Effect of nitrendipine on the function of the upper gastrointestinal tract

A double-blind crossover-trial comparing the influence of orally administered nitrendipine and placebo on the function of the upper gastrointestinal tract was carried out in ten healthy volunteers. Esophageal motility, intestinal transit time, size and motility of the gallbladder, serum gastrin levels and gastric secretion (basal and after stimulation with pentagastrin) were determined. No statistically significant differences between nitrendipine and placebo could be observed. Most parameters remained unchanged in both groups. Serum gastrin levels slightly increased after nitrendipine but did not exceed the normal range. The results demonstrate that nitrendipine given in an antihypertensive dosage, in contrast to other calcium antagonists, does not influence the function of the upper gastrointestinal tract.     

重型颅脑损伤患者血清及脑脊液胃泌素水平测定及其意义

目的探讨重型颅脑损伤患者血清及脑脊液胃泌素水平与颅脑损伤程度及其与消化道出血的关系,探讨血清与脑脊液胃泌素含量的相关性。方法对71例重型颅脑损伤患者,根据伤后是否合并消化道出血分为出血组及无出血组,用放射免疫法分别于入院时及第3、7、14天测定血清及脑脊液胃泌素含量并与正常对照组进行比较。结果重型颅脑损伤早期血清胃泌素含量均明显．高于正常对照组（P〈0．01）;3～7d达高峰,伤后1周内有、无出血组间差异显著（P〈0．01）;随着病情好转,血清胃泌素值逐渐下降,伤后2周,出血组血清胃泌素水平明显高于无出血组（P〈0．01）。脑脊液胃泌素不能检出。结论血清胃泌素水平与颅脑损伤程度及消化道出血呈正相关,脑脊液胃泌素水平测定与颅脑损伤程度及消化道出血无相关性,血清与脑脊液胃泌素含量无相关性,早期动态观察血清胃泌素含量变化对判断病情及预后有重要意义。     

The effect of cholecystokinin-pancreozymin on circulating gastrin levels in man and dog.

Perfusion of the jejunum with a mixture of amino acids (MAA) stimulates cholecystokinin-pancreozymin (CCK) release in man. Since gastrin is normally found in the small intestine, studies were conducted to determine if MAA perfusion had an effect on circulating serum gastrin levels in man. In man, endogenous stimulation of CCK had no effect on gastrin release; however, when CCK was given exogenously (10% pure form), serum gastrin levels were significantly increased. In dogs, the 10% pure CCK given exogenously also significantly increased gastrin concentrations, while the pure CCK octapeptide did not. Cross-reactivity between CCK and the gastrin antibody was minimal and could not be shown to be responsible for the serum gastrin elevations. Neither the physiological release of CCK in humans nor exogenous administration of CCK octapeptide in dogs at a dose equivalent to maximal stimulation of pancreatic secretion in humans significantly altered peripheral venous serum levels of immunoreactive gastrin. Therefore, we conclude that the gastrinemic response of exogenous CCK (10% pure) in man and dog is probably due to an impurity in the CCK preparation; when studying the effects of CCK on the gastrointestinal tract, only the pure CCK or the octapeptide should be used.     

胃肠激素检测在小于胎龄儿变化中临床意义

应用放射免疫法对68例小于胎龄儿(其中早产36例;足月32例)生后喂奶前及第7日空腹血中生长抑素(soma-tostatin,SS)、胃动素(motilin,MOT)、胃泌素(gastrin,Gas)浓度进行测定,并以30例足月新生儿作为对照组。结果小于胎龄儿组生后喂奶前及第7日空腹血浆胃动素、胃泌素均明显低于对照组,而生长抑素浓度明显高于对照组.并且与胎龄、开始喂养时间及当日进奶等因素相关。结论小于胎龄儿消化道机能适应胃肠道营养,在严密观察下应用合理的喂养方式早日开始胃肠道营养,将能促进小于胎龄儿胃肠道的发育和成熟。     

Autoimmune atrophic gastritis with hypergastrinemia.

Elevation in fasting serum gastrin levels was found in three patients being evaluated for persistent upper abdominal pain without radiographic evidence of peptic ulcer disease. Fiberoptic endoscopy of the upper gastrointestinal tract in each patient revealed characteristic changes of chronic atrophic gastritis. Gastric biopsies showed diffuse chronic inflammation in the lamina propria, a decrease in the number of parietal cells, and "intestinalization" of gastric mucosa. Total achlorhydria was demonstrated after a maximal histalog stimulus; however, serum levels of vitamin B12 and Schilling test values were normal in all three patients. Parietal cell antibodies were found in the serum in all patients in a dilution of 1:20 to 1:80. These cases represent autoimmune (type A) chronic atrophic gastritis and should be distinguished from chronic simple (type B) gastritis, in which serum gastrin levels are normal and no parietal cell antibodies are found in the serum. Patients with autoimmune gastritis should be observed at frequent intervals for the occurrence of pernicious anemia or gastric carcinoma.     

Processing and proliferative effects of human progastrin in transgenic mice.

Incompletely processed gastrins have been postulated to play a role in growth of the gastrointestinal tract, but few studies have examined the effects of progastrin on mucosal proliferation in vivo. Human gastrin gene expression and progastrin processing were therefore studied in transgenic mice containing a human gastrin (hGAS) minigene, and compared to processing in mice bearing an insulin gastrin (INS-GAS) transgene that overexpresses amidated gastrin. Progastrin processing was studied using region-specific antisera and radioimmunoassays, biosynthetic labeling, immunoprecipitation, and HPLC. Proliferative effects due to overexpression of processed and unprocessed gastrin in INS-GAS and hGAS mice, respectively, were determined using routine histology and BrdU incorporation. The pancreatic islets of INS-GAS mice were able to produce carboxyamidated G-17, resulting in a twofold elevation of serum amidated gastrin, marked thickening of the oxyntic mucosa, and an increased BrdU labeling index (LI) of the gastric body. In contrast, livers of adult hGAS mice expressed abundant human gastrin mRNA and human progastrin but were unable to process this peptide to the mature amidated form, resulting in markedly elevated serum progastrin levels and normal amidated gastrin levels. Nevertheless, there was a marked increase in the BrdU labeling index of the colon in hGAS mice (LI 7.46+/-1.90%), as well as in INS-GAS mice (LI 6.16+/-1.17%), compared to age-matched, wild type control mice (LI 4.01+/-0.98%, P < 0.05). These studies suggest that incompletely processed gastrin precursors may contribute to colonic mucosal proliferation in vivo.     

Circulating gastrin and ghrelin levels in patients with colorectal cancer: correlation with tumour stage, Helicobacter pylori infection and BMI.

Many studies have pointed out a possible role of gut peptides, including gastrin and ghrelin, in the pathogenesis and natural history of gastrointestinal malignancies, one of the most common death cause in the Western world. The objective of this work is to check gastrin and ghrelin serum levels in patients with colorectal cancer according to tumour's location, stage, Helicobacter pylori infection and BMI, in order to understand the two peptides' behaviour through the tumour's natural history and evaluate their assay's use in research and clinical practice. Twenty-nine subjects affected by colorectal cancer and 50 healthy controls were studied. Circulating gastrin and ghrelin levels and H. pylori serum antibodies were assessed by radioimmunologic assay and ELISA method. Gastrin and ghrelin serum levels were respectively slightly higher and significantly lower in colon cancer patients than in controls. Gastrin levels were higher in patients carrying left colon cancer and H. pylori infection while ghrelin levels were lower in both these groups. Both hormones' serum levels decreased from tumour earlier to later stages. Significant differences persisted in the correlation between BMI and ghrelin levels in controls but not in patients. Additional studies are necessary to ascertain the significance of gastrin and ghrelin opposite behaviour in colon cancer probably linked with interferences in endocrine pathways involving other gut peptides in this compromised condition.     

食管空肠Roux-en-Y吻合与间置空肠代胃在胃癌根治术后的应用效果比较

目的比较食管空肠Roux-en-Y吻合与间置空肠代胃在胃癌根治术后的应用效果及对患者消化道功能恢复的影响。方法将63例早期近端胃癌患者根据吻合方法不同分为A组(n=33)和B组(n=30)。A组给予根治性近端全胃切除+食管空肠Roux-en-Y吻合术,B组给予根治性近端胃大部切除+食管残胃间置空肠代胃治疗。比较两组的手术指标、术后胃肠功能恢复指标、营养状况、血清胃肠激素水平、胃肠道症状评分和并发症发生情况。结果B组的手术时间长于A组,消化道重建时间、肠鸣音恢复时间、肛门排气时间、术后首次进流食时间、住院时间均短于A组,术中出血量少于A组,淋巴结清扫数目多于A组(P<0.05)。术后10 d,两组的血红蛋白、总蛋白、血清胃泌素、胃动素水平均低于术前,但B组高于A组(P<0.05);术后半年,两组的血红蛋白、总蛋白水平高于术后10 d,血清胃泌素、胃动素水平低于术后10 d,但B组均高于A组(P<0.05)。术后3、6个月,两组的胃肠道症状评分均低于术前,且B组低于A组(P<0.05)。两组的并发症总发生率无显著差异(P>0.05)。结论根治性近端胃大部切除+食管残胃间置空肠代胃治疗胃癌患者,可明显改善消化道功能,提高术后营养状况,且对胃肠激素水平影响较小。     

小于胎龄儿血中胃肠激素水平对其胃肠道营养影响的研究

目的探讨小于胎龄儿生后血中胃肠激素水平变化及其对胃肠道营养的影响。方法应用放射免疫法监测118例小于胎龄儿（其中早产62例;足月52例）生后喂奶前及第7日胃动素（MOT）、胃泌素（GAS）浓度,并与85例正常足月新生儿作为对照组。结果①小于胎龄儿组生后喂奶前及第7d空腹血浆MOT、GAS均明显低于对照组;但随胎龄、日龄、奶量增加而升高,呈正相关;第7d时已超过足月儿对照组生后开奶前水平;②喂养不耐受组小于胎龄儿生后空腹血中MOT、GAS浓度均较喂养正常组低;③早期喂养能改善小于胎龄儿MOT水平和胃肠道动力,提高肠道喂养的耐受性。结论小于胎龄儿消化道机能适应胃肠道营养,在严密观察下早期喂养,将能促进小于胎龄儿胃肠道的发育和成熟。     

CEA、GT、MG、EGF 对消化道肿瘤诊断价值的比较

为评价癌胚抗原（ＣＥＡ）、胃泌素（ＧＴ）、胃癌ＭＧ抗原（ＭＧ）、人上皮细胞生长因子（ＥＧＦ）等单独测定及联合检测对消化道肿瘤的诊断价值，用放射免疫法对２５例消化道良性疾病及３９例消化道肿瘤病人测定血清ＣＥＡ、ＧＴ、ＭＧ、ＥＧＦ，并对１３例肿瘤病人手术前、后的这４项指标进行了对比。结果消化道肿瘤病人的血清ＣＥＡ、ＧＴ、ＭＧ、ＥＧＦ水平，均明显高于消化道良性疾病；消化道肿瘤病人手术后这４项指标均较手术前明显降低；单独检测各项指标时其灵敏度、诊断正确率均以ＣＥＡ为最高；ＣＥＡ与其它指标分别二项联合检测可提高灵敏度和诊断正确率，以ＣＥＡ与ＧＴ联合检测的灵敏度、诊断正确率最高。认为ＣＥＡ、ＧＴ、ＭＧ、ＥＧＦ对消化道肿瘤均有一定诊断价值，并可作为动态观察、判断疗效及预后的参考指标，ＣＥＡ与其它指标联合检测可提高灵敏度和诊断正确率。     

CCK-B/gastrin receptors in human colorectal cancer

BACKGROUND: Mature amidated gastrin (G17 amide) mediates its effects in the gastrointestinal tract by activating G protein-coupled CCK-B/gastrin receptors. Although trophic actions of gastrin on the gastric mucosa have been well-established, the effect of G17 amide, progastrin and intermediates to colon neoplasia in humans is controversial. While epidemiological evidence from patients with elevated serum gastrin levels related to pernicious anaemia does not support an increased risk for colon cancer, a recent study suggests that prolonged hypergastrinaemia is associated with an increased risk for colon cancer. The extent to which trophic actions of gastrin in colorectal cancer are mediated by functional gastrin receptors remains to be defined. The aim of the present study was to determine CCK-B/gastrin receptor expression, structure, and function in 79 patients with colon cancer. MATERIALS AND METHODS: CCK-B/gastrin receptor cDNAs were isolated from 79 human colorectal cancer specimens and 15 control tissues, subcloned into the eukaryotic expression vector pCR3.1 and subjected to DNA sequence analysis. Wild-type and mutant cDNAs were transiently expressed in COS-7 cells to determine ligand affinities by 125I-labelled CCK-8S competition binding. Activation of the MAP kinase signalling cascade by G17 amide was determined in transfected Colo 320 cells expressing the wild-type or mutant CCK-B/gastrin receptors. Clonal expansion of single cells was quantified in transfected Colo 320 cells. RESULTS: Gastrin mRNA is expressed in 44% of colorectal cancers and in 13% of control tissues. CCK-B/gastrin receptor mRNA is expressed in 38% of colorectal cancers and 13% of normal colonic tissue. Co-expression of gastrin and CCK-B/gastrin receptor message is significantly increased in colorectal cancer specimens (32% vs. 0%). There is no correlation between CCK-B/gastrin receptor expression and disease stage or histological grading. DNA sequence analysis revealed one spontaneous CCK-B/gastrin receptor mutation within the third intracellular loop with an exchange of valine-287 for phenylalanine. Pharmacological characterisation of the 287V --> F CCK-B/gastrin receptor reveals wild-type affinities for G17 amide, glycine-extended gastrin, CCK-8S and L-365,260. Mutation 287V --> F is associated with a loss of gastrin-induced MAPK p44/p42 signalling in Colo 320 cells while clonal expansion from single cells is increased by 53.1 +/- 15.9% when compared to Colo 320 cells expressing wild-type CCK-B/gastrin receptors. CONCLUSIONS: Structural alterations of CCK-B/gastrin receptors may account for increased growth-promoting effects of amidated gastrins in colorectal cancer.     

胃肠道手术患者氧化应激反应对胃肠道功能恢复、切口愈合的影响及相关机制

目的 探讨胃肠道手术患者氧化应激反应对胃肠道功能恢复、切口愈合的影响及相关机制.方法 选取2018年8月至2019年8月在广西中医药大学第一附属医院外科行胃肠道手术的患者137例为手术组,另选取73例健康体检者为对照组.检测两组血清活性氧自由基(ROS)、D-乳酸、内毒素水平.比较手术组术前与对照组,以及术后不同胃肠道...     

Serum levels of gastric-acid-stimulating factors in children undergoing open heart surgery

Purpose  Upper gastrointestinal (GI) bleeding is a feared consequence of open heart surgery in children. Increased gastric acid secretion is a known key factor in the pathogenesis of gastritis and upper intestinal ulcerations. The aim of this study is to evaluate the serum kinetics of acid-stimulating factors and associated perioperative parameters after heart surgery in children. Methods  Fifteen pediatric patients after open heart surgery and 15 children with cardiac catheterization were included in this study. Serum levels of gastrin, histidine, alanine, and tryptophan were analyzed before and up to 26 h after surgery. Results  In the postoperative period there was a significant elevation of gastrin with a peak at 4 h after surgery. Serum histidine was increased significantly immediately after surgery only in patients undergoing heart surgery with cardioplegia. No association of gastrin and histidine elevation with ischemia, perfusion time or lactate was observed. Conclusion  Factors that are responsible for postoperative gastrin elevation still have to be determined. Circumstances of extracorporeal circulation (ECC) in low-risk patients most likely do not lead to relevant elevation of amino acids with acid-stimulatory effect in our study population.     

Is there a feed-back mechanism between serum gastrin concentration and gastrin release (author's transl)]

The dialysability of gastrin heptadecapeptide was investigated in a model arrangement. The amounts of gastrin passing through the dialysis membrane during a 6-hour dialysis procedure are very small. Furthermore, the serum gastrin concentrations were measured during a 6-hour haemodialysis session with and without simultaneous pentagastrin infusion (0.003 mug/kg/h) in 8 patients on intermittent haemodialysis. There is a continuous decrease in the serum gastrin concentration during the 6-hour dialysis period with simultaneous pentagastrin infusion, while in the investigation without pentagastrin infusion phases of increase in serum gastrin levels are observed. In view of this different response of the serum gastrin curve it is suggested that a direct feed-back mechanism exists between the serum gastrin concentration and gastrin release, a mechanism which was interrupted by the pentagastrin infusion in the present investigation.     

Patterns of immunoreactive trypsin in serum from patients with acute abdominal disorders

Immunoreactive trypsin in serum can be divided into trypsinogen and trypsin-alpha 1-proteinase inhibitor (alpha 1PI) complexes. These were studied separately in serum from 204 patients with acute gastro-intestinal symptoms. Elevated levels of both trypsinogen and trypsin-alpha 1PI complexes were seen in patients with acute pancreatitis. Elevated levels of trypsinogen and normal or slightly elevated levels of trypsin-alpha 1PI complexes were seen in patients with biliary tract diseases. An isolated increase in the concentration of trypsin-alpha 1PI complexes with normal trypsinogen and amylase levels were seen in patients with perforated ulcer. This third cluster may result from an absorption of active trypsin from the peritoneal cavity. Small amounts of trypsin-alpha 1PI complexes were present also in serum from patients free from pancreatic disease. The results in this study show that high levels of trypsin-alpha 1PI complexes in serum are seen mainly in patients with acute pancreatitis. However, elevated levels are also seen in other pathological conditions in the upper gastrointestinal tract; therefore an assay for these complexes is not a specific diagnostic test for acute pancreatitis.     

Is GastroPanel serum assay useful in the diagnosis of Helicobacter pylori infection and associated gastritis in children?

GastroPanel (Biohit, Helsinki, Finland) is a serum test kit that measures Helicobacter pylori antibodies (HPABs) and pepsinogens I and II and gastrin 17, which reflect the degree of atrophic gastritis. We assessed whether GastroPanel can replace endoscopic biopsies in the diagnostics of H. pylori in children and whether the H. pylori-infected children show markers for atrophic gastritis. Eighty children (median age, 6.8 years; range, 0.6-18.7 years) underwent gastroscopy for H. pylori-related abdominal complaints (n = 40), surveillance after surgery for gastrointestinal tract malformations (n = 20), gastroesophageal reflux (GER) (n = 10), and miscellaneous diseases (n = 10). Gastric biopsies and a serum sample were obtained from all 80 children. HPAB levels of 38 and 15 IU were tested as cutoff values for H. pylori gastritis. The biopsies showed H. pylori-positive gastritis in 30 children, 9 had gastritis not associated with H. pylori, and 41 had normal biopsies. Atrophic gastritis was not found. The sensitivity and specificity of HPAB for H. pylori were 47% and 98% (cutoff, 38 IU), and 73% and 85% (cutoff, 15 IU), respectively. The assays of pepsinogens and gastrin did not improve sensitivity. None of the markers of pepsinogen (PG) I, PGII, and gastrin 17 (G17) indicated atrophic gastritis. GastroPanel is too insensitive for H. pylori screening and does not replace endoscopy. Markers indicative of atrophic gastritis were negative in all children with H. pylori gastritis.     

Ratio between serum IL-8 and pepsinogen A/C: a marker for atrophic body gastritis

BACKGROUND AND AIMS: Elevated serum gastrin and a low pepsinogen A/C ratio are well-recognized markers for atrophic body gastritis (ABG). We have shown that the presence of body atrophy is also associated with elevated serum pro-inflammatory cytokines. This study tested the hypothesis that serum cytokines provide additional information to gastrin and pepsinogens in screening for ABG. METHODS: Two hundred and twenty-six consecutive patients were investigated on referral for upper gastrointestinal endoscopy: 150 were patients with gastro-oesophageal reflux disease, receiving acid inhibitory medication either with proton pump inhibitors (n = 113) or with histamine2-receptor antagonists (n = 37), and 76 were nontreated controls, who had normal endoscopic findings. Gastric mucosal biopsies were sampled for histological examination (Sydney classification). Serum samples were analyzed for gastrin, chromogranin A (CgA), and pepsinogens A and C by RIA, and for the interleukins (IL)-1beta, IL-6, and IL-8 by ELISA. RESULTS: Subjects with ABG had significantly higher serum gastrin (P < 0.01) and serum CgA (P < 0.01) levels and significantly lower pepsinogen A/C ratios (P < 0.001) than those without ABG. Additionally, serum IL-1beta, IL-6 and, especially, IL-8 levels were significantly higher in the subjects with than in those without ABG (P < 0.0001, for all cytokines). To optimize the detection of body atrophy we defined the ABG index: the ratio between the simultaneously measured IL-8 and pepsinogen A/C. The area under the ROC curve for the ABG index was significantly greater than that for serum gastrin and for serum pepsinogen A/C alone (0.91 +/- 0.029 vs. 0.72 +/- 0.042, and vs. 0.83 +/- 0.031, P = 0.018 and P = 0.049). Using the ABG index at a cut-off value of 1.8 pg mL-1, 91% of the cases were classified correctly. CONCLUSIONS: The ratio between serum IL-8 and pepsinogen A/C accurately predicts the presence of ABG. We therefore propose the ABG index as a noninvasive screening test for ABG in population-based studies.     

Specificity of commercially available antibodies used for gastrin measurement

We examined the specificity of commercially available antibodies used in measurement of serum gastrin. Antibodies were obtained from five commercial laboratories, and antibody immunoreactivity with gastrin and cross-reactivity with cholecystokinin (CCK) were determined. All antibodies were equally immunoreactive with gastrin, and cross-reactivity of three antibodies with CCK was minimal (less than 5%). In contrast, substantial cross-reactivity with CCK was found with two antibodies. To determine the clinical significance of cross-reactivity with CCK, secretin injection tests were performed in 24 individuals: seven in normal health, four with Zollinger-Ellison syndrome, three with antral gastrin cell hyperfunction, six with ordinary duodenal ulcer disease, and four with atrophic gastritis. Serum gastrin levels were measured with all five gastrin antibodies. The response to secretin was negative in all normal subjects and in those with duodenal ulcer and antral gastrin cell hyperfunction. The response to secretin was positive in all four patients with gastrinoma with use of the five antisera. All four patients with atrophic gastritis had normal responses to secretin when antibodies with minimal CCK cross-reactivity were used; however, two of four had false positive secretin test results when serum gastrin levels were measured with the two antibodies with a high degree of cross-reactivity with CCK. These studies indicate that significant cross-reactivity of gastrin antibodies with CCK can result in false positive secretin injection test results and can lead potentially to the erroneous diagnosis of Zollinger-Ellison syndrome.     

危重病患者血清胃泌素测定的临床意义

报告８个病种３２５例危重病患者血清胃泌素的测定结果并与５８例正常人对比。结果表明：危重病患者不管是否伴有消化道出血，其血清胃泌素均有意义地升高（Ｐ＜０．００１）。说明危重病患者有高胃泌素血症存在。并与消化道出血和ｐＨ值降低可能有一定关系。提示在危重病治疗时，不管是否有消化道出血，及早应用抑制胃泌素分泌的药物对保护胃粘膜，预防消化道出血可能有一定益处。     

大鼠脑出血时胃肠局部生长抑素的表达

背景:有关脑-胃肠综合征的研究国内外多从临床应激性消化道出血角度来探讨,缺乏相关实验理论依据。目的:观察脑出血血肿高峰阶段,胃肠局部生长抑素通过旁分泌机制,对胃黏膜组织中胃泌素的调节作用,阐明脑出血时脑-胃肠综合征的发生与胃肠局部脑肠肽平衡失调的内在联系。设计:随机对照的实验研究。地点和对象:实验地点:解放军第三军医大学大坪医院动物实验中心,动物采用Wistar大鼠40只。干预:建立大鼠脑出血动物模型,应用原位杂交技术分析胃肠局部表达生长抑素mRNA的阳性细胞变化,同期测定胃黏膜组织中胃泌素的含量,并与表达生长抑素mRNA阳性细胞计数值进行相关分析。主要观察指标:生长抑素mRNA的表达及胃泌素的活性测定。结果:脑出血的高峰期,胃肠局部生长抑素mRNA表达明显增强。与此同时,相同部位组织中胃泌素的含量明显升高,两者之间呈现显著的正相关(r=0.36;P<0.05)。结论:脑出血血肿形成的高峰期,通过上调生长抑素mRNA的表达和抑制胃泌素的产生,预防脑胃肠综合征的发生。