Rett syndrome is an X-linked neurodevelopmental disorder characterised by cognitive, attentional, and communicative impairments along with sensory and motor deficits. Optimal activation of dopamine D1 receptor signalling in the prefrontal cortex (PFC) is essential for cognition and object-based attention. Ghrelin has been observed to modulate dopaminergic neurotransmission and improve cognitive function and attention impairments in various animal models. Herein, we investigated the effects of ghrelin on D1 receptor-mediated dopaminergic neurotransmission in the PFC of male Mecp2 knockout (KO) mice, a mouse model of Rett syndrome, using in vivo microdialysis. External stimuli, such as saline injection and novelty induced increases in the dopamine levels in the PFC of wild-type mice, and the dopamine release was bidirectionally regulated by D1 receptors. In the PFC of Mecp2 KO mice, the dopaminergic responses to external stimuli were attenuated, and the dopamine reuptake system was upregulated. Pharmacological analyses revealed that the ability of D1 receptor signalling to inhibit dopamine release would be upregulated and/or its ability to stimulate dopamine release would be downregulated in Mecp2 KO mice. Ghrelin injection (8.6 μg/mouse, s.c.) restored dopaminergic responses to external stimuli by adjusting the altered function of D1 receptor signalling. While ghrelin injection failed to improve the impaired object recognition ability in Mecp2 KO mice, it enhanced attention and exploratory activity toward objects. These findings in Mecp2 KO mice suggest that ghrelin may enhance D1 receptor-mediated dopaminergic neurotransmission and exert beneficial effects on dopamine-related behaviour, such as attention and investigatory motivation towards objects, in Rett syndrome.

Few reports exist in dentistry about the use of general anesthesia in children after liver transplant. In this paper, we report our experience utilizing general anesthesia for oral surgery in a 9-year-old girl who had undergone living donor liver transplantation. She was diagnosed with hepatoblastoma at 4 months of age and underwent a living donor liver transplant at 7 months of age. Due to a maxillary odontoma, impacted maxillary supernumerary teeth, and retained maxillary primary teeth, the patient was scheduled for general anesthesia. Preoperative blood tests revealed mild liver dysfunction, but no other abnormalities were noted. General anesthesia was administered with sevoflurane, rocuronium, fentanyl, and remifentanil, and no complications arose during the perioperative period. The patient was discharged without any significant issues the day after surgery. Precautions for the anesthetic management of children who have undergone living donor liver transplantation include assessing the patient for preoperative liver dysfunction and avoiding liver dysfunction caused by drugs used in conjunction with general anesthesia. Anesthetic agents and adjunctive medications should be carefully considered for use in patients with liver disease.

Drug repositioning is a method for exploring new effects of existing drugs, the safety and pharmacokinetics of which have been confirmed in humans. Here, we demonstrate the potential drug repositioning of midazolam (MDZ), which is used for intravenous sedation, as an inhibitor of inflammatory bone resorption. We cultured a mouse macrophage-like cell line with or without MDZ and evaluated its effects on the induction of differentiation of these cells into osteoclasts. For in vivo investigations, we administered lipopolysaccharide (LPS) together with MDZ (LPS+MDZ) to the parietal region of mice and evaluated the results based on the percentage of bone resorption and calvaria volume. Furthermore, we examined the effects of MDZ on the production of reactive oxygen species (ROS) in cells and on its signaling pathway. MDZ inhibited osteoclast differentiation and bone resorption activity. In animal studies, the LPS+MDZ group showed a decreasing trend associated with the rate of bone resorption. In addition, the bone matrix volume in the LPS+MDZ group was slightly higher than in the LPS only group. MDZ inhibited osteoclast differentiation by decreasing ROS production and thereby negatively regulating the p38 mitogen-activated protein kinase pathway. Thus, we propose that MDZ could potentially be used for treating inflammatory bone resorption, for example, in periodontal disease.

Trigeminal neuralgia (TN) is an exemplary condition of neuropathic pain. The characteristics of TN pain are that it is unilateral, electroshock-like, and evoked by light touch. The main vessel causing TN are the arteries, although rare cases occur in which a vein is responsible. In that cases, TN may be ruled out and dental disease may be suspected as venous compression on the trigeminal nerve often does not show up on magnetic resonance imaging (MRI). This factor can result in unnecessary treatment and years of pain. A 63-year-old male patient presented to our department with uncontrolled pain. The patient consulted several hospitals and MRI images showed no obvious nerve compression, TN was ruled out, and 2 years had passed since the appearance of the pain with no known cause. Based on the interview, the patient had the characteristic clinical features of TN. In addition, we had the patient perform actions that increased venous pressure such as laying supine, bending forward, straining, and sniffing, which resulted in electric shock pain. Therefore, we diagnosed the patient with TN caused by something other than compression by an artery. Another imaging study revealed that TN was caused by compression by the transverse pontine vein. Our experience showed that, in the diagnosis of TN, trying to understand the characteristic clinical features is important, rather than placing undue emphasis on MRI. Furthermore, we advocate a new technique of performing trigger movements to increase venous pressure can aid in the diagnosis of TN caused by venous compression.

Objective Remimazolam is a new, ultra-short-acting benzodiazepine that can be used for induction and maintenance of general anesthesia. We compared the hemodynamic stability and depth of anesthesia during general anesthesia using remimazolam or propofol along with remifentanil for oral and maxillofacial surgery. Methods A total of 95 patients were divided into remimazolam and propofol groups and then subdivided into bispectral index (BIS) and patient state index (PSI) groups. Blood pressure, heart rate, and BIS/PSI values were compared at fixed time points perioperatively. Time to loss of consciousness and total opioid doses were also compared across groups. Other items that were compared included intraoperative arousal and postoperative nausea and vomiting. Results Propofol produced more significant hemodynamic depression than remimazolam, although both groups were stable. BIS/PSI values were similar in both groups. Time to loss of consciousness was significantly shorter in the remimazolam group. Total opioid dosing was higher in the remimazolam group, and there were no differences regarding other postoperative complications. Conclusion The perioperative hemodynamics with remimazolam were more stable that with propofol, especially during induction. Therefore, remimazolam may be a safe alternative to propofol for providing TIVA general anesthetics.

Arytenoid cartilage dislocation can occur as a complication of tracheal intubation and laryngeal trauma, but its occurrence with indirect video laryngoscopy has not been reported. This paper reports anterior arytenoid dislocation occurring after nasotracheal intubation performed under indirect laryngoscopy using a video laryngoscope (McGRATH MAC; Medtronic). The dislocation is presumed to have resulted from the laryngoscope blade being initially inserted too deeply and applying pressure to the posterior aspect of the left cricoarytenoid joint. This patient’s anterior arytenoid dislocation was treated conservatively using speech therapy with resolution occurring approximately 40 days postoperatively. On the 74th day after surgery, fibroscopic examination confirmed recovery and healing of the dislocation. However, other types of arytenoid dislocations and laryngeal injuries may require alternative treatment. Early consultation with an otolaryngologist is recommended if arytenoid dislocation is suspected.

Rett syndrome is an X-linked neurodevelopmental disorder characterized by cognitive impairments along with sensory and motor deficits. Ghrelin is known to improve cognitive function in various animal models with cognitive deficits. Optimum activation of dopamine D1 receptor signaling in the prefrontal cortex (PFC) plays a critical role in cognitive performance. In this study, we investigated the effects of ghrelin on cognitive function and D1 receptor-mediated dopamine neurotransmission in the PFC of Mecp2 knockout (KO) mice, a mouse model for Rett syndrome. In the modified novel object recognition test, cognitive function was impaired in Mecp2 KO mice, and ghrelin injection (8.6 µg/mouse, s.c.) improved the cognition of objects and investigatory behaviors. In in vivo microdialysis studies, external stimuli such as saline injection and novelty induced increases in dopamine levels in the PFC of wild-type mice, and the dopamine release was bidirectionally regulated by D1 receptors. In the PFC of Mecp2 KO mice, the dopamine responses to external stimuli were attenuated and the dopamine reuptake system was upregulated. Pharmacological analyses revealed that the ability of D1 receptor signaling to inhibit dopamine release would be upregulated and/or its ability to stimulate dopamine release would be downregulated in Mecp2 KO mice. Ghrelin injection restored dopamine responses to external stimuli by adjusting the altered function of D1 receptor signaling. These results suggest that the ability of ghrelin to restore dopamine neurotransmission via D1 receptor-mediated mechanisms likely contributes to its therapeutic effects on cognitive deficits in Mecp2 KO mice.

We report a case of severe bradycardia during general anesthesia due to reduced atrioventricular conduction capacity believed to have been caused by the trigeminocardiac reflex (TCR). A 46-year-old woman was scheduled for intraoral scar revision under general anesthesia. When the surgeon opened her mouth intraoperatively, the patient's blood pressure immediately increased, and she developed significant bradycardia and a transient Mobitz type II second-degree atrioventricular block. It was assumed that the mandibular division of the trigeminal nerve (V-3) was stimulated by the surgeon stretching the patient's mouth open while remifentanil simultaneously provided sympatholytic effects, resulting in activation of the TCR. The patient quickly responded well to atropine and had no additional complications.

Cast immobilization causes sensory hypersensitivity, which is also a symptom of neuropathic pain and chronic pain. However, the mechanisms underlying immobilization-induced hypersensitivity remain unclear. The present study investigated the role of dopamine neurotransmission in the nucleus accumbens shell (NAcSh) of rats with cast immobilization-induced mechanical hypersensitivity using in vivo microdialysis. Cast immobilization of the hind limb decreased the paw withdrawal threshold (PWT). Mechanical stimulation of the cast-immobilized hind limb induced a decrease in dopamine in the NAcSh, and this decrease was associated with the upregulation of presynaptic D2-like receptors. A D2-like receptor antagonist infused into the NAcSh reversed the decrease in PWT in rats with cast immobilization, whereas a D2-like receptor agonist infused into the NAcSh induced a decrease in PWT in control rats. In addition, the expression of the D2 receptor (Drd2) mRNA in the NAcSh was increased by cast immobilization. Importantly, systemic administration of the D2-like receptor antagonist reversed the decrease in PWT in rats with cast immobilization. As dopamine levels regulated by presynaptic D2-like receptors did not correlate with the PWT, it is presumed that the D2-like receptor antagonist or agonist acts on postsynaptic D2-like receptors. These results suggest that immobilization-induced mechanical hypersensitivity is attributable to the upregulation of postsynaptic D2-like receptors in the NAc. Blockade of D2-like receptors in the NAcSh is a potential therapeutic strategy for immobilization-induced hypersensitivity.

We recently reported a positive relationship between occlusal disharmony and cardiovascular disease via activation of β-adrenergic signaling in mice. Furthermore, inhibition of type 5 adenylyl cyclase (AC5), a major cardiac subtype in adults, protects the heart against oxidative stress. Here, we examined the role of AC5 in the development of occlusal-disharmony-induced cardiovascular disease in bite-opening (BO) mice, prepared by cementing a suitable appliance onto the mandibular incisor. We first examined the effects of BO treatment on cardiac function in mice treated or not treated for 2 weeks with vidarabine, which we previously identified as an inhibitor of cardiac AC. Cardiac function was significantly decreased in the BO group compared to the control group, but vidarabine ameliorated the dysfunction. Cardiac fibrosis, myocyte apoptosis and myocyte oxidative DNA damage were significantly increased in the BO group, but vidarabine blocked these changes. The BO-induced cardiac dysfunction was associated with increased phospholamban phosphorylation at threonine-17 and serine-16, as well as increased activation of the Ca 2+ -calmodulin-dependent protein kinase II/receptor-interacting protein 3 signaling pathway. These data suggest that AC5 inhibition with vidarabine might be a new therapeutic approach for the treatment of cardiovascular disease associated with occlusal disharmony.

Abstract Background Dopamine neurotransmission plays a critical role in reward in drug abuse and drug addiction. However, the role of dopamine in the recognition of drug-associated environmental stimuli, retrieval of drug-associated memory, and drug-seeking behaviors is not fully understood. Methods Roles of dopamine neurotransmission in the prefrontal cortex (PFC) and nucleus accumbens (NAc) in the cocaine-conditioned place preference (CPP) paradigm were evaluated using in vivo microdialysis. Results In mice that had acquired cocaine CPP, dopamine levels in the PFC, but not in the NAc, increased in response to cocaine-associated cues when mice were placed in the cocaine chamber of an apparatus with 2 separated chambers. The induction of the dopamine response and the development of cocaine CPP were mediated through activation of glutamate NMDA (N-methyl-D-aspartate)/AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor signaling in the PFC during conditioning. Activation of dopamine D1 or D2 receptor signaling in the PFC was required for cocaine-induced locomotion, but not for the induction of the dopamine response or the development of cocaine CPP. Interestingly, dopamine levels in the NAc increased in response to cocaine-associated cues when mice were placed at the center of an apparatus with 2 connected chambers, which requires motivated exploration associated with cocaine reward. Conclusions Dopamine neurotransmission in the PFC is activated by the exposure to the cocaine-associated cues, whereas dopamine neurotransmission in the NAc is activated in a process of motivated exploration of cues associated with cocaine reward. Furthermore, the glutamate signaling cascade in the PFC is suggested to be a potential therapeutic target to prevent the progression of drug addiction.

Although a significant association between periodontal disease and atherosclerotic cardiovascular disease has been reported, their cause-to-effect relationship remains controversial. This randomized controlled clinical trial aimed to investigate the effect of advanced self-care on atherosclerotic cardiovascular disease-related vascular function markers flow-mediated brachial artery dilatation (FMD) and serum asymmetric dimethylarginine (ADMA) level in patients with early-stage periodontal disease. The study was designed as a parallel group, 3-month follow-up, open-label, randomized controlled trial. The control group received standard care for periodontal diseases, whereas the test group additionally applied disinfectant using a custom-fabricated prescription tray for advanced self-care twice a day. Overall, 110 patients provided data for FMD and serum ADMA level. No significant improvements in FMD were observed in the control (mean increase, −0.1%; 95% confidence interval [CI], −1.0–0.8; P = 0.805) or test (mean increase, −0.3%; 95% CI, −1.1–0.4; P = 0.398) group. No significant changes in serum ADMA levels were observed (mean reduction, 0.01 μmol/L; 95% CI, −0.00–0.02; P = 0.366 and mean reduction, 0.00 μmol/L; 95% CI, −0.01–0.01; P = 0.349, respectively). No significant between-group differences were found in FMD (mean difference, −0.2%; 95% CI, −1.4–0.9; p = 0.708) or serum ADMA levels (mean difference, 0.01 nmol/L; 95% CI, −0.00–0.03; p = 0.122). Significant improvements in the average probing pocket depth were observed in the control and test groups. The bleeding on probing score in the test group was significantly reduced, while that in the control group was reduced, although not significantly. Periodontal care for a 3-month duration did not provide better endothelial function although improvements of periodontal status in patients with early-stage periodontal diseases. This trial is registered in UMIN Clinical Trials Registry (www.umin.ac.jp/ctr/; ID: UMIN000023395).

Role of dopamine neurotransmission in retrieval of drug-associated memory is not fully understood. The present study provides direct evidences that dopamine neurotransmission is differentially activated in the prefrontal cortex (PFC) and nucleus accumbens (NAc) in the cocaine conditioned place preference (CPP) paradigm in behaving mice using in vivo microdialysis. In mice that had acquired cocaine CPP, the dopamine levels in the PFC, but not in the NAc, increased in response to the cocaine-associated cue, when mice were placed in the cocaine chamber of two-separated chamber apparatus. The induction of the dopamine response and the development of cocaine CPP were mediated through activation of glutamate NMDA/AMPA receptor signaling in the PFC during conditioning. Activation of dopamine D1 or D2 receptors signaling in the PFC was required for the cocaine-induced locomotion, but not for the induction of the dopamine response or the development of cocaine CPP. Interestingly, dopamine levels in the NAc increased in response to the cocaine-associated cue, when mice were placed at the center of two-connected chamber apparatus, which requires the motivated exploratoration of cocaine reward. In summary, dopamine neurotransmission in the PFC is activated to retrieve the context-associated reward memory of cocaine, whereas dopamine neurotransmission in the NAc is activated in the process of motivated exploration of cocaine reward. The present findings suggest the nature of difference in dopamine transmission in the PFC and NAc to the psychological reward cues.

The dopamine (DA) D1 receptors in the nucleus accumbens (NAc) is implicated in cocaine-induced conditioned place preference (CPP), which is driven by the cocaine-associated cue. However, the effect of the cocaine-associated cue on DA release in the prefrontal cortex (PFC) has little been studied. The present study examined the effects of cocaine-associated cues on the extracellular DA levels in the NAc and PFC using in vivo microdialysis. Furthermore, the role of D1, D2, and ionotropic glutamate receptors in cocaine (7.5 mg/kg i.p.)-induced CPP, locomotor and DA release were investigated. Cocaine-associated cues increased DA levels in the PFC, but unexpectedly had no effects on DA levels in the NAc. Pharmacological inhibition of D1 and D2 receptors and chemogenetic inhibition of D1 receptor-expressing cells by Gi-DREADD in the PFC during the cocaine conditioning procedure suppressed the cocaine-induced locomotor response, but did not affect the CPP. Pharmacological modulation of ionotropic glutamate receptors by antagonists and agonists in the PFC suppressed the cocaine-induced CPP, but did not affect the locomotor response. The DA response to the cocaine-associated cue in the PFC was abolished by pharmacological inhibition of ionotropic glutamate receptors, but not of D1 or D2 receptors.

In drug repositioning research, a new concept in drug discovery and new therapeutic opportunities have been identified for existing drugs. Midazolam (MDZ) is an anesthetic inducer used for general anesthesia. Here, we demonstrate the combined effects of bone morphogenetic protein-2 (BMP-2) and MDZ on osteogenic differentiation. An immortalized mouse myoblast cell line (C2C12 cell) was cultured in the combination of BMP-2 and MDZ (BMP-2+MDZ). The differentiation and signal transduction of C2C12 cells into osteoblasts were investigated at biological, immunohistochemical, and genetic cell levels. Mineralized nodules formed in C2C12 cells were characterized at the crystal engineering level. BMP-2+MDZ treatment decreased the myotube cell formation of C2C12 cells, and enhanced alkaline phosphatase activity and expression levels of osteoblastic differentiation marker genes. The precipitated nodules consisted of randomly oriented hydroxyapatite nanorods and nanoparticles. BMP-2+MDZ treatment reduced the immunostaining for both α1 and γ2 subunits antigens on the gamma-aminobutyric acid type A (GABAA) receptor in C2C12 cells, but enhanced that for BMP signal transducers. Our investigation showed that BMP-2+MDZ has a strong ability to induce the differentiation of C2C12 cells into osteoblasts and has the potential for drug repositioning in bone regeneration.

Purpose: The objective of this study was to verify growth suppression of methicillin-resistant Staphylococcus aureus (MRSA) involved in ventilator-associated pneumonia (VAP) aggravation by the probiotic candidate bacterium Lactobacillus gasseri (L. gasseri) in the oral cavity. Materials and Methods: L. gasseri YIT 12321 (Lg YIT 12321) and MRSA JCM 8702 (MRSA-JCM) were used as test bacteria. Both Lg YIT 12321 and MRSA-JCM were cultured in lactobacilli MRS medium, and MRSA-JCM was also cultured in TS medium anaerobically at 37˚C for 18-24 hours. The antibacterial activity of Lg YIT 12321 against MRSA-JCM was examined by competition assay and radial diffusion assay (RDA). A fraction obtained from the Lg YIT 12321 culture supernatant by 50% (w/v) saturated ammonium sulfate (50% sat. ammonium) precipitation was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Results: In the competition assay, inhibition of MRSA-JCM proliferation by Lg YIT 12321 was observed. Moreover, it was confirmed that the growth of MRSA-JCM was inhibited by neutralized culture supernatant of Lg YIT 12321 in the RDA, suggesting that the growth of MRSA-JCM was suppressed by an antibacterial substance produced by Lg YIT 12321. Conclusion: Lg YIT 12321 is a candidate probiotic that produces a class II bacteriocin that suppresses the growth of MRSA-JCM.

Although in clinical dentistry the major method used for pain relief is oral administration of analgesics, alternative methods are available, such as transcutaneous electrical nerve stimulation (TENS), acupuncture, vibration and conditioned pain modulation (CPM), formerly termed diffuse noxious inhibitory control. The aim of the present study was to investigate the combined effects of non-noxious (TENS) and noxious (CPM) stimuli on postoperative pain after extraction of an impacted wisdom tooth. The study involved 44 patients who were scheduled to undergo impacted wisdom tooth extraction. The patients were randomly allocated into four groups: noxious stimuli, non-noxious stimuli, combined noxious and non-noxious stimuli, and a sham group. On the day after tooth extraction, stimulation procedures for pain relief were performed and changes in the level of perceived pain were scored using a visual analog scale (VAS). The combination of non-noxious and noxious stimuli decreased the VAS scores by 63.7%, indicating a more potent analgesic effect than that in the non-noxious, noxious, and sham groups. This method of analgesia using a combination of non-noxious and noxious stimuli can be applied to patients who are unable to tolerate analgesics, such as those with allergy, hypersensitivity or digestive disorders, and those who are pregnant.

Purpose: The objective of this study was to investigate inhibitory effect of lactic acid bacteria and antibiotics on the growth of Streptococcus pneumoniae ATCC 33400.Materials and Methods: Antibiotic activities of five oral probiotic candidate bacteria including two strains of Lactobacillus crispatus, Lactobacillus fermentum, Lactobacillus gasseri and Streptococcus mitis and several antibiotics against S. pneumoniae were investigated using radial diffusion assay and competition assay. The biofilm formation of S. pneumoniae in the presence of 50% saturated ammonium sulfate precipitation fraction from L. gasseri and several concentrations of gentamicin were monitored by real time cell analyzer, xCELLigence. Results: The growth of S. pneumoniae was inhibited by two strains of Lactobacillus crispatus, Lactobacillus fermentum and Lactobacillus gasseri. The saturated ammonium sulfate precipitation fraction (0-30% and 30-50%) from L. gasseri effectively inhibited growth of S. pneumoniae. The biofilm formation of S. pneumoniae monitored by real time cell analyzer (xCELLigence) was suppressed by gentamicin in dose dependent manner. Antibacterial substance from L. gasseri against S. pneumoniae was suggested to be small molecular weight substance.Conclusion: L. gasseri inhibited the growth of S. pneumoniae suggesting that L. gasseri will be a candidate of probiotics.

Drug repositioning promises the advantages of reducing costs and expediting approval schedules. An induction of the anesthetic and sedative drug; midazolam (MDZ), regulates inhibitory neurotransmitters in the vertebrate nervous system. In this study we show the potential for drug repositioning of MDZ for dentin regeneration. A porcine dental pulp-derived cell line (PPU-7) that we established was cultured in MDZ-only, the combination of MDZ with bone morphogenetic protein 2, and the combination of MDZ with transforming growth factor-beta 1. The differentiation of PPU-7 into odontoblasts was investigated at the cell biological and genetic level. Mineralized nodules formed in PPU-7 were characterized at the protein and crystal engineering levels. The MDZ-only treatment enhanced the alkaline phosphatase activity and mRNA levels of odontoblast differentiation marker genes, and precipitated nodule formation containing a dentin-specific protein (dentin phosphoprotein). The nodules consisted of randomly oriented hydroxyapatite nanorods and nanoparticles. The morphology, orientation, and chemical composition of the hydroxyapatite crystals were similar to those of hydroxyapatite that had transformed from amorphous calcium phosphate nanoparticles, as well as the hydroxyapatite in human molar dentin. Our investigation showed that a combination of MDZ and PPU-7 cells possesses high potential of drug repositioning for dentin regeneration.

We retrospectively investigated the efficacy and safety of propofol administration alone and in combination with midazolam for gag reflex suppression during dental treatment under intravenous sedation. We included 56 patients with an overactive gag reflex who were to undergo dental treatment under intravenous sedation. They were divided into propofol (P group, n = 22) and midazolam with propofol (MP group, n = 34) groups. The P group received propofol alone, while the MP group received midazolam (0.04 mg/kg) prior to target-controlled infusion (TCI) of propofol (titrated for adequate sedation). The patients' anesthetic records were evaluated for vital sign changes, adverse cardiovascular or respiratory event frequency, the number of forced treatment interruptions, and the TCI-predicted cerebral propofol concentration at gag reflex suppression (posterior tongue stimulation with a dental mirror). No significant differences were observed between the 2 groups preoperatively. There were no cases of forced interruptions or significant respiratory compromise in either group. Cardiovascular adverse event frequency was lower in the MP group than in the P group (all p < .05). Our results suggest that propofol, when combined with midazolam, minimized cardiovascular effects compared with propofol alone when used to suppress the gag reflex in patients during dental treatment under intravenous sedation.