asymmetry has been suggested: bulk transport of extracellular morphogens by rotating primary cilia during gastrulation. This model is appealing because it ‘bootstraps’ morphological asymmetry of the embryo from the intrinsic structural (molecular) chirality of motile cilia. However, conceptual and practical problems remain with this hypothesis. Indeed, the genetic data are also consistent with a different mechanism: cytoplasmic transport roles of motor proteins. This review outlines the progress and remaining questions in the field of left-right asymmetry, and focuses on an alternative model for ‘Step 1’ of asymmetry. More specifically, based on wide-ranging data on ion fluxes and motor protein function in several species, it is suggested that laterality is driven by pH/voltage gradients across the midline, which are established by chiral movement of motor proteins with respect to the cytoskeleton.
The Wrickkened Pathways of FGF23, MEPE and PHEX
Authors: Rowe Peter S.N.
Published: January 2009

The last 350 years since the publication of the first medical monograph on rickets (old English term wrickken) ( Glisson et al., 1651 ) have seen spectacular advances in our understanding of mineral-homeostasis. Seminal and exciting discoveries have revealed the roles of PTH, vitamin D, and calcitonin in regulating calcium and phosphate, and maintaining healthy teeth and skeleton. However, it is clear that the PTH/Vitamin D axis does not account for the entire picture, and a new bone-renal metabolic milieu has emerged, implicating a novel set of matrix proteins, hormones, and Zn-metallopeptidases. The primary defects in X-linked hypophosphatemic rickets (HYP) and autosomal-dominant hypophosphatemic rickets (ADHR) are now identified as inactivating mutations in a Zn-metalloendopeptidase (PHEX) and activating mutations in fibroblast-growth-factor-23 (FGF23), respectively. In oncogenic hypophosphatemic osteomalacia (OHO), several tumor-expressed proteins (MEPE, FGF23, and FRP-4) have emerged as candidate mediators of the bone-renal pathophysiology. This has stimulated the proposal of a global model that takes into account the remarkable similarities between the inherited diseases (HYP and ADHR) and the tumor-acquired disease OHO. In HYP, loss of PHEX function is proposed to result in an increase in uncleaved full-length FGF23 and/or inappropriate processing of MEPE. In ADHR, a mutation in FGF23 results in resistance to proteolysis by PHEX or other proteases and an increase in half-life of full-length phosphaturic FGF23. In OHO, over-expression of FGF23 and/or MEPE is proposed to result in abnormal renal-phosphate handling and mineralization. Although this model is attractive, many questions remain unanswered, suggesting a more complex picture. The following review will present a global hypothesis that attempts to explain the experimental and clinical observations in HYP, ADHR, and OHO, plus diverse mouse models that include the MEPE null mutant, HYP-PHEX transgenic mouse, and MEPE-PHEX double-null-mutant.
Virulence Factors ofEnterococcus faecalis: Relationship to Endodontic Disease
Authors: Kayaoglu Güven , Ørstavik Dag
Published: January 2009

Enterococcus faecalis is a micro-organism that can survive extreme challenges. Its pathogenicity ranges from life-threatening diseases in compromised individuals to less severe conditions, such as infection of obturated root canals with chronic apical periodontitis. In the latter situation, the infecting organisms are partly shielded from the defense mechanisms of the body. In this article, we review the virulence factors of E. faecalis that may be related to endodontic infection and the periradicular inflammatory response. The most-cited virulence factors are aggregation substance, surface adhesins, sex pheromones, lipoteichoic acid, extracellular superoxide production, the lytic enzymes gelatinase and hyaluronidase, and the toxin cytolysin. Each of them may be associated with various stages of an endodontic infection as well as with periapical inflammation. While some products of the bacterium may be directly linked to damage of the periradicular tissues, a large part of the tissue damage is probably mediated by the host response to the bacterium and its products.
Pathogenesis of Apical Periodontitis and the Causes of Endodontic Failures
Authors: Nair P.N.R.
Published: January 2009

Apical periodontitis is a sequel to endodontic infection and manifests itself as the host defense response to microbial challenge emanating from the root canal system. It is viewed as a dynamic encounter between microbial factors and host defenses at the interface between infected radicular pulp and periodontal ligament that results in local inflammation, resorption of hard tissues, destruction of other periapical tissues, and eventual formation of various histopathological categories of apical periodontitis, commonly referred to as periapical lesions. The treatment of apical periodontitis, as a disease of root canal infection, consists of eradicating microbes or substantially reducing the microbial load from the root canal and preventing re-infection by orthograde root filling. The treatment has a remarkably high degree of success. Nevertheless, endodontic treatment can fail. Most failures occur when treatment procedures, mostly of a technical nature, have not reached a satisfactory standard for the control and elimination of infection. Even when the highest standards and the most careful procedures are followed, failures still occur. This is because there are root canal regions that cannot be cleaned and obturated with existing equipments, materials, and techniques, and thus, infection can persist. In very rare cases, there are also factors located within the inflamed periapical tissue that can interfere with post-treatment healing of the lesion. The data on the biological causes of endodontic failures are recent and scattered in various journals. This communication is meant to provide a comprehensive overview of the etio-pathogenesis of apical periodontitis and the causes of failed endodontic treatments that can be visualized in radiographs as asymptomatic post-treatment periapical radiolucencies.
It Makes Nothing Happen: Reasons for Studying the History of Law
Authors: Dale Elizabeth
Published: January 2009

In place of the idea that legal history should search for a new grand narrative of law, written to persuade lawyers and judges and change the world, this article suggests that legal historians focus their attention on writing and teaching more particularized histories targeting a popular audience.
The Strait Gate: The Past, History, and Legal Scholarship
Authors: Tomlins Christopher
Published: January 2009

For many years, history has furnished a conceptual and methodological standpoint, historicism, which scholars have employed to enter into engagements with law. But how do the exponents of historicism — whether conventional or critical — define that standpoint, and what is the nature of the object (the past) that their definitions isolate for contemplation? This essay seeks illumination through counterpoint — an exposition of Walter Benjamin's philosophy of history and its key components: recollection, actualization and constellation. I propose that history can and should be a dangerous form of knowledge, and that Benjamin worked hard to show us how. To make it so, however, requires that one abandon what most forms of contemporary historical inquiry take for granted, history-as-science. To show why, I develop an examination and critique of historicist sense-making in the domain of law, both conventional and critical. I also engage with two recent scholarly attempts to move beyond historicism: how they succeed, where they fail, and what we learn from them.
Socrates and the Moral Limits of Legal Obligation
Authors: Howenstein Mark S.
Published: January 2009

This article presents a critical analysis of Plato's Apology and Crito — focusing on the moral limits of legal obligation that ground both Socrates' resistance to state injustice and his acceptance of his unjust sentence. It does so by juxtaposing Socrates' advocacy of the priority of right action in the Apology to his equally ardent rationalization of legal obligation in the Crito, thereby placing him at a critical juncture in the evolution of western legal thought. Throughout this work, a particularly Heideggerian perspective is used to manifest this transition as clearly as possible.

This article proceeds in four distinct stages. Part one presents the contextual background of Socrates' trial as depicted in the Apology. Part two develops the primacy of justice set forth in the first half of the Crito, and upon this basis recreates the genealogy of legal obligation that crowns this work. Part three raises two paradoxes that haunt these works — those of the apparently contradictory alternatives of “persuade or obey” and the dichotomy of “doing versus suffering injustice.” Part four projects the insights so gained onto modern legal positivism and back to ancient Greek tragedy.
American Indian Languages and the Law of Property in Colonial America
Authors: Goodman Nan
Published: January 2009

This paper argues for a new view of land transfers in seventeenth-century New England that attends not only to the Puritans' conception of land but also to the competing conceptualization of land by the Indians. To get an historically accurate picture of land transfers, I argue, we must look beyond the existing archive of deeds, charters, and patents, to the artifacts of culture that reside not only in the written language used by the Puritans, but in the spoken language used by the Algonkian Indians as it was represented by writers like Roger Williams and John Eliot in phrase books, grammars, dialogues, and translations.
England's Legal Monsters
Authors: Sharpe Andrew N.
Published: January 2009

This article offers a history of the English legal category monster, a legal category that entered English law in the mid-thirteenth and survived until the mid-nineteenth century. The aim of the article is to provide a close textual analysis of an otherwise absent legal history and to locate law's monsters, and the anxieties that they suggest, within their appropriate contexts: social, political, religious and legal. However, while the principal aim of the article is to address a lacuna in legal historical scholarship, and perhaps precisely because of this fact, the history to be detailed offers a series of valuable insights for future study, particularly in the areas of legal history, philosophy and feminist theory. While full elaboration of these themes is beyond its ambit, the article will draw attention to four different and specific contexts in relation to which future scholarship might benefit from an historical study of England's legal monsters.
Apoptosis and haemorrhagic shock
Authors: Mach William J , Knight Amanda R , Orr James A , Pierce Janet D
Published: January 2009

Abstract

This is a review paper that provides an overview of current information on programmed cell death in haemorrhagic shock, including the identification of different molecular receptor signals. A PubMed search for all dates was undertaken using the search terms apoptosis, trauma and haemorrhagic shock. Original research, sentinel and review papers from peer-reviewed journals were included for identification of key concepts. Haemorrhagic shock remains a primary cause of death in civilian and military trauma. Apoptosis is accelerated following haemorrhagic shock. Many methods are used to detect and quantify apoptosis. Fluid resuscitation regimens vary in their effect on the extent of apoptosis. Investigators are examining the effects of haemorrhagic shock and fluid resuscitation on apoptotic signalling pathways. Molecular information is becoming available and being applied to the care of patients experiencing haemorrhagic shock, making it essential for nurses and other health care providers to consider the mechanisms and consequences of apoptosis.