Effect of Sevoflurane on the Proliferation of A549 Lung Cancer Cells.

Background and Objectives: Sevoflurane has opposing effects on cancer progression, depending on its concentration and the cancer type. This study investigated the effects of sevoflurane on the proliferation of A549 lung cancer cells. Materials and Methods: In vitro, the number of A549 cells exposed to different concentrations of sevoflurane was counted. The size and weight of tumors from a xenograft mouse model exposed to air or sevoflurane were measured in vivo experiments. Additionally, hematoxylin and eosin staining and immunohistochemical detection of Ki-67 in the harvested tumor tissues were performed. Results: A total of 72 culture dishes were used and 24 dishes were assigned to each group: Air group; 2% Sevo group (air + 2% sevoflurane); and 4% Sevo group (air + 4% sevoflurane). The number of A549 cells in the 2% Sevo group was less than that in the Air and 4% Sevo groups (Air: 7.9 ± 0.5; 0.5, 2% Sevo: 6.8 ± 0.4, 4% Sevo: 8.1 ± 0.3; p = 0.000). The tumor size was not significantly different between the two groups (Air: 1.5 ± 0.7, 2% Sevo: 2.4 ± 1.9; p = 0.380). Conclusions: The in vitro data showed that sevoflurane inhibited the proliferation of A549 lung cancer cells in a concentration-specific manner. However, the in vivo data showed no correlation between sevoflurane exposure and A549 cell proliferation. Thus, further research is required to understand fully the effects of sevoflurane on cancer progression and to reconcile differences between the in vitro and in vivo experimental results.

Hemidiaphragmatic paralysis following costoclavicular versus supraclavicular brachial plexus block: a randomized controlled trial.

Costoclavicular brachial plexus block is emerging as a promising infraclavicular approach performed just below the clavicle. However, there are relatively little data regarding the hemidiaphragmatic paralysis (HDP) compared to the commonly performed supraclavicular block. We hypothesized that the incidence of HDP in costoclavicular block is lower than supraclavicular block like classical infraclavicular approach. Eighty patients were randomly assigned to ultrasound-guided supraclavicular (group S) or costoclavicular (group C) block with 25 mL of local anesthetics (1:1 mixture of 1% lidocaine and 0.75% ropivacaine). The primary outcome was the incidence of HDP, defined as less than 20% of fractional change in the diaphragm thickness on ultrasound M-mode. Also, pulmonary function test and chest radiograph were assessed before and after the surgery. The incidence of HDP was 4/35 (11.4%) in the group C and 19/40 (47.5%) in the group S (risk difference, - 36%; 95% CI - 54 to - 17%; P = 0.002). The mean (SD) change of DTF values were 30.3% (44.0) and 56.9% (39.3) in the group C and S, respectively (difference in means, - 26.6%; 95% CI - 45.8 to - 7.4%; P = 0.007). The pulmonary function was more preserved in group C than in group S. The determined diagnostic cut off value of the diaphragm elevation on chest radiograph was 29 mm. Despite the very contiguous location of the two approaches around the clavicle, costoclavicular block can significantly reduce the risk of HDP compared with supraclavicular block.

IKBKB siRNA-Encapsulated Poly (Lactic-co-Glycolic Acid) Nanoparticles Diminish Neuropathic Pain by Inhibiting Microglial Activation.

Activation of nuclear factor-kappa B (NF-κB) in microglia plays a decisive role in the progress of neuropathic pain, and the inhibitor of kappa B (IκB) is a protein that blocks the activation of NF-κB and is degraded by the inhibitor of NF-κB kinase subunit beta (IKBKB). The role of IKBKB is to break down IκB, which blocks the activity of NF-kB. Therefore, it prevents the activity of NK-kB. This study investigated whether neuropathic pain can be reduced in spinal nerve ligation (SNL) rats by reducing the activity of microglia by delivering IKBKB small interfering RNA (siRNA)-encapsulated poly (lactic-co-glycolic acid) (PLGA) nanoparticles. PLGA nanoparticles, as a carrier for the delivery of IKBKB genes silencer, were used because they have shown potential to enhance microglial targeting. SNL rats were injected with IKBKB siRNA-encapsulated PLGA nanoparticles intrathecally for behavioral tests on pain response. IKBKB siRNA was delivered for suppressing the expression of IKBKB. In rats injected with IKBKB siRNA-encapsulated PLGA nanoparticles, allodynia caused by mechanical stimulation was reduced, and the secretion of pro-inflammatory mediators due to NF-κB was reduced. Delivering IKBKB siRNA through PLGA nanoparticles can effectively control the inflammatory response and is worth studying as a treatment for neuropathic pain.

Does Demineralized Bone Matrix Enhance Tendon-to-Bone Healing after Rotator Cuff Repair in a Rabbit Model?

BACKGROUD: The purpose of this study was to compare the histologic outcomes of rotator cuff (RC) repair with demineralized bone matrix (DBM) augmentation and those without DBM augmentation and to evaluate the role of DBM for tendon-to-bone (TB) healing in a rabbit model. METHODS: Twenty-six adult male New Zealand white rabbits were randomly allocated to the control group (n = 13) or the DBM group (n = 13). Repair was performed 8 weeks after complete transection of the right supraspinatus tendon of all rabbits. In the control group, RC repair was achieved by a standard transosseous technique. In the DBM group, RC repair was achieved using the same technique, and DBM was interposed between the cuff and bone. After 8 weeks, the RC tendon entheses from all rabbits were processed for gross and histologic examination. RESULTS: On gross TB healing, 2 of 11 specimens in the control group were unhealed and no specimen was grossly unhealed in the DBM group (p = 0.421). In the control group, the tendon midsubstance was disorganized with randomly and loosely arranged collagen fibers and rounded fibroblastic nuclei. The TB interface was predominantly fibrous with small regions of fibrocartilage, especially mineralized fibrocartilage. In the DBM group, the tendon midsubstance appeared normal and comprised densely arranged collagen fibers, with orientated crimped collagen fibers running in the longitudinal direction of the tendon. These fibers were interspersed with elongated fibroblast nuclei. The TB interface consisted of organized collagen fibers with large quantities of fibrocartilage and mineralized fibrocartilage. CONCLUSIONS: The use of DBM for TB interface healing in rabbit experiments showed good results in gross and histologic analysis. However, it is difficult to draw a solid conclusion because the sample size is small. Further evaluation in the in vivo setting is necessary to determine clinical recommendations.

Circadian regulation of chemotherapy-induced peripheral neuropathic pain and the underlying transcriptomic landscape.

Growing evidence demonstrates circadian rhythms of pain hypersensitivity in various chronic disorders. In chemotherapy-induced peripheral neuropathy (CIPN), agents such as paclitaxel are known to elicit chronic neuropathic pain in cancer patients and seriously compromise their quality of life. Here, we report that the mechanical threshold for allodynia in paclitaxel-treated rats exhibited a robust circadian oscillation, reaching the nadir during the daytime (inactive phase). Using Per2::LucSV circadian reporter mice expressing a PER2::LUC fusion protein, we isolated dorsal root ganglia (DRG), the primary sensory cell body for peripheral nerve injury generated hypersensitivity, and monitored ex vivo reporter bioluminescence. We observed strong circadian reporter rhythms in DRG neurons which are highly entrainable by external cues. Paclitaxel treatment significantly lengthened DRG circadian periods, with little effects on the amplitude of oscillation. We further observed the core protein BMAL1 and PER2 in DRG neurons and satellite cells. Using DRG and dorsal horn (DH; another key structure for CIPN pain response) tissues from vehicle and paclitaxel treated rats, we performed RNA-sequencing and identified diurnal expression of core clock genes as well as clock-controlled genes in both sites. Interestingly, 20.1% and 30.4% of diurnal differentially expressed genes (DEGs) overlapped with paclitaxel-induced DEGs in the DRG and the DH respectively. In contrast, paclitaxel-induced DEGs displayed only a modest overlap between daytime and nighttime (Zeitgeber Time 8 and 20). Furthermore, paclitaxel treatment induced de novo diurnal DEGs, suggesting reciprocal interaction of circadian rhythms and chemotherapy. Our study therefore demonstrates a circadian oscillation of CIPN and its underlying transcriptomic landscape.

Costoclavicular brachial plexus block reduces hemidiaphragmatic paralysis more than supraclavicular brachial plexus block: retrospective, propensity score matched cohort study.

BACKGROUND: Hemidiaphragmatic paralysis, a frequent complication of the brachial plexus block performed above the clavicle, is rarely associated with an infraclavicular approach. The costoclavicular brachial plexus block is emerging as a promising infraclavicular approach. However, it may increase the risk of hemidiaphragmatic paralysis because the proximity to the phrenic nerve is greater than in the classical infraclavicular approach. METHODS: This retrospective analysis compared the incidence of hemidiaphragmatic paralysis in patients undergoing costoclavicular and supraclavicular brachial plexus blocks. Of 315 patients who underwent brachial plexus block performed by a single anesthesiologist, 118 underwent costoclavicular, and 197 underwent supraclavicular brachial plexus block. Propensity score matching selected 118 pairs of patients. The primary outcome was the incidence of hemidiaphragmatic paralysis, defined as a postoperative elevation of the hemidiaphragm > 20 mm. Factors affecting the incidence of hemidiaphragmatic paralysis were also evaluated. RESULTS: Hemidiaphragmatic paralysis was observed in three patients (2.5%) who underwent costoclavicular and 47 (39.8%) who underwent supraclavicular brachial plexus blocks (P < 0.001; odds ratio, 0.04; 95% confidence interval, 0.01-0.13). Both the brachial plexus block approach and the injected volume of local anesthetic were significantly associated with hemidiaphragmatic paralysis. CONCLUSIONS: The incidence of hemidiaphragmatic paralysis is significantly lower with costoclavicular than with supraclavicular brachial plexus block.

Anesthetics and long-term survival after cancer surgery-total intravenous versus volatile anesthesia: a retrospective study.

BACKGROUND: Intravenous anesthesia has been reported to have a favorable effect on the prognosis of cancer patients. This study was performed to analyze data regarding the relation between anesthetics and the prognosis of cancer patients in our hospital. METHODS: The medical records of patients who underwent surgical resection for gastric, lung, liver, colon, and breast cancer between January 2006 and December 2009 were reviewed. Depending on the type of anesthetic, it was divided into total intravenous anesthesia (TIVA) or volatile inhaled anesthesia (VIA) group. The 5-year overall survival outcomes were analyzed by log-rank test. Cox proportional hazards modeling was used for sensitivity. RESULTS: The number of patients finally included in the comparison after propensity matching came to 729 in each group. The number of surviving patients at 5 years came to 660 (90.5%) in the TIVA and 673 (92.3%) in the VIA. The type of anesthetic did not affect the 5-year survival rate according to the log-rank test (P = 0.21). Variables associated with a significant increase in the hazard of death after multivariable analysis were male sex and metastasis at surgery. CONCLUSIONS: There were no differences in 5-year overall survival between two groups in the cancer surgery. TRIAL REGISTRATION: Trial registration: CRIS KCT0004101. Retrospectively registered 28 June 2019.

Thoracic Paravertebral Block with Adjuvant Dexmedetomidine in Video-Assisted Thoracoscopic Surgery: A Randomized, Double-Blind Study.

BACKGROUND: The addition of the adjuvant dexmedetomidine to a nerve block improves the quality of the block and reduces perioperative opioid consumption. The aim of this study was to assess the effect of dexmedetomidine as an adjuvant for the thoracic paravertebral block (TPVB) in postoperative pain control after video-assisted thoracoscopic surgery (VATS). METHODS: Sixty-six males, aged 15⁻40 years, with spontaneous pneumothorax scheduled for VATS wedge resection were enrolled. Following surgery, ultrasound-guided TPVB was performed on the T3 and T5 levels with 30 mL of 0.5% ropivacaine, plus adjuvant dexmedetomidine 50 µg or normal saline. The primary outcome was cumulative fentanyl consumption at 24 h. Pain severity, the requirement for additional rescue analgesics, hemodynamic variations, and side effects were also evaluated. RESULTS: Median postoperative cumulative fentanyl consumption at 24 h was significantly lower in the dexmedetomidine group (122.6 (interquartile range (IQR) 94.5⁻268.0) µg vs. 348.1 (IQR, 192.8⁻459.2) µg, p-value = 0.001) with a Hodges⁻Lehman median difference between groups of 86.2 (95% confidence interval (CI), 4.2⁻156.4) mg. Coughing numeric rating scale (NRS) was lower in the dexmedetomidine group at postoperative 2, 4, 8, and 24 h. However, resting NRS differed significantly only after 4 h postoperative. CONCLUSIONS: Dexmedetomidine as an adjunct in TPVB provided effective pain relief and significantly reduced opioid requirement in VATS.

Bone regeneration with umbilical cord blood mesenchymal stem cells in femoral defects of ovariectomized rats.

OBJECTIVES: Current treatments for osteoporosis were prevention of progression, yet it has been questionable in the stimulation of bone growth. The mesenchymal stem cells (MSCs) treatment for osteoporosis aims to induce differentiation of bone progenitor cells into bone-forming osteoblasts. We investigate whether human umbilical cord blood (hUCB)-MSCs transplantation may induce bone regeneration for osteoporotic rat model induced by ovariectomy. METHODS: The ovariectomized (OVX) group (n = 10) and OVX-MSCs group (n = 10) underwent bilateral ovariectomy to induce osteoporosis, while the Sham group (n = 10) underwent sham operation at aged 12 weeks. After a femoral defect was made at 9 months, Sham group and OVX group were injected with Hartmann solution, while the OVX-MSCs group was injected with Hartmann solution containing 1 × 107 hUCB-MSCs. The volume of regenerated bone was evaluated using micro-computed tomography at 4 and 8 weeks postoperation. RESULTS: At 4- and 8-week postoperation, the OVX group (5.0% ±â€¯1.5%; 6.1% ±â€¯0.7%) had a significantly lower regenerated bone volume than the Sham group (8.6% ±â€¯1.3%; 12.0% ±â€¯1.8%, P < 0.01), respectively. However, there was no significant difference between the OVX-MSCs and Sham groups. The OVX-MSCs group resulted in about 53% and 65% significantly higher new bone formation than the OVX group (7.7% ±â€¯1.9%; 10.0% ±â€¯2.9%, P < 0.05). CONCLUSIONS: hUCB-MSCs in bone defects may enhance bone regeneration in osteoporotic rat model similar to nonosteoporotic bone regeneration. hUCB-MSCs may be a promising alternative stem cell therapy for osteoporosis.

Expression of granulocyte colony-stimulating factor 3 receptor in the spinal dorsal horn following spinal nerve ligation-induced neuropathic pain.

In previous studies that have profiled gene expression in patients with complex regional pain syndrome (CRPS), the expression of granulocyte colony-stimulating factor 3 receptor (G­CSFR) was elevated, as were a number of pain­associated genes. The present study determined the expression of G­CSFR and the mechanisms by which it may affect hypersensitivity, focusing on the signal transducer and activator of transcription 3 (STAT3)/transient receptor potential cation channel subfamily V 1 (TRPV1) signaling pathway in particular, which is an important mediator of pain. Following L5 spinal nerve ligation (SNL) surgery, the protein and mRNA levels of G­CSFR increased in the ipsilateral spinal dorsal horn when compared with the sham and/or contralateral control. Double immunofluorescence further demonstrated that G­CSFR colocalized with TRPV1 and phosphorylated STAT in the neurons of the spinal dorsal horn. G­CSF treatment led to an increase in G­CSFR and TRPV1 expression and phosphorylation of STAT3. These results indicate that G­CSF­induced G­CSFR expression may activate TRPV1 by promoting phosphorylation of STAT3. Collectively, the results suggest, for the first time, that the expression of G­CSFR in neurons following peripheral nerve injury may be involved in the induction and maintenance of neuropathic pain through the STAT3 and TRPV1 signaling pathway.

Effect of an epinephrine mixture for interscalene block on hemodynamic changes after the beach chair position under general anesthesia: a retrospective study.

BACKGROUND: The beach chair position (BCP) can cause significant hypotension. Epinephrine is used to prolong the duration of local anesthetics; it is also absorbed into blood and can exert systemic effects. This study determined the effects of epinephrine mixed with ropivacaine for an interscalene block (ISB) on hemodynamic changes related to BCP. METHODS: Patient data collected from March 2013 to August 2014 were used retrospectively. We divided the patients into three groups: 1) ISB only, 2) I+G (general anesthesia after ISB without epinephrine), and 3) I+E+G (general anesthesia after ISB with epinephrine). Mean blood pressure (MBP) and heart rate (HR) were measured for 30 minutes at 5-minute intervals. RESULTS: The study analyzed data from 431 patients. MBP tended to decrease gradually in the groups I+G and I+E+G. There were significant differences in MBP between the groups I+G and I, and between the groups I+G and I+E+G. Group I+E+G showed a significant increase in HR compared with the other two groups. CONCLUSIONS: ISB with an epinephrine mixture did not prevent hypotension caused by the BCP after general anesthesia. HR increased only in response to the epinephrine mixture. A well-planned prospective study is required to compare hemodynamic changes in that context.

Effects of nicardipine on the onset time and intubation conditions of rocuronium-induced neuromuscular blockade.

STUDY OBJECTIVE: The objective of this study was to identify the effects of nicardipine on neuromuscular blockade of rocuronium, such as the onset time and intubation conditions, using a nicardipine dose that attenuates cardiovascular responses during endotracheal intubation. DESIGN: Randomized, double-blinded, placebo-controlled clinical comparison was used as the design of this study SETTING: The study was conducted at the operating room of a university hospital. PATIENTS: Participants of this study comprise 78 American Society of Anesthesiologists physical status 1 and 2 patients, aged 18 to 60 years who were undergoing elective surgery under general anesthesia. INTERVENTIONS: The nicardipine group was given an intravenous bolus of 20 µg/kg nicardipine before tracheal intubation: the control group was given an intravenous bolus of a comparable volume of normal saline before tracheal intubation. MEASUREMENTS: Using a TOF-Watch SX monitor, the time from the end of the injection of rocuronium to maximum depression of T1 (onset time) was measured. Intubation was performed 1 minute after rocuronium administration, and the status of the intubation conditions was assessed. The mean blood pressure and heart rate were each measured after endotracheal intubation. Rate pressure product values were also calculated. MAIN RESULTS: Intubation conditions were clinically acceptable in 37 (94.9%) of 39 patients in group N compared with 29 (74.4%) of 39 in group C (P < .05). The onset time of rocuronium was significantly faster in group N than in group C (P < .05). The mean blood pressure was significantly lower in group N than in group C (P < .05). The heart rate was significantly higher in group N than in group C (P < .05). Rate pressure product values showed no significant difference between the two groups (P > .05). CONCLUSIONS: Pretreatment with 20 µg/kg nicardipine improves intubation conditions, shortens the onset time of rocuronium, and attenuates cardiovascular responses to tracheal intubation.

TWIK-Related Spinal Cord K⁺ Channel Expression Is Increased in the Spinal Dorsal Horn after Spinal Nerve Ligation.

PURPOSE: The TWIK-related spinal cord K⁺ channel (TRESK) has recently been discovered and plays an important role in nociceptor excitability in the pain pathway. Because there have been no reports on the TRESK expression or its function in the dorsal horn of the spinal cord in neuropathic pain, we analyzed TRESK expression in the spinal dorsal horn in a spinal nerve ligation (SNL) model. MATERIALS AND METHODS: We established a SNL mouse model by using the L5-6 spinal nerves ligation. We used real-time polymerase chain reaction and immunohistochemistry to investigate TRESK expression in the dorsal horn and L5 dorsal rot ganglion (DRG). RESULTS: The SNL group showed significantly higher expression of TRESK in the ipsilateral dorsal horn under pain, but low expression in L5 DRG. Double immunofluorescence staining revealed that immunoreactivity of TRESK was mostly restricted in neuronal cells, and that synapse markers GAD67 and VGlut2 appeared to be associated with TRESK expression. We were unable to find a significant association between TRESK and calcineurin by double immunofluorescence. CONCLUSION: TRESK in spinal cord neurons may contribute to the development of neuropathic pain following injury.

Growth Differentiation Factor 15 Expression in Astrocytes After Excitotoxic Lesion in the Mouse Hippocampus.

Growth differentiation factor 15 (GDF15) is, a member of the transforming growth factor ß (TGF-ß) superfamily of proteins. Although GDF15 is well established as a potent neurotrophic factor for neurons, little is known about its role in glial cells under neuropathological conditions. We monitored GDF15 expression in astrocyte activation after a kainic acid (KA)-induced neurodegeneration in the ICR mice hippocampus. In control, GDF15 immunoreactivity (IR) was evident in the neuronal layer of the hippocampus; however, GDF15 expression had increased in activated astrocytes throughout the hippocampal region at day 3 after the treatment with KA. LPS treatment in astrocytes dramatically increased GDF15 expression in primary astrocytes. In addition, LPS treatment resulted in the decrease of the IκB-α degradation and increase of the phosphorylation level of RelA/p65. These results indicate that GDF15 has a potential link to NF-κB activation, making GDF15 a valuable target for modulating inflammatory conditions.

Endoplasmic reticulum stress impairment in the spinal dorsal horn of a neuropathic pain model.

Endoplasmic reticulum (ER) stress has been implicated in neurodegenerative diseases, but its role in neuropathic pain remains unclear. In this study, we examined the ER stress and the unfolded protein response (UPR) activation in a L5 spinal nerve ligation (SNL)-induced rat neuropathic pain model. SNL-induced neuropathic pain was assessed behaviorally using the CatWalk system, and histologically with microglial activation in the dorsal spinal horn. L5 SNL induced BIP upregulation in the neuron of superficial laminae of dorsal spinal horn. It also increased the level of ATF6 and intracellular localization into the nuclei in the neurons. Moreover, spliced XBP1 was also markedly elevated in the ipsilateral spinal dorsal horn. The PERK-elF2 pathway was activated in astrocytes of the spinal dorsal horn in the SNL model. In addition, electron microscopy revealed the presence of swollen cisternae in the dorsal spinal cord after SNL. Additionally, inhibition of the ATF6 pathway by intrathecal treatment with ATF6 siRNA reduced pain behaviors and BIP expression in the dorsal horn. The results suggest that ER stress might be involved in the induction and maintenance of neuropathic pain. Furthermore, a disturbance in UPR signaling may render the spinal neurons vulnerable to peripheral nerve injury or neuropathic pain stimuli.

Treatment with epidural blood patch for iatrogenic intracranial hypotension after spine surgery.

Intracranial hypotension syndrome typically occurs spontaneously or iatrogenically. It can be associated with headache, drowsy mentality and intracranial heamorrhage. Iatrogenic intracranial hypotension can occur due to dural pucture, trauma and spine surgery. Treatment may include conservative therapy and operation. We report a case of a 54-year-old man who was successfully treated with epidural blood patches for intracranial hypotension due to cerebrospinal fluid (CSF) leakage into the lumbosacral area after spine surgery.

Vomiting after a pediatric adenotonsillectomy: comparison between propofol induced sevoflurane-nitrous oxide maintained anesthesia and TIVA with propofol-remifentanil.

BACKGROUND: Anesthesia methods and drugs affect postoperative nausea and vomiting. Propofol is known to have antiemetic effects. We compared the incidence of postoperative vomiting (POV) in children undergoing an adenotonsillectomy; anesthesia in one group was induced with propofol and maintained with sevoflurane and nitrous oxide, and the other group received total intravenous anesthesia (TIVA) with propofol-remifentanil. METHODS: Ninety children, ASA physical status I, were assigned randomly to one of two groups. In the PSN group, anesthesia was maintained with 2-3 vol% sevoflurane and 50% nitrous oxide. In the PR group, anesthesia was maintained with 10 mg/kg/h propofol and 0.25 µg/kg/min remifentanil. In both groups, anesthesia was induced with 0.5 µg /kg remifentanil and 2 mg/kg propofol. The incidence of POV and the need for rescue antiemetics were assessed in the postanesthesia care unit at 6, 12, and 24 hours postoperatively. RESULTS: The total incidence of POV was not significantly different between the groups; POV occurred in eight (17.7%) and three (6.7%) children in the PSN and PR groups, respectively. Postoperative frequency of retching in the recovery room was significantly higher in the PSN group, with four children (8.9%) in the PSN group compared to none (0%) in the PR group (P = 0.041). The frequency of POV 24 hrs after exiting the recovery room tended to be higher in the PSN group than the PR group, but no statistically significant difference was observed. CONCLUSIONS: If the development of POV in the early anesthetic recovery phase of children undergoing adenotonsillectomy is adequately prevented, propofol-induced anesthesia maintained with sevoflurane-nitrous oxide is as safe as TIVA with propofol-remifentanil.