Linalool, a Fragrance Compound in Plants, Protects Dopaminergic Neurons and Improves Motor Function and Skeletal Muscle Strength in Experimental Models of Parkinson's Disease.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), resulting in reduced dopamine levels in the striatum and eventual onset of motor symptoms. Linalool (3,7-dimethyl-1,6-octadien-3-ol) is a monoterpene in aromatic plants exhibiting antioxidant, antidepressant, and anti-anxiety properties. The objective of this study is to evaluate the neuroprotective impacts of linalool on dopaminergic SH-SY5Y cells, primary mesencephalic and cortical neurons treated with 1-methyl-4-phenylpyridinium ion (MPP+), as well as in PD-like mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Cell viability, α-tubulin staining, western blotting, immunohistochemistry and behavioral experiments were performed. In MPP+-treated SH-SY5Y cells, linalool increased cell viability, reduced neurite retraction, enhanced antioxidant defense by downregulation of apoptosis signaling (B-cell lymphoma 2 (Bcl-2), cleaved caspase-3 and poly ADP-ribose polymerase (PARP)) and phagocyte NADPH oxidase (gp91phox), as well as upregulation of neurotrophic signaling (brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF)) and nuclear factor-erythroid 2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. In MPP+-treated primary mesencephalic neurons, linalool enhanced the expressions of tyrosine hydroxylase (TH), Sirtuin 1 (SirT1), and parkin. In MPP+-treated primary cortical neurons, linalool upregulated protein expression of SirT1, γ-Aminobutyric acid type A-α1 (GABAA-α1), and γ-Aminobutyric acid type B (GABAB). In PD-like mice, linalool attenuated the loss of dopamine neurons in SNpc. Linalool improved the motor and nonmotor behavioral deficits and muscle strength of PD-like mice. These findings suggest that linalool potentially protects dopaminergic neurons and improves the impairment symptoms of PD.

Trachway® flexible stylet facilitates the correct placement of double-lumen endobronchial tube: a prospective, randomized study.

BACKGROUND: The mainstream facilitation of one-lung ventilation is using double-lumen endobronchial tubes. However, it is more difficult to be positioned properly and more likely to cause airway injuries. How to place double-lumen endobronchial tubes rapidly and correctly is important for thoracic anesthesiologists. METHODS: One hundred eight patients with an American Society of Anesthesiologists physical status of I to III were 20 years of age or over, and required one-lung ventilation for thoracic surgery. They were randomly assigned to the conventional technique group (n = 36), the flexible fiberoptic bronchoscopy group (n = 36), or the Trachway® flexible stylet group (n = 36). The primary endpoint was the time needed for intubation. T1, the time from the tip of the blade passing between the patient's lips to identification of the vocal cords; and T2, the time from identification of the vocal cords to the bronchial lumen was in the correct position. RESULTS: T1 had no significant difference between groups, but T2 was significantly shorter in the Trachway® flexible stylet group (p < 0.0001) and longer in the conventional technique group (p < 0.0001). CONCLUSIONS: Using Trachway® flexible stylet for correct placement of double-lumen endobronchial tubes not only significantly shortened the intubation time, but also reduced incidence of carinal injuries. It is an alternative, and a choice with good safety. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02364622, 18/02/2015, Retrospectively registered.

Naringenin, a dietary flavanone, enhances insulin-like growth factor 1 receptor-mediated antioxidant defense and attenuates methylglyoxal-induced neurite damage and apoptotic death.

Objectives: Recent studies revealed the neuroprotective effects of naringenin (NGEN), a common dietary bioflavonoid contained in citrus fruits. However, there are limited data on its protection against methylglyoxal (MG), the most potent precursor of advanced glycation end-products. The present study was to investigate the protection of NGEN on MG-induced neurotoxicity and the involvement of insulin-like growth factor 1 receptor (IGF-1R) signaling. Methods: NSC34 motor neuron-like cells was used. Cell viability was measured by MTT assay. Protein expressions were analyzed by western blots. Morphological changes of neurites were observed by an inverted microscope. Reactive oxygen species (ROS) production and apoptotic cell numbers were measured by flow cytometer. Glutathione (GSH) level and superoxide dismutase (SOD) activity were measured by ELISA. Results: >NGEN attenuated ROS production and increased GSH level, SOD activity and nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear expression in MG-treated NSC34 cells. NGEN also increased neurite length and enhanced IGF-1R and p-Akt in MG-treated NSC34 cells. Furthermore, NGEN attenuated MG-induced apoptotic death accompanied with down-regulation of cleaved-poly (ADP-ribose) polymerase (PARP) and up-regulation of B-cell lymphoma-2 (Bcl-2). However, AG1024, an IGF-1R antagonist, attenuated the anti-oxidative and anti-apoptotic effects of NGEN in MG-treated cells. Discussion: The present results demonstrated that NGEN decreased neuronal apoptosis and improved antioxidant defense in MG-treated NSC34 cells. Moreover, IGF-1R-mediated antioxidant defense plays an important role in this protective mechanism. These findings suggest the potential benefits of NGEN on the prevention of MG-induced or diabetes/hyperglycemia-related neurotoxicity. In vivo studies are needed for further confirmation on NGEN-mediated neuroprotection.

Characterization of Convergent Suppression by UCL-2077 (3-(Triphenylmethylaminomethyl)pyridine), Known to Inhibit Slow Afterhyperpolarization, of erg-Mediated Potassium Currents and Intermediate-Conductance Calcium-Activated Potassium Channels.

UCL-2077 (triphenylmethylaminomethyl)pyridine) was previously reported to suppress slow afterhyperpolarization in neurons. However, the information with respect to the effects of UCL-2077 on ionic currents is quite scarce. The addition of UCL-2077 decreased the amplitude of erg-mediated K+ current (IK(erg)) together with an increased deactivation rate of the current in pituitary GH3 cells. The IC50 and KD values of UCL-2077-induced inhibition of IK(erg) were 4.7 and 5.1 µM, respectively. UCL-2077 (10 µM) distinctly shifted the midpoint in the activation curve of IK(erg) to less hyperpolarizing potentials by 17 mV. Its presence decreased the degree of voltage hysteresis for IK(erg) elicitation by long-lasting triangular ramp pulse. It also diminished the probability of the opening of intermediate-conductance Ca2+-activated K+ channels. In cell-attached current recordings, UCL-2077 raised the frequency of action currents. When KCNH2 mRNA was knocked down, a UCL-2077-mediated increase in AC firing was attenuated. Collectively, the actions elaborated herein conceivably contribute to the perturbating effects of this compound on electrical behaviors of excitable cells.

Resveratrol prevents nanoparticles-induced inflammation and oxidative stress via downregulation of PKC-α and NADPH oxidase in lung epithelial A549 cells.

BACKGROUND: Exposure to carbon black nanoparticles (CBNPs), a well-known industrial production, promotes pulmonary toxicity through inflammation and oxidative stress. Recent studies show that some polyphenols exert their antioxidant properties through regulation of protein kinase C-α (PKC-α) and NADPH oxidase (Nox) signaling. Resveratrol, a dietary polyphenol in fruits, possesses various health beneficial effects including anti-inflammatory and antioxidative properties. In this study, we aimed to elucidate the involvement of PKC-α and Nox in CBNPs-induced inflammation and oxidative stress, and to investigate the protective effects of resveratrol on CBNP-induced inflammation and oxidative stress in human lung epithelial A549 cells. METHODS: The production of reactive oxygen species (ROS) and the change of mitochondrial membrane potential (ΔΨm) were measured by flow cytometry. Nitric oxide (NO) was measured using the Griess reagent, and prostaglandin E2 (PGE2) production was detected by ELISA, while protein expressions were measured by Western blotting analysis. RESULTS: In lung epithelial A549 cells, CBNPs significantly enhanced oxidative stress by upregulation of Nox2 and membrane expression of p67phox accompanied with increase of ROS production. CBNPs also increased inflammatory factors, including iNOS, COX-2, NO and PGE2. However, resveratrol attenuated the above effects induced by CBNPs in A549 cells; additionally, CBNPs-induced activation of PKC-α was observed. We found that PKC-α inhibitor (Gö6976) could attenuate CBNPs-induced inflammation by down-regulation of ROS, NO and PGE2 production in A549 cells, suggesting PKC-α might be involved in CBNPs-induced oxidative stress and inflammation. Our results also found resveratrol was able to inhibit protein expression of PKC-α induced by CBNPs. Moreover, ROS scavenger (NAC) and Nox inhibitor (DPI) attenuated CBNPs-induced expressions of iNOS and COX-2. DPI could also attenuate CBNPs-induced ROS, NO and PGE2 production. CONCLUSIONS: Resveratrol attenuated CBNPs-induced oxidative and inflammatory factors in lung epithelial A549 cells, at least in part via inhibiting PKC-α- and Nox-related signaling.

Important modifications by sugammadex, a modified γ-cyclodextrin, of ion currents in differentiated NSC-34 neuronal cells.

BACKGROUND: Sugammadex (SGX) is a modified γ-cyclodextrin used for reversal of steroidal neuromuscular blocking agents during general anesthesia. Despite its application in clinical use, whether SGX treatment exerts any effects on membrane ion currents in neurons remains largely unclear. In this study, effects of SGX treatment on ion currents, particularly on delayed-rectifier K+ current [I K(DR)], were extensively investigated in differentiated NSC-34 neuronal cells. RESULTS: After cells were exposed to SGX (30 µM), there was a reduction in the amplitude of I K(DR) followed by an apparent slowing in current activation in response to membrane depolarization. The challenge of cells with SGX produced a depolarized shift by 15 mV in the activation curve of I K(DR) accompanied by increased gating charge of this current. However, the inactivation curve of I K(DR) remained unchanged following SGX treatment, as compared with that in untreated cells. According to a minimal reaction scheme, the lengthening of activation time constant of I K(DR) caused by cell treatment with different SGX concentrations was quantitatively estimated with a dissociation constant of 17.5 µM, a value that is clinically achievable. Accumulative slowing in I K(DR) activation elicited by repetitive stimuli was enhanced in SGX-treated cells. SGX treatment did not alter the amplitude of voltage-gated Na+ currents. In SGX-treated cells, dexamethasone (30 µM), a synthetic glucocorticoid, produced little or no effect on L-type Ca2+ currents, although it effectively suppressed the amplitude of this current in untreated cells. CONCLUSIONS: The treatment of SGX may influence the amplitude and gating of I K(DR) and its actions could potentially contribute to functional activities of motor neurons if similar results were found in vivo.

Ability of naringenin, a bioflavonoid, to activate M-type potassium current in motor neuron-like cells and to increase BKCa-channel activity in HEK293T cells transfected with α-hSlo subunit.

BACKGROUND: Naringenin (NGEN) is a citrus bioflavonoid known to have beneficial health properties; however, the ionic mechanism of its actions remains largely unclear. In this study, we attempted to evaluate the possible effects of NGEN on K(+) currents in NSC-34 neuronal cells and in HEK293T cells expressing α-hSlo. RESULTS: NGEN increased M-type K(+) current (I(K(M))) in a concentration-dependent manner with an EC50 value of 9.8 µM in NSC-34 cells. NGEN shifted the activation curve of I(K(M)) conductance to the more negative potentials. In cell-attached recordings, NGEN or flupirtine enhanced the activity of M-type K(+) (K(M)) channels with no changes in single-channel amplitude. NGEN (10 µM) had minimal effect on erg-mediated K(+) currents. Under cell-attached voltage-clamp recordings, NGEN decreased the frequency of spontaneous action currents and further application of linopirdine can reverse NGEN-induced inhibition of firing. In HEK293T cells expressing α-hSlo, this compound increased the amplitude of Ca(2+)-activated K(+) current (I(K(Ca))). Under inside-out recordings, NGEN applied to the intracellular side of the detached patch enhanced the activity of large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels. Moreover, from the study of a modeled neuron, burst firing of simulated action potentials (APs) was reduced in the presence of the increased conductances of both K(M) and K(Ca) channels. Fast-slow analysis of AP bursting from this model also revealed that as the conductances of both K(M) and BK(Ca) channels were increased by two-fold, the voltage nullcline was shifted in an upward direction accompanied by the compression of burst trajectory. CONCLUSIONS: The present results demonstrate that activation of both K(M) and BK(Ca) channels caused by NGEN might combine to influence neuronal activity if similar channels were functionally co-expressed in central neurons in vivo.

A modified technique to improve the outcome of intubation with a left-sided double-lumen endobronchial tube.

BACKGROUND: The use of a video-assisted laryngoscope (VL) has been shown to reduce the time to achieve intubation with a double-lumen endobronchial tube (DLT). As the blade of the VL is curved differently to a standard laryngoscope, the DLT must be angled into a hockey stick shape to fit properly. We conducted a study to establish which direction of angulation was best to facilitate correct positioning of the DLT when using a VL. METHODS: We enrolled patients scheduled for thoracic surgery who required intubation with a DLT. They were prospectively randomized into one of two groups: those intubated with a DLT angled to conceal the tracheal orifice (the tracheal orifice-covered, TOC) group or the tracheal orifice-exposed (TOE) group. The composite primary outcome measures were time taken to intubate and the frequency of first-time success. The time taken to intubate was divided into: T1, the time from mouth opening to visualization of the vocal cords with the VL; and T2, the time taken to advance the DLT through the cords until its tip lay within the trachea and three carbon dioxide waveforms had been detected by capnography. The hemodynamic responses to intubation and intubation-related adverse events were also recorded. RESULTS: Sixty-six patients completed the study, with 33 in each group. Total intubation time was significantly shorter in the TOC group (mean 30.6 ± standard deviation 2.7 seconds versus 38.7 ± 3.3 seconds, p <0.0001). T2 was also significantly shorter in the TOC group than the TOE group (27.2 ± 2.5 seconds versus 34.9 ± 3.0 seconds, p <0.0001). The severity of hoarseness on the first postoperative day and sore throat on the fourth postoperative day were significantly lower in the TOC group than the TOE group (p = 0.02 and <0.0001, respectively). The hemodynamic responses to intubation were broadly similar between the groups. CONCLUSION: When placing a left-sided DLT using a VL, angling the bronchial lumen to a hockey stick shape that conceals the tracheal lumen saves time and ameliorates the severity of post-intubation complications. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01605591.

Techniques for the insertion of the ProSeal laryngeal mask airway: comparison of the Foley airway stylet tool with the introducer tool in a prospective, randomized study.

BACKGROUND: Many tools have been developed to facilitate the insertion of the ProSeal laryngeal mask airway (LMA) insertion, which can be impeded by folding of its soft cuff. The aim of this study was to compare the efficiency of ProSeal LMA insertion guided by a soft, direct optical Foley Airway Stylet Tool (FAST) with the standard introducer tool (IT). METHODS: One hundred sixty patients undergoing general anesthesia using the ProSeal LMA as an airway management device were randomly allocated to either FAST-guided or IT-assisted groups. Following ProSeal LMA insertion, the glottic and esophageal openings were identified using a fiberoptic bronchoscope introduced through the airway and the drain tube. The primary outcomes were time taken to insert the ProSeal LMA and the success rate at the first attempt. Secondary end points included ease of insertion, hemodynamic response to insertion, and postoperative adverse events recorded in the recovery room and on the first postoperative morning. RESULTS: One hundred forty patients were included in the final analysis: 66 in the FAST-guided group and 74 in the IT-assisted group. The success rate of FAST device-guided ProSeal LMA insertion (95.7%) was broadly comparable with IT-assisted insertion (98.7%). However, the time taken to insert the ProSeal LMA was significantly longer when the FAST technique was used (p <0.001). The incidence of correct alignment of the airway tube and the drain tube did not differ significantly between the groups. There were no significant differences in ease of insertion or hemodynamic responses to insertion, except that the incidence of postoperative sore throat was significantly higher in the FAST group on the first postoperative day (22.2% compared with 6.8% in the IT group; p = 0.035). CONCLUSION: Both FAST-guided and IT-assisted techniques achieved correct ProSeal LMA positioning, but the IT technique was significantly quicker and less likely to cause a sore throat. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02048657.

Spatheliachromen mitigates methylglyoxal-induced myotube atrophy by activating Nrf2, inhibiting ubiquitin-mediated protein degradation, and restoring mitochondrial function.

BACKGROUND: Methylglyoxal (MGO) is a potent precursor of glycative stress that leads to oxidative stress and muscle atrophy in diabetes. Spatheliachromen (FPATM-20), derived from Ficus pumila var. awkeotsang, exhibited potential antioxidant activity. PURPOSE: This study aimed to evaluate the potential impact and underlying mechanisms of FPATM-20 on MGO-induced myotube atrophy and mitochondrial dysfunction in mouse skeletal C2C12 myotubes. METHODS: Atrophic and antioxidant factors were evaluated using immunofluorescence, enzyme-linked immunosorbent assay, and western blotting. Mitochondrial function was assessed using the ATP assay and Seahorse Cell Mito Stress Test. The glycogen content was determined using periodic acid-Schiff staining. Molecular docking was performed to determine the interaction between FPATM-20 and Keap1. RESULTS: In myotubes treated with MGO, FPATM-20 activated the Nrf2 pathway, reduced ROS levels, enhanced antioxidant defense, and increased glycogen content. FPATM-20 improved myotube viability and size, upregulated myosin heavy chain (MyHC) expression, modulated ubiquitin-proteasome molecules (nuclear FoxO3a, atrogin-1, MuRF-1, and p62/SQSTM1), and inhibited apoptosis (Bax/Bcl-2 ratio and cleaved caspase 3). Moreover, FPATM-20 restored mitochondrial function, including mitochondrial membrane potential, mitochondrial oxygen consumption rate, and mitochondrial biogenesis pathway (nuclear PGC-1α/TFAM/FNDC5). The inhibition of Nrf2 with ML385 reversed the effects of FPATM-20 on MGO. Furthermore, molecular docking confirmed the binding of FPATM-20 to Keap1, a suppressor of Nrf2, showing the crucial role of Nrf2 in protective effects. CONCLUSIONS: FPATM-20 protects myotubes from MGO toxicity by activating the Nrf2 antioxidant defense, reducing protein degradation and apoptosis, and enhancing mitochondrial function. Thus, FPATM-20 may be a novel agent for preventing skeletal muscle atrophy.

Suspended particulate matter-bound per- and polyfluoroalkyl substances (PFASs) in a river-coastal system: Possible correlation with transparent exopolymer particles.

The transport and ultimate fate of per- and polyfluoroalkyl substances (PFASs) are generally considered to be influenced by partitioning behavior between water, suspended particulate matters (SPM), and sediments. This study examined the distribution and partitioning of the PFASs in the water, SPM, and sediments in a densely populated urban river-coastal system. The total concentrations of eight PFASs (∑8 PFASs) in the water phase, SPM, and sediments varied from 0.59 to 7.40 ng/L, 0.54 to 9.08 ng/g, and 0.05 to 0.13 ng/g, respectively. The PFAS concentrations in the water and SPM phase decreased as the salinity increased, confirming contaminant inputs from the upstream of the river to the estuary zone. Notably, the positive correlation between SPM-bound PFASs and transparent exopolymer particles (TEPs) content, providing first evidence that TEPs may accumulate and concentrate more PFASs on the SPM. Collectively, this results offers useful information about roles of TEPs in determining environmental fate of PFASs.

Guilu Erxian Jiao enhances protein synthesis, glucose homeostasis, mitochondrial biogenesis and slow-twitch fibers in the skeletal muscle.

Guilu Erxian Jiao (GEJ) is a commonly used nutritional supplement due to its rich content of amino acids. It is also a traditional herbal medicine for improving degenerative joint. This study aimed to investigate the effect and mechanism of GEJ water extract (GEJ-WE) on skeletal muscle in C2C12 myotubes and C57BL/6J mice. Analysis of GEJ-WE were performed by high-performance liquid chromatography fingerprinting with chemical standards. Protein expression, mRNA level, glycogen content, mitochondria activity and ATP level were evaluated by western blots, real-time PCR, PAS staining, MTT and ATP bioluminescence assay, respectively. Skeletal muscle strength was evaluated by grip strength. Skeletal muscle volume, mass and fiber types were evaluated by micro computed tomography, histological analysis and immunofluorescence staining, respectively. Motor function was evaluated by rotarod performance and locomotor activity. In C2C12 myotubes, GEJ-WE significantly enhanced myogenic differentiation and myotube growth, protein synthesis signaling IGF-1/IGF-1R/IRS-1/Akt, Glut4 translocation, glycogen content, mitochondrial biogenesis signaling PGC-1α/NRF1/TFAM, mitochondrial activity and ATP production. However, IGF-1R antagonist AG1024 and PI3K inhibitor wortmannin reduced GEJ-WE-induced protein expression of MyHC, p-Akt, p-mTOR and p-GSK-3ß, Glut4 translocation and glycogen content. In C57BL/6J mice, GEJ-WE not only upregulated protein synthesis and mitochondrial biogenesis signaling, but it also increased muscle volume, relative muscle weight, cross-sectional area of myofibers, glycogen content and transition of fast-to-slow type fibers of skeletal muscles. Moreover, GEJ-WE enhanced grip strength and motor activity of mice. In conclusion, the upregulation of protein synthesis, myogenic differentiation, glucose homeostasis, mitochondrial biogenesis and slow-twitch fibers contributes to the mechanisms of GEJ-WE on the enhancement of skeletal muscle mass and motor function.

Neuroprotective Effects of San-Huang-Xie-Xin-Tang in the MPP(+)/MPTP Models of Parkinson's Disease In Vitro and In Vivo.

San-Huang-Xie-Xin-Tang (SHXT), composed of Coptidis rhizoma, Scutellariae radix, and Rhei rhizoma, is a traditional Chinese medicine used for complementary and alternative therapy of cardiovascular and neurodegenerative diseases via its anti-inflammatory and antioxidative effects. The aim of this study is to investigate the protective effects of SHXT in the 1-methyl-4-phenylpyridinium (MPP(+))/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models of Parkinson's disease. Rat primary mesencephalic neurons and mouse Parkinson disease model were used in this study. Oxidative stress was induced by MPP(+) in vitro and MPTP in vivo. In MPP(+)-treated mesencephalic neuron cultures, SHXT significantly increased the numbers of TH-positive neurons. SHXT reduced apoptotic signals (cytochrome and caspase) and apoptotic death. MPP(+)-induced gp91(phox) activation and ROS production were attenuated by SHXT. In addition, SHXT increased the levels of GSH and SOD in MPP(+)-treated neurons. In MPTP animal model, SHXT markedly increased TH-positive neurons in the substantia nigra pars compacta (SNpc) and improved motor activity of mice. In conclusion, the present results reveal the evidence that SHXT possesses beneficial protection against MPTP-induced neurotoxicity in this model of Parkinson's disease via its antioxidative and antiapoptotic effects. SHXT might be a potentially alternative and complementary medicine for neuroprotection.

Hyperbaric Oxygen Therapy Improves Parkinson's Disease by Promoting Mitochondrial Biogenesis via the SIRT-1/PGC-1α Pathway.

Hyperbaric oxygen therapy (HBOT) has been suggested as a potential adjunctive therapy for Parkinson's disease (PD). PD is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The aim of this study was to investigate the protective mechanisms of HBOT on neurons and motor function in a 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD and 1-methyl-4-phenylpyridinium (MPP+)-mediated neurotoxicity in SH-SY5Y cells on the potential protective capability. In vivo: male C57BL/6 mice were randomly divided into three groups: control, MPTP group and MPTP+HBOT group. The MPTP-treated mice were intraperitoneally received MPTP (20 mg/kg) four times at 2 h intervals within a day. The day after MPTP treatment, MPTP+HBOT mice were exposed to hyperbaric oxygen at 2.5 atmosphere absolute (ATA) with 100% oxygen for 1 h once daily for 7 consecutive days. In vitro: retinoic acid (RA)-differentiated SH-SY5Y cells were treated with MPP+ for 1 h followed by hyperbaric oxygen at 2.5 ATA with 100% oxygen for 1 h. The results showed that MPTP induced a significant loss in tyrosine hydroxylase (TH)-positive neurons in the SNpc of mice. HBOT treatment significantly increased the number of TH-positive neurons, with enhanced neurotrophic factor BDNF, decreased apoptotic signaling and attenuated inflammatory mediators in the midbrain of MPTP-treated mice. In addition, MPTP treatment decreased the locomotor activity and grip strength of mice, and these effects were shown to improve after HBOT treatment. Furthermore, MPTP decreased mitochondrial biogenesis signaling (SIRT-1, PGC-1α and TFAM), as well as mitochondrial marker VDAC expression, while HBOT treatment was shown to upregulate protein expression. In cell experiments, MPP+ reduced neurite length, while HBOT treatment attenuated neurite retraction. Conclusions: the effects of HBOT in MPTP-treated mice might come from promoting mitochondrial biogenesis, decreasing apoptotic signaling and attenuating inflammatory mediators in the midbrain, suggesting its potential benefits in PD treatment.

Risk factors for the development of metachronous liver metastasis in colorectal cancer patients after curative resection.

BACKGROUND: Metachronous liver metastasis (MLM) occurs in 20-40% of colorectal cancer (CRC) patients following surgical treatment. The aim of the present study was to determine the risk factors affecting the development of MLM in CRC patients following curative resection. METHODS: A total of 1,356 patients who underwent curative intent resection for CRC were retrospectively studied. Of these patients, those who with 30 days postoperative mortality (n=23), incomplete medical record (n=32), synchronous liver metastasis (n=148) and UICC stage IV (n=54) were excluded, and finally 1,099 patients were analyzed, including 977 patients without liver metastasis and 122 patients with MLM-only. Clinical and pathological records for each patient were reviewed from medical charts. The clinicopathologic characteristics of 1,099 patients were investigated. RESULTS: The median timing of developing MLM was 13 months with a range of 4 to 79 months. Univariate analysis identified that preoperative serum carcinoembryonic antigen (CEA) level, depth of invasion, lymph nodes metastasis, vascular invasion, and perineural invasion were significantly correlated with the development of MLM (all P<0.05). Meanwhile, a multivariate analysis showed that preoperative serum carcinoembryonic antigen (CEA) level>5 ng/ml (Odds Ratio [OR]=1.591; 95% Confidence Interval [CI], 1.065-2.377; P=0.024), tumor depth (OR=2.294; 95% CI, 1.103-4.768; P=0.026), positive lymph node metastasis (OR=2.004; 95% CI, 1.324-3.031; P=0.001) and positive vascular invasion (OR=1.872; 95% CI, 1.225-2.861; P=0.004) were independent prognostic factors contributing to the occurrence of MLM. CONCLUSIONS: The present study demonstrates that preoperative serum CEA level, tumor depth, lymph node metastasis, and positive vascular invasion could affect the occurrence of MLM in CRC patients following curative resection, and thus could help to define these high-risk patients who would benefit from enhanced surveillance and therapeutic program(s).

The effectiveness of dexmedetomidine infusion for sedating oral cancer patients undergoing awake fibreoptic nasal intubation.

BACKGROUND AND OBJECTIVE: Dexmedetomidine is characterized with effects of sedation, analgesia, amnesia and lack of respiratory depression. Hence, it should be suitable for awake fibreoptic intubation (AFOI). METHODS: We enrolled 30 oral cancer patients with limited mouth openings who were undergoing AFOI for elective surgery. Patients were randomly allocated into two groups; the Dex group (n = 16) that received dexmedetomidine (1.0 microg kg(-1)) infusion and the Control group (n = 14) that received fentanyl (1.0 microg kg(-1)) infusion. Main outcomes were evaluated by grading scores presenting conditions for nasal intubation and postintubation. Other analysed parameters included airway obstruction, haemodynamic changes, consumption time for intubation, amnesia level and satisfaction. RESULTS: Intubation score (1-5) representing condition for nasal intubation was significantly better in the Dex group [2(1-3)] than in the Control group [3(2-5)] (P = 0.001). Postintubation score (1-3) representing tolerance to intubation also showed more favourable results in the Dex group [1(1-3)] than in the Control group [2(2-3)] (P = 0.002). The Dex group showed significantly reduced haemodynamic response to intubation than the Control group. Incidence requiring temporary haemodynamic support was higher in the Dex group but not of significance. Both levels of amnesia and satisfaction score were significant in the Dex group. Other analysed parameters such as consumption time for intubation, airway obstruction score and postoperative adverse events did not differ significantly. CONCLUSION: Combination of dexmedetomidine loading with topical anaesthesia provides significant benefit for AFOI in intubation condition, patient tolerance, haemodynamic response, amnesia and satisfaction. Dexmedetomidine is effective for AFOI in anticipated difficult airway with only minor and temporary haemodynamic adverse effects.

Casting of a superhydrophobic membrane composed of polysulfone/Cera flava for improved desalination using a membrane distillation process.

Superhydrophobic membranes are necessary for effective membrane-based seawater desalination. This paper presents the successful fabrication of a novel electrospun nanofibrous membrane composed of polysulfone and Cera flava, which represents a novel class of enhanced performance membranes consisting of a superhydrophobic nanofibrous layer and hydrophobic polypropylene (PP). Cera flava, which helps lower the surface energy, was found to be the ideal additive for increasing the hydrophobicity of the polysulfone (PSF) polymeric solution because of its components such as long-chain hydrocarbons, free acids, esters, and internal chain methylene carbons. In the fabricated membrane, consisting of 10 v/v% Cera flava, the top PSF-CF nanofibrous layer is active and the lower PP layer is supportive. The hybrid membrane possesses superhydrophobicity, with an average contact angle of approximately 162°, and showed high performance in terms of rejection and water flux. This work also examined the surface area, pore size distribution, fiber diameter, surface roughness, mechanical strength, water flux, and rejection percentage of the membrane. The salt rejection was above 99.8%, and a high permeate flux of approximately 6.4 LMH was maintained for 16 h of operation.

Lateral rotation of the lower extremity increases the distance between the femoral nerve and femoral artery: an ultrasonographic study.

Femoral nerve block (FNB) is by far the most useful lower extremity regional anesthetic technique for the anesthesiologist, and high-resolution ultrasonography is a useful tool with which to guide the performance of FNB. However, the relationships between the femoral nerve and the femoral artery in different lower extremity positions have rarely been discussed. The purpose of this study was to evaluate the relative positions of the femoral nerve and artery at different lateral rotational angles of the lower extremities using ultrasonographic imaging. We enrolled 41 healthy volunteers in this study. Two-dimensional ultrasonographic images of the femoral nerve were obtained using an ultrasound unit, in the inguinal crease, for four positions of the bilateral lower extremities: 0 degrees , 15 degrees , 30 degrees and 45 degrees lateral rotation of each extremity. The following assessments were made in each position: minimal skin-to-nerve distance (SN) and deviation of nerve-to-landmark (femoral artery pulsation) horizontal distance (NF). A trend towards lateral rotation of both lower extremities was identified. The Pearson correlation values between rotational degree to SN and rotational degree to NF were -0.216 and 0.430, with p values of 0.001 and less than 0.001, respectively. Body mass index had a good correlation ( r = 0.76-0.78) with SN. The results of our ultrasound study revealed that the more lateral the rotation of both lower extremities, the closer the femoral nerve was to the skin and the farther away it was from the femoral artery. In order to increase the success rate and decrease the rate of complications, a suggested lateral 45 rotation of both lower extremities is strongly recommended when performing FNB using the peripheral nerve stimulator technique or the field block technique. In any situation, individual ultrasound guidance is recommended for FNB whenever possible.

Expedite recovery from esophagectomy and reconstruction for esophageal squamous cell carcinoma after perioperative management protocol reinvention.

BACKGROUND: Surgery for esophageal cancer is invasive and challenging, and always to be followed with arduous post-operative care and recovery. This study, maybe one of the first in Asian populations, is to determine whether a reinvented protocol for perioperative management for esophageal cancer surgery which is being implemented in our department, will lead to a faster convalescence and also significantly decrease financial burdens garnered by patients during hospitalization. METHODS: Operated on by the same surgeon and team in the same hospital, consecutive patients who had received esophagectomy and reconstruction for esophageal squamous cell carcinoma were retrospectively reviewed. On the basis of two different treatment periods, patients were divided into two groups: A and B. Group A was patients who had received the new reinvented protocol between 2012 and 2016, while group B patients were those having received the previous protocol between 2008 and 2011. Their demographics, post-operative outcome, and hospital charges were collected and compared. RESULTS: There were 64 patients in group A, and 69 in group B. Ventilator days (P<0.001), ICU stay (P<0.001), and post-operative stay (P<0.001) were significantly shorter in group A patients. Complication rates were similar between the two groups. No hospital mortality was noted in either group. Hospital charges in group A were found to be perceptively lower, although not statistically significant (P value =0.078). CONCLUSIONS: The current protocol of perioperative care effectively ameliorated convalescence after esophagectomy and reconstruction for esophageal squamous cell carcinoma without increasing complication rate or mortality. It is also potentially more practical in future health care policies during this era of financial shortage.

Quality improvement program reduces perioperative dental injuries - A review of 64,718 anesthetic patients.

BACKGROUND: Perioperative dental injury (PDI) is a common adverse event associated with anesthesia that can easily lead to medicolegal litigation. A quality improvement program was conducted with the electronic, standardized dental chart to document dentition before anesthesia and dentist consultation when necessary. This study aimed to reduce PDIs through execution of a quality improvement program. METHODS: We reviewed the 42-month interval anesthetic records of 64,718 patients who underwent anesthesia. A standardized electronic dental chart was designed to identify any dental prosthetics, fixed and removable dentures, and degree of loose teeth. The incidence of dental injuries associated with anesthesia was separated into three time periods: baseline, initiative (Phase I), and execution (Phase II). Primary outcome measurement was the incidence of PDIs related to anesthesia. RESULTS: The overall incidence of dental injury related to anesthesia was 0.059% (38/64,718 patients). During the baseline period, the dental injury rate was 0.108% (26/24,137 patients), and it decreased from 0.051% in the initiative period (10/19,711 patients) to 0.009% in the execution period (2/20,870 patients) during implementation of the quality improvement program. Most dental injuries were associated with laryngeal mask airway (42.1%) and laryngoscopy (28.9%). The most commonly involved teeth were the upper incisors. CONCLUSION: Dental injury incidence was significantly reduced and remained at low levels after implementation of the quality improvement program. We suggest the implementation of a standardized dental examination into the preoperative evaluation system adding pathologic teeth fixed or protected devices to minimize dental injury associated with anesthesia.