Propofol inhibits the expression of Abelson nonreceptor tyrosine kinase without affecting learning or memory function in neonatal rats.

OBJECTIVE: Propofol is one of the most commonly used intravenous drugs to induce and maintain general anesthesia. In vivo and in vitro studies have shown that propofol can affect neuronal growth, leading to apoptosis and impairing cognitive function. The Abelson nonreceptor tyrosine kinase (c-Abl) is associated with both neuritic plaques and neurofibrillary tangles in the brains of patients with Alzheimer's disease and other neurodegenerative diseases. This study aimed to explore the effect of propofol on apoptosis and neurocognition through its regulation of c-Abl expression in vivo and in vitro. MATERIALS AND METHODS: In this study, primary hippocampal neurons were cultured and exposed to propofol at different concentrations. Protein expression was measured by Western blotting and coimmunoprecipitation. The c-Abl transcription level was verified by fluorescence quantitative PCR. Reactive oxygen species (ROS) levels were detected by flow cytometry. In addition, an animal experiment was conducted to assess neuronal apoptosis by immunofluorescence staining for caspase-3 and to evaluate behavioral changes by the Morris water maze (MWM) test. RESULTS: The in vitro experiment showed that propofol significantly decreased c-Abl expression and ROS levels. In addition, propofol has no cytotoxic effect and does not affect cell activity. Moreover, in the animal experiment, intraperitoneal injection of 50 mg/kg propofol for 5 days obviously decreased the expression of c-Abl in the neonatal rat brain (p < .05) but did not significantly increase the number of caspase-3-positive cells. Propofol treatment did not significantly reduce the number of platform crossings (p > .05) or prolong the escape latency of neonatal rats (p > .05) in the MWM test. CONCLUSIONS: The present data suggest that reduced expression of this nonreceptor tyrosine kinase through consecutive daily administration of propofol did not impair learning or memory function in neonatal rats.

[Prognostic analysis of plantar fasciitis treated by pneumatic ballistic extracorporeal shock wave versus ultrasound guided intervention].

OBJECTIVE: To compare the medium- and long-term effect of pneumatic ballistic extracorporeal shock wave versus ultrasound-guided hormone injection in the treatment of plantar fasciitis. METHODS: The clinical data were collected from patients with plantar fasciitis admitted to PLA General Hospital pain department from September, 2015 to February, 2017. The patients were randomly divided into ultrasound-guided drug injection group and shock wave group. The therapeutic parameters including the numerical rating scale (NRS) scores in the first step pain in the morning, American Orthopedic Foot and Ankle Society (AOFAS) Ankle Hindfoot Scale, and thickness of the plantar fascia were monitored before and at 1 week, 1 month, 3 months, and 6 months after the treatment. The recurrence rate, effectiveness, and patient satisfaction were compared between the two groups at 6 months after the treatment. RESULTS: Thirty-nine patients were enrolled in shock wave group and 38 patients in ultrasound group. The NRS scores in the first step pain in the morning were lowered after treatment in both groups (P<0.05), and the scores were significantly lower in ultrasound group than in shock wave group at 1 week and 1 month (P<0.01), but significantly higher in ultrasound group than in shock wave group at 3 and 6 months after treatment (P<0.05). The AOFAS functional scores were increased in both groups (P<0.05) at 6 months after treatment, was significantly lower in ultrasound group than in shock wave group than group B (90.44∓13.27 vs 75.76∓21.40; P<0.05). The effective rates in shock wave group and ultrasound group were 92.31% and 76.32%, respectively (P<0.05). Recurrence was found in 1 patient (2.56%) in shock wave group and in 8 (21.05%) in ultrasound group (P<0.05). The patient satisfaction scores were significantly higher in shock wave group than in ultrasound group (8.13∓2.67 vs 6.63∓3.75, P=0.048). CONCLUSION: Pneumatic ballistic extracorporeal shock achieves better medium- and long-term outcomes than ultrasound-guided hormone injection in the treatment of plantar fasciitis.

Pulse pressure variation shows a direct linear correlation with tidal volume in anesthetized healthy patients.

BACKGROUND: The settings of mechanical ventilation, like tidal volume (VT), occasionally need to be adjusted in the process of anesthesia for some special reasons. The aim of this study was therefore to assess the relationship between pulse pressure variations (PPVs) in different settings of VT in anesthetized healthy patients under mechanical ventilation. METHODS: Sixty nine ASA I-II patients scheduled for gastrointestinal surgery under general anesthesia were included in this prospective study. All the patients were ventilated at a VT of 6, 8 or 10 ml/kg (predicted body weight) with no positive end expiratory pressure (PEEP) in a random order after intubation. PPV, mean arterial blood pressure, and other hemodynamic and respiratory parameters were recorded in each VT setting respectively after Partial Pressure of End-Tidal Expiration Carbon Dioxide (PetCO2) maintained between 30 mmHg and 40 mmHg by changing Respiratory Rate (RR) before incision. RESULTS: The values of PPV at different settings of VT showed a tight correlation between each other (6 vs. 8 ml/kg: r = 0.97, P < 0.0001; 6 vs.10 ml/kg: r = 0.95, P < 0.0001; 8 vs. 10 ml/kg: r = 0.98, P < 0.0001, respectively). CONCLUSION: There is a direct linear correlation between PPVs at different tidal volumes in anesthetized ASA I-II patients. PPV in any of the 3 VT settings (6, 8 or 10 ml/kg) can deduce that in any other 2 settings. Further studies are needed to explore the effect of intraoperative confounders for this knowledge to be clinically applied. TRIAL REGISTRATION: NCT01950949 , www.clinicaltrials.gov , July 26, 2013.

Comparative outcomes of peripheral nerve blocks versus general anesthesia for hip fractures in geriatric Chinese patients.

BACKGROUND: Geriatric patients undergoing hemiarthroplasty for hip fractures have unacceptably high rates of postoperative complications and mortality. Whether anesthesia type can affect the outcomes has still been inconclusive. OBJECTIVES: We compared general anesthesia (GA) and peripheral nerve blocks (PNBs) on postoperative complications and mortality in elderly patients with femoral neck fractures (FNF) undergoing hemiarthroplasty. MATERIALS AND METHODS: This retrospective study involved data collection from an electronic database. Two hundred and seventeen patients underwent hemiarthroplasty for FNF between January 2008 and December 2012 at the Chinese People's Liberation Army General Hospital. Data on mortality within in-hospital, 30-day, and 1-year, complications, comorbidities, blood loss and transfusion, operative time, postoperative hospital length of stay, intensive care unit admission, and hospital charge were collected and analyzed. Univariate and multivariate Cox regression analyses of all variables were used for 30-day and 1-year mortality. RESULTS: Seventy-two patients receiving GA and 145 receiving PNBs were eventually submitted and analyzed. Mortality was 6.9%, 14.7%, and 23.5% at in-hospital, 30-day, and 1-year, respectively postoperatively, while mortality and cardiovascular complications did not differ between the two anesthetic techniques. Preoperative comorbidities and intraoperative parameters were not statistically different except that patients receiving GA were more likely to have dementia (χ (2)=10.45, P=0.001). The most common complications were acute cardiovascular events, electrolyte disturbances, and delirium. Postoperative acute respiratory events and hypoxemia both were also common, but no differences were found between groups (χ (2)=0.68, P=0.410; χ (2)=3.42, P=0.065, respectively). Key factors negatively influencing mortality included: age, male gender, American Society of Anesthesiologists status, dementia, perioperative cardiovascular events and respiratory events, postoperative stroke, myocardial infarction, and hypoxia. CONCLUSION: Mortality and postoperative complications are not statistically significantly different between PNBs and GA among eldery patients undergoing hemiarthroplasty for FNF.

Differential regulation of primary afferent input to spinal cord by muscarinic receptor subtypes delineated using knockout mice.

Stimulation of muscarinic acetylcholine receptors (mAChRs) inhibits nociceptive transmission at the spinal level. However, it is unclear how each mAChR subtype regulates excitatory synaptic input from primary afferents. Here we examined excitatory postsynaptic currents (EPSCs) of dorsal horn neurons evoked by dorsal root stimulation in spinal cord slices from wild-type and mAChR subtype knock-out (KO) mice. In wild-type mice, mAChR activation with oxotremorine-M decreased the amplitude of monosynaptic EPSCs in ∼67% of neurons but increased it in ∼10% of neurons. The inhibitory effect of oxotremorine-M was attenuated by the M2/M4 antagonist himbacine in the majority of neurons, and the remaining inhibition was abolished by group II/III metabotropic glutamate receptor (mGluR) antagonists in wild-type mice. In M2/M4 double-KO mice, oxotremorine-M inhibited monosynaptic EPSCs in significantly fewer neurons (∼26%) and increased EPSCs in significantly more neurons (33%) compared with wild-type mice. Blocking group II/III mGluRs eliminated the inhibitory effect of oxotremorine-M in M2/M4 double-KO mice. In M2 single-KO and M4 single-KO mice, himbacine still significantly reduced the inhibitory effect of oxotremorine-M. However, the inhibitory and potentiating effects of oxotremorine-M on EPSCs in M3 single-KO and M1/M3 double-KO mice were similar to those in wild-type mice. In M5 single-KO mice, oxotremorine-M failed to potentiate evoked EPSCs, and its inhibitory effect was abolished by himbacine. These findings indicate that activation of presynaptic M2 and M4 subtypes reduces glutamate release from primary afferents. Activation of the M5 subtype either directly increases primary afferent input or inhibits it through indirectly stimulating group II/III mGluRs.

[Anesthesia management of laparoscopic radical cystectomy and orthotopic bladder surgery with a robotic-assisted surgical system].

OBJECTIVE: To summarize anesthesia management of laparoscopic radical cystectomy and orthotopic bladder surgery with a robotic surgical system. METHODS: In the study of 10 cases of bladder cancer, the robot-assisted radical cystectomy+expand lymphadenectomy+orthotopic bladder surgery with 60 degrees of Trendelenburg surgical position, was inserted into the manipulator under the video system monitor positioning, to complete the removal of the diseased tissue dissection and orthotopic ileal neobladder intra-abdominal. The respiratory parameters, hemodynamic parameters, arterial blood gas analysis were monitored and the waking time, intake and output, and intraoperative concurrent recorded. RESULTS: All the patients were operated successfully. The intraoperative blood loss was (342.9 ± 303.4) mL; the peak airway pressure increased after trendelenburg and high pneumoperitoneum; the mean arterial pressure heart rate and central venous pressure increased compared with the endotracheal intubation 15 minutes after two cases of the disease popularity abdominal end-expiratory CO2 partial pressure more than 50 mmHg, and PaCO2 higher than 60 mmHg in the arterial blood gas. When the respiratory parameters were adjusted, the hyperventilation showed no improvement, and when the pressure was reduced to less than 15 mmHg, the pneumoperitoneum improved; when metabolic acidosis occured in 2 patients, sodium bicarbonate post-correction was given; during surgery, 2 patients potassium rose to more than 5.5 mmol/L, gluconate and insulin were given; 5 patients developed multiple subcutaneous emphysema, of whom 1 was confined to the chest and abdomen, and 1 showed significant sense of gripping the snow from face to feet, associated with hypercapnia and temperature drop; the wake time (withdrawal to the extubation time) was (94.2 ± 35.6) min. CONCLUSION: Robot-assisted radical cystectomy + orthotopic bladder surgery is a newly-performed clinical surgery. Because of the huge machines, long time pneumoperitoneum and over-head-down, it is prone to acid-base balance and ion imbalance, thus increasing the difficulty and complexity to anesthesia management. It's necessary to further summarize the impact on the respiratory, hemodynamic, and nervous system.

Increased presynaptic and postsynaptic α2-adrenoceptor activity in the spinal dorsal horn in painful diabetic neuropathy.

Diabetic neuropathy is a common cause of chronic pain that is not adequately relieved by conventional analgesics. The α(2)-adrenoceptors are involved in the regulation of glutamatergic input and nociceptive transmission in the spinal dorsal horn, but their functional changes in diabetic neuropathy are not clear. The purpose of the present study was to determine the plasticity of presynaptic and postsynaptic α(2)-adrenoceptors in the control of spinal glutamatergic synaptic transmission in painful diabetic neuropathy. Whole-cell voltage-clamp recordings of lamina II neurons were performed in spinal cord slices from streptozotocin-induced diabetic rats. The amplitude of glutamatergic excitatory postsynaptic currents (EPSCs) evoked from the dorsal root and the frequency of spontaneous EPSCs (sEPSCs) were significantly higher in diabetic than vehicle-control rats. The specific α(2)-adrenoceptor agonist 5-bromo-6-(2-imidazolin-2-ylamino)quinoxaline (UK-14304) (0.1-2 µM) inhibited the frequency of sEPSCs more in diabetic than vehicle-treated rats. UK-14304 also inhibited the amplitude of evoked monosynaptic and polysynaptic EPSCs more in diabetic than control rats. Furthermore, the amplitude of postsynaptic G protein-coupled inwardly rectifying K(+) channel (GIRK) currents elicited by UK-14304 was significantly larger in the diabetic group than in the control group. In addition, intrathecal administration of UK-14304 increased the nociceptive threshold more in diabetic than vehicle-control rats. Our findings suggest that diabetic neuropathy increases the activity of presynaptic and postsynaptic α(2)-adrenoceptors to attenuate glutamatergic transmission in the spinal dorsal horn, which accounts for the potentiated antinociceptive effect of α(2)-adrenoceptor activation in diabetic neuropathic pain.

Dynamic control of glutamatergic synaptic input in the spinal cord by muscarinic receptor subtypes defined using knockout mice.

Activation of muscarinic acetylcholine receptors (mAChRs) in the spinal cord inhibits pain transmission. At least three mAChR subtypes (M(2), M(3), and M(4)) are present in the spinal dorsal horn. However, it is not clear how each mAChR subtype contributes to the regulation of glutamatergic input to dorsal horn neurons. We recorded spontaneous excitatory postsynaptic currents (sEPSCs) from lamina II neurons in spinal cord slices from wild-type (WT) and mAChR subtype knock-out (KO) mice. The mAChR agonist oxotremorine-M increased the frequency of glutamatergic sEPSCs in 68.2% neurons from WT mice and decreased the sEPSC frequency in 21.2% neurons. Oxotremorine-M also increased the sEPSC frequency in ∼50% neurons from M(3)-single KO and M(1)/M(3) double-KO mice. In addition, the M(3) antagonist J104129 did not block the stimulatory effect of oxotremorine-M in the majority of neurons from WT mice. Strikingly, in M(5)-single KO mice, oxotremorine-M increased sEPSCs in only 26.3% neurons, and J104129 abolished this effect. In M(2)/M(4) double-KO mice, but not M(2)- or M(4)-single KO mice, oxotremorine-M inhibited sEPSCs in significantly fewer neurons compared with WT mice, and blocking group II/III metabotropic glutamate receptors abolished this effect. The M(2)/M(4) antagonist himbacine either attenuated the inhibitory effect of oxotremorine-M or potentiated the stimulatory effect of oxotremorine-M in WT mice. Our study demonstrates that activation of the M(2) and M(4) receptor subtypes inhibits synaptic glutamate release to dorsal horn neurons. M(5) is the predominant receptor subtype that potentiates glutamatergic synaptic transmission in the spinal cord.

[The ability of pleth variability index to predict fluid responsiveness in mechanically ventilated patients under general anaesthesia].

OBJECTIVE: To evaluate the ability of pleth variability index (PVI) in predicting fluid responsiveness in mechanically ventilated patients under general anesthesia. METHODS: From August to November 2009, 25 patients were enclosed in this study following anesthesia induction. PVI was continuously displayed by the Masimo Radical 7. All patients were also monitored with Vigileo/FloTrac system. Haemodynamic data such as cardiac index (CI), stroke volume variability (SVV), mean arterial pressure, heart rate, central venous pressure, PVI, perfusion index were recorded before and after volume expansion (hetastar 6%, 7 ml/kg). Fluid responsiveness was defined as an increase in CI ≥ 15% (ΔCI ≥ 15). RESULTS: SVV and PVI were significantly higher in the responders (16.0% ± 2.6% and 20.5% ± 3.7%) than those in non-responders (11.6% ± 1.4% and 13.8% ± 2.6%) respectively (P < 0.05). The SVV threshold of 13.5% before volume expansion was able to discriminate the responders from the non-responders with a sensitivity of 88.2% and a specificity of 87.5%. The threshold for PVI was 15.5%, the same sensitivity of 88.2% and specificity of 87.5% were obtained. There was a significant relationship between PVI before volume expansion and change in CI after volume expansion (r = 0.683, P < 0.01), the same as the changes of SVV (r = 0.600, P < 0.01). CONCLUSION: PVI as a new dynamic indices can predict fluid responsiveness non-invasively in mechanically ventilated patients during general anesthesia.