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Background Remifentanil is a rapid onset and rapid recovery opioid. The combination of remifentanil and propofol for deep sedation decreases the incidents of movement, cough, and hiccup. We evaluated the efficacy and safety of remifentanil during endoscopic ultrasound-guided tissue acquisition. Methods We retrospectively reviewed patients in whom endoscopic ultrasound-guided tissue acquisition was performed for solid mass lesions of the upper gastrointestinal tract and adjacent organs. All patients were premedicated with midazolam (2 mg), and target-controlled infusion of propofol, opioid, and Bispectral Index (BIS) monitoring were administered as necessary to maintain moderate-to-deep sedation. The opioids used were a bolus of alfentanil or remifentanil infusion. The discharge time, consumption of propofol and opioid, adverse events, diagnostic accuracy, and sensitivity and specificity for malignancy, were compared. Results Tissue acquisition was achieved in 123 patients (alfentanil group, n = 64; remifentanil group, n = 59). The discharge time of the remifentanil group (16.5 ± 3.2 min) was significantly shorter than that of the alfentanil group (19.0 ± 4.9 min, P = 0.001). The consumption of propofol, adverse events, diagnostic accuracy, sensitivity, and specificity for malignancy in the alfentanil group were not significantly different from those in the remifentanil group. Conclusions Use of alfentanil or remifentanil for target-controlled infusion of propofol–BIS monitoring can provide good sedative and diagnostic quality for endoscopic ultrasound-guided tissue acquisition. However, remifentanil resulted in faster recovery than alfentanil.

Lin-lin Pei,1,* Wen-zhu Yang,1,* Jing-yuan Fu,1,* Meng-xi Liu,1 Ting-ting Zhang,1 Dong-bo Li,1 Ruo-yue Huang,1 Li Zhang,1 Guang-neng Peng,1 Gang Shu,1 Zhi-xiang Yuan,2 Ju-chun Lin,1 Wei Zhang,1 Zhi-jun Zhong,1 Ling Zhao,1 Hua-lin Fu1 1Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, People’s Republic of China; 2College of Pharmacy, Southwest Minzu University, Chengdu, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hua-lin FuDepartment of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, People’s Republic of ChinaTel +86 028-86291162Email fuhl2005@sohu.comIntroduction: Enrofloxacin is used in the treatment of a wide variety of bacterial infections in mammals. However, its poor solubility limits the clinical use.Methods: In order to improve the solubility of enrofloxacin, the enrofloxacin mesylate (EM) were obtained by a chemical synthesis method. The characterization of EM was carried out using ultraviolet scan (UV), synchronous thermal analysis (SDT), fourier transform infrared spectrometer (FTIR) and mass spectrometry (MS), nuclear magnetic resonance (NMR) and X-ray powder diffraction analysis (XRPD). Acute toxicity of EM in Kunming mice was studied. Besides, pharmacokinetic studies were performed in New Zealand rabbits at a single oral dose of 10 mg/kg, and the antibacterial activity of EM was also evaluated.Results: EM was successfully synthesized and purified. The stoichiometric ratio of mesylate to enrofloxacin was 1:1 and the aqueous solubility of EM was 483.01± 4.06 mg/mL, the solubility of EM was about 2000 times higher than enrofloxacin. The oral lethal dose (LD50) of EM was 1168.364 mg/kg, and the pharmacokinetics indicated that the oral relative bioavailability of EM was about 1.79 times and 1.48 times higher than that of enrofloxacin and enrofloxacin hydrochloride, respectively. In addition, the in vitro antibacterial activity of EM was not significantly changed compared with enrofloxacin and enrofloxacin hydrochloride.Conclusion: EM has higher solubility, low toxicity for oral use, and increases the oral bioavailability in rabbit. This study may be of benefit for the development of new enrofloxacin drugs.Keywords: enrofloxacin mesylate, characterization, antibacterial effect, acute toxicity, pharmacokinetics

GP IIb/IIIa receptor activation plays an important role in thrombosis. The mechanism of early activation of GP IIb/IIIa receptors in diabetic conditions remains unknown. The purpose of this study was to investigate the release of Endothelial microparticle (EMP)-associated protein disulfide isomerase (PDI) after endothelial cell injury induced in diabetes and the changes in platelet activation. We produced an animal model of type 2 diabetes mellitus using ApoE−/− mice. Normal ApoE−/− and diabetic mice were allocated to four groups (n = 15): normal diet, normal diet plus rutin, diabetic, and diabetes plus rutin. The EMP-PDI content and GP IIb/IIIa expression of mice platelets were determined. In addition, EMPs obtained from the four groups were pretreated with the PDI inhibitor rutin; then, their effects on the platelets of normal C57 mice were characterized. Compared with the normal diet group, the diabetic group had significantly increased plasma EMP-PDI content and accelerated platelet activation by increased GP IIb/IIIa expression. In conclusion, EMP-PDI promotes early platelet activation through glycoprotein (GP) IIb/IIIa receptors present on platelet surface in the diabetic state. However, this process could be partially suppressed by the administration of rutin.

Background In residency programs, it is well known that autonomic regulation is influenced by night duty due to workload stress and sleep deprivation. A less investigated question is the impact on the autonomic nervous system of residents before or when anticipating a night duty shift. In this study, heart rate variability (HRV) was evaluated as a measure of autonomic nervous system regulation. Methods Eight residents in the Department of Anesthesiology were recruited, and 5 minutes of electrocardiography were recorded under 3 different conditions: (1) the morning of a regular work day (baseline); (2) the morning before a night duty shift (anticipating the night duty); and (3) the morning after a night duty shift. HRV parameters in the time and frequency domains were calculated. Repeated measures analysis of variance was performed to compare the HRV parameters among the 3 conditions. Results There was a significant decrease of parasympathetic-related HRV measurements (high-frequency power and root mean square of the standard deviation of R-R intervals) in the morning before night duty compared with the regular work day. The mean difference of high-frequency power between the 2 groups was 80.2 ms (95% confidence interval, 14.5-146) and that of root mean square of the standard deviation of R-R intervals was 26 milliseconds (95% confidence interval, 7.2-44.8), with P = .016 and .007, respectively. These results suggest that the decrease of parasympathetic activity is associated with stress related to the condition of anticipating the night duty work. On the other hand, the HRV parameters in the morning after duty were not different from the regular workday. Conclusions The stress of anticipating the night duty work may affect regulation of the autonomic nervous system, mainly manifested as a decrease in parasympathetic activity. The effect of this change on the health of medical personnel deserves our concern.

Identifying risk factors for premature totally implantable venous access device (TIVAD) catheter removal is crucial; however, because of the diversity of study methodologies, there is no consensus on such factors. The objective of the present study was to identify such risk factors by applying a cohort design study with a long-term follow-up period. For this cohort study, we selected cancer patients who had newly implanted TIVADs between July 2008 and December 2008. The follow-up period lasted until September 2012. Univariate analysis was performed for age, gender, cancer type, TIVAD brand, puncture site, sidedness of puncture, and catheter tip position. The hazard ratio (HR) of potential risk factors was calculated using the Cox proportional hazards regression model, and Kaplan–Meier curves were applied for catheter survival analysis. Our study consisted of 240 people, with 5 people lost to follow-up. The cumulative premature catheter removal rate of all TIVADs was 9.8%, with the most common reason for premature removal being port-associated blood stream infection (PABSI), which proved to be highest in patients with hematology cancer (27.8%) and upper gastrointestinal cancer (19.4%). Suboptimal tip position (HR 5.13, 95% confidence interval 1.73–15.21) was also a risk factor for premature removal, and it was correlated with symptomatic TIVAD occlusion (p = 0.0004). PABSI was the most common reason for premature catheter removal, with a varied incidence rate between different cancer types. Suboptimal tip position was also a risk factor. Confirming the final tip position after implantation is crucial. Infection control is important for TIVAD care, especially in high-risk cancer patients.

Pain is a major primary health care problem. Emerging studies show that inhibition of spinal microglial activation reduces pain. However, the precise mechanisms by which microglial activation contributes to nociceptive synaptic transmission remain unclear. In this study, we measured spontaneous synaptic activity of miniature excitatory postsynaptic currents (mEPSCs) in rat spinal cord superficial dorsal horn (SDH, laminae I and II) neurons. Lipopolysaccharide (LPS) and adenosine triphosphate (ATP) increased the frequency, but not amplitude, of mEPSCs in SDH neurons. Microglial inhibitors minocycline and paeonol, as well as an astrocyte inhibitor, a P2Y1 receptor (P2Y1R) antagonist, and a metabotropic glutamate receptor 5 (mGluR5) antagonist, all prevented LPS-induced enhancement of mEPSC frequency. In mouse behavioral testing, minocycline and paeonol effectively reduced acetic acid-induced writhing and LPS-induced hyperalgesia. These results indicate that LPS-activated microglia release ATP, which stimulates astrocyte P2Y1Rs to release glutamate, triggering presynaptic mGluR5 receptors and increasing presynaptic glutamate release, leading to an increase in mEPSC frequency and enhancement of nociceptive transmission in SDH neurons. We propose that these effects can serve as a new electrophysiological model for evaluating pain. Moreover, we predict that pharmacologic agents capable of inhibiting the LPS-induced enhancement of mEPSC frequency in SDH neurons will have analgesic effects.

Background and aim Target-controlled infusion (TCI) uses averaged pharmacokinetic datasets derived from population samples to automatically control the infusion rate. Bispectral index (BIS) technology non-invasively measures levels of consciousness during surgical procedures. We compared the efficacy and safety of propofol TCI with or without BIS monitoring for sedation during advanced gastrointestinal endoscopy. Methods This prospective study enrolled 200 patients who were premedicated with midazolam 2 mg and alfentanil 0.4 mg before undergoing advanced gastrointestinal endoscopy. The initial target blood concentration of propofol was set at 1.0 μg/mL, and adjustments of 0.2 μg/mL were made as necessary to maintain moderate-to-deep sedation. Patients were randomized to either the BIS-blind group and evaluated for depth of anesthesia by monitoring scores of 1-2 on the Modified Observer's Assessment of Alertness/Sedation scale (n = 100) or to the BIS-open group and monitored by BIS scores of 60-80 (n = 100). The primary outcome was the total amount of propofol required to maintain anesthesia. Secondary outcomes were sedation-induced adverse events, recovery, and quality of sedation (endoscopist and patient satisfaction). Results The mean propofol infusion rate was significantly higher in patients not monitored by BIS scores than in those who were (5.44 ± 2.12 vs 4.76 ± 1.84 mg/kg/h; P = 0.016). Levels of satisfaction were higher for endoscopists who used BIS monitoring than in those who did not. Conclusions Mean infusion rates were higher in propofol TCI without BIS monitoring compared with propofol TCI with BIS during advanced gastrointestinal endoscopy. Endoscopists expressed satisfaction with BIS monitoring.

Background: Double-lumen endotracheal tubes and bronchial blockers are the two lung separation devices most commonly used for lung resection. The preference and outcomes of choosing different lung separation devices have not been discussed in the literature. Methods: This study was conducted using the data of 2 million patients randomly chosen from the National Health Insurance Research Database between 2011 and 2016. We selected patients who underwent lung resection surgery and surveyed their demographic data and trends of double-lumen endotracheal tube and bronchial blocker use. To determine the influence of endotracheal tubes on clinical outcomes, we computed multiple linear regressions of the number of deaths within 30 days after surgery, intensive care unit stay, hospital stay, and medical cost. Results: The use of bronchial blockers in Taiwan has steadily increased from 6.13% to 11.33% from 2011 to 2016. Anaesthesiologists working in regions with higher thoracic surgery volumes preferred bronchial blockers over double-lumen endotracheal tubes. Bronchial blockers were the preferred choice in women, elderly individuals, patients with more comorbidities, and those undergoing video-assisted thoracoscopic surgeries. After adjustment for sex, age, Charlson Comorbidity Index, and video-assisted thoracoscopic surgeries, we found that patients in whom bronchial blockers were applied had shorter hospital stays. Conclusion: The use of bronchial blockers is increasing as the experience of anaesthesiologists increases. Although double-lumen endotracheal tubes remain the principal choice for lung separation in Taiwan, clinical outcomes of the bronchial blocker group were not inferior to those of the double-lumen endotracheal tube group. Keywords: Bronchial blocker, Double-lumen endotracheal tube, Lung separation, Thoracic surgery

Pruritus, or itch, is a frequent complaint amongst patients with cholestatic hepatobiliary disease and is difficult to manage, with many patients refractory to currently available antipruritic treatments. In this study, we examined whether manual acupuncture (MA) at particular acupoints represses deoxycholic acid (DCA)-induced scratching behavior and microglial activation and compared these effects with those induced by another pruritogen, 5'-guanidinonaltrindole (GNTI, a kappa opioid receptor antagonist). MA at Hegu (LI4) and Quchi (LI11) acupoints significantly attenuated DCA- and GNTI-induced scratching, whereas no such effects were observed at the bilateral Zusanli acupoints (ST36). Interestingly, GNTI-induced scratching was reduced similarly by both MA and electroacupuncture (EA) at the LI4 and LI11 acupoints. MA at non-acupoints did not affect scratching behavior. Intraperitoneal injection of minocycline (a microglial inhibitor) reduced GNTI- and DCA-induced scratching behavior. In Western blot analysis, subcutaneous DCA injection to the back of the neck increased spinal cord expression of ionized calcium-binding adapter molecule 1 (Iba1) and tumor necrosis factor-alpha (TNF-α) as compared with saline injection, while MA at LI4 and LI11 reduced these DCA-induced changes. Immunofluorescence confocal microcopy revealed that DCA-induced Iba1-positive cells with thicker processes emanated from the enlarged cell bodies, while this effect was attenuated by pretreatment with MA. It is concluded that microglia and TNF-α play important roles in the itching sensation and MA reduces DCA-induced scratching behavior by alleviating spinal microglial activation. MA may be an effective treatment for cholestatic pruritus.

Background The optimal volume status for neurosurgery has yet to be determined. We compared two fluid protocols based on different stroke volume variation (SVV) cut-offs for goal-directed fluid therapy (GDFT) during supratentorial brain tumour resection. Methods A randomized, single-blind, open-label trial was conducted. Eighty adult patients undergoing elective supratentorial brain tumour resection were randomly divided into a low SVV and a high SVV group. The SVV cut-offs were used to determine when to initiate colloid infusion. Clinical outcomes and perioperative changes in serum neuronal biomarkers, including S100β, neurone-specific enolase (NSE) and glial fibrillary acidic protein (GFAP), were compared. Results Patients in the low SVV group received a higher volume of colloid [869 (SD 404) vs 569 (453) ml; P=0.0025], had a higher urine output [3.4 (2.4) vs 2.5 (1.7) ml kg−1 h−1; P=0.0416] and a higher average cardiac index [3.2 (0.7) vs 2.8 (0.6) litres min−1 m−2; P=0.0204]. Patients in the low SVV group also had a shorter intensive care unit stay [1.4 (0.7) vs 2.6 (3.3) days, P=0.0326], fewer postoperative neurological events (17.5 vs 40%, P=0.0469), attenuated changes in the NSE and GFAP levels, lower intraoperative serum lactate and a higher Barthel index at discharge (all P Conclusions During GDFT for supratentorial brain tumour resection, fluid boluses targeting a lower SVV are more beneficial than a restrictive protocol. Clinical trial registration NCT02113358.

// Chung-Chih Shih 1 , Tzong-Shiun Lee 1 , Fon-Yih Tsuang 2 , Pei-Lin Lin 1 , Ya-Jung Cheng 1 , Hsiao-Liang Cheng 1, * and Chun-Yu Wu 1, * 1 Department of Anesthesiology, National Taiwan University Hospital, Taipei, Taiwan 2 Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan * These authors have contributed equally to this work Correspondence to: Chun-Yu Wu, email: longersolo@gmail.com Hsiao-Liang Cheng, email: B87401032@ntu.edu.tw Keywords: lactate, brain tumor, tumor marker, prognostic factor, glioma Received: March 09, 2017 Accepted: June 05, 2017 Published: June 29, 2017 ABSTRACT Introduction: Malignant primary brain tumors are one of the most aggressive cancers. Pretreatment serum nonneuronal biomarkers closely associated with postoperative outcomes are of high clinical relevance. The present study aimed to identify potential pretreatment serum biomarkers that may influence oncological outcomes in patients with primary brain tumors. Methods: A total of 74 patients undergoing supratentorial primary brain tumor resection were enrolled. Before tumor resection, serum neuronal biomarkers, namely neuron-specific enolase (NSE), S100β, and glial fibrillary acidic protein (GFAP), and serum nonneuronal biomarkers, namely neutrophil gelatinase-associated lipocalin (NGAL), lactate dehydrogenase (LDH), and lactate, were measured and associated postoperative oncological outcomes, including brain tumor grading, progression-free survival (PFS), and overall survival (OS), were compared. Results: Patients with high-grade brain tumors had significantly higher pretreatment serum lactate levels ( p = 0.011). By contrast, other biomarkers were comparable between patients with high-grade and low-grade brain tumors. Receiver operating characteristic curve analysis of serum lactate levels yielded an area under the curve of 0.71 for differentiating between high-grade and low-grade brain tumors. Kaplan–Meier survival analysis revealed patients with high serum lactate levels (≧2.0 mmol/L) had shorter PFS and OS ( p = 0.021 and p = 0.093, respectively). In a multiple regression model, only elevated serum lactate levels were associated with poor PFS and OS ( p = 0.021 and p = 0.048, respectively). Conclusions: An elevated pretreatment serum lactate level is a prognostic biomarker of high-grade primary brain tumors and is significantly associated with poor PFS in patients with supratentorial brain tumors undergoing tumor resection. By contrast, other serum biomarkers are not significantly associated with oncological outcomes.

Objectives Patient-controlled epidural analgesia (PCEA) and continuous epidural infusion (CEI) are popular and effective methods for pain relief during labor; however, there are concerns about increasing rates of cesarean section (C/S) and instrumental delivery. This prospective study investigated the effect of PCEA and CEI with different formulas on labor and the mode of delivery in nulliparous women. Materials and methods A total of 480 nulliparous women were randomized into four groups, with 120 in each. Group A received a loading dose of 10 mL of 1 mg/mL ropivacaine with 2 μg/mL fentanyl, then an intermittent bolus of 5 mL with a background infusion of 5 mL/hour by PCEA. Group B received the same PCEA formula as Group A with 0.8 mg/mL bupivacaine. Group C received the same formula as Group A by CEI with 1 mg/mL ropivacaine at a rate of 10 mL/hour. Group D received the same formula as Group C with 0.8 mg/mL bupivacaine. The rates of C/S and instrumental delivery and the incidence of side effects were recorded. Results The rates of C/S were significantly different between Groups A and C, Groups A and D, and Groups B and D. The rates of instrumental delivery for normal spontaneous delivery were significantly different between Groups A and B, A and D, B and C, and C and D. Conclusion The C/S rate was higher in Groups C and D; however, the instrumental delivery rate was lower in Groups A and C. We conclude that PCEA with 1 mg/mL ropivacaine might provide the greatest benefit for labor analgesia.

We hypothesized that body shape metrics influence the anatomy of spinal canal and intraabdominal pressure in three dimensions. We explored the effects of abdominal circumference, trunk length, and their combination on the level of spinal anesthesia in the term parturient in this study. Thirty term parturients, ASA class I–II, from 20 to 41 years of age, scheduled for cesarean section were enrolled in this observational study. Abdominal circumference (AC) and trunk length (TL) were recorded preoperatively. Spinal anesthesia was performed with 10 mg 0.5 % hyperbaric bupivacaine at the L4–L5 intervertebral space in all parturients. Correlation between maximal sensory spinal anesthesia level and physical parameters was analyzed with Spearman rank correlation coefficients. The calculated r value was compared with r = 0 with p

Minocycline is a second-generation tetracycline that has been reported to have powerful neuroprotective properties. In our previous studies, we found that d -amphetamine (AMPH) elicited action potential bursts in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. This study sought to determine the effects of minocycline on the AMPH-elicited action potential pattern changes in the central snail neuron, using the two-electrode voltage clamping method. Extracellular application of AMPH at 300 μM elicited action potential bursts in the RP4 neuron. Minocycline dose-dependently (300–900 μM) inhibited the action potential bursts elicited by AMPH. The inhibitory effects of minocycline on AMPH-elicited action potential bursts were restored by forskolin (50 μM), an adenylate cyclase activator, and by dibutyryl cAMP (N 6 ,2′-O-Dibutyryladenosine 3′,5′-cyclic monophosphate; 1 mM), a membrane-permeable cAMP analog. Co-administration of forskolin (50 μM) plus tetraethylammonium chloride (TEA; 5 mM) or co-administration of TEA (5 mM) plus dibutyryl cAMP (1 mM) also elicited action potential bursts, which were prevented and inhibited by minocycline. In addition, minocycline prevented and inhibited forskolin (100 μM)-elicited action potential bursts. Notably, TEA (50 mM)-elicited action potential bursts in the RP4 neuron were not affected by minocycline. Minocycline did not affect steady-state outward currents of the RP4 neuron. However, minocycline did decrease the AMPH-elicited steady-state current changes. Similarly, minocycline decreased the effects of forskolin-elicited steady-state current changes. Pretreatment with H89 (N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride; 10 μM), a protein kinase A inhibitor, inhibited AMPH-elicited action potential bursts and decreased AMPH-elicited steady-state current changes. These results suggest that the cAMP-protein kinase A signaling pathway and the steady-state current are involved in the inhibitory effects of minocycline upon AMPH-elicited action potential bursts.

The role of ionic currents on procaine-elicited action potential bursts was studied in an identifiable RP1 neuron of the African snail, Achatina fulica Ferussac, using the two-electrode voltage clamp method. The RP1 neuron generated spontaneous action potentials and bath application of procaine at 10 mM reversibly elicited action potential bursts in a concentration-dependent manner. Voltage clamp studies revealed that procaine at 10 mM decreased [1] the Ca2+ current, [2] the Na+ current, [3] the delayed rectifying K+ current I(KD), and [4] the fast-inactivating K+ current (I(A)). Action potential bursts were not elicited by 4-aminopyridine (4-AP), an inhibitor of I(A), whereas they were seen after application of tetraethylammonium chloride (TEA), a blocker of the I(K)(Ca) and I(KD) currents, and tacrine, an inhibitor of I(KD). Pretreatment with U73122, a phospholipase C inhibitor, blocked the action potential bursts elicited by procaine. U73122 did not affect the I(KD) of the RP1 neuron; however, U73122 decreased the inhibitory effect of procaine on the I(KD). Tacrine decreased the TEA-sensitive I(KD) of RP1 neuron but did not significantly affect the I(A). Tacrine also successfully induced action potential bursts in the RP1 neuron. It is concluded that the inhibition on the I(KD) is responsible for the generation of action potential bursts in the central snail RP1 neuron. Further, phospholipase C activity is involved in the procaine-elicited I(KD) inhibition and action potential bursts.

This study sought to determine the effects of (+) methamphetamine (METH) and its ring-substituted analog (+/-)3,4-methylenedioxymethamphetamine (MDMA; ecstasy) on electrophysiological behavior and their relationships to second messenger systems in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. Extracellular application of MDMA at 1mM and METH at 3mM elicited action potential bursts that were not blocked after immersing the neurons in Ca(2+)-free solution. Notably, MDMA- (1mM) elicited action potential bursts were blocked by pretreatment with the protein kinase C (PKC) inhibitors chelerythrine (20 microM) and Ro 31-8220 (20 microM), but not by the PKA inhibitors KT-5720 (10 microM) and H89 (10 microM). The PKC activator phorbol 12,13-dibutyrate (PDBu; 3 microM), but not the PKA activator forskolin (50 microM), facilitated the induction of bursts elicited by MDMA at a lower concentration (0.3mM). In contrast, METH- (3mM) elicited action potential bursts were blocked by pretreatment with KT-5720 (10 microM) and H89 (10 microM), but not by chelerythrine (20 microM) and Ro 31-8220 (20 microM). Forskolin (50 microM), but not PDBu (3 microM) facilitated the induction of bursts elicited by METH at a lower concentration (1mM). Tetraethylammonium chloride (TEA), a blocker of the delayed rectifying K(+) current (I(KD)), did not elicit bursts at a concentration of 5mM but did facilitate the induction of action potential bursts elicited by both METH and MDMA. Voltage clamp studies revealed that both METH and MDMA decreased the TEA-sensitive I(KD) of the RP4 neuron. Forskolin (50 microM) or dibutyryl cAMP (1mM), a membrane-permeable cAMP analog, alone did not elicit action potential bursts. However, co-administration with forskolin (50 microM) and TEA (5mM) or co-administration with dibutyryl cAMP (1mM) and TEA (50mM) elicited action potential bursts in the presence of the PKC inhibitor chelerythrine (20 microM). Similarly, PDBu (10 microM) or phorbol 12-myristate 13-acetate (PMA; 3 microM) alone did not elicit action potential bursts. However, co-administration with PDBu (10 microM) and TEA (5mM) or co-administration with PMA (3 microM) and TEA (5mM) elicited action potential bursts in the presence of the PKA inhibitor KT-5720 (10 microM). These data suggest that action potential bursts in the RP4 neuron were not due to Ca(2+)-dependent synaptic effects. Rather, action potential bursts may be elicited through (1) combined activation of the cAMP-PKA signaling pathway and inhibition of the I(KD) and (2) combined activation of PKC and inhibition of the I(KD).

Background and Objectives: Although lidocaine patch 5% has been widely used for postherpetic neuralgia, its analgesic effect on the intense pain associated with acute herpes zoster has not been investigated because of its potential hazard to damaged skin. Methods: Forty-six patients suffering from moderate to severe pain caused by acute herpes zoster infection (within 4 weeks of onset) were enrolled in a randomized, double-blind, vehicle-controlled, parallel study. Lidocaine patch 5% or vehicle patch were applied to the intact portion of the painful skin area without blisters at 12-hour intervals twice a day for 2 consecutive days. Analgesic efficacy and side effect profiles were assessed before and 48 hours after patch application. Results: We found that both groups of patients experienced significant pain relief during rest and movement. Differences of mean reduction of pain intensity between the two groups were 14.7 (4.7-24.8, P = 0.005) during rest and 10.4 (1.6-19.3, P = 0.007) during movement, favoring the lidocaine patch. The lidocaine patch produced a greater percentage change in a patient9s global impression than the vehicle patch. The incidence and severity of adverse events were low with both treatments. Conclusions: This study demonstrates that lidocaine patch 5%, applied twice a day, could serve as a well tolerated and effective modality to relieve moderate to severe pain associated with acute herpes zoster presumably through its pharmacological action and physical barrier effect on sensitized skin.

Background/Purpose Ropivacaine has been shown to induce convulsion following overdose or accidental intravenous injection, but the mechanisms are poorly understood. Using an identifiable central neuron from giant African snail, the authors studied the mechanism of ropivacaine-elicited bursts of potential and explored the possible mechanisms of ropivacaine-induced neurotoxicity. Methods Ropivacaine action on a central neuron (RP4) of the giant African snail (Achatina fulica Ferussac) was recorded by conventional electrophysiologic technique. Interactions between ropivacaine and prazosin, propranolol, atropine, d-tubocurarine, calcium-free solution, H89, U73122, neomycin, high-magnesium solution, and chelerythrine were also observed. Results The RP4 neuron showed spontaneous firing of action potentials. Extracellular application of ropivacaine (900 μM) reversibly elicited bursts of potential in the RP4 neuron. The bursts of potential elicited by ropivacaine were not blocked after administration of: (1) prazosin, propranolol, atropine, d-tubocurarine; (2) calcium-free solution; and (3) pretreatment with H89 or chelerythrine. The bursts of potential elicited by ropivacaine were blocked by pretreatment with U73122 (30 μM) or by adding neomycin (3.5 mM) or high-magnesium solution (30 mM). Conclusion Ropivacaine reversibly elicited bursts of potential in the central snail neuron. The ropivacaine-elicited bursts of potential were associated with phospholipase C activity in the RP4 snail neuron. Our results suggest that ropivacaine-induced neurotoxicity is highly associated with phospholipase C activity and phospholipase C inhibitor may offer a novel therapeutic approach for managing local anesthetic-induced convulsion or other transient neurologic toxicity.

Effects of inhibitors of phosphodiesterases (PDE) on bursting activity, produced by d-amphetamine (d-AM) was studied in PPa4 neurons of the giant African snail Achatina fulica F. Action of the following PDE inhibitors was analyzed: vinpocetine (selective to PDE I), erythro-9-(2-hydroxi-3-nonyl) adenine (EHNA; selective to PDE 2), milrinone (selective to PDE 3), rolipram (selective to PDE 4), sildenafil citrate (Viagra@; selective to PDE 5), and caffeine, a non-selective phosphodiesterase inhibitor. Amphetamine at a low concentration (67.5 × 10−5 M) did not produce the bursting firing in the neurons; however, the convulsive activity appeared on addition to this solution of any if the PDE inhibitors except for sildenafil. Forskolin (an adenylyl cyclase activator, 10−4 M) also decreased the neuronal threshold to the d-AM action. The bursting activity produced by d-AM did not develop after a previous administration of the protein kinase A inhibitor KT-5720. The phospholipase C blocker U73122 had no effect on the bursting activity produced by d-AM. It is concluded that the neuronal convulsive activity induced by d-AM is associated with the phosphodiesterase activity.

Composition of fatty acids (FA) was studied in bacteria Vibrio anguillarum, total and lysosomal lipids of cestodes Eubothrium crassum and Diphyllobothrium dendriticum, and roe of the roach Rutilus rutilus, carp Cyprinus carpio, and salmon Salmo salar. Bacteria collected from different geographic zones but cultivated under the similar conditions have been found to maintain the FA spectra peculiarities substantially corresponding to temperature conditions of their habitat region. Unsaturation of total lipids in D. dendriticum, determined from the ratio between saturated, monoenoic, and polyenoic acids was higher than that of lysosome membrane lipids. This phenomenon might be due to pre-adaptation of the lipid FA composition of eggs produced in huge amounts by a parasite to low temperatures of environment, in which embryos are to be developed. Quantitative ratios of lipid FA in the roach, carp, and salmon roes correspond to the spawning thermal tolerance diapason specific of some particular fish species and to some extent do not depend on real temperature conditions existing at the moment of development.

Background The transient effects of epidural bupivacaine 0.25–0.5% on the Doppler velocimetry of umbilical and uterine arteries had been reported, but the effects of continuous lower dose epidural bupivacaine (0.05–0.1%) infusion for labour analgesia have never been reported. In this study, we evaluated the effects of continuous epidural bupivacaine 0.075% on the Doppler velocimetry of uterine arteries. Methods Twenty pregnant women for labour analgesia received continuous epidural bupivacaine 0.075% infusion. We used a 4-MHz continuous-wave Doppler probe (Multigon 500A) with a 200 Hz thump filter to detect uterine blood flow velocity. We recorded the velocimetry data for uterine relaxation and contraction during five time periods: pre-epidural insertion, 1, 2, and 4 h post-epidural infusion, and after delivery of fetus. Results Our data showed that the velocimetric indices of uterine vascular resistance were significantly increased 1, 2, and 4 h after epidural infusion when compared with the pre-epidural level; these returned to the baseline after delivery. Conclusion Continuous epidural analgesia with bupivacaine 0.075% increases the resistance of uterine artery and therefore possibly reduces the uterine blood flow.

The effects of 7-bromo-1,4-dihydro-2-phenyl-4,4-bis(4-pyridinylmethyl)2H-isoquinolin-3-one dihydrochloride (BDPBI) on induction of action potential bursts were studied pharmacologically on the RP4 central neuron of the giant African snail (Achatina fulica Ferussac). The effects of m-3M3FBS, a phospholipase activator and HTMT, a histamine (H1) receptor agonist, on the neuron were also tested. The RP4 neuron showed spontaneous firing of action potential. Extracellular application of BDPBI (150 µmol/l) reversibly elicited bursts of potential (BoP) on the neuron. m-3M3FBS and HTMT also elicited BoP on the RP4 neuron. The BoP elicited by BDPBI were blocked by U73122 (6 µmol/l), a compound commonly used as a phospholipase C (PLC) inhibitor. Neomycin (3.5 mmol/l), a high-magnesium solution (30 mmol/l), replacing the physiological sodium ion with lithium ion or adding diphenhydramine, chloropheniramine decreased the BoP elicited by BDPBI. The BoP elicited by BDPBI were not inhibited after administration with (1) prazosin, propranolol, atropine, d-tubocurarine, hexamethonium, haloperidol, cimetidine, (2) calcium-free solution, (3) high-potassium (12 mmol/l) solution, and (4) pretreatment with KT-5720. The BoP elicited by HTMT was not inhibited after administration of diphenhydramine or chloropheniramine. Voltage-clamped studies revealed that BDPBI decreased the amplitudes of calcium and steady-state outward currents while it did not alter the amplitude of the fast inward current. No negative slope relationship of the steady-state current voltage relationship was found in BDPBI-treated neurons. It is concluded that BDPBI reversibly elicited BoP in the central snail neuron. The effect was not due to (1) the extracellular calcium ion fluxes, or (2) the activation of cholinergic, adrenergic or histamine receptors. The BDPBI-elicited BoP were dependent on the phospholipase activity in the neuron.

We report a 24-year-old man who developed postoperative pulmonary edema and desaturation, after open reduction with internal fixation for left femoral shaft fracture sustained in a motorcycle accident. Cardiac catheterization revealed a left anterior descending coronary artery dissection. Review of his present history, showed that he neither had chest discomfort nor suffered from hemodynamic decompensation preoperatively. Only the abnormal 12-lead ECG with moderate tachycardia was suggestive of myocardial ischemia. Coronary artery dissection, although uncommon, is a disastrous complication following blunt chest trauma, and needs thorough preoperative evaluation to exclude its occurrence.

We have examined the spectral components of heart rate variability (HRV) during induction of anaesthesia with thiopentone, tracheal intubation and subsequent inhalation of isoflurane-nitrous oxide. Commonly used spectral analysis methods such as fast Fourier transformation or autoregressive modelling require stationary data and are not suitable for the rapidly changing HRV data in this period. An advanced spectral analysis method, time-frequency analysis, which can treat non-stationary data, was used in this study. Multiple spectra were generated to demonstrate the time-related spectral components of HRV. Mid-frequency power (MF, 0.08-0.15 Hz), high-frequency power (HF, 0.15-0.5 Hz) and MF/HF ratio at baseline, after induction (before intubation), immediately after intubation and during maintenance periods were calculated and compared. MF and HF powers decreased after induction and were reduced further in the maintenance period but MF/HF ratio remained unchanged after induction. Immediately after intubation MF and HF powers did not differ significantly from the immediate pre-intubation values, but MF/HF ratio did.

Objective Conventional, intermittent, epidural morphine is widely applied as a post-Cesarean delivery analgesia. We compared the analgesic efficacy, motor weakness, and side effects of administering a patient-controlled epidural analgesia (PCEA) of pure ropivacaine versus the intermittent administration of epidural morphine after Cesarean delivery. Materials and Methods This randomized, double-blind study included 120 full-term parturients who underwent elective Cesarean delivery and received either PCEA with pure ropivacaine or an intermittent bolus epidural of 2 mg/10 mL morphine in normal saline twice per day. The efficacy of pain relief, post-Cesarean side effects, motor blockades, time to first ambulation, and global satisfaction scores were evaluated. Results Pain scores were recorded at the four evaluation times (2, 12, 24, and 48 hours post-Cesarean delivery), and the time to first ambulation did not statistically differ between the two groups. Patients in the ropivacaine group experienced more motor weakness at 2 and 12 hours, fewer side effects, and higher global satisfaction scores than those in the morphine group ( p Conclusion The analgesic efficacy after cesarean delivery was almost equivalent between two groups. PCEA with pure ropivacaine induced significant motor blockade during the first 12 hours, but without delaying the time to first ambulation. Patients in the ropivacaine group reported higher patient satisfaction scores due to the significant reduction of annoying side effects, such as pruritus, nausea, vomiting, and urinary retention.

to investigate the effects of 2'-hydroxy-4'-methoxyacetophenone (paeonol) on the electrophysiological behavior of a central neuron (right parietal 4; RP4) of the giant African snail (Achatina fulica Ferussac).intracellular recordings and the two-electrode voltage clamp method were used to study the effects of paeonol on the RP4 neuron.the RP4 neuron generated spontaneous action potentials. Bath application of paeonol at a concentration of ≥ 500 micromol/L reversibly elicited action potential bursts in a concentration-dependent manner. Immersing the neurons in Co(2+)-substituted Ca(2+)-free solution did not block paeonol-elicited bursting. Pretreatment with the protein kinase A (PKA) inhibitor KT-5720 or the protein kinase C (PKC) inhibitor Ro 31-8220 did not affect the action potential bursts. Voltage-clamp studies revealed that paeonol at a concentration of 500 micromol/L had no remarkable effects on the total inward currents, whereas paeonol decreased the delayed rectifying K(+) current (I(KD)) and the fast-inactivating K(+) current (I(A)). Application of 4-aminopyridine (4-AP 5 mmol/L), an inhibitor of I(A), or charybdotoxin 250 nmol/L, an inhibitor of the Ca(2+)-activated K(+) current (I(K(Ca))), failed to elicit action potential bursts, whereas tetraethylammonium chloride (TEA 50 mmol/L), an I(KD) blocker, successfully elicited action potential bursts. At a lower concentration of 5 mmol/L, TEA facilitated the induction of action potential bursts elicited by paeonol.paeonol elicited a bursting firing pattern of action potentials in the RP4 neuron and this activity relates closely to the inhibitory effects of paeonol on the I(KD).

Background: Previous studies have shown that ropivacaine has biphasic vascular effects, causing vasoconstriction at low concentrations and vasorelaxation at high concentrations. This study was designed to examine the role of the endothelium during accidental intravascular absorption of ropivacaine, and to elucidate the mechanisms responsible. Methods: Isolated guinea pig aortic rings were suspended for isometric tension recording. The effects of ropivacaine on endothelium-intact and endothelium-denuded aortic rings were assessed. Endothelium-intact aortic rings were pre-contracted with phenylephrine before being exposed to ropivacaine and acetylcholine, in order to generate and compare concentration–response curves. In the absence and presence of yohimbine, propranolol, atropine, indometacin, NG-nitro-l-arginine methyl ester (l-NAME), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or methylene blue, the contractile response induced by ropivacaine was assessed on endothelium-intact aortic rings pre-contracted with phenylephrine. Results: Ropivacaine (3 × 10−4 to 10−2 mol/l) produced vasoconstriction in endothelium-denuded aortic rings, whereas no such response was observed in aortic rings with intact endothelium. In phenylephrine pre-contracted intact aortic rings, ropivacaine induced a greater degree of vasorelaxation than did acetylcholine. Yohimbine, propranolol and atropine all failed to affect the relaxation responses induced by ropivacaine. However, pre-treatment with indometacin (cyclo-oxygenase inhibitor), l-NAME (nitric oxide synthase inhibitor), methylene blue (soluble guanylyl cyclase inhibitor) or ODQ (soluble guanylyl cyclase inhibitor), significantly decreased the ropivacaine-induced relaxation of endothelium-intact aortic rings (3 × 10−4 to 10−2 mol/l). Conclusions: Ropivacaine elicits an endothelium-dependent vasorelaxation in phenylephrine pre-contracted aortic rings via the nitric oxide–cyclic guanosine 3′,5′-monophosphate pathway and the prostaglandin system.

Effects of sodium azide (NaN(3)) on spontaneously generated action potential and bursts of potential elicited by d-amphetamine (d-amphetamine-elicited BoP) were studied on the right parietal 4 (RP4) neuron of the snail Achatina fulica Ferussac in vitro. Sodium azide altered the spontaneous action potential of RP4 neuron in a concentration-dependent manner. In lower concentrations, neither NaN(3) (30, 100, 300 microM; 1 and 3 mM) nor d-amphetamine (135 microM) affect the resting membrane potential, amplitude and frequency of RP4 neurons, while in the higher concentrations NaN(3) (30 mM) did abolish the spontaneous action potential on RP4 neurons and depolarized the RP4 neurons reversibly. At lower concentration, NaN(3) (30 microM) facilitated the d-amphetamine-elicited BoP. The BoP elicited by NaN(3) (30 microM) and d-amphetamine (135 microM) were decreased following treatment with KT5720 (protein kinase A inhibitor), or intracellular injection of EGTA [ethylene glycol-bis(2-aminoethyl ether)-N,N,N',N'-tetraacetic acid]. However, the BoP was not affected by applying U73122 (1-[6-[((17beta)-3-methoxyestra-1,3,5[10]-trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dione) or neomycin (phospholipase inhibitors). Voltage clamp studies revealed that NaN(3) (30 microM) did not alter the total fast inwards currents (70 msec.) and the steady-state outwards currents (5 sec.). It appeared that the BoP elicited by NaN(3) (30 microM) and d-amphetamine (135 microM) was mainly due to protein kinase A-related messenger system and intracellular calcium. It is concluded that d-amphetamine-elicited BoP was not mainly due to inhibition of the function of mitochondria in the neuron while the function of mitochondria did alter the BoP elicited by amphetamine.