Fast-track preparation of lung specimens for electron microscope observations of the pulmonary endothelial glycocalyx.

The glycocalyx (GCX) covers the luminal surface of blood vessels and regulates vascular permeability. As GCX degradation predicts various types of vasculopathy, confirming the presence of this structure is useful for diagnosis. Since the GCX layer is very fragile, careful fixation is necessary to preserve its structure. We explored appropriate and feasible methodologies for visualizing the GCX layer using lung tissue specimens excised from anesthetized mice. Each specimen was degassed and immersed in Alcian blue (ALB) fixative solution, and then observed using electron microscopy. Specimens from septic mice were prepared as negative GCX controls. Using these immersion-fixed specimens, the GCX layer was successfully observed using both transmission and scanning electron microscopy; these observations were similar to those obtained using the conventional method of lanthanum perfusion fixation. Spherical aggregates of GCX were observed in the septic mouse specimens, and the GCX density was lower in the septic specimens than in the non-septic specimens. Of note, the presently reported methodology reduced the specimen preparation time from 6 to 2 days. We, therefore, concluded that our novel method could be applied to human lung specimens and could potentially contribute to the further elucidation of vasculopathies.

A survey on the safety of anesthesia management provided by dental anesthesiologists in Japan: a 5-year survey by the Japanese Dental Society of Anesthesiology.

OBJECTIVES: The Japanese Dental Society of Anesthesiology (JDSA) has conducted a survey on the safety of anesthetic practice provided by dental anesthesiologists. This report includes information on the incidence of life-threating events, which is necessary for evaluating the safety of dental anesthesia. MATERIAL AND METHODS: This study was designed as a retrospective observational questionnaire-based survey. All 32 JDSA accredited training facilities participated in this study. The accredited facilities were requested to provide annual data on basic demographic information concerning anesthetic management during the 5-year period from 2014 to 2018, inclusive. Details regarding life-threatening events were also requested. RESULTS: During the survey period between 2014 and 2018, a total of 219,343 cases of anesthetic management (80,138 cases of general anesthesia, 127,819 cases of sedation, and 11,386 cases of monitoring) were reported by the 32 JDSA accredited training facilities. The overall incidence of life-threatening events occurring during clinical dental anesthesia was 2.14/10,000, while the incidence of anesthesia-related events was 0.96/10,000. No deaths arising from anesthesia-related events occurred. CONCLUSIONS: This is the first survey on clinical outcomes of dental anesthesia to be conducted. The survey results provide evidence supporting the safety of anesthetic management as performed by dental anesthesiologists. CLINICAL RELEVANCE: The results of this study will provide a basis for benchmarking the safety of dental anesthesia not only in Japan, but also around the world.

Control of Tongue Position in Patients with Obstructive Sleep Apnea: Concept and Protocol for a Randomized Controlled Crossover Trial.

We hypothesize that the control of tongue position using a newly developed tongue position retainer, where the tongue is held in a protruded position (i.e., intervention A) or in its resting position (i.e., intervention B), is effective for maintaining upper airway patency in obstructive sleep apnea (OSA) compared with no control of tongue position. This is a randomized, controlled, non-blinded, crossover, and two-armed trial (i.e., sequence AB/BA) in 26 male participants (i.e., sample size) who are scheduled to undergo a dental operation under intravenous sedation with OSA (10 ≤ respiratory event index < 30/h). Participants will be randomly allocated into either sequence by a permuted block method, stratified by body mass index. Under intravenous sedation, participants will undergo two interventions, separated by a washout period after receiving intervention A or intervention B using a tongue position retainer after baseline evaluation, before each intervention is provided. The primary outcome is the abnormal breathing index of apnea as determined by the frequency of apnea per hour. We expect that, compared with no control of tongue position, both intervention A and intervention B will improve the abnormal breathing events with superior effects achieved by the former, offering a therapeutic option for OSA.

Exploring the pathophysiological mechanism of interstitial edema focusing on the role of macrophages and their interaction with the glycocalyx.

OBJECTIVES: Glycocalyx lines the vascular intraluminal space that regulates fluid movement between the intra- and extra-vascular compartments. The depletion of glycocalyx (GCX) is associated with leukocyte accumulation, possibly causing the endothelial cells to become hyperpermeable in various organs, including oral tissues. Whether neutrophils or macrophages are responsible for developing interstitial edema remains controversial. We explored the pathophysiological mechanism of interstitial edema by examining the role of reactive neutrophils and macrophages and their interactions with GCX. METHODS: An anti-MHC class I antibody was administered intravenously to male BALB/c mice to induce pulmonary edema. Pulmonary edema was evaluated by measuring the lung wet-to-dry weight ratio. Changes in the GCX were evaluated by electron microscopy and measurements of the serum level of soluble syndecan-1. Heparin sulfate was administered to examine its protective effect on the GCX. The macrophages were depleted using clodronate to examine their role in developing edema. RESULTS: The GCX degradation induced by the anti-MHC class I antibody was accompanied by increased serum syndecan-1 and heparan sulfate levels. Macrophage depletion inhibited the development of pulmonary edema, and the administration of supplemental heparin suppressed the edema. CONCLUSIONS: We demonstrated that the degradation of the GCX induced by the anti-MHC class I antibody was suppressed by macrophage depletion. These results suggest that macrophages may play a key role in interstitial edema. Heparin inhibited both the degradation of the GCX and interstitial edema. This study's results may be extrapolated to develop an interventional strategy for inhibiting interstitial edema in various organs.

Anesthesia Management of a Patient With Familial Cold Autoinflammatory Syndrome: A Case Report.

Familial cold autoinflammatory syndrome (FCAS) is a rare phenotype of cryopyrin-associated periodic syndrome (CAPS) and is characterized by repetitive systemic inflammation triggered by cold stimulation. Recently, we treated a 13-year-old female with FCAS/CAPS scheduled to undergo removal of an impacted tooth. To minimize perioperative heat loss, a forced-air warming system was utilized to prewarm the patient for 10 minutes before induction of general anesthesia. The patient's core and peripheral temperatures were monitored with axillary, superficial temporal artery, and rectal thermometers. The difference in temperatures at these 3 locations decreased to 0.4° C within 60 minutes as a result of the forced-air warming system before induction. Perioperative use of the warming system successfully prevented the occurrence any significant redistribution hypothermia and any symptoms of FCAS/CAPS.

Optimal Timing of Intravenous Acetaminophen Administration for Postoperative Analgesia.

OBJECTIVE: Acetaminophen (APAP) is widely used as an analgesic for postoperative pain relief. However, the pharmacokinetic-pharmacodynamic (PK-PD) properties of intravenous APAP administration remain unclear. We developed a PK-PD model in adult volunteers. METHODS: APAP (1 g) was intravenously administered to 15 healthy volunteers. The pain equivalent current (PEC) was then measured using the pulse current, corresponding to the quantitative value of pain perception. The PK model was developed using a 2-compartment model, and the PD model was developed using a linear model and an effect compartment model. RESULTS: APAP plasma concentration peaked just administration, whereas PEC significantly increased at 90 minutes and lasted through the experimental period (300 minutes). APAP plasma concentrations and PEC were processed for use in the PK-PD model. The developed PK-PD model delineates the analgesic effect profile, which peaked at 188 minutes and lasted until 327 minutes. CONCLUSION: We developed the PK/PD model for APAP administered intravenously. The analgesic effect can be expected ∼90 minutes after administration and to last >5 hours. It is suggested that APAP be administered ∼90 minutes prior to the onset of anticipated postoperative pain.

Intrinsic properties and synaptic connectivity of Phox2b-expressing neurons in rat rostral parvocellular reticular formation.

The paired-like homeobox 2b gene (Phox2b) is critical for the development of the autonomic nervous system. We have previously demonstrated the distinct characteristics of Phox2b-expressing (Phox2b+) neurons in the reticular formation dorsal to the trigeminal motor nucleus (RdV), which are likely related to jaw movement regulation. In this study, we focused on Phox2b+ neurons in the rostral parvocellular reticular formation (rPCRt), a critical region for controlling orofacial functions, using 2-11-day-old Phox2b-EYFP rats. Most Phox2b+ rPCRt neurons were glutamatergic, but not GABAergic or glycinergic. Approximately 65 % of Phox2b+ rPCRt neurons fired at a low frequency, and approximately 24 % of Phox2b+ rPCRt neurons fired spontaneously, as opposed to Phox2b+ RdV neurons. Stimulation of the RdV evoked inward postsynaptic currents in more than 50 % of Phox2b+ rPCRt neurons, while only one Phox2b+ rPCRt neuron responded to stimulation of the nucleus of the solitary tract. Five of the 10 Phox2b+ neurons sent their axons that ramified within the trigeminal motor nucleus (MoV). Of these, the axons of the two neurons terminated within both the MoV and rPCRt. Our findings suggest that Phox2b+ rPCRt neurons have distinct electrophysiological and synaptic properties that may be involved in the motor control of feeding behavior.

Time-Dependent Dynamics Required for the Degradation and Restoration of the Vascular Endothelial Glycocalyx Layer in Lipopolysaccharide-Treated Septic Mice.

The endothelial glycocalyx (GCX) plays a key role in the development of organ failure following sepsis. Researchers have investigated GCX degradation caused by pathological conditions. Nonetheless, the GCX restoration process remains poorly understood. Herein, we developed a model in which GCX restoration could be reproduced in mice using in vivo imaging and a dorsal skinfold chamber (DSC). The severity of sepsis was controlled by adjusting the dose of lipopolysaccharide (LPS) used to trigger GCX degradation in BALB/c mice. We evaluated the GCX thickness, leukocyte-endothelial interactions, and vascular permeability using in vivo imaging through DSC under intravital microscopy. The plasma concentration of syndecan-1(Sdc-1), a GCX structural component, was also determined as a marker of GCX degradation. Thus, we developed a reproducible spontaneous GCX recovery model in mice. Degraded GCX was restored within 24 h by the direct visualization of the endothelial GCX thickness, and leukocyte-endothelial interactions. In contrast, indirectly related indicators of recovery from sepsis, such as body weight and blood pressure, required a longer recovery time. This model can be used to study intractable angiopathy following sepsis.

Exploring the mechanism of hyperpermeability following glycocalyx degradation: Beyond the glycocalyx as a structural barrier.

Pathological hyperpermeability is a morbidity involved in various systemic diseases, including sepsis. The endothelial glycocalyx layer (GCX) plays a key role in controlling vascular permeability and could be a useful therapeutic target. The purpose of the present study was to analyze the functional role of the GCX in vascular permeability and to elucidate its role in pathological conditions. First, male C57BL/6J wild-type mice were used as in vivo models to study the effects of sepsis and the pharmacological digestion of glycosaminoglycans (GAGs) on the GCX. Vascular permeability was evaluated using fluorescein isothiocyanate (FITC)-labeled dextran. Second, the changes in gene expression in vascular endothelial cells after GAGs digestion were compared between a control and a septic model using RNA sequencing. In the in vivo study, the glycocalyx was depleted in both the septic model and the group with pharmacological GAGs digestion. FITC-labeled dextran had leaked into the interstitium in the septic group, but not in the other groups. In the in vitro study, histamine decreased the transendothelial electrical resistance (TEER), indicating an increase in permeability. GAGs digestion alone did not change the TEER, and the effect of histamine on the TEER was not enhanced by GAGs digestion. The gene expression profiles after GAGs digestion differed from the control condition, indicating the initiation of signal transduction. In conclusion, we demonstrated that the structural barrier of the GCX does not solely determine the fluid permeability of the endothelial layer, since enzymatic depletion of the GCX did not increase the permeability. The gene expression findings suggest that the digestion of GAGs alone did not induce hyperpermeability either in vitro or in vivo, although sepsis did induce hyperpermeability. While GAGs degradation by itself does not appear to induce hyperpermeability, it may play an important role in initiating signal transductions.

Cdc42 has important roles in postnatal angiogenesis and vasculature formation.

Cdc42, a Rho family low molecular weight G protein, has important roles in various cell functions, including cytoskeletal rearrangement, cell adhesion and cell proliferation and differentiation. To investigate the involvement of Cdc42 in the activities of vascular endothelial cells, we generated Cdc42 conditional knockout mice in which Cdc42 was time -specifically deficient in vascular endothelial cells (Cdc42 â€‹fl/fl; VE-Cad CreERT: Cdc42 cKO). When the Cdc42 gene was deleted after birth, Cdc42 cKO mice were smaller than the control mice, and died between postnatal day 8 (P8) and P10. Necropsy findings confirmed that these mice had various pathological aberrances in the vessels of most organs, such as blood flow congestion and blood cell invasion. Electron microscopic observations also revealed that capillary endothelial cells were detached from the basement membrane as well as phagocytosis of dead endothelial cells induced by macrophages. Moreover, vascular sprouting from aortic rings induced by VEGF-A was diminished in samples from the Cdc42 cKO mice because of an endothelial cell proliferation defect. These results suggest that Cdc42 in vascular endothelial cells has important roles in blood vessel formation after birth.

Effect of remifentanil on intraoperative fluid balance: a retrospective statistical examination of factors contributing to fluid balance.

BACKGROUND: Postoperative fluid retention is a factor that causes delay in recovery and unexpected adverse events. It is important to prevent intraoperative fluid retention, which is putatively caused by intraoperative release of stress hormones, such as ADH (anti-diuretic hormone) or others. We hypothesized that intraoperative analgesia may prevent pathological fluid retention. We retrospectively explored the relationship between analgesics and in-out balance in surgical patients from anesthesia records. METHODS: Anesthetic records of 80 patients who had undergone orthognathic surgery were checked in this study. Patients were anesthetized with either TIVA (propofol and remifentanil) or inhalational anesthesia (sevoflurane and remifentanil). During surgery, acetated Ringer's solution was infused for maintenance at a rate of 3-5 ml/kg/h at the discretion of the anesthetist. The perioperative parameters, including the amount of crystalloid and colloid infused, and the amount of urine and bleeding were checked. Furthermore, we checked the amount and administration rate of remifentanil during the surgical procedure. The correlation coefficient between the remifentanil dose and the in-out balance or the urinary output was analyzed using the Pearson correlation coefficient. The contributing factor to fluid retention, including urinary output, was statistically examined by means of multivariate logistic regression analysis. RESULTS: A significant positive correlation was found between remifentanil dose and urinary output. Urinary output less than 0.04 ml/kg/min was suggested to cause positive fluid balance. Although in-out balance approaches zero balance with increase in remifentanil administration rate, no contributing factor for near-zero fluid balance was statistically picked up. The remifentanil administration rate was statistically picked up as the significant factor for higher urinary output (> 0.04 ml/kg/min) (OR, 2,644; 95% CI, 3.2-2.2 × 106) among perioperative parameters. CONCLUSIONS: In conclusion, remifentanil contributes in maintaining the urinary output during general anesthesia. Although further prospective study is needed to confirm this hypothesis, it was suggested that fluid retention could be avoided through suppressing intraoperative stress response by means of appropriate maintenance of remifentanil infusion rate.

Intra-vital Observation of Lung Water Retention Following Intravenous Injection of Anti-MHC-class I (H-2K) Monoclonal Antibody in Mice.

BACKGROUND/AIM: Leukocyte activation is thought to be a major step in sepsis-induced pulmonary edema. We attempted to confirm whether pulmonary edema can be reproduced under intravital microscopy in a model of transfusion-related acute lung injury (TRALI) using MHC class I-specific antibody. MATERIALS AND METHODS: The surface pulmonary microcirculation was observed using an epi-fluorescence microscope through a thoracic window in 50 male mice. Monoclonal MHC class I-specific antibody (Ab) was administered to the animals, while the control group received saline. The leukocytes and macro-molecular leakage in the pulmonary circulation were analyzed. RESULTS: Leukocytes accumulated in the capillaries (52.5±12.7 leukocytes per designated area in Ab group vs. 20.8±3.1 in control). The air-containing alveolus area significantly shrank from 2,224.9±934.9 µm2 to 509.7±380.8 µm2 in the Ab group. CONCLUSION: Pulmonary edema develops rapidly following leukocyte accumulation in the lung. We confirmed that leukocyte accumulation without an underlining condition is sufficient to induce pulmonary edema.

A Formula for Estimating the Appropriate Tube Depth for Intubation.

An estimation of the appropriate tubing depth for fixation is helpful to prevent inadvertent endobronchial intubation and prolapse of cuff from the vocal cord. A feasible estimation formula should be established. We measured the anatomical length of the upper-airway tract through the oral and nasal pathways on cephalometric radiographs and tried to establish the estimation formula from the height of the patient. The oral upper-airway tract was measured from the tip of the incisor to the vocal cord. The nasal upper-airway tract was measured from the tip of the nostril to the vocal cord. The tracts were smoothly traced by using software. The length of the oral upper-airway tract was 13.2 ± 0.8 cm, and the nasal upper-airway tract was 16.1 ± 0.9 cm. We found no gender difference ( p > .05). The correlations between the patients' height and the length of the oral and nasal upper-airway tracts were 0.692 and 0.760, respectively. We found that the formulas (height/10) - 3 (in cm) for oral upper-airway and (height/10) + 1 (in cm) for nasal upper-airway tract are the simple fit estimation formulas. The average error and standard deviation of the estimated values from the measured values were 0.50 ± 0.66 cm for the oral tract and 0.39 ± 0.63 cm for the nasal tract. Thus, considering the length of the intubation marker of each product (DM), we would like to propose the length of tube fixation as (height/10) + 1 + DM for nasal intubation and (height/10) - 3 + DM for oral intubation. In conclusion, the estimation formulas of (height/10) - 3 + DM and (height/10) + 1 + DM for oral and nasal intubation, respectively, are within almost 1 cm error in most cases.

Nasopharyngeal Tube Effects on Breathing during Sedation for Dental Procedures: A Randomized Controlled Trial.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: Dental procedures under sedation can cause hypoxic events and even death. However, the mechanism of such hypoxic events is not well understood. WHAT THIS ARTICLE TELLS US THAT IS NEW: Apnea and hypopnea occur frequently during dental procedures under sedation. The majority of the events are not detectable with pulse oximetry. Insertion of a nasal tube with small diameter does not reduce the incidence of apnea/hypopnea. BACKGROUND: Intravenous sedation is effective in patients undergoing dental procedures, but fatal hypoxemic events have been documented. It was hypothesized that abnormal breathing events occur frequently and are underdetected by pulse oximetry during sedation for dental procedures (primary hypothesis) and that insertion of a small-diameter nasopharyngeal tube reduces the frequency of the abnormal breathing events (secondary hypothesis). METHODS: In this nonblinded randomized control study, frequency of abnormal breathing episodes per hour (abnormal breathing index) of the patients under sedation for dental procedures was determined and used as a primary outcome to test the hypotheses. Abnormal breathing indexes were measured by a portable sleep monitor. Of the 46 participants, 43 were randomly allocated to the control group (n = 23, no nasopharyngeal tube) and the nasopharyngeal tube group (n = 20). RESULTS: In the control group, nondesaturated abnormal breathing index was higher than the desaturated abnormal breathing index (35.2 [20.6, 48.0] vs. 7.2 [4.1, 18.5] h, difference: 25.1 [95% CI, 13.8 to 36.4], P < 0.001). The obstructive abnormal breathing index was greater than central abnormal breathing index (P < 0.001), and half of abnormal breathing indexes were followed by irregular breathing. Despite the obstructive nature of abnormal breathing, the nasopharyngeal tube did not significantly reduce the abnormal breathing index (48.0 [33.8, 64.4] h vs. 50.5 [36.4, 63.9] h, difference: -2.0 [95% CI, -15.2 to 11.2], P = 0.846), not supporting the secondary hypothesis. CONCLUSIONS: Patients under sedation for dental procedure frequently encounter obstructive apnea/hypopnea events. The majority of the obstructive apnea/hypopnea events were not detectable by pulse oximetry. The effectiveness of a small-diameter nasopharyngeal tube to mitigate the events is limited.

Acute tramadol enhances brain activity associated with reward anticipation in the nucleus accumbens.

BACKGROUND: Tramadol is an analgesic with monoamine reuptake inhibition and µ-opioid receptor activation. Although tramadol has been widely used for treatment of various pain conditions, there is controversy over the risk of abuse potential. We examined the effects of tramadol on the reward system in humans using functional magnetic resonance imaging (fMRI) to assess the potential of tramadol for drug abuse or dependence. METHODS: A randomized, double-blind, placebo-controlled, crossover study was conducted for 19 healthy adults under tramadol or placebo. In association with subjective mood questionnaires, monetary incentive delay (MID) task was performed to assess the neural response to reward anticipation during fMRI. Subjective mood measures and blood oxygenation level-dependent (BOLD) signal during gain and loss anticipation were compared between tramadol and placebo. RESULTS: Tramadol significantly reduced anxiety (Z = - 2.513, p = 0.012) and enhanced vigor (Z = - 2.725, p = 0.006) compared with placebo. By Mood Rating Scale, tramadol provoked contented (Z = - 2.316, p = 0.021), relaxed (Z = - 2.236, p = 0.025), and amicable feelings (Z = - 2.015, p = 0.044) as well as increased alertness (Z = - 1.972, p = 0.049) and contentedness domains (Z = - 2.174, p = 0.030) compared with placebo. Several brain regions including nucleus accumbens (NAc) were activated during gain anticipation in the MID task under both tramadol and placebo. Tramadol increased the %BOLD signal change in NAc at +¥500 cue significantly more than the placebo (Z = - 2.295, p = 0.022). CONCLUSION: Tramadol enhances the reward system and thereby may have abuse potential or precipitate drug abuse in human.

FGF-2 suppresses expression of nephronectin via JNK and PI3K pathways.

Nephronectin (Npnt), an extracellular matrix protein, is a ligand for integrin α8ß1 and is involved in the development of various organs, such as the kidneys, bones, liver, and muscles. Previously, we found that Npnt expression was inhibited by various cytokines including transforming growth factor-ß (Tgf-ß) and oncostatin M (Osm). Fibroblast growth factor (Fgf)-2, otherwise known as basic Fgf, also plays important roles in skeletal development and postnatal osteogenesis. In this study, Npnt expression was found to be suppressed by Fgf-2 in MC3T3-E1 cells, an osteoblast-like cell line, in a dose- and time-dependent manners. Furthermore, Fgf-2-mediated Npnt mRNA suppression was shown to involve the Jun N-terminal kinase (JNK) and phosphoinositide-3 kinase (PI3K) pathways. Together, our results suggest that FGF-2 suppresses Npnt gene expression via JNK and PI3K pathways.

Cooperation of Rho family proteins Rac1 and Cdc42 in cartilage development and calcified tissue formation.

Rac1 and Cdc42, Rho family low molecular weight G proteins, are intracellular signaling factors that transmit various information from outside to inside cells. Primarily, they are known to control various biological activities mediated by actin cytoskeleton reorganization, such as cell proliferation, differentiation, and apoptosis. In order to investigate the functions of Rac1 and Cdc42 in bone formation, we prepared cartilage-specific double conditional knockout mice, Rac1fl/fl; Cdc42fl/fl; Col2-Cre (Rac1: Cdc42 dcKO mice), which died just after birth, similar to Cdc42fl/fl; Col2-Cre mice (Cdc42 cKO mice). Our findings showed that the long tubule bone in Rac1: Cdc42 dcKO mice was shorter than that in Rac1fl/fl; Col2-Cre mice (Rac1 cKO mice) and Cdc42 cKO mice. Abnormal skeleton formation was also observed and disordered columnar formation in the growth plate of the Rac1: Cdc42 dcKO mice was more severe as compared to the Rac1 cKO and Cdc42 cKO mice. Together, these results suggest that Rac1 and Cdc42 have cooperating roles in regulation of bone development.

Sudden Tachycardia Due to Submucosal Migration of an Epinephrine-Soaked Swab During Nasal Intubation.

A 23-year-old healthy man was scheduled for extraction of his mandibular third molars under general anesthesia with nasotracheal intubation. Sudden sinus tachycardia up to 170 beats/min occurred when applying an epinephrine solution-soaked swab into the nasal cavity for preventing epistaxis during intubation. This was presumably evoked by submucosal migration of the swab into a false passage created because of the force applied during a prior failed attempt at nasal passage of the tracheal tube, and rapid epinephrine absorption by the traumatized mucosa. The causes of the unexpected severe tachycardia in our patient are discussed.

Whole Blood Platelet Aggregation Test and Prediction of Hemostatic Difficulty After Tooth Extraction in Patients Receiving Antiplatelet Therapy.

When patients on antiplatelet therapy (APT) require minor invasive surgery, APT is usually continued to limit the risk of thrombosis. However, the possibility of hemostatic difficulties necessitates the monitoring of platelet aggregation to prevent unexpected bleeding. We examined whether whole blood aggregometry as a point-of-care testing (POCT) could be useful as a tool for predicting hemostatic difficulties. Sixty-five patients receiving APT and 15 patients who were not receiving APT were enrolled in the present study; all patients were scheduled to undergo a tooth extraction. Whole blood samples were obtained and were examined using multiple electrode aggregometry. The aggregometry was performed using arachidonic acid (AA), adenosine diphosphate (ADP), and thrombin receptor activating peptide. Hemostatic difficulty was defined as a need for more than 10 minutes of compression to achieve hemostasis. The AA test results were significantly lower in patients treated with aspirin (control: 97.7 [29.0] U, aspirin: 14.5 [7.2] U, P < .001). The ADP test results were also significantly lower in patients treated with a P2Y12 inhibitor (control: 77.7 [21.7] U, P2Y12 inhibitor: 37.3 [20.4] U, P < .01). Six of the examined cases exhibited hemostatic difficulties. The cutoff values for the prediction of hemostatic difficulty were 16.5 U for the AA test (sensitivity, 0.833; specificity, 0.508) and 21 U for the ADP test (sensitivity, 0.847; specificity, 0.500). Our study showed that whole blood aggregometry was useful as a POCT for the prediction of hemostatic difficulties after tooth extraction in patients receiving APT.

IL-1ß suppresses nephronectin expression in osteoblasts via ERK1/2 and JNK.

Nephronectin (Npnt), an extracellular matrix protein, is considered to play critical roles in development of various tissues and their functions. In basic science experiments, we found that interleukin-1ß (IL-1ß), well known to have an important role in inflammatory response, inhibited Npnt gene expression in MC3T3-E1 cells, a mouse osteoblastic cell line. The purpose of this study was to investigate mechanisms that govern the regulation of Npnt gene expression by IL-1ß in osteoblasts.