Eucalyptol induces osteoblast differentiation through ERK phosphorylation in vitro and in vivo.

Eucalyptol (EU) is monoterpene oxide that is the main component of the essential oil extracted from aromatic plants such as Eucalyptus globules. EU has therapeutic effects such as antibacterial, anti-inflammatory and antioxidant in chronic diseases including inflammation disorder, respiratory disease, and diabetic disease. However, the effects of EU on osteoblast differentiation and bone diseases such as osteoporosis have not been studied. The present study investigated the effects of EU on osteoblast differentiation and bone formation. EU induces mRNA and protein expression of osteogenic genes in osteoblast cell line MC3T3-E1 and primary calvarial osteoblasts. EU also promoted alkaline phosphatase (ALP) activity and mineralization. Here, the osteoblast differentiation effect of EU is completely reversed by ERK inhibitor. These results demonstrate that osteoblast differentiation effect of EU is mediated by ERK phosphorylation. The efficacy of EU on bone formation was investigated using surgical bone loss-induced animal models. EU dose-dependently promoted bone regeneration in zebrafish caudal fin rays. In the case of ovariectomized mice, EU increased ERK phosphorylation and ameliorated bone loss of femurs. These results indicate that EU ameliorates bone loss by promoting osteoblast differentiation through ERK phosphorylation. We suggest that EU, plant-derived monoterpenoid, may be useful for preventing bone loss. KEY MESSAGES: Eucalyptol (EU) increases osteoblast differentiation in pre-osteoblasts. EU up-regulates the osteogenic genes expression via ERK phosphorylation. EU promotes bone regeneration in partially amputated zebrafish fin rays. Oral administration of EU improves ovariectomy-induced bone loss and increases ERK phosphorylation.

Concealed congenital long QT syndrome during velopharyngeal dysfunction correction: a case report.

The congenital long QT syndrome (LQTS) is an inherited cardiac disorder characterized by increased QT intervals and a tendency to experience ventricular tachycardia, which can cause fainting, heart failure, or sudden death. A 4-year-old female patient undergoing velopharyngeal correction surgery under general anesthesia suddenly developed Torsades de pointes. Although the patient spontaneously resolved to sinus rhythm without treatment, subsequent QT prolongation persisted. Here, we report a case of concealed LQTS with a literature review.

A prospective pilotstudy comparing the anesthetic effects of an alpha-2 agonist during holmium laser resection of the prostate and transurethral resection for prostate surgery for benign prostatic hyperplasia patients using selective alpha-1 blockers.

BACKGROUND: To examine the response to an α2receptor agonist used as a sedative for patients using long-term selective α1 blockers. METHODS: Sixty-nine consecutive patients undergoing transurethral prostate resection or holmium laser resection of the prostateunder spinal anesthesia were divided into two groups; group N (n = 37), which did not receive α1 blockers, and group T (n = 32), which was administered tamsulosin for at least 1 month before the study. Bispectral index scores, Modified Observer's Assessment of Alertness/Sedation scale scores, heart rate, and mean blood pressure were obtained under sedation using dexmedetomidine for 30 min during surgery. RESULTS: The only significant difference found between the groups were mean bloodpressure 15 min after the first loading dose injection of dexmedetomidine. Differencesbetween both groupswere noted at 15 min(group T: 100.2 ± 12.9 mmHg; group N: 90.0 ± 17.5 mmHg; P = 0.08), 20 min (group T: 99.8 ± 12.3 mmHg; group N: 87.4 ± 15.0 mmHg; P < 0.00), 25 min (group T: 99.3 ± 13.4 mmHg; group N: 85.4 ± 13.8 mmHg; P < 0.00), and 30 min (group T: 98.8 ± 13.1 mmHg; group N: 84.5 ± 13.5 mmHg; P < 0.00). CONCLUSIONS: The use of α2 agonists is appropriate during surgery for benign prostatic hyperplasia patients using tamsulosin, and there is no need to alter the dose. Alertness with anesthesia involving α2 agents was maintained for patients using long-term tamsulosin and patients who did not use tamsulosin. TRIAL REGISTRATION: The study was retrospectively registered with the Clinical Research Informational Service ( KCT0002967 , July 2, 2018).

Propofol attenuates osteoclastogenesis by lowering RANKL/OPG ratio in mouse osteoblasts.

Bone remodeling plays an important role in the bone healing process; for example, following fracture. The relative ratio of the receptor activator of nuclear factor kappa B ligand (RANKL)/ osteoprotegerin (OPG) controls osteoclast differentiation, thereby playing a pivotal role in the regulation of bone remodeling. Propofol, a widely used anesthetic agent in orthopedic procedures, is considered to possess potential antioxidant properties owing to its structural similarity to α-tocopherol. Antioxidants are known to enhance bone healing. Accordingly, in the present study, we aimed to investigate osteoblastic differentiation and RANKL/OPG expression following propofol administration, in order to assess the potentially beneficial effects of this drug on the bone remodeling process, using calvarial primary osteoblasts from newborn mice. Calvarial pre-osteoblast cells were cultured in media containing clinically relevant concentrations of propofol, and cytotoxicity, effects on cell proliferation, osteogenic activity, and osteoclastogenesis were examined. The present findings indicated that propofol did not exert cytotoxic effects or alter cell proliferation in primary calvarial osteoblasts. Further, propofol did not affect osteoblast differentiation. The RANKL/OPG ratio was found to be decreased following propofol administration, and osteoclastogenesis was significantly reduced, indicating that propofol attenuated the osteoclastogenesis-supporting activity of osteoblasts. The results demonstrate that propofol, at clinically relevant concentrations, exerts beneficial effects on bone remodeling by attenuating osteoclastogenesis via suppression of the RANKL/OPG expression axis.

Observations on significant hemodynamic changes caused by a high concentration of epidurally administered ropivacaine: correlation and prediction study of stroke volume variation and central venous pressure in thoracic epidural anesthesia.

BACKGROUND: Thoracic epidural anesthesia (TEA) exacerbates hypotension due to peripheral vasodilator effects following the use of general anesthetics. This study aimed to compare the hemodynamic changes caused by three different concentrations of epidural ropivacaine and to evaluate the performance of the stroke-volume variation (SVV) and central venous pressure (CVP) during TEA with general anesthesia. METHODS: A total of 120 patients were administered 8 mL of ropivacaine solution via epidural injection, following randomization into one of three groups based on the concentration of ropivacaine in the study solution: 0.75%, 0.375%, or 0.2%. Hemodynamics were monitored for 30 min after loading. We analyzed the hemodynamic changes in the subgroups according to an age cutoff of 60 years. Receiver operating characteristic (ROC) analysis was performed to characterize the relationship of the SVV, CVP, and a 20% decrease in the mean arterial pressure (MAP) following TEA. RESULTS: Data from 109 patients were analyzed. MAP and systemic vascular resistance index were significantly decreased, and SVV was significantly increased after epidural loading only in the 0.75% ropivacaine group. There was a significant difference in hemodynamics between young and elderly subgroups in the 0.75% ropivacaine group. SVV showed a negative correlation with MAP, whereas CVP showed no correlation. The ROC analysis of SVV demonstrated a weak predictive ability of a 20% decrease in MAP at 10 min after the loading dose, with an area-under-the-curve of 0.687 and a 9.5% optimal cutoff value (sensitivity, 60.6%; specificity, 68.9%). CONCLUSIONS: A high concentration of ropivacaine through TEA caused a significant decrease in the systemic vascular resistance and blood pressure. More significant decreases were shown in the elderly patients. Though the change of SVV showed a negative correlation with hypotension and indicated functional hypovolemia after TEA, the predictability was limited. CLINICAL TRIALS REGISTRATION: Number: NCT01559285 , date: January 24, 2013.

Carbon monoxide regulates glycolysis-dependent NLRP3 inflammasome activation in macrophages.

Low dose of carbon monoxide (CO) has anti-inflammatory role through various signaling pathways. Cellular metabolism has been implicated in the activation of inflammation in immune cells. However, the mechanisms by which CO-dependent metabolic regulation affect the immune response remain unclear. Here we show that CO-dependent metabolic pathway regulates the activation of the nucleotide-binding domain, leucine-rich-repeat-containing receptor (NLR), pyrin-domain-containing 3 (NLRP3) inflammasome. CO-releasing molecule-3 (CORM-3) resulted in reduced glycolysis-dependent NLRP3 inflammasome activation in macrophages. The reduced mTORC1 activation by CORM-3 resulted in less glycolysis during NLRP3 inflammasome activation. CORM-3 suppressed caspase-1 activation and the secretion of interleukin (IL)-1ß and IL-18 in macrophages in response to lipopolysaccharide (LPS) and ATP. Moreover, CORM-3 inhibits the oligomerization of the adaptor protein apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), which is required for NLRP3-dependent caspase-1 activation. Furthermore, CORM-3-treated mice showed substantial reduction in IL-1ß production by hyperglycemia in a mouse model of streptozotocin (STZ)-induced diabetes. Our results suggest that CO regulates glycolysis-dependent NLRP3 inflammasome activation and may provide a therapeutic approach for inflammation in metabolic diseases.

Anesthetic experience of frontotemporal dementia patient with severe autonomic dysfunction: a case report.

Anesthetic experience in frontotemporal dementia (FTD) with severe hypotension associated autonomic dysfunction has not yet been reported. Here in case, we report on the case of treatment with vasopressin to refractory hypotension in FTD patient. A 54-year-old male presented with a ten-year history of FTD with frequent syncope. The patient was scheduled to undergo subtotal gastrectomy for resection of stomach cancer. During the operation, sudden hypotension occurred and it was refractory to fluid and 1 unit of blood resuscitation and did not respond to catecholamine. Transesophageal echocardiography showed normal heart with adequate volume state. After intravenous administration of arginine vasopressin, the patient's vital signs returned to baseline values. Arginine vasopressin might be considered as a valuable alternative for treatment of severe refractory hypotension in autonomic dysfunction patients with FTD.

The effect of tulobuterol patches on the respiratory system after endotracheal intubation.

BACKGROUND: Endotracheal intubation during anesthesia induction may increase airway resistance (Raw) and decrease dynamic lung compliance (Cdyn). We hypothesized that prophylactic treatment with a transdermal ß2-agonist tulobuterol patch (TP) would help to reduce the risk of bronchospasm after placement of the endotracheal tube. METHODS: Eighty-two American Society of Anesthesiologists (ASA) category I or II adult patients showing obstructive patterns were divided randomly into a control and a TP group (n = 41 each). The night before surgery, a 2-mg TP was applied to patients in the TP group. Standard monitors were recorded, and target controlled infusion (TCI) with propofol and remifentanil was used for anesthesia induction and maintenance. Simultaneously, end-tidal carbon dioxide, Raw, and Cdyn were determined at 5, 10, and 15 min intervals after endotracheal intubation. RESULTS: There was no significant difference in demographic data between the two groups. The TP group was associated with a lower Raw and a higher Cdyn, as compared to the control group. Raw was significantly lower at 10 min (P < 0.05) and 15 min (P < 0.01), and Cdyn was significantly higher at 5 min (P < 0.05) and 15 min (P < 0.01) in the TP group. A trend towards a lower Raw was observed showing a statistically significant difference 5 min after endotracheal intubation (P < 0.01) in each group. CONCLUSIONS: Prophylactic treatment with TP showed a bronchodilatory effect through suppressing an increase in Raw and a decrease in Cdyn after anesthesia induction without severe adverse effects.

Pretreatmet with 5% lidocaine patch reduces cannula-induced and propofol-induced pain: a randomized, double-blind, placebo-controlled study.

BACKGROUND: The purpose of this study was to determine the efficacy of 5% lidocaine patch in reducing propofol-induced pain and cannula-induced pain. METHODS: In a randomized, double-blind study, 126 patients were divided into one of three groups: pretreatment with a 5% lidocaine patch (Lidotop®) and premixed 2 ml of normal saline with 1.5 mg/kg of 1% propofol (Group A); pretreatment with a placebo patch and premixed 2 ml of normal saline with 1.5 mg/kg of 1% propofol (Group B); or pretreatment with a placebo patch and premixed 2 ml of 2% lidocaine (40 mg) with 1.5 mg/kg of 1% propofol (Group C) for induction of anesthesia. Pain severity was evaluated on a four-point verbal rating scale during intravenous cannulation, propofol injection, and 24 h after the operation (recall). RESULTS: Eighteen patients (47.4%) in Group A complained of cannula-induced pain compared with 35 (94.6%) in Group B and 36 (94.7%) in Group C (P < 0.001). Group A patients showed significantly lower incidence of propofol-induced pain and recall of propofol-induced pain compared with Group B (P < 0.001 and P = 0.01), whereas there was no difference compared with Group C. CONCLUSIONS: Preoperative transdermal administration of 5% lidocaine patch is an effective and simple method in reducing propofol-induced pain as well as cannula-induced pain.

Combined spinal-epidural anesthesia for radical hysterectomy in a patient with Sjȍgren syndrome with progressive interstitial lung disease.

INTRODUCTION: Interstitial lung disease (ILD), which is the most common form of respiratory involvement of Sjȍgren syndrome (SS), is highly associated with postoperative pulmonary complications after surgery. We report the successful anesthetic management of a cervical cancer patient with SS and ILD under combined spinal-epidural anesthesia (CSE) to avoid postoperative pulmonary complications. CASE DESCRIPTION: A 41-year-old woman with SS complicated by recently progressive ILD was scheduled for an elective radical hysterectomy under the diagnosis of cervical cancer. We performed CSE with separate needle technique (SNT) using two different interspaces. An epidural catheter was inserted at T11-T12 before administration of spinal medication at L3-L4. We could achieve successful anesthetic management for radical hysterectomy, maintaining stable hemodynamic variables. Postoperative analgesia, using epidural catheter, was effective and devoid of any postoperative pulmonary morbidity. DISCUSSION AND EVALUATION: CSE could offer a high level of sensory blockade, profound muscular blockade, longer duration of surgical anesthesia, excellent postoperative pain control, and reduction in the incidence of pulmonary morbidity. Therefore it would be excellent anesthetic option for the patients with pulmonary impairment. CONCLUSION: CSE with SNT may be particularly advantageous in patients with pulmonary impairment such as progressive ILD when general anesthesia is associated with high risk of postoperative complications.

Trichostatin A Protects Liver against Septic Injury through Inhibiting Toll-Like Receptor Signaling.

Sepsis, a serious clinical problem, is characterized by a systemic inflammatory response to infection and leads to organ failure. Toll-like receptor (TLR) signaling is intimately implicated in hyper-inflammatory responses and tissue injury during sepsis. Histone deacetylase (HDAC) inhibitors have been reported to exhibit anti-inflammatory properties. The aim of this study was to investigate the hepatoprotective mechanisms of trichostatin A (TSA), a HDAC inhibitor, associated with TLR signaling pathway during sepsis. The anti-inflammatory properties of TSA were assayed in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Polymicrobial sepsis was induced in mice by cecal ligation and puncture (CLP), a clinically relevant model of sepsis. The mice were intraperitoneally received TSA (1, 2 or 5 mg/kg) 30 min before CLP. The serum and liver samples were collected 6 and 24-h after CLP. TSA inhibited the increased production of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in LPS-stimulated RAW264.7 cells. TSA improved sepsis-induced mortality, attenuated liver injury and decreased serum TNF-α and IL-6 levels. CLP increased the levels of TLR4, TLR2 and myeloid differentiation primary response protein 88 (MyD88) protein expression and association of MyD88 with TLR4 and TLR2, which were attenuated by TSA. CLP increased nuclear translocation of nuclear factor kappa B and decreased cytosolic inhibitor of kappa B (IκB) protein expression, which were attenuated by TSA. Moreover, CLP decreased acetylation of IκB kinase (IKK) and increased association of IKK with IκB and TSA attenuated these alterations. Our findings suggest that TSA attenuates liver injury by inhibiting TLR-mediated inflammatory response during sepsis.

A Randomized Clinical Trial of Nefopam versus Ketorolac Combined With Oxycodone in Patient-Controlled Analgesia after Gynecologic Surgery.

OBJECTIVES: Nefopam is a centrally-acting non-opioid analgesic, which has no effect on bleeding time and platelet aggregation. There has been no study about nefopam and oxycodone combination for postoperative analgesia. In this study, we present efficacy and side effects of nefopam/oxycodone compared with ketorolac/oxycodone in patient-controlled analgesia (PCA) after gynecologic surgery. METHODS: 120 patients undergoing gynecologic surgery were divided randomly into two groups: Nefopam group treated with oxycodone 1 mg and nefopam 1 mg bolus; and Ketorolac group treated with oxycodone 1 mg and ketorolac 1.5 mg bolus. After the operation, a blinded observer assessed the pain with a numeric rating scale (NRS), infused PCA dose and sedation score at 1, 4, 24, and 48 h, nausea, vomiting, headache, shivering, pruritus and delirium at 6, 24 and 48 h, and satisfaction at 48 h after the operation. RESULTS: Nefopam group showed less nausea than Ketorolac group within 6 h after the operation. There were no significant differences in demographic data and other complications between both groups. At 48 h after operation, satisfaction and the infused PCA volumes of Nefopam group (34.0± 19.7 ml) showed no significant differences compared to Ketorolac group (30.7± 18.4 ml, P-value= 0.46). CONCLUSION: Nefopam showed a similar efficacy and lower incidence of nausea within 6 h after the operation to that of ketorolac in PCA. Nefopam may be a useful analgesic drug for the opioid-based PCA after gynecologic surgery. Further evaluation of accurate equivalent dose of nefopam as well as pharmacokinetics of bolus administration is required.

Comparisons of recursive partitioning analysis and conventional methods for selection of uncuffed endotracheal tubes for pediatric patients.

BACKGROUND: Numerous studies have investigated the best method of selecting the appropriate size of endotracheal tube (ETT) for children. However, none of the methods or formulae for selection of ETT size have shown better prediction over another, and they have required complex formulae calculation or even use of cumbersome equipment. Recursive partitioning analysis creates a decision tree that is more likely to enable clearer and easier visualization of decision charts compared to other data mining methods. OBJECTIVES: The aim of the current study was to develop a clinically practical and intuitive chart for prediction of ETT size. METHODS: Pediatric patients aged 2-9 years undergoing general anesthesia were intubated with uncuffed ETT. The tube size was considered optimal when a tracheal leak was detected at an inflation pressure between 10 and 25 cmH2 O. The observed ETT size was compared with the predicted ETT size calculated using Cole's formula, multivariate regression analysis, ultrasonographic measurements, and recursive partitioning tree structure analysis. Preference among the prediction methods was also investigated by asking physicians about their preference of methods. RESULTS: Correct prediction rates were 33.3%, 50%, 61.9%, and 59.5%, and close prediction rates were 61.9%, 83.3%, 88.1%, and 93.7% for Cole's formulae, multivariate regression analysis, ultrasonographic measurements, and recursive partitioning tree model, respectively. Fourteen of 16 physicians prefer to use the easy-to-interpret tree model. CONCLUSIONS: Analysis of the tree model by recursive partitioning structure analysis accomplished a high correct and close prediction rate for selection of an appropriate ETT size. The intuitive and easy-to-interpret tree model would be a quick and helpful tool for selection of an ETT tube for pediatric patients.

Modeling of safe window for percutaneous thoracic sympathectomy.

PURPOSE: Despite the many benefits of percutaneous thoracic sympathectomy, it also has serious complications such as pneumothorax. This study was conducted in order to determine the safe percutaneous entering window and angles for the needle during T2 and T3 thoracic sympathectomy avoiding pneumothorax. METHODS: Transverse section of CT images that crosses at the middle of the T2 or T3 vertebral body was selected. Medial and lateral imaginary lines were drawn from the dorsoventrally midpoint on the lateral surface of the vertebral body (v) to the skin. The medial one was drawn to the skin medially as much as possible tangent to the vertebral body (vM). The lateral one was drawn to the skin tangent to parietal pleura (vL). c was defined as the point where the midsagittal line meets the skin. The distance cM and cL, the angle aM and aL made between the midsagittal line and vM or vL lines were measured. To determine the relations between patients' covariates and measured data, mixed-effect population analysis was performed for the cL, aL, and vL. RESULTS: In males, the mean values of cL were 85.3 and 79.2 mm for T2 and T3, respectively. In females, they were 71.5 and 63.7 mm for T2 and T3, respectively. Population analysis revealed that cL was best described with age, weight, gender covariates, and interindividual variability. The aL was best described with BMI and gender covariates. CONCLUSIONS: The covariates' relationship and interindividual variability resulting from the mixed-effect analysis enhanced individual prediction for safe widows.

Oxycodone vs. fentanyl patient-controlled analgesia after laparoscopic cholecystectomy.

OBJECTIVES: Oxycodone is semi-synthetic opioid, oral and parenteral preparations have been widely used for acute and chronic pain. The aim of this study was to assess the efficacy and side effects of oxycodone and fentanyl in patient controlled analgesia (PCA) after laparoscopic cholecystectomy. METHODS: A prospective, randomized, double-blind study was conducted. 81 patients were randomly divided into two groups; fentanyl (10 mcg fentanyl and 1.5 mg ketorolac) and oxycodone group (1 mg oxycodone and 1.5 mg ketorolac). After the operation, a blinded observer assessed pain using a numerical rating scale (NRS), infused PCA dose, side effects, sedation levels, and satisfaction. RESULTS: Cumulative PCA dose of oxycodone group at 48 h (31.4 ± 16.0 ml) was significantly less than that of fentanyl group (43.8 ± 23.1 ml, P = 0.009). Oxycodone group showed more nausea at 6-24 h after the operation (P = 0.001), but there was no difference in satisfaction score (P = 0.073). There were no significant differences in other side effects, sedation and NRS scores between two groups. CONCLUSION: Oxycodone showed comparable effects for pain relief compared to fentanyl in spite of less cumulative PCA dose. Based on these results, we could conclude that oxycodone may be useful as an alternative to fentanyl for PCA after laparoscopic cholecystectomy.

Effect of nitrous oxide inhalation on pain after propofol and rocuronium injection.

PURPOSE: This prospective, double-blind, placebo-controlled study was designed to determine the efficacy of nitrous oxide (N(2)O) in alleviating the pain that followed sequential injection of propofol and rocuronium. METHODS: A total of 205 adult patients (age, 18-68 years) received one of the following combinations: NaCl and 100 % O(2) (group C); 0.5 mg/kg lidocaine and 100 % O(2) (group L); NaCl and a mixture of 67 % N(2)O/O(2) (group N); or 0.5 mg/kg lidocaine and a mixture of 67 % N(2)O/O(2) (group LN). Vein occlusion was released after 1 min, and 5 ml propofol was injected over 10 s. Pain was evaluated on a visually enlarged, laminated, numeric rating (0-10) scale. The remainder of the induction dose of propofol (with a 3-ml bolus of normal saline and 0.6 mg/kg rocuronium) was then injected. The response to the rocuronium injection was assessed with a four-point scale (0-3). RESULTS: The incidence and severity of pain from the propofol injection in groups L, N, and LN were significantly lower than those in group C (P < 0.001). Frequency and intensity of the withdrawal response were significantly less in groups N and LN than in groups C and L (no response, P < 0.001; severe response, P < 0.001). CONCLUSIONS: Pretreatment with inhaled N(2)O can reduce the pain associated with propofol and rocuronium injection. Moreover, N(2)O (with or without lidocaine) is more effective than lidocaine alone in reducing rocuronium-related withdrawal reactions associated with sequential injection of propofol and rocuronium.