Effects of Intrathecal Ketamine on Cerebrospinal Fluid Levels of Brain-Derived Neurotrophic Factor and Mechanical Allodynia in a Rat Model of Mild Traumatic Brain Injury.

BACKGROUND Ketamine, a compelling candidate for neuropathic pain management, has attracted interest for its potential to elevate brain-derived neurotrophic factor (BDNF) levels. We aimed to assess the effects of intrathecally administered ketamine on the cerebrospinal fluid (CSF) levels of BDNF(c-BDNF) and allodynia in a rat model of traumatic brain injury (TBI). MATERIAL AND METHODS Forty-five rats were divided into 3 groups: sham operation (Group S), untreated TBI (Group T), and ketamine-treated TBI (Group K), with 15 rats in each group. Rats were anesthetized, and their skulls were secured in a stereotactic frame before undergoing craniotomy. A controlled cortical impact (CCI) was induced, followed by injection of ketamine (3.41 µg/g) into the CSF in Group K. In Group T, no drug was injected after CCI delivery. On postoperative days (POD) 1, 7, and 14, the 50% mechanical withdrawal threshold (50% MWT) and c-BDNF levels were assessed. RESULTS Groups T and K exhibited a significantly lower 50% MWT than Group S on POD 1(6.6 [5.7, 8.7] g, 10.0 [6.8, 11.6] g, and 18.7 [11.6, 18.7] g, respectively; P<0.001). The c-BDNF levels in Group K were significantly higher than those in Groups S and T on POD 1 (18.9 [16.1, 23.0] pg/ml, 7.3 [6.0, 8.8] pg/ml, and 11.0 [10.6, 12.3] pg/ml, respectively; P=0.006). CONCLUSIONS Intrathecal ketamine administration did not exhibit anti-allodynic effects following mild TBI. c-BDNF level is a promising potential indicator for predicting the expression of allodynia after mild TBI.

Impaired Capillary Recruitment Capacity in Obesity: A Subgroup Analysis of Prospective Observational Study on Anesthesia Effects.

BACKGROUND This subgroup analysis of prospective observational research, involving 71 participants, compared the effects of anesthesia on microvascular reactivity in obese vs lean individuals using near-infrared spectroscopy and vascular occlusion tests. The correlation between the body mass index (BMI) and microvascular reactivity under general anesthesia was also investigated. MATERIAL AND METHODS This study enrolled adult patients classified as American Society of Anesthesiologists physical status I or II, undergoing elective surgery under general anesthesia. The microcirculatory variables measured before (Tpre) and 30 min following the induction of anesthesia (Tpost) were as follows: baseline tissue oxygen saturation (StO2), occlusion slope (∇occl), and recovery slope (∇recov). The patients were grouped according to their BMI (lean [BMI <25 kg/m²] vs obese [BMI ≥25 kg/m²]). Data are presented as medians and interquartile ranges. RESULTS There were 43 patients in the lean group and 28 in the obese group. At Tpre, baseline StO2, ∇occl, and ∇recov were not different between the 2 groups (P=0.860, 0.659, and 0.518, respectively). At Tpost, the baseline StO2 and ∇occl were not different between the 2 groups (P=0.343 and 0.791); however, the ∇recov was lower in the obese group than in the lean group (3.245 [2.737, 3.977] vs 4.131 [3.491, 4.843], P=0.003). At Tpost, BMI showed a moderate correlation with ∇recov (correlation coefficient: -0.319, P=0.007). CONCLUSIONS In obese patients, capillary recruitment capacity during general anesthesia is compromised compared to lean patients.

Energy Efficient All-Electric-Field-Controlled Multiferroic Magnetic Domain-Wall Logic.

Magnetic domain wall (DW)-based logic devices offer numerous opportunities for emerging electronics applications allowing superior performance characteristics such as fast motion, high density, and nonvolatility to process information. However, these devices rely on an external magnetic field, which limits their implementation; this is particularly problematic in large-scale applications. Multiferroic systems consisting of a piezoelectric substrate coupled with ferromagnets provide a potential solution that provides the possibility of controlling magnetization through an electric field via magnetoelastic coupling. Strain-induced magnetization anisotropy tilting can influence the DW motion in a controllable way. We demonstrate a method to perform all-electrical logic operations using such a system. Ferromagnetic coupling between neighboring magnetic domains induced by the electric-field-controlled strain has been exploited to promote noncollinear spin alignment, which is used for realizing essential building blocks, including DW generation, propagation, and pinning, in all implementations of Boolean logic, which will pave the way for scalable memory-in-logic applications.

Melatonin inhibits Japanese encephalitis virus replication and neurotoxicity via calcineurin-autophagy pathways.

BACKGROUND: Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that has no specific treatment except for supportive medical care. JEV is a neurotropic virus that affects the nervous system and triggers inflammation in the brain. METHODS: Melatonin is used as a sleep-inducing agent in neurophysiology and may serve as a protective agent against neurological and neurodegenerative diseases. Herein, we investigated the effects of melatonin and the critical roles of the serine/threonine protein phosphatase calcineurin during JEV infection in SK-N-SH neuroblastoma cells. RESULTS: Melatonin treatment decreased JEV replication and JEV-mediated neurotoxicity. Calcineurin activity was increased by JEV infection and inhibited by melatonin treatment. Through calcineurin regulation, melatonin decreased the JEV-mediated neuroinflammatory response and attenuated JEV-induced autophagy. CONCLUSIONS: Calcineurin inactivation has a protective effect in JEV-infected neuronal cells, and melatonin is a novel resource for the development of anti-JEV agents.

A Study of 57 Patients with Prostate Cancer to Compare Outcomes of Estimated Blood Loss and Postoperative Pain Between Robot-Assisted Laparoscopic Radical Prostatectomy and Standard Laparoscopic Radical Prostatectomy.

BACKGROUND Robot-assisted radical prostatectomy (RARP) is becoming an increasingly common method for treatment of prostate cancer. This study aimed to compare outcomes of estimated blood loss and postoperative pain, determined by patient-controlled analgesia (PCA), between RARP and standard laparoscopic radical -prostatectomy (LRP). MATERIAL AND METHODS We enrolled 57 patients who had localized prostate cancer (28 patients in RARP, 29 patients in LRP). Primary outcomes were estimated blood loss (EBL) measured by gravimetric method for gauze and visual estimation for suction bottle, and PCA bolus count that the bolus doses were injected at the 1st, the 6th, the 24th, and the 48th hour after the operation. We recorded anesthesia and operation time, pneumoperitoneum duration, vital signs, fluid volume, and remifentanil use. Using the numeric rating scale (NRS), adverse effects were checked at the 1st, the 6th, the 24th, and the 48th hour and patient satisfaction was assessed at the 48th hour after the operation. RESULTS Anesthesia time, operation time, and gas insufflation time were longer (P=0.001, P=0.003, P=0.021), and patient-controlled analgesia (PCA) bolus counts at the 1st hour after the operation and volumes of administered crystalloid and remifentanil were higher in the RARP group than in the LRP group (P=0.013, P=0.011, P=0.031). There were no significant differences in EBL. CONCLUSIONS The RARP group required longer anesthetic time and more analgesics during the acute postoperative period compared to the LRP group. Regarding anesthesia, LRP is as good a surgical procedure as RARP until the operation time and the number of ports are reduced.

BTT-105 ameliorates hepatic fibrosis in non-alcoholic fatty liver animal model.

BTT-105 (1-O-hexyl-2,3,5-trimethylhydroquinone), a hydroquinone derivative, is a potent anti-oxidant that was safe and tolerable in phase I clinical trial. This study examined the anti-fibrotic effect of BTT-105 in a mouse model of non-alcoholic fatty liver disease (NAFLD) along with the underlying mechanisms. In vivo, efficacy of BTT-105 evaluated from three kinds of NAFLD models (methionine/choline deficient diet (MCD), high fat diet (HF) and western diet (WD)). Metabolomics and transcriptomics profiling analysis in liver tissues were conducted. In vitro, anti-fibrotic effect of BTT-105 assessed in human hepatic stellated cells (HSCs) and primary mouse HSCs. BTT-105 improved NAFLD activity score in three kinds of NAFLD animal models (MCD, HF, and WD). BTT-105 also decreased levels of hepatic pro-collagen and collagen fibers deposition in liver tissue. Metabolome and transcriptome analysis revealed that BTT-105 decreased lipid metabolites and increased antioxidants in NAFLD mice. In HepG2 cells, BTT-105 enhanced Nrf2-ARE reporter activity in a dose-dependent manner and increased the levels of antioxidant gene expression. BTT-105 showed inhibition of HSCs activation and migration. Gene expression profiling and protein expression showed that BTT-105 increased Nrf2 activation as well as decreased PI3K-Akt pathway in activated HSCs. BTT-105 attenuated ameliorates steatohepatitis and hepatic fibrosis.

Ovarian carcinoma immunoreactive antigen domain 2 controls mitochondrial apoptosis in lung adenocarcinoma.

Ovarian carcinoma immunoreactive antigen domain 2 (OCIAD2) has been reported to show significantly higher expression in invasive lung adenocarcinoma than in lung adenocarcinoma in situ, and its abnormal expression is associated with poorer prognosis of the patients. However, the cellular function of OCIAD2 in this tumor remains poorly understood. In the present study, we first validated that OCIAD2 showed higher expression in human lung adenocarcinoma tissues or cell lines than in normal lung tissue or immortalized normal bronchial epithelial cells. OCIAD2 was localized predominantly at the mitochondrial membrane in lung adenocarcinoma cells. Interestingly, suppression of OCIAD2 led to loss of mitochondrial structure and a reduction in the number of mitochondria. Moreover, OCIAD2 suppression led to downregulation of cellular growth, proliferation, migration, and invasion, and upregulation of mitochondria-related apoptosis. We also showed that OCIAD2 suppression induced a decrease in mitochondrial membrane potential and release of cytochrome c. Transcriptional profiling using RNA sequencing revealed a total of 137 genes whose expression was commonly altered after OCIAD2 knockdown in three lung adenocarcinoma cell lines (A549, HCC827, and PC9). Pathway enrichment analysis of those genes demonstrated significant enrichment in apoptotic signaling or endoplasmic reticulum (ER) stress pathways. Our data suggest that OCIAD2 inhibits the mitochondria-initiated apoptosis and thus promotes the survival of lung cancer cells. Therefore, OCIAD2 may be an effective target for treatment of lung adenocarcinoma.

Sleep quality and emergence delirium in children undergoing strabismus surgery: a comparison between preschool- and school-age patients.

BACKGROUND: Emergence delirium (ED) is common in pediatric patients undergoing general anesthesia with sevoflurane. Preoperative sleep quality is associated with the risk factors for ED. However, research on the relationship between sleep quality and ED is limited. We aimed to investigate the relationship between ED and preoperative sleep quality in pediatric patients undergoing strabismus surgery. METHODS: This clinical trial included pediatric patients aged 4-12 years who underwent elective strabismus surgery. The patients and their parents were questioned about the patients' preoperative sleep quality using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. For anesthesia induction, thiopental (5 mg/kg) and rocuronium (0.6 mg/kg) were used, and anesthesia was maintained with sevoflurane (minimum alveolar concentration, 1-1.5). After administration of a reversal drug, extubation was performed, and the patients were transferred to a post-anesthesia recovery unit. At 10 min after extubation, the degree of ED was measured using the pediatric anesthesia emergence delirium (PAED) and Watcha scale scores. RESULTS: Of the 62 enrolled patients, three pediatric patients were excluded. The overall incidence of ED was 22%. A total of 59 patients were divided into the two groups. The ED group and the non-ED group comprised 13 and 46 patients. Age, height and weight were significantly lower in the ED group than in the non-ED group. Preoperative PSQI and Watcha scale score were significantly higher in the ED group than in the non-ED group. Multivariate analysis showed that age (adjusted OR [95% CI]: 0.490 [0.290-0.828], p = 0.008) and preoperative PSQI score (adjusted OR [95% CI]: 2.149[1.224-3.771], p = 0.008) was associated with ED. In sub-group analysis, PAED scale and Watcha scale scores showed a moderate correlation with preoperative sleep quality in preschool-age patients. CONCLUSION: In conclusion, the incidence of ED tended to be higher in younger age and poorer preoperative sleep quality in pediatric patients. In particular, the poorer sleep quality score was associated with higher incidence of ED in the preschool-age. Large-scale clinical studies and long-term follow-up studies on ED and sleep quality are required. TRIAL REGISTRATION: This study was registered with Clinicaltrials.gov ( NCT03332407 ) at November 5th 2017.

The effect of combined Epidural-general Anesthesia on Hemodynamic Instability during Pheochromocytoma and Paraganglioma Surgery: A multicenter retrospective cohort study.

Objectives: The purpose of this study was to compare the effects of combined epidural-general anesthesia with those of general anesthesia alone on hemodynamic instability (intraoperative hypotension and hypertensive crisis) during pheochromocytoma and sympathetic paraganglioma surgery. Methods: A total of 119 patients' medical records were reviewed who were diagnosed as having pheochromocytoma and sympathetic paraganglioma on the basis of histological findings. Intraoperative hypotension was defined as a mean blood pressure < 60 mmHg or a decrease > 30% in baseline systolic blood pressure after adrenal vein ligation. Hypertensive crisis was defined as a systolic blood pressure > 200 mmHg or an increase > 30% in baseline systolic blood pressure during the operation. The predictor variables for intraoperative hypotension and hypertensive crisis were analyzed with logistic regression models. Data were presented as adjusted odds ratio with 95% confidence interval. Results: The independent predictors of intraoperative hypotension were an increased attenuation number on unenhanced computed tomography (1.112 [1.009-1.226], p = 0.033), a high baseline mean blood pressure (1.063 [1.012-1.117], p = 0.015), and the combined epidural-general anesthesia (5.439 [1.410-20.977], p = 0.014). In contrast, an increased attenuation number on unenhanced computed tomography was the only independent predictor of hypertensive crisis (1.087 [1.021-1.158], p = 0.009). Conclusions: The combined epidural-general anesthesia was not effective in attenuating hypertensive responses, but could have exacerbated intraoperative hypotension. These findings should be taken into account before selecting the anesthetic technique in pheochromocytoma and sympathetic paraganglioma surgery.

Clinical characteristics and treatment outcomes of Enterococcus durans bacteremia: a 20-year experience in a tertiary care hospital.

While the clinical characteristics and treatment outcomes of Enterococcus faecalis and E. faecium bacteremia are well known, those of E. durans bacteremia are still largely unclear. We retrospectively identified 80 adult E. durans bacteremia cases treated at our 2700-bed tertiary care hospital between January 1997 and December 2016. We compared the clinical characteristics and treatment outcomes of the adult patients with E. durans bacteremia (case group) with those of E. faecalis and E. faecium bacteremia cases (two control groups). The case and control groups were matched for sex, age, and date of onset of bacteremia. E. durans was responsible for 1.2% of all enterococcal bacteremia cases at our hospital. Of 80 cases, 39 (48.8%) had biliary tract infection and 18 (22.5%) had urinary tract infection. Community-onset bacteremia was more frequent in the case group than in the control groups (56.2% vs. 35.0% vs. 21.2%, p < 0.01). Infective endocarditis tended to be more common in the E. durans group (7.5% vs. 1.2% vs. 1.2%, p = 0.05). The majority of E. durans isolates were susceptible to penicillin (66/76, 86.8%), ampicillin (67/76, 88.2%), and vancomycin (75/76, 98.7%). The case group had significantly lower all-cause mortality (20.0% vs. 31.2% vs. 42.5%, p < 0.01) and bacteremia-related mortality (2.5% vs. 16.2% vs. 18.8%, p < 0.01) than the control groups. E. durans bacteremia mainly originates from the biliary or urinary tract and is associated with a lower risk of mortality.

Lipid emulsion attenuates the vasodilation induced by a toxic dose of a calcium channel blocker through its partitioning into the lipid phase.

The present in vitro study examined whether lipid emulsion attenuates the vasodilation evoked by toxic doses of calcium channel blockers (bepridil, verapamil, nifedipine and diltiazem) via their partitioning into the lipid phase. The effects of the calcium channel blockers alone, the lipid emulsion and calcium channel blocker mixture, and the centrifuged aqueous extract (CAE) obtained from ultracentrifugation of the lipid emulsion and calcium channel blocker mixture on isolated endothelium-denuded rat aortas precontracted with phenylephrine were observed. The effects of lipid emulsion on calcium channel blocker concentration in the Krebs solution were examined using ultraperformance liquid chromatography. A mixture of lipid emulsion with either bepridil or verapamil and the corresponding CAE more effectively attenuated vasodilation than either bepridil or verapamil alone, whereas the vasodilation induced by the mixture of lipid emulsion and either bepridil or verapamil was not significantly different from that induced by the corresponding CAE. The magnitude of the lipid emulsion-mediated reduction in vasodilation and calcium channel blocker concentration was as follows: bepridil > verapamil > nifedipine or diltiazem. These results suggest that lipid emulsion attenuates vasodilation induced by a toxic dose of bepridil and verapamil, seemingly through partitioning of the calcium channel blocker into the lipid phase.

Highly Secure Physically Unclonable Cryptographic Primitives Based on Interfacial Magnetic Anisotropy.

Information security is of great importance for the approaching Internet of things (IoT) era. Physically unclonable functions (PUFs) have been intensively studied for information security. However, silicon PUFs are vulnerable to hazards such as modeling and side-channel attacks. Here we demonstrate a magnetic analogue PUF based on perpendicularly magnetized Ta/CoFeB/MgO heterostructures. The perpendicular magnetic anisotropy originates from the CoFeB/MgO interface, which is sensitive to the subnanometer variation of MgO thickness within a certain range (0.6-1.3 nm). When the MgO layer is thinned, a thickness variation resulting from ion milling nonuniformity induces unclonable random distributions of eas y-axis magnetization orientations in heterostructures. The analogue PUF can provide a much larger key size than a conventional binary-bit counterpart. Moreover, after the thinning process, the unique eas y-axis magnetization orientation in each single device was formed, which can avoid setting random states to realize low power consumption and high-density integration. This magnetic PUF is a promising innovative primitive for secret key generation and storage with high security in the IoT era.

Reconfigurable Skyrmion Logic Gates.

Magnetic skyrmion, a nanosized spin texture with topological property, has become an area of significant interest due to the scientific insight that it can provide and also its potential impact on applications such as ultra-low-energy and ultra-high-density logic gates. In the quest for the reconfiguration of single logic device and the implementation of the complete logic functions, a novel reconfigurable skyrmion logic (RSL) is proposed and verified by micromagnetic simulations. Logic functions including AND, OR, NOT, NAND, NOR, XOR, and XNOR are implemented in the ferromagnetic (FM) nanotrack by virtue of various effects including spin orbit torque, skyrmion Hall effect, skyrmion-edge repulsions, and skyrmion-skyrmion collision. Different logic functions can be selected in an RSL by applying voltage to specific region(s) of the device, changing the local anisotropy energy of FM film. Material properties and geometrical scaling studies suggest RSL gates fit for energy-efficient computing as well as provide the guidelines for the design and optimization of this new logic family.

BST106 Protects against Cartilage Damage by Inhibition of Apoptosis and Enhancement of Autophagy in Osteoarthritic Rats.

Chrysanthemum zawadskii var. latilobum (CZ) has been used as a traditional medicine in Asian countries for the treatment of inflammatory diseases. Recently, CZ extract was shown to inhibit differentiation of osteoclasts and provide protection against rheumatoid arthritis. The aim of this study was to investigate the molecular mechanisms of BST106, the ethanol extract of CZ, for cartilage protection in monosodium iodoacetate (MIA)-induced osteoarthritis (OA), particularly focusing on apoptosis and autophagy. BST106 (50, 100, and 200 mg/kg) was orally administered once daily to MIA-induced OA rats. Swelling, limping, roentgenography, and histomorphological changes were assessed 28 d after MIA injection. Biochemical parameters for matrix metalloproteinase (MMP), apoptosis, and autophagy were also assessed. BST106 ameliorated the severity of swelling and limping after MIA injection. Roentgenographic and histomorphological examinations revealed that BST106 reduced MIA-induced cartilage damage. BST106 decreased MIA-induced increases in MMP-2 and MMP-13 mRNA levels. Increased levels of serum cartilage oligomeric matrix protein and glycosaminoglycan release were attenuated by BST106. Furthermore, BST106 suppressed the protein expression of proapoptotic molecules and increased the protein expression of autophagosome- and autolysosome-related molecules. These findings indicate that BST106 protects against OA-induced cartilage damage by inhibition of the apoptotic pathway and restoration of impaired autophagic flux.

Lipid Emulsion for Treating Local Anesthetic Systemic Toxicity.

Lipid emulsion has been shown to be an effective treatment for systemic toxicity induced by local anesthetics, which is reflected in case reports. A systemic review and meta-analysis confirm the efficacy of this treatment. Investigators have suggested mechanisms associated with the lipid emulsion-mediated recovery of cardiovascular collapse caused by local anesthetic systemic toxicity; these mechanisms include lipid sink, a widely accepted theory in which highly soluble local anesthetics (particularly bupivacaine) are absorbed into the lipid phase of plasma from tissues (e.g., the heart) affected by local-anesthetic-induced toxicity; enhanced redistribution (lipid shuttle); fatty acid supply; reversal of mitochondrial dysfunction; inotropic effects; glycogen synthase kinase-3ß phosphorylation associated with inhibition of the mitochondrial permeability transition pore opening; inhibition of nitric oxide release; and reversal of cardiac sodium channel blockade. The current review includes the following: 1) an introduction, 2) a list of the proposed mechanisms, 3) a discussion of the best lipid emulsion treatment for reversal of local anesthetic toxicity, 4) a description of the effect of epinephrine on lipid emulsion-mediated resuscitation, 5) a description of the recommended lipid emulsion treatment, and 6) a conclusion.

Switching of perpendicularly polarized nanomagnets with spin orbit torque without an external magnetic field by engineering a tilted anisotropy.

Spin orbit torque (SOT) provides an efficient way to significantly reduce the current required for switching nanomagnets. However, SOT generated by an in-plane current cannot deterministically switch a perpendicularly polarized magnet due to symmetry reasons. On the other hand, perpendicularly polarized magnets are preferred over in-plane magnets for high-density data storage applications due to their significantly larger thermal stability in ultrascaled dimensions. Here, we show that it is possible to switch a perpendicularly polarized magnet by SOT without needing an external magnetic field. This is accomplished by engineering an anisotropy in the magnets such that the magnetic easy axis slightly tilts away from the direction, normal to the film plane. Such a tilted anisotropy breaks the symmetry of the problem and makes it possible to switch the magnet deterministically. Using a simple Ta/CoFeB/MgO/Ta heterostructure, we demonstrate reversible switching of the magnetization by reversing the polarity of the applied current. This demonstration presents a previously unidentified approach for controlling nanomagnets with SOT.

Linoleic Acid Attenuates the Toxic Dose of Bupivacaine-Mediated Reduction of Vasodilation Evoked by the Activation of Adenosine Triphosphate-Sensitive Potassium Channels.

The goal of this study was to investigate the effect of lipid emulsion on a toxic dose of local anesthetic-mediated reduction of vasodilation evoked by the ATP-sensitive potassium (KATP) channel agonist levcromakalim. The effect of lipid emulsion (LE) and linoleic acid on the local anesthetic-mediated reduction of vasodilation and membrane hyperpolarization evoked by levcromakalim was assessed in isolated endothelium-denuded vessels (rat aorta and mesenteric artery) and aortic vascular smooth muscle cells. The effect of LE and linoleic acid on KATP channel activity in transfected HEK-293 cells was investigated, as was the effect of LE on bupivacaine concentration. The efficacy of LE in attenuating the local anesthetic-mediated reduction of vasodilation evoked by levcromakalim was correlated with the lipid solubility of the local anesthetic. Linoleic acid attenuated the bupivacaine-mediated reduction of vasodilation evoked by levcromakalim. LE decreased the bupivacaine-mediated reduction of membrane hyperpolarization evoked by levcromakalim but did not significantly alter the mepivacaine-mediated reduction. LE and linoleic acid both reversed the bupivacaine-mediated decrease of KATP activity and enhanced KATP activity. LE decreased the bupivacaine concentration. Linoleic acid may be the major contributor to LE-induced attenuation of bupivacaine-mediated reduction of vasodilation evoked by levcromakalim via the direct activation of KATP channels and indirect effects.

miR-3941: A novel microRNA that controls IGBP1 expression and is associated with malignant progression of lung adenocarcinoma.

Immunoglobulin (CD79a) binding protein 1 (IGBP1) is universally overexpressed in lung adenocarcinoma and exerts an anti-apoptotic effect by binding to PP2Ac. However, the molecular mechanism of IGBP1 overexpression is still unclear. In the present study, we used a microRNA (miRNA) array and TargetScan Human software to detect IGBP1-related miRNAs that regulate IGBP1 expression. The miRNA array analysis revealed more than 100 miRNAs that are dysregulated in early invasive adenocarcinoma. On the other hand, in silico analysis using TargetScan Human revealed 79 miRNAs that are associated with IGBP1 protein expression. Among the miRNAs selected by miRNA array analysis, six (miR-34b, miR-138, miR-374a, miR-374b, miR-1909, miR-3941) were also included among those selected by TargetScan analysis. Real-time reverse transcription PCR (real-time RT-PCR) showed that the six microRNAs were downregulated in invasive adenocarcinoma (IGBP1+) relative to adjacent normal lung tissue (IGBP1-). Among these microRNAs, only miR-34b and miR-3941 depressed luciferase activity by targeting 3'UTR-IGBP1 in the luciferase vector. We transfected miR-34b and miR-3941 into lung adenocarcinoma cell lines (A549, PC-9), and both of them suppressed IGBP1 expression and cell proliferation. Moreover, the transfected miR-34b and miR-3941 induced apoptosis of a lung adenocarcinoma cell line, similarly to the effect of siIGBP1 RNA. As well as miR-34b, we found that miR-3941 targeted IGBP1 specifically and was able to exclusively downregulate IGBP1 expression. These findings indicate that suppression of miR-3941 has an important role in the progression of lung adenocarcinoma at an early stage.

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.

A Lipid Emulsion Reverses Toxic-Dose Bupivacaine-Induced Vasodilation during Tyrosine Phosphorylation-Evoked Contraction in Isolated Rat Aortae.

The goal of this in vitro study was to examine the effect of a lipid emulsion on toxic-dose bupivacaine-induced vasodilation in a model of tyrosine phosphatase inhibitor sodium orthovanadate-induced contraction in endothelium-denuded rat aortae and to elucidate the associated cellular mechanism. The effect of a lipid emulsion on vasodilation induced by a toxic dose of a local anesthetic during sodium orthovanadate-induced contraction was examined. In addition, the effects of various inhibitors, either bupivacaine alone or a lipid emulsion plus bupivacaine, on protein kinase phosphorylation induced by sodium orthovanadate in rat aortic vascular smooth muscle cells was examined. A lipid emulsion reversed the vasodilation induced by bupivacaine during sodium orthovanadate-induced contraction. The lipid emulsion attenuated the bupivacaine-mediated inhibition of the sodium orthovanadate-induced phosphorylation of protein tyrosine, c-Jun NH2-terminal kinase (JNK), myosin phosphatase target subunit 1 (MYPT1), phospholipase C (PLC) γ-1 and extracellular signal-regulated kinase (ERK). These results suggest that a lipid emulsion reverses toxic-dose bupivacaine-induced vasodilation during sodium orthovanadate-induced contraction via the activation of a pathway involving either tyrosine kinase, JNK, Rho-kinase and MYPT1 or tyrosine kinase, PLC γ-1 and ERK, and this reversal is associated with the lipid solubility of the local anesthetic and the induction of calcium sensitization.