小儿颞下颌关节强直手术的麻醉处理

目的: 探讨小儿颞下颌关节强直手术的麻醉和困难气道管理。方法: 回顾性分析43例小儿颞下颌关节强直开口受限,困难气道病例资料,在保留自主呼吸的情况下,分为氯胺酮组（K1组）和氯胺酮复合右美托咪定组（K2组）。K1组和K2组均静脉给予氯胺酮1~2 mg/kg,K2组则追加静注右美托咪定1 μg/kg。患者意识消失后,辅以气管内和咽喉区表面麻醉。采用纤维支气管镜经鼻腔气管插管。插管过程中,根据患者反应小剂量滴定氯胺酮,维持麻醉深度。采用GraphPad Prism 6.0软件对数据进行统计学分析。结果: 所有患儿均在纤维支气管镜下经鼻腔成功气管插管。插管过程中,氧饱和度<95%发生率K2组略低于K1组,差异无统计学意义（P>0.05）。插管过程中追加氯胺酮次数和氯胺酮总剂量K2组显著低于K1组（P<0.05）,插管时心率变化和插管用时K2组显著低于K1组（P<0.05）。结论: 氯胺酮麻醉辅以良好的气管内和咽喉区表面麻醉,可完成小儿颞下颌关节强直开口受限的困难气道纤维支气管镜插管,氯胺酮复合右美托咪定可使小儿困难气道的插管过程更短、更平稳。     

DOC2 isoforms play dual roles in insulin secretion and insulin-stimulated glucose uptake

Aims/hypothesis

Glucose-stimulated insulin secretion (GSIS) and insulin-stimulated glucose uptake are processes that rely on regulated intracellular vesicle transport and vesicle fusion with the plasma membrane. DOC2A and DOC2B are calcium-sensitive proteins that were identified as key components of vesicle exocytosis in neurons. Our aim was to investigate the role of DOC2 isoforms in glucose homeostasis, insulin secretion and insulin action.

Methods

DOC2 expression was measured by RT-PCR and western blotting. Body weight, glucose tolerance, insulin action and GSIS were assessed in wild-type (WT), Doc2a ^?/? (Doc2aKO), Doc2b ^?/? (Doc2bKO) and Doc2a ^?/?/Doc2b ^?/? (Doc2a/Doc2bKO) mice in vivo. In vitro GSIS and glucose uptake were assessed in isolated tissues, and exocytotic proteins measured by western blotting. GLUT4 translocation was assessed by epifluorescence microscopy.

Results

Doc2b mRNA was detected in all tissues tested, whereas Doc2a was only detected in islets and the brain. Doc2aKO and Doc2bKO mice had minor glucose intolerance, while Doc2a/Doc2bKO mice showed pronounced glucose intolerance. GSIS was markedly impaired in Doc2a/Doc2bKO mice in vivo, and in isolated Doc2a/Doc2bKO islets in vitro. In contrast, Doc2bKO mice had only subtle defects in insulin secretion in vivo. Insulin action was impaired to a similar degree in both Doc2bKO and Doc2a/Doc2bKO mice. In vitro insulin-stimulated glucose transport and GLUT4 vesicle fusion were defective in adipocytes derived from Doc2bKO mice. Surprisingly, insulin action was not altered in muscle isolated from DOC2-null mice.

Conclusions/interpretation

Our study identifies a critical role for DOC2B in insulin-stimulated glucose uptake in adipocytes, and for the synergistic regulation of GSIS by DOC2A and DOC2B in beta cells.     

Acute kidney injury model established by systemic glutathione depletion in mice

Glutathione (GSH) is one of the most extensively studied tripeptides. The roles for GSH in redox signaling, detoxification of xenobiotics and antioxidant defense have been investigated. A drug‐induced rhabdomyolysis mouse model was recently established in L‐buthionine‐(S,R)‐sulfoximine (BSO; a GSH synthesis inhibitor)‐treated normal mice by co‐administration of antibacterial drug and statin. In these models, mild kidney injury was observed in the BSO only‐treated mice. Therefore, in this study, we studied kidney injury in the GSH‐depleted mouse. BSO was intraperitoneally administered twice a day for 7 days to normal mice. The maximum level of plasma creatine phosphokinase (351 487 ± 53 815 U/L) was shown on day 8, and that of aspartate aminotransferase was shown on day 6. Increased levels of blood urea nitrogen, plasma creatinine, urinary kidney injury molecule‐1 and urinary creatinine were observed. An increase of mRNA expression level of renal lipocalin 2/neutrophil gelatinase‐associated lipocalin was observed. Degeneration and necrosis in the skeletal muscle and high concentrations of myoglobin (Mb) in blood (347‐203 925 ng/mL) and urine (2.5‐68 583 ng/mL) with large interindividual variability were shown from day 5 of BSO administration. Mb‐stained regions in the renal tubule and renal cast were histologically observed. In this study, the GSH‐depletion treatment established an acute kidney injury mouse model due to Mb release from the damaged skeletal muscle. This mouse model would be useful for predicting potential acute kidney injury risks in non‐clinical drug development.