人胚胎胃肠及胰腺D细胞发生的研究

用免疫细胞化学方法研究人胚胎各时期胃肠胰的Ｄ细胞发生及其形态与功能的关系。结果发现：Ｄ细胞最早出现于６周零５天胚的十二指肠，７周零３天胚的胰、胃、空肠，７周零６天胚的回肠，８周零４天胎的结肠及１０周零５天胎的阑尾；细胞密度在胚期低，胎期逐增，至胎晚期又依次在胰、胃窦、十二指肠、胃体、空肠、回肠、升结肠及阑尾中降低，且肠绒毛顶端可见衰老的Ｄ细胞。提示胚胎Ｄ细胞的发生与胃肠胰的发育有关。     

Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome

BACKGROUND & AIMS: Serotonin (5-HT) is a critical signaling molecule in the gut. 5-HT released from enterochromaffin cells initiates peristaltic, secretory, vasodilatory, vagal, and nociceptive reflexes. Despite being pathophysiologically divergent, ulcerative colitis (UC) and irritable bowel syndrome (IBS) are both associated with clinical symptoms that include alterations in the normal patterns of motility, secretion, and sensation. Our aim was to test whether enteric 5-HT signaling is defective in these disorders. METHODS: Rectal biopsy specimens were obtained from healthy controls and patients with UC, IBS with diarrhea (IBS-D), and IBS with constipation (IBS-C). Key elements of 5-HT signaling, including measures of 5-HT content, release, and reuptake, were analyzed with these samples. RESULTS: Mucosal 5-HT, tryptophan hydroxylase 1 messenger RNA, serotonin transporter messenger RNA, and serotonin transporter immunoreactivity were all significantly reduced in UC, IBS-C, and IBS-D. The enterochromaffin cell population was decreased in severe UC samples but was unchanged in IBS-C and IBS-D. When 5-HT release was investigated under basal and mechanical stimulation conditions, no changes were detected in any of the groups relative to controls. CONCLUSIONS: These data show that UC and IBS are associated with similar molecular changes in serotonergic signaling mechanisms. While UC and IBS have distinct pathophysiologic properties, these data suggest that shared defects in 5-HT signaling may underlie the altered motility, secretion, and sensation. These findings represent the first demonstration of significant molecular alterations specific to the gut in patients with IBS and support the assertion that disordered gastrointestinal function in IBS involves changes intrinsic to the bowel.     

Adaptive changes of the enterochromaffin and gastrin cells in the rat gastrointestinal tract following subtotal colectomy

Objective. Colectomized patients often have diarrhoea and increased gastric acid secretion. Although serotonin influences gastrointestinal (GI) motility and secretion, GI serotonin-producing enterochromaffin (EC) cells have not been investigated after colectomy, nor have the antral gastrin cells. The aim of this experimental study was to investigate the GI tract in rats 8 weeks after subtotal colectomy, with particular emphasis on the frequency and distribution of EC and gastrin cells. Material andmethods. Immunohistochemical techniques were used to identify the two endocrine cell types. Results. The colectomized animals had diarrhoea. Body-weight was lower and the small intestine shorter in the colectomized animals compared with sham-operated and untreated controls. In the two surgically treated groups, the antral mucosa was thinner and the small intestinal mucosa was thicker compared with that of the untreated rats, whereas the thickness of the rectum of the colectomized rats was increased compared with that of the control groups. In the colectomized animals, the number of EC cells was increased in the small intestine and rectum, whereas the numbers of both EC and gastrin cells were decreased in the antrum. Conclusions. The results indicate that colectomy exerts a significant influence on the GI mucosa and on the endocrine cell systems studied. An increased number of EC cells can result in alterations in motility and secretion, which may be important in the pathogenesis of the diarrhoea that often occurs after colectomy.     

Treatment of type I gastric neuroendocrine tumors with somatostatin analogs

Background and Aim: There are limited data on response and long‐term follow‐up of octreotide therapy in type‐I gastric neuroendocrine tumors. The objective of the present study was to assess the response of type‐I gastric neuroendocrine tumors to octreotide‐long acting, repeatable (LAR) therapy and evaluate long‐term follow up of such patients after therapy. Methods: Three patients with documented type‐I gastric neuroendocrine tumors from a tertiary gastroenterology centre were studied. Octreotide‐LAR therapy 20 mg intramuscularly every 28 days was administered for one year. Serum gastrin and chromogranin levels, gastroscopies and biopsies from tumor nodules at 6 months and one year on therapy and every 6 months after completion of drug therapy were taken. Follow‐up after completion of therapy extended for 3 years in two and 2.5 years in one patient. Results: During octreotide therapy there was normalization of serum gastrin levels and serum chromogranin levels. Tumors in all three patients had regressed at 6 months of treatment. Following cessation of therapy, there was progressive rise of serum gastrin to pre‐treatment levels. Serum chromogranin levels remained within normal limits. Gastroscopic and histologic examination of gastric biopsies did not reveal recurrence of tumors in any patients. All patients tolerated therapy well and became asymptomatic soon after drug therapy. Conclusions: Octreotide‐LAR therapy causes regression of type‐I gastric neuroendocrine tumors. After completion of drug therapy there was no recurrence of tumors even with continued hypergastrinemia. Octreotide therapy should be considered as one of the treatment options in such patients.     

Detection of the 5-HT1A receptor and 5-HT1A receptor mRNA in the rat bowel and pancreas: Comparison with 5-HT1Preceptors

We tested the hypothesis that the rat bowel and pancreas contain 5-HT_1A receptors. ₃H-8-hydroxy-2-(di-n-propylamino) tetralin (₃H-8-OH-DPAT) was used as a radioligand. Binding of ₃H-8-OH-DPAT to membranes derived from the myenteric plexus and the pancreas was investigated by rapid filtration. Alternatively, radioautography was employed to locate ₃H-8-OH-DPAT binding sites in frozen sections of unfixed bowel or pancreas. An excess of 5-HT (10 μM) was used to define nonspecific binding. Saturable, high affinity binding of ₃H-8-OH-DPAT to enteric (K_d= 2.8 ± 1.1 nM; B_max =83.8 ± 4.3 fmol/mgproteim) and pancreatic (K_d = 6.6 ± 1.3 nM; B_max = 44 ± 2.2 fmol/mg protein) membranes was found. The binding of ₃H-8-OH-DPAT to enteric and pancreatic membranes was inhibited by 8-OH-DPAT, NAN-190, and spiperone. In contrast, the binding of ₃H-8-OH-DPAT to enteric and pancreatic membranes was not inhibited by 5-carboxyamidotryptamine, or by avariety of compounds known to bind to other subtypes of 5-HT receptor. Digoxigenin-labeled oligonucleotides were found to detect mRNA encoding the 5-HT_1A receptor in a subset of neurons in myenteric and submucosal ganglia. In contrast, 5-HT_1A mRNA was not found in the pancreas. Radioautography revealed that the highest density of ₃H-8-OH-DPAT binding sites was found in the stomach. These sites were especially numerous in the lamina propria adjacent to gastric glands, and in myenteric ganglia. Pancreatic 5-HT_1Areceptors were located on nerves, lymphoid tissue (especially the capsule of nodes), and on cells scattered in the pancreatic parenchyma. The concentration of ₃H-8-OH-DPAT binding sites in the rat bowel and pancreas was less than that of ₃H-5-HT binding sites; however, the distribution of ₃H-8-OH-DPAT binding sites was similar to that of sites that bind ₃H-5-HT. It is concluded that the rat gut and its extension in the pancreas contains 5-HT_1A receptors. Many, if not all, of the nerve cells and processes that express 5-HT_1A receptors express 5-HT_1p receptors as well. The function of these receptors in the physiology of the entero-pancreatic innervation remains to be determined. © 1993 Wiley-Liss, Inc.     

气管上皮嗜银细胞和5-羟色胺免疫反应细胞的定位

用银染色及免疫组织化学ＰＡＰ法，对狗、家兔、豚鼠、大鼠、小鼠气管粘膜上皮内嗜银细胞和５－羟色胺（５－ＨＴ）免疫反应（ｉｍｍｕｎｏｒｅａｃｔｉｏｎ）细胞的分布及形态进行观察。结果显示：５种动物气管上皮中均可见散在的嗜银细胞，家兔气管内嗜银细胞密度较大，而狗、大鼠的较少。５－ＨＴ－ＩＲ细胞仅见家兔、豚鼠、小鼠的气管粘膜上皮。气管中的内分泌细胞可分为开放型和闭合型，并可见旁突伸至邻近细胞。相邻切片观察未     

The alteration of enterochromaffin cell,mast cell,and lamina propria T lymphocyte numbers in irritable bowel syndrome and its relationship with psychological factors

Background/Aims: Psychological factors and subtle histopathological changes have been implicated in irritable bowel syndrome (IBS). The aims of the present study were to investigate whether the numbers of enterochromaffin (EC) cells, mast cells, and lamina propria T lymphocytes are altered in IBS, and evaluate the relationship of such alterations with psychological factors. Methods: Forty‐two consecutive IBS patients (M : F = 17:25, mean age 48 years) fulfilling the Rome III criteria and twelve asymptomatic healthy controls underwent rectal biopsy. Immunostaining was performed for EC cells, mast cells, and lamina propria T lymphocytes. Results: The IBS group included five post‐infectious (PI) IBS and 37 non‐PI IBS patients. Significantly more EC cells, mast cells and lamina propria T lymphocytes were observed in PI IBS patients. Mast cells significantly increased in non‐PI IBS‐D (diarrhea) patients, but not in non‐PI IBS‐C (constipation) and non‐PI IBS‐M (mixed) patients. Enterochromaffin cell numbers were not significantly altered in non‐PI IBS patients. Anxiety and depression scores did not differ between IBS patients with and without abnormal increase in EC cell or mast cell counts, defined as more than the mean of controls + 2 standard deviations. Enterochromaffin cell, mast cell, or lamina propria T lymphocyte numbers were poorly correlated with anxiety and depression scores in the IBS group. Conclusions: Enterochromaffin cells, mast cells, and lamina propria T lymphocytes significantly increase in PI IBS, whereas only mast cells significantly increase in non‐PI IBS‐D. Such histopathological changes do not seem to be directly associated with psychological factors.