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Gastrodin is a major active phenolic glycoside extract from Gastrodia elata, an important herb used in traditional medicine. Previous research has reported that gastrodin possesses anti-inflammatory and anti-oxidant properties. Therefore, we aimed to investigate its hepatoprotective effects and mechanisms on acetaminophen (APAP)-induced liver injury in a mouse model. Mice included in this study were intraperitoneally administered with a hepatotoxic APAP dose (300 mg/kg). At 30 min after APAP administration, gastrodin was intraperitoneally injected at concentrations of 0, 15, 30, and 45 mg/kg. Then, all mice were sacrificed at 16 h after APAP injection for further analysis. The results showed that gastrodin treatment ameliorated acute liver injury caused by APAP, as indicated by serum alanine aminotransferase level, hepatic myeloperoxidase activity, and cytokine (TNF-α, IL-1β, and IL-6) production. It also significantly decreased hepatic malondialdehyde activity but increased superoxide dismutase activity. In addition, gastrodin decreased ERK/JNK MAPK expression but promoted Nrf2 expression. These results demonstrated that gastrodin may be a potential therapeutic target for the prevention of APAP-induced hepatotoxicity via amelioration of the inflammatory response and oxidative stress, inhibition of ERK/JNK MAPK signaling pathways, and activation of Nrf2 expression levels.

Background Diabetes mellitus (DM) has detrimental effects on the function of microvascular beds, resulting in blood–brain barrier (BBB) dysfunction. The objective of the study was to investigate whether DM affects the brain physiology through composition of cerebrospinal fluid (CSF) and compare gas tension and electrolyte levels in CSF between the diabetic and nondiabetic populations. Methods Patients aged between 20 and 70 years scheduled for elective orthopedic or urologic surgery requiring spinal anesthesia were enrolled. They were assigned to either of the two groups (control or type 2 DM). Gas tension and electrolytes in the CSF and whole blood samples were measured in both groups. Results All 49 enrolled patients (24 in the control and 25 in the DM group) completed the study. The concentrations of Na+ and Mg2+ in the blood were significantly lower in the DM group than those in the control. The levels of pCO2 and HCO 3 − {\text{HCO}}_{3}^{-} in the CSF were lower in the DM group than in the control group. In addition, there was a marked increase in the glucose level in both the blood and CSF in the DM group. Conclusion The results show that there were some homeostatic changes in blood and CSF in patients with DM.

Background: Analysis of cerebrospinal fluid (CSF) parameters helps clinicians identify patients with central nervous system (CNS) disease. In previous literature, reference values for CSF may be based on patients who were not truly healthy, other species, or outdated information. In the present study, we performed lumbar puncture in patients requiring spinal anesthesia by a reasonable indication to evaluate CSF parameters in healthy adults. Methods: All patients between the ages of 20 and 70 years scheduled for elective orthopedic or urologic surgery requiring spinal anesthesia were enrolled in this study. We measured electrolytes and gas tension analysis in CSF and whole blood samples in adult humans. Results: A total of 28 patients were included with an average age of 44.2 years. The pH of blood and CSF were both neutral, but it was slightly lower in blood. The concentration of Na+ in blood was slightly lower compared with that in CSF. There were significantly higher levels of K+ and Ca2+ in the blood compared with CSF. Significantly lower levels of Cl- and Mg2+ in the blood were observed compared with CSF. The glucose level of CSF was about half of that in blood. Conclusions: We provided updated reference values for various solutes in blood and CSF in adults. Although normal CSF constituents are quite similar to that of blood, there is still a small difference in normal values between them. Analysis of CSF parameters and relevant paired blood samples is highly informative, helping clinicians diagnose a variety of CNS diseases. Trial registration: This present study was approved by the Institutional Review Board of Chang Gung Medical Foundation, Taiwan (approval number: 201600122A3), and is registered under Clinical Trials Registry (ClinicalTrials.gov Identifier: NCT03725709).

Dual photothermal and photodynamic therapy (PTT and PDT) is an attractive approach that generates a synergistic effect for inhibiting keratinocyte hyperproliferation in the treatment of psoriasis. Here, we developed phototheranostic nanocarriers capable of producing hyperthermia and reactive oxygen species (ROS) in response to near-infrared (NIR) illumination. To this end, IR820 with photothermal and photodynamic features was embedded in nano-sized polydopamine (PDA) acting as a PTT agent. A comprehensive characterization of the PDA/IR820 nanosystem was performed according to its morphology, size, zeta potential, UV absorbance, and heat generation. Its therapeutic efficacy was assessed by a keratinocyte-based study and using an imiquimod (IMQ)-stimulated psoriasiform murine model. PDA/IR820 nanoparticles were facilely internalized into keratinocytes and mainly resided in lysosomes. Upon irradiation with NIR light, ROS were generated inside the keratinocytes to cause a photodynamic effect. The live/dead cell assay and cytotoxicity assay demonstrated that PDA and IR820 acted as effective photoabsorbers to induce keratinocyte death. The highest cytotoxic effect was detected in the group of NIR-irradiated PDA/IR820 nanoparticles, which killed 52% of keratinocytes. The nanosystem acted through the caspase and poly ADP-ribose polymerase (PARP) pathways to induce keratinocyte apoptosis.

Background Bacteremia-induced sepsis is a leading cause of mortality in intensive care units. To control a bacterial infection, an immune response is required, but this response might contribute to organ failure. Kidneys are one of the main organs affected by bacteremia. Combination therapies with antibacterial and anti-inflammatory effects may be beneficial in treating bacteremia. This study aimed to develop nanostructured lipid carriers (NLCs) loaded with ciprofloxacin and rolipram that exert a combination of anti-methicillin-resistant Staphylococcus aureus (MRSA) and anti-inflammatory effects. Retinol was incorporated into the nanoparticles to transport retinol-binding protein 4 (RBP4) to the kidneys, which abundantly express RBP receptors. The NLCs were fabricated by high-shear homogenization and sonication, and neutrophils were used as a model to assess their anti-inflammatory effects. Mice were injected with MRSA to establish a model of bacteremia with organ injury. Results The mean nanoparticle size and zeta potential of the NLCs were 171 nm and − 39 mV, respectively. Ciprofloxacin (0.05%, w/v) and rolipram (0.02%) achieved encapsulation percentages of 88% and 96%, respectively, in the nanosystems. The minimum bactericidal concentration of free ciprofloxacin against MRSA increased from 1.95 to 15.63 µg/ml when combined with rolipram, indicating a possible drug-drug interaction that reduced the antibacterial effect. Nanoparticle inclusion promoted the anti-MRSA activity of ciprofloxacin according to time-kill curves. The NLCs were found to be largely internalized into neutrophils and exhibited superior superoxide anion inhibition than free drugs. Retinol incorporation into the nanocarriers facilitated their efficient targeting to the kidneys. The NLCs significantly mitigated MRSA burden and elastase distribution in the organs of MRSA-infected animals, and the greatest inhibition was observed in the kidneys. Bacterial clearance and neutrophil infiltration suppression attenuated the bacteremia-induced cytokine overexpression, leading to an improvement in the survival rate from 22% to 67%. Conclusions The dual role of our NLCs endowed them with greater efficacy in treating MRSA bacteremia than that of free drugs.

Esculetin, a coumarin derivative from various natural plants, has an anti-inflammatory property. In the present study, we examined if esculetin has any salutary effects against lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Acute lung injury (ALI) was induced via the intratracheal administration of LPS, and esculetin (20 and 40 mg/kg) was given intraperitoneally 30 min before LPS challenge. After 6 h of LPS administration, lung tissues were collected for analysis. Pretreatment with esculetin significantly attenuated histopathological changes, inflammatory cell infiltration, and production of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, in the lung tissue. Furthermore, esculetin inhibited the protein kinase B (AKT), extracellular signal-regulated kinase (ERK), and nuclear factor-kappa B (NF-κB) pathways and downregulated the expression of RORγt and IL-17 in LPS-induced ALI. Our results indicated that esculetin possesses anti-inflammatory and protective effects against LPS-induced ALI via inhibition of the AKT/ERK/NF-κB and RORγt/IL-17 pathways.

Purpose Dexmedetomidine [DEX; (S)-4-[1-(2,3-dimethylphenyl)ethyl]-3H-imidazole] is a selective α2-adrenergic receptor (α2-AR) agonist that attenuates the liver damage associated with local or systemic inflammation. However, it remains unclear whether DEX has protective effects against acetaminophen (Paracetamol, PARA)-induced liver toxicity (PILT). Methods PILT mice were established by intraperitoneal administration of a hepatotoxic dose of acetaminophen (300 mg/kg). Thirty minutes later, the mice were treated with DEX at a concentration of 0, 5, 25, or 50 μg/kg. Blood and liver samples were obtained for further analysis. Results DEX treatment significantly attenuated PILT in mice, with the strongest beneficial effects at a dose of 25 μg/kg. The levels of hepatic cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), in addition to myeloperoxidase (MPO) activity, were significantly decreased following DEX treatment. Moreover, DEX treatment reduced macrophage recruitment around the area of hepatotoxicity and the expression levels of hepatic phosphorylated mitogen-activated protein kinase kinase 4 (MAP2K4), c-jun N-terminal kinase (JNK), and c-Jun expression induced by acetaminophen overdose. Conclusion The data suggest that DEX likely downregulates the JNK signaling pathway and its downstream effectors to promote its hepatoprotective effect, providing a clinical application of DEX for the attenuation of PILT.

Acetaminophen (APAP) overdose is the major cause of drug-induced liver injury and acute liver failure. Approximately 10% of APAP is metabolized by cytochrome P450 (CYP2E1) into toxic N-acetyl-p-benzoquinone imine (NAPQI). CYP2E1 also contributes to ethanol metabolism, especially during conditions of high blood ethanol concentration. Acute and chronic ethanol consumption appears to have opposite effects on APAP-induced liver injury. We determined the effects of different doses, pre- and post-treatment, and various schedules of ethanol exposure in APAP-induced liver injury. Treatment with ethanol (0.5 g/kg) after 1 h of APAP (300 mg/kg) administration decreased serum ALT levels, histopathological features, and inflammatory cell infiltration. Moreover, ethanol treatment 1 h after APAP treatment reduced APAP-induced liver injury compared with later administration. Interestingly, ethanol pretreatment did not provide any protective effect. Furthermore, ethanol treatment was associated with a significant decrease in ERK and AKT phosphorylation during the acute injury phase. Ethanol exposure also increased CYP2E1 expression and decreased PCNA expression during the liver regeneration phase.

Objective The aim of this study was to explore the relationship between preoperative right ventricular (RV) function and high vasoactive-inotropic score (VIS) after cardiac surgery. Design Prospective observational study. Setting A single medical center setting. Participants One hundred three patients undergoing elective cardiac surgery. Interventions None. Measurements and Main Results Consecutive patients referred for cardiac surgery were enrolled prospectively. Comprehensive transesophageal echocardiography was performed before sternal incision. Specific RV indices, encompassing RV fractional area change, tricuspid annular plane systolic excursion, and RV global longitudinal strain (RVGLS), were measured offline. High VIS was defined as a maximum VIS of ≥20 in 24 hours postoperatively. Postoperative adverse events were recorded. One hundred three patients (mean age 61.2 ± 11.0, 72 men) were included in this study, where 17 patients (16.5%) achieved high VIS with a mean maximum VIS of 39 in 24 hours postoperatively. Patients with high VIS encountered increased occurrence of extracorporeal membrane oxygenation placement, acute kidney injury, and mortality. Risk factors for high VIS included operation type, cardiopulmonary bypass duration, left atrium size, and pre-incisional RV indices. After adjustment for age, left ventricular ejection fraction, and the covariates, only RVGLS (odds ratio 1.19, p = 0.011) showed an independent association with high VIS. The optimal cutoff of RVGLS was −16.7% (sensitivity of 88.2%, specificity of 75.6%). Conclusion Preoperative RV dysfunction is an independent risk factor for postoperative high VIS. Pre-incisional RVGLS is a reliable tool to predict high VIS after cardiac surgery. Patients with high VIS had increased adverse events postoperatively.

Corilagin is a major active polyphenolic tannins extracted from Phyllanthus urinaria, an important herb used in traditional medicine. Previous reports demonstrated that corilagin possesses antioxidant and anti-inflammatory properties. Therefore, this study aimed to evaluate its hepatoprotective effects and mechanisms on acetaminophen (APAP)-induced liver injury in mice. Mice included in this study were intraperitoneally injected with a hepatotoxic APAP dose (300 mg/kg). After a 30 min of APAP administration, corilagin was injected intraperitoneally at concentrations of 0, 1, 5, 10, and 20 mg/kg. Then, after 16 h of corilagin treatment, mice were sacrificed for further analysis. APAP overdose significantly elevated the serum ALT level, hepatic myeloperoxidase (MPO) activity, cytokines (TNF-α, IL-1β, and IL-6) production, malondialdehyde (MDA) activity, and ERK/JNK MAPK and NF-κB protein expressions. Corilagin treatment significantly decreased these parameters in a dose-dependent manner (1-20 mg/kg). This study demonstrated that corilagin may be a potential therapeutic target for the prevention of APAP-induced hepatotoxicity by down-regulating the inflammatory response and by inhibiting ERK/JNK MAPK and NF-κB signaling pathways.

Background The relationship between perioperative right ventricular (RV) performance and hemodynamic instability after cardiac surgery seemed less portrayed. Therefore, we sought to elucidate this relationship and compare the accuracy of different RV systolic indices in predicting outcome of cardiac surgery. Methods This study enrolled consecutive patients referred for cardiac surgeries. Exclusion criteria were non-sinus rhythm or contraindications to transesophageal echocardiography (TEE). TEE exam and simultaneous pulmonary hemodynamics were recorded in two stages: after induction of anesthesia and before sternotomy (stage 1), and after sternal closure (stage 2). RV measurements performed offline included fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), peak systolic tricuspid annular velocity (RVS′), myocardial performance index (RVMPI), and global longitudinal strain (RVGLS). The end point was defined as prolonged use (>24 h) of postoperative inotropic agent in the intensive care unit (ICU). Results The study population included 68 patients (mean age 61 ± 11 y; 49 men). Twenty-two of these patients (32%) were administered inotropic agents for a prolonged period with a mean duration of 63.9 ± 5.3 h, accompanied with significantly longer ventilator use ( p = 0.006) and longer ICU stay ( p = 0.001) than patients without a prolonged inotropic agent use. Multivariable analysis demonstrated that only RVGLS in either stage 1 (odds ratio [OR] 1.11, p = 0.048) or stage 2 (OR 1.15, p = 0.018) was significantly associated with the outcome, especially a RVGLS > −13.5% in stage 2 demonstrating high risk of prolonged inotropic agent use after cardiac surgery (OR 7.37, p = 0.016). Conclusion RVGLSs performed using perioperative TEE are reliably associated with hemodynamic instability following cardiac surgery. This finding adds substantial information to postoperative critical care.

INTRODUCTION The study aimed to reveal how the fraction of inspired oxygen (FIO2) affected the value of mixed venous oxygen saturation (SvO2) and the accuracy of Fick-equation-based cardiac output (Fick-CO). METHODS Forty two adult patients who underwent elective cardiac surgery were enrolled and randomly divided into 2 groups: FIO2 0.85. Under stable general anesthesia, thermodilution-derived cardiac output (TD-CO), SvO2, venous partial pressure of oxygen, hemoglobin, arterial oxygen saturation, arterial partial pressure of oxygen, and blood pH levels were recorded before surgical incision. RESULTS Significant differences in FIO2 values were observed between the 2 groups (0.56 ± 0.08 in the 0.85 group; P

Purpose Dexmedetomidine [DEX; (S)-4-[1-(2,3-dimethylphenyl)ethyl]-3H-imidazole] is a selective α2-adrenergic receptor (α2-AR) agonist that attenuates the liver damage associated with local or systemic inflammation. However, it remains unclear whether DEX has protective effects against acetaminophen (Paracetamol, PARA)-induced liver toxicity (PILT). Methods PILT mice were established by intraperitoneal administration of a hepatotoxic dose of acetaminophen (300 mg/kg). Thirty minutes later, the mice were treated with DEX at a concentration of 0, 5, 25, or 50 μg/kg. Blood and liver samples were obtained for further analysis. Results DEX treatment significantly attenuated PILT in mice, with the strongest beneficial effects at a dose of 25 μg/kg. The levels of hepatic cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), in addition to myeloperoxidase (MPO) activity, were significantly decreased following DEX treatment. Moreover, DEX treatment reduced macrophage recruitment around the area of hepatotoxicity and the expression levels of hepatic phosphorylated mitogen-activated protein kinase kinase 4 (MAP2K4), c-jun N-terminal kinase (JNK), and c-Jun expression induced by acetaminophen overdose. Conclusion The data suggest that DEX likely downregulates the JNK signaling pathway and its downstream effectors to promote its hepatoprotective effect, providing a clinical application of DEX for the attenuation of PILT.

Oximeter is an important clinical device used for measuring peripheral capillary oxygen saturation (SpO2) in blood and hence accurate results are needed in order to help physicians predict clinical problems in the initial stage(s) of liver or kidney diagnosis. Different issues associated with the accuracy of SpO2 and heart rate measurement accuracy are studied in this work. With the understanding of these issues, a new SpO2 monitoring system is proposed that comprises of a better detection method, novel discrete time signal processing (DTSP) algorithm, and a custom-made oximeter probe head. The proposed SpO2 measurement system is capable of determining low levels of SpO2 present in human blood and produce the results in a short time that enable real-time monitoring of a patient SpO2. It can also distinguish low level of SpO2 against background noise.

Acetaminophen (APAP) overdose may lead to the formation of oxidative stress, hepatocyte apoptosis and necrosis, and, eventually result in acute liver failure. Escin, a major extracted component of Aesculus hippocastanum, reportedly exerts anti-inflammatory, anti-edematous and anti-oxidant properties. Previous studies have demonstrated these protective effects of A. hippocastanum extracts on ischemia/reperfusion intestinal injury and endotoxin-induced lung injury. In this study, we aimed to evaluate the effect of escin on APAP-induced liver injury in mice. Mice were intraperitoneally administrated with APAP (300 mg/kg) or an equal volume of saline (control), followed by a treatment with various concentrations of escin (0, 0.5, 1, 2 and 4 mg/kg) for 30 min. The animals were sacrificed 16 h following APAP administration for serum and liver tissue assay. Escin treatment attenuated the damage of APAP-induced liver injury in a dose-dependent manner (0.5-4 mg/kg). Escin also attenuated the hepatic myeloperoxidase (MPO) activity and hepatic pro-inflammatory cytokines (i.e., TNF-α, IL-1β, IL-6 and IL-17). Furthermore, escin treatment decreased the hepatic phosphorylation expression of extracellular signal-regulated kinase (ERK). Our data indicates that escin shows protective effects on APAP-induced hepatotoxicity in a dose-dependent manner through anti-inflammatory mechanism and the inhibition of ERK signaling pathway.

Background: Dexmedetomidine [DEX; (S) 4 [1 (2,3 dimethylphenyl)ethyl] 3H imidazole] is a selective α2 adrenergic receptor (α2 AR) agonist that attenuates the liver damage associated with local or systemic inflammation. However, it remains unclear whether DEX has hepatoprotective effects against acetaminophen (APAP)-induced liver injury. Methods: APAP-induced hepatotoxic mice were established by intraperitoneal administration of a hepatotoxic dose of APAP (300 mg/kg). Thirty minutes later, the mice were treated with DEX at a concentration of 0, 5, 25, or 50 μg/kg. Blood and liver samples were obtained for further analysis. Findings: DEX treatment significantly attenuated APAP-induced liver injury in mice, with the strongest beneficial effects at a dose of 25 μg/kg. The levels of hepatic cytokines (TNF-α and IL-6), in addition to myeloperoxidase (MPO) activity, were significantly decreased following DEX treatment. Moreover, DEX treatment reduced macrophage recruitment around the area of hepatotoxicity and the expression levels of hepatic phosphorylated mitogen-activated protein kinase 4 (MAP2K4), c-jun N-terminal kinase (JNK), and c-Jun expression induced by APAP overdose. Interpretation: The data suggests that DEX likely downregulates the JNK signaling pathway and its downstream effectors to promote its hepatoprotective effect, providing a clinical application of DEX for the attenuation of APAP-induced hepatotoxicity. Funding: The present study was supported by a grant from the Chang Gung Medical Research Project (BMRPC19, CMRPG3D1471, CMRPG3D1472, CMRPG3D1473), Chang Gung Memorial Hospital, Linkou, Taiwan, and the Ministry of Science and Technology, Taiwan (MOST 106-2314-B-182A- 061- MY2). Declaration of Interest: The authors have declared that no conflict of interest exists. Ethical Approval: All animal study protocols were reviewed and approved by the Institutional Animal Care and Use Committee of Chang Gung University. All experiments were performed according to the guidelines of the Animal Welfare Act and the Guide for Care and Use of Laboratory Animals from the National Institutes of Health.

Study Objective To compare ventilation variables, changes in oxidative stress, and the quality of recovery in 2 different ventilation strategies (volume-controlled ventilation [VCV] and pressure-controlled ventilation [PCV]) during gynecologic laparoscopic surgery. Design A prospective randomized controlled trial (Canadian Task Force classification I). Setting One university teaching hospital in Taiwan. Patients Women scheduled for laparoscopic gynecologic surgery. Interventions Women were randomly assigned to receive either VCV or PCV during surgery. Measurements and Main Results Ventilation variables were recorded 1 minute before and 1 hour after pneumoperitoneum. Blood samples were collected for malondialdehyde measurement at 7 points: 1 minute before and 1 hour after pneumoperitoneum; 30, 60, 90, and 120 minutes after deflation; and 24 hours after surgery. Postoperative recovery was assessed by using a 9-item quality of recovery score at 24 hours after surgery. A total of 52 women randomly allocated to the VCV (n = 27) or PCV (n = 25) group completed the study. We found that after 1 hour of insufflation the PCV group had lower peak airway pressure (22.0 ± 3.4 vs 26.6 ± 4.1 cm H 2 O, p 2 O, p Conclusion PCV is an alternative ventilation mode in gynecologic laparoscopic surgery. However, PCV offered lower peak airway pressure and higher compliance than VCV but no advantages over VCV in oxidative stress or quality of recovery.

Objectives. To investigate the protective effects of tropisetron on acetaminophen- (APAP-) induced liver injury in a mice model.Methods. C57BL/6 male mice were given tropisetron (0.3 to 10 mg/kg) 30 minutes before a hepatotoxic dose of acetaminophen (300 mg/kg) intraperitoneally. Twenty hours after APAP intoxication, sera alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, hepatic myeloperoxidase (MPO), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) activities, and liver histopathological changes were examined. The MAP kinases were also detected by western blotting.Results. Our results showed that tropisetron pretreatment significantly attenuated the acute elevations of the liver enzyme ALT level, hepatic MPO activity, and hepatocytes necrosis in a dose-dependent manner (0.3–10 mg/kg) in APAP-induced hepatotoxicity mice. Tropisetron (1 and 3 mg/kg) suppressed APAP-induced hepatic lipid peroxidation expression and alleviated GSH and SOD depletion. Administration of tropisetron also attenuated the phosphorylation of c-Jun-NH2-terminal protein kinase (JNK) and extracellular signal-regulated kinase (ERK) caused by APAP.Conclusion. Our data demonstrated that tropisetron’s hepatoprotective effect was in part correlated with the antioxidant, which were mediated via JNK and ERK pathways on acetaminophen-induced liver injury in mice.

Introduction Video laryngoscopy-assisted tracheal intubation devices have become alternatives to traditional laryngoscopes in recent years. This review will provide information on commonly used video laryngoscopes and their clinical applications in airway management. Areas covered In this review, the differences between video laryngoscopy and direct laryngoscopy, and the utilization of video laryngoscopes in specific clinical settings are discussed. Expert commentary Video laryngoscopy should be embraced as an initial approach to intubation in patients with suspected difficult airway. Acute care providers should be familiar with more than one intubation techniques so that a rescue attempt can be applied promptly. Continual practice and familiarity with new video laryngoscopes are still essential to maximize the effectiveness and minimize the complications of using these devices.

Acetaminophen (APAP) overdose results in the production of reactive oxygen species (ROS), hepatocyte necrosis, and cell death, and leads to acute liver failure. Interleukin-17 (IL-17), a pro-inflammatory cytokine, plays a key role in the recruitment of neutrophils into sites of inflammation and subsequent damage after liver ischemia-reperfusion injury. In this study, we employed IL-17 knockout (KO) mice to investigate the role of IL-17 in APAP-induced hepatotoxicity. IL-17 wide type (WT) and IL-17 KO mice received an intraperitoneal injection of APAP (300 mg/kg). After 16 h of treatment, the hepatic injury, inflammatory mediators, immune cell infiltration, and western blotting were examined and analyzed. The serum alanine transferase (ALT) enzyme levels and hepatic myeloperoxidase (MPO) activity were significantly elevated 16 h after APAP treatment in the WT mice. IL-17 deficiency significantly attenuates APAP-induced liver injury, MPO activity, pro-inflammatory cytokines (tumor necrosis factor-α, IL-6 and interferon-γ) levels and inflammatory cell (neutrophils, macrophage) infiltration in the liver. Moreover, phosphorylated extracellular signal-regulated kinase (ERK) was significantly decreased at 16 h after APAP treatment in the IL-17 KO mice compared with the IL-17 WT mice. Our data suggests that IL-17 plays a pivotal role in APAP-induced hepatotoxicity through modulation of inflammatory response, and perhaps in part through the ERK signaling pathway. Blockade of IL-17 could be a potential therapeutic target for APAP-induced hepatotoxicity.

CCL5/RANTES, a chemoattractant for myeloid cells, is induced by hepatic ischemia/reperfusion injury (IRI). The roles of CCL5 in hepatic IRI were carried out by means of CCL5 immunodepletion, antagonistic competition by Met-CCL5, and treatment with recombinant murine CCL5 (rmCCL5). Depletion or inhibition of CCL5 reduced severity of hepatic IRI, whereas rmCCL5 treatment aggravated liver IRI as manifested in elevated serum alanine aminotransferase (ALT) and tissue myeloperoxidase (MPO) levels. Moreover, IRI severity was reduced in CCL5-knockout (CCL5-KO) mice versus wildtype (WT) mice, with drops in serum ALT level, intrahepatic MPO activity, and histological pathology. Bone marrow transplantion (BMT) studies show that myeloid cells and tissue cells are both required for CCL5-aggravated hepatic IRI. The profile of liver-infiltrating leukocyte subsets after hepatic reperfusion identified CD11b+ cells as the only compartment significantly reduced in CCL5-KO mice versus WT controls at early reperfusion phase. The role of CCL5 recruiting CD11b+ cells in early reperfusion was validated by in vitro transwell migration assay of murine primary macrophages (broadly characterized by their CD11b expression) in response to liver lysates after early reperfusion. Taken together, our results demonstrate a sequence of early events elicited by CCL5 chemoattracting macrophage that result in inflammatory aggravation of hepatic IRI.

Acetaminophen (APAP) overdose causes hepatocytes necrosis and acute liver failure. Baicalin (BA), a major flavonoid of Scutellariae radix, has potent hepatoprotective properties in traditional medicine. In the present study, we investigated the protective effects of BA on a APAP-induced liver injury in a mouse model. The mice received an intraperitoneal hepatotoxic dose of APAP (300[Formula: see text]mg/kg) and after 30[Formula: see text]min, were treated with BA at concentrations of 0, 15, 30, or 60[Formula: see text]mg/kg. After 16[Formula: see text]h of treatment, the mice were sacrificed for further analysis. APAP administration significantly elevated the serum alanine transferase (ALT) enzyme levels and hepatic myeloperoxidase (MPO) activity when compared with control animals. Baicalin treatment significantly attenuated the elevation of liver ALT levels, as well as hepatic MPO activity in a dose- dependent manner (15–60[Formula: see text]mg/kg) in APAP-treated mice. The strongest beneficial effects of BA were seen at a dose of 30[Formula: see text]mg/kg. BA treatment at 30[Formula: see text]mg/kg after APAP overdose reduced elevated hepatic cytokine (TNF-[Formula: see text] and IL-6) levels, and macrophage recruitment around the area of hepatotoxicity in immunohistochemical staining. Significantly, BA treatment can also decrease hepatic phosphorylated extracellular signal-regulated kinase (ERK) expression, which is induced by APAP overdose. Our data suggests that baicalin treatment can effectively attenuate APAP-induced liver injury by down-regulating the ERK signaling pathway and its downstream effectors of inflammatory responses. These results support that baicalin is a potential hepatoprotective agent.

Local anesthetics are commonly used for pain relief by regional nerve blocking. In this study, we fabricated solvent-free biodegradable pellets to extend the duration of lidocaine release without any significant local or systemic toxicity levels. To manufacture the pellets, poly[(d,l)-lactide-co-glycolide] (PLGA) was first pre-mixed with lidocaine powder into different ratios. The powder mixture was then compressed with a mold (diameter of 1, 5, 8 or 10 mm) and sintered at 65 °C to form pellets. The in vitro release study showed that the lidocaine/PLGA pellets exhibited a tri-phase release behavior (a burst, a diffusion-controlled release and a degradation-dominated release) and reached completion around day 28. Scanning electron microscope (SEM) photos show that small channels could be found on the surfaces of the pellets on day 2. Furthermore, the polymer matrix swelled and fell apart on day 7, while the pellets became viscous after 10 days of in vitro elution. Perineural administration of the lidocaine/PLGA pellets produced anti-hypersensitivity effects lasting for at least 24 h in rats, significant when compared to the control group (a pure PLGA was pellet administered). In addition, no inflammation was detected within the nerve and in the neighboring muscle by histopathology.

Interleukin-17 (IL-17) is involved in a wide range of inflammatory disorders and in recruitment of inflammatory cells to injury sites. A recent study of IL-17 knock-out mice revealed that IL-17 contributes to neuroinflammation and neuropathic pain after peripheral nerve injury. Surprisingly, little is known of micro-environment modulation by IL-17 in injured sites and in pathologically related neuroinflammation and chronic neuropathic pain. Therefore, we investigated nociceptive sensitization, immune cell infiltration, myeloperoxidase (MPO) activity, and expression of multiple cytokines and opioid peptides in damaged nerves of wild-type (IL-17(+/+)) and IL-17 knock-out (IL-17(-/-)) mice after partial sciatic nerve ligation. Our results demonstrated that the IL-17(-/-) mice had less behavioral hypersensitivity after partial sciatic nerve ligation, and inflammatory cell infiltration and pro-inflammatory cytokine (tumor necrosis factor-α, IL-6, and interferon-γ) levels in damaged nerves were significantly decreased, with the levels of anti-inflammatory cytokines IL-10 and IL-13, and expressions of enkephalin, β-endorphin, and dynorphin were also decreased compared to those in wild-type control mice. In conclusion, we provided evidence that IL-17 modulates the micro-environment at the level of the peripheral injured nerve site and regulates progression of behavioral hypersensitivity in a murine chronic neuropathic pain model. The attenuated behavioral hypersensitivity in IL-17(-/-) mice could be a result of decreased inflammatory cell infiltration to the injured site, resulting in modulation of the pro- and anti-inflammatory cytokine milieu within the injured nerve. Therefore, IL-17 may be a critical component for neuropathic pain pathogenesis and a novel target for therapeutic intervention for this and other chronic pain states.

Growing evidence suggests that leukocyte extravasation is initiated by the interaction of selectins with their ligands; as well as an essential role for P-selectin in the initial recruitment of inflammatory cells to sites of inflammation. In this study, P-selectin-deficient (P-sel-/-) mice were used to test the hypothesis that lack of P-selectin would attenuate the recruitment of inflammatory cells to the site of inflammation, thereby modulating pain in a murine chronic neuropathic pain model. Nociceptive sensitization and the microenvironment of the peripheral injury site were studied in wild-type (P-sel+/+) and P-selectin-deficient (P-sel-/-) mice after partial sciatic nerve ligation (PSNL). Variables measured included myeloperoxidase (MPO) activity, several inflammatory cell infiltration profiles, cytokines, and endogenous opioid peptide expression in damaged nerves. Results indicate that behavioral hypersensitivity, MPO activity, and infiltration of neutrophils and macrophages were attenuated in P-sel-/- mice after PSNL. Proinflammatory cytokines, tumor necrosis factor α, and interleukin (IL)-6, were reduced in damaged nerves following PSNL; however, several antiinflammatory cytokines - IL-1Ra, IL-4, and IL-10 - were significantly increased in P-sel-/- mice. In addition, endogenous opioid peptides mRNA was significantly lower in P-sel-/- mice compared with P-sel +/+ mice. The current results demonstrated that the absence of P-selectin in mice leads to an altered microenvironment that attenuated behavioral hypersensitivity. The specific role of P-selectin could have been a result of decreased neutrophils, as well as the accumulation of macrophages at the site of injury, which may subsequently modulate the inflammatory cytokine expression and impact behavioral hypersensitivity within the injured nerve.

Background IL-17 has been shown to be involved in liver inflammatory disorders in both mice and humans. Baicalin (BA), a major compound extracted from traditional herb medicine (Scutellariae radix), has potent hepatoprotective properties. Previous study showed that BA inhibits IL-17-mediated lymphocyte adhesion and downregulates joint inflammation. The aim of this study is to investigate the role of IL-17 in the hepatoprotective effects of BA in an acetaminophen (APAP)-induced liver injury mouse model. Methods Eight weeks male C57BL/6 (B6) mice were used for this study. Mice received intraperitoneal hepatotoxic injection of APAP (300 mg/kg) and after 30 min of injection, the mice were treated with BA at a concentration of 30 mg/kg. After 16 h of treatment, mice were killed. Blood samples and liver tissues were harvested for analysis of liver injury parameters. Results APAP overdose significantly increased the serum alanine transferase (ALT) levels, hepatic activities of myeloperoxidase (MPO), expression of cytokines (TNF-α, IL-6, and IL-17), and malondialdehyde (MDA) activity when compared with the control animals. BA treatment after APAP administration significantly attenuated the elevation of these parameters in APAP-induced liver injury mice. Furthermore, BA treatment could also decrease hepatic IL-17-producing γδT cells recruitment, which was induced after APAP overdose. Conclusion Our data suggested that baicalin treatment could effectively decrease APAP-induced liver injury in part through attenuation of hepatic IL-17 expression. These results indicate that baicalin is a potential hepatoprotective agent.

The purpose of this study was to compare the results of thoracic epidural analgesia (TEA) and parecoxib in controlling postoperative pain after the Nuss procedure.Between August 2005 and July 2014, 120 adolescents and adults underwent Nuss procedures and received either TEA or parecoxib for postoperative pain control. Demographic data, preoperative preparation times, visual analog scale (VAS) pain scores from postoperative day 1 to day 5, medical costs of pain control, days to Foley catheter removal, days to being able to sit up, days to being able to walk, days of hospital stay, nausea/vomiting scores, and complications related to pain control were compared.A total of 106 patients received TEA, and 14 received parecoxib. No between-group differences in demographics were observed. Patients in the parecoxib group had shorter preparation times (p0.001), lower VAS pain scores from postoperative day 2 to day 5 (day 2, p=0.006; day 3, p=0.006; day 4, p0.001; day 5, p0.001), shorter hospital stays (p0.001), lower pain control costs (p0.001), and lower nausea/vomiting scores (p=0.046).For adolescents and adults undergoing the Nuss procedure, parecoxib affords better pain control efficacy, a shorter hospital stay, lower medical pain control costs, and fewer side effects compared with TEA.

Pruritus is the most common side effect of epidural morphine analgesia. Diphenhydramine is a widely used agent for the treatment of urticarial pruritus. Nalbuphine is a mixed opioid agonist-antagonist and has been reported to be effective in treating opioid-induced pruritus. We compared the effectiveness of intramuscular diphenhydramine and nalbuphine for the prevention of epidural morphine-induced pruritus after cesarean section.One hundred and fifty, American Society of Anesthesiologists physical status I or II, women undergoing cesarean section with epidural anesthesia were randomly assigned to three groups. Group S, group D, and group N received intramuscular normal saline (1 ml; n = 50), diphenhydramine (30 mg/1 ml; n = 50), and nalbuphine (10 mg/1 ml; n = 50), respectively, after delivery of the baby. The occurrence and the severity of pruritus were assessed at 1, 4, 12, and 24 hours after surgery.The overall incidence of pruritus during the 24 hr follow-up period was 72%, 68%, and 44% for group S, group D, and group N, respectively. Pruritus occurred less frequently in group N than group D (p = 0.027). At 4 and 12 hrs postoperatively, the pruritus severity was significantly different (p = 0.003 and p = 0.002) and was significantly less in group N than group D in the intergroup comparison (p = 0.013 and p = 0.012).Nalbuphine proved better than diphenhydramine for prevention of epidural morphine-induced pruritus in patients who underwent cesarean section. Prophylactic intramuscular nalbuphine (10 mg) is effective in decreasing the incidence and severity of pruritus and does not affect analgesia.

Roughly 60,000 operations are performed at our medical center every year, so making efficient use of operating rooms (OR) is an important issue. Decreasing the cancellation rate of surgery is one method that could increase efficiency. We reviewed all OR cancellations in 2007 to survey the cancellation rates and causes.The present study was retrospective. Data were collected from the Department of Anesthesiology Quality Assurance Database of Chang Gung Memorial Hospital. We analyzed medical records for cancellations from January 1 to December 31, 2007. Data were analyzed using SPSS 16.0, employing descriptive measures and logistic regression.There were 61855 operations scheduled during this period; 229 were cancelled (0.37%). The mean age of patients in the cancelled group was significantly higher than that in the the non-cancelled group. We found a positive correlation between the cancellation rate and American Society of Anesthesiologists physical status. Cancellations for outpatient surgery were most frequent, as were those in the ophthalmology department. Forty-seven cases were cancelled because of cardiovascular problems; 136 operations were done later after the original cancellation issues were addressed while 11 were done under local anesthesia.Of all causes of cancellation of surgery, 54.1% were avoidable. Medical teams must communicate better with patients and relatives, identify and treat relevant comorbidities, and make adequate preparations for surgery.

Although epidural analgesia reduces the postoperative stress response and provides good pain relief for patients, potential complications associated with the technique may decrease its acceptability for some patients. We describe a 76-year-old female who underwent surgery for carcinoma of the urinary tract. Postoperative epidural analgesia was performed at the postanesthesia care unit. Neither a repeat attempt nor accidental dural puncture was encountered during the procedure. Unfortunately, she sustained neurological impairment of the bilateral lower limbs following an episode of myocardial ischemia during the early postoperative period. When the neurological deficit was recognized following epidural anesthesia, poor puncture technique was the first to be blamed. In fact, a high level of sensory blockade could markedly decrease blood pressure and heart rate, particularly in the presence of hypovolemia, which might lead to impairment of coronary perfusion and result in my ocardial ischemia. Severe systemic hypotension might further lead to hypoperfusion of the spinal cord, most possibly in the mid-thoracic region (T4 to T8) due largely to its relative hypovascularity. Therefore, we recommend that maintaining sufficient circulatory volume of the patient, evaluating and recording the neurological function of the patient and determining the possible risk factors associated with coronary arterial disease are imperative prior to performing an epidural procedure.