蛋白激酶C在异氟醚诱导原代培养大鼠心肌细胞分泌血管内皮生长因子中的作用

目的 探讨蛋白激酶C(PKC)在异氟醚诱导原代培养大鼠心肌细胞分泌血管内皮生长因子(VEGF)中的作用.方法 1～3 d SD新生大鼠,分离培养原代心肌细胞,随机分为6组(n=6):对照组(C组)培养后的细胞不经任何处理;不同浓度异氟醚组(Ⅰ1组～Ⅰ3组)细胞分别经0.7%、1.4%、2.1%异氟醚处理6 h;PKC抑制剂组(P组)细胞培养液中给予PKC抑制剂--calphostin C,终浓度50 nmol/L;PKC抑制剂+异氟醚组(PI组)心肌细胞培养液中加入calphostin C 50 nmol/L后,置入无菌密闭容器,持续输入1.4%异氟醚6 h.采用ELISA法测定细胞培养液VEGF浓度,Western blot法测定心肌细胞PKC亚型的表达.结果 与C组比较,Ⅰ2组和Ⅰ3组细胞培养液VEGF浓度升高,Ⅰ2组胞浆PKCε表达下调,胞膜PKCε表达上调(P＜0.01),胞浆和胞膜PKCα、PKCδ和PKCζ表达差异无统计学意义(P＞0.05),P组上述指标差异无统计学意义(P＞0.05).与胞膜比较,C组和Ⅰ2组胞浆PKCα、PKCδ和PKCζ表达上调(P＜0.05).随异氟醚浓度升高细胞培养液VEGF浓度升高(P＜0.05).与Ⅰ2组比较,PI组细胞培养液VEGF浓度降低(P＜0.05).结论 异氟醚可通过PKCε从胞浆转位到胞膜的途径诱导心肌细胞分泌VEGF,是异氟醚心肌保护作用的机制之一.     

氯胺酮雾化吸入对哮喘大鼠气道炎症的影响

目的 观察氯胺酮雾化吸入对哮喘大鼠气道炎症的影响及其机制。方法 雄性SD大鼠40只,随机分成对照组(N组)、哮喘模型组(A组)和不同浓度氯胺酮预处理组(K1组、K2组和K3组),每组8只。A组用卵蛋白(OA)辅以百日咳杆菌菌苗和氢氧化铝为佐剂注射致敏,两周后雾化吸入OA激发。K1、K2、K3组大鼠以同样方法致敏,但在激发前分别雾化吸入氯胺酮12.5、25、50mg／ml。N组注射和吸入生理盐水。取血分离淋巴细胞,检测胞浆和胞膜内蛋白激酶C(PKC)的活性,并作肺组织病理学检查。结果 A组肺组织切片显示为急性气道炎症性病理改变。K1组气道壁上皮细胞脱落、结构破坏、炎性细胞浸润等改变多见。K2组支气管壁、肺泡间隔仅见少量的炎症细胞。K3组气道黏膜上皮水肿脱落、黏膜下炎症细胞浸润等程度减轻。与N组比较,A、K1、K3组淋巴细胞PKC总活性(PKCT)、胞浆PKC活性(PKCC)、胞膜PKC活性(PKCM)及PKCM％(PKCM占PKCT的百分比)均增高(P<0.01),K2组PKCT、PKCC、PKCM增高(P<0.01)、PKCM％差异无显著性(P>0.05)。与A组比较,K2、K3组PKCT、PKCC、PKCM及PKCM％均减低(P<0.05或0.01),K1组PKCT、PKCC、PKCM均降低(P<0.01)、PKCM％差异无显著性(P>0.05)。结论 雾化吸入氯胺酮25 mg／ml或50 mg/ml通过PKC途径而发挥抗炎效应,对致敏原所激发的气     

蛋白激酶C在肾上腺素抑制人正常皮肤及增生性瘢痕成纤维细胞增殖中作用的实验研究

目的观察蛋白激酶C(PKC)在肾上腺素诱导人正常皮肤成纤维细胞(NFb)和增生性瘢痕成纤维细胞(SFb)增殖抑制中的作用。方法体外培养人NFb和SFb,均加入酚妥拉明(终浓度为0×10-6、3×10-6μmol/L)培养1h,再加入肾上腺素(终浓度0.00、0.05、0.10、0.20μmol/L)培养24h.用噻唑蓝(MTT)法检测NFb和SFb的增殖活力,计算细胞存活率。收集细胞培养上清液,检测乳酸脱氢酶(LDH)活性。用蛋白印迹(Western blot)法检测两种细胞磷酸化PKC的表达水平并进行半定量分析。结果(1)与未刺激时(酚妥拉明0×10-6μmol/L 肾上腺素0.00μmol/L)比较,单独用0.05、0.10、0.20μmol/L肾上腺素刺激以及3×10-6μmol/L酚妥拉明与0.20μmol/L肾上腺素联用时,NFb、SFb增殖活力及存活率均明显下降(P<0.05或0.01)。(2)与未刺激时比较,单独应用0·20μmol/L肾上腺素或3×10-6μmol/L酚妥拉明与各种剂量肾上腺素联用后,SFb、NFb培养上清液中LDH活性差异均无统计学意义(P>0.05).(3)单独应用0.05、0.10、0.20μmol/L肾上腺素时,NFb、SFb磷酸化PKC表达水平均明显高于未刺激时(P<0.01).单用3×10-6μmol/L酚妥拉明时,NFb磷酸化PKC表达水平为123±5,高于未刺激时(80±5,P<0.01),而SFb磷酸化PKC表达水平与未刺激时接近(P>0.05).3×10-6μmol/L酚妥拉明分别与0.05、0.10、0·20μmol/L肾上腺素联用时,两种细胞的磷酸化PKC表达水平低于3种剂量肾上腺素单独作用时(P<0.01).结论肾上腺素通过与α受体结合激活PKC,从而抑制NFb和SFb增殖。     

H2O2诱导ECV304细胞凋亡与Cyclophilin-D蛋白表达的研究

目的 探讨人脐静脉内皮细胞凋亡模型中Cyclophilin-D蛋白的表达及意义.方法 分别应用100、300、500 μmol/L H2O2按时间依从处理人脐静脉ECV3O4细胞,对照组单纯磷酸盐缓冲液(PBS)处理.检测细胞凋亡率、Cyclophilin-D蛋白及其编码基因ppif的表达量的变化.结果 500 pLmol/L H2O2处理组的ECV304细胞凋亡率、Cyclophilin-D蛋白表达量和Cyelophilin-D编码基因ppff的表达量均高于对照组(P<0.01).Cyclophilin-D表达量与H2O2作用时间和凋亡率呈显著正相关,r分别为0.967(P<0.01)和0.971(P<0.01).结论 H2O2可成功诱导血管内皮细胞氧化损伤与凋亡,Cyclophilin-D蛋白可作为细胞凋亡严重程度的预测因子.     

三氧化二砷对小鼠肝脏祖细胞生物学特性的影响

目的 观察三氧化二砷(As2O3)对小鼠肝脏祖细胞(AHPCs)增殖及代谢的影响.方法 应用改良Seglen二步法原位灌注结合机械离心获取AHPCs,体外培养并持续观察超过40 d.应用免疫荧光技术对AHPC及其形成的克隆进行白蛋白、甲胎蛋白(AFP)和细胞角蛋白19 (CK19)染色.取原代培养12d的细胞随机分为3组:对照组(不含As2O3)、低浓度组(含2μmol/L As2O3)和高浓度组(含4 μmol/L As2 O3).干预48 h后,采用免疫荧光法观察细胞核增殖抗原(Ki-67)阳性细胞所占的比例,逆转录-聚合酶链反应(RT-PCR)技术检测Ki-67基因的表达,Western blot技术检测增殖细胞核抗原(PCNA)蛋白的表达.酶联免疫吸附试验(ELISA)检测细胞上清液中尿素浓度的变化.结果 体外培养的AHPC可持续扩增超过40 d,培养第1天强阳性表达白蛋白,培养第5天细胞克隆开始表达AFP,第35天表达CK19.阴性对照组所含Ki-67阳性细胞的比例较高(25.1±2.8)％,而As2O3(2μmol/L)组[(18.8±1.0)％]和As2O3(4μmol/L)组[(11.8±2.0)％]的Ki-67阳性细胞比例逐渐降低.Ki-67 mRNA的表达量在As2 O3(2μmol/L)组(0.823 ±0.012)明显下降,并以As2O3(4μmol/L)组(0.309 ±0.002)降低最为明显.随着As2O3浓度的增加,PCNA表达逐渐下降,并呈剂量-效应关系.阴性对照组细胞代谢产物尿素浓度较高[(0.586 ±0.056) mmol/L]随着As2O3浓度增加As2O3(2μmol/L)组[(0.506±0.058) mmol/L]与As2O3 (4 μmol/L)组[(0.410±0.045) mmol/L]尿素浓度逐渐下降.结论 成功建立AHPC体外培养模型.As2O3能抑制原代AHPC的增殖,并降低其代谢能力.     

细胞信号转导调控剂对严重烫伤小鼠T淋巴细胞分泌功能的影响及机制

目的观察不同信号转导调控剂对严重烫伤小鼠脾脏T淋巴细胞分泌白细胞介素(IL)2、IL-10功能的影响,并探讨其机制。方法分离正常小鼠及高压热蒸气烫伤小鼠(烧伤面积18％TBSA,Ⅲ度)伤后12、96 h的脾脏T淋巴细胞。分为正常对照组(不加T淋巴细胞活化相关信号转导分子调控剂)、调控剂组[正常细胞分别加入以下调控剂:膜蛋白激酶C(PKC)抑制剂H-7(50μmol／L,1 ml)、PKC激活剂佛波酯(TPA,30μmol／L,1 ml)、非受体型蛋白酪氨酸激酶(PTK)抑制剂Herbimycin(10μmol／L,1 ml)、丝裂原活化蛋白激酶激酶(MAPKK)抑制剂PD098059(25μg／ml,1 ml)和Ca2 导入剂A23187(100 nmol/L,1 ml)]、烫伤组(不加调控剂)、烫伤 调控剂组(加入上述调控剂)。检测各组细胞IL-2、IL-10的分泌水平。结果伤后各组细胞中IL-2、IL-10含量均低于正常对照组(P<0．05或0．01);烫伤12 h H-7组、烫伤96 h H-7组分别低于烫伤12 h组和烫伤96 h组(P<0．01)。TPA能使IL-2、IL-10分泌明显升高,但对IL-2升高效能更显著。加入PD098059的各组IL-2、IL-10值均低于正常对照组(P<0．05或0．01)。Herbimycin能显著降低烫伤12 h Herbi- mycin组及烫伤96 h Herbimycin组IL-2的分泌,对IL-10亦有明显抑制。烫伤12 h A21387组中IL-2、IL-10含量为(2417±39)、(2793±25)pg／ml,烫伤96 h A21387组为(921±50)、(2633±35) pg／ml均明显高于烫伤12 h组[(1542±40)、(2390±15)pg／ml]和烫伤96 h组[(328±19)、(1618±21)pg／ml(P<0．05或0．01)]。结论PKC、Ca2 、MAPKK和PTK在严重烫伤小鼠脾脏T淋巴细胞分泌IL-2、IL-10的功能紊乱中起重要作用,其中PKC和PTK主要作用于IL-2的分泌而MAPKK影响IL-10的分泌。TPA和A21387均能显著提高烫伤后IL-2的分泌,并明显纠正伤后IL-2／IL-10分泌比值的失调。     

三氧化二砷抑制肾癌细胞系786-0增殖及诱导凋亡的研究

目的探讨三氧化二砷(As2O3)对人肾癌细胞系786-0的增殖抑制和诱导凋亡的作用及可能机制。方法采用细胞增殖检测、形态学观察、琼脂糖凝胶电泳和肿瘤克隆形成等方法观察As2O3对786-0细胞的增殖抑制和诱导凋亡的作用,以免疫组织化学和逆转录-聚合酶链反应(RT-PCR)技术等探讨As2O3的作用机制。结果2μmol/L以上浓度As2O3可显著抑制786-0细胞的增殖、降低细胞核分裂指数并出现凋亡的形态学改变和DNA片段化,经2.0μmol/LAs2O3处理72h后,其抑制786-0细胞增殖率为69.13%(P<0.01),使其核分裂指数由6.00降低至1.80(P<0.01),肿瘤细胞克隆形成抑制率达到100.00%。As2O3使786-0细胞内bcl-2、PCNA和Ki-67基因表达降低(P<0.01),其作用随药物浓度升高和时间延长而增加。结论As2O3对786-0细胞具有显著的增殖抑制作用,并具有浓度和时间依赖性特点,可能通过下调其PCNA和Ki-67基因表达抑制增殖,抑制bcl-2基因的表达诱导细胞凋亡。     

三氧化二砷对肺腺癌耐药细胞A549/R耐药性的影响

目的 探讨三氧化二砷（As2O3）对肺腺癌耐药细胞株（A549／R）耐药性的影响及调节机制。方法 采用四甲基偶氮唑蓝（MTT）法及荧光分光光度计分别检测As2O3的细胞毒性、A549／R细胞的药敏性及As2O3作用前后细胞内药浓的变化；采用生物化学方法检测A549／R细胞谷胱甘肽-S-转移酶（GSTs）活性。观察非细胞毒性剂量（0．150μmol／L）和低毒剂量（0．375μmol／L）的As2O3对肺腺癌A549／R耐药细胞内GSTs活性的影响；以逆转录-聚合酶链反应（RT—PCR）方法同步检测GST-π、多药耐药性相关蛋白（MRP）mRNA表达水平及变化。结果 As2O3在非细胞毒剂量下可显著降低耐药细胞对ADM的IC50值；As2O3作用后A549／R细胞内ADM积聚增加，其逆转倍数为2、3倍；A549／R细胞中GSTs活性增高。GST-π及MRPmRNA呈过表达状态；不同浓度的As2O3可降低GSTs活性；同时可下调GST-π、MRPmRNA的表达水平。结论 As2O3可通过下调GST-π、MRPmRNA的表达而部分逆转A549／R细胞对ADM耐药。     

三氧化二砷抑制骨肉瘤细胞及二倍体细胞增殖的研究

目的　研究三氧化二砷 (As2 O3 )对骨肉瘤细胞及二倍体细胞增殖的影响。方法　应用噻唑蓝 (MTT)法和集落形成能力测定、形态学观察、流式细胞术和电镜观察等方法检测和观察As2 O3 对骨肉瘤细胞株MG 63及二倍体细胞株MRC 5增殖的影响。结果　As2 O3 对骨肉瘤细胞及二倍体细胞株的增殖有抑制作用 ,并具有时间依赖性和一定范围内的剂量依赖性。≥ 1μmol/L浓度的As2 O3 对MG 63骨肉瘤细胞的抑制率达 70 % ,而≥ 8μmol/L浓度的As2 O3 对MRC 5细胞的增殖才达到相近的抑制率 ;0 .5～ 2 .0 μmol/L浓度的As2 O3 对MG 63细胞的生长抑制率高 ,而对MRC 5细胞的生长抑制率低 ,表现为明显的选择性抑制 ( P <0 .0 1)。 1μmol/LAs2 O3 处理的MG 63细胞第 3天呈典型的凋亡形态学改变 ;流式细胞仪分析显示 ,在G1期细胞前出现明显亚二倍体峰 ,凋亡率与As2 O3 处理时间呈正相关 ;MRC 5细胞则未见明显凋亡峰。结论　As2 O3 通过诱导细胞凋亡抑制骨肉瘤细胞和二倍体细胞增殖 ,在一定浓度内As2 O3 可选择性抑制骨肉瘤细胞的生长增殖。     

三氧化二砷对乳腺癌细胞血管内皮生长因子表达的影响

目的研究低氧条件下人乳腺癌细胞株MDA-MB-435S血管内皮生长因子(VEGF)的表达及三氧化二砷(As2O3)对其表达的影响。方法建立MD-MBA-435S细胞体外低氧培养模型。采用逆转录-聚合酶链反应(RT—PCR)、免疫细胞化学染色和Wester blot分别检测0．5、2．0、5．0μmol／L As2O3对缺氧12h后乳腺癌细胞VEGF基因及蛋白的表达变化；噻唑蓝(MTT)比色法检测不同浓度As2O3对乳腺癌细胞生存的影响。结果高浓度As2O3可以抑制乳腺癌细胞的生存，而低浓度则对此影响较小。缺氧12h后VEGF mRNA和蛋白皆明显增加；3种浓度As2O3对常氧下乳腺癌细胞VEGF mRNA和蛋白无明显影响，而对缺氧12h后细胞VEGF mRNA和蛋白的表达明显抑制，且呈剂量递增效应。结论缺氧可以显著增加乳腺癌细胞VEGF的表达；常氧下As2O3对乳腺癌细胞VEGF的表达无明显抑制，而在低氧下可以明显抑制，其机制可能是通过调控VEGF的上游基因实现的。     

Histochemical and contractile properties of striated muscles of urethra and levator ani of dogs and sheep

AIMS: To understand their possible importance in long- and short-term control of continence, some properties of the striated muscles of the urethra and pelvic floor (levator ani) of dogs and sheep were investigated, especially fiber types and contractile characteristics. MATERIALS AND METHODS: Striated muscles of urethra and levator ani of 29 male and 6 female dogs and 11 male and 6 female sheep were removed and cut into strips. Some strips were frozen and stained for ATPase at pH 9.4 and 4.3 for fiber typing; others were set up in an organ bath to study contractile responses to nerve stimulation. RESULTS: All muscles contained both type I (slow) and type II fibers, ranging from 97% type II in female greyhound urethra to 60% in female sheep levator ani. For each muscle, there were fewer type II muscles in sheep than in dog. The diameters of the urethral fibers were about 60% of the levator ani in dogs and 34% in sheep. Contraction of the urethral muscle was faster than for levator ani and declined to about 80% of the peak, 500 msec after the beginning of stimulation at 20 Hz. The levator ani contraction rose to a steady level as long as stimulation continued. CONCLUSIONS: Both the levator ani and urethral striated muscles contain slow and fast fiber types. The levator ani muscles are capable of sustained contraction with rapid onset which will produce long-term closure of the urethra. The circular urethral muscle contraction was faster but less well maintained.     

Recognition and management of phaeochromocytoma and paraganglioma

Phaeochromocytomas and paragangliomas (PPGL) are catecholamine-secreting neuroendocrine tumours arising from the chromaffin cells in the adrenal medulla. These tumours may be identified incidentally, as part of a work-up for multiple endocrine neoplasia or following haemodynamic surges during unrelated procedures. Advances in perioperative management and improved management of intraoperative haemodynamic instability have significantly reduced surgical mortality from around 40% to less than 3%. Surgery is the definitive treatment in most cases and laparoscopic resection where possible is associated with improved outcomes. Anaesthetic management of PPGL cases represents a unique haemodynamic challenge both before and after tumour resection. In this article we describe the physiology of these tumours, their diagnosis, preoperative optimization methods, intraoperative anaesthetic management and management of postoperative complications.     

Instrumented ligamentotaxis and stabilization of compression and burst fractures of dorsolumbar and mid-lumbar spines

Background:

Controversy continues regarding the best treatment for compression and burst fractures. The axial distraction reduction utilizing the technique employing the long straight rod or curved short rod without derotation to reduce fracture are practised together with short segment posterolateral fusion (PLF). Effects of the early postoperative mobilization without posterolateral fusion on reduction maintenance and fracture consolidation were not evaluated so far. The present prospective study is designed to assess the effectiveness of i) reduction and restoration of sagittal alignment, ii) no posterolateral fusion on the reduced, fractured vertebral body and injured disc, iii) fracture consolidation and iv) the fate of the unfused cephalad and caudal injured motion segments of the fractured vertebra.

Materials and Methods:

The study includes 15 Denis burst and two Denis type D compression fractures between T₁₂ and L₃. The lordotic distraction technique was used for ligamentotaxis utilizing the contoured short rods and pedicle screw fixator. Three vertebrae including the fractured one were fixed. The patients after surgery were braced for ten weeks with activity restriction for 2-4 weeks. The patients were evaluated for change in vertebral body height, sagittal curve, reduction of retropulsion, improvement in neural deficit. The unfused motion segments, residual postoperative pain and bone and metal failure were also evaluated.

Results:

The preoperative and postreduction percentile vertebral heights at, zero (immediate postoperative), at three, six and 12 months followup were 62.4, 94.8, 94.6, 94.5 and 94.5%, respectively. The percentages of the intracanal fragment retropulsion at preoperative, and postoperative at zero, 3, 6 and 12 months followup were 59.0, 36.2,, 36.0, 32.3, and 13.6% respectively.The preoperative and postreduction percentile loss of the canal dimension and at zero, three, six and 12 months were 52.1, 45.0, 44.0, 41.0 and 29% respectively suggesting that the under-reduced fragment was being resorbed gradually by a remodeling process. The mean initial kyphosis of 33° became mean 2° immediately after reduction and mean 3° at the final followup. The fractured vertebral bodies consolidated in an average period of ten weeks (range 8-14 weeks). The restored disc heights were relatively well maintained throughout the observation period. All paraparetic patients recovered neurologically. There were no postoperative complications.

Conclusion:

Instrument-aided ligamentotaxis for compression and burst fractures utilizing the short contoured rod derotation technique and the instrumented stabilization of the fractured spine are found to be effective procedures which contribute to the fractured vertebral body consolidation without recollapse and maintain the motion segment function.     

Incorporation and release of85Sr and14C-proline-hydroxyproline in mineral and collagen of bone and incisor teeth of growing rats

The extent to which exchange and reutilization processes of mineral tracers affect skeletal mineral accretion and resorption measurements was evaluated by comparing the rates of appearance and disappearance of⁸⁵Sr and¹⁴C-proline-hydroxyproline in bones and teeth in growing rats for 12 days following simultaneous parenteral injection of these tracers. Expressions for the relative rates of collagen synthesis and breakdown, which unlike mineral metabolism are considered not to be complicated by exchange phenomena, were based on¹⁴C-proline conversion to¹⁴C-hydroxyproline; the specific activity of the latter was determined. Both the mineral and the collagen specific activities reflected the rates and patterns of growth of the samples assayed; rapid growth and a short interval of time between formation and resorption of tissue in themetaphyseal bone which contains the cartilagineous growth plate, slow growth and an interval of time between formation and resorption of tissue indiaphyseal bone and incisor teeth which is longer than the 12 days of the experiment. However, in metaphyseal bone the specific activity collagen/mineral ratio dropped by one half during the 4–12 day interval in contrast to diaphyseal bone and incisor teeth in which no change in this ratio was observed during this period of time. The data indicate that collagen in the metaphyseal growth zone is removed by resorption before it has become fully mineralized, and that exchange is a relatively unimportant factor in the long term kinetics of bone mineral.

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Zusammenfassung Das Ausmaß, bis zu welchem Austausch- und Wiederverwendungsprozesse der mineralen Tracer die Messungen des mineralen Skelett-Auf- und Abbaues beeinflussen können, wurde ausgewertet; zu diesem Zweck wurde die Geschwindigkeit des Auftretens und Verschwindens von⁸⁵Sr und von¹⁴C-Prolin-Hydroxyprolin in Knochen und Zähnen von wachsenden Ratten während der 12 auf die simultane parenterale Injektion dieser Tracer folgenden Tage verglichen.Der Ausdruck für die relative Geschwindigkeit des Kollagen-Auf- und Abbaues, bei welchem im Gegensatz zum Mineralmetabolismus kein Mitwirken des Austauschphänomens vermutet wird, basiert auf der Umwandlung von¹⁴C-Prolin zu¹⁴C-Hydroxyprolin; die spezifische Aktivität des letzteren wurde bestimmt.Aus der spezifischen Aktivität des Minerals sowie jener des Kollagens konnten die Geschwindigkeit und die Art des Wachstums der untersuchten Proben ersehen werden, d.h.schnelles Wachstum und ein kurzes Zeitintervall zwischen Bildung und Resorption des Gewebes imKnochen der Metaphyse, die auch die knorpelige Wachstumsplatte enthält, und andererseitslangsames Wachstum und längeres Zeitintervall (länger als die 12 Tage des Experimentes) zwischen Bildung und Resorption des Gewebes imKnochen der Diaphyse und in den Schneidezähnen. Immerhin fiel die spezifische Aktivität des Kollagen/Mineral-Anteils im Knochen der Metaphyse während dem 4–12tägigen Zeitintervall auf die Hälfte, im Gegensatz zum Knochen der Diaphyse und der Schneidezähne, bei welchen während dieser Zeitspanne kein Unterschied in diesem Verhältnis beobachtet wurde.Diese Ergebnisse zeigen, daß Kollagen in der Wachstumszone der Metaphyse durch Resorption verschwindet, bevor es ganz mineralisiert ist, und daß der Austausch ein relativ unwichtiger Faktor in der Kinetik auf lange Sicht des Knochenminerals ist.

     

Physiology and pharmacology of nausea and vomiting

Nausea and vomiting are both very unpleasant experiences. The physiology is poorly understood; however, understanding what we do know is key to tailoring a preventative or therapeutic antiemetic regime. There are two key sites in the central nervous system implicated in the organization of the vomiting reflex: the vomiting centre and the chemoreceptor trigger zone. There are five key neurotransmitters involved in afferent feedback to these areas. These are histamine (H₁ receptors), dopamine (D₂), serotonin (5-HT₃), acetyl choline (muscarinic) and neurokinin (substance P). Postoperative nausea and vomiting will occur in around one-third of elective patients who have no prophylaxis. This can result in many detrimental effects including patient dissatisfaction, unplanned admission and prolonged recovery. It is therefore essential that clinicians understand how they can prevent and treat nausea and vomiting using either a single agent or a combination of antiemetics to target relevant receptors. Commonly used drugs include antihistamines, dopamine antagonists, serotonin antagonists and steroids. More novel agents are being developed such as aprepitant, a neurokinin receptor antagonist, palonosetron, a 5HT₃ receptor antagonist and nabilone, a synthetic cannabinoid.     

Physiology and pharmacology of nausea and vomiting

Nausea and vomiting are both very unpleasant experiences. The physiology is poorly understood; however, understanding what we do know is key to tailoring a preventative or therapeutic antiemetic regime. There are two key sites in the central nervous system implicated in the organization of the vomiting reflex: the vomiting centre and the chemoreceptor trigger zone. There are five key neurotransmitters involved in afferent feedback to these areas. These are histamine (H₁ receptors), dopamine (D₂), serotonin (5-HT₃), acetyl choline (muscarinic) and neurokinin (substance P). Postoperative nausea and vomiting will occur in around one-third of elective patients who have no prophylaxis. This can result in many detrimental effects including patient dissatisfaction, unplanned admission and prolonged recovery. It is therefore essential that clinicians understand how they can prevent and treat nausea and vomiting using either a single agent or a combination of antiemetics to target relevant receptors. Commonly used drugs include antihistamines, dopamine antagonists, serotonin antagonists and steroids. More novel agents are being developed such as aprepitant, a neurokinin receptor antagonist, palonosetron, a 5HT₃ receptor antagonist, and nabilone, a synthetic cannabinoid.     

动静脉穿刺网络课件的开发及其应用

目的:确保护理教学效果,提高教学水平。方法:应用多项信息技术将动静脉穿刺技术制作成教学网络课件,并用于临床教学。结果:该课件在本校园网上运行半年余,2000余人次对其进行访问,受到师生好评。结论:该课件能及时反映动静脉穿刺的最新研究进展及具体操作步骤和使用方法,实现护理教学的直观性和交互性,对护理教学和临床带教指导有一定的借鉴作用。     

Physiology and pharmacology of nausea and vomiting

The physiology of nausea and vomiting is poorly understood. The initiation of vomiting varies and may be due to motion, pregnancy, chemotherapy, gastric irritation or postoperative causes. Once initiated, vomiting occurs in two stages, retching and expulsion. The muscles responsible for this sequence of events are controlled by either a vomiting centre or a central pattern generator, probably in the area postrema and the nearby nucleus tractus solitarius. Drugs which induce vomiting include ipecacuanha, a gastric irritant, and apomorphine, a dopamine-receptor agonist. Opioid drugs also induce vomiting, but opioid antagonists are not useful to treat nausea and vomiting. Anti-emetic drugs consist of a variety of neurotransmitter antagonists and may act in the periphery, the central nervous system or both sites. The most important drugs are antagonists at muscarinic, dopamine D₂, 5-HT₃, histamine H₁ and neurokinin NK₁ receptors. These drugs are discussed with particular attention to post-operative nausea and vomiting (PONV).