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1.
Spec Care Dentist ; 2024 May 02.
Article En | MEDLINE | ID: mdl-38698537

AIMS: Potocki-Lupski syndrome (PTLS), which is caused by the partial duplication of the short arm of autosome 17, is characterized by feeding difficulties associated with muscle hypotonia and dysphagia in infancy, followed by growth retardation and low body weight in later stages. Speech and motor developmental disorders are observed in childhood, accompanied by autism spectrum disorders in several cases. Other disorders include dental and skeletal abnormalities, and associated sleep apnea. Herein, we describe the first case of dental evaluation and treatment under intravenous sedation in a patient with PTLS. METHODS: A 13-year-old boy with PTLS and intellectual disability was referred for the treatment of dental caries. Routine intraoral examination and dental treatment were not feasible. As the patient had no muscle hypotonia, dysphagia, or severe growth delay, intraoral examination and dental treatment were successfully performed under intravenous sedation. No incidence of intraoral airway obstruction or aspiration was reported. The patient was followed-up post-operatively. CONCLUSION: PTLS, a newly identified syndrome, is associated with cardiovascular abnormalities, dysphagia, failure to thrive, and sleep apnea, which are potential risk factors for sedation. This case report highlights the importance of facial and oral findings in determining the risks of difficulties in airway management.

2.
J Dent Sci ; 19(2): 878-884, 2024 Apr.
Article En | MEDLINE | ID: mdl-38618079

Background/purpose: The possibility of triggering the trigeminocardiac reflex (TCR) during oral surgery is considerably lower than that during other surgeries. A reduced heart rate (HR) of ≥20% from baseline is usually considered a diagnostical criterion for the TCR. Our automated anesthesia charting system often revealed cases of slight transient HR decrease during sedation. We aimed to explore its incidence and associated factors during local anesthesia administration under intravenous sedation. Materials and methods: This study analyzed the data of 2636 cases that received infiltration anesthesia under intravenous sedation from 2008 to 2010 and had vital signs recorded using an automated anesthesia charting system. Especially, data concerning the average HR before anesthesia and the minimum HR between the initiation and end of anesthesia from anesthetic records were extracted. Moreover, data regarding patients' medical history and unusual reactions during dental treatment were collected. Multivariate logistic regression analysis was performed to identify factors associated with transient bradycardia (TB). Results: TB occurred in 472 patients (17.9%); no patient developed hypotension or any associated symptoms, suggesting that intravenous sedation was effective in stabilizing vital signs. The factors associated with TB were younger age, gag reflex, and allergy to local anesthetics. There were no differences in sex, patient history, or dose of sedatives between patients with TB and those without TB. Conclusion: The incidence of TB during infiltration anesthesia under sedation was found to be higher than that previously reported. Additionally, young age and gag reflex were identified as factors associated with bradycardia development.

3.
Invest Ophthalmol Vis Sci ; 64(15): 2, 2023 Dec 01.
Article En | MEDLINE | ID: mdl-38038618

Purpose: Vitreoretinal lymphoma is a high-grade malignant non-Hodgkin lymphoma with poor prognosis. The objective of this study was to elucidate the proteome profile of the vitreous in patients with vitreoretinal lymphoma (VRL), aiming to advance understanding of the pathophysiology of VRL. Methods: Comprehensive proteomic analyses of vitreous humor using liquid chromatography with tandem mass spectrometry were performed for 10 patients with VRL, 10 control patients with idiopathic epiretinal membrane or macular hole, and 10 patients with ocular sarcoidosis. Differentially expressed proteins (DEPs) were identified by comparing VRL with controls and sarcoidosis, and functional pathway analysis was performed. Finally, vitreous concentrations of representative DEPs that were significantly upregulated in proteomics study were measured by ELISA using a separate cohort. Results: In total, 1594 proteins were identified in the vitreous humor of VRL, control, and sarcoidosis samples. Also, 282 DEPs were detected in VRL, 249 upregulated and 33 downregulated, compared with controls. Enrichment pathway analysis showed alterations in proteasome-related pathways. Compared to controls and sarcoidosis, 14 DEPs in VRL showed significant upregulation. In the validation study, ELISA confirmed significantly higher vitreous concentrations of PSAT1, YWHAG, and 20S/26S proteasome complex in VRL compared with controls and sarcoidosis. Among the upregulated DEPs, vitreous PITHD1 and NCSTN concentrations correlated positively with vitreous IL-10 concentrations. Conclusions: This study highlights aberrations in protein expression pattern in the vitreous of patients with VRL. The DEPs identified in this study may play pivotal roles in VRL pathogenesis, providing insights to enhance understanding of VRL pathophysiology and contribute to the development of VRL biomarkers.


Lymphoma, Non-Hodgkin , Retinal Neoplasms , Sarcoidosis , Humans , Vitreous Body/metabolism , Retinal Neoplasms/pathology , Proteomics , Lymphoma, Non-Hodgkin/metabolism , Lymphoma, Non-Hodgkin/pathology , Sarcoidosis/metabolism , Sarcoidosis/pathology , Proteins/metabolism , 14-3-3 Proteins/analysis , 14-3-3 Proteins/metabolism
4.
Anesth Prog ; 70(1): 25-30, 2023 03 01.
Article En | MEDLINE | ID: mdl-36995959

Sudden cardiac arrest (SCA) is an uncommon event in dental practice; however, the frequency of dentists encountering SCA and other major medical emergencies is increasing. We report the successful resuscitation of a patient who developed SCA while awaiting examination and treatment at a dental hospital. The emergency response team was called upon, and cardiopulmonary resuscitation/basic life support (CPR/BLS), including chest compression and mask ventilation, was promptly initiated. An automated external defibrillator was used, which indicated that the patient's cardiac rhythm was unsuitable for electrical defibrillation. The patient returned to spontaneous circulation after 3 cycles of CPR and intravenous epinephrine. The knowledge and skill levels of dentists regarding resuscitation under emergency circumstances should be addressed. Emergency response systems must be well established, and CPR/BLS knowledge and training should be updated regularly, including optimal management of both shockable and nonshockable rhythms.


Cardiopulmonary Resuscitation , Emergency Medical Services , Heart Arrest , Humans , Heart Arrest/diagnosis , Heart Arrest/etiology , Heart Arrest/therapy , Death, Sudden, Cardiac/etiology , Death, Sudden, Cardiac/prevention & control , Defibrillators
5.
J Pers Med ; 13(3)2023 Mar 01.
Article En | MEDLINE | ID: mdl-36983643

Implant surgery is a lengthy dental procedure, and sedation is often used to reduce discomfort. The effectiveness of sedation has traditionally been evaluated in terms of patient and surgeon satisfaction, but the most important goal is not to induce a deep sleep in the patient, but rather to ensure that the surgery is performed safely and as planned. Additionally, adequate pain control is a necessary requirement for patient and surgeon satisfaction. Most patients undergoing implant surgery are middle-aged or older, and a relatively large number of them have cardiovascular disease. Infiltration anesthesia using articaine or lidocaine in combination with adrenaline is widely used, but its use in patients with cardiovascular disease is limited because of adrenaline's effects on the cardiovascular system. The use of long-acting local anesthetics and the potential efficacy of ultrasound-guided jaw nerve block have been investigated to enhance analgesia without resorting to adrenaline. Midazolam and propofol are usually used for sedation, but dexmedetomidine, which causes less respiratory depression, and the ultrashort-acting benzodiazepine remimazolam are emerging as potential alternatives. Monitoring of anesthetic depth using electroencephalography is effective in maintaining a constant level of sedation. In addition, sedation promotes the stabilization of heart rate and blood pressure, reducing the risks associated with adrenaline and allowing for safer management.

6.
Anesth Prog ; 69(4): 37-39, 2022 12 01.
Article En | MEDLINE | ID: mdl-36534773

Prior to a scheduled operation for a 45-year-old male patient with tongue cancer, a tracheotomy performed under intravenous sedation to prevent asphyxia due to extensive bleeding resulted in pneumomediastinum and subcutaneous emphysema. The planned operations were postponed until reduction of the pneumomediastinum was confirmed. During operation, airway pressure was kept low to prevent tension pneumomediastinum along with a sufficient depth of anesthesia, controlled analgesia, and continuous administration of muscle relaxants. Postoperatively, sedation was used to avoid stress and complications with the vascular anastomosis site. In this case, air leakage into the soft tissues was one of the possible causes of the event associated with increased airway pressure. Although the incidence of such complications is relatively low, caution should be exercised after tracheostomy.


Mediastinal Emphysema , Subcutaneous Emphysema , Tongue Neoplasms , Male , Humans , Middle Aged , Tracheostomy/adverse effects , Tongue Neoplasms/complications , Tongue Neoplasms/surgery , Subcutaneous Emphysema/complications , Subcutaneous Emphysema/surgery
7.
J Clin Med ; 11(14)2022 Jul 07.
Article En | MEDLINE | ID: mdl-35887725

Pulse wave transit time (PWTT) is the time difference between the occurrence of an R-wave on an electrocardiogram and the detection of pulsatile signals on a pulse oximeter, which reflects changes in blood pressure (BP) corresponding to the vessel wall compliance. However, the factors affecting PWTT variability have not been determined. Thus, we investigated the BP changes associated with variations in PWTT and identified the clinical characteristics associated with these variations. Data related to 605 cases of dental procedures performed under intravenous conscious sedation from April 2020 to November 2021 were collected, and 485 cases were enrolled. Heart rate, systolic blood pressure before and after local anesthesia (LA) administration, and crest and trough PWTT waves during LA administration were recorded. Thereafter, PWTT variability was calculated; cases were divided into two groups: large PWTT variability (LPV, n = 357) and small PWTT variability (SPV, n = 128). The index of large PWTT variability could not detect changes in BP. Logistic regression analysis revealed that factors, such as LA use, age, hypertension, and dental treatment phobia were associated with PWTT variability. The use of epinephrine more than 36.25 µg in each LA resulted in PWTT variability of more than 15 ms.

8.
J Clin Med ; 11(13)2022 Jun 22.
Article En | MEDLINE | ID: mdl-35806888

Ocular sarcoidosis is an inflammatory disease that manifests as uveitis, and is often difficult to distinguish from other forms of uveitis based on nonspecific findings alone. Comprehensive proteomic analyses of vitreous humor using LC-MS/MS were performed in each patient with ocular sarcoidosis, vitreoretinal lymphoma (VRL), and controls with epiretinal membrane or macular hole. Differential expression proteins (DEPs) were identified by comparing with VRL and controls, and functional pathway analysis was performed. The candidate biomarker proteins for ocular sarcoidosis were validated using enzyme-linked immunosorbent assay. A total of 1590 proteins were identified in all samples. Of these, 290 and 174 DEPs were detected in vitreous of ocular sarcoidosis compared with controls and VRL, respectively. Enrichment pathway analysis revealed that pathways related to the immune system were most upregulated. Validation of two candidate biomarkers for ocular sarcoidosis, neutrophil gelatinase-associated lipocalin (NGAL) and junctional adhesion molecules B (JAMB), confirmed upregulated NGAL and JAMB protein expressions in ocular sarcoidosis compared to controls and VRL. The results of this study revealed that altered vitreous protein expression levels may discriminate ocular sarcoidosis from other uveitis diseases. Vitreous NGAL and JAMB are potential biomarkers and may serve as an auxiliary tool for the diagnosis of ocular sarcoidosis.

9.
Invest Ophthalmol Vis Sci ; 62(1): 15, 2021 01 04.
Article En | MEDLINE | ID: mdl-33439228

Purpose: To identify tissue metabolomic profiles in biopsy specimens with IgG4-related ophthalmic disease (IgG4-ROD) and mucosa-associated lymphoid tissue (MALT) lymphoma and investigate their potential implication in the disease pathogenesis and biomarkers. Methods: We conducted a comprehensive analysis of the metabolomes and lipidomes of biopsy-proven IgG4-ROD (n = 22) and orbital MALT lymphoma (n = 21) specimens and matched adjacent microscopically normal adipose tissues using liquid chromatography time-of-flight mass spectrometry. The altered metabolomic profiles were visualized by heat map and principal component analysis. Metabolic pathway analysis was performed by Metabo Analyst 4.0 using differentially expressed metabolites. The diagnostic performance of the metabolic markers was evaluated using receiver operating characteristic curves. Machine learning algorithms were implemented by random forest using the R environment. Finally, an independent set of 18 IgG4-ROD and 17 orbital MALT lymphoma specimens were used to validate the identified biomarkers. Results: The principal component analysis showed a significant difference of both IgG4-ROD and orbital MALT lymphoma for biopsy specimens and controls. Interestingly, lesions in IgG4-ROD were uniquely enriched in arachidonic metabolism, whereas those in orbital MALT lymphoma were enriched in tricarboxylic acid cycle metabolism. We identified spermine as the best discriminator between IgG4-ROD and orbital MALT lymphoma, and the area under the receiver operating characteristic curve of the spermine to discriminate between the two diseases was 0.89 (95% confidence interval, 0.803-0.984). A random forest model incorporating a panel of five metabolites showed a high area under the receiver operating characteristic curve value of 0.983 (95% confidence interval, 0.981-0.984). The results of validation revealed that four tissue metabolites: N1,N12-diacetylspermine, spermine, malate, and glycolate, had statistically significant differences between IgG4-ROD and orbital MALT lymphoma with receiver operating characteristic values from 0.708 to 0.863. Conclusions: These data revealed the characteristic differences in metabolomic profiles between IgG4-ROD and orbital MALT lymphoma, which may be useful for developing new diagnostic biomarkers and elucidating the pathogenic mechanisms of these common orbital lymphoproliferative disorders.


Biomarkers, Tumor/metabolism , Immunoglobulin G/blood , Lymphoma, B-Cell, Marginal Zone/metabolism , Metabolome/physiology , Orbital Diseases/metabolism , Orbital Neoplasms/metabolism , Paraproteinemias/metabolism , Adult , Aged , Aged, 80 and over , Chromatography, High Pressure Liquid , Female , Glycolates/metabolism , Humans , Lymphoma, B-Cell, Marginal Zone/diagnosis , Malates/metabolism , Male , Mass Spectrometry , Metabolomics , Middle Aged , Orbital Diseases/diagnosis , Orbital Neoplasms/diagnosis , Paraproteinemias/diagnosis , Principal Component Analysis , ROC Curve , Retrospective Studies , Spermine/analogs & derivatives , Spermine/metabolism
10.
J Clin Med ; 9(12)2020 Dec 06.
Article En | MEDLINE | ID: mdl-33291298

The activities of various metabolic pathways can influence the pathogeneses of autoimmune diseases, and intrinsic metabolites can potentially be used to diagnose diseases. However, the metabolomic analysis of patients with uveitis has not yet been conducted. Here, we profiled the serum metabolomes of patients with three major forms of uveitis (BehÒ«et's disease (BD), sarcoidosis, and Vogt-Koyanagi-Harada disease (VKH)) to identify potential biomarkers. This study included 19 BD, 20 sarcoidosis, and 15 VKH patients alongside 16 healthy control subjects. The metabolite concentrations in their sera were quantified using liquid chromatography with time-of-flight mass spectrometry. The discriminative abilities of quantified metabolites were evaluated by four comparisons: control vs. three diseases, and each disease vs. the other two diseases (such as sarcoidosis vs. BD + VKH). Among 78 quantified metabolites, 24 kinds of metabolites showed significant differences in these comparisons. Four multiple logistic regression models were developed and validated. The area under the receiver operating characteristic (ROC) curve (AUC) in the model to discriminate disease groups from control was 0.72. The AUC of the other models to discriminate sarcoidosis, BD, and VKH from the other two diseases were 0.84, 0.83, and 0.73, respectively. This study provides potential diagnostic abilities of sarcoidosis, BD, and VKH using routinely available serum samples that can be collected with minimal invasiveness.

11.
Clin Ophthalmol ; 14: 4109-4113, 2020.
Article En | MEDLINE | ID: mdl-33299292

PURPOSE: Low power mode (LPM) can be used for subthreshold retinal laser treatment by simply adjusting the laser parameters. Herein, we report the use of a modified LPM laser treatment for four cases of central serous chorioretinopathy (CSCR). PATIENTS AND METHODS: We retrospectively reviewed the medical records of four patients (four eyes) with persistent CSCR who underwent modified LPM laser for leakage. The laser power was first titrated with a barely visible burn, and then treatment was applied using 33% laser energy by manually adjusting the laser power and duration. RESULTS: Serous retinal detachment completely resolved in all cases by 2 months after treatment. Autofluorescence images did not show any specific changes induced by laser burns. CONCLUSION: A modified LPM laser may provide a feasible treatment for persistent CSCR.

12.
J Mater Chem B ; 7(44): 7026-7032, 2019 11 28.
Article En | MEDLINE | ID: mdl-31638628

Lidocaine has been used as a local anesthetic by injection. The controlled release of lidocaine loaded into nanospheres is necessary to reduce the onset time of the anesthetic effect or increase the anesthetic analgesia duration. In this study, mesoporous silica nanoparticles (MSNs) with a large specific surface area were prepared by a sol-gel method, and the interfacial interaction between MSNs and lidocaine positively charged in aqueous solutions at different concentrations was investigated by adsorption tests, Fourier-transformed infrared spectroscopy, thermogravimetry-differential thermal analysis, and Brunauer-Emmett-Teller (BET) measurements. The electrostatic interaction between Si-OH on MSNs and lidocaine-NH+ was of importance for the adsorption phenomenon in aqueous solutions, indicating the monolayer adsorption of lidocaine. BET measurements also supported the decrease of pore volumes, and the hysteresis loop of the isotherm curve was not closed since the condensation of lidocaine in the mesopores formed micropores of less than 1.5 nm in size. The release profiles in phosphate buffered saline containing calcium and magnesium ions showed a rapid and higher release of lidocaine compared with that in phosphate buffered saline without divalent cations. The released lidocaine concentrations were sufficient for the expression of the anesthetic effect in dental anesthesia.


Anesthetics, Local/chemistry , Lidocaine/chemistry , Nanoparticles/chemistry , Silicon Dioxide/chemistry , Adsorption , Drug Liberation
13.
Biol Pharm Bull ; 42(6): 929-936, 2019.
Article En | MEDLINE | ID: mdl-31155589

Bisphosphonates (BPs) containing nitrogen (N-BPs) exhibit far stronger anti-bone-resorptive effects than non-N-BPs. However, repeated administration of N-BPs causes osteonecrosis selectively in jawbones. As BPs accumulate in large amounts within inflamed bones, any N-BP released from the pool accumulated within jawbones might directly act on cells in the surrounding soft-tissues and induce inflammation or necrosis. Here, we examined the local and systemic effects of zoledronate (the most potent N-BP with the highest incidence of jawbone-necrosis) on inflammatory cytokines in mice. Locally within ear-pinnas: (i) zoledronate induced long-lasting accumulation of interleuikin-1ß (IL-1ß) and IL-18, but not tumor necrosis factor-α (TNF-α), (ii) zoledronate and lipopolysaccharide (LPS, a cell-wall component of Gram-negative bacteria) mutually augmented the productions of IL-1ß, IL-18, and TNF-α, and (iii) oxidronate (a toxic non-N-BP) by itself produced not only IL-1ß and IL-18, but also TNF-α. In systemic experiments using intraperitoneal injection of zoledronate and/or LPS, (i) zoledronate by itself increased none of the above cytokines in serum, and (ii) in mice pretreated (3 d before) with zoledronate, the LPS-induced increases in serum IL-1ß and IL-18 were greatly augmented with a delayed slight TNF-α augmentation. These results, together with previous ones, suggest that (a) pro-IL-1ß and pro-IL-18 accumulate within cells in soft-tissues exposed to N-BPs, and infection may augment not only their production, but also the release of their mature forms, (b) IL-1ß and IL-18 (possibly together with TNF-α) may play important roles in N-BP-induced inflammation and/or necrosis, and (c) mechanisms underlying the cytotoxic effects of BPs may differ between N-BPs and non-N-BPs.


Bone Density Conservation Agents/pharmacology , Ear Auricle/drug effects , Interleukin-18/metabolism , Interleukin-1beta/metabolism , Tumor Necrosis Factor-alpha/metabolism , Zoledronic Acid/pharmacology , Animals , Ear Auricle/metabolism , Lipopolysaccharides/pharmacology , Mice, Inbred BALB C
14.
Clin Case Rep ; 6(6): 1077-1081, 2018 Jun.
Article En | MEDLINE | ID: mdl-29881568

During intravenous sedation, a decrease in SpO2 is usually the result of respiratory failure. However, we experienced a case with SpO2 decrease that was caused by methemoglobinemia in prilocaine infiltration anesthesia during sedation. This indicates that methemoglobinemia should be considered if low SpO2 is sustained unrelated to sedation level.

15.
Sci Rep ; 7(1): 3944, 2017 06 21.
Article En | MEDLINE | ID: mdl-28638085

Norepinephrine modulates synaptic plasticity in various brain regions and is implicated in memory formation, consolidation and retrieval. The cerebellum is involved in motor learning, and adaptations of the vestibulo-ocular reflex (VOR) and optokinetic response (OKR) have been studied as models of cerebellum-dependent motor learning. Previous studies showed the involvement of adrenergic systems in the regulation of VOR, OKR and cerebellar synaptic functions. Here, we show differential contributions of ß- and α2-adrenergic receptors in the mouse cerebellar flocculus to VOR and OKR control. Effects of application of ß- or α2-adrenergic agonist or antagonist into the flocculus suggest that the ß-adrenergic receptor activity maintains the VOR gain at high levels and contributes to adaptation of OKR, and that α2-adrenergic receptor counteracts the ß-receptor activity in VOR and OKR control. We also examined effects of norepinephrine application, and the results suggest that norepinephrine regulates VOR and OKR through ß-adrenergic receptor at low concentrations and through α2-receptor at high concentrations.


Cerebellum/physiology , Nystagmus, Optokinetic , Receptors, Adrenergic, alpha-2/physiology , Receptors, Adrenergic, beta/physiology , Reflex, Vestibulo-Ocular , Adaptation, Physiological , Adrenergic alpha-2 Receptor Agonists/administration & dosage , Adrenergic alpha-2 Receptor Antagonists/administration & dosage , Adrenergic beta-Agonists/administration & dosage , Adrenergic beta-Antagonists/administration & dosage , Animals , Cerebellum/drug effects , Male , Mice, Inbred C57BL
16.
J Med Dent Sci ; 63(4): 71-77, 2016.
Article En | MEDLINE | ID: mdl-28049939

The present study investigates how effectively lidocaine ions are transported across a cellophane membrane through the application of either a direct current (DC) or alternating current (AC). The cellophane membrane was set on a parallelplate- type acrylic cell with platinum electrodes at both ends, filled with a donor cell of a 1 % aqueous solution of lidocaine and a receptor cell with distilled water. Lidocaine concentrations were measured for 60 min while the following voltages were applied, with changes every 10 min: 3 V DC and 7.5 V sine wave AC; frequency at 1 kHz. As a result, lidocaine concentrations in the receptor cell increased in a time-dependent manner. Significant increases in lidocaine concentrations were observed in groups where the voltage combination consisted of DC 30 min/AC 30 min, DC 50 min/AC 10 min, DC 60 min and AC 10 min/DC 50 min, compared with the passive diffusion group or in groups where voltage application was performed for 20, 30 , 40, 50 and 60 min. Significant increases were also observed in groups where the voltage combination consisted of A C 6 0 min, D C 10 min/AC 5 0 min, AC 3 0 min/ DC 30 min and AC 50 min/DC 10 min, compared with the passive diffusion group or in groups where voltage application was performed for 40, 50 and 60 min. These results suggest that lidocaine was delivered more rapidly with DC than with AC, and that its ions are transported faster when voltage is switched from DC to AC than from AC to DC, which is presumably due to the contribution of electrorepulsion by DC voltage application and the vibration energy infiltration mechanism owning to AC. Iontophoresis in combination with DC and AC was found to enable highly efficient drug delivery that shares the benefits of both forms of current application.


Anesthetics, Local/administration & dosage , Drug Delivery Systems/methods , Iontophoresis/methods , Lidocaine/administration & dosage , Anesthetics, Local/chemistry , Cellophane/chemistry , Electricity , Lidocaine/chemistry , Membranes/chemistry , Membranes, Artificial , Temperature , Water/chemistry
17.
J Med Dent Sci ; 61(2): 41-8, 2014 Jun 27.
Article En | MEDLINE | ID: mdl-25952356

Iontophoresis (IOP) is a noninvasive method of delivering medication transcutaneously through the skin. The electrodes used in this method should tightly fit to rough and irregular surfaces and be biologically safe, easy to handle and prepare, and cost-effective. To satisfy these requirements, calcium alginate gel can be a candidate electrode for IOP. Using calcium alginate gel electrodes, we examined whether lidocaine can be effectively transported across an excised rat skin by squarewave alternating current (AC) application. A squarewave AC with either a 70% or 80% duty cycle was continuously applied to 0.5% calcium alginate gel electrodes containing 10% lidocaine at 10 V and 1 kHz for 60 min. Lidocaine concentration was measured using a spectrophotometer and the temperature of the gel was determined. The lidocaine concentrations for AC-IOP at the 70% and 80% duty cycles were significantly higher than that without AC-IOP. Furthermore, the group with the 80% duty cycle showed higher lidocaine concentrations than the group with the 70% duty cycle. The temperatures of all the groups were lower than 28 °C throughout the procedure. In conclusion, the calcium alginate gel can be used as a possible matrix for IOP electrodes.


Alginates/chemistry , Anesthetics, Local/administration & dosage , Biocompatible Materials/chemistry , Electrodes , Iontophoresis/instrumentation , Lidocaine/administration & dosage , Animals , Diffusion , Drug Delivery Systems , Equipment Design , Gels , Glucuronic Acid/chemistry , Hexuronic Acids/chemistry , In Vitro Techniques , Iontophoresis/methods , Male , Materials Testing , Rats , Rats, Wistar , Skin Absorption/drug effects , Spectrophotometry/methods , Temperature , Time Factors
18.
Am J Respir Cell Mol Biol ; 50(1): 115-24, 2014 Jan.
Article En | MEDLINE | ID: mdl-23962082

ß-Agonists are the first-line therapy to alleviate asthma symptoms by acutely relaxing the airway. Purified components of ginger relax airway smooth muscle (ASM), but the mechanisms are unclear. By elucidating these mechanisms, we can explore the use of phytotherapeutics in combination with traditional asthma therapies. The objectives of this study were to: (1) determine if 6-gingerol, 8-gingerol, or 6-shogaol potentiate ß-agonist-induced ASM relaxation; and (2) define the mechanism(s) of action responsible for this potentiation. Human ASM was contracted in organ baths. Tissues were relaxed dose dependently with ß-agonist, isoproterenol, in the presence of vehicle, 6-gingerol, 8-gingerol, or 6-shogaol (100 µM). Primary human ASM cells were used for cellular experiments. Purified phosphodiesterase (PDE) 4D or phospholipase C ß enzyme was used to assess inhibitory activity of ginger components using fluorescent assays. A G-LISA assay was used to determine the effects of ginger constituents on Ras homolog gene family member A activation. Significant potentiation of isoproterenol-induced relaxation was observed with each of the ginger constituents. 6-Shogaol showed the largest shift in isoproterenol half-maximal effective concentration. 6-Gingerol, 8-gingerol, or 6-shogaol significantly inhibited PDE4D, whereas 8-gingerol and 6-shogaol also inhibited phospholipase C ß activity. 6-Shogaol alone inhibited Ras homolog gene family member A activation. In human ASM cells, these constituents decreased phosphorylation of 17-kD protein kinase C-potentiated inhibitory protein of type 1 protein phosphatase and 8-gingerol decreased myosin light chain phosphorylation. Isolated components of ginger potentiate ß-agonist-induced relaxation in human ASM. This potentiation involves PDE4D inhibition and cytoskeletal regulatory proteins. Together with ß-agonists, 6-gingerol, 8-gingerol, or 6-shogaol may augment existing asthma therapy, resulting in relief of symptoms through complementary intracellular pathways.


Adrenergic beta-Agonists/pharmacology , Cytoskeletal Proteins/metabolism , Muscle Relaxation/drug effects , Muscle, Smooth/drug effects , Plant Extracts/pharmacology , Zingiber officinale/chemistry , Asthma/drug therapy , Asthma/metabolism , Catechols/pharmacology , Cell Line , Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism , Fatty Alcohols/pharmacology , HSP20 Heat-Shock Proteins/metabolism , Humans , Intracellular Signaling Peptides and Proteins , Muscle Proteins , Muscle, Smooth/metabolism , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/metabolism , Myosin Light Chains/metabolism , Phosphatidylinositols/antagonists & inhibitors , Phosphatidylinositols/metabolism , Phospholipase C beta/antagonists & inhibitors , Phospholipase C beta/metabolism , Phosphoprotein Phosphatases/antagonists & inhibitors , Phosphoprotein Phosphatases/metabolism , Phosphoric Monoester Hydrolases/metabolism , Phosphorylation/drug effects , Plant Extracts/chemistry , Potassium Channels/metabolism , rhoA GTP-Binding Protein/antagonists & inhibitors , rhoA GTP-Binding Protein/metabolism
19.
J Med Dent Sci ; 60(3): 63-71, 2013 Sep 30.
Article En | MEDLINE | ID: mdl-24146168

The aim of this study was to determine transport of lidocaine ions through a hairless rat skin in vivo and to compare the efficacy of alternating current (AC) with that of direct current (DC) iontophoresis (IOP). We measured the concentration of lidocaine transported through a cellophane membrane or a hairless rat dorsal skin applying either AC-IOP or DC-IOP. The results revealed that lidocaine concentration increased in a time-dependent manner in vitro in both DC-IOP and AC-IOP. However, the in vivo study showed different tendencies in lidocaine concentration. In the DCIOP group, lidocaine concentration reached its maximum 20 min after current application and then decreased rapidly; the AC-IOP group showed an increase in lidocaine concentration in a time-dependent manner. There were no side effects such as electrical burns in the rats. In conclusion, AC can be applied for long periods and DC for short periods, or their application time can be appropriately scheduled. Our study also suggests the mechanism by which voltage waveforms affect the skin when applied by IOP. In the future, these findings will be a solid foundation for developing various kinds of medical equipment such as scheduled drug delivery system that can easily deliver various types of drug.


Anesthetics, Local/administration & dosage , Iontophoresis/methods , Lidocaine/administration & dosage , Administration, Cutaneous , Anesthetics, Local/chemistry , Animals , Cellophane/chemistry , Electricity , Lidocaine/chemistry , Male , Membranes, Artificial , Microdialysis/methods , Rats , Rats, Hairless , Skin Absorption , Time Factors
20.
Anesth Prog ; 59(2): 62-8, 2012.
Article En | MEDLINE | ID: mdl-22822992

Dexmedetomidine (DEX) has a minimal respiratory depressive effect, which is beneficial for dentistry; however, it has the disadvantage of permitting an intraoperative arousal response such that the patient appears to be suddenly no longer sedated, and it has a variable amnestic effect. Since midazolam (MDZ) in an appropriate dose has a profound amnesic effect, we investigated whether additional MDZ compensates for the disadvantage of DEX and enables a better quality of sedation. Forty-three subjects were randomly divided into 4 groups. In group 1, MDZ (0.02 mg/kg) was administered intravenously, followed by a dose of 0.01 mg/kg every 45 minutes. After the first dose of MDZ, preloading with DEX (2 µg/kg/h for 10 minutes) was started and maintained with a dosage of 0.5 µg/kg/h. In group 2, MDZ was infused in the same manner as in group 1, followed by preloading with DEX (1 µg/kg/h for 10 minutes) and maintenance (0.3 µg/kg/h). In group 3, MDZ was infused 0.03 mg/kg, and a dose of 0.01 mg/kg was given every 30 minutes; DEX was administered at the same as in group 2. In group 4, DEX was infused using the same method as in group 1 without MDZ. The sedation levels, amnesia, and patient satisfaction were also investigated. Group 2 had a lower sedation level and a poor evaluation during the first half of the operation. Group 4 did not exhibit an amnesic effect at the beginning of the operation. An evaluation of the degree of patient satisfaction did not reveal any differences among the groups. Optimal sedation was achieved through the combined use of MDZ (0.02 mg/kg with the addition of 0.01 mg/kg every 45 minutes) and DEX (2 µg/kg/h for 10 minutes followed by 0.5 µg/kg/h).


Anesthesia, Dental/methods , Anesthetics, Combined/administration & dosage , Conscious Sedation/methods , Dexmedetomidine/administration & dosage , Hypnotics and Sedatives/administration & dosage , Midazolam/administration & dosage , Adult , Aged , Amnesia/chemically induced , Analysis of Variance , Anesthesia, Intravenous/methods , Dental Implantation, Endosseous , Female , Humans , Male , Middle Aged , Patient Satisfaction , Statistics, Nonparametric , Young Adult
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