The correlation of gagging threshold with intra-oral tactile and psychometric profiles in healthy subjects: A pilot study.

Excessive gag reflex could be problematic for adequate dental care. Although various factors may increase the susceptibility to gagging, its contributing factors have not been fully determined. This study aimed to determine whether gag reflex was associated with tactile sensitivity and psychological characteristics. Fifteen volunteers of healthy males and females each were recruited for this study. After completing a questionnaire describing the self-perceived gag reflex activity, a disposable saliva ejector was inserted along the palate into the mouth until gagging was evoked. The ratio of the insertion depth to the palatal length was used as an index for the gagging threshold. The two-point discrimination (TPD) and Semmes-Weinstein monofilament (SWM) tests were performed to assess the tactile sensitivity of the palatal regions (hard palate, anterior and posterior soft palate). The Symptom Checklist-90-Revised was used to investigate the relationship between the gagging threshold and the psychological status. Our findings showed that the gagging threshold had a significant positive correlation with the TPD and SWM thresholds on the hard palate. The psychological profiles of psychoticism and hostility score were also significantly correlated with the gagging threshold. However, there were no significant differences in the tactile and gagging thresholds, as well as the psychological profiles, between males and females. Our results suggested that the tactile sensitivity of the anterior palate is a determining factor for the gagging threshold and implied that the initial response of the oral entry site to stimulation may lead to the development of gag reflex.

A case report of a tongue ulcer presented as the first sign of occult tuberculosis.

BACKGROUND: Tuberculosis (TB) is a serious infectious disease with considerable fatality, typically affecting the pulmonary system and, rarely, other body organs including the oral cavity. Due to the rarity of oral TB, it is frequently overlooked in differential diagnosis of oral lesions. Despite a declining trend in TB incidence in recent years, it is still a major public health problem with high contagiousness, thereby requiring the early diagnosis and prompt treatment. CASE PRESENTATION: A 57-year-old male patient presented with chief complaint of painful ulcer on tip of his tongue. He reported that the ulcer developed without any remarkable event such as mechanical trauma, vesicle formation or systemic illness. His past medical history revealed the TB over 40 years ago, which had reportedly healed after pharmacological treatments. As the ulceration persisted after topical steroid application and careful education about avoiding possible mechanical stimuli, biopsy was performed and histological finding showed typical findings of oral tuberculosis including intense granulomatous inflammatory features with small red rods of mycobacterial organisms as well as epithelioid cells and Langhans giant cells. After suitable antituberculosis treatments, oral tuberculosis ulcer was almost completely healed. We present a case of oral TB affecting tip of the tongue in a patient with a history of pulmonary TB and emphasize the understanding of intraoral manifestations for early diagnosis and prompt treatment of TB. CONCLUSIONS: The present case represented the importance of understanding oral tuberculosis manifestations for dental clinicians who might be frequently the first health care professionals to encounter various oral lesions.

Loss of toll-like receptor 3 aggravates hepatic inflammation but ameliorates steatosis in mice.

The importance of toll-like receptor (TLR) 4 in the pathogenesis of steatohepatitis has been well documented; however, little is known about the role of TLR3. In this study, we determined whether the depletion of TLR3 modulated hepatic injury in mice and further aimed to provide mechanistic insights into the TLR3-mediated modulation of diet-induced hepatic inflammation and fat accumulation. Hepatic steatosis and inflammatory response were induced by feeding wild-type (WT) or TLR3 knockout mice a high-fat diet for 8 weeks. Primary liver resident cells, including hepatocytes, Kupffer cells, and hepatic stellate cells (HSCs), were treated with palmitic acid. TLR3 knockout mice fed a high-fat diet showed severe hepatic inflammation accompanied by nuclear factor-κB and IRF3 activation, which is mainly induced by the activation of Kupffer cells. Decreased TLR4 expression was restored in hepatic mononuclear cells and Kupffer cells in TLR3 knockout mice compared to that in the WT. Moreover, hepatic steatosis was decreased in TLR3 knockout mice. Hepatocytes from TLR3 knockout mice exhibited reduced expression of cannabinoid receptors. HSCs from TLR3 knockout mice showed decreased expression of the enzymes involved in endocannabinoid synthesis. In conclusion, this study suggests that the selective modulation of TLR3 could be a novel therapeutic target for the treatment of hepatic inflammation and steatosis.

The presence of altered craniocervical posture and mobility in smartphone-addicted teenagers with temporomandibular disorders.

[Purpose] Smartphones are widely used by teenagers and adults for various purposes. As teenagers use smartphones more actively than adults, they are more prone to be addicted to smartphones. Furthermore, excessive usage of smartphones can lead to various psychosocial and physical symptoms. [Subjects and Methods] One hundred teenage subjects were recruited and divided into normal and addiction groups, based on the criteria of the smartphone addiction scale-short version questionnaire. Craniocervical posture and mobility were examined by lateral cephalometric analysis and a cervical range of motion instrument. [Results] Cephalometric analysis showed no significant difference in the craniocervical angles of the resting positions of the two groups. However, measurement using an inclinometer revealed a significantly flexed cervical posture while using smartphones and decreased cervical range of motion in the smartphone-addicted teenagers. The clinical profile of temporomandibular disorders revealed that muscular problems were more frequently presented in the smartphone-addicted teenagers. [Conclusion] These findings suggest that smartphone addiction has a negative influence on craniocervical posture and mobility. Further, it can be postulated that smartphone addiction among teenagers may have contributed to the occurrence of myogenous temporomandibular disorders. In conclusion, smartphone-addicted teenagers may be more frequently subjected to muscular disturbance in the craniocervical area, which probably affects the pathologic process of temporomandibular disorders in teenagers.

Morphological and cellular examinations of experimentally induced malocclusion in mice mandibular condyle.

Occlusal alignment is known clinically to have a widespread influence on the stomatognathic system, including the temporomandibular joint and masticatory muscles. However, while occlusion is still an important determinant of most dental treatments, the exact effect of occlusal alignment is unclear because of a lack of conclusive scientific evidence. In this study, a malocclusion model system is used to examine the cellular and histologic alterations in the contralateral condyle of mice after a malocclusion was induced by a build-up of resin on the left maxillary molars. A significant decrease in the thickness of the condylar cartilage was found in the 1-week experimental group, together with increased apoptosis and decreased proliferation in the condylar head, which included cartilage and subchondral bone. Additionally, the number of TRAP-positive osteoclasts and MPO- and F4/80-positive inflammatory cells in the subchondral bone were significantly higher in the 1-week experimental group. Unbalanced malocclusion caused increased bone remodeling, as evidenced by increased osteoclastic activity and inflammatory responses (macrophages and neutrophils, respectively). However, these alterations in the 1-week experimental group were subsequently attenuated and restored almost to the baseline at 3 weeks after the induction of the malocclusion.

The effect of mucosal dryness on the electrogustometric threshold.

Electrogustometry (EGM) is one of the most useful diagnostic tools widely used to evaluate the taste function by measuring the perception threshold to electrogustatory stimuli on the tongue. However, the effects of oral environments on electrogustometric threshold (EGMT) remain to be established despite its simple applicability. Thus, this study aims to determine the effect of mucosal dryness on EGMT in 68 healthy subjects. The experiment was conducted in two different conditions. First, the baseline EGMT was measured when the dryness of the tongue surface was normal. Second, the EGMT was remeasured after the tongue was intentionally desiccated. The current study showed that the mean of the EGMT was significantly increased when the tongue was desiccated, possibly indicating the reduced sensitivity to electrogustatory stimuli. Such an alteration may be related to the disturbed EGM electrical circuit through the dried mucosa with enhanced impedance. Thus, these findings suggested that mucosal dryness should be considered for better evaluation of gustatory function using EGM.

Ginsenoside F2 attenuates chronic-binge ethanol-induced liver injury by increasing regulatory T cells and decreasing Th17 cells.

BACKGROUND: Recently, beneficial roles of ginsenoside F2 (GF2), a minor constituent of Panax ginseng, have been demonstrated in diverse inflammatory diseases. However, its roles in alcoholic liver inflammation and injury have not been clearly understood. Here, we investigated the underlying mechanism by which GF2 ameliorated alcoholic liver injury. METHODS: To induce alcoholic liver injury, C57BL/6J wild type (WT) or interleukin (IL)-10 knockout (KO) mice were orally administered with ethanol (3 g/kg) or ethanol-containing GF2 (50 mg/kg) for 2 wk. Liver injury and infiltration of macrophages and neutrophils were evaluated by serum biochemistry and immunohistochemistry, respectively. The changes of hepatic immune cells were assessed by flow cytometry and polymerase chain reaction analysis. In vitro differentiation of naïve T cells was performed. RESULTS: GF2 treatment significantly attenuated alcoholic liver injury, in which infiltrations of inflammatory macrophages and neutrophils were decreased. Moreover, the frequencies of Foxp3+ regulatory T cells (Tregs) increased but IL-17-producing T (Th17) cells decreased in GF2-treated mice compared to controls. Furthermore, the mRNA expression of IL-10 and Foxp3 was significantly increased, whereas IL-17 mRNA expression was suppressed in GF2-treated mice. However, these beneficial roles of GF2 were not observed in GF2-treated IL-10 KO mice, suggesting a critical role of IL-10. Similarly, GF2 treatment suppressed differentiation of naïve T cells into Th17 cells by inhibiting RORγt expression and stimulating Foxp3 expression. CONCLUSION: The present study suggests that GF2 treatment attenuates alcoholic liver injury by increasing IL-10 expression and Tregs and decreasing IL-17 expression and Th17 cells.

The Effect of Applied Force on Two-Point Discrimination Threshold in the Trigeminal Region.

AIMS: To determine the effect of alterations in applied force on the two-point discrimination (TPD) threshold and to evaluate whether these effects were gender- or site-dependent. METHODS: A total of 62 healthy adults were enrolled in the study and divided into two groups based on gender (men and women, n = 31 each). The TPD test was performed using a modified compass on the forehead, upper labium, and lower labium, and each site was tested with Semmes-Weinstein monofilaments (SWMs) of sizes 4.56, 5.07, and 5.46 that exerted bending forces of 6, 10, and 26 g, respectively. The differences in thresholds according to alterations in the applied forces were evaluated for different genders and sites. RESULTS: Both gender groups showed a significant decrease in TPD thresholds with the 5.46-size monofilament than with the 4.56- or 5.07-size monofilaments. This decrease was more apparent on the forehead regardless of gender. CONCLUSION: These findings suggest that increased intensity of mechanical stimuli could increase tactile acuity as measured by the TPD test.

Focal localization of inflammatory cytokines and neurotrophins in a tongue chronic injury model.

OBJECTIVES: Chronic injury in tongue causes the variety of reactions in the oral cavity, frequently leading to its functional and structural disintegrity including inflammation and sensory dysfunction, but its detailed profiles were not elucidated yet. One of the chronically injured tongue such as tongue piercing, as a pathological aspect, is currently popular among younger people but may be associated with severe side effects, leading to pathophysiological complications. However, the pathophysiological aspects and related cellular and molecular mechanisms underlying tongue injury are not clearly understood. DESIGN: In this study, we designed an experimental model system using C57BL/6 male mice that mimics a chronically injured situation by penetrating the middle part of tongue with silk suture. After 5 and 10 days mice were sacrificed and tongues were collected and processed for histological evaluation and immunohistochemistry. RESULTS: We found that the anterior tongue showed localization of neuro-inflammatory signaling molecules such as myeloperoxidase (MPO), matrix metalloproteinase 2 (MMP2), tumor necrosis factor-α (TNF-α), nerve growth factor, and transient receptor potential cation channel subfamily V member 1 (TRPV1) without any apparent inflammation in temporal manner. In addition, the signal for AM1-43, an activity-dependent nerve terminal probe, decreased within the fungiform papillae on the anterior tongue after injury. CONCLUSIONS: These results implied that the distinct localizations of inflammatory cytokines and neurotrophin would contribute altered sensory function in anterior tongue following the chronic injury. Our study indicates the possible pathophysiologic mechanism underlying neuro-inflammation following chronically injury of tongue. In addition, it could be cautiously postulated that mechanical injury should be avoided to prevent chronic pain disorders from being triggered.

Adenosine A1 receptors inhibit GABAergic transmission in rat tuberomammillary nucleus neurons.

The adenosinergic modulation of GABAergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs) was investigated in mechanically dissociated rat tuberomammillary nucleus (TMN) neurons using a conventional whole-cell patch clamp technique. Adenosine (100 microM) reversibly decreased mIPSC frequency without affecting the current amplitude, indicating that adenosine acts presynaptically to decrease the probability of spontaneous GABA release. The adenosine action on GABAergic mIPSC frequency was completely blocked by 1 microM DPCPX, a selective A(1) receptor antagonist, and mimicked by 1 microM CPA, a selective A(1) receptor agonist. This suggests that presynaptic A(1) receptors were responsible for the adenosine-mediated inhibition of GABAergic mIPSC frequency. CPA still decreased GABAergic mIPSC frequency even either in the presence of 200 microM Cd(2+), a general voltage-dependent Ca(2+) channel blocker, or in the Ca(2+)-free external solution. However, the inhibitory effect of CPA on GABAergic mIPSC frequency was completely occluded by 1 mM Ba(2+), a G-protein coupled inwardly rectifying K(+) (GIRK) channel blocker. In addition, the CPA-induced decrease in mIPSC frequency was completely occluded by either 100 microM SQ22536, an adenylyl cyclase (AC) inhibitor, or 1 muM KT5720, a specific protein kinase A (PKA) inhibitor. The results suggest that the activation of presynaptic A(1) receptors decreases spontaneous GABAergic transmission onto TMN neurons via the modulation of GIRK channels as well as the AC/cAMP/PKA signal transduction pathway. This adenosine A(1) receptor-mediated modulation of GABAergic transmission onto TMN neurons may play an important role in the fine modulation of the excitability of TMN histaminergic neurons as well as the regulation of sleep-wakefulness.

Effects of carbamazepine and amitriptyline on tetrodotoxinresistant Na+ channels in immature rat trigeminal ganglion neurons.

Although anticonvulsant drugs that block voltage-dependent Na+ channels have been widely used for neuropathic pain, including peripheral nerve injury-induced pain, much less is known about the actions of these drugs on immature trigeminal ganglion (TG) neurons. Here we report the effects of carbamazepine (CBZ) and amitriptyline (ATL) on tetrodotoxin-resistant (TTX-R) Na' channels expressed on immature rat TG neurons. TTX-R Na+ currents (I(Na)) were recorded in the presence of 300 nM TTX by use of a conventional whole-cell patch clamp method. Both CBZ and ATL inhibited TTX-R I(Na) in a concentration-dependent manner, but ATL was more potent. While CBZ and ATL did not affect the overall voltage-activation relationship of TTX-R Na+ channels, both drugs shifted the voltage-activation relationship to the left, indicating that they inhibited TTX-R Na+ channels more efficiently at depolarized membrane potentials. ATL showed a profound use-dependent blockade of TTX-R I(Na), but CBZ had little effect. The present results suggest that both CBZ and ATL, common drugs used for treating neuropathic pain, efficiently inhibit TTX-R Na+ channels expressed on immature TG neurons, and that these drugs might be useful for the treatment of trigeminal nerve injury-induced neuropathic pain, as well as the inhibition of ongoing central sensitization, even during immature periods.

Effect of Jaw and Head Position on Airway Resistance in Obstructive Sleep Apnea.

This study evaluated whether changes in jaw and neck position caused substantial airway resistance (Raw) changes in normal controls and obstructive sleep apnea (OSA) subjects. Subject groups included 12 male nocturnal polysomnographically diagnosed OSA patients and 16 healthy male control subjects. Raw was assessed plethysmographically and measured under the following conditions: neutral head posture with 0/3, 1/3, 2/3, or 3/3 of the subjects maximum forward jaw position; normal jaw (0/3 forward) with fully flexed, extended, right or left rotated head position. Both groups showed a similar significant decrease in Raw upon jaw protrusion. OSA patients showed a significantly higher baseline (normal jaw, neutral head posture). Raw and both subject groups also had a clear increase in their airway resistance with flexion and to a lesser extent with neck rotation and extension. These data document that airway resistance can be significantly influenced by head and jaw positioning with protrusion of the jaw reducing Raw and flexing the neck increasing Raw.

Effects of mandibular advancement on upper airway dimension and collapsibility in patients with obstructive sleep apnea using dynamic upper airway imaging during sleep.

OBJECTIVES: The objective of this study was to evaluate the effects of mandibular advancement on oropharyngeal dimension and collapsibility and reveal the predominate site of change produced by mandibular advancement in patients with obstructive sleep apnea (OSA). STUDY DESIGN: Sixteen adults (13 males and 3 females) with symptomatic mild to severe OSA participated. Custom-made silicone mandibular positioners were used to keep the mandible at 67% of maximum advancement. Changes in the oropharyngeal size and collapsibility with mandibular advancement were evaluated using ultrafast computed tomography taken during wakefulness and midazolam-induced sleep. Cross-sectional areas were assessed using electron beam tomography at 4 levels: high retropalatal (HRP), low retropalatal (LRP), high retroglossal (HRG), and low retroglossal (LRG). RESULTS: During sleep, the minimum cross-sectional areas decreased 36.5%, 67.8%, 75.5%, and 65.8% at each level of HRP, LRP, HRG, and LRG respectively, as compared with those measured during wakefulness. Mandibular advancement during sleep increased 75.7%, 141.3%, 128.1%, and 119.9% at each level. The oropharynx showed 70.3%, 110.4%, 140.3%, and 156.9% increase in the Collapsibility Indices during sleep at each level of HRP, LRP, HRG, and LRG, respectively, compared with wakefulness. However, collapsibility indices decreased 29.1%, 23.2%, 21.4%, and 34.1% at each level with mandibular advancement. CONCLUSION: Mandibular advancement increases oropharyngeal diameter and decreases oropharyngeal collapsibility during midazolam-induced sleep respiration at the retropalatal as well as the retroglossal region in most patients with OSA.

New quantitative method for bone tracer uptake of temporomandibular joint using Tc-99m MDP skull SPECT.

OBJECTIVES: Quantitative bone SPECT studies have several advantages over qualitative studies for evaluating a temporomandibular joint (TMJ), yet in certain cases additional images are still needed. Accordingly, the current study developed a new easy SPECT quantification method for the bone tracer uptake in a TMJ and evaluated its usefulness and inter-observer variability in patients with TMJ pain. METHODS: Sixty-six adult patients (11 males, 55 females) with a mean age of 31 years (range 22-79 years) suffering from TMJ pain were questioned regarding the history of their condition, and then subjected to an oromaxillofacial examination and bone SPECT. New quantitative data for TMJs (TMJ index) were calculated from a formula using TMJ and skull counts. RESULTS: TMJs with spontaneous pain had higher TMJ indices than those without spontaneous pain (8.87 vs. 6.87, P = 0.032). TMJs with mouth-opening pain or palpatory pain also exhibited higher TMJ indices than those without such pains, although the differences were not statistically significant. Positive TMJs, according to a visual SPECT interpretation, had much higher TMJ indices than the negative ones (8.99 vs. 5.37, P < 0.001). The reference skull count, mean TMJ count and TMJ index obtained using the proposed TMJ quantification method demonstrated an excellent correlation based on two independent observers (r = 0.996, r = 0.993 and r = 0.989, respectively; P < 0.001). CONCLUSIONS: The current results indicate that the proposed quantitative TMJ bone SPECT is easy to perform, plus the resulting TMJ index has a lower inter-observer variability, making it an effective TMJ evaluation method for patients with painful TMJs, and especially useful for serial studies.

Age-related changes in the microarchitecture of collagen fibrils in the articular disc of the rat temporomandibular joint.

The microarchitecture of collagen fibrils in the articular disc of the temporomandibular joint (TMJ) plays an important role in dissipating the mechanical load during jaw movement. However, little information is available on its adaptations to the biomechanical environment during development. To address this issue, we analyzed the diameter of collagen fibrils of the articular disc of the rat TMJ with quantitative ultrastructural analysis during postnatal development. The mean diameter of the collagen fibrils significantly increased and the arrangement of the collagen fiber networks became compact during development. Articular discs of suckling rat pups were composed of thin, uniformly sized collagen fibrils (range: 30-60 nm, peak: 40-50 nm). At the age of 4 weeks, thicker collagen fibrils began to appear in articular discs, shortly after weaning (range: 20-70 nm, peak: 40-50 nm). In articular discs of adult rats, collagen fibrils varied widely in diameter, with thick fibrils predominating (range: 10-120 nm, peak: 40-70 nm). These age-related changes in the microarchitecture of collagen fibrils in articular discs may reflect changes in their biomechanical environment during development.