Reported concepts for the treatment modalities and pain management of temporomandibular disorders.

BACKGROUND: Pain related to temporomandibular disorders (TMD) is a common problem in modern societies. The aim of the article is to present the concepts of TMD pain clinical management. METHODS: A survey was performed using the PubMed, SCOPUS and CINAHL databases for documents published between 1994 and 2014. The following search keywords were selected using MeSH terms of the National Library of Medicine in combination: TMD pain, TMD, TMJ, TMJ disorders, occlusal splint, TMD physiotherapy, TMJ rheumatoid disorders and TMJ surgery. Original articles and review papers which presented the clinical relevance and practical validity regarding the possibility of application in TMD management have been included. Authors have excluded articles without outstanding practical aspect and evidence-based background. A first selection was carried out by reviewing titles and abstracts of all articles found according to the criteria. After that the full texts of potentially suitable articles were assessed. In line with these criteria, among 11467 results the writers have included 66 papers. RESULTS: The most commonly reported conservative treatments are massage therapy and individually fabricated occlusal splints. In addition to massage, other popular methods include manual therapy and taping, warming/cooling of aching joints, and light and laser therapy. Drugs are also commonly used. In the most severe cases of the temporomandibular joint degeneration, surgical restoration of the joint is sometimes applied. CONCLUSIONS: The authors concluded that conservative treatment including counselling, exercises, occlusal splint therapy, massage, manual therapy and others should be considered as a first choice therapy for TMD pain because of their low risk of side effects. In the case of severe acute pain or chronic pain resulting from serious disorders, inflammation and/or degeneration pharmacotherapy, minimally invasive and invasive procedures should be considered.

Temporomandibular joint structural derangement and general joint hypermobility.

AIM: To explore the relationship between general joint hypermobility (GJH) and displacement of the temporomandibular joint (TMJ) disc as evident from magnetic resonance imaging (MRI). METHODS: Fifth finger extension, thumb apposition, elbow extension, knee extension, trunk flexion, and ankle dorsiflexion were measured in 66 young female patients with MRI-evident TMJ internal derangement (ID) and in 30 age-matched female controls. The Beighton score of each subject was measured quantitatively. The possible association between TMJ ID and mobility of a single joint or index of GJH, ie, the Beighton score, were assessed with one-way ANOVA with post-hoc Bonferroni and chi-square test, respectively. Correlations of the mobility of every measured joint were also explored. RESULTS: Very few of the TMJ ID patients and control subjects were diagnosed with GJH according to the Beighton score. The Beighton score did not differentiate between subjects with and without TMJ ID. Subjects with TMJ ID, especially patients with MRI-evident disc displacement without reduction, seemed to have a stiffer trunk than controls, but this may not be of clinical relevance. The mobilities of paired joints were significantly correlated; however, the mobilities of different anatomical joints seemed to be independent. CONCLUSION: Based on the Beighton score, GJH does not seem to be a reliable indicator of the presence of TMJ ID.

Low bone mineral density and temporomandibular joint derangement in young females.

AIMS: To analyze the bone mineral density (BMD) in a group of young female patients with a disc displacement in at least 1 temporomandibular joint (TMJ) as well as in a group of age-matched young females with a normal condyle-disc relationship. METHODS: Fifty-six young female patients with anterior disc displacement based on magnetic resonance imaging (MRI) and 40 age- and gender-matched controls with asymptomatic TMJs were recruited for this study. Subjects between 18 and 30 years were recruited. Based on the MRI findings, 10 of the 40 subjects in the control group also had anterior disc displacement. In all, 16 subjects had an anterior disc displacement with reduction (DDwR), 50 had an anterior disc displacement without reduction (DDw/oR), and 30 had a normal condyle-disc relationship. BMD was measured in the lumbar area by means of dual-energy x-ray absorptiometry. The relationship between the 3 types of condyle-disc relationship and BMD was then analyzed. RESULTS: Patients with a DDw/oR had a significantly lower mean BMD value in the lumbar area than the subjects with a normal condyle-disc relationship (P < .05, analysis of variance, post-hoc with Bonferroni test). Twenty-two (44%) of 50 patients with DDw/oR had osteopenia. CONCLUSION: Low BMD is often associated with DDw/oR in young Taiwanese female patients.

Magnetic resonance images of the temporomandibular joints of patients with acquired open bite.

OBJECTIVES: Acquired anterior open bites were reported as the consequence of condylar collapse, which was associated with inflammatory TMJ disorders. However, we have seen such malocclusion patients whose condylar changes seemed to be related to TMJ degeneration associated with internal derangement. The aims of this study were to review the clinical history and to study the TMJ MRI of these patients. STUDY DESIGN: TMJ MRIs of patients, who had presented acquired anterior open bite at first visit, were retrieved from the image database for the analysis. Clinical histories focused on internal derangement were collected retrospectively. The soft tissue and hard tissue changes disclosed by MRI were also studied. RESULTS: All patients had experienced common signs/symptoms of TMJ internal derangement. All affected TMJs had anteriorly displaced disks and degenerative changes. Horizontally destructed condylar forms were seen significantly more frequently in these patients. CONCLUSION: TMJ degeneration associated with displaced disks might be a cause leading to the development of acquired anterior open bite.

Structural basis of binding and inhibition of novel tarantula toxins in mammalian voltage-dependent potassium channels.

Voltage-dependent potassium channel Kv2.1 is widely expressed in mammalian neurons and was suggested responsible for mediating the delayed rectifier (I(K)) currents. Further investigation of the central role of this channel requires the development of specific pharmacology, for instance, the utilization of spider venom toxins. Most of these toxins belong to the same structural family with a short peptide reticulated by disulfide bridges and share a similar mode of action. Hanatoxin 1 (HaTx1) from a Chilean tarantula was one of the earliest discussed tools regarding this and has been intensively applied to characterize the channel blocking not through the pore domain. Recently, more related novel toxins from African tarantulas such as heteroscordratoxins (HmTx) and stromatoxin 1 (ScTx1) were isolated and shown to act as gating modifiers such as HaTx on Kv2.1 channels with electrophysiological recordings. However, further interaction details are unavailable due to the lack of high-resolution structures of voltage-sensing domains in such mammalian Kv channels. Therefore, in the present study, we explored structural observation via molecular docking simulation between toxins and Kv2.1 channels based upon the solution structures of HaTx1 and a theoretical basis of an individual S3(C) helical channel fragment in combination with homology modeling for other novel toxins. Our results provide precise chemical details for the interactions between these tarantula toxins and channel, reasonably correlating the previously reported pharmacological properties to the three-dimensional structural interpretation. In addition, it is suggested that certain subtle structural variations on the interaction surface of toxins may discriminate between the related toxins with different affinities for Kv channels. Evolutionary links between spider peptide toxins and a "voltage sensor paddles" mechanism most recently found in the crystal structure of an archaebacterial K(+) channel, KvAP, are also delineated in this paper.

Structural analysis of the functional influence of the surface peptide Gtf-P1 on Streptococcus mutans glucosyltransferase C activity.

Glucosyltransferases (GtfB/C/D) in Streptococcus mutans are responsible for synthesizing water-insoluble and water-soluble glucans from sucrose and play very crucial roles in the formation of dental plaque. A monoclonal antibody against a 19-mer peptide fragment named Gtf-P1 was found in GtfC to reduce the enzyme activity to 50%. However, a similar experiment suggested almost unchanged activity in GtfD, despite of the very high sequence homology between the two enzymes. No further details are yet available to elucidate the biochemical mechanism responsible for such discrimination. For a better understanding of the catalytic behavior of these glucosyltransferases, structural and functional analyses were performed. First, the exact epitope was identified to specify the residue(s) required for monoclonal antibody recognition. The results suggest that the discrimination is determined solely by single residue substitution. Second, based on a combined sequence and secondary structure alignment against known crystal structure of segments from closely related proteins, a three-dimensional homology model for GtfC was built. Structural analysis for the region communicating between Gtf-P1 and the catalytic triad revealed the possibility for an "en bloc" movement of hydrophobic residues, which may transduce the functional influence on enzyme activity from the surface of molecule into the proximity of the active site. Figure Side chain interactions between Gtf-P1 and catalytic Asp-477 in GtfC. Calpha-tracing of GtfC with the two crucial peptides (Gtf-P1, orange; Gtf-P2, blue) and the catalytic triad residues ( red) highlighted to show their relative spatial organization. Side chains for the residues are also depicted according to their atom types. The structure is viewed with the barrel opening facing down

A possible molecular mechanism of hanatoxin binding-modified gating in voltage-gated K+-channels.

While S4 is known as the voltage sensor in voltage-gated potassium channels, the carboxyl terminus of S3 (S3C) is of particular interest concerning the site for gating modifier toxins like hanatoxin. The thus derived helical secondary structural arrangement for S3C, as well as its surrounding environment, has since been intensively and vigorously debated. Our previous structural analysis based on molecular simulation has provided sufficient information to describe reasonable docking conformation and further experimental designs (Lou et al., 2002. J. Mol. Recognit. 15: 175-179). However, if one only relies on such information, more advanced structure-functional interpretations for the roles S3C may play in the modification of gating behavior upon toxin binding will remain unknown. In order to have better understanding of the molecular details regarding this issue, we have performed the docking simulation with the S3C sequence from the hanatoxin-insensitive K+-channel, shaker, and analyzed the conformational changes resulting from such docking. Compared with other functional data from previous studies with respect to the proximity of the S3-S4 linker region, we suggested a significant movement of drk1 S3C, but not shaker S3C, in the direction presumably towards S4, which was comprehended as a possible factor interfering with S4 translocation during drk1 gating in the presence of toxin. In combination with the discussions for structural roles of the length of the S3-S4 linker, a possible molecular mechanism to illustrate the hanatoxin binding-modified gating is proposed.

Molecular determinants of the hanatoxin binding in voltage-gated K+-channel drk1.

The carboxyl terminus of S3 segment (S3(C)) in voltage-gated potassium channels was proposed to bear the binding site for gating modifier toxins like Hanatoxin and a helical secondary structural arrangement was suggested. Due to the lack of complete structure in high resolution for such a channel molecule, no further direct experimental data to elucidate the mechanism for their binding conformations could thus far be derived. In order to examine the putative three-dimensional structure of S3(C) and to illustrate the residues required for Hanatoxin binding, molecular simulation and docking were performed, based on the solution structure of Hanatoxin and the structural information from lysine-scanning results for S3(C) fragment. From our results, it is indicated that both hydrophobic and electrostatic interactions are utilized to stabilize the toxin binding. Detailed docking residues and appropriate orientation for binding regarding hydrophobic/-philic environments are also described. Compared with the functional data proposed by previous studies, the helical structural arrangement for the C-terminus of S3 segment in voltage-gated potassium channels can therefore be further emphasized.

Molecular simulation reveals structural determinants of the hanatoxin binding in Kv2.1 channels.

The carboxyl terminus of the S3 segment (S3C) in voltage-gated potassium channels was suggested to be the binding site of gating modifier toxins like hanatoxin. It has also been proposed to have a helical secondary structural arrangement. The currently available structures in high resolution for such channel molecules are restricted to regions illustrating the pore function. Therefore no further direct experimental data to elucidate the detailed mechanism for such toxin binding can be derived. In order to examine the putative three-dimensional structure of S3C and to analyze the residues required for hanatoxin binding, molecular simulation and docking were performed, based on the solution structure of hanatoxin and the structural information from mutational scanning data for the S3C fragment in Kv2.1. Our results indicate that hydrophobic and electrostatic interactions are both utilized to stabilize the toxin binding. Precise docking residues and the appropriate orientation for binding regarding amphipathic environments are also described. Compared with the functional data proposed by previous studies, the helical structural arrangement for the C-terminus of the S3 segment in voltage-gated potassium channels can therefore be further emphasized and analyzed. The possible location/orientation for toxin binding with respect to membrane distribution around the S3C segment is also discussed in this paper.

Influence of different convergence angles and tooth preparation heights on the internal adaptation of Cerec crowns.

STATEMENT OF PROBLEM: Because of an imagining principle called active triangulation in the Cerec system, a shadow is cast distal to the illuminated objects. This distal shadow may be enlarged when the occlusal-cervical height of the prepared tooth is increased. Depth data of the shadow are unreliable, so the internal fit of Cerec crowns has been questioned. PURPOSE: This study evaluated the influence of different convergence angles and tooth preparation heights on the internal adaptation of Cerec crowns. MATERIAL AND METHODS: Tooth preparations were made on typodont teeth with different combinations of convergence angles and occlusal-cervical heights: Group I = 20 degrees angle, 6 mm height; Group II = 20 degrees angle, 4 mm height; Group III = 12 degrees angle, 6 mm height; and Group IV = 12 degrees angle, 4 mm height. Ten Cerec crowns were fabricated for each type of tooth preparation. Measurements of the internal fit were performed with the cement space replica technique and an image analysis system. Three-way analysis of variance was used to analyze the differences in cement space with different tooth preparations and the number of times that milling tools were used to prepare the Cerec crowns (P<.05). Multiple comparisons were made to evaluate differences between groups (P<.0083). RESULTS: Cerec crowns with a 12 degrees convergence angle demonstrated the best internal fit (cement space in Groups III and IV = 121 +/- 41 microm and 115 +/- 42 microm, respectively). The difference between the 2 convergence types was within the range of the scanning error (25 microm) produced by the Cerec camera. The number of times that milling tools were used had no significant effect on internal fit (P=.78). Tooth preparation height equal to or shorter than 6 mm occlusal-cervically with both 12 degrees and 20 degrees convergence angles also had no significant effect on internal fit (P>.0083). Cement space at distal walls (185 +/- 28 microm) was the thickest among all axial walls (P=.0001) and was twice as thick as that at the facial (90 +/- 14 microm) and palatal walls (92 +/- 15 microm). CONCLUSION: Within the limitations of this study, there was little difference in the internal fit of Cerec crowns prepared with convergence angles of 12 degrees and 20 degrees. Distal shadows influenced the thickness of the cement spaces, particularly at the distal walls. However, tooth preparations with an occlusal-cervical height not greater than 6 mm did not exaggerate the effect of the distal shadows.