bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Potential Role of Doxycycline in the Treatment of Osteoarthritis of the Temporomandibular Joint
Authors: Israel H.A. , Ramamiurthy N.S. , Greenwald R. , Golub L. 
Published: January 2009

Collagenase and gelatinase are matrix metalloproteinases (MMPs) which play an important role in tissue destruction in arthritic joints. Studies have demonstrated that tetracyclines can inhibit MMPs and prevent tissue destruction independent of their antimicrobial activity. The purpose of this pilot study is to assess the potential therapeutic role of Doxycycline in patients with advanced osteoarthritis of the temporomandibular joint (TMJ). This ongoing investigation includes patients with a diagnosis of osteoarthritis of the TMJ based on clinical and diagnostic imaging findings, symptoms (localized TMJ pain, limited mobility, dysfunction) for a minimum of 36 months, and failure of previous non-surgical and surgical modalities to alleviate the symptoms. A synovial fluid sample is collected by a saline injection and aspiration technique, followed by diagnostic arthroscopy. Patients are placed on Doxycycline 50 mg BID for three months and then undergo repeat diagnostic arthroscopy and synovial fluid collection. The samples are stored at -80°C. Collagenase activity is determined by a combination of SDS-polyacrylamide gel electrophoresis and fluorography and calculated based on the percentage of collagen alpha chains that are degraded into alphaA breakdown products. Three patients have completed the three-month course of Doxycycline thus far, and 5 joints with osteoarthritis have been analyzed. All patients were female (mean age = 35, mean duration of symptoms = 132 months) and had undergone previous bilateral arthroscopies. One patient had undergone unilateral arthroplasty. The mean collagenase activity showed 55% collagen lysis prior to Doxycycline treatment and 19% after three months of therapy. The mean gelatinase activity was 28% prior to Doxycycline treatment and 7% after three months of therapy. The mean interincisal opening was 33 mm initially and 41 mm after three months of Doxycycline. Subjectively, two of the three patients reported significant improvement in their overall symptoms, which they had not experienced over the previous three years. One patient did not experience any change in symptoms, in spite of a marked reduction in collagenase activity from 86.4% to 9.6%. Because of the very small numbers of patients enrolled in this pilot study so far, no statistically significant differences could be appreciated. However, the dramatic reduction in collagenase activity in these patients, with a long history of TMJ symptoms from osteoarthritis, suggests the potential promising role of Doxycycline in the management of osteoarthritis, and further investigation is warranted.
Biochemical Composition of Human Saliva in Relation To Other Mucosal Fluids
Authors: Schenkels Léon C.P.M. , Veerman Enno C.I. , Nieuw Amerongen Arie V. 
Published: January 2009

This paper describes several salivary components and their distribution in other mucosal secretions. Histatins are polypeptides which possess exceptional anti-fungal and anti-bacterial activities, but are nevertheless present only in saliva. Proline-rich proteins (PRPs) are members of a closely related family, of which the acidic PRPs are found solely in saliva, whereas the basic PRPs are also found in other secretions. Mucins are a group of glycoproteins that contribute to the visco-elastic character of the mucosal secretions. Despite the similarities in their structure and behavior, mucins have distinct tissue distributions and amino acid sequences. Other salivary proteins are present in one or more mucosal secretions. Lysozyme is an example of a component belonging to an ancient self-defense system, whereas secretory immunoglobulin A (slgA) is the secreted part of a sophisticated adaptive immune system. Cystatins are closely related proteins which belong to a multigene family. a-Amylase is a component that is believed to play a specific role in digestion, but is nevertheless present in several body fluids. Kallikrein and albumin are components of blood plasma. But whereas albumin diffuses into the different mucosal secretions, kallikrein is secreted specifically by the mucosal glands. The presence of these proteins specifically in saliva, or their distribution in other mucosal secretions as well, may provide important clues with respect to the physiology of those proteins in the oral cavity.
Prenatal Craniofacial Development: New Insights on Normal and Abnormal Mechanisms
Authors: Johnston M.C. , Bronsky P.T. 
Published: January 2009

Technical advances are radically altering our concepts of normal prenatal craniofacial development. These include concepts of germ layer formation, the establishment of the initial head plan in the neural plate, and the manner in which head segmentation is controlled by regulatory (homeobox) gene activity in neuromeres and their derived neural crest cells. There is also a much better appreciation of ways in which new cell associations are established. For example, the associations are achieved by neural crest cells primarily through cell migration and subsequent cell interactions that regulate induction, growth, programmed cell death, etc. These interactions are mediated primarily by two groups of regulatory molecules: "growth factors" (e.g., FGF and TGFa) and the so-called steroid/thyroid/retinoic acid superfamily. Considerable advances have been made with respect to our understanding of the mechanisms involved in primary and secondary palate formation, such as growth, morphogenetic movements, and the fusion/merging phenomenon. Much progress has been made on the mechanisms involved in the final differentiation of skeletal tissues. Molecular genetics and animal models for human malformations are providing many insights into abnormal development. A mouse model for the fetal alcohol syndrome (FAS), a mild form of holoprosencephaly, demonstrates a mid-line anterior neural plate deficiency which leads to olfactory placodes being positioned too close to the mid-line, and other secondary changes. Work on animal models for the retinoic acid syndrome (RAS) shows that there is major involvement of neural crest cells. There is also major crest cell involvement in similar syndromes, apparently including hemifacial microsomia. Later administration of retinoic acid prematurely and excessively kills ganglionic placodal cells and leads to a malformation complex virtually identical to the Treacher Collins syndrome. Most clefts of the lip and/or palate appear to have a multifactorial etiology. Genetic variations in TGFαs, RARαs. NADH dehydrogenase, an enzyme involved in oxidative metabolism, and cytochrome P-450, a detoxifying enzyme, have been implicated as contributing genetic factors. Cigarette smoking, with the attendant hypoxia, is a probable contributing environmental factor. It seems likely that few clefts involve single major genes. In most cases, the pathogenesis appears to involve inadequate contact and/or fusion of the facial prominences or palatal shelves. Specific mutations in genes for different FGF receptor molecules have been identified for achondroplasia and Crouzon's syndrome, and in a regulatory gene (Msx2) for one type of craniosynostosis. Poorly co-ordinated control of form and size of structures, or groups of structures (e.g., teeth and jaws), by regulatory genes should do much to explain the very frequent "mismatches" found in malocclusions and other dentofacial "deformities". Future directions for research, including possibilities for prevention, are discussed.
Keratinocyte Gene Transfer and Gene Therapy
Authors: Garlick J.A. , Fenjves E.S. 
Published: January 2009

Gene therapy has moved beyond the pre-clinical stage to the treatment of a variety of inherited and acquired diseases. For such therapy to be successful, genes must be efficiently delivered to target cells and gene products must be expressed for prolonged periods of time without toxic effects to the host. This may be achieved by means of an in vivo strategy where genes are transferred directly into a host cell, or by means of an ex vivo approach through which cells are removed, cultured, targeted for gene delivery, and grafted back to the host. Several obstacles continue to delay safe and effective clinical application of gene therapy in a variety of target cells. The limited survival of transplanted cells, transient expression of transferred genes, and difficulties in targeting stem cells are technical issues requiring further investigation. Epidermal and oral keratinocytes are potential vehicles for gene therapy. Several features of these tissues can be utilized to achieve delivery of therapeutic gene products for local or systemic delivery. These qualities include: (1) the presence of stem cells; (2) the cell-, strata-, and site-specific regulation of keratinocyte gene expression; (3) tissue accessibility; and (4) secretory capacity. Such features can be exploited by the use of gene therapy strategies to facilitate: (1) identification, enrichment, and targeting of stem cells to ensure the continued presence of the transferred gene; (2) high-level and persistent transgene expression using keratinocyte-specific promoters; (3) tissue access needed for culture and grafting for ex vivo therapy and direct in vivo gene transfer; (4) secretion of transgene product for local or systemic delivery; and (5) monitoring of genetically modified tissue and removal if treatment termination is required. Optimal gene therapy strategies are being tested in a variety of tissues to treat dominant and recessive genetic disorders as well as acquired diseases such as neoplasia and infectious disease. This experience provides a basis for the application of such clinical studies to a spectrum of diseases effecting epidermal and oral keratinocytes. Gene therapy is in an early stage yet holds great promise for its ultimate clinical application.
Advanced Imaging Methods
Authors: Matteson S.R. , Deahl S.T. , Alder M.E. , Nummikoski P.V. 
Published: January 2009

Recent developments in imaging sciences have enabled dental researchers to visualize structural and biophysical changes effectively. New approaches for intra-oral radiography allow investigators to conduct densitometric assessments of dento-alveolar structures. Longitudinal changes in alveolar bone can be studied by computer-assisted image analysis programs. These techniques have been applied to dimensional analysis of the alveolar crest, detection of gain or loss of alveolar bone density, peri-implant bone healing, and caries detection. Dental applications of computed tomography (CT) include the detailed radiologic anatomy of alveolar processes, orofacial soft tissues and air spaces, and developmental defects. Image analysis software permits bone mass mineralization to be quantified by means of CT data. CT has also been used to study salivary gland disease, injuries of the facial skeleton, and dental implant treatment planning. Magnetic resonance imaging (MRI) has been used extensively in retrospective and prospective studies of internal derangements of the temporomandibular joint. Assessments based on MRI imaging of the salivary glands, paranasal sinuses, and cerebrovascular disease have also been reported. Magnetic resonance spectroscopy (MRS) has been applied to the study of skeletal muscle, tumors, and to monitor the healing of grafts. Nuclear imaging provides a sensitive technique for early detection of physiological changes in soft tissue and bone. It has been used in studies of periodontitis, osteomyelitis, oral and maxillofacial tumors, stress fractures, bone healing, temporomandibular joint, and blood flow. This article includes brief descriptions of the technical principles of each imaging modality, reviews their previous uses in oral biology research, and discusses potential future applications in research protocols.
Short-Chain Carboxylic-Acid-Stimulated, PMN-Mediated Gingival Inflammation
Authors: Niederman Richard , Jie Zhang  , Kashket Shelby 
Published: January 2009

This communication reviews the effects of short-chain carboxylic acids on human cells of importance to the periodontium. The central hypothesis is that these acids can alter both cell function and gene expression, and thus contribute to the initiation and prolongation of gingival inflammation. Short-chain carboxylic acids [CH3-(CH2)x-COOH, x < 3] are metabolic intermediates with a broad range of apparently paradoxical biological effects. For example, lactic acid (CH3-CHOH-COOH), a 3-carbon alpha-hydroxy-substituted acid, is widely recognized for its cariogenicity. Lactic acid, however, also occurs in tropical fruits, and is the active ingredient in a variety of anti-wrinkle creams developed by dermatologists. In marked contrast, the unsubstituted 3-carbon propionic acid (CH3-CH 2-COOH) is used as a food preservative and is the active principle for one class of non-steroidal anti-inflammatory agents. Interestingly, the addition of one carbon to propionic acid dramatically changes the biological effects. The unsubstituted 4-carbon butyric acid (CH3-CH2-CH2-COOH) is used by hematologists as a de-differentiating agent for the treatment of sickle cell anemia, but by oncologists as a differentiating agent for cancer chemotherapy. Finally, acting either individually or in concert, these acids can increase vascular dilation. Clearly, these acids, while metabolically derived, have a number of very divergent activities which are cell-type-specific (Fig. 1). It may be telling that periodontal bacteria produce these acids in millimolar concentrations, and that these bacteria can be characterized by their acid production profiles. It is no less interesting that these acids occur in the gingival crevices of human subjects with severe periodontal disease at millimolar levels which are > 10-fold higher than those found in mildly diseased subjects, and are undetectable in healthy subjects. Further, when applied directly to healthy human gingiva, short-chain carboxylic acids stimulate a gingival inflammatory response and inflammatory cytokine release. At the cellular level, these acids inhibit proliferation of gingival epithelial and endothelial cells, and inhibit leukocyte apoptosis and function, but can stimulate leukocyte cytokine release. At the molecular level, these acids can stimulate neutrophil gene transcription, translation, and protein expression. Thus, the likelihood is high that these acids, in addition to their cariogenic activity, can promote and prolong gingival inflammation. Our challenge will be to identify the cell or cells of the periodontium which respond to short-chain carboxylic acids, to delineate their responses and the molecular mechanism(s) of these effects, and to categorize the aspects of the inflammatory components which damage and those which protect the host. With this information, it may be possible to begin to rationally identify and test pharmaceutical agents which diminish the harmful aspects, while enhancing the beneficial components, of the inflammatory response.
Infrared Spectrometric Study of Acid-degradable Glasses
Authors: De Maeyer E.A.P. , Verbeeck R.M.H. , Vercruysse C.W.J. 
Published: January 2009

The composition of glasses used in glass-ionomer cements affects their leaching behavior and hence the properties of the cement. The aim of this study was to correlate the composition and leaching behavior of these glasses with their infrared absorption characteristics. The wavenumber of the absorption band of the Si-O asymmetric stretching vibration ῡAS shifts to a higher value with decreasing content of mono- and bivalent cations in the glass. This effect can be ascribed to the influence of these extraneous ions on the glass network order and connectivity. Preferential leaching of these ions induces an increase of ῡAS and a general modification of the band profile. The results can be correlated with the x-ray diffraction characteristics of the glass. A decrease in the Si-O-Si angle could be caused by a decrease in the distortions in the (arrangement of the) SiO4 tetrahedra; the tetrahedra as well as their arrangement can be distorted.
Biomedical Informatics Training for Dental Researchers
Authors: Johnson L.A. 
Published: January 2009

Dental researchers collaborating closely with biomedical informaticians have achieved many advances in oral health research, such as in mapping human genetics and addressing oral health disparities. Advances will continue to increase as dental researchers and biomedical informaticians study each others’ disciplines to increase the effectiveness of their collaborative research. The combined skills will greatly increase the effectiveness of dental research. This manuscript summarizes the core of biomedical informatics curriculum (biomedical informatics knowledge, data management, and software engineering) for dental research. It also summarizes the obstacles that must be overcome for all dental research students to receive the training in biomedical informatics they require. These issues are: a lack of biomedical informatics faculty, a lack of biomedical informatics courses, and a lack of accreditation standards. Last, intra- and inter-institutional collaboration solutions are described. “The decades ahead will be witness to advances in science and technology as yet unforeseen. Dentistry will benefit from these advances and must be intimately involved in their progression.” ( American Dental Association, 2002 )
Designing Clinically Useful Systems: Examples from Medicine and Dentistry
Authors: Koch S. 
Published: January 2009

Despite promising results in medical informatics research and the development of a large number of different systems, few systems get beyond a prototype state and are really used in practice. Among other factors, the lack of explicit user focus is one main reason. The research projects presented in this paper follow a user-centered system development approach based on extensive work analyses in interdisciplinary working groups, taking into account human cognitive performance. Different medical and health-care specialists, together with researchers in human-computer interaction and medical informatics, specify future clinical work scenarios. Special focus is put on analysis and design of the information and communication flow and on exploration of intuitive visualization and interaction techniques for clinical information. Adequate choice of the technical access device is made depending on the user’s work situation. It is the purpose of this paper to apply this method in two different research projects and thereby to show its potential for designing clinically useful systems that do support and not hamper clinical work. These research projects cover IT support for chairside work in dentistry ( http://www.dis.uu.se/mdi/research/projects/orquest ) and ICT support for home health care of elderly citizens ( http://www.medsci.uu.se/mie/project/closecare ).
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.
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.
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.