Role of dietary fiber and short-chain fatty acids in the colon

Luminal nutrition is important for maintenance of gastrointestinal mucosal structure and function. In particular, short chain fatty acids (SCFAs), metabolic products of anaerobic bacterial fermentation of dietary fiber and resistant starch, are particularly important as the preferred respiratory fuel of the colonocytes. A variety of biological effects of SCFAs have been reported, and there is now increasing number of experimental works showing new aspects of these molecules. For example, as the mechanisms mediating anti-inflammatory effects of SCFAs, several investigators identified the inhibitory effect of butyrate on proinflammatory cytokine-induced NF-kappaB activation. Various inflammatory responses are now discussed with the central role of NF-kappaB activation, and thus the inhibition of NF-kappaB activation represents the efficacy of dietary fiber and SCFAs in the treatment with inflammatory bowel disease. Furthermore, recent advance in molecular technology has identified mechanisms mediating anti-tumor effects of SCFAs. SCFAs modulate expression of cell cycle-regulating proteins and induce apoptosis in colon cancer cells. SCFAs increase the susceptibility of colon cancer cells to complement-mediated cell injury. In this review, new aspects of functions of SCFAs are focused and summarized.     

Enteral and parenteral nutrition therapy for Crohn's disease

Even with the development of new therapeutic agents, such as infliximab, enteral nutrition (EN) and parenteral nutrition (PN) therapies remain important for the treatment of Crohn's disease because Crohn's patients often require nutritional support. Furthermore, nutritional therapies can be used in the control of disease activity. Elemental diets, which are mainly used in EN therapy, consist of a refined amino acid mixture, glucose or maltodextrins and minimal essential fatty acids. EN therapy can reduce mucosal inflammation by the elimination of dietary antigens, which induce inflammation, and by reductions in fat, which activates inflammation. EN is applied not only as induction therapy, but also as maintenance therapy after remission (home EN). However, the unpalatability of elemental diets, difficulties related to self-intubation and the high cost of EN have limited its application as a primary therapy in western countries. PN is utilized as complete bowel rest supporting nutrition. However, since the therapeutic efficacies of EN and PN are similar, the indications for PN are limited and PN is mainly utilized in patients with bowel obstructions or severe fistulas. PN is also used as home therapy in the treatment of Crohn's patients with short bowel syndrome. However, long-term PN sometimes causes life-threatening complications including catheter-induced sepsis, liver failure and lethal mineral deficiencies. We suggest that gastroenterologists should recognize the advantages and limitations of all therapies and choose carefully or combine various therapies in order to maintain the quality of life in individual patients even if in cases where remission can not be achieved.     

Tension pneumothorax manifested after extubation in a patient who underwent total gastrectomy

A patient developed tension pneumothorax immediately after extubation. The patient was a 53-year-old man, who underwent total gastrectomy under general anesthesia combined with epidural anesthesia. The posterior mediastinum drainage tube was placed near the site of esophago-jejunum anastomosis. Surgeons reported that they might have injured left diaphragmatic pleura during the procedure. Postoperative chest X-ray showed no abnormal findings in the both lung fields. Patient's trachea was extubated when he emerged from anesthesia. However, Spo2 rapidly dropped from 100 to 88. Re-intubation was performed, and positive pressure ventilation was resumed. The Spo2 returned quickly to 100 without hemodynamic change. Auscultation revealed reduced respiratory sound from the left lung. Diagnosis of tension pneumothorax was made from emergency chest X-ray. Patient's respiration improved when chest tube was inserted, but a large amount of air was continuously drained. Air leakage decreased significantly when the mediastinum drainage tube was tentatively occluded. The possible mechanism of the positive pressure in the thoracic cavity was assumed that air was introduced with spontaneous inspiration from the drainage tube, and damaged pleura played as a check valve.     

Supplement of a chitosan and ascorbic acid mixture for Crohn's disease: a pilot study

OBJECTIVE: Although the pathogenesis of Crohn's disease remains unclear, dietary fat is thought to exacerbate intestinal inflammation. Chitosan is a water-insoluble dietary fiber, and a chitosan and ascorbic acid mixture has been shown in rats to increase fecal fat excretion without affecting protein digestibility. However, it remains unclear whether a chitosan and ascorbic acid mixture is safe and effective for patients with Crohn's disease. We designed a pilot trial to investigate the tolerability and amount of fat excretion after the oral administration of a chitosan and ascorbic mixture for inactive Crohn's disease. METHODS: Eleven outpatients were given seven tablets daily of a chitosan and ascorbic mixture (chitosan was given at 1.05 g/d) for 8 wk. Patients did not interrupt their respective therapies for Crohn's disease. RESULTS: The bowel movements of most patients increased slightly during the study. Nutritional and inflammatory markers in patients did not differ before and after treatment. The chitosan and ascorbic acid mixture significantly increased the fat concentration in the feces during treatment. CONCLUSIONS: These results indicated that oral administration of a chitosan and ascorbic acid mixture in patients with Crohn's disease is tolerable and increases fecal fat excretion without affecting disease activity.     

SCCA2-like serpins mediate genetic predisposition to skin tumors

Reasons for early onset skin cancer are poorly understood. Microarray analysis revealed overexpression of the Scca2 gene in the 12-O-tetradecanoylphorbol-13-acetate-treated skin of Car-S mice, or line phenotypically selected for high susceptibility to two-stage skin carcinogenesis, as compared with 12-O-tetradecanoylphorbol-13-acetate-treated skin of Car-R mice, which is resistant. A human skin squamous cell carcinoma cell line (NCI-H520) transfected with mouse Scca2 or a related gene, Scca2-rs1, both expressed in the skin, showed significantly increased tumor growth as compared with controls when injected in nude mice. Immunohistochemical analysis of samples from two independent series of Italian and Korean patients with squamous cell carcinoma of the skin indicated a significant association between SCCA2 protein expression and younger age at tumor onset. These findings provide evidence that SCCA2-like serpins mediate genetic predisposition to skin cancer in a mouse model and in humans.     

The cytotoxicity of hydrophobic bile acids is ameliorated by more hydrophilic bile acids in intestinal cell lines IEC-6 and Caco-2

Bile acids, especially those with hydrophobic properties, are known to possess cytotoxicity. However, the mechanisms responsible for the cytotoxicity of bile acids are still under investigation. On the other hand, the hydrophilic bile acid, ursodeoxycholic acid has been reported to exhibit therapeutic effects against cytotoxic hydrophobic bile acids. The aim of the present study was to investigate the cytotoxicity of individual bile acids and combinations of bile acids using the intestinal cell lines IEC-6 and Caco-2 cells. The cytotoxicities of individual bile acids and the effects of various bile acid combinations were evaluated using the MTS [3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay. The bile acids induced cytotoxic effects depending on their hydrophobicity except for hyodeoxycholic acid. In the study for the effects of combined bile acids, not only ursodeoxycholic acid but other hydrophilic bile salts such as cholic acid and hyocholic acid exhibited cytoprotection against deoxycholic acid-induced cytotoxicity. Moreover, even some hydrophobic bile acids, such as chenodeoxycholic acid also exhibited cytoprotection. It is possible that the cytotoxicity of hydrophobic bile acids is ameliorated by more hydrophilic bile acids under certain conditions. The understanding of the precise mechanism of this phenomenon remains to be determined.     

MALT lymphoma at the base of the tongue developing without any background of immunodeficiency or autoimmune disease

We report a very rare case of a mucosa-associated lymphoid tissue (MALT) lymphoma of the base of the tongue. A 61-year-old woman was admitted to our hospital for further examination of a 12 mm x 15 mm x 5 mm tongue tumor. Histological examination of the tumor revealed a marked lymphoepithelial lesion. Lymphoma cells expressed CD5(-), CD10(-), CD19(+), CD20(+) on the surface of the cells by fluorescence activated cell sorter, and the genotypic analysis of the tumor cells revealed the presence of immunoglobulin heavy chain rearrangement and the absence of BCL-2 gene rearrangement by southern blot hybridization. Furthermore, neither the t(11;18) (q21;q21) translocation nor trisomy 3 was detected in lymphoma cells by fluorescence in situ hybridization method. The tongue tumor was completely resected and no recurrence has been noted in the 13 months to date.     

Gene expression profile of normal lungs predicts genetic predisposition to lung cancer in mice

Genetic susceptibility to lung tumorigenesis shows large variations among mouse strains. To test whether genetic predisposition to lung tumorigenesis is associated with a specific gene expression profile in normal lungs, we analyzed gene expression in 16 inbred strains of known susceptibility/resistance to lung tumorigenesis, using the RIKEN mouse full-length cDNA 19K microarray set. The strain-specific expression profile of 91 cDNA clones correlated with strain lung tumor susceptibility/resistance and predicted, by principal component analysis, the genetic predisposition to lung tumorigenesis in mice.     

Identification of env CRF-10 among HIV variants circulating in rural western Kenya

As part of a program to determine the genetic diversity of human immunodeficiency virus in rural Kenya, we carried out a molecular analysis of the C2-V3 region of HIV-infected blood samples obtained from 30 antenatal clinic attendees of seven health centers in western Kenya. Direct sequencing was carried out on the envelope C2-V3 region of proviral DNA. On phylogenetic analysis with reference strains, 20 were subtype Al, 2 were subtype D, 1 was subtype C, 1 was subtype G, 1 was CRF-10, 2A/D, 2A/C, and 2 were unclassified. The presence of CRF-10 and the great variety of subtypes and recombinants in such a limited sample size suggest that western Kenya may be a potential hotspot for HIV recombination in the country.     

Matrix Metalloproteinase Inhibitor, Marimastat, Decreases Peritoneal Spread of Gastric Carcinoma in Nude Mice

Marimastat, a matrix metalloproteinese inhibitor, was examined for the ability to prevent peritoneal dissemination of a human gastric cancer xenograft, TMK–1. Even with novel approaches such as molecular targeting of cancer chemotherapy, peritoneal dissemination of gastric cancer has little sensitivity to anticancer drugs, and it is impossible to inhibit its growth completely. Intraperitoneal injection of TMK–1 into nude mice at 5 × 10⁵ cells/body resulted in carcinomatous peritonitis that mimicked clinical cases. Continuous administration of marimastat (18 mg/kg/day) from 24 h after the tumor inoculation successfully inhibited the growth of peritoneal dissemination nodules. Combined administration of marimastat (18 mg/kg/day) and mitomycin C (MMC, 2 mg/kg) showed synergistic inhibition of growth of peritoneal dissemination, being superior to MMC alone (2 mg/kg). Although marimastat alone could not increase survival tune with statistical significance, combined administration of marimastat and MMC had a survival benefit with statistical significance. The combination of marimastat and MMC increased the preventive effect on peritoneal dissemination. Marimastat seems to be a candidate for the prevention of peritoneal spread of gastric carcinoma.