The Adenomatous Polyposis Coli (APC) mutation spectra in different anatomical regions of the large intestine in colorectal cancer.

The enhanced incidence of colorectal cancer (CRC) in the U.S.A. has been linked to promutagens, such as heterocyclic aromatic amines, in the western diet that are produced by high temperature cooking of meat. However, a prior analysis of driver nonsense mutations in the Adenomatous Polyposis Coli (APC) gene, which is mutated in 75% of human CRC, indicated that the C·G → A·T transversions produced by this class of mutagens were not enriched but actually lower than what would be statistically anticipated. Moreover, the APC mutation patterns in the U.S.A. vs. China were indistinguishable despite differences in diet. In the present study, we have dissected the APC mutation pattern in tumors that arise in the different anatomical regions of the large intestine. The results show that the nonsense mutation pattern in APC differ in the different regions and that there is a statistically significant increase in C·G → A·T transversions in the rectum vs. the other regions, albeit, the percent of C·G → A·T mutations still remains lower than predicted based on random mutagenesis.

Effects of five candidate laxatives derived from Liriope platyphylla on the 5-HT receptor signaling pathway in three cell types present in the transverse colon.

The laxative effects of aqueous extract of Liriope platyphylla (AEtLP) on loperamide (Lop)­induced constipation have been reported; however, the key compounds and the mechanism underlying these effects remain unclear. Therefore, the laxative effects of five candidates derived from L. platyphylla: Diosgenin (DG), 5-hydroxymethylfurfural (5-HMF), adenosine (AD), hydroxypropyl cellulose (HPC) and uridine (UD) were investigated by examining the alteration of G protein α (Gα) expression, protein kinase C (PKC) phosphorylation and inositol triphosphate (IP3) concentration levels in the 5-hydroxytryptamine (5­HT; serotonin) receptor signaling pathway. Primary rat intestine smooth muscle cells (pRISMCs), intestinal epithelial cells (IEC)­18 and B35 cells were cotreated with Lop and the five compounds in order to screen the candidates. AEtLP, prucalopride (PCP) and bisacodyl (BS) served as positive controls. In pRISMCs, Gα expression levels were recovered in the majority of candidate­treated groups, whereas PKC phosphorylation recovery was observed only in the DG, 5­HMF and AD treatment groups. In IEC­18 cells, the AD treatment group mimicked the effects of PCP on PKC phosphorylation levels, whereas the DG, 5­HMF, HPC and UD treatment groups mimicked the effects of AEtLP and BS. In B35 cells, a greater upregulation of PKC phosphorylation levels were observed in the UD treatment group compared with the PCP and BS treatment groups, whereas DG, 5­HMF and AD treatment reduced the PKC phosphorylation levels to a greater extent than AEtLP treatment. However, effects similar to AEtLP, PCP and BS on Gα expression levels were not detected in any treatment groups in IEC­18 and B35 cells. Furthermore, the level of IP3 was enhanced only in pRISMCs, in which all five candidates were effective, while the greatest concentration was observed in the UD treatment group. In conclusion, the results of the present study suggest that UD may be considered the compound with the greatest laxative activity, which may regulate the 5­HT receptor signaling pathway.

Acute necrotizing emphysematous pancreatitis with air in the wirsung duct mimicking duodenal perforation: a case report

A 74-year old hemodynamically unstable woman with an acute abdomen presented at the emergency department. Laboratory findings indicated leukocytosis (21000/µl), increased CRP (300mg/l) and lipase (3792kU/l). CT abdomen without contrast showed multiple air pockets in and around the pancreas body, retroperitoneal along the duodenum as well as air in the Wirsung duct. A duodenal perforation was suspected. On explorative laparoscopy however no immediate sign of perforation was seen despite infusion of methylene blue through a nasogastric catheter. Further exploration showed a necrotizing exudative pancreatitis. Because of perioperative hemodynamic instability, further invasive actions were put off. Acute necrotizing emphysematous pancreatitis is a severe pathology with a high mortality (25-70%). Air in the Wirsung duct is rarely described in literature and so far an underlying explanation remains unclear. In this case gas-forming organisms may have entered the pancreas through haematogenous or lymphatic spread, as well as directly through the ampulla or by transmural passage from the transverse colon

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Co-localisation of cocaine- and amphetamine-regulated transcript peptide and vasoactive intestinal polypeptide in the myenteric plexus of the porcine transverse colon.

Cocaine- and amphetamine-regulated transcript peptide (CART) is a substance,which can play the role of neuromediator and/or neuromodulator in nerve structures within the gastrointestinal tract. However knowledge concerning its functions and co-localisation with other neuronal factors is rather scarce. During the present investigation the co-localisation of CART and vasoactive intestinal polypeptide (VIP) in the neurons of meyenteric plexus within the porcine transverse colon was studied using double immunofluorescence technique and semiquantitative arbitrary scale of the frequency of presence CART+/VIP+, CART+/VIP- and CART-/VIP+ neuronal cells. The most often (+++) CART-/VIP+ neurons were encountered, neurons simultaneously immunoreactive to CART and VIP were observed somewhat rarer (++) and only single (+) CART+/VIP- perikarya were visible. The present study reports for the first time on the co-localisation of CART and VIP in myenteric neurons of the porcine transverse colon.

Relaxin exerts two opposite effects on mechanical activity and nitric oxide synthase expression in the mouse colon.

The hormone relaxin exerts a variety of functions on the smooth muscle of reproductive and nonreproductive organs, most of which occur through a nitric oxide (NO)-mediated mechanism. In the stomach and ileum, relaxin causes muscle relaxation by modulating the activity and expression of different nitric oxide synthase (NOS) isoforms region-dependently. Nothing is known on the effects of relaxin in the colon, the gut region expressing the highest number of neuronal (n) NOSß-immunoreactive neurons and mainly involved in motor symptoms of pregnancy and menstrual cycle. Therefore, we studied the effects of relaxin exposure in the mouse proximal colon in vitro evaluating muscle mechanical activity and NOS isoform expression. The functional experiments showed that relaxin decreases muscle tone and increases amplitude of spontaneous contractions; the immunohistochemical results showed that relaxin increases nNOSß and endothelial (e) NOS expression in the neurons and decreases nNOSα and eNOS expression in the smooth muscle cells (SMC). We hypothesized that, in the colon, relaxin primarily increases the activity and expression of nNOSß and eNOS in the neurons, causing a reduction of the muscle tone. The downregulation of nNOSα and eNOS expression in the SMC associated with increased muscle contractility could be the consequence of continuous exposue of these cells to the NO of neuronal origin. These findings may help to better understand the physiology of NO in the gastrointestinal tract and the role that the "relaxin-NO" system plays in motor disorders such as functional bowel disease.

Quantity and distribution of eosinophils in the gastrointestinal tract of children.

There are a lack of data on the quantity and location of eosinophils in the gastrointestinal tract of healthy individuals. Accordingly, we examined gastrointestinal biopsies obtained during endoscopic evaluation of pediatric patients. Biopsies were previously interpreted as having no diagnostic abnormality. The presence of extracellular eosinophil constituents and the quantity of eosinophils in atopic versus nonatopic individuals was determined. In the esophagus, eosinophils were present in only 2.7% of high-power fields (hpf), with a mean value of 0.03+/-0.10 eosinophils/hpf (mean+/-standard deviation) and a maximum of 1 eosinophil/hpf. Examination of the antrum and fundus revealed similar numbers of eosinophils in the lamina propria (1.9+/-1.3 and 2.1+/-2.4 eosinophils/hpf, respectively), with no eosinophils observed in the surface epithelium. In the small intestine, there were 9.6+/-5.3 (maximum, 26 eosinophils/hpf) and 12.4+/-5.4 eosinophils/hpf (maximum, 28 eosinophils/hpf) in the intercryptal lamina propria of the duodenum and ileum, respectively. The number of eosinophils in the surface epithelium and crypt epithelium was minimal. In the large intestine, the highest concentration of eosinophils was observed in the cecum (20.3+/-8.2 eosinophils/hpf; maximum, 50 eosinophils/hpf), and there were lower concentrations in the transverse and sigmoid colon (16.3+/-5.6 and 8.3+/-5.9 eosinophils/hpf, respectively). The percentage of fields demonstrating extracellular eosinophil granules in all gastrointestinal segments was 70% to 93%, and extracellular granules were most numerous at the edge of the biopsy (P<0.05). Atopic and nonatopic patients had comparable numbers of eosinophils. These data establish baseline gastrointestinal eosinophil values in pediatric patients without apparent pathological disease.