肿瘤坏死因子相关诱导凋亡配体联合化疗药物治疗膀胱癌的研究

目的　探讨肿瘤坏死因子相关诱导凋亡配体 (TRAIL)治疗膀胱肿瘤的作用 ,以及与化疗药物的协同作用。方法　将T2 4及 5 63 7膀胱肿瘤细胞接种至 96孔培养板后分别加入浓度为1、10、10 0 μg/L的TRAIL ,0 .1、1.0、10 .0mg/L的阿霉素 (ADM )和丝裂霉素 (MMC) ,不同浓度的TRAIL、ADM、TRAIL和MMC ,噻唑蓝比色 (MTT)法分别检测肿瘤细胞的生存率。将膀胱肿瘤细胞接种至 12孔板 ,培育 2 4h后加入不同浓度的TRAIL、ADM、MMC、TRAIL联合ADM、MMC。用流式细胞术检测不同处理组肿瘤细胞的凋亡率和死亡率。结果　 10 0 μg/LTRAIL引起T2 4、5 63 7细胞的凋亡率分别为 2 0 .1%、45 .3 % ,与无药物组 1.1%、3 .5 %的凋亡率比较差异有非常显著性(P <0 .0 1)。单独运用 10mg/LMMC、ADM对T2 4、5 63 7的抑制率分别为 3 6.0 %、44 .1%、2 6.7%、3 0 .2 % ;而 10 0 μg/LTRAIL和 10mg/LMMC、ADM联合后对T2 4、5 63 7的抑制率分别达到 5 8.4%、73 .7%、90 .7%、88.2 % ,两者有明显的协同作用 (P <0 .0 5 )。结论　在体外实验中 ,TRAIL可通过诱导肿瘤细胞的凋亡而产生抗膀胱肿瘤的作用 ;TRAIL与化疗药物ADM、MMC有协同抗肿瘤作用     

人参二醇组皂苷增强顺铂对人前列腺癌DU145细胞凋亡的效应

目的 探讨人参二醇组皂苷(panoxadiol saponin PDS)与顺铂(cisplatin,DDP)联合应用对DU145前列腺癌细胞增殖及凋亡的影响.方法 采用MTT比色法检测PDS与DDP联合应用对DUl45细胞增殖活力的影响;吖啶橙染色观察诱导细胞凋亡情况;流式细胞仪分析细胞周期及凋亡,并计算细胞平均凋亡率;免疫化学和Western blot技术观察细胞内激活的caspase3的表达.结果 100mg/L,PDS与0.2 u mol/L DDP联合给药:(1)48h后可使单独应用0.2 1.tmol/L DDP组其肿瘤细胞生长抑制率由16.35%提高到47.13%;(2)吖啶橙荧光染色可见细胞呈现明显凋亡形态,其凋亡率与2μmol/L DDP组相当:(3)流式细胞术结果显示,可使单独应用0.2μmol/L DDP组其诱导DU145细胞凋亡率从5.53%提高到19.39%,相当于其10倍剂量即2.0 μmol/L DDP的诱导凋亡效应(21.05%),明显高于PDS单独应用的凋亡率:(4)免疫化学和Western blot结果显示,可使单独应用O.2 μmol/L DDP组细胞内激活的caspase3阳性细胞率与2 μmol/L DDP组相当.结论 PDS能增强DDP对DU145前列腺癌细胞的致凋亡效应.     

蛋白激酶A活性下降对膀胱移行细胞癌凋亡的影响

目的探讨蛋白激酶A(PKA)活性下降对膀胱移行细胞癌细胞株T24增殖和化疗敏感性的影响及其机制。方法用0、15、30μmol/L H-89(PKA活性抑制剂)诱导T24细胞后,用放射免疫法检测H-89作用下T24细胞中PKA活性的变化；用流式细胞仪检测H-89作用下细胞凋亡的变化；用噻唑蓝(MTT)比色法检测丝裂霉素和表阿霉素单独作用下以及与15μmol/L H-89共同作用下T24细胞活力的变化；用Western blot检测15μmol/L H-89作用下T24细胞中bcl-2表达的变化。结果H-89能够使T24细胞中的PKA活性下降；在15μmol/LH-89作用36h后,流式细胞仪检测可见T24细胞凋亡率为57．81%,显著高于对照组4．37%(F=311．35,P＜0．01)。丝裂霉素(MMC)和表阿霉素(Epirubicin)对T24细胞的半数致死量分别为120mg/L和100mg/L；加入15μmol/L H-89后,细胞的存活率分别降为(31．14±4．37)%和(24．91±3．59)%,两组间差异有统计学意义(丝裂霉素组：F=23．94,P＜0．01；表阿霉素组：F=50．64,P＜0．01)。用15μmol/L H-89诱导T24细胞后,bcl-2表达呈下降趋势,并显著低于对照组。结论抑制PKA活性能够使bcl-2的表达下降,从而诱导膀胱癌T24细胞株凋亡,并提高其对化疗药物的敏感性。     

新维甲类化合物4HPR对人胆管癌细胞周期和凋亡的影响及可能机制

目的　探讨N hydroxyphenyl retinamide(4HPR)对人胆管癌细胞QBC939细胞增殖和凋亡的影响及其可能机制。方法　采用四甲基氮唑蓝实验 (MTT)、免疫组织化学染色、流式细胞术等技术 ,检测经 5× 10 -6mol/L 4HPR处理后 ,QBC939细胞生长增殖、细胞周期和凋亡的变化 ,以及对P2 1waf1、P2 7kip1、P5 3蛋白表达的影响。结果　 4HPR显著抑制人胆管癌细胞QBC939细胞的生长增殖 ,并呈时间、剂量依赖性。用 5× 10 -6mol/L 4HPR处理细胞后 ,细胞周期停滞于G1期。流式细胞术检测发现 ,4HPR处理 12h细胞凋亡率达 9 7% ,至 4 8h达 5 7 2 %。而P2 1waf1、P2 7kip1蛋白表达呈上升趋势 ,P5 3蛋白表达则无明显变化。结论　 4HPR具有抗增殖和诱导QBC939细胞发生凋亡的作用 ,并可导致细胞周期停滞于G1期。此种机制与其上调P2 1waf1、P2 7kip1蛋白表达有关 ,而与P5 3蛋白表达无关。     

线粒体促凋亡蛋白促进化疗药物诱导膀胱癌细胞凋亡的分子学机理研究

目的　探讨线粒体促凋亡蛋白 (Smac)促进化疗药物诱导膀胱癌细胞凋亡的分子学机理。　方法　脂质体介导Smac基因转染膀胱癌T2 4细胞 3d后 ,低剂量丝裂霉素诱导凋亡启动 ,MTT比色分析检测癌细胞生长活性 ,流式细胞术检测细胞凋亡 ;免疫组织化学法和逆转录聚合酶链反应检测Smac、XIAP、caspase 3的表达。　结果　各组癌细胞在低剂量丝裂霉素诱导下均出现凋亡 ,0 .0 5mg/ml、0 .0 0 5mg/ml丝裂霉素处理的T2 4细胞凋亡率分别为 18.84 %、10 .72 % ,转染Smac后经 0 .0 5mg/ml、0 .0 0 5mg/ml丝裂霉素处理的T2 4细胞凋亡率分别为 33.5 2 %、2 6 .2 4 % ,差异有显著性意义 (P1<0 .0 5、P2 <0 .0 1) ;同组凋亡相关基因XIAP表达下降、caspase 3表达上调 ,其表达差异均有统计学意义 (P <0 .0 5 )。　结论　Smac在癌细胞中的活化表达可以明显增强细胞在刺激信号下的凋亡 ,其作用机理是通过抑制凋亡抑制蛋白IAPs ,解除了对凋亡下游效应半胱氨酸蛋白酶caspase的抑制活性。     

吡柔比星诱导膀胱癌细胞凋亡的实验研究及预防膀胱癌术后复发的效果

目的　探讨吡柔比星诱导膀胱癌细胞凋亡的机制和膀胱内灌注预防术后复发的效果。　方法　采用MTT法、流式细胞术和透射电子显微镜技术 ,研究不同浓度的吡柔比星对人膀胱癌细胞株T2 4的抑制作用。对 6 0例经尿道电切术的膀胱移行细胞癌患者 ,术后以 30～ 40mg吡柔比星膀胱内灌注 ,观察预防复发的效果。　结果　吡柔比星浓度为 10mg/L和 10 0mg/L时 ,对T2 4细胞生长的抑制率分别为 80 %和 94% ,G1期前出现明显的凋亡峰 ,可见胞浆内空泡形成、核染色质凝聚等典型细胞凋亡特征。当浓度为 10 0 0mg/L时 ,细胞出现坏死特征。共 5 8例完成 1个以上疗程 ,平均随访 18.8个月 ,复发 5例 (8.6 % )。　结论　抑制癌细胞生长和诱导细胞凋亡甚至死亡是吡柔比星抗肿瘤的机制之一。用吡柔比星进行膀胱内灌注预防膀胱癌术后复发安全、有效     

低剂量阿霉素联合TRAIL诱导人前列腺癌细胞LNCAP凋亡的实验研究

目的 研究低剂量阿霉素联合肿瘤坏死因子相关凋亡诱导配体(TRAIL)诱导人前列腺癌细胞LNCAP凋亡的作用和机制,为提高肿瘤治疗效果提供理论依据.方法 采用蛋白印迹、流式细胞术、MTT等实验技术,检测TRAIL和低剂量阿霉素分别或者联合处理LNCAP细胞后细胞的生存率变化、相关受体及其配体系统、凋亡相关蛋白(c-FLIP,BCL-2,XIAP)的变化.结果 低剂量阿霉素(0.86 μmol/L)可以增加细胞表面DR4和DR5的表达,同时减少凋亡抑制蛋白c-FLIP的表达,增强TRAIL诱导LNCAP细胞凋亡的敏感性.结论 低剂量阿霉素(0.86 μmol/L)可以增强TRAIL对LNCAP细胞的凋亡诱导效应.     

二十二碳六烯酸联合5氟尿嘧啶对胃癌细胞生长及bcl-2、bcl 2l12和bax表达的影响

目的 评估二十二碳六烯酸(DHA)联合5氟尿嘧啶(5-Fu)对胃癌细胞SGC 7901生长以及bcl-2、bcl 2l12和bax基因表达的影响.方法 采用台盼蓝拒染方法检测两药物单用和联用对细胞活力的影响,用联合系数判断两药合用效果,倒置显微镜下观察细胞生长状况,PI染色流式细胞术检测亚二倍体峰比并拟合细胞周期曲线,Annexin-V/PI双标记方法检测早期细胞凋亡,RT-PCR方法检测bcl-2、bcl 2l12和bax基因的表达.结果 DHA可抑制胃癌SGC 7901细胞生长,且呈剂量和时间依赖性(P<0.05),24 h、48 h的半数抑制浓度分别为67.81 μg/ml、45.76 μg/ml;DHA联合5-FU对细胞生长的抑制具有协同作用(CI<1,P<0.01),倒置显微镜下可见两药联合处理后细胞稀疏;亚二倍体峰比、Annexin-V早期凋亡率示DHA、5-FU均能诱导细胞凋亡且联合用药后细胞凋亡更明显(DHA、5-FU、联合组的亚二倍体峰比分别为5.2%、6.2%、13.9%;早期细胞凋亡率分别为4.00%、5.37%、13.11%);细胞周期曲线在联合组停滞于G0/G1和S期;RT-PCR显示DHA、5-FU可下调bcl-2和bcl 2l12表达,两药联合表达时下调更显著,bax表达则无明显改变.结论 DHA能抑制胃癌SGC 7901细胞增殖,联合5-FU后对细胞生长抑制和周期阻滞具有协同作用,可能通过下调bcl-2和bcl 2l12基因诱导胃癌SGC 7901细胞发生凋亡.     

磁介导热疗联合顺铂化疗对肝癌细胞的影响及其机制

目的　探讨用电磁场诱导磁性微球热疗联合顺铂化疗对人肝癌细胞的影响及机制。方法　在体外培养的人肝癌细胞BEL 740 2中加入磁性微球 (5、10 g/L)和顺铂 (1、3mg/L) ,用 40kHz、2 4kA/min的电磁场诱导热疗 3 0min ,光纤温度仪监测温度的变化 ,与未加磁性微球和 /或顺铂组对照 ,采用细胞计数法绘制肝癌细胞的生长曲线 ,细胞集落形成计算集落形成率 ,流式细胞仪分析细胞周期及凋亡率。结果　磁场下 ,加入磁性微球各组的温度均升高 ,10 g/L磁性微球组的温度明显高于 5g/L磁性微球组 (4 4℃ :3 8.5℃ ,P <0 .0 1) ,随磁性微球和顺铂的浓度增加 ,肝癌细胞的生长曲线变低平 ,集落形成率降低 ,G0 /G1期下降 ,S期增加 ,凋亡率增加 (P <0 .0 1)。结论　磁介导热疗可抑制肝癌细胞的增殖 ,对顺铂的抗癌作用有明显的协同作用。磁介导热化疗的抗癌作用机制主要是诱导凋亡 ,S期阻滞。     

沙利霉素逆转P-gp介导的肾癌ACHN细胞多药耐药的实验研究

目的 探讨沙利霉素对肾癌ACHN细胞多药耐药的逆转及其机制.方法 实验分为对照组、阿霉素组、沙利霉素组及阿霉素和沙利霉素联合用药组,药物作用24 h后,CCK-8方法 检测肾癌细胞的生长活性,免疫细胞化学法检测肾癌细胞P-糖蛋白(P-gp)的表达情况.结果 10 μg/ml 阿霉素对肾癌ACHN细胞的生长抑制率仅为4.758%.沙利霉素组对肾癌ACHN细胞生长抑制率呈剂量依赖性,并高于阿霉素组(P<0.05),其中以10 μmol/L组抑制率最高(达17.555%).联合用药组的生长抑制率高于沙利霉素组及阿霉素组(P<0.05),以10 μmol/L 沙利霉素 +10 μg/ml 阿霉素组的抑制率最高(达45.447%).与阿霉素组比较,经沙利霉素处理过的肾癌ACHN细胞中的P-gp蛋白表达下降(P<0.05).结论 沙利霉素增强了肾癌ACHN细胞对阿霉素的敏感性,耐药性逆转的机制之一可能与沙利霉素下调癌细胞中P-gp的表达有关.     

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.     

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.

     

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.     

Principles and Practice of Hemofiltration and Hemodiafiltration

There is growing interest in the convective dialysis therapies, hemofiltration (HF) and hemodiafiltration (HDF). Both require dialysis membranes which are highly permeable to solutes as well as fluid, and in both cases large volumes of ultrafiltration are the condition for convective transport. In HDF the convection is combined with diffusion, and as a consequence, maximum clearance over the entire molecular weight spectrum is achieved. Optimal forms of HDF provide urea clearance 10–15% higher than the corresponding diffusive mode. The larger the solute, the greater is the impact of convection, and β₂-microglobulin (β₂m) levels may be up to 70% reduced. Traditional postdilution HF provides high clearance of medium sized and large molecules. Satisfactory clearance of small solutes requires blood flows in excess of 500 ml/min. With access to practically unlimited volumes of substitution solution through on-line ultrafiltration, predilution HF can now be used. This increases the clearance of small solutes to an acceptable range. For HDF as well as HF, large patient populations consistently treated for longer periods of time are needed to make valid outcome comparisons with other therapies.     

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.     

骨折不愈合与延迟愈合的成因与治疗

目的探讨骨折不愈合与延迟愈合的成因、报肯治疗的方法与设果。方法对1990年7月～2004年12月间收治的107例骨折不愈台、54例骨折延迟愈合2例先天性胫骨骨不连进行回顾性研究，分析原因，随访治疗结果。18例延迟愈合行保守治疗，本组其他145例行手术治疗，结果除2例先天性胫骨骨不连外，其余161例的成因中均有医源性因素。10例失去随访，153例平均随访17（6-28）个月，骨折均获骨性连接，愈合时间平均10（6-14）个月，肢体功能恢复良好，结论医源性技术缺陷是骨折不愈合与延迟愈合的主要原因，针对各种不同因素进行合理治疗可获得满意效果。     

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.