Factors associated with transient bradycardia during local anesthesia administration to the oral cavity under intravenous sedation: A retrospective cohort study.

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.

Considerations for Satisfactory Sedation during Dental Implant Surgery.

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.

Combined Use of a Gum Elastic Bougie and Video Laryngoscopy for Intubating a Patient With an Unexpected Laryngeal Papilloma.

This is a case report of a 75-year-old man scheduled for apical resection and cystectomy of odontogenic cysts involving both maxillary central incisors who presented with a previously unknown laryngeal mass that was discovered prior to intubation. Following induction and easy mask ventilation, direct laryngoscopy revealed a large mass on the right side of the glottis that impeded passage of a standard oral endotracheal tube. Successful atraumatic intubation was performed with the combination of a video laryngoscope (King Vision, Ambu Inc, Ballerup, Denmark) and a gum elastic bougie (GEB). Although a GEB may not be used routinely for tracheal intubation, it facilitated smooth advancement of the endotracheal tube without damaging the laryngeal mass when used in combination with video laryngoscopy.

Efficiency of Gastrointestinal Cancer Detection by Nematode-NOSE (N-NOSE).

BACKGROUND/AIM: Early detection of gastrointestinal cancer may reduce mortality. Recently, Caenorhabditis elegans has been reported to be capable of differentiating patients with cancers from healthy persons by the smell of urine. This novel technique using C. elegans olfaction has been named as Nematode-NOSE (N-NOSE). MATERIALS AND METHODS: We collected 180 urine samples from patients with gastrointestinal cancer and 76 samples from healthy subjects. N-NOSE test was performed using these samples and N-NOSE index was obtained. Quantification of the olfactory behavior of C. elegans was performed as established in past studies. By receiver operating characteristic (ROC) analysis, we examined the diagnostic capability of N-NOSE. RESULTS: ROC analysis revealed that N-NOSE showed an area under the curve value of more than 0.80, even in early-stage cancers. CONCLUSION: C. elegans olfaction enabled the detection of gastrointestinal cancers from urine with high sensitivity, which can provide the basis for the development of N-NOSE as a gastrointestinal cancer screening test.

Behavioural Response Alteration in Caenorhabditis elegans to Urine After Surgical Removal of Cancer: Nematode-NOSE (N-NOSE) for Postoperative Evaluation.

The technique used for cancer monitoring is essential for effective cancer therapy. Currently, several methods such as diagnostic imaging and biochemical markers have been used for cancer monitoring, but these are invasive and show low sensitivity. A previous study reported that Caenorhabditis elegans sensitively discriminated patients with cancer from healthy subjects, based on the smell of a urine sample. However, whether C. elegans olfaction can detect the removal of cancerous tumours remains unknown. This study was conducted to examine C. elegans olfactory behaviour to urine samples collected from 78 patients before and after surgery. The diagnostic ability of the technique termed Nematode-NOSE (N-NOSE) was evaluated by receiver operating characteristic (ROC) analysis. The ROC curve of N-NOSE was higher than those of classic tumour markers. Furthermore, we examined the change in C. elegans olfactory behaviour following exposure to preoperative and postoperative samples. The results suggest that a reduction in attraction indicates the removal of the cancerous tumour. This study may lead to the development of a noninvasive and highly sensitive tool for evaluating postoperative cancer patients.

Perioperative airway management of a 16-year-old boy with progressive airway obstruction due to juvenile nasopharyngeal angiofibroma.

Juvenile nasopharyngeal angiofibroma (JNA) involves difficult anesthetic management because of the risk of massive bleeding, while airway management is rarely a problem in JNA. This report presents an unusual case of JNA causing airway obstruction.

TGF-ß-induced phosphorylation of Akt and Foxo transcription factors negatively regulates induced regulatory T cell differentiation.

Transforming growth factor-ß (TGF-ß) is a pivotal cytokine in the differentiation of regulatory T cells, and Foxo transcription factors positively regulate this process. On the other hand, the function of Foxo transcription factors is negatively regulated by PI3K/Akt signaling, which is activated by TGF-ß in many types of cells; yet the role of TGF-ß in Akt activity and its downstream substrates in CD4+ T cells, including Foxo transcription factors, remains to be determined. Herein, we demonstrate that TGF-ß selectively induces Akt phosphorylation at Ser473 but not at Thr308 in a class IA PI3K-dependent manner in CD4+ T cells, resulting in the phosphorylation and inhibition of Foxo transcription factors and negatively regulating the differentiation of induced regulatory T cells (iTregs). These observations reveal a novel negative regulatory mechanism involving Akt and Foxo transcription factors induced by TGF-ß in the iTreg differentiation process.

PI3K-Akt-mTORC1-S6K1/2 axis controls Th17 differentiation by regulating Gfi1 expression and nuclear translocation of RORγ.

The PI3K-Akt-mTORC1 axis contributes to the activation, survival, and proliferation of CD4(+) T cells upon stimulation through TCR and CD28. Here, we demonstrate that the suppression of this axis by deletion of p85α or PI3K/mTORC1 inhibitors as well as T cell-specific deletion of raptor, an essential component of mTORC1, impairs Th17 differentiation in vitro and in vivo in a S6K1/2-dependent fashion. Inhibition of PI3K-Akt-mTORC1-S6K1 axis impairs the downregulation of Gfi1, a negative regulator of Th17 differentiation. Furthermore, we demonstrate that S6K2, a nuclear counterpart of S6K1, is induced by the PI3K-Akt-mTORC1 axis, binds RORγ, and carries RORγ to the nucleus. These results point toward a pivotal role of PI3K-Akt-mTORC1-S6K1/2 axis in Th17 differentiation.

Autoimmunity against M2muscarinic acetylcholine receptor induces myocarditis and leads to a dilated cardiomyopathy-like phenotype.

Patients with dilated cardiomyopathy (DCM) often have autoantibodies against cardiac antigens including the M(2) muscarinic acetylcholine receptor (M(2)R). To elucidate the role of autoimmunity against M(2)R in disease development, we induced an immune response against M(2)R by adoptive transfer into Rag2(-/-) mice of splenocytes from M(2)R(-/-) mice immunized with a recombinant M(2)R protein. T lymphocytes transiently infiltrated the heart in recipient mice followed by morphological changes in cardiomyocytes. These mice produced IgG antibodies against M(2)R, which bound to cardiomyocytes in vivo and decreased the amplitude of calcium signals in isolated rat cardiomyocytes in vitro. Recipient mice showed increased heart weights associated with increased intraventricular diameter, decreased systolic function, and increased action potential duration, which are characteristics of DCM. Our results suggest that myocarditis and DCM associated with the presence of anti-M(2)R antibodies are autoimmune diseases with a risk of progressing to the terminal stage. Our mouse model will be useful in the analysis of the molecular mechanisms of disease progression and the development of new therapies for DCM.

Listerial invasion protein internalin B promotes entry into ileal Peyer's patches in vivo.

Listeria monocytogenes (Lm) invades the host intestine using listerial invasion proteins, internalins. The in vivo role of internalin A (InlA) and internalin B (InlB) is reported here. Intragastric (i.g.) administration and ligated loop assays with ΔinlB-Lm demonstrated that a lack of InlB significantly attenuates the invasive ability of Lm into various organs. On the other hand, InlA(m)-Lm expressing a mutant InlA with two substitutions, S192N and Y369S, which has been reported to increase the affinity of InlA to mouse E-cadherin, resulted in little increase in intestinal infection according to both ligated loop and i.g. infection assays. Lm preferentially enters ileal Peyer's patch (PP) via M cells and ΔinlB-Lm showed severely reduced ability to invade though these cells. The present results reveal the importance of InlB, which accelerates listerial invasion into M cells on ileal PPs in vivo.

Critical roles of NK and CD8+ T cells in central nervous system listeriosis.

Listeria monocytogenes (LM) causes a life-threatening infectious disease affecting the brain of humans and domestic animals. Unfortunately, no adequate murine models for CNS listeriosis exist. Using intraparenchymal injection, we have established a new murine model for CNS listeriosis. Injection of a small volume of bacterial suspension limits the bacteria to the brain parenchyma with no leakage into the ventricular system. This new method enabled us to investigate the progression of and recovery from listerial brain infection, revealing roles for both innate and adaptive immune cells in CNS listeriosis. In the early phase of CNS listeriosis, NK cell-derived IFN-gamma is a critical cytokine in the limitation of bacterial growth by the host defense. During the later phase, CD8(+) but not CD4(+) T cells play a critical role and LM-specific CD8(+) T cells kill LM-infected microglia. Thus, innate and adaptive immune responses combine to successfully eliminate bacteria from the brain.

Role of Peyer's patches in the induction of Helicobacter pylori-induced gastritis.

Helicobacter pylori is a Gram-negative spiral bacterium that causes gastritis and peptic ulcer and has been implicated in the pathogenesis of gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. Although Th1 immunity is involved in gastritis and the accumulation of H. pylori-specific CD4(+) T cells in the H. pylori-infected gastric mucosa in human patients, how T cells are primed with H. pylori antigens is unknown because no apparent lymphoid tissues are present in the stomach. We demonstrate here that Peyer's patches (PPs) in the small intestine play critical roles in H. pylori-induced gastritis; no gastritis is induced in H. pylori-infected mice lacking PPs. We also observed that the coccoid form of H. pylori is phagocytosed by dendritic cells in PPs. We propose that H. pylori converts to the coccoid form in the anaerobic small intestine and stimulates the host immune system through PPs.

Maternal ghrelin plays an important role in rat fetal development during pregnancy.

Ghrelin, an acylated peptide serving as an endogenous ligand for GH secretagogue receptor (GHS-R), was originally isolated from rat and human stomach. In this study, we report the critical role of maternal ghrelin in fetal development. High levels of ghrelin receptor (GHS-R) mRNA were detected in various peripheral fetal tissues beginning at embryonic d 14 and lasting until birth. Fetal GHS-R expression was also confirmed in fetal tissues by immunohistochemistry. Autoradiography revealed that both des-acyl ghrelin and acyl ghrelin bind to fetal tissues. Chronic treatment of mothers with ghrelin resulted in a significant increase in birth weight in comparison to newborns from saline-treated mothers. Even when maternal food intake after ghrelin treatment was restricted through paired feeding, significant stimulation of fetal development still occurred. Conversely, active immunization of mothers against ghrelin decreased fetal body weight during pregnancy. A single ghrelin injection into the mother increased circulating ghrelin levels in the fetus within 5 min of injection, suggesting that maternal ghrelin transits easily to the fetal circulation. High levels of des-acyl ghrelin were detected in fetal blood and amniotic fluid. Both acylated and des-acyl ghrelin increased [3H]thymidine and 5-bromo-2'-deoxyuridine incorporation of cultured fetal skin cells in a dose-dependent manner, and calcium-imaging analysis revealed that acyl and des-acyl ghrelin increased the Ca2+ influx in discrete cultured fetal skin cells, respectively. These results indicate that maternal ghrelin regulates fetal development during the late stages of pregnancy.