Salivary trefoil factor family peptide 3 (TFF3) and flow rate in persons with and without obstructive sleep apnea: A preliminary study.

OBJECTIVES: Obstructive sleep apnea (OSA) is one of the most common chronic diseases. Trefoil factor family 3 (TFF3) peptides are secreted by major and minor salivary glands and may be involved in the pathogenesis of OSA. This study aimed to evaluate salivary TFF3 and flow rate between those with and without OSA. MATERIAL AND METHODS: This was a prospective experimental study that enrolled patients with OSA and non-OSA. Total unstimulated saliva was collected, the salivary flow rate was measured, and the TFF3 level was analyzed by using a modified sandwich enzyme-linked immunosorbent assay. Baseline characteristics, TFF3 level, and salivary flow rate were compared between both groups. Factors associated with the TFF3 level and flow rate were computed by using multivariate linear regression analysis. RESULTS: Twenty-eight participants were recruited in the study: 20 patients with OSA (71.42%) and 8 non-OSA as control. The TFF3 and salivary flow rates between both groups of non-OSA versus OSA were comparable (TFF3 non-OSA 61.06 vs. OSA 96.00 ng/mg; p = .276 and flow rate non-OSA 0.40 vs. OSA 0.35 mL/min; p = .320). Factors associated with the TFF3 level were neck circumference with a negative coefficient of -16.419 (p = .042). For the salivary flow rate, only age was a significant factor with the coefficient of -0.013 (p = .044). CONCLUSIONS: TFF3 and salivary flow rate were comparable between patients with OSA and non-OSA. The factor associated with TFF3 level was neck circumference, while age was negatively associated with the salivary flow rate in patients with OSA.

Aberrant plasticity of peripheral sensory axons in a painful neuropathy.

Neuronal cells express considerable plasticity responding to environmental cues, in part, through subcellular mRNA regulation. Here we report on the extensive changes in distribution of mRNAs in the cell body and axon compartments of peripheral sensory neurons and the 3' untranslated region (3'UTR) landscapes after unilateral sciatic nerve entrapment (SNE) injury in rats. Neuronal cells dissociated from SNE-injured and contralateral L4 and L5 dorsal root ganglia were cultured in a compartmentalized system. Axonal and cell body RNA samples were separately subjected to high throughput RNA sequencing (RNA-Seq). The injured axons exhibited enrichment of mRNAs related to protein synthesis and nerve regeneration. Lengthening of 3'UTRs was more prevalent in the injured axons, including the newly discovered alternative cleavage and polyadenylation of NaV1.8 mRNA. Alternative polyadenylation was largely independent from the relative abundance of axonal mRNAs; but they were highly clustered in functional pathways related to RNA granule formation in the injured axons. These RNA-Seq data analyses indicate that peripheral nerve injury may result in highly selective mRNA enrichment in the affected axons with 3'UTR alterations potentially contributing to the mechanism of neuropathic pain.

The preservative effect of Thai propolis extract on the viability of human periodontal ligament cells.

BACKGROUND/AIM: Tooth avulsion causes an injury to the periodontal ligament (PDL). The success of tooth replantation depends on the quantity and quality of PDL cells. The aim of this study was to examine the preservative and proliferative effects of Thai propolis extract, previously shown to exert anti-inflammatory and antioxidant activities, on human PDL cells. MATERIALS AND METHODS: Ninety-six premolars were left to air dry for 30 min and stored in Hank's balanced salt solution (HBSS), milk, or various concentrations of propolis extract from 0.25 to 10 mg ml-1 for 3 h. PDL cells were isolated by collagenase and trypsin digestion, and their viability was determined by a trypan blue dye exclusion assay. PDL tissues were also scraped off the root surface and cultured to determine cell growth and morphology. The alamarBlue® and BrdU assays were performed to determine the cytotoxic and proliferative effects of the extract on cultured PDL cells, respectively. RESULTS: A non-toxic dose of 2.5 mg ml-1 of propolis extract yielded the greatest percentage of cell viability (78.84 ± 3.34%), which was significantly higher than those of the other concentrations (P < 0.001). Nevertheless, this percentage was not significantly different from that of HBSS (80.14 ± 2.44%; P = 1.00), but was significantly higher than that of milk (71.27 ± 2.79%; P < 0.001). The cells grown from PDL explants looked like fibroblasts. However, 2.5 mg ml-1 of the extract did not induce PDL cell proliferation. CONCLUSION: Thai propolis extract at 2.5 mg ml-1 appears to be the most effective dose for preserving the viability of PDL cells, and this was comparable to HBSS.

Which oropharyngeal factors are significant risk factors for obstructive sleep apnea? An age-matched study and dentist perspectives.

OBJECTIVE: Obstructive sleep apnea (OSA) is a common sleep breathing disorder. Untreated OSA may lead to a number of cardiovascular complications. Dentists may play an important role in OSA detection by conducting careful oral examinations. This study focused on the correlation of oral anatomical features in Thai patients who presented with OSA. METHODS: We conducted a prospective comparative study at a sleep/hypertension clinic and a dental clinic at Khon Kaen University in Thailand. Patients with OSA were enrolled in the study, along with age-matched patients with non-OSA (controls). Baseline characteristics, clinical data, and oropharyngeal data of all patients were compared between the two groups. Oropharyngeal measurements included tongue size, torus mandibularis, Mallampati classification, palatal space, and lateral pharyngeal wall area. Multivariate logistic regression analysis was used to identify the factors associated with OSA. RESULTS: During the study period, there were 156 patients who met the study criteria; 78 were patients with OSA and the other 78 were healthy control subjects. In the OSA group, there were 43 males with a mean age of 53 (standard deviation 12.29) years and a mean BMI of 30.86 kg/mm(2). There were 37 males in the control group with a mean age of 50 (standard deviation 12.04) years and a mean BMI of 24.03 kg/mm(2). According to multivariate logistic analysis, three factors were perfectly associated with OSA, including torus mandibularis class 6, narrow lateral pharyngeal wall, and Mallampati class 4. There were two other significant factors associated with having OSA, namely, BMI and Mallampati classification. The adjusted odds ratios (95% confidence interval) of these two factors were 1.445 (1.017, 2.052) and 5.040 (1.655, 15.358), respectively. CONCLUSION: Dentists may play an important role in the detection of OSA in patients with high BMI through careful oropharyngeal examination in routine dental treatment. A large torus mandibularis, Mallampati class 4, and a narrow lateral pharyngeal wall are important anatomical risk factors for OSA.

Relationship of axonal voltage-gated sodium channel 1.8 (NaV1.8) mRNA accumulation to sciatic nerve injury-induced painful neuropathy in rats.

Painful peripheral neuropathy is a significant clinical problem; however, its pathological mechanism and effective treatments remain elusive. Increased peripheral expression of tetrodotoxin-resistant voltage-gated sodium channel 1.8 (NaV1.8) has been shown to associate with chronic pain symptoms in humans and experimental animals. Sciatic nerve entrapment (SNE) injury was used to develop neuropathic pain symptoms in rats, resulting in increased NaV1.8 mRNA in the injured nerve but not in dorsal root ganglia (DRG). To study the role of NaV1.8 mRNA in the pathogenesis of SNE-induced painful neuropathy, NaV1.8 shRNA vector was delivered by subcutaneous injection of cationized gelatin/plasmid DNA polyplex into the rat hindpaw and its subsequent retrograde transport via sciatic nerve to DRG. This in vivo NaV1.8 shRNA treatment reversibly and repeatedly attenuated the SNE-induced pain symptoms, an effect that became apparent following a distinct lag period of 3-4 days and lasted for 4-6 days before returning to pretreatment levels. Surprisingly, apparent knockdown of NaV1.8 mRNA occurred only in the injured nerve, not in the DRG, during the pain alleviation period. Levels of heteronuclear NaV1.8 RNA were unaffected by SNE or shRNA treatments, suggesting that transcription of the Scn10a gene encoding NaV1.8 was unchanged. Based on these data, we postulate that increased axonal mRNA transport results in accumulation of functional NaV1.8 protein in the injured nerve and the development of painful neuropathy symptoms. Thus, targeted delivery of agents that interfere with axonal NaV1.8 mRNA may represent effective neuropathic pain treatments.

Increased peripheral nerve excitability and local NaV1.8 mRNA up-regulation in painful neuropathy.

BACKGROUND: Neuropathic pain caused by peripheral nerve injury is a chronic disorder that represents a significant clinical challenge because the pathological mechanisms have not been fully elucidated. Several studies have suggested the involvement of various sodium channels, including tetrodotoxin-resistant NaV1.8, in affected dorsal root ganglion (DRG) neurons. We have hypothesized that altered local expression of NaV1.8 in the peripheral axons of DRG neurons could facilitate nociceptive signal generation and propagation after neuropathic injury. RESULTS: After unilateral sciatic nerve entrapment injury in rats, compound action potential amplitudes were increased in both myelinated and unmyelinated fibers of the ipsilateral sciatic nerve. Tetrodotoxin resistance of both fiber populations and sciatic nerve NaV1.8 immunoreactivity were also increased. Further analysis of NaV1.8 distribution revealed that immunoreactivity and mRNA levels were decreased and unaffected, respectively, in the ipsilateral L4 and L5 DRG; however sciatic nerve NaV1.8 mRNA showed nearly an 11-fold ipsilateral increase. Nav1.8 mRNA observed in the sciatic nerve was likely of axonal origin since it was not detected in non-neuronal cells cultured from nerve tissue. Absence of changes in NaV1.8 mRNA polyadenylation suggests that increased mRNA stability was not responsible for the selective peripheral mRNA increase. Furthermore, mRNA levels of NaV1.3, NaV1.5, NaV1.6, NaV1.7, and NaV1.9 were not significantly different between ipsilateral and contralateral nerves. We therefore propose that selective NaV1.8 mRNA axonal transport and local up-regulation could contribute to the hyperexcitability of peripheral nerves in some neuropathic pain states. CONCLUSION: Cuff entrapment injury resulted in significantly elevated axonal excitability and increased NaV1.8 immunoreactivity in rat sciatic nerves. The concomitant axonal accumulation of NaV1.8 mRNA may play a role in the pathogenesis of this model of neuropathic pain.

Superior head of human lateral pterygoid muscle: single motor unit firing rates during isometric force.

The superior head of the human lateral pterygoid muscle (SHLP) has been classically considered to have functions that are independent of the inferior head of the lateral pterygoid (IHLP). Recent evidence however suggests that some of the functional properties of the SHLP are similar to those of the IHLP. The aim was to determine whether the functional properties in terms of single motor unit (SMU) firing rates within the SHLP vary with horizontal isometric force (400-800gwt) and direction (i.e., contralateral (CL), protrusive (P), ipsilateral (IL) and intermediate directions, CL-P, IL-P) in a manner similar to those identified for the IHLP, and as would be expected if both SHLP and IHLP should be regarded as one muscle. In eight subjects, the firing rates of 40 SMUs were recorded from computer tomography (CT)-verified SHLP sites while each subject exerted horizontal isometric forces with their lower jaw onto a force transducer in the five directions. Firing rates increased significantly with horizontal isometric force from 400 to 800gwt. Firing rates also changed significantly (p<0.01) with direction with CL, CL-P and P having comparable firing rates (13.3, 12.6 and 12.6impulses/s, respectively) which were significantly higher than IL-P. The similarity of these data to previous IHLP data, provide additional support for the hypothesis that the SHLP and the IHLP should be regarded as two parts of one muscle.