Erythromycin Enhances Solid-Phase Gastric Emptying in Induced-Hyperglycemia in Patients with Truncal Vagotomy and Pyloroplasty

Erythromycin has been found to be a gastrointestinal prokinetic agent while acute hyperglycemia has been associated with delayed gastric emptying in healthy controls and diabetics. The aim of this study was to investigate whether hyperglycemia, per se, alters gastric motility, during erythromycin-induced acceleration of gastric emptying of solids in patients with truncal vagotomy and pyloroplasty (TVP) and the role of vagus nerves. Eight TVP patients and six controls underwent scintigraphic measurement of gastric emptying of a solid meal, during placebo in normoglycemia (5–8.9 mmol/liter glucose) or 200 mg intravenous erythromycin lactobionate in normo- or hyperglycemia (16–19 mmol/liter glucose) induced by intravenous glucose infusion, on separate days in random order. In the TVP patients during normoglycemia, the erythromycin compared to placebo accelerated the meal gastric half-emptying time (T ), (37.12 ± 6.87 vs 91.88 ± 11.53, P < 0.001) and decreased the lag-phase duration (P < 0.001) and the percentage of meal retained in the stomach at 120 min (P < 0.001). Erythromycin in hyperglycemia compared to normoglycemia increased T (61.25 ± 10.67 vs 37.12 ± 6.87, P < 0.001), prolonged lag-phase duration (P < 0.001), and the percentage of isotope retained in the stomach at 120 min (P < 0.001). The T , the lag phase duration, and the meal retained in the stomach at 120 min, after giving placebo was significantly increased, compared to erythromycin administration in hyperglycemia (P < 0.001). Significant differences among patients and controls were found during gastric emptying after giving placebo and after erythromycin in hyperglycemia (P = 0.04 and P = 0.007, respectively), while nonsignificant differences were found after giving erythromycin in normoglycemia. We conclude that the effect of erythromycin-induced acceleration on gastric emptying is related to the plasma glucose level. Hyperglycemia reduces the erythromycin-induced acceleration of gastric emptying of solids in both controls and TVP patients. A significant increase in the delay of gastric emptying was achieved in TVP patients compared to controls after giving erythromycin in hyperglycemia and after placebo. Despite the inhibitory effect of induced hyperglycemia on gastric emptying, erythromycin is still able to accelerate the emptying rate and could prove to be a useful prokinetic agent under hyperglycemic conditions. Hyperglycemia may indicate a cholinergic-antagonist pathway that delays the erythromycin-induced acceleration of gastric emptying of solids and is more evident in vagotomized patients than controls, who retain the functional integrity of the vagus nerves.     

静脉用小剂量红霉素对极低体重早产儿的影响

目的探讨静脉缓慢滴人小剂量红霉素防治早产儿喂养不耐受与口服方式的疗效及不良反应差异。方法我科收治的VLBW患儿随机分为三组,分别给予小剂量静脉滴注红霉素、口服红霉素及对照组,观察三组患儿疗效及不良反应等方面差异。结果口服与静脉使用红霉素两组的喂养不耐受发生率、住院时间、体重增长情况等均无差异（P〉0．05）,静脉组早产儿达到足量喂养的平均时间要略短于口服治疗组（P〉0．05）。静脉滴注红霉素与口服红霉素后不良反应发生情况无差异（P〉0．05）。结论口服红霉素治疗早产儿喂养不耐受是有效的,静脉小剂量红霉素防治早产儿喂养不耐受效果与口服类似,并且更易操作,不良反应发生率无明显升高。     

Kinetic studies on the decomposition of erythromycin A in aqueous acidic and neutral buffers

The results of a study are presented on the effect of pH, buffer concentration and temperature on the decomposition of erythromycin A in aqueous solution. The decomposition proceeds via the known intermediate erythromycin A-6,9-hemiketal and observed rate coefficients (k_obs) for both erythromycin A and hemiketal degradation are reported. Both reactions are subject to specific acid catalysis and catalysis by buffer species. Buffer independent rate coefficients have been obtained and these show a linear increase with decreasing pH. The mechanistic implications of these observations are discussed.     

清胰汤对急性胰腺炎大鼠肠动力的影响

目的：探讨清肠汤对大鼠急性胰腺炎（AP）肠动力的影响及其机制。方法：由胆总管逆行注射牛磺胆酸钠诱导大鼠AP，随后灌服清胰汤，红霉素，观察小肠推进比和血清胃动素水平，结果：AP组较对照组小肠推进比明显减低，血清胃动素水平亦降低，与AP组相比，清胰汤组和红霉素组大鼠的小肠推进比明显提高，清胰汤组胃动素水平明显增高，结论：清胰汤能改善AP大鼠的胃肠动力，其机制可能与其提高血清胃动素的水平有关。     

小剂量强地松、红霉素和富露施联用对大鼠肺纤维化及其转化生长因子β1干预的实验观察

目的 提供更合理的肺纤维化治疗方案。方法 100只wistar大鼠，随机抽出20只作为正常组，气管内注入生理盐水(作为阴性对照)，剩余80只经气管内注入博莱霉素造模成功后随机分为模型组20只(作为阳性对照)，大剂量强地松组20只，红霉素和富露施组20只，小剂量强地松、红霉素和富露施组20只，分别给予相应药物治疗。以上各组动物在第七，十四，三十，六十天每组随机抽出5只处死进行病理切片观察，电子计算机图像分析仅进行组织形态学、胶原和转化生长因子(TGF)β1定量分析。结果 小剂量强地松、红霉素和富露施组对模型动物干预最强。结论 小剂量强地松、红霉素和富露施联合应用治疗大鼠肺纤维化伏于经典方法。     

红霉素肠溶颗粒和肠溶片的相对生物利用度

红霉素碱肠溶片不便于小儿分剂量服用,我们研制了一种肠溶颗粒新剂型。本文采用微生物法(琼脂打孔法)测定了12名健康志愿者单剂量交叉口服三种不同工艺和辅料制成的红霉素肠溶颗粒(EI、EII、EIII)及一种市售红霉素肠溶片(EIV)各500mg后的血药浓度,经计算机处理:EI、EII和EIII之间各药代动力学参数都较接近(P>0.5),体内吸收(t_(lag)、t_(max)和K_a)均比EIV快(P<0.05),且个体差异小,血峰浓度(C_(max))分别是EIV的1.15、1.30和1.34倍,相对生物利用度(颗粒AUC/片剂AUC)分别为126.3、136.1和133.3％。     

5—羟色胺M受体和胆碱能受体阻断剂在红霉素所致小肠动力紊乱和呕吐中的作用

本实验对８条犬进行小肠肌电测定，并在记录期间分别静注胆碱能神经阻断剂，阿托品和六甲季胺，以及５－羟色胺（５－ＨＴ）Ｍ受体阻断剂，灭吐灵，以观察其对红霉素所致肠道副作用的影响。结果发现阿托品和六甲季胺不仅能明显地抑制空腹时正常传播性肌电综合波（ＭＭＣ）的发生和传播，降低红霉素促进小肠动力的作用，还能减轻红霉素所致饱腹动物的快波数增加，但对呕吐无明显影响。灭吐灵的实验结果显示红霉素的致吐作用是由５－ＨＴＭ受体介导的，与其促进小肠动力的作用无明显因果关系。     

Motilin, erythromycin, and the gastric migrating motor complex: site of action

Motilin is a putative hormone which induces a premature migrating motor complex when administered exogenously, but the target organ for this hormonal effect is undetermined. Our aim was to determine whether motilin and the motilin agonist, erythromycin, induce a premature migrating motor complex via an effect directly on the stomach. Six dogs underwent splenectomy and ligation of all branches of the splenic artery except the left gastroepiploic and short gastric arteries to the proximal stomach. An intra-arterial catheter was placed in the proximal splenic artery for close intra-arterial injection of motilin and erythromycin directly to the gastric corpus/proximal antrum. After recovery, the minimum effective dose required to induce a premature migrating motor complex was determined for motilin and for erythromycin given close intra-arterially or intravenously (systemically) by monitoring upper gut myoelectric activity. Minimum effective doses of motilin and erythromycin were the same whether given intra-arterially or intravenously. The latency interval or the time to onset of a premature Phase III was less than 2 minutes for intra-arterial or intravenous administration (P > 0.05). The characteristics of induced-Phase HI activity (appearance, duration, velocity) did not differ from spontaneous Phase HI activity (P > 0.05). Although plasma motilin concentrations increased after threshold doses of both motilin and erythromycin, increases in plasma motilin occurred later after erythromycin (lOmin) than after exogenous motilin (3 min). Our findings suggest that motilin initiation of the migrating motor complex does not occur by independent stimulation of putative receptors in the gastric corpus or proximal antrum.