Comparison of the effectiveness of metoclopramide and dexamethasone in the prevention of cytostatic-induced vomiting

Efficiency of anti-emetic properties of metoclopramide and dexamethasone was compared. Both drugs were administered to 22 patients with newly diagnosed untreated previously Hodgkin's disease during ABVD therapy. Number of vomiting episodes, nausea intensity and everyday patients' activity on the day of cytostatics administration were evaluated. Metoclopramide prevented vomiting in 55% of patients while dexamethasone in 65%. This difference was statistically insignificant. Patients' everyday activity was statistically significantly more frequently normal in patients receiving dexamethasone in comparison with placebo and decreased in patients receiving metoclopramide. Therefore, patients preferred dexamethasone.     

Regulative effects of essential oil from Atractylodes lancea on delayed gastric emptying in stress-induced rats

Gastric motor dysfunction induced by psychological stress results in many symptoms of functional dyspepsia (FD). There are a number of herbal medicines that are reported to improve gastrointestinal motor. However, the mechanisms of considerable herbal medicines are not explicit. In the present study, the effects of an essential oil (EO) extracted from Atractylodes lancea on delayed gastric emptying, gastrointestinal hormone and hypothalamic corticotropin-releasing factor (CRF) abnormalities induced by restraint stress in rats were investigated and the mechanism of the EO is also explored.Oral administration of EO for 7 days did not affect normal gastric emptying, but accelerated delayed gastric emptying induced by restraint stress in rats. The EO significantly increased the levels of motilin (MTL) and gastrin (GAS) and decreased the levels of somatostatin (SS) and CRF. The EO did not modify gastric emptying in vagotomized rats that underwent restraint stress, but antagonized delayed gastric emptying induced by intracisternal injection of CRF. These results suggest that the regulative effects of the EO on delayed gastric emptying are preformed mainly via inhibition of the release of central CRF and activation of vagal pathway, which are also involved in the release of gastrointestinal hormones such as MTL, GAS and SS.     

Effect of pentagastrin on adrenocorticotropin hormone and thyroid-stimulating hormone release in normal subjects

The possible role of gastrin on TSH, ACTH and cortisol secretion was evaluated by intravenous administration of pentagastrin, the carboxyl-terminal tetrapeptide of gastrin (0.5 microgram/kg b.w.) into 12 healthy subjects. Pentagastrin produced a significant rise in plasma ACTH and cortisol levels but did not alter TSH basal release. These preliminary results suggest that gastrin can influence basal activity of ACTH-cortisol axis. However, further investigation is required to determine its physiological role and mechanisms of action.     

Effect of metoclopramide on adrenal secretion in sheep: influence of dexamethasone and sodium intake

Metoclopramide, a competitive dopamine antagonist, stimulates aldosterone in man and monkey without affecting cortisol secretion. In sheep, metoclopramide also stimulates aldosterone but ist action on adrenocortical secretion is more controversial. To clarify the action of metoclopramide in conscious sheep, the response of plasma aldosterone, cortisol, angiotensin II and potassium were studied after 0.16 and 0.64 mg/kg metoclopramide, with and without pretreatment with dexamethasone. The effect of sodium status on the response was also studied by repeating the experiments after 7 days of dietary sodium restriction. In the absence of dexamethasone, plasma aldosterone was significantly increased by metoclopramide in both sodium-replete and restricted sheep. In sodium-replete sheep, plasma cortisol was also increased by 0.64 mg/kg, and by both doses when salt-restricted. However all cortisol responses were completely suppressed by dexamethasone pretreatment. Dexamethasone also suppressed the aldosterone response to metoclopramide in sodium-replete but not in sodium-restricted sheep where significant responses of aldosterone to both doses of metoclopramide still occurred without changes in plasma angiotensin II or potassium. While a nonspecific stress effect of metoclopramide can contribute to the aldosterone response, these results show that the sheep's adrenal glomerulosa is capable of responding to metoclopramide without change in ACTH, angiotensin or potassium.     

Comparison of the antiemetics metoclopramide and promethazine in labour.

A double blind trial was conducted in 477 mothers in labour to compare the antiemetics metoclopramide 10 mg and promethazine 25 mg and placebo when added to the first dose of pethidine. Metoclopramide and promethazine were equally effective, and both better than placebo, in reducing the incidence of nausea and vomiting after the administration of pethidine. Seventy seven per cent of mothers were drowsy, and 8% slept in the hour after the pethidine injection, with no difference between the groups. The sedative effect was more persistent in the promethazine group, 66% of whom were still drowsy after delivery. One third of the mothers in each group needed further analgesia, with 77% of these ultimately requesting an epidural. The reduction in pain half an hour and one hour after pethidine, assessed by a visual analogue scale, were, respectively, 22% and 22% for placebo; 26% and 23% for metoclopramide; 13% and 9% for promethazine. Analgesia after metoclopramide was significantly better than that after promethazine in terms of pain score, duration of first injection, and need for Entonox. Metoclopramide is therefore to be preferred to promethazine as an antiemetic in labour.     

The distribution of endocrine cells in the mucosa of the gastrointestinal tract of the house musk shrew,Suncus murinus (Insectivora)

Summary The distribution of endocrine cells in the gastrointestinal tract of the house musk shrew, Suncus murinus (Family Soricidae, Order Insectivora) was studied immunohistochemically. The hormones investigated were gastrin, cholecystokinin (CCK), somatostatin, secretin, glucagon, gastric inhibitory polypeptide (GIP), motilin and neurotensin. In the gastric mucosa, gastrin and somatostatin cells were only found in the pyloric regions, and no other hormonal cell-types were observed. In the intestinal mucosa, the largest number of endocrine cells belonged to the gastrin and glucagon/glicentin cell-types, whereas CCK-33/39 and secretin cells were the least numerous. Numbers of other cell-types were intermediate between these two groups. The gastrin and GIP cells were mostly localized in the proximal portion of the intestine, decreasing in number towards the distal portion. The motilin and CCK-33/39 cells were restricted to the proximal half. The glucagon/glicentin and neurotensin cells were most abundant in the middle portion. The somatostatin and secretin cells, although only present in small numbers, were randomly distributed throughout the intestine. This characteristic distribution of gastrointestinal endocrine cells is discussed in comparison with the distribution patterns of other mammals.Dr. Munemitsu Hoshino, who was Professor of the Department of Pathology and directed this study, passed away on May 23rd 1988     

Motilin effects on the proximal stomach in patients with functional dyspepsia and healthy volunteers

This study investigates motilin effects on the proximal stomach in patients with functional dyspepsia (FD) and healthy volunteers. Eight healthy volunteers and 12 patients with FD were infused with synthetic motilin or placebo. Proximal gastric volume was measured with a barostat at constant pressure and during isobaric distensions. Abdominal symptoms were scored by visual analog scales. Plasma motilin concentrations were measured by radioimmunoassay. Motilin concentrations and baseline gastric volumes were similar for patients and healthy volunteers. Motilin, compared with placebo, reduced gastric volume by 112 ml [F(29,195); confidence interval (CI) 95%] in patients and by 96 ml [F(-7,200); CI 95%] in healthy volunteers. In patients, motilin decreased compliance by 76 ml/mmHg [F(9,143); CI 95%] compared with placebo, which was similar in volunteers [66 ml/mmHg; F(11,120); CI 95%]. Patients were more nauseous during motilin compared with placebo (P = 0.04), whereas healthy volunteers did not experience nausea. We conclude that in a fasted condition, FD patients have a similar proximal gastric motor response to motilin as healthy volunteers, but experience an exaggerated sensation of nausea.     

Dual effect of bombesin and gastrin releasing peptide on gastric emptying in conscious cats

The effect of bombesin (BBS) and gastrin releasing peptide (GRP) on gastric emptying was studied in conscious cats. This effect was measured simultaneously with antral motility. Acid and pepsin secretions as well as blood hormonal peptide release were additionally measured. A dual effect was observed. First, BBS and GRP slowed gastric emptying of liquids, while antral motility was decreased, then after 60 minutes of continuous intravenous infusion, antral motility returned to basal values and gastric emptying effect reversed. The mechanism of this peculiar action is independent of gastrin, pancreatic polypeptide, somatostatin and motilin release and most probably connected with a cholinergic stimulation induced by the peptides, the late predominance of which counterbalances the inhibitory effect of bombesin-like peptides on antral motility.     

Motilin release by intravenous infusion of nutrients and somatostatin in conscious dogs

to investigate the regulatory mechanism of motilin release, plasma motilin was measured by radioimmunoassay in healthy dogs during the fasting state and after intravenous administration of various nutrients and somatostatin. The fasting plasma motilin levels of these dogs were found to fluctuate intermittently. Intravenous glucose loading lowered plasma motilin, but immediately after the end of the glucose infusion as abrupt rise of plasma motilin was observed. Mixed amino acids administered intravenously abruptly inhibited motilin secretion, and plasma motilin levels remained low even 45 min after the end of the infusion. On the other hand, no remarkable change in plasma motilin was noted after the fat infusion. Following somatostatin infusion, plasma motilin was significantly decreased, remaining low even 30 min after the end of the infusion. These observations led us to conclude than motilin secretion is regulated by somatostatin and by nutrients coming through intravenous routes.     

磁场对急性胃损伤的治疗效应及其机制的实验研究

目的:探讨腹部磁场作用,对大鼠血液及胃粘膜组织中胃泌素(gastrin,GAS)、胃动素(motilin,MTL)和生长抑素(somatostain,SS),以及胃排空的效应。方法:10只Wistar健康雄性大鼠,腹部接受表面磁强度为1300-1600GS,钡铁氧体恒磁场作用3小时,以放射免疫法,分别测定大鼠血及胃粘膜组织中GAS、MLT及SS含量,用99mTc标记的碳粉糊剂灌胃法,测试胃排空率。结果:恒磁场腹部作用后,大鼠血GAS、MLT及SS水平较对照组,均无显著变化(p均>0.05);胃粘膜组织中,GAS含量无明显改变(p>0.05),MLT水平明显升高(p<0.01),SS水平明显降低(p<0.01);胃排空率无明显改变(p>0.05)。结论:腹部1300-1600GS恒磁场作用3小时,均不能显著调节大鼠血中MLT和SS,以及血和胃粘膜组织内GAS水平;可明显影响胃粘膜内MLT及SS水平;对大鼠胃排空率无明显效应。     

磁场对血浆和胃粘膜内胃肠激素及胃动力效应的实验研究

目的:探讨腹部恒磁场作用,对大鼠急性胃损伤模型的治疗效应及其作用机制。方法:10只健康SD大鼠,以indomethacin胃灌注法复制急性胃损伤模型,以表面磁强度为1300-1600GS,钡铁氧体恒磁场作用大鼠腹部3小时,观察胃损伤指数及病理损伤积分,同时对血浆中内皮素(endothelin,ET)、一氧化氮(nitricoxide,NO)、谷胱甘肽过氧化物酶(GSH-Px)及超氧化物岐化酶(SOD)水平进行比较。结果:恒磁场腹部作用后,大鼠胃损伤指数及病理损伤积分较对照组均显著减轻(p均<0.05);血浆ET-1和NO水平却无无明显改变(p均>0.05),血GSH-Px和SOD含量较对照组均明显升高(p均<0.05)。结论:腹部1300-1600GS恒磁场作用3小时,对大鼠急性胃损伤具有明显的治疗效应,磁场的这一效应可能与其增加血浆中清除氧自由基的GSH-Px和SOD活性有关。     

Rate dependent stimulation of insulin and glucagon but not gastrin and somatostatin release during the intestinal phase of a meal

Previous studies have indicated a possible influence of gastric emptying on postprandial pancreatic endocrine function and the present study was designed to determine if the rate at which nutrients enter the small intestine may play a role in the postprandial regulation of insulin, glucagon, somatostatin and gastrin release in conscious dogs. In response to an intraduodenal instillation of a liver extract--sucrose test meal postprandial insulin and glucagon levels increased significantly with increasing infusion rates of the test meal, whereas somatostatin and gastrin levels did not change. The rise of the endocrine factors preceded any increase of peripheral vein plasma glucose levels. The present data demonstrate that during the intestinal phase of a meal the rate of nutrient entry into the duodenum favours insulin and glucagon but not somatostatin and gastrin release. This mechanism could be of importance in the regulation of nutrient homeostasis during the ingestion of certain carbohydrate containing meals.     

Stress-induced reduction of gastric acid in the rat is not associated with increased tissue somatostatin

In zero, mildly and severely stressed rats, gastric acid secretion, aortal and portal venous gastrin, venous glucagon and somatostatin in gastric, duodenal mucosa and in pancreas were examined. Serum gastrin and gastric acid secretion are reduced markedly by both kinds of stress, whereas plasma glucagon rises steadily with stress. As somatostatin in the tissues of stressed rats is not different from unstressed controls, gastrin and gastric acid reduction may not be attributed to an endocrine or paracrine action of somatostatin.     

Influence of acute exposure to high altitude on Basal and postprandial plasma levels of gastroenteropancreatic peptides

Acute mountain sickness (AMS) is characterized by headache often accompanied by gastrointestinal complaints that vary from anorexia through nausea to vomiting. The aim of this study was to investigate the influence of high altitude on plasma levels of gastroenteropancreatic (GEP) peptides and their association to AMS symptoms. Plasma levels of 6 GEP peptides were measured by radioimmunoassay in 11 subjects at 490 m (Munich, Germany) and, after rapid passive ascent to 3454 m (Jungfraujoch, Switzerland), over the course of three days. In a second study (n = 5), the same peptides and ghrelin were measured in subjects who consumed standardized liquid meals at these two elevations. AMS symptoms and oxygen saturation were monitored. In the first study, both fasting (morning 8 a.m.) and stimulated (evening 8 p.m.) plasma levels of pancreatic polypeptide (PP) and cholecystokinin (CCK) were significantly lower at high altitude as compared to baseline, whereas gastrin and motilin concentrations were significantly increased. Fasting plasma neurotensin was significantly enhanced whereas stimulated levels were reduced. Both fasting and stimulated plasma motilin levels correlated with gastrointestinal symptom severity (r = 0.294, p = 0.05, and r = 0.41, p = 0.006, respectively). Mean O₂-saturation dropped from 96% to 88% at high altitude. In the second study, meal-stimulated integrated ( = area under curve) plasma CCK, PP, and neurotensin values were significantly suppressed at high altitude, whereas integrated levels of gastrin were increased and integrated VIP and ghrelin levels were unchanged. In summary, our data show that acute exposure to a hypobaric hypoxic environment causes significant changes in fasting and stimulated plasma levels of GEP peptides over consecutive days and after a standardized meal. The changes of peptide levels were not uniform. Based on the inhibition of PP and neurotensin release a reduction of the cholinergic tone can be postulated.     

Cholecystokinin, gastrin and stress hormone responses in marathon runners.

The purpose of this investigation was to determine the influence of long-distance running on the secretion of the gastrointestinal peptide hormones cholecystokinin (CCK) and gastrin. Several known stress hormones, ACTH, cortisol and norepinephrine, were also measured. The hormones were estimated before and after a competitive marathon run of 46.5 km and under control conditions a few weeks later. Except gastrin, all hormones were significantly higher under prerun conditions than under control conditions and were highest after the run. The most marked prerun elevation was in CCK. Therefore, CCK seems to be an important regulation factor in response to anticipatory stress.     

Dopaminergic control of aldosterone secretion in hypertensive patients chronically treated with an angiotensin converting enzyme inhibitor

To investigate whether dopamine plays a role in the regulation of aldosterone secretion during long-term blockade of the renin-angiotensin system, we studied the effect of metoclopramide, a competitive antagonist of dopamine, in 6 patients with essential hypertension chronically treated with the angiotensin converting enzyme inhibitor enalapril. All but one of these patients received a diuretic in addition to enalapril. Six hours after the daily morning dose of enalapril (10-40 mg p.o.) a 10 mg bolus dose of metoclopramide was injected intravenously. In one patient a hypotensive episode developed following metoclopramide administration. In the 5 other patients plasma aldosterone significantly rose within 30 min after metoclopramide from 51 +/- 8.7 to 128.2 +/- 29.2 pg/ml. This metoclopramide-induced release of aldosterone occurred in the absence of concomitant changes in circulating angiotensin 11, potassium and ACTH levels. Metoclopramide given during chronic blockade of the renin-angiotensin system caused anxiety and agitation in 2 patients. The increase in plasma aldosterone following competitive dopamine blockade in the face of chronic angiotensin converting enzyme inhibition, unchanged plasma potassium and ACTH levels strongly suggests that in hypertensive patients, dopamine exerts a direct inhibitory effect on aldosterone secretion.     

Effect of oral CCK-1 agonist GI181771X on fasting and postprandial gastric functions in healthy volunteers

CCK influences satiation and gastric and gallbladder emptying. GI181771X is a novel oral CCK-1 agonist; its effects on gastric emptying of solids, accommodation, and postprandial symptoms are unclear. Effects of four dose levels of the oral CCK-1 agonist GI181771X and placebo on gastric functions and postprandial symptoms were compared in 61 healthy men and women in a randomized, gender-stratified, double-blind, double-dummy placebo-controlled, parallel group study. Effects of 0.1, 0.5, and 1.5 mg of oral solution and a 5.0-mg tablet of GI181771X on gastric emptying of solids by scintigraphy, gastric volume by (99m)Tc-single photon emission computed tomographic imaging, maximum tolerated volume of Ensure, and postprandial nausea, bloating, fullness, and pain were studied. On each of 3 study days, participants received their randomly assigned treatment. Adverse effects and safety were monitored. There were overall group effects of GI181771X on gastric emptying (P < 0.01) and fasting and postprandial volumes (P = 0.036 and 0.015, respectively). The 1.5-mg oral solution of GI181771X significantly delayed gastric emptying of solids (P < 0.01) and increased fasting (P = 0.035) gastric volumes without altering postprandial (P = 0.056) gastric volumes or postprandial symptoms relative to placebo. The effect of the 5.0-mg tablet on gastric emptying of solids did not reach significance (P = 0.052). Pharmacokinetic profiles showed the highest area under the curve over 4 h for the 1.5-mg solution and a similar area under the curve for the 0.5-mg solution and 5-mg tablet. Adverse effects were predominantly gastrointestinal and occurred in a minority of participants. GI181771X delays gastric emptying of solids and exhibits an acceptable safety profile in healthy participants. CCK-1 receptors can be modulated to increase fasting gastric volume.     

Prevention and treatment of the gastric symptoms of radiation sickness

Currently available treatments for radiation-induced nausea and vomiting either are ineffective or reduce performance. The new antiemetic and gastrokinetic agent zacopride was tested in rhesus monkeys to assess its behavioral toxicity and its ability to inhibit radiation-induced emesis. Zacopride (intragastric, 0.3 mg/kg) or a placebo was given blindly and randomly in the basal state and 15 min before a whole-body 800 cGy 60Co gamma-radiation dose (except for the legs which were partially protected to permit survival of some bone marrow). We determined (1) gastric emptying rates; (2) the presence and frequency of retching and vomiting; and (3) the effect of zacopride on the performance of a visual discrimination task in nonirradiated subjects. No vomiting, retching, or decreased performance was observed after either placebo or zacopride in the control state. Following irradiation plus placebo, 70 emeses were observed in 5 of 6 monkeys, and 353 retches were observed in all 6 monkeys. In contrast, only 1 emesis was observed in 1 of 6 monkeys and 173 retches were seen in 4 of 6 monkeys after irradiation plus zacopride (P less than 0.01). Zacopride also significantly inhibited radiation-induced suppression of gastric emptying. When given after the first vomiting episode in a separate group of irradiated monkeys, zacopride completely prevented any subsequent vomiting. The present results demonstrate that intragastric administration of zacopride significantly inhibited radiation-induced retching, vomiting, and suppression of gastric emptying in rhesus monkeys and did not cause detectable behavioral side effects when given to nonradiated monkeys. This observation has important implications in the treatment of radiation sickness.     

Relationship between increasing duodenal lipid doses, gastric perception, and plasma hormone levels in humans

Duodenal lipid causes gastric relaxation, CCK secretion, and nausea. Vasopressin has been implicated in motion sickness-related nausea. We hypothesized that increasing doses of lipid enhance gastric relaxation and CCK-vasopressin secretion, resulting in a dose-related exacerbation of nausea. Nine healthy subjects received isotonic saline or lipid (1, 2, or 3 kcal/min, L1, L2, L3) duodenally. Changes in gastric volume, sensations, and plasma hormone levels were assessed during infusions and isobaric gastric distensions. Lipid infusions increased gastric volume, plasma CCK (but not vasopressin) levels, and gastric compliance during distensions, compared with saline. Plasma CCK levels were related to the dose of lipid administered [CCK levels at 30 min (pmol/l), saline: 1.1 +/- 0.2, L1: 1.8 +/- 0.2, L2: 3.0 +/- 0.2, L3: 4.3 +/- 0.6]. During distensions, nausea increased in intensity with increasing doses of lipid [score (where 0 is no sensation and 100 is strongest sensation), saline: 7 +/- 4, L1: 19 +/- 7, L2: 44 +/- 7, L3: 66 +/- 8]; however, no further rise in plasma CCK occurred. Because neither lipid nor distension alone induced significant nausea, we conclude that the interaction between these stimuli together with a modulation by CCK is responsible for the effects observed. Vasopressin is not involved in lipid- and distension-induced nausea.     

Effects of a long-acting somatostatin analogue on pituitary-adrenocortical secretion in normal human subjects

A potent and long-acting somatostatin analogue, SMS 201-995 (SMS) is currently employed for the treatment of various diseases with hypersecretion of hormones such as acromegaly and gastrinoma. The suppressive effects of SMS are also reported on the other pituitary and gastrointestinal hormones. The corticotropic-adrenocortical axis is a crucial hormonal complex in maintaining normal activity and life itself. In this study, the effects of SMS on corticotropic-adrenocortical functions were studied, since the effects of SMS on this hormonal axis are not well established. Seven normal males received a sc injection of 100 micrograms SMS or placebo at 0830 h and 100 micrograms synthetic human corticotropin-releasing hormone (hCRH) intravenously (SMS-hCRH study). Five of the 7 subjects were given an injection of a synthetic (1-24) ACTH (250 micrograms or 63 micrograms) at 0900 h after 100 micrograms SMS or a placebo at 0830 h (SMS-ACTH study). Blood samples were drawn at -30, 0, 15, 30, 60, 90 and 120 min after the hCRH injection for the determination of ACTH and cortisol in the SMS-hCRH study, and cortisol and aldosterone in the SMS-ACTH study. Although significant rises in plasma ACTH and cortisol levels were observed regardless of the preinjection of SMS, their responses to hCRH were significantly lower with the pretreatment with SMS than without SMS. A significant increase in plasma cortisol and aldosterone was observed in response to synthetic ACTH with both ACTH alone and the combined administration of SMS and ACTH, at either dose of ACTH. However, no significant difference in cortisol and aldosterone secretion was detected with and without SMS.(ABSTRACT TRUNCATED AT 250 WORDS)