Gastric myoelectric activity during cisplatin-induced acute and delayed emesis reveals a temporal impairment of slow waves in ferrets: effects not reversed by the GLP-1 receptor antagonist, exendin (9-39).

Preclinical studies show that the glucagon-like peptide-1 (GLP-1) receptor antagonist, exendin (9-39), can reduce acute emesis induced by cisplatin. In the present study, we investigate the effect of exendin (9-39) (100 nmol/24 h, i.c.v), on cisplatin (5 mg/kg, i.p.)-induced acute and delayed emesis and changes indicative of 'nausea' in ferrets. Cisplatin induced 37.2 ± 2.3 and 59.0 ± 7.7 retches + vomits during the 0-24 (acute) and 24-72 h (delayed) periods, respectively. Cisplatin also increased (P<0.05) the dominant frequency of gastric myoelectric activity from 9.4 ± 0.1 to 10.4 ± 0.41 cpm and decreased the dominant power (DP) during acute emesis; there was a reduction in the % power of normogastria and an increase in the % power of tachygastria; food and water intake was reduced. DP decreased further during delayed emesis, where normogastria predominated. Advanced multifractal detrended fluctuation analysis revealed that the slow wave signal shape became more simplistic during delayed emesis. Cisplatin did not affect blood pressure (BP), but transiently increased heart rate, and decreased heart rate variability (HRV) during acute emesis; HRV spectral analysis indicated a shift to 'sympathetic dominance'. A hyperthermic response was seen during acute emesis, but hypothermia occurred during delayed emesis and there was also a decrease in HR. Exendin (9-39) did not improve feeding and drinking but reduced cisplatin-induced acute emesis by ~59 % (P<0.05) and antagonised the hypothermic response (P<0.05); systolic, diastolic and mean arterial BP increased during the delayed phase. In conclusion, blocking GLP-1 receptors in the brain reduces cisplatin-induced acute but not delayed emesis. Restoring power and structure to slow waves may represent a novel approach to treat the side effects of chemotherapy

【分子標的治療による特異的な副作用とその対策】 Infusion Reaction

著者最終原稿版近年、目覚ましい発展を遂げているがんの分子標的治療の代表的治療法としてモノクローナル抗体療法があり、その有効性と副作用の少なさからがん治療において不可欠な治療法となっている。この抗体治療に共通した特徴的な急性期毒性としてinfusion reactionがあり、過敏症やアレルギー反応に類似した有害反応の総称を指す。一般に初回投与の最初の2時間以内に発症し、薬剤の一時的な中断やステロイド剤投与・酸素吸入・補液などで対処可能な軽微から中等度のものが多いが、時に重篤な事象も報告されており、投与後の注意深い観察が重要である。安全ながん治療の実践のためにも出現時期や頻度、前処置や出現時の対処法などを医療者が熟知し迅速に実践できる体制が確立されているだけでなく、患者自身にも十分なインフォームド・コンセントを行うことが望まれる

【大腸癌の診断と治療 最新の研究動向】 大腸癌の診断 注腸X線検査

図は説明の順番に並んでいます。 著者