Efficacy and Safety of Opioids for the Prevention of Etomidate-Induced Myoclonus: A Meta-Analysis.

Etomidate is a widely used hypnotic drug for induction of general anesthesia and sedation, especially in elderly patients and hemodynamically unstable patients. Myoclonus, however, is the most prominent problem during induction of anesthesia with etomidate. Many agents have been used to prevent it and opioid is one of them. This meta-analysis was to evaluate effects of opioids pretreatment for preventing etomidate-induced myoclonus. We searched the PubMed, EMBASE, and the Cochrane Library databases and published studies in English updated to September 2015. Randomized controlled trials of opioids versus placebo/control in patients were included. We evaluated the prophylactic effect of opioids on etomidate-induced myoclonus. All statistical analysis was performed using RevMan 5.2 software. Nine randomized controlled trials involving 604 participants were included. The results indicated that compared with placebo/control, opioids allow more patients to experience no myoclonic movements after etomidate injection [risk ratio (RR) 2.76, 95% confidence interval (CI) 1.75-4.37, P < 0.0001]. The numbers of patients with mild myoclonus [(RR) 0.53, 95% (CI) 0.36-0.78, P = 0.001], moderate myoclonus [(RR) 0.36, 95% (CI) 0.23-0.55, P < 0.00001], and severe myoclonus [(RR) 0.20, 95% (CI) 0.08-0.52, P = 0.0009] after etomidate injection were significantly decreased with the pretreatment of opioids. This meta-analysis suggests that pretreatment with opioids before injecting etomidate was effective for preventing etomidate-induced myoclonus and can reduce the intensity of myoclonus without any adverse effects.

Intrathecal siRNA against Toll-like receptor 4 reduces nociception in a rat model of neuropathic pain.

BACKGROUND: Neuropathic pain is characterized by hyperalgesia, allodynia and spontaneous pain. It often occurs as a result of injury to peripheral nerves, dorsal root ganglions (DRG), spinal cord, or brain. Recent studies have suggested that Toll-like receptor 4 (TLR4) might play a role in neuropathic pain. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the role of TLR4 in a rat chronic constriction injury (CCI) model and explored the feasibility of treating neuropathic pain by inhibiting TLR4. Our results demonstrated that intrathecal siRNA-mediated suppression of TLR4 attenuated CCI-induced mechanical allodynia and thermal hyperalgesia through inhibiting the activation of NF-kappaB p65 and production of proinflammatory cytokines (e.g., TNF-alpha and IL-1 beta). CONCLUSIONS/SIGNIFICANCE: These findings suggest that suppression of TLR4 mediated by intrathecally administered siRNA may be a new strategy for the treatment of neuropathic pain.

Human signal peptide had advantage over mouse in secretory expression.

The signal peptide is a critical component in the secretory expression of protein in eukaryotic cells. It has been verified that the signal peptide of mouse nerve growth factor could mediate the secretory expression of beta-endorphin in cultured non-neuronal cells. Although there is a counterpart of nerve growth factor in human genome, no research about the signal sequence from human genome has been reported. The function of mediating secretory expression is affected by many factors. We assumed that the counterpart from human genome could function as the signal peptide from mouse nerve growth factor does and these two signal sequences had different efficiency in mediating secretory expression of beta-endorphin, but we could not figure out which one had a better function. To validate our hypothesis and give an answer to the question, we constructed two eukaryotic vectors, pcDNA3.1-hEP and pcDNA3.1-mEP, containing human and mouse signal sequences in fusion genes, respectively. RT-PCR showed that the constructed fusion genes were expressed in NIH3T3 cells. We also found that the detected beta-endorphin by the immunofluorescent technique was mainly in the cytoplasm of NIH3T3 cells. The concentration of beta-endorphin in the culture medium by RIA is 280.33 +/- 24.16 (pg/ml) and 191.04 +/- 7.96 (pg/ml) from pcDNA3.1-hEP and pcDNA3.1-mEP, respectively, and there was a significant statistical difference between them (P < 0.05). A difference existed between them and that from blank vector individually (P < 0.01). These findings suggest that our constructed fusion gene containing the signal sequence of human nerve growth factor can be secretorily expressed and the efficiency of the signal peptide from human nerve growth factor is higher than that of mouse signal peptide.

Baroreflex sensitivity is impaired in patients with obstructive jaundice.

BACKGROUND: Obstructive jaundice is associated with enhanced susceptibility to hypotensive shock, renal failure, and toxic effects of endotoxin, which results in high perioperative morbidity and mortality. Since the normal arterial baroreflex function is necessary for hemodynamic homeostasis and improving survival in sepsis, this study aimed to determine whether baroreflex sensitivity was impaired in jaundiced patients. METHODS: Thirty-five patients with obstructive jaundice scheduled for surgery were included, and 30 nonjaundiced patients served as controls. A modified Oxford pharmacologic technique was used for evaluating baroreflex sensitivity immediately before the surgery. Potential factors that may affect baroreflex sensitivity in jaundice, such as liver biochemistry, plasma concentrations of methionine-enkephalin, atrial natriuretic peptide and nitrate, were also measured. RESULTS: Patients with obstructive jaundice had decreased sensitivity in both the sympathetic and vagal components of the baroreflex, as compared with the controls (P < 0.01). There was a significant inverse correlation between plasma atrial natriuretic peptide concentration and decreased sympathetic baroreflex sensitivity in the jaundiced group (r = -0.44, P = 0.008). CONCLUSIONS: Baroreflex sensitivity is impaired in patients with obstructive jaundice, which may contribute to their enhanced susceptibility to the well-known perioperative complications. The underlying mechanisms for such a change may be associated with an increased level of plasma atrial natriuretic peptide.

[Experimental study of compatibility between chondrocytes and allogenic cartilage microparticle acellular tissue matris in vitro].

OBJECTIVE: To construct tissue engineered cartilage using cartilage microparticle acellular tissue matrix (CMACTM) as scaffold. METHODS: To determine the content of hydroxyproline, glycosaminoglycan and DNA of CMACTM prepared from sheep's articular cartilage with multistep enzymic method, and to analyze CMACTM with gross observation, histology and scanning electron microscopy. Allogenic chondrocytes were mixed with CMACTM and cultured in vitro from 0 to 35 days. Observations through inverted microscope, scanning and transmission electron microscope, quantifications of hydroxyproline, glycosaminoglycan and DNA in the composite, cells adhesion rate were applied to analyze the results. RESULTS: The diameter of CMACTM was 0.100-0.154 mm, which contain extracellular matrix only. Hydroxyproline, glycosaminoglycan and DNA quantifications in CMACTM were 204.374 +/- 3.120 microg/mg, 18.302 +/- 2.037 microg/mg and 0.042 +/- 0.013 microg/mg respectively. Allogenic chondrocytes enclosed CMACTM tightly, hydroxyproline, glycosaminoglycan and DNA quantifications in the composite of the two formers increased with difference on 7th day compared with that on 0 day, reached to the peaks on 14th day (hydroxyproline, DNA) and on 21st day (glycosaminoglycan), and retained at a high level on the following days. Cells adhesion rate was 92%. CONCLUSION: Allogenic CMACTM possessed satisfactory biocompatibility for chondrocytes and provided a new scaffold for cartilage tissue engineering.

[Construction and analysis of in vitro expression of adenovirus/adeno-associated hybrid virus containing the fusion gene of human beta-endorphin].

The fusion gene of human beta-endorphin was cloned into the shuttle plasmid pDC312-AAVEE with the method of molecular bilology. The latter and genomic plasmids were cotransfected into HEK293 to package the Adenovirus/Adeno-associated hybrid virus containing fusion gene of human beta-endorphin. The hybrid virus was identified with the method of PCR. The titer of proliferated virus, after purified, was determined by TCID50. The expression of transgene was studied after the hybrid virus infected the cultured cells, through testing the concentration of expressed product in the culture liquid by ELISA. It was identified that the sequence of fusion gene of human beta-endorphin was correctly inserted into the genome of hybrid virus, and not contaminated by wild type virus. The titer of Ad/AAV-EE is 1.29 x 10(10) PFU/mL after purification. The ascending trend of transgene expression was observed from the 1st to the 14th day, and the protein concentration reached 3141 pg/mL at the 14th day.

Suppression of acute morphine withdrawal syndrome by adenovirus-mediated ß-endorphin in rats.

BACKGROUND: Endogenous ß-endorphin (ß-EP) in the central nervous system (CNS) is decreased upon opioid addiction. The current study examined whether exogenous ß-EP, delivered using an adenoviral vector into the CNS could attenuate morphine withdrawal syndrome in rats. METHODS: The model of opioid-dependent rats was set up by receiving subcutaneous injection of morphine using an escalating regimen for 6days (5, 10, 20, 40, 50, 60mg/kg, three times/day). The adenovirus mediated ß-EP gene was constructed based on our previous work. The ilea of opioid-dependent rats were isolated and treated with the supernatant of Ad-NEP. The basic and naloxone-induced (4µm/l) contractions of dependent ilea were recorded. The Ad-NEP was injected into the left lateral ventricle of the addition rats. The expression of the ß-EP gene was verified by radioimmunoassay of the cerebrospinal fluid (CSF) and immunocytochemistry for ß-EP. Withdrawal syndrome was evaluated after intraperitoneal injection of naloxone. RESULTS: The contractions of dependent ilea were attenuated with supernatant containing ß-EP expressed by Ad-NEP. Injection of the Ad-NEP resulted in significant increases in ß-EP level in the CSF and ß-EP-positive neurons. Rats receiving adenovirus carrying the ß-EP gene had significantly less severe withdrawal symptoms upon naloxone challenge. CONCLUSIONS: Exogenous ß-EP mediated by adenovirus could attenuate withdrawal syndrome in morphine-dependent rats.

[The neurovascular anatomy and its clinical implication of the rectus femoris muscle].

OBJECTIVE: The objective of this anatomic study was to investigate the intramuscular neurovascular configuration and to evaluate whether the muscle could be split into two functional units in transplantation. METHODS: Ten fresh cadavers and ten preserved cadavers were used in the study. A mixture of lead oxide, gelatin and water was injected to the femoral artery of the fresh cadaver. The rectus femoris muscle with its neurovascular pedicles was dissected and radiographed. RESULTS: Three vascular patterns of the rectus femoris muscle were found in the 40 cadaver legs. The muscle received its blood supply through a single vascular pedicle (12.5%), or a dominant pedicle with 1-2 ramified (80%), or two dominant vascular pedicles (7.5%). CONCLUSIONS: The study provided a detailed description on the intramuscular neurovascular territories of the rectus femoris muscle. Based on the neurovascular supply of the muscle, it is possible to subdivide the muscle into two functional units for segmental muscle transfer.

[Transferring neurovascular rectus femoris muscle segment for treatment of facial paralysis].

OBJECTIVE: To investigate a new technique for functional treatment of chronic facial paralysis. METHODS: Based on anatomy of intramuscular neurovascular structure in the rectus femoris muscle, 7 consecutive patients with facial paralysis were treated by using a technique of microsurgically free-transferring neurovascular rectus femoris muscle segment to the face in one-stage. Follow-ups were 10 to 24 months. RESULTS: All of the 7 patients showed significantly improvement in the appearance of the oral commissure and oral competence. No complications occurred in the donor site. CONCLUSIONS: The above mentioned technique may have the advantages of preventing the intramuscular nerve and vessel from the surgical injury during splitting the muscle. It could also maintain the transferred muscular segment in a proper tension in the recipient site.