Video Imaging and Spatiotemporal Maps to Analyze Gastrointestinal Motility in Mice

The enteric nervous system (ENS) plays an important role in regulating gastrointestinal (GI) motility and can function independently of the central nervous system. Changes in ENS function are a major cause of GI symptoms and disease and may contribute to GI symptoms reported in neuropsychiatric disorders including autism. It is well established that isolated colon segments generate spontaneous, rhythmic contractions known as Colonic Migrating Motor Complexes (CMMCs). A procedure to analyze the enteric neural regulation of CMMCs in ex vivo preparations of mouse colon is described. The colon is dissected from the animal and flushed to remove fecal content prior to being cannulated in an organ bath. Data is acquired via a video camera positioned above the organ bath and converted to high-resolution spatiotemporal maps via an in-house software package. Using this technique, baseline contractile patterns and pharmacological effects on ENS function in colon segments can be compared over 3-4 hr. In addition, propagation length and speed of CMMCs can be recorded as well as changes in gut diameter and contraction frequency. This technique is useful for characterizing gastrointestinal motility patterns in transgenic mouse models (and in other species including rat and guinea pig). In this way, pharmacologically induced changes in CMMCs are recorded in wild type mice and in the Neuroligin-3^R451C mouse model of autism. Furthermore, this technique can be applied to other regions of the GI tract including the duodenum, jejunum and ileum and at different developmental ages in mice.     

Human gut endogenous proteins as a potential source of angiotensin-I-converting enzyme (ACE-I)-, renin inhibitory and antioxidant peptides

It is well known that endogenous bioactive proteins and peptides play a substantial role in the body's first line of immunological defence, immune-regulation and normal body functioning. Further, the peptides derived from the luminal digestion of proteins are also important for body function. For example, within the peptide database BIOPEP (http://www.uwm.edu.pl/biochemia/index.php/en/biopep) 12 endogenous antimicrobial and 64 angiotensin-I-converting enzyme (ACE-I) inhibitory peptides derived from human milk and plasma proteins are listed. The antimicrobial peptide database (http://aps.unmc.edu/AP/main.php) lists over 111 human host-defence peptides. Several endogenous proteins are secreted in the gut and are subject to the same gastrointestinal digestion processes as food proteins derived from the diet. The human gut endogenous proteins (GEP) include mucins, serum albumin, digestive enzymes, hormones, and proteins from sloughed off epithelial cells and gut microbiota, and numerous other secreted proteins. To date, much work has been carried out regarding the health altering effects of food-derived bioactive peptides but little attention has been paid to the possibility that GEP may also be a source of bioactive peptides. In this review, we discuss the potential of GEP to constitute a gut cryptome from which bioactive peptides such as ACE-I inhibitory, renin inhibitory and antioxidant peptides may be derived.     

PACAP—A Multifacetted Neuropeptide

Pituitary adenylate cyclase activating polypeptide (PACAP) was originally isolated from ovine hypothalamus based on its ability to stimulate cAMP production in pituitary cell cultures. The peptide exists in two forms, both of which are derived from the same precursor. PACAP38 and the C‐terminal truncated PACAP27 can interact with three subtypes of receptors activating adenylate cyclase and/or phospholipase C. Since its discovery, numerous studies have provided evidence that PACAP is a pleiotropic substance having a broad spectrum of biological functions; the peptide can act as a hormone, neurohormone, autocrine/paracrine substance, neurotransmitter, neuromodulator, neurotrophic factor, and immunomodulator. Two examples of the functional role of PACAP on the biological timing system are presented: 1) the transient expression of PACAP during the periovulatory period in ovarian cells, in which PACAP functions as an autocrine/paracrine inducer of progesterone secretion and subsequent luteinization; and 2) the role of PACAP as a neurotransmitter in the retinohypothalamic tract mediating photic regulation of the brain's biological clock.     

多潘立酮对慢性阻塞性肺疾病机械通气患者胃肠功能障碍的临床效果观察

目的:探讨多潘立酮对慢性阻塞性肺疾病(COPD)机械通气患者胃肠功能障碍的临床效果.方法:采用前瞻性随机对照研究方法,选择2010年11月～2012年11月我院重症医学科收治的需要机械通气且存在胃肠功能障碍的COPD患者48例,按抽签法随机分为两组,对照组(n=24)为常规治疗组,治疗组(n_24)在常规治疗基础上给予鼻饲多潘立酮片10 mg,3次/天.观察周期为1周,通过观察患者胃肠功能障碍症状的恢复情况、胃排空情况及实验室检查指标评价多潘立酮的疗效.结果:治疗组和对照组胃肠功能障碍临床症状改善的有效率分别为87.5％和62.5％,治疗组显著高于对照组(P＜0.05);治疗组和对照组胃排空功能的有效率分别为83.33％和58.33％,治疗组显著高于对照组(P＜0.05);对照组治疗前后血红蛋白、离子、白蛋白、肌酐、尿素氮水平比较无显著差异(P＞0.05),治疗组治疗前后各指标亦无统计学差异(P＞0.05).治疗后两组血红蛋白,白蛋白有所升高,但各指标比较无统计学差异(P＞0.05).结论:多潘立酮辅助治疗可以有效改善COPD机械通气患者的胃肠功能障碍,促进胃排空,提高肠内营养的耐受性.     

Chronotherapy of colorectal cancer

Chronotherapy consists of chemotherapy delivery according to circadian rhythms. These genetically based rhythms modulate cellular metabolism and cell proliferation in normal tissues. As a result, both the host tolerance and antitumor efficacy of 5-fluorouracil (5-FU) and oxaliplatin (l-OHP), like 30 other anticancer drugs, vary largely according to the dosing time in laboratory rodents. The transfer of this concept to the clinic is aimed primarily at increasing the dose-intensity of the therapy through adjustment of drug-delivery to 24h rhythms in host tolerance. A specific technology (programmable-in-time infusion pumps) enables administration of chronotherapy to fully ambulatory patients. Phase I–III clinical trials show chronotherapy significantly increases tolerance to high doses of cancer drugs and improves antitumor activity in patients with metastatic colorectal cancer. These safe conditions of drug-delivery led to the first demonstration of the high activity of the 5-FU–leucovorin–l-OHP protocol. Chronotherapy with these three drugs also allows surgical removal of previously unresectable liver and lung metastases. This novel medico-surgical management provides hope for the cure of metastatic disease in patients with unresectable colorectal cancer metastases.     

再水合溶液能有效改善急性脱水女举重运动员的运动表现

本研究旨在探讨女子举重运动员急性脱水后口服4种不同组成的溶液,对液体存留率、胃肠道舒适度、血液值和无氧动力的影响。本研究以12位大学生女子举重运动员为对象,采交叉、平衡次序设计;研究参与者于脱水2%体重后分别补充相当于1.5倍脱水量的低渗透压电解质液(HES)、等渗透压电解质液(IES)、运动饮料(SB)或纯水(W),补充时间为脱水后立即、再水合期的30 min、60 min及90 min。再水合期间记录胃肠舒适分数、测量体重(计算液体存留率),并采集静脉血以测量血液渗透压、葡萄糖及钠、钾与氯离子,于脱水前与再水合期120 min时进行Wingate无氧动力测验。研究结果显示:补充HES、IES及运动饮料(SB)于再水合期90 min时的胃肠道舒适分数显著低于补充纯水(W)、而补充3种溶液于再水合期60 min时的血糖值则显著高于补充纯水(W),补充HES于再水合期120 min时的血钾值显著高于补充运动饮料(SB)及纯水(W);但补充4种溶液后的无氧动力与液体存留率并无显著差异。本研究证实举重运动员急性脱水后补充4种不同口服再水合溶液并不会影响再水合后的无氧动力,但补充含有糖类及电解质的溶液能有较佳的胃肠道舒适度,并血糖与血液电解质有维持的效果。     

粪菌移植联合乳果糖对顽固性功能性便秘患者胃肠功能、生活质量及心理状态的影响*

目的:研究粪菌移植联合乳果糖对顽固性功能性便秘患者胃肠功能、生活质量及心理状态的影响。方法:选取2016年6月至2018年5月我院消化内科收治的顽固性功能性便秘患者100例为研究对象,按照随机数字表法将患者分为对照组(n=45)和研究组(n=55)。对照组给予乳果糖口服治疗,研究组则采用粪菌移植联合乳果糖治疗,两组均治疗6周。对比两组临床疗效、胃肠功能以及治疗前后生活质量和心理状态的变化,并观察两组治疗期间不良反应发生情况。结果:与对照组比较,研究组总有效率明显升高(P0.05)。研究组首次自主排便时间、肛门首次排气时间、肠鸣音恢复时间均短于对照组,胃肠减压引流量高于对照组(P0.05)。治疗6周后,两组患者生活质量自评量表(PAC-QOL)评分、Zung焦虑自评量表(SAS)评分和抑郁自评量(SDS)评分均较治疗前降低,且与对照组比较,研究组PAC-QOL评分、SAS评分、SDS评分均降低(P0.05)。两组不良反应发生率比较差异无统计学意义(P0.05)。结论:粪菌移植联合乳果糖对顽固性功能性便秘具有较好的疗效,可改善患者胃肠功能和心理状态,同时可提高患者生活质量,无严重不良反应发生。     

Regulation of feeding behavior,gastrointestinal function and fluid homeostasis by apelin

Apelin was first identified and characterized from bovine stomach extracts as an endogenous ligand for the APJ receptor. Apelin/APJ system is abundantly present in peripheral tissues and central nervous system. Apelin plays a broad role in regulating physiological and pathological functions. Recently, many reports have showed the effects of apelin on feeding behavior, however the results are inconsistent, due to different administration routes, animal species, forms of apelin, etc. Apelin has been involved in stimulating gastric cell proliferation, cholecystokinin (CCK) secretion, histamine release, gastric acid and bicarbonate secretion, and regulation of gastrointestinal motility. In addition, apelin produced regulatory effects on drinking behavior, diuresis, arginine vasopressin (AVP) release and glucocorticoids secretion. This article reviews the role of apelin on feeding behavior, gastrointestinal function and fluid homeostasis.     

Chronobiological Aspects of Jejunum Function in Humans

This review is intended to present our knowledge on both chronomorphology and chronophysiology of jejunum mainly in humans, as well as on implications of chronobiologic principles in the practice of gastroenterology.