Sevoflurane (Sev) is one of the most widely used pediatric anesthetics. The major concern of neonatal repeated application of Sev is its potential long-term impairment of cognition and learning/memory, for which there still lacks effective treatment. At the cellular level, Sev exerts toxic effects in multiple aspects, making it difficult for effective interference. Melatonin is a pineal hormone regulated by and feedbacks to biological rhythm at physiological condition. Recent studies have revealed significant neuroprotective effects of exogenous melatonin or its agonists under various pathological conditions. Whether melatonin could prevent the long-term toxicity of Sev remains elusive. Here, we report that neonatal repeated Sev exposure up-regulated MT1 receptor in hippocampal neurons and oligodendrocytes. Pretreatment with melatonin significantly alleviated Sev-induced synaptic deficiency, dysmyelination, and long-term learning impairment. Both MT1-shRNA and MT1 knockout effectively blocked the protective effects of melatonin on synaptic development, myelination, and behavior performance. Interestingly, long-lasting suppression of Wnt signaling, instead of cAMP/PKA signaling, was observed in hippocampal neurons and oligodendrocytes after neonatal Sev exposure. Pharmacologically activating Wnt signaling rescued both the long-term synaptic deficits and dysmyelination induced by Sev. Further analysis showed that MT1 receptor co-expressed well with β-catenin and Axin2 and bound to β-catenin by its C-terminal. Melatonin pretreatment effectively rescued Sev-induced Wnt suppression. Wnt signaling inhibitor XAV939 significantly compromised the protective effects of melatonin. Taken together, our data demonstrated a beneficial effect of melatonin pretreatment on the long-term synaptic impairment and dysmyelination induced by neonatal Sev exposure, and a novel MT1 receptor-mediated interaction between melatonin and canonical Wnt signaling, indicating that melatonin may be clinically applied for improving the safety of pediatric Sev anesthesia.
Objective To investigate the effects of minimal-flow sevoflurane anesthesia combined with a new CO2 adsorbent Amsorb Plus calcium lime on the hepatic and renal functions in patients.Methods Seventytow ASA Ⅰ or Ⅱ patients,aged 20-60 yr,scheduled for gastrointestinal surgery under general anesthesia,were randomized into 2 groups (n =36 each):middle-flow anesthesia group (group G1 ) and minimal-flow anesthesia group (group G2 ).Amsorb Plus calcium lime was added into the CO2 absorption canister and the core temperature of the calcium lime was continuously monitored and recorded.The patients were tracheal intubated after anesthesia induction and mechanically ventilated.The initial sevoflurane concentration was set at 4％ and the fresh gas flow of oxygen was set at 4 L/min.After the end-tidal concentration of sevoflurane reached 2.6％,the fresh gas flow of oxygen was adjusted to 2 L/min in group G1 or 0.5 L/min in group G2.The end-tidal concentration of sevoflurane was maintained at 2.4％-2.8％ during operation.Venous blood samples were taken 24 h before and 24 h after operation for determination of the serum concentrations of total bilirubin (TBIL),direct bilirubin (DBIL),blood urea nitrogen (BUN) and creatinire (Cr) and activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST).Urine samples were obtained at 24 h before and after operation to detect the concentration of glucose and protein.The urine glucose and protein positive patients were recorded.Results There was no significant difference in the core temperature of calcium lime at different time points between the two groups ( P ＞ 0.05 ).Compared with that at 24 h before operation,AST activity,TBIL and DBIL concentrations were significantly increased,BUN concentration was significantly decreased,but no significant change was found in the Cr concentration and the number of urine glucose and protein positive patients at 24 h after operation in group G1,and DBIL concentration was significantly increased,while BUN concentration was significantly decreased at 24 h after operation in group G2 ( P ＜ 0.05 ).There was no significant difference in the parameters of hepatic and renal functions between the two groups ( P ＞ 0.05).Conclusion The combination of minimal-flow sevoflurane anesthesia and Amsorb Plus calcium lime exerts no effect on the hepatic and renal functions,the effect is similar to that of middle-flow anesthesia,and it can be safely used in patients.
Key words:
Anesthetics,inhalation; Anesthesia,inhalation; Liver function tests; Kidney function tests
Zhao, Hui, Wei Chai, Wei Gao, Lixian Xu, Hui Zhang, and Yonghui Yang. Hyperoxygenated solution: effects on acute hypobaric hypoxia-induced oxidative damage in rabbits. High Alt. Med. Biol. 10:283–291, 2009.—High altitude (HA) exposure disrupts the efficiency of the antioxidant system and can lead to oxidative damage in various organs and tissues. The present study investigated the effect of hyperoxygenated solution (HOS) intravenous infusion therapy on oxidative damage induced by acute hypobaric hypoxia. Experimental rabbits were exposed to a simulated high altitude (HA), equivalent to 8500 m, in an animal decompression chamber for 3 h. HOS infusion attenuated the rise in malondialdehyde (MDA) levels and the decrease of the reduced oxidized glutathione (GSH/GSSG) ratio. HOS also increased the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px); the arterial partial pressure of oxygen (Pao2); and arterial blood oxygen saturation (Sao2) levels. Animals treated with HOS had higher Pao2 compared with those subjected to airway oxygen therapy (p < 0.01) during HA exposure. These observations suggest that HOS intravenous infusion exerts protective effects against acute hypobaric hypoxia-induced oxidative damage.
Colorectal cancer (CRC) remains an enormous challenge to human health worldwide. Unfortunately, the mechanism underlying CRC progression is not well understood. Mounting evidence has confirmed that exosomes play a vital role in CRC progression, which has attracted extensive attention among researchers. In addition to acting as messengers between CRC cells, exosomes also participate in the CRC immunomodulatory process and reshape immune function. As stable message carriers and liquid biopsy option under development, exosomes are promising biomarkers in the diagnosis or treatment of CRC. In this review we have described and analyzed the biogenesis and release of exosomes and current research on the role of exosomes in immune regulation and metastasis of CRC. Moreover, we have discussed candidate exosomal molecules as potential biomarkers to diagnose CRC, predict CRC progression, or determine CRC chemoresistance, and described the significance of exosomes in the immunotherapy of CRC. This review provides insight to further understand the role of exosomes in CRC progression and identify valuable biomarkers that facilitate the clinical management of CRC patients.
Objective To express core region of HCV1b (Hebei strain) E2 protein (E2c) by eukaryotic system, and establish the detection method of specific anti-HCV E2 antibody in the sera from hepatitis C patients. Methods Based on the literature, the E2c gene was modified from the HCV1b gene and synthesized via overlapping PCR. Thereafter, the E2c gene including tissue-type plasminogen activator (tPA) signal peptide was cloned into the pCI-neo eukaryotic expression vector, and the product was named pCI-tpa-1bE2c. After HEK293T cells were transfected with pCI-tpa-1bE2c, the supernatant was collected, condensed and purified. Its specificity was identified by Western blotting. Galanthus nivalis agglutinin (GNA)-based ELISA was used to detect the antibody against HCVE2 in the sera from hepatitis C patients. Results Modified HCV E2c protein was successfully expressed in HEK293T cells and the GNA-based ELISA was developed for detecting the antibody against HCV E2 in the sera from hepatitis C patients. Conclusion HCV-1bE2c protein can be effectively expressed in HEK293T cells and applied clinically.
Objective To investigate the effect of propefol on regional cerebral blood flow (rCBF) in healthy volunteers. Methods Seven healthy volunteers aged 24-34 yr weighing 50-69 kg were enrolled in this study. The volunteers were kept in 3 sensorium states in a random order-- waking, sedated and unconscious states by administering normal saline iv at 4 ml·kg-1·h-1(awake), propofol by TCI at a target-effect site concentration of 1.5 μg/ml (sedated) and 3.0 μg/ml (unconscious) respectively. The interval between the two sensorium states was at least 48 h.99Tcm-ECD 0.5 mCi/kg was given iv after normal saline had been infused for 10 min or target effect-site concentration had been set for 10 min. TCI of propefol was stopped at 10 min after 99Tcm-ECD injection and rCBF was determined by using single photon emission computer tomography within 10 min.Results Compaired with the waking state, rCBF decreased throughout the brain, mainly in thalamus, cerebral cortex, hippocampus, cerebellum in sedated and uncouscious state. Conclusion Propofol induces a decrease in global CBF. Low doses of propefol affect preferentially the CBF in cortical areas while high doses of propofol .affect not only CBF in cortex but also subcortical brain structures, particularly thalamus, hippocampus and cingulated gyms, which may be the primary targets for anesthetic action.
Key words:
Propofoi; Cerebral blood flow; Single photon emission computed tomography
AIM: To explore the biological effects of survivin antisense olignucleotide (ASODN) on the growth, apoptosis and sensitivity to chemotherapy of human hepatocarcinoma cells. METHODS: ASODN targeting survivin gene was designed and synthezised. Using hepatocarcinoma cell line SMMC 7721 with over expression of survivin gene as target cell and ASODN as gene expression blocking agent, cell growth inhibition by survivin ASODN was determined by MTT assay. Cell morphological changes were observed under microscope, survivin expression was detected by Western blot and cell growth and mitotic characteristics were analyzed by flow cytometry. Effect of ASODN on sensitivity of the cells to chemotherapy was also identified by MTT assay. RESULTS: The expression of survivin in ASODN treated hepatocarcinoma cells was significantly blocked and the growth of hepatocarcinoma cells was suppressed by ASODN. The SMMC 7721 cell cycle was arrested in metaphase and cell apoptosis and abnormal morphological changes were observed in these cells. MTT assay results showed that the IC50 of Taxol to ASODN treated cells and control cells was (16.2±2.2) μg/L and (35.5±4.3) μg/L, respectively, with significant difference between the two groups ( P 0 01). CONCLUSION: Survivin ASODN can effectively block survivin gene expression in hepatocarcinoma cells, induce apoptosis of these cells, inhibit the cell proliferation and increase the cell sensitivity to Taxol therapy, indicating that survivin gene may become a new target for hepatocarcinoma bio treatment.
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