Analgesic Mechanisms of Steroid Ointment against Oral Ulcerative Mucositis in a Rat Model.

Despite the long history of use of steroid ointments for oral mucositis, the analgesic mechanism has not been fully elucidated. In this study, we examined the effects of triamcinolone acetonide (Tmc) on oral ulcerative mucositis-induced pain in conscious rats by our proprietary assay system. Based on evaluations of the physical properties and retention periods in the oral mucosa of human volunteers and rats, we selected TRAFUL® ointment as a long-lasting base. In oral ulcerative mucositis model rats, TRAFUL® with Tmc suppressed cyclooxygenase-dependent inflammatory responses with upregulations of glucocorticoid receptor-induced anti-inflammatory genes and inhibited spontaneous nociceptive behavior. When an ointment with a shorter residual period was used, the effects of Tmc were not elicited or were induced to a lesser extent. Importantly, TRAFUL® with Tmc also improved oral ulcerative mucositis-induced mechanical allodynia, which has been reported to be independent of cyclooxygenase. Ca2+ imaging in dissociated trigeminal ganglion neurons showed that long-term preincubation with Tmc inhibited the hypertonic stimulation-induced Ca2+ response. These results suggest that the representative steroid Tmc suppresses oral ulcerative mucositis-induced pain by general anti-inflammatory actions and inhibits mechanical sensitivity in peripheral nerves. For drug delivery, long-lasting ointments such as TRAFUL® are needed to sufficiently induce the therapeutic effects.

Changes in tonsillolith characteristics detected in a follow-up CT study.

BACKGROUND: Tonsilloliths are related clinically to halitosis and tonsillar abscess. However, the dynamics of tonsilloliths over time are unknown. The aim of the study was to evaluate change in the characteristics of tonsilloliths in a time-dependent fashion by follow-up computed tomography (CT). METHODS: Tonsilloliths were analyzed in 326 CT scan pair sets of initial and at least two follow-up CT examinations of patients with whole palatine tonsils and various diseases of the oral and maxillofacial regions. RESULTS: Over the follow-up period, 12.1% of tonsilloliths disappeared. Approximately 26.1% of tonsilloliths changed in size during follow-up, mostly increasing in size. In tonsilloliths that showed enlargement, the mean (± standard deviation) growth rate was 0.61 ± 0.41 mm per year. Approximately 37.3% of tonsilloliths changed position during the follow-up period; of these, movement was toward the respiratory tract in 92% at a mean rate of - 1.38 ± 1.59 mm per year. The calcification levels of almost all tonsilloliths showed dynamic change: HU number increased in 84.3% and decreased in 12.7% of tonsilloliths over the follow-up period. The mean rate of HU increase was 63.8 ± 96.3 HU/year, and the mean rate of HU decrease was - 38.4 ± 66.8 HU/year. CONCLUSIONS: The calcification levels of all tonsilloliths showed dynamic fluctuation, and a tendency for excretion of tonsilloliths from the body. Their dynamics over time suggest that tonsilloliths may be in a permanently active phase which functions to remove foreign matter.

Novel approaches to the study of viscosity discrimination in rodents.

Texture has enormous effects on food preferences. The materials used to study texture discrimination also have tastes that experimental animal can detect; therefore, such studies must be designed to exclude taste differences. In this study, to minimize the effects of material tastes, we utilized high- and low-viscosity forms of carboxymethyl cellulose (CMC-H and CMC-L, respectively) at the same concentrations (0.1-3%) for viscosity discrimination tests in rats. In two-bottle preference tests of water and CMC, rats avoided CMC-H solutions above 1% (63 mPa·s) but did not avoid less viscous CMC-L solutions with equivalent taste magnitudes, suggesting that rats spontaneously avoided high viscosity. To evaluate low-viscosity discrimination, we performed conditioned aversion tests to 0.1% CMC, which initially showed a comparable preference ratio to water in the two-bottle preference tests. Conditioning with 0.1% CMC-L (1.5 mPa·s) did not induce aversion to 0.1% CMC-L or CMC-H. However, rats acquired a conditioned aversion to 0.1% CMC-H (3.6 mPa·s) even after latent inhibition to CMC taste by pre-exposure to 0.1% CMC-L. These results suggest that rats can discriminate considerably low viscosity independent of CMC taste. This novel approach for viscosity discrimination can be used to investigate the mechanisms of texture perception in mammals.

Isoliquiritigenin, an active ingredient of Glycyrrhiza, elicits antinociceptive effects via inhibition of Nav channels.

Glycyrrhiza extract has been used for the treatment of oral and gastric ulcers, but the analgesic mechanism remains unknown. In the present study, we investigated the effects of isoliquiritigenin, an active ingredient of Glycyrrhiza, on Nav channels in vitro and nociceptive behaviors in vivo. In an autopatch-clamp study, isoliquiritigenin inhibited the currents of Nav1.1, Nav1.3, Nav1.6, Nav1.7, and Nav1.8 in a channel expression system. In small- and medium-sized cultured trigeminal ganglion neurons, the compound suppressed Nav currents in many neurons (78%) and Kv currents in all neurons, dose-dependently. In current-clamp mode, isoliquiritigenin blocked action potential generation in many neurons (64%), but it conversely accelerated action potential generation in the remaining neurons. The opposing effects on action potentials were reproduced in a computational simulation of a modified Hodgkin-Huxley-based model, based on the electrophysiological data. In behavioral experiments, local treatment with isoliquiritigenin suppressed nociceptive behaviors in response to oral ulcer development or nociceptive TRP channel agonists in the oral mucosa and hind paw. These results suggest that isoliquiritigenin exerts an analgesic effect predominantly via inhibitory action on Nav channels on sensory nociceptive fibers. This pharmacological mechanism indicates that isoliquiritigenin is useful for pain relief and provides scientific evidence for Glycyrrhiza at the ingredient level.

The effect of flavor on the oral perception and palatability of viscosity in healthy human subjects.

OBJECTIVES: Thickeners are frequently used in various foods, including ice cream and sauces, to impart viscosity. Generally, viscous foods have some flavor (smell and taste). In this study, we examined the effects of flavor on the oral perception and palatability of viscosity in humans. METHODS: Viscous fluids were prepared by adding the commercial thickener Tsururinko® (0.5 and 3.0%) to water and apple juice, which were used as the control and flavor fluids, respectively. The viscosity and palatability perception of the test fluids were evaluated in nine healthy volunteers using a visual analog scale. In the other seven volunteers, fluid viscosities were measured before and after spitting following retention in the mouth for 5 s to investigate the dilution of viscous fluids by flavor-stimulated saliva. RESULTS: With 1.5% Tsururinko®, there was no difference between the physical viscosity of water and apple juice, but the perceived viscosity of apple juice was significantly lower than that of water. With 3.0% Tsururinko®, the viscosity of apple juice was significantly higher than that of water, but the perceived viscosities did not differ significantly. The addition of Tsururinko® reduced palatability in water in a dose-dependent manner. Apple juice suppressed this Tsururinko®-induced reduction. The reduction in viscosity after spitting was significantly larger in apple juice than in water. CONCLUSION: Our results suggest that a favorable flavor reduces the perception of oral viscosity, which is due to mixing with stimulated saliva, and suppresses the unpalatability of thickeners.

Orthodontic force-induced oxidative stress in the periodontal tissue and dental pulp elicits nociception via activation/sensitization of TRPA1 on nociceptive fibers.

Orthodontic patients complain of pain for the first few days after insertion of appliances. Mechanical force has been reported to produce oxidants in periodontal ligament (PDL) cells. It has not been studied whether orthodontic force-induced oxidative stress elicits nociception. Herein, we focused on the role of the oxidant-sensitive channel TRPA1 on nociception in orthodontic pain. In a rat model of loaded orthodontic force between the maxillary first molar and incisor, the behavioral signs of orofacial nociception, facial rubbing and wiping, increased to a peak on day 1 and gradually diminished to the control level on day 5. Administration of free radical scavengers (Tempol and PBN) and TRPA1 antagonist (HC-030031) inhibited nociceptive behaviors on day 1. In the PDL, the oxidative stress marker 8-OHdG was highly detected on day 1 and recovered on day 5 to the sham-operated level. The dental pulp showed similar results as the PDL. TRPA1 mRNA was abundantly expressed in the trigeminal ganglion relative to PDL tissue, and there were TRPA1-immunopositive neuronal fibers in the PDL and pulp. In dissociated trigeminal ganglion neurons, H2O2 at 5 mM induced a Ca2+ response that was inhibited by HC-030031. Although H2O2 at 100 µM did not yield any response, it enhanced the mechanically activated TRPA1-dependent Ca2+ response. These results suggest that oxidative stress in the PDL and dental pulp following orthodontic force activates and/or mechanically sensitizes TRPA1 on nociceptive fibers, resulting in orthodontic nociception. Later, the disappearance of nociception seems to be related to a decrease in oxidative stress, probably due to tissue remodeling.

Can the lower rate of CT- or MRI-related adverse drug reactions to contrast media due to stricter limitations on patients undergoing contrast-enhanced CT or MRI?

OBJECTIVE: The aim of this study was to examine whether a decreased occurrence rate of adverse drug reactions (ADRs) to contrast media in contrast-enhanced CT and MRI was attributable to appropriate criteria for patients with some diseases. A secondary aim was to elucidate safety profiles for contrast media and factors influencing the occurrence of ADRs. METHODS: Clinical data of patients who underwent contrast-enhanced CT (5576 cases) or MRI (3357 cases) were retrospectively analyzed to evaluate rates of ADRs to contrast media, symptoms of ADRs, treatments for ADRs, and differences in medical history, blood test results, and other factors between patients with and without ADRs in a dental hospital. RESULTS: The rate of ADRs to contrast media was 0.54% for CT and 0.09% for MRI. The most frequent ADRs in contrast-enhanced CT or MRI were nausea and vomiting as physiologic reactions. Two serious reactions were seen for CT, but none for MRI. Significant differences between patients with and without ADRs were seen in liver function according to blood tests for CT, and in digestive disorders elicited from medical interviews for MRI. CONCLUSION: The lower occurrence rate of ADRs to contrast media in dental hospitals could be due to the adoption of appropriate criteria for patients with some diseases undergoing enhanced CT or MRI. Complete suppression of ADRs to contrast media for CT or MRI is unrealistic, so attention is warranted for patients with decreased liver function when performing enhanced CT, and for patients with digestive disorders when performing enhanced MRI.

First Report of Sublingual Gland Ducts: Visualization by Dynamic MR Sialography and Its Clinical Application.

This study was done to determine whether the sublingual gland ducts could be visualized and/or their function assessed by MR sialography and dynamic MR sialography and to elucidate the clinical significance of the visualization and/or evaluation of the function of sublingual gland ducts by clinical application of these techniques. In 20 adult volunteers, 19 elderly volunteers, and 7 patients with sublingual gland disease, morphological and functional evaluations were done by MR sialography and dynamic MR sialography. Next, four parameters, including the time-dependent changes (change ratio) in the maximum area of the detectable sublingual gland ducts in dynamic MR sialographic images and data were analyzed. Sublingual gland ducts could be accurately visualized in 16 adult volunteers, 12 elderly volunteers, and 5 patients. No significant differences in the four parameters in detectable duct areas of sublingual glands were found among the three groups. In one patient with a ranula, the lesion could be correctly diagnosed as a ranula by MR sialography because the mass was clearly derived from sublingual gland ducts. This is the first report of successful visualization of sublingual gland ducts. In addition, the present study suggests that MR sialography can be more useful in the diagnosis of patients with lesions of sublingual gland ducts.

Real-time evaluation of swallowing in patients with oral cancers by using cine-magnetic resonance imaging based on T2-weighted sequences.

OBJECTIVE: The aim of this study was to evaluate whether a new cine-magnetic resonance imaging (CMRI) technique might be useful for evaluating swallowing function in patients with different types of oral cancers by assessing 12 CMRI-related parameters. STUDY DESIGN: In total, 111 patients with oral cancers were evaluated. We examined whether visualization of fluid flow and determination of flow direction to the trachea or the esophagus were possible with CMRI. We evaluated the correlations between CMRI-related parameters and self-reported dysphagia scores as the status of dysphagia, T classification groups as tumor staging for preoperative patients, alterations in CMRI-related parameters between pre- and postoperative patients, and the degree of invasiveness of oral cancer surgery. RESULTS: We could judge the flow direction to the esophagus on CMRI in all 111 patients. Six CMRI-related parameters showed significant correlations with dysphagia status. Increases in CMRI-related parameters were significantly related to deterioration of swallowing status, as shown by a decrease in self-reported dysphagia scores, advances in the T classification, and degree of invasiveness of oral cancer surgery. CONCLUSIONS: The results of the present study suggest that CMRI can be used to directly visualize swallowing dynamics and objectively evaluate the swallowing complaints of patients with oral cancer.

Advocacy of diagnostic criteria for maxillary incisive canal cysts based on alteration of normal maxillary incisive canals according to aging in Japanese populations.

BACKGROUND: The purpose of the present study was to describe the CT imaging findings of normal incisive canals and incisive canal cysts and propose cut-off values to differentiate between them. METHODS: A total of 220 normal subjects and 40 patients with incisive canal cysts on multi-detector row computed tomography (MDCT) were retrospectively analyzed. The shapes, sizes, anatomic variations, Hounsfield scale values, and so on of maxillary incisive canals and the sizes and Hounsfield scale values of maxillary incisive canal cysts were analyzed. RESULTS: A significant difference in sizes of maxillary incisive canals in normal subjects was found between males and females. The sizes of maxillary incisive canals were significantly wider during aging, but shapes, anatomic variations, and Hounsfield scale values in the maxillary incisive canals were not significantly different with aging. A significant difference in sizes but not Hounsfield scale values was found between normal maxillary incisive canals and maxillary incisive canal cysts. Based on a cut-off of over 6 mm in the width of incisive canals, maxillary incisive canal cysts could not be appropriately diagnosed for subjects over 60 years of age. Over 60 years of age, maxillary incisive canal cysts could be appropriately diagnosed based on a cut-off of over 7.1 mm in width of incisive canals. When maxillary incisive canals of the hourglass types were seen on sagittal sections, significantly more patients had maxillary incisive canal cysts than other types. CONCLUSION: In coincidentally diagnosing asymptomatic incisive canal cysts on imaging, we should apply different cut-offs for the size of the maxillary incisive canal for patients over and under 60 years of age. Specifically, the cut-offs for the long axis of maxillary incisive canal cysts were 7.1 mm for patients over 60 years of age and 6.0 mm for those under 60 years of age. In addition, we should pay attention to wider canals with hourglass shapes as indicative of cystic change of maxillary incisive canals.

Characteristics of diffusion-weighted images and apparent diffusion coefficients of ranulas and other masses in and around the floor of the mouth.

OBJECTIVE: The aim of this study was to evaluate the characteristics of diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) values of ranulas. In addition, to elucidate DWI findings and ADC values of other representative masses in and around the floor of the mouth. STUDY DESIGN: DWI findings and ADC values in 35 patients with ranulas and 33 patients with other masses were retrospectively reviewed with a central focus on cystic masses or lesions that may have cyst-like components in and around the floor of the mouth based on the diagnosis of each respective disease. RESULTS: Ranulas were all well-defined, homogeneous masses with high signal intensity on DWI. The mean ± standard deviation ADC value of the 35 ranulas was 2.59 ± 0.31 × 10-3 mm2/s. There was a significant difference in ADC values between simple and plunging ranulas. On DWI, most other masses were heterogeneous, and most ADC values, except those for thyroglossal duct cysts, hemangiomas, and pleomorphic adenomas, were significantly lower than those for ranulas. CONCLUSIONS: The characteristic DWI and ADC findings of ranulas can be determined accurately, and these data can be significantly useful in the differential diagnosis of many kinds of diseases in and around the oral floor.

Significance and usefulness of imaging characteristics of gubernaculum tracts for the diagnosis of odontogenic tumors or cysts.

We aimed to determine the significance and usefulness of imaging characteristics of gubernaculum tracts (GT) for the diagnosis of odontogenic tumors or cysts. This was a retrospective analysis of relationships between odontogenic or non-odontogenic tumors or cysts and the GT that were visualized using multi-detector computed tomography (MDCT). The relationship between the size of a mass and expansion of the GT in all odontogenic tumors or cysts to which GTs were contiguous on MDCT, was statistically analyzed. Intact or expanded GTs were detected in MDCT images on the top of almost all odontogenic tumors or cysts, but not on non-odontogenic tumors or cysts. Characteristic image findings regarding the relationship between the GT and the odontogenic mass were detected for the respective odontogenic tumors or cysts in which the GTs were contiguous to the mass on MDCT. In ameloblastomas, expansion of the GTs significantly and very strongly correlated with tumor size (r = 0.741, p = 0.0001), but this correlation was very weak in dentigerous cysts (r = 0.167, p = 0.028) and there was no correlation between these parameters in odontogenic keratocysts (r = -0.089, p = 0.557). The imaging characteristics of GTs at the top of masses should be very useful for both the differential diagnosis of the pathological diagnosis of odontogenic masses and for differentiation between odontogenic and non-odontogenic masses.

Multiple mandibular static bone depressions attached to the three major salivary glands.

A Stafne bone defect is a static bone depression in the mandible that is commonly observed in cortical bone near the mandibular angle. We herein present a rare case in which static bone depressions attached to the three major salivary glands were observed on panoramic radiography and computed tomography (CT). The three static bone depressions in the mandible were visualized on a panoramic radiograph and CT as oval radiolucent masses in a 68-year-old man. The CT numbers in the bone depressions ranged from 10 to 50 HU, and they were close to those of the respective salivary glands. Based on the CT numbers, the areas in the bone depressions were determined to be a normal parotid gland, sublingual gland, and submandibular gland. The patient underwent a follow-up examination and did not request further consultation.

Functional evaluation of swallowing in patients with tongue cancer before and after surgery using high-speed continuous magnetic resonance imaging based on T2-weighted sequences.

OBJECTIVES: The aim of this study was to determine the usefulness of evaluating the function of swallowing before and after surgery in patients with tongue cancer by using T2-weighted sequences of high-speed continuous magnetic resonance imaging (HSCMRI). STUDY DESIGN: The imaging findings and related parameters on HSCMRI along with those on routine MRI examinations before and after surgery were examined in 19 patients with tongue cancer. In addition, changes in various parameters during 1 year after surgery were evaluated in 10 patients. RESULTS: In most patients examined, the direction of flow to the esophagus could be seen on HSCMRI before and after surgery. Significant correlations were observed among 4 parameters and in the responses to a dysphagia questionnaire. CONCLUSIONS: The results of the present study suggest that the dynamics of swallowing can be directly visualized on HSCMRI by using 4 parameters that permit the evaluation of changes before and after surgery, and this enables objective evaluation of patients' swallowing complaints.