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Clinical evaluation of dental hard tissue applications of carbon dioxide lasers.

This clinical study examined the pulpal safety of selected CO2 laser hard tissue applications. A total of 187 hard tissue procedures were performed on 54 patients. The mean period of follow-up following laser treatment was 13.5 months (range 2-24 months). The procedures included etching (n = 96), desensitizing (n = 56), laser-enhanced fluoride (n = 28), treatment of external resorption (n = 4), and pulp capping or pulpotomy (n = 3). Only the latter two procedure types were performed with anesthesia. The total irradiation received during these procedures ranged from 2 to 12 J. No patients complained of sensation or discomfort during any procedure. Pulp vitality was maintained in all teeth, and no instances of postlasing thermal sensitivity or pulpitis were reported. These results indicate that pulp vitality can be maintained provided that conditions of irradiance are controlled carefully to minimize thermal effects.

Adolescent↗

Induction of dental pulp fibroblast matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 gene expression by interleukin-1alpha and tumor necrosis factor-alpha through a prostaglandin-dependent pathway.

Matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) are involved in the degradation of extracellular matrix in many inflammatory diseases. Little is known regarding the expression of these mediators in dental pulp fibroblasts. The effects of proinflammatory cytokines (interleukin (IL)-1alpha and tumor necrosis factor-alpha (TNF-alpha)) and prostaglandin E2 (PGE2) on pulp fibroblast MMP-1 and TIMP-1 gene expression were investigated. Northern hybridization showed that IL-1alpha and TNF-alpha induced significant MMP-1 gene expression, with only little effect on TIMP-1 gene. Exogenous PGE2, however, upregulated TIMP-1 mRNA synthesis but not MMP-1. Concomitant addition of IL-1alpha and PGE2 or TNF-alpha and PGE2 suppressed MMP-1 mRNA production, compared with the groups treated with IL-1alpha or TNF-alpha alone. In contrast, PGE2 enhanced the upregulatory effects of TIMP-1 mRNA by IL-1alpha or TNF-alpha. Furthermore, cytokine stimulation of MMP-1 and TIMP-1 gene expressions can be enhanced or blocked by indomethacin, respectively, and reversed by exogenous PGE2. These results suggested that cytokine-stimulated MMP-1 and TIMP-1 gene expression in dental pulp fibroblasts was mediated, at least in part, by a prostaglandin-dependent pathway. The differential regulation of IL-1alpha or TNF-alpha-induced MMP-1 and TIMP-1 mRNA synthesis, as well as the direct upregulation of TIMP-1 gene expression by PGE2, also implied that prostaglandin may serve as a protective mechanism from excessive tissue breakdown during pulpitis.

Anti-Inflammatory Agents, Non-Steroidal↗

Conservative management of an accidentally resected root: a 3-year follow-up.

Despite all the effort by dentists to provide high levels of dental care in clinical practice, there is always the possibility of accidents occurring. This report describes a referred case that presented with irreversible pulpitis in tooth #19. The situation developed after accidental resectioning of the distal root of tooth #19 during the surgical extraction of tooth #18 by another dentist. The resultant open apex in the distal root of tooth #19 was managed conservatively. A positive apical stop was prepared at the root end of the distal root and sterile calcium hydroxide powder was used to create an apical barrier against which a gutta-percha filling was condensed. The treatment appeared successful at 3-year follow-up.

Calcium Hydroxide↗

The application of tissue engineering to regeneration of pulp and dentin in endodontics.

Caries, pulpitis, and apical periodontitis increase health care costs and attendant loss of economic productivity. They ultimately result in premature tooth loss and therefore diminishing the quality of life. Advances in vital pulp therapy with pulp stem/progenitor cells might give impetus to regenerate dentin-pulp complex without the removal of the whole pulp. Tissue engineering is the science of design and manufacture of new tissues to replace lost parts because of diseases including cancer and trauma. The three key ingredients for tissue engineering are signals for morphogenesis, stem cells for responding to morphogens and the scaffold of extracellular matrix. In preclinical studies cell therapy and gene therapy have been developed for many tissues and organs such as bone, heart, liver, and kidney as a means of delivering growth factors, cytokines, or morphogens with stem/progenitor cells in a scaffold to the sites of tissue injury to accelerate and/or induce a natural biological regeneration. The pulp tissue contains stem/progenitor cells that potentially differentiate into odontoblasts in response to bone morphogenetic proteins (BMPs). There are two strategies to regenerate dentin. First, is in vivo therapy, where BMP proteins or BMP genes are directly applied to the exposed or amputated pulp. Second is ex vivo therapy and consists of isolation of stem/progenitor cells from pulp tissue, differentiation into odontoblasts with recombinant BMPs or BMP genes and finally transplanted autogenously to regenerate dentin. This review is focused on the recent progress in this area and discusses the barriers and challenges for clinical utility in endodontics.

Animals↗

Immunolocalization of bone-resorptive cytokines in rat pulp and periapical lesions following surgical pulp exposure.

The bone-resorptive cytokines interleukin 1 (IL-1) and tumor necrosis factor (TNF) have been implicated in the pathogenesis of many chronic inflammatory diseases, including pulpitis and apical periodontitis.To further elucidate their role in these disorders, we have identified cells that express IL-1 alpha and TNF alpha in infected pulps and in developing rat periapical lesions after surgical pulp exposure. As detected by immunohistochemistry, IL-1 alpha- and TNF alpha-positive cells were present as early as 2 days after pulp exposure in both the pulp and periapical region. The numbers of cytokine-expressing cells increased up to day 4 in the pulp and up to day 30 in the periapex. In contrast, cells expressing IL-1 beta and TNF beta, the homologous forms of these mediators, were not found in pulp or periapical lesions during this period. Cells expressing IL-1 alpha and TNF alpha were identified primarily as macrophages and fibroblasts, with occasional staining of polymorphonuclear leukocytes. Osteoblasts and osteoclasts were also positive, whereas lymphocytes were negative. In general, cytokine-expressing cells were located proximal to abscesses and the root apex. These findings demonstrate that cells that express bone-resorptive cytokines IL-1 alpha and TNF alpha are present immediately after pulp exposure in this model, which supports the hypothesis that these mediators play a key role in pulpal and periapical pathogenesis, including the concomitant bone destruction. They also indicate that both resident connective tissue cells as well as infiltrating cells express bone-resorptive cytokines in response to infection in these lesions.

Alveolar Bone Loss↗

Occupational dermatitis in the aircraft industry: 35 years of progress.

A comparison of the occupational dermatitis occurring in the same aircraft factory during 2 separate decades, 1955-1965 and 1981-1990, is presented. Subungual pulpitis is highly specific to this industry, because of the handling of resins and sealing agents. The number of cases dropped from 122 to 40, in accordance with progress in preventive medicine and technological changes in the factory. Irritant contact dermatitis nevertheless remained appreciable, while allergic contact dermatitis greatly decreased.

Aircraft↗

Changes in the fine structure of the human dental pulp subsequent to carious exposure.

Sections of human pulp tissue taken from the region of a carious exposure in four young patients each having a clinical history of spontaneous dental pain were examined with the electron microscope. All the tissues examined exhibited a generalized edema, and an infiltration with lymphocytes, plasma cells, polymorphonuclear leukocytes and macrophages. Varying degree of lysis of pulp and inflammatory cells were evident. The unmyelinated nerve axons of the pulp appeared to be least affected. Extracellular lysosomes were present in many of the necrotic areas. Edematous vacuoles were noted in two of the pulp specimens. In some of the sections these vacuoles appeared to be responsible for a physical distortion of adjacent unmyelinated nerve axons. It was postulated that such distortion may be a contributing factor to the pain of pulpitis. In another of the pulp specimens, micro-organisms were found intracellularly and extracellularly. Intracellularly they were present within the cytoplasm of polymorphonuclear leukocytes and macrophages and exhibited evidence of lysis. Only two morphological forms, a gram positive rod, and a gram positive coccus were identified.

Axons↗

Recent development in endodontic research.

In essence, endodontics as a clinical discipline is concerned with the prevention and treatment of pulpal and periapical infection. In recent research the infective process has been investigated as well as the mechanisms by which the pulp and periodontium deal with microbial insults. With regard to the pulp, findings on the hemodynamics of pulpitis suggest that the inflammatory response in this tissue is much less influenced by the special anatomic environment of the tooth than was previously believed. Pulpal diseases are being underdiagnosed, mostly because of inadequate examination methods. Laser Doppler flowmetry which gives a vascular rather than a nervous response may gain importance in pulpal diagnostics in the future. It is established that apical periodontitis with bone resorption cannot develop in the absence of bacteria in the root canal system. Root canal infection is characterized by a wide variety of combinations of relatively few anaerobic bacteria, and bacterial synergism plays an important role in maintaining the infection. Microbial invasion of an apical granuloma may take place. Non-oral and environmental organisms like Pseudomonas aeruginosa are frequently isolated from treatment-resistant cases. Success of endodontic treatment depends on the reduction or elimination of the infecting bacteria. This may predictably be obtained after a thorough chemo-mechanical instrumentation and disinfection of the root canal with calcium hydroxide. The standardized technique which entails the preparation of a cylindrical apical box with removal of significant amounts of dentin near the root apex predictably gives a clean canal. This technique has provided excellent clinical and radiographic results in well documented follow-up studies.

Dental Pulp Diseases↗

Internal resorption occurring after accidental extrusion of iodoform paste into the mandibular canal.

The precise etiology of internal resorption is unknown but it is generally believed that triggering factors are infection and persistent chronic pulpitis. A case is presented with internal resorption, which developed subsequent to extrusion of iodoform paste from the adjacent tooth into the mandibular canal. According to clinical and radiographic examinations made after 7 years, the tooth was clinically asymptomatic, vital and the internal resorption was arrested without treatment.

Adult↗

Maturogenesis of a cariously exposed immature permanent tooth using MTA for direct pulp capping: a case report.

Successful direct pulp capping of cariously exposed permanent teeth with reversible pulpitis and incomplete apex formation can prevent the need for root canal treatment. A case report is presented which demonstrates the use of mineral trioxide aggregate (MTA) as a direct pulp capping material for the purpose of continued maturogenesis of the root. Clinical and radiographic follow-up demonstrated a vital pulp and physiologic root development in comparison with the contralateral tooth. MTA can be considered as an effective material for vital pulp therapy, with the goal of maturogenesis.

Aluminum Compounds↗

Responses of intradental nerve fibres to stimulation of dentine and pulp.

In the present work responses of intradental nerve fibres to stimuli that induce fluid flow in dentinal tubules as well as to direct mechanical irritation of the exposed pulp were studied on 9 young adult beagle dogs. Under pentobarbitone anesthesia 31 single functional intradental fibre units were dissected from the mandibular nerve. Stimuli were applied to the lower left canine tooth. Exposed dentine surface was irritated by scraping, air blasts and dry absorbent paper and the pulp mechanically with a von Frey hair. Ten fibre units responded to stimulation of dentine. Six of them were also tested with mechanical irritation of the pulp and were all responsive. Fifteen of twenty fibres responded to mechanical stimulation of the pulp. The mechanosensitive nerve fibres were all A-type according to conduction velocities (mean 25.6 +/- 8.1 (SD) m/s). It is concluded that there exist mechanosensitive intradental A-nerve fibres in the dog which are activated by stimuli that induce fluid flow in dentinal tubules. Nerve fibres of this type could be responsible for dentine sensitivity in man. Consequently, the present study gives support to the hydrodynamic hypothesis of dentine sensitivity. Moreover, mechanosensitive nerve fibres could also be responsible for the pain symptoms of pulpal inflammation, because pulpitis may also create suitable circumstances for their activation.

Animals↗

Lipopolysaccharide enhances the production of vascular endothelial growth factor by human pulp cells in culture.

We investigated whether vascular endothelial growth factor (VEGF) production by human pulp cells (HPC) is regulated by lipopolysaccharide (LPS) in relation to the pathogenesis of pulpitis. Although HPC incubated with medium alone only marginally expressed VEGF mRNA and produced a low level of VEGF as detected by enzyme-linked immunosorbent assay, the VEGF mRNA expression and VEGF production were markedly enhanced upon stimulation with LPS from Escherichia coli. Prevotella intermedia LPS, phorbol 12-myristate 13-acetate, and interleukin-6 also induced VEGF mRNA expression in HPC. A simian virus 40-infected HPC line also exhibited increased VEGF mRNA expression in response to E. coli LPS, but lung and skin fibroblasts did not. Fetal bovine serum (FBS) increased the sensitivity of HPC to LPS in a dose-dependent manner. HPC did not express membrane CD14 on their surfaces. However, the anti-CD14 monoclonal antibody MY4 inhibited VEGF induction upon stimulation with LPS in HPC cultures in the presence of 10% FBS but not in the absence of FBS. LPS augmented the VEGF production in HPC cultures in the presence of recombinant human soluble CD14 (sCD14). To clarify the mechanisms of VEGF induction by LPS, we examined the possible activation of the transcription factor AP-1 in HPC stimulated with LPS, by a gel mobility shift assay. AP-1 activation in HPC was clearly observed, whereas that in skin fibroblasts was not. The AP-1 inhibitor curcumin strongly inhibited LPS-induced VEGF production in HPC cultures. In addition, a protein synthesis inhibitor, cycloheximide, inhibited VEGF mRNA accumulation in response to LPS. These results suggest that the enhanced production of VEGF in HPC induced by LPS takes place via an sCD14-dependent pathway which requires new protein synthesis and is mediated in part through AP-1 activation.

Animals↗

Insertional inactivation of pac and rmlB genes reduces the release of tumor necrosis factor alpha, interleukin-6, and interleukin-8 induced by Streptococcus mutans in monocytic, dental pulp, and periodontal ligament cells.

Streptococcus mutans possesses different cell wall molecules, such as protein of the I/II family, the serotype f polysaccharide rhamnose glucose polymer (RGP), and lipoteichoic acid (LTA), which act as adhesins and modulins, allowing S. mutans to colonize teeth and cause dental caries and pulpitis. We tested several isogenic mutants of S. mutans defective in protein I/II and/or RGP, as well as purified modulins such as protein I/II, RGP, and LTA, for their binding and activation abilities on monocytic, dental pulp (DP), and periodontal ligament (PDL) cells. Our results demonstrate that both protein I/II and RGP play important roles in streptococcal adherence to human monocytic and fibroblastic cells, whereas LTA is only a minor adhesin. In the activation process, the cytokine response elicited is polarized toward a Th1 response which seems principally due to protein I/II and RGP. Even if protein I/II seems to be more efficient in its purified form in triggering cells to release interleukin-8 (IL-8), RGP is the most efficient cytokine-stimulating component in intact bacteria, while LTA plays only a minor role. In cell activation, we showed, by using either cytochalasin D or coated ligands, that internalization of either S. mutans, S. mutans isogenic mutants, or purified ligands is not necessary to trigger cells to release IL-8. We also showed that, besides the implication of monocytes in pulpal inflammation, fibroblast-like cells such as DP and PDL cells are also actively implicated in local inflammation and in the generation of a Th1 response after stimulation with S. mutans cells or antigens.

Adhesins, Bacterial↗

Erythema multiforme-like drug eruption with oral involvement after intake of leflunomide.

Leflunomide is an antirheumatic agent of the type of a 'disease-modifying antirheumatic drug'. In rare cases, severe skin reactions up to the extreme expression of toxic epidermal necrolysis have been observed. A female patient with rheumatoid arthritis had been treated with systemic steroids and methotrexate for 2 years. Five weeks prior to admission to our hospital methotrexate was replaced by leflunomide. Three weeks after initiation of leflunomide therapy a progressive generalized erythema with blistering formation occurred accompanied by increase of body temperature, chills and erosive lesions on the lips and oral mucosa. The palmar and plantar surfaces revealed edema, erythema and pulpitis with epidermolysis. On histologic examination necrotic keratinocytes and epidermal spongiosis were observed. After administration of high-dose prednisolone and topical treatment the patient recovered within 14 days. This is one of the few cases of severe drug reaction after intake of leflunomide. Therefore, the indication of this relatively new drug should be considered carefully.

Anti-Inflammatory Agents, Non-Steroidal↗

How 'clean' must a cavity be before restoration?

The metabolic activity in dental plaque, the biofilm at the tooth surface, is the driving force behind any loss of mineral from the tooth or cavity surface. The symptoms of the process (the lesion) reflect this activity and can be modified by altering the biofilm, most conveniently by disturbing it by brushing with a fluoride-containing toothpaste. The role of operative dentistry in caries management is to restore the integrity of the tooth surface so that the patient can clean. Thus, the question, 'how clean must a cavity be before restoration?' may be irrelevant. There is little evidence that infected dentine must be removed prior to sealing the tooth. Leaving infected dentine does not seem to result in caries progression, pulpitis or pulp death. However, some of the bacteria survive. What is their fate and if they are not damaging, why is this?

Dental Caries↗

Myeloencephalitis associated with a viridans group Streptococcus in a colony of Japanese macaques (Macaca fuscata).

Five weaned immature Japanese macaques (Macaca fuscata), bred in captivity, showed nervous signs over a 12-month period. Hemorrhagic cerebral infarcts with vasculitis were detected in four necropsied animals. The distribution and nature of the lesions were consistent with bacterial embolism, and a Streptococcus isolate, biochemically similar to S. salivarius, was recovered from the cerebral lesions from three of the four necropsied macaques. Treatment with antibacterial agents (enrofloxacin) improved the clinical condition of the surviving affected animal. These observations strongly suggest that this Streptococcus spp., member of the viridans group, is responsible for this outbreak. Dental pulpitis, present in two of the four macaques, probably served as the entry for this bacterium.

Animals↗

Lipoteichoic acid up-regulates VEGF expression in macrophages and pulp cells.

Vascular endothelial growth factor (VEGF) is a potent inducer of angiogenesis, vascular permeability, and edema. Up-regulation of VEGF expression in the dental pulp may result in increased intra-pulpal pressure, and contribute to pain and irreversible tissue damage. Lipoteichoic acid (LTA) is an amphiphilic molecule from Gram-positive bacteria that has been associated with the pathogenesis of pulpitis. To investigate if LTA regulates expression of VEGF, we exposed mouse odontoblast-like cells (MDPC-23), undifferentiated pulp cells (OD-21), fibroblasts, or macrophages to streptococcal LTA, and evaluated VEGF expression by ELISA and RT-PCR. LTA induced up to a nine-fold increase in VEGF protein expression in macrophages, a 2.4-fold increase in MDPC-23, and a 1.6-fold increase in OD-21 as compared with controls. In contrast, LTA did not induce VEGF expression in fibroblasts. VEGF mRNA expression remained constant upon exposure to LTA, which suggests that VEGF regulation in these cells is primarily post-transcriptional. This work constitutes the first demonstration that lipoteichoic acid is sufficient to induce expression of a pro-angiogenic factor.

Analysis of Variance↗

Invasion of dentinal tubules by oral bacteria.

Bacterial invasion of dentinal tubules commonly occurs when dentin is exposed following a breach in the integrity of the overlying enamel or cementum. Bacterial products diffuse through the dentinal tubule toward the pulp and evoke inflammatory changes in the pulpo-dentin complex. These may eliminate the bacterial insult and block the route of infection. Unchecked, invasion results in pulpitis and pulp necrosis, infection of the root canal system, and periapical disease. While several hundred bacterial species are known to inhabit the oral cavity, a relatively small and select group of bacteria is involved in the invasion of dentinal tubules and subsequent infection of the root canal space. Gram-positive organisms dominate the tubule microflora in both carious and non-carious dentin. The relatively high numbers of obligate anaerobes present-such as Eubacterium spp., Propionibacterium spp., Bifidobacterium spp., Peptostreptococcus micros, and Veillonella spp.-suggest that the environment favors growth of these bacteria. Gram-negative obligate anaerobic rods, e.g., Porphyromonas spp., are less frequently recovered. Streptococci are among the most commonly identified bacteria that invade dentin. Recent evidence suggests that streptococci may recognize components present within dentinal tubules, such as collagen type I, which stimulate bacterial adhesion and intra-tubular growth. Specific interactions of other oral bacteria with invading streptococci may then facilitate the invasion of dentin by select bacterial groupings. An understanding the mechanisms involved in dentinal tubule invasion by bacteria should allow for the development of new control strategies, such as inhibitory compounds incorporated into oral health care products or dental materials, which would assist in the practice of endodontics.

Animals↗