Rosiglitazone is a thiazolidinedione-class antidiabetic drug that reduces blood glucose and glycated hemoglobin levels. We here investigated the interaction of rosiglitazone with Kv3.1 expressed in Chinese hamster ovary cells using the wholecell patch-clamp technique. Rosiglitazone rapidly and reversibly inhibited Kv3.1 currents in a concentration-dependent manner (IC 50 = 29.8 µM) and accelerated the decay of Kv3.1 currents without modifying the activation kinetics. The rosiglitazonemediated inhibition of Kv3.1 channels increased steeply in a sigmoidal pattern over the voltage range of –20 to +30 mV, whereas it was voltage-independent in the voltage range above +30 mV, where the channels were fully activated. The deactivation of Kv3.1 current, measured along with tail currents, was also slowed by the drug. In addition, the steady-state inactivation curve of Kv3.1 by rosiglitazone shifts to a negative potential without significant change in the slope value. All the results with the use dependence of the rosiglitazone-mediated blockade suggest that rosiglitazone acts on Kv3.1 channels as an open channel blocker.

Objective: This study examined whether the changes in reimbursement coverage of brain magnetic resonance image (MRI) affected practice for patients who visited the emergency department with dizziness as the chief complaint. Methods: Among the 5,423 patients who visited the emergency department for dizziness in 2017, 2019, and 2021, 4,497 patients were included in the study retrospectively and investigated by brain diffusion-weighted MRI and the presence of cerebral infarction on brain diffusion-weighted MRI. This study examined whether there was a significant difference before and after the change. Results: In 2017, 2019, and 2021, 1,489, 1,570, and 1,438 patients with dizziness visited the emergency department, respectively. The number of patients who underwent a brain MRI scan gradually increased from 237 (15.9%) in 2017 to 628 (40.0%) in 2019 and 948 (65.9%) in 2021 (P<0.001). The number of positive findings on brain MRI scan increased gradually from 30 patients (2.0%) in 2017 to 47 patients (3.0%) in 2019 and 53 patients (3.7%) in 2021 (P=0.025). The ratio of positive findings of brain MRI scans to the number of patients who underwent brain MRI scans decreased gradually to 12.7% in 2017, 7.5% in 2019, and 5.6% in 2021 (P=0.001). Conclusion The changes in the reimbursement coverage of brain MRI affect the number of brain MRI scans and the detection of cerebral infarction.

An antidiabetic drug, rosiglitazone is a member of the drug class of thiazolidinedione. Although restrictions on use due to the possibility of heart toxicity have been removed, it is still a drug that is concerned about side effects on the heart. We here examined, using Chinese hamster ovary cells, the action of rosiglitazone on Kv1.5 channels, which is a major determinant of the duration of cardiac action potential. Rosiglitazone rapidly and reversibly inhibited Kv1.5 currents in a concentrationdependent manner (IC 50 = 18.9 µM) and accelerated the decay of Kv1.5 currents without modifying the activation kinetics. In addition, the deactivation of Kv1.5 current, assayed with tail current, was slowed by the drug. All of the results as well as the usedependence of the rosiglitazone-mediated blockade indicate that rosiglitazone acts on Kv1.5 channels as an open channel blocker. This study suggests that the cardiac side effects of rosiglitazone might be mediated in part by suppression of Kv1.5 channels, and therefore, raises a concern of using the drug for diabetic therapeutics.

In patients with epilepsy, depression is a common comorbidity but difficult to be treated because many antidepressants cause pro-convulsive effects. Thus, it is important to identify the risk of seizures associated with antidepressants. To determine whether paroxetine, a very potent selective serotonin reuptake inhibitor (SSRI), interacts with ion channels that modulate neuronal excitability, we examined the effects of paroxetine on Kv3.1 potassium channels, which contribute to highfrequency firing of interneurons, using the whole-cell patch-clamp technique. Kv3.1 channels were cloned from rat neurons and expressed in Chinese hamster ovary cells. Paroxetine reversibly reduced the amplitude of Kv3.1 current, with an IC₅₀ value of 9.43 µM and a Hill coefficient of 1.43, and also accelerated the decay of Kv3.1 current. The paroxetine-induced inhibition of Kv3.1 channels was voltage-dependent even when the channels were fully open. The binding (k₊₁) and unbinding (k₋₁) rate constants for the paroxetine effect were 4.5 µM⁻¹s⁻¹ and 35.8 s⁻¹, respectively, yielding a calculated K(D) value of 7.9 µM. The analyses of Kv3.1 tail current indicated that paroxetine did not affect ion selectivity and slowed its deactivation time course, resulting in a tail crossover phenomenon. Paroxetine inhibited Kv3.1 channels in a usedependent manner. Taken together, these results suggest that paroxetine blocks the open state of Kv3.1 channels. Given the role of Kv3.1 in fast spiking of interneurons, our data imply that the blockade of Kv3.1 by paroxetine might elevate epileptic activity of neural networks by interfering with repetitive firing of inhibitory neurons.
Animals ; Antidepressive Agents ; Clone Cells ; Comorbidity ; Cricetinae ; Cricetulus ; Depression ; Epilepsy ; Female ; Fires ; Humans ; Interneurons ; Ion Channels ; Neurons ; Ovary ; Paroxetine* ; Patch-Clamp Techniques ; Rats ; Seizures ; Serotonin ; Shaw Potassium Channels* ; Tail

BACKGROUND: Mandibular contouring surgery to produce a more slender and small face has become popular, especially in East Asia. Narrowing genioplasty should be simultaneously performed with mandibular angle resection to achieve satisfactory results. In Korea, T-genioplasty has been frequently performed for chin narrowing. The authors developed a new, safe, and reliable method, termed M-genioplasty, that can provide a more slender and attractive lower face. METHODS: From June 2013 to December 2017, 36 patients underwent M-genioplasty with mandibular angle resection for lower facial contouring. Horizontal and vertical osteotomies were performed obliquely. The resected bone segments were wedge-shaped. The remaining two bone segments were rotated and approximated centrally. The lateral mandible bony stepoff was trimmed off for mandibular angle resection. RESULTS: In all patients, the facial contour sufficiently improved, and most patients were satisfied with the outcome. No severe complications took place during postoperative follow-up. CONCLUSIONS: M-genioplasty can provide more mandibular angle resection and can create a more acute chin angle without bone resorption than other methods, including T-genioplasty. M-genioplasty with mandibular angle resection is a safer, more accurate, and more reliable method for lower facial contouring.
Bone Resorption ; Chin ; Far East ; Follow-Up Studies ; Genioplasty ; Humans ; Korea ; Mandible ; Methods* ; Osteotomy

OBJECTIVES: The purpose of this study was to explore the effects of injection laryngoplasty (IL) with hyaluronic acid in patients with vocal fold paralysis (VFP). METHODS: A total of 50 patients with VFP participated in this study. Pre- and post-IL assessments were performed, which included analyzing the sustained vowel /a/ phonation, and the patient reading 1 Korean sentence from the “Walk” passage that comprised 25 syllables in 10 words. To investigate the effect of IL on vocal fold function, acoustic analysis (acoustic voice quality index, cepstral peak prominence, maximum phonation time, speaking fundamental frequency) was conducted and auditory-perceptual (grade and overall severity), visual judgment (gap), and self-questionnaire (voice handicap index-10) assessments were performed. RESULTS: The patients with VFP showed statistically significant differences between pre-and post-IL assessments for acoustic and auditory-perception, visual judgment, and self-questionnaire assessments. CONCLUSION: The patients with VFP showed positive change in vocal fold function between pre- and post-IL measurements. The findings showed that IL with hyaluronic acid is an effective method to improve vocal fold function in patients with VFP.
Acoustics ; Humans ; Hyaluronic Acid* ; Judgment ; Laryngoplasty* ; Methods ; Paralysis* ; Phonation ; Vocal Cords* ; Voice Quality

BACKGROUND AND OBJECTIVES: The purpose of this study was to investigate the criterion-related concurrent validity of two standardized auditory-perceptual assessments and the Acoustic Voice Quality Index (AVQI) for measuring dysphonia severity in patients with vocal cord paralysis (VCP). MATERIALS AND METHODS: Total 210 patients with VCP and 236 normal voice subjects were asked to sustain the vowel [a:] and to read aloud the Korean text “Walk”. A 2 second mid-vowel portion of the sustained vowel and two sentences (with 26 syllables) were recorded. And then voice samples were edited, concatenated, and analyzed according to Praat script. Two standardized auditory-perceptual assessment (GRBAS and CAPE-V) were performed by three raters. RESULTS: The VCP group showed higher AVQI, Grade (G) and Overall Severity (OS) values than normal voice group. And the correlation among AVQI, G, and OS ranged from 0.904 to 0.926. In ROC curve analysis, cutoff values of AVQI, G, and OS were < 3.79, < 0.00, and < 30.00, respectively, and the AUC of each analysis was over .89. CONCLUSION: AVQI and auditory evaluation can improve the early screening ability of VCP voice and help to establish effective diagnosis and treatment plan for VCP-related dysphonia.
Acoustics* ; Area Under Curve ; Diagnosis ; Dysphonia* ; Humans ; Mass Screening ; ROC Curve ; Vocal Cord Paralysis* ; Vocal Cords* ; Voice ; Voice Quality

Sertraline, a selective serotonin reuptake inhibitor (SSRI), has been reported to lead to cardiac toxicity even at therapeutic doses including sudden cardiac death and ventricular arrhythmia. And in a SSRI-independent manner, sertraline has been known to inhibit various voltage-dependent channels, which play an important role in regulation of cardiovascular system. In the present study, we investigated the action of sertraline on Kv1.5, which is one of cardiac ion channels. The eff ect of sertraline on the cloned neuronal rat Kv1.5 channels stably expressed in Chinese hamster ovary cells was investigated using the whole-cell patch-clamp technique. Sertraline reduced Kv1.5 whole-cell currents in a reversible concentration-dependent manner, with an IC50 value and a Hill coefficient of 0.71 microM and 1.29, respectively. Sertraline accelerated the decay rate of inactivation of Kv1.5 currents without modifying the kinetics of current activation. The inhibition increased steeply between -20 and 0 mV, which corresponded with the voltage range for channel opening. In the voltage range positive to +10 mV, inhibition displayed a weak voltage dependence, consistent with an electrical distance delta of 0.16. Sertraline slowed the deactivation time course, resulting in a tail crossover phenomenon when the tail currents, recorded in the presence and absence of sertraline, were superimposed. Inhibition of Kv1.5 by sertraline was use-dependent. The present results suggest that sertraline acts on Kv1.5 currents as an open-channel blocker.
Animals ; Arrhythmias, Cardiac ; Cardiovascular System ; Clone Cells ; Cricetinae ; Cricetulus ; Death, Sudden, Cardiac ; Female ; Inhibitory Concentration 50 ; Ion Channels ; Kinetics ; Neurons ; Ovary ; Patch-Clamp Techniques ; Rats ; Serotonin ; Sertraline* ; Tail

Paroxetine, a selective serotonin reuptake inhibitor (SSRI), has been reported to have an effect on several ion channels including human ether-a-go-go-related gene in a SSRI-independent manner. These results suggest that paroxetine may cause side effects on cardiac system. In this study, we investigated the effect of paroxetine on Kv1.5, which is one of cardiac ion channels. The action of paroxetine on the cloned neuronal rat Kv1.5 channels stably expressed in Chinese hamster ovary cells was investigated using the whole-cell patch-clamp technique. Paroxetine reduced Kv1.5 whole-cell currents in a reversible concentration-dependent manner, with an IC50 value and a Hill coefficient of 4.11 microM and 0.98, respectively. Paroxetine accelerated the decay rate of inactivation of Kv1.5 currents without modifying the kinetics of current activation. The inhibition increased steeply between -30 and 0 mV, which corresponded with the voltage range for channel opening. In the voltage range positive to 0 mV, inhibition displayed a weak voltage dependence, consistent with an electrical distance delta of 0.32. The binding (k(+1)) and unbinding (k(-1)) rate constants for paroxetine-induced block of Kv1.5 were 4.9 microM(-1)s(-1) and 16.1 s-1, respectively. The theoretical K(D) value derived by k(-1)/k(+1) yielded 3.3 microM. Paroxetine slowed the deactivation time course, resulting in a tail crossover phenomenon when the tail currents, recorded in the presence and absence of paroxetine, were superimposed. Inhibition of Kv1.5 by paroxetine was use-dependent. The present results suggest that paroxetine acts on Kv1.5 currents as an open-channel blocker.
Animals ; Clone Cells ; Cricetinae ; Cricetulus ; Female ; Humans ; Inhibitory Concentration 50 ; Ion Channels ; Kinetics ; Neurons ; Ovary ; Paroxetine* ; Patch-Clamp Techniques ; Rats ; Serotonin ; Tail