Protective Effects of Aqueous Garlic Extract in Reducing Water Avoidance Stress-Induced Degeneration of the Stomach, Ileum, and Liver: Morphological and Biochemical Study

We investigated the effect of aqueous garlic extract (AGE) on water avoidance stress (WAS)-induced degeneration of the gastric and ileal mucosa and liver parenchyma. Wistar albino rats were exposed to WAS (WAS group) for 5 days. After exposure of the animals to WAS, a 1 ml/kg aqueous garlic extract (AGE) was injected i.p. (WAS+AGE group). The stomach, ileum, and liver samples were investigated under light microscope for general morphology. Topography of gastric and ileal mucosa was investigated by scanning electron microscopy, and hepatocyte ultastructure by transmission electron micsroscopy. Malondialdehyde (MDA) and glutathione (GSH) levels of all tissues were also determined. In the WAS group, the epithelium of the stomach showed ulceration in some areas, dilatations of the gastric glands, and degeneration of gastric glandular cells. Severe vascular congestion and degeneration of ileal epithelium were observed. Prominent vascular congestion and dilated sinusoids, activated Kupffer cells with prominent morphology, dilated granular endoplasmic reticulum membranes, and focal picnotic nuclei were observed in liver parenchyma. AGE treatment reduced the degeneration of the gastric and ileal mucosa and liver parenchyma. Increased MDA levels and decreased GSH levels in the WAS group were reversed to control values after AGE treatment. Based on these results, AGE treatment significantly prevented WAS-induced degeneration in both morphology and biochemistry of gastrointestinal mucosa and liver parenchyma due to its potent free radical scavenging and antioxidant properties.     

回肠代膀胱术后肠粘膜组织学的变化

目的：初步探讨回肠代膀胱术后贮尿囊粘膜的变化及意义。方法：选择12例平均年龄61岁、平均术后时间35个月患者的肠贮尿囊粘膜取材作光镜及电镜检查，并同时作血气分析。结果：随术后时间延长，肠绒毛及绒毛均逐渐萎缩，而上皮细胞的其他形态结构及层次均未见异常。1例术后半年者发生轻度酸中毒，其余患者正常。绒毛萎缩可导致杯状细胞总数减少。结论：随术后时间延长，回肠代膀胱酸中毒发生率下降，粘液堵塞尿道现象也可能减轻；随访期内肠上皮细胞未见增生等改变。     

Reduction of 5-fluorouracil (5-FU) gastrointestinal (GI) toxicity resulting from the protection of thymidylate synthase (TS) in GI tissue by repeated simultaneous administration of potassium oxonate (Oxo) in rats

Purpose: An important cytotoxic effect of 5-fluorouracil (5-FU) is the inactivation of thymidylate synthase (TS) (EC 2.1.1.45) activity by the formation of a ternary complex consisting of covalently bound 5-fluorodeoxyuridine 5′-monophosphate (FdUMP), TS and 5,10-methylenetetrahydrofolate (CH₂FH₄). The gastrointestinal (GI) toxicity of 5-FU is also caused by its phosphorylation in the GI tract. Potassium oxonate (Oxo) competitively inhibits pyrimidine phosphoribosyltransferase (EC 2.4.2.10), which converts 5-FU to 5-fluorouridine 5′-monophosphate (FUMP) in vitro. In this study the benefits of combining Oxo and tegafur (FT), which is a masked compound of 5-FU, in reducing the GI toxicity of 5-FU and in protecting the activity of TS in the normal GI tissues were evaluated. Methods: We administered orally a preparation of 1 M FT and 0.4 M 5-chloro-2,4-dihydroxypyridine (CDHP) with or without 1 M Oxo (called S-1 and FT + CDHP, respectively) or vehicle only (control) to rats for ten consecutive days and compared the toxicity, the histopathological findings and the free TS activity in the GI tissues of the treated rats. Results: During the experimental periods, the signs of toxicity, such as a decrease in body weight, diarrhea and death, were only observed in the rats treated with FT + CDHP. The histopathological findings in the ileum and colon samples from rats treated consecutively with S-1 on day 1, day 4, day 7 and day 10 were less frequent and more mild than in the samples from rats treated with FT + CDHP. Furthermore, the free TS activities in the ileum samples of rats given S-1 and FT + CDHP were significantly decreased compared with the activity in samples from the control rats throughout the experimental periods. The free TS activities in GI tissues of rats treated with S-1 were higher than the TS activities in tissues from rats treated with FT + CDHP daily from day 4 to day 10, although activities in S-1-treated rat were decreased to almost same low levels as in FT + CDHP-treated rats on day 1. Conclusions: Our results suggest that repeated simultaneous administration of Oxo and FT can effectively protect the activity of TS by decreasing FdUMP via FUMP from 5-FU in GI tissue, and may lead to a reduction in GI toxicity. Received: 13 August 1999 / Accepted: 24 February 2000     

Secretory transport of irinotecan metabolite SN-38 across isolated intestinal tissue

Purpose The purpose of this study was to investigate the transport mechanisms of transporters that contribute to the intestinal efflux of 7-ethyl-10-hydroxycamptothecin (SN-38).Methods The intestinal transport of SN-38 was studied in rat intestinal tissue mounted in Ussing chambers.Results In the ileum, the level of transport from the serosal layer to the mucosal layer was significantly greater than that from the mucosal layer to the serosal layer, whereas a significant difference was not observed in the jejunum. This secretory transport required metabolic energy and was diminished by sulfobromophthalein. However, mitoxantrone, an inhibitor of breast cancer resistance protein (BCRP), did not affect the ileal secretion of SN-38.Conclusions The results suggest that a specific transport system, which is distinct from BCRP, plays a major role in the secretion of SN-38 and that this secretory transport system predominantly exists in the ileum.     

Two cases of adult T-cell leukemia/lymphoma involving the terminal ileum

We describe two cases of adult T-cell leukemia/lymphoma (ATLL) with terminal ileal involvement. The first case, a 71-year-old man with lymphoma subtype of ATLL, had a polypoid lesion in the terminal ileum, in addition to a duodenal mass. The second case, a 58-year-old woman with lymphoma subtype of ATLL, had an irregular ulcerative lesion in the terminal ileum and multiple ulcers throughout the stomach. Biopsies from these lesions revealed mucosal invasion of ATLL cells in each case. In the second case, combination chemotherapy was transiently effective, resulting in the disappearance of gastric and terminal ileal lesions. Prospective and careful examination of additional cases should further characterize the clinicopathological features of terminal ileal involvement in ATLL.     

Immunocytochemical localization of rat intestinal 15 kDa protein,a member of cytoplasmic fatty acid-binding proteins

Rat intestinal 15 kDa protein (I-15P) is a member of the family of cytoplasmic fatty acid-binding proteins. Using a specific antiserum against I-15P, we studied the tissue distribution and subcellular localization of this protein in the entire rat body. By immunoblot analysis of cytosolic proteins, I-15P was detected not only in the distal portion of small intestine but also in the ovary and adrenal gland. Immunohistochemically, I-15P was localized to the absorptive epithelial cells as well as a subpopulation of enterochromaffin cells in the intestine, the lutein cells in the ovary, and subpopulations of cortical cells in the adrenal gland. Furthermore, I-15P-like immunoreactivity was also demonstrated in the surface mucous cells of stomach and the granular convoluted tubule cells of submandibular gland. Immuno-electron microscopy showed that the immunoreactivity was confined to the cytoplasmic matrix region, except in the enterochromaffin cells and granular convoluted tubule cells, where it was localized in the secretory granules. The present findings suggest that I-15P plays a role in the cellular metabolism of steroids.© Willey-Liss, Inc.     

MN9202对缺血后大鼠回肠肌间神经丛一氧化氮合酶阳性神经元的影响

目的　实验用 β NADPH脱氢酶组织化学研究MN92 0 2对缺血后大鼠回肠肌间神经丛一氧化氮合酶 (NOS)阳性神经元的影响。方法　用无创伤动脉夹夹闭大鼠肠系膜上动脉使回肠缺血。 1h后松夹复流 ,分别于缺血前 15min和再灌前 1min腹腔注射MN92 0 2 (1μg/kg)。缺血对照组腹腔注射等量生理盐水。动物存活 1d后取回肠进行β NADPH组化反应。 结果　肠缺血后NOS阳性神经元明显增多 (P <0 0 5 ) ,在缺前后应用MN92 0 2可使肌间神经丛内NOS阳性神经元较缺血对照组显著减少 (P <0 0 5 )。结论　MN92 0 2减少大鼠减少大鼠肠缺血后NOS阳性神经元 ,其NO量相应减少 ,可能是其对大鼠肠缺血再灌注损伤的保护作用机制之一     

Lymphoid tissues of the ileum in young horses: distribution, structure, and epithelium

Lymphoid tissues in the ileum of young horses form raised plaques that are macroscopically visible from the mucosal surface. These are termed ileal lymphoid patches. These patches are variable in size, shape and position within the ileal wall, occasionally lying along the site of mesenteric attachment. Within lymphoid patches, follicles exist in three different morphological forms: follicle/dome structures, proprial follicles, and lymphoglandular complexes (LGCs). In follicle/dome structures, the majority of the follicle lies in the submucosa and merges with a dome in the lamina propria through a gap in the muscularis mucosae. In proprial follicles, the majority, or all, of the follicle is found in the lamina propria, and in LGCs, the follicles lie in the submucosa and communicate with the intestinal lumen via a central invagination of epithelium that extends vertically through a gap in the muscularis mucosae. Follicle-associated epithelium covers the follicle/dome structures and proprial follicles. It consists of enterocytes, cells morphologically resembling M cells, intraepithelial lymphocytes, goblet cells, and amine-precursor uptake and decarboxylation (APUD) cells. The epithelium of LGCs is mainly populated by immature enterocytes, intraepithelial lymphocytes and goblet cells. Cells with coarse, long microvilli are also present. Information regarding the presence of LGCs in the small intestine is scant, but LGCs have been well described in the large intestine of many species. Further investigation will be required to determine if factors exist that are common to both the ileum of the horse and the large intestine of other species to influence the development of LGCs at these specific sites.     

Characterisation of some pharmacological effects of the venom from Vipera lebetina.

Vipera lebetina is one of the most venomous snakes on the Iran plateau. Serious clinical problems such as edema, hemorrhage and tissue necrosis are observed in humans following V. lebetina envenomating. However, little information on the pharmacological properties of the venom is available. To determine haemodynamic actions of the venom of V. lebetina, the changes in the mean arterial blood pressure of anaesthetised rats following the administration of the venom were recorded. Venom (1 mg/kg, i.v.) produced rapid cardiovascular collapse, while 0.3 mg/kg (i.v.) caused only a small transient decrease in mean arterial blood pressure. Effects of the venom on perfusion pressure in the isolated rat mesenteric bed, and on contractions of the isolated rat right atrium and the isolated guinea-pig ileum, were also studied. Exposure of the isolated rat right atrium to venom (0.1-1 mg/ml) caused a transient increase followed by a sustained reduction in the amplitude and frequency of spontaneous contractions. The transient positive inotropic and chronotropic effects were abolished when the preparation was preincubated with propranolol, but not with tolazoline. N(G)-nitro-l-arginine methyl ester pretreatment attenuated the vascular hyporeactivity to phenylephrine induced by the venom in the isolated rat mesenteric vascular bed. This suggests that nitric oxide (NO) or NO-like compounds may be present in the venom and involved in its hypotensive effect. The venom (0.3-1 mg/ml) caused concentration-dependant blockade of isolated guinea-pig ileum contractions induced by electrical field stimulation, acetylcholine or KCl. This inhibitory effect of the venom was significantly reduced by prior incubation of the venom with manoalide (1 microM) indicating involvement of a phospholipase A(2) component. Further, investigation is required to identify specific toxins responsible for the above pharmacological effects.