Association of masticatory muscle activity with sleep arousal and other concomitant movements during sleep.

OBJECTIVE: This study aims to verify the associations among sleep bruxism (SB), sleep arousal (SA) and concurrent body movements. MATERIAL AND METHODS: Subjects underwent a standard overnight polysomnography test and audio-video recordings. Sleep quality was evaluated according to the Rechtschaffen and Kales criteria, while SA was determined as per the American Sleep Disorders Association criteria. Analyses were performed by an external institution after masking of the subjects' information. SB was assessed based on the presence/absence of rhythmic masticatory muscle activity (RMMA) episodes, which were identified by using electromyography of the masseter muscle. The observed simultaneous movements included lower leg movement (LLM), swallowing, face scratching, head movement, body movement, eye blinking, coughing, licking, sighing, body scratching, lip sucking, somniloquy and yawning. The LLM was determined visually, as well as through an increase in the tibialis electromyogram signal. Other movements were visually assessed using audio-video recordings. The incidences of all the simultaneous movements were compared between RMMA with intercurrent SA (SAwRMMA; RMMA episode derived from a masseter electromyogram showing more than 10% of maximum voluntary contraction) and SA without RMMA (SAw/oRMMA). RESULTS: Fourteen subjects were included in this study (females/males: 4/10, mean age: 31.5 ± 5.7 years). Among these, LLM, swallowing, body movement, licking, body scratching and lip sucking were frequently observed in SAwRMMA episodes than in SAw/oRMMA episodes, significantly. However, the non-specific simultaneous movements were higher observed in SAw/oRMMA episodes than that in SAwRMMA. CONCLUSION: Our results suggest that SB is concurrently activated with LLM in relation to arousal.

Loss of oral self-care ability results in a higher risk of pneumonia in older inpatients: A prospective cohort study in a Japanese rural hospital.

OBJECTIVES: To identify significant risk factors associated with incidence of mortality and pneumonia in whole-community-based older inpatients resident in Japanese rural region. METHODS: Patients older than 65 years admitted between 1 April and 15 April 2010 to a core hospital located in a rural region were exhaustively recruited, and incidence of mortality and pneumonia during the 32-month follow-up period were evaluated. Independent variables at baseline measurement included age, gender, body mass index, Charlson comorbidity index, functional dependency, oral self-care ability index, number of remaining teeth, hyposalivation and nutritional status. Dependent variables were incidence of mortality and pneumonia. Survival and non-pneumonia curves were drawn using Kaplan-Meier analysis. Cox proportional hazards analysis was performed to identify the risk factors related to incidence of mortality and pneumonia. RESULTS: The survival rate of 46 patients (male/female: 11/35; mean age: 83.8 ± 6.8 years) was 52.1%, and the incidence of pneumonia was 60.9%. Malnutrition and gender (male) were identified as significant risk factors for mortality (odds ratio [OR]: 8.18 and 4.90; 95% confidence interval [CI]: 1.77-37.3 and 1.50-16.0; P < 0.01 and <0.01, respectively). Loss of oral self-care ability and gender (male) were identified as significant risk factors for incidence of pneumonia (OR: 8.97 and 4.58; 95% CI: 1.70-47.4 and 1.50-14.0; P = 0.01 and <0.01, respectively). CONCLUSIONS: Malnutrition and loss of oral self-care ability were significant risk factors for incidence of mortality and pneumonia, respectively. In response, supplying nutrition with appropriate diet and personalised oral care might contribute to reduction in mortality and prevention of pneumonia.

Sleep bruxism frequency and platelet serotonin transporter activities in young adult subjects.

PURPOSE: To evaluate correlations between serotonin transporter (SERT) uptake ability in human peripheral platelets and sleep bruxism (SB) frequency. METHODS: Subjects were consecutively recruited from sixth-year students at Okayama University Dental School. Subjects were excluded if they (1) were receiving orthodontic treatment, (2) had a dermatological disease, (3) had taken an antidepressant within 6 months, or (4) had used an oral appliance within 6 months. SB frequency was determined as the summary score of three consecutive night assessments using a self-contained electromyography detector/analyzer in their home. Fasting peripheral venous blood samples were collected in the morning following the final SB assessment. SERT amount and platelet number were quantified via an ELISA assay and flow cytometry, respectively. Functional SERT characterization, 5-hydroxytryptamine (5-HT) uptake, maximum velocity (V max), and an affinity constant (K m ) were assessed with a [(3)H] 5-HT uptake assay. The correlations between these variables and SB level were evaluated. RESULTS: Among 50 eligible subjects (26 males, mean age 25.4 ± 2.41 years), 7 were excluded because of venipuncture failure, smoking, and alcohol intake during the experimental period. A small but significant negative correlation between SB level and [(3)H] 5-HT uptake was observed (Spearman's correlation R (2) = 0.063, p = 0.04). However, there were no significant correlations between SB level and total platelet amount, SERT, V max, and K m values (p = 0.08, 0.12, 0.71, and 0.68, respectively). CONCLUSIONS: Platelet serotonin uptake is significantly associated with SB frequency, yet only explains a small amount of SB variability.

Comparison of platelet serotonin transporter activity in subjects with severe sleep bruxism and control.

PURPOSE: The aim of this study was to evaluate the correlation between sleep bruxism (SB) frequency and serotonin transporter (SERT)-driven serotonin (5-HT)-uptake in platelets. METHODS: Subjects were dental trainee residents and faculty members of Okayama University Hospital who were aware of having severe or no SB. SB frequency was assessed for 3-consecutive nights by a self-contained electromyographic detector/analyzer, which indicated individual SB levels as one of four grades (score 0, 1, 2 and 3). Subjects were classified as normal control (NC) when SB scores indicated only 0 or 1 during the 3 nights, or as severe SB for scores 2 or 3. Those subjects whose scores fluctuated from 0 to 3 during the 3 nights were omitted from further analysis. Fasting peripheral venous blood samples were collected in the morning following the final SB assessment. Amounts of SERTs proteins collected from peripheral platelets were quantified using ELISA, and SERTs transport activity was assessed by uptake assay using [3H]-5-HT. RESULTS: Thirteen severe SB subjects and 7 NC subjects were eligible. Gender distribution, mean age, 5-HT concentration and total amounts of SERT protein in platelets showed no significant differences between NC and severe SB (p=0.85: Chi-squared test; p=0.64, 0.26, 0.46: t-test). However, [3H]-5-HT uptake by platelets was significantly greater in NC compared to severe SB subjects (12.79±1.97, 8.27±1.91 fmol/10(5) platelets/min, p<0.001, t-test). CONCLUSION: The results of this pilot study suggest a possible correlation between peripheral platelet serotonin transporter uptake ability and SB severity.

A problem-based learning tutorial for dental students regarding elderly residents in a nursing home in Japan.

This educational trial was an eight-day problem-based learning (PBL) course for fourth-year predoctoral students at Okayama University's dental school who interviewed elderly residents living in a nursing home. The purpose of this PBL course was to introduce geriatric dentistry to the students by allowing them, independently, to discover the clinical problems of elderly patients as well as the solutions. The sixty-five students were divided into nine small groups and received patient information (age, gender, degree of care needed, medical history, food type, medications, and oral condition) in datasheets before visiting the nursing home. Each group of students directly interviewed one patient and the caregivers and identified the patient's medical, psychological, and social problems. After the interview, the students participated in a PBL tutorial to delineate a management approach for the patient's problems. To measure the efficacy of this program, the students completed a questionnaire before and after the course regarding their level of understanding of and attitudes toward geriatric dentistry, clinical research, and self-study. The results showed that student's perceptions of their knowledge about and attitudes toward oral health care for the elderly significantly increased after the PBL course, which suggests that such tutorials should be an option for dental curricula.

Curcumin and genistein additively potentiate G551D-CFTR.

BACKGROUND: The G551D mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) is a common cause of cystic fibrosis (CF). G551D-CFTR is characterized by an extremely low open probability despite its normal trafficking to the plasma membrane. Numerous small molecules have been shown to increase the activity of G551D-CFTR presumably by binding to the CFTR protein. METHODS: We investigated the effect of curcumin, genistein and their combined application on G551D-CFTR activity using the patch clamp technique. RESULTS: Curcumin increased G551D-CFTR whole-cell and single-channel currents less than genistein did at their maximally effective concentrations. However, curcumin further increased the channel activity of G551D-CFTR that had been already maximally potentiated by genistein, up to ~50% of the WT-CFTR level. In addition, the combined application of genistein and curcumin over a lower concentration range synergistically rescued the gating defect of G551D-CFTR. CONCLUSIONS: The additive effects between curcumin and genistein not only support the hypothesis that multiple mechanisms are involved in the action of CFTR potentiators, but also pose pharmaceutical implications in the development of drugs for CF pharmacotherapy.

Potentiation of disease-associated cystic fibrosis transmembrane conductance regulator mutants by hydrolyzable ATP analogs.

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel belonging to the ATP-binding cassette transporter superfamily. CFTR is gated by ATP binding and hydrolysis at its two nucleotide-binding domains (NBDs), which dimerize in the presence of ATP to form two ATP-binding pockets (ABP1 and ABP2). Mutations reducing the activity of CFTR result in the genetic disease cystic fibrosis. Two of the most common mutations causing a severe phenotype are G551D and DeltaF508. Previously we found that the ATP analog N(6)-(2-phenylethyl)-ATP (P-ATP) potentiates the activity of G551D by approximately 7-fold. Here we show that 2'-deoxy-ATP (dATP), but not 3'-deoxy-ATP, increases the activity of G551D-CFTR by approximately 8-fold. We custom synthesized N(6)-(2-phenylethyl)-2'-deoxy-ATP (P-dATP), an analog combining the chemical modifications in dATP and P-ATP. This new analog enhances G551D current by 36.2 +/- 5.4-fold suggesting an independent but energetically additive action of these two different chemical modifications. We show that P-dATP binds to ABP1 to potentiate the activity of G551D, and mutations in both sides of ABP1 (W401G and S1347G) decrease its potentiation effect, suggesting that the action of P-dATP takes place at the interface of both NBDs. Interestingly, P-dATP completely rectified the gating abnormality of DeltaF508-CFTR by increasing its activity by 19.5 +/- 3.8-fold through binding to both ABPs. This result highlights the severity of the gating defect associated with DeltaF508, the most prevalent disease-associated mutation. The new analog P-dATP can be not only an invaluable tool to study CFTR gating, but it can also serve as a proof-of-principle that, by combining elements that potentiate the channel activity independently, the increase in chloride transport necessary to reach a therapeutic target is attainable.

Does the sedative agent, JM-1232(-) cause QT prolongation with subsequent torsades de pointes?

AIMS: JM-1232(-) ((-)-3-[2-(4-methyl-1-piperazinyl)-2-oxoethyl]-2-phenyl-3,5,6,7-tetrahydrocyclopenta[f] isoindole-1(2H)-one) is a novel isoindoline compound that acts on benzodiazepine receptors. Clinical trials are being conducted to assess its potential clinical use as an intravenous anesthetic or sedative agent. In the present study, we investigated the possibility of QT prolongation caused by JM-1232(-). MAIN METHODS: We examined telemetry electrocardiogram (ECG) recordings from unrestrained guinea pigs after intravenous administration of 1, 10, 25 or 50mg/kg of JM-1232(-). We also examined in situ measurements of monophasic action potential duration at 30 and 90% of repolarization (MAP(30) and MAP(90), respectively) and MAP triangulation (MAP(90-30)) from guinea pig hearts that were perfused on a Langendorff apparatus with 0, 0.1, 1, 5, 10 and 20 microg/ml of JM-1232(-). The telemetry ECG recordings showed QTc prolongation 20 min after administration of JM-1232(-) at 50mg/kg. KEY FINDINGS: In Langendorff-perfused hearts, MAP(30), which indicates Ca(2+) current, was significantly shortened after perfusion with JM-1232(-) at 10 and 20 microg/ml. MAP(90), which indicates K(+) current, was significantly prolonged after perfusion with JM-1232(-) at 20 microg/ml; therefore, this prolongation was attributed to a decreased heart rate. MAP triangulation (MAP(90-30)) was significantly prolonged after perfusion with JM-1232(-) at 5, 10 and 20 microg/ml; however, this prolongation was attributed to the shortened MAP(30), suggesting a possible inhibition of Ca(2+) influx. SIGNIFICANCE: High-dose (more than 50 times the hypnotic dose) JM-1232(-) treatment associated with a high plasma concentration of the drug is unlikely to cause QT prolongation with subsequent torsades de pointes.

[Availability of drug information on bioequivalence of generic products--findings of graduate interns at a university pharmacy].

Access to drug information (DI) needed to evaluate generic product bioequivalence was studied to identify problems with the current status of DI availability and encourage proper use of DI. Ten items were chosen from among the stock of branded products at the University Pharmacy, and five corresponding generics were selected for each item. Conditions of access to information on pharmacokinetic tests and dissolution tests were rated and the assigned ratings compared. In the case of pharmacokinetic parameters obtainable from makers of generic drugs, we also performed Welch's t-test to compare the difference between values reported for branded and generic products. From the standpoint of individual tests, the pharmacokinetic tests yielded higher scores on the whole than did the dissolution tests, and low scores were obtained for the half-life of blood drug concentration (T1/2). We observed a tendency for the adequacy of information to depend more upon the drug item itself than upon the nature of the test. The percentage of tests allowing for comparison with branded products varied from 0%-75% (average 49%). Parameter by parameter, the range of variation was from 35% of Tmax to 63% of Cmax. Factors precluding comparison included insufficient data on branded products, mismatch in assayed chemical species between branded and generic, mismatch between final sampling time in AUC(t) measurement, dosage inconsistency, and insufficient data on generic products. DI should be provided in a manner that facilitates comparison of information supplied by generic drug makers with data released by makers of branded products.