Convergence of Genetic, Nutritional and Inflammatory Factors in Gastrointestinal Cancers

Gastrointestinal cancers account for 20% of all cancer incidences worldwide. Colorectal cancer is the second most common cause of all cancer-related mortality and is increasing in Western societies. Infection and inflammation contribute to 15–20% of all malignancies, and are predisposing risk factors for gastrointestinal cancers. Helicobacter pylori infection is commonly associated with gastric cancers, and chronic inflammation increases the risk of colorectal cancer by 1% per year. Micronutrient status and common genetic variations in human populations modify risk for gastrointestinal cancer. Chronic inflammation promotes carcinogenesis by inducing gene mutations, inhibiting apoptosis, and stimulating an-giogenesis and cell proliferation. Inflammation also induces epigenetic alterations that are associated with cancer development. Two key genes in the inflammatory process, cyclooxygenase-2 (COX-2) and nuclear factor-kappa B (NF-kB), provide a mechanistic link between inflammation and cancer and are targets for chemoprevention. Dietary components, and human genetic variation that affects nutrient utilization, can directly modify inflammatory processes and/or suppress genomic alterations that are the molecular antecedents of cancers. The present report focuses on the convergence of genetic, nutritional, and inflammatory factors in the initiation and progression of gastrointestinal cancers, and the emerging dietary strategies for cancer prevention.     

Central tumour necrosis factor-α mediates the early gastrointestinal motor disturbances induced by lipopolysaccharide in sheep

Cytokines are involved in fever and other symptoms of the acute phase response induced by endotoxins. The aim of this work was to study the involvement of central tumour necrosis factor-alpha (TNF-alpha) in the changes induced by lipopolysaccharide (LPS) on gastrointestinal (GI) motility in sheep. Body temperature and myoelectric activity of the antrum, duodenum and jejunum was recorded continuously. Intravenous (i.v.) administration of LPS (0.1 micro g kg-1)-induced hyperthermia, decreased gastrointestinal myoelectric activity and increased the frequency of the migrating motor complex (MMC). These effects started 40-50 min after LPS and lasted for 6-7 h. TNF-alpha (50 and 100 ng kg-1) mimicked these effects when injected intracerebroventricularly (i.c.v.) but not i.v. Pretreatment with soluble recombinant TNF receptor (TNFR:Fc, 10 micro g kg-1, i.c.v.) abolished the TNF-induced actions and reduced those evoked by LPS. Furthermore, the effects induced by either LPS or TNF were suppressed by prior i.c.v. injection of indomethacin (100 micro g kg-1). In contrast, the i.v. injections of TNFR:Fc or indomethacin were ineffective. Our data suggest that LPS disturbs GI motility in sheep through a central pathway that involves TNF-alpha and prostaglandins sequentially.     

Splanchnic ischaemia and its role in multiple organ failure

Multiple organ failure remains the leading cause of death in the intensive care unit. Increasing numbers of investigators have focused their attention on the role of gastrointestinal tract in the pathogenesis of this syndrome. Their data indicate that inadequate gut perfusion leads to a measurable imbalance between oxygen delivery and the needs of the tissues, i.e., ischaemia. Gut ischaemia of sufficient duration impairs gastrointestinal tract barrier function, facilitating the passage of enteric bacterial endotoxin into the circulation. It has been hypothesized that production of tumor necrosis factor α, and other biologic mediators by endotoxin–stimulated macrophages, triggers a generalized and uncontrolled inflammatory response that ultimately leads to multiple organ failure.
Preliminary evidence suggests that survival can be improved significantly if gut ischaemia is promptly identifed and aggressively treated by administration of fluids and inotropic drugs, using gastric intramucosal pH as the therapeutic endpoint. Future studies are needed to determine whether additional treatment modalities can improve outcome once the inflammatory response has fully developed.     

Upper Gastrointestinal Irritation and Arrhythmia

Abstract: The influence of endoscopic examination on the occurrence of arrhythmia was investigated electrocardiographically in 30 patients with cardiovascular disease who underwent transesophageal echocardiography (TEE) (group A) and 38 patients with digestive tract disease who underwent upper gastrointestinal endoscopy (UGIE) (group B). The mode and frequency of arrhythmia during the examination were compared between the two groups. (1) Arrhythmia was more frequently observed in group A (22 of 30, 73.3%) than in group B (9 of 38, 23.7%) patients (p<0.001). The common arrhythmias in both groups were supraventricular premature beat and ventricular premature beat. Serious arrhythmias, such as 2nd degree atrioventricular block and ventricular fibrillation were detected only in group A patients. (2) The region of the esophagus where the tip of the probe or scope was located was classified into three segments: upper (0–15 cm), middle (15–35 cm) and lower (35 cm<). Arrhythmias tended to be frequent when the tip of the probe or scope was located in the middle segment of the esophagus. These data indicate that arrhythmias observed during TEE or UGIE are related to the underlying heart disease. Furthermore, the middle segment of the esophagus appears to be particularly susceptible to the provocation of arrhythmia.     

Effect of single-dose omeprazole and ranitidine on gastric juice acidity and volume in patients undergoing laparotomy

The effects of oral omeprazole and oral ranitidine on gastric fluid volume and pH were compared in 95 elective surgical patients, randomly assigned to one of three groups. The patients received either 80 mg of omeprazole or 300 mg of ranitidine orally at 6.00 on the morning of surgery. One third of the patients received no antacid therapy. Following induction, a no. 18 nasogastric tube was passed into the stomach and all available gastric fluid was aspirated. pH and volumes were measured. In the omeprazole- and ranitidine-treated groups, the mean pH was > 5.4 after induction, at completion of surgery and 1 h after operation, although at least one patient in both groups had pH < 2.5. The volumes of gastric aspirates were reduced equally by both drugs. Two patients in the omeprazole group, none in the ranitidine group and eight in the control group (26%) had pH <2.5 with volume> 25 ml at induction. Both drugs appeared to be effective in reducing the volume of intragastric fluid and acidity to acceptable values.     

Bioavailability of 1-deamino-8-D-arginine vasopressin with an enzyme inhibitor (aprotinin) from the small intestine in healthy volunteers

Objective: The bioavailability of an aqueous solution of 1-deamino-8-D-arginine vasopressin (dDAVP), with and without an enzyme inhibitor, was studied in six healthy, male volunteers aged 19–34 years, followed for 8 h after each drug administration. Methods: For i.v. administration the subjects received 4 μg dDAVP. For intestinal administration 500 μg dDAVP was administered directly, in two separate sessions, in the first part of the duodenum via a triple-lumen channel tube. In one session a solution of isotonic polyethylene glycol (PEG) was given as a continuous enteral perfusion. In the other session a solution of PEG and aprotinin was administered enterally at the constant rate of 5 ml⋅min⁻¹ for 4 h. Plasma dDAVP was measured using a specific, sensitive radioimmunoassay and intestinal juice was collected for measurement of lipase, chymotrypsin and pH every 30 min for 5 h. Results: The intestinal chymotrypsin activity was decreased after perfusion of aprotinin while the lipase activity was not modified. After i.v. administration, the half-life of elimination of dDAVP was 1.56 h and plasma clearance 1.24 ml⋅min⋅kg⁻¹. The mean bioavailability after duodenal administration of dDAVP + aprotinin was 0.46% compared with 0.09% after duodenal administration of dDAVP alone. The bioavailability of dDAVP after direct duodenal administration of an aqueous solution was similar to that after swallowing a tablet in a previous study and increased 5 times when given together with a perfusion of an enzyme inhibitor. Received: 27 October 1995/Accepted in revised form: 26 February 1996     

Effects of epidural bupivacaine and epidural morphine on bowel function and pain after hysterectomy

A comparison was made of the effects of continuous epidural analgesia with bupivacaine and intermittent epidural morphine on bowel function after abdominal hysterectomy. The duration of postoperative ileus was assessed as the time from the end of operation to the first postoperative passage of flatus and feces. Twenty-two patients were randomly allocated to two equal groups. An "epidural morphine" group received general anesthesia and epidural morphine for postoperative pain relief, and an "epidural bupivacaine" group was given combined general anesthesia and epidural anesthesia with 0.5% bupivacaine intraoperatively and epidural analgesia with 0.25% bupivacaine postoperatively. Epidural morphine or bupivacaine was given for 42 h postoperatively. Pain intensity (visual analog scale) was low in both groups, but lower (P less than 0.05) in the epidural bupivacaine group. The time to first passage of flatus was 22 +/- 16 h in the epidural bupivacaine group and 56 +/- 22 h in the epidural morphine group (P less than 0.001). The time to first postoperative passage of feces was shorter (P less than 0.05) in the former than in the latter 57 +/- 44 h vs 92 +/- 22 h). The patients of the epidural bupivacaine group started intake of oral fluids earlier (P less than 0.01) and to a greater extent (P less than 0.05) than those in the epidural morphine group. It is concluded that the duration of postoperative ileus after hysterectomy is shorter when epidural bupivacaine is given for postoperative pain relief than when this is achieved by epidural morphine.     

Histological score for cells with irregular nuclear contours for the diagnosis of reflux esophagitis in children

Histological criteria for the diagnosis of reflux esophagitis include basal zone hyperplasia, stromal papillae elongation, and inflammatory infiltrate. However, endoscopic esophageal biopsy specimens may include little or no lamina propria. Intraepithelial T lymphocytes, seen in hematoxylin and eosin-stained sections as cells with irregular nuclear contours (CINC), may have a higher density in children with esophagitis. We evaluated the diagnostic accuracy of a numerical score built up by grading the "classical" parameters and its correlation with CINC density in grasp biopsy specimens obtained from children undergoing esophagogastroduodenoscopy with and without esophagitis. We analyzed esophageal biopsy specimens from 349 children (median age, 5 years) subdivided in 4 groups according to the previous routine histology report: group 1, 144 children with esophagitis; group 2, 65 controls; group 3, 51 children with dubious esophagitis; and group 4, 75 children with esophagitis on endoscopy but a normal histology report. A numerical value was assigned to each parameter; the sum of these values represented the histological score. We also evaluated intraepithelial CINC density (ie, number of CINC per high-power field). We separately analyzed histological sections with and without lamina propria. For both total score and for CINC density, we calculated a cutoff using a receiver operating characteristic curve. Cutoffs of 6 for score and of 4 for CINC density provided the best sensitivity and specificity. Sensitivity of the histological score was better in biopsy specimens containing lamina propria (94%) than in those without lamina propria (4%). Sensitivity of CINC density was satisfactory in both specimens with (78%) and without (75%) lamina propria. Specificity was satisfactory for both parameters. In conclusion, when lamina propria was present in sections of endoscopic esophageal biopsy specimens, histological score provided a better diagnostic accuracy for the diagnosis of esophagitis. However, when no lamina propria was present, as was the case in 67% of our children, CINC density had better sensitivity. In addition, this latter parameter showed esophageal mucosa damage in 34% of previously dubious cases or cases with esophagitis at endoscopy but a previous routine histology report of normal mucosa.     

Cutis laxa: autosomal dominant inheritance in five generations

Cutis laxa is described in three cases: a 17-year-old man, his mother and his maternal grandmother. The onset of skin symptoms occurred from puberty to early adulthood. The skin was loose-hanging, wrinkled and without elasticity. X-ray examination showed numerous gastrointestinal diverticulae in the two older patients, and both had been operated on for abdominal hernia and genital prolapse. There were no cardiopulmonary symptoms. Histopathological investigation showed a reduction in the amount of elastic tissue in the dermis, but normally localized and ultrastructurally normal components. The family history revealed clinically similar cases in at least five generations, consistent with autosomal dominant inheritance.     

bFGF在骨组织工程学中的研究进展

碱性成纤维细胞生长因子 (b FGF)是近年来研究较为广泛的生长因子之一 ,对骨组织有着广泛的生物学效应。本文就 b FGF的研究进展及其目前在骨组织工程学研究方面的应用做一综述