Phytic acid improves intestinal mucosal barrier damage and reduces serum levels of proinflammatory cytokines in a 1,2-dimethylhydrazine-induced rat colorectal cancer model.

Phytic acid (PA) has been demonstrated to have a potent anticarcinogenic activity against colorectal cancer (CRC). Defects of the intestinal mucosal barrier and inflammation processes are involved in the development and progression of CRC. In the present study, we evaluated the effect of PA on the intestinal mucosal barrier and proinflammatory cytokines. After a 1-week acclimatisation period, sixty Wistar male rats were divided into the following five groups, with twelve rats per group: the control group (CG), model group (MG), low-PA-dose group (0·25 g/kg per d), middle-PA-dose group (0·5 g/kg per d), and high-PA-dose group (1 g/kg per d). 1,2-Dimethylhydrazine (DMH) at a dosage of 30 mg/kg of body weight was injected weekly to induce CRC for 18 weeks. We examined the expression of genes related to the intestinal mucosal barrier in the model. The results demonstrated that tumour incidence was decreased following PA treatment. The mRNA and protein expression of mucin 2 (MUC2), trefoil factor 3 (TFF3) and E-cadherin in the MG were significantly lower than those in the CG (P<0·05). The mRNA and protein expression of claudin-1 in the MG were significantly higher than those in the CG (P<0·05). PA elevated the mRNA and protein expression of MUC2, TFF3 and E-cadherin, and diminished the mRNA and protein expression of claudin-1. Furthermore, PA decreased serum levels of proinflammatory cytokines, which included TNF-α, IL-1ß and IL-6. In conclusion, this study suggests that PA has favourable effects on the intestinal mucosal barrier and may reduce serum proinflammatory cytokine levels.

The Histogenesis of the Third Pathway of Colonic Carcinogenesis in Rats.

BACKGROUND/AIM: Conventional (tubular or villous) adenomas, and the more recently described serrated adenomas, are non-invasive neoplasias that precede colon carcinomas in carcinogen-treated rats. In contrast, the histological steps antedating carcinomas in gut-associated lymphoid tissue (GALT) in rats, i.e. the third pathway of colonic carcinogenesis, remain unidentified. Aim of the study was to investigate the histological changes preceding colonic GALT carcinomas in Sprague-Dawley (SD) rats. MATERIALS AND METHODS: Archived sections from previous experiments showing GALT mucosal domains in 292 rats were re-evaluated: 276 were injected with 1,2-dimethylhydrazine (DMH) suspended in ethylenedia-minetetra-acetic acid (EDTA), and 16 were controls (8 EDTA-treated, and 8 untreated). RESULTS: A total of 402 colonic GALT mucosal domains were found in the 292 rats: 382 in 276 DMH-treated, 10 in eight EDTA-treated, and 10 in eight-untreated rats. In DMH-treated rats, corrupted crypts (CCS; i.e. with asymmetric fission or abnormal crypt-alignment) were recorded in 50% of the GALT domains (15% had no dysplasia and 35% had epithelial dysplasia). Adenomas on top of GALT domains were found in 7%, and GALT carcinomas in 53%. Histology of the 146 colonic GALT carcinomas revealed highly differentiated carcinomas or signet-ring cell carcinomas. EDTA-treated and untreated animals showed no dysplastic CCS, or other neoplasia. CONCLUSION: This study demonstrated that GALT mucosal domains in carcinogen-treated rats often develop dysplastic CCS. Non-dysplastic CCS appear to act as scaffolds for the top-down replacement/transformation by dysplastic cells. Importantly, highly differentiated carcinomas were seen to evolve from dysplastic CCS and from adenomas, and signet-ring cell carcinomas from dysplastic goblet cells present at the base of crypts. This is the first study showing that non-invasive neoplastic lesions (dysplastic CCS and adenomas) antedate colonic GALT carcinomas in DMH-treated SD rats. The DMH-SD paradigm permits detailed study of the histological events preceding GALT carcinoma under standard laboratory conditions.

Pervaporation performance of PPO membranes in dehydration of highly hazardous mmh and udmh liquid propellants.

Polyphenylene oxide (PPO) membranes synthesized from 2,6-dimethyl phenol monomer were subjected to pervaporation-based dehydration of the highly hazardous and hypergolic monomethyl hydrazine (MMH) and unsymmetrical dimethyl hydrazine (UDMH) liquid propellants. Membranes were characterized by TGA, DSC and SEM to study the effect of temperature besides morphologies of surface and cross-section of the films, respectively. Molecular dynamics (MD) simulation was used to study the diffusion behavior of solutions within the membrane. CFD method was employed to solve the governing mass transfer equations by considering the flux coupling. The modeling results were highlighted by the experimental data and were in good agreement. High separation factors (35-70) and reasonable water fluxes (0.1-0.2 kg/m(2)h) were observed for separation of the aqueous azeotropes of MMH (35 wt%) and UDMH (20 wt%) and their further enrichment to >90% purity. Effect of feed composition, membrane thickness and permeate pressure on separation performance of PPO membranes were investigated to determine optimum operating conditions.

Synthesis of o-chlorophenols via an unexpected nucleophilic chlorination of quinone monoketals mediated by N,N'-dimethylhydrazine dihydrochloride.

An unexpected nucleophilic chlorination of a quinone monoketal while carrying out a pyrazolidine synthesis has led to a general preparation of multisubstituted phenols. The products are obtained in good to high yields under mild conditions. The bridged pyrazolidines that were the original targets are obtained in the presence of a protic solvent.

Unsymmetrical DMH - an isomer of 1,2 DMH - is it potent to induce gastrointestinal carcinoma in rats?

Very few animal studies have used 1,1-dimethyl hydrazine (unsymmetrical dimethyl hydrazine - UDMH) as a carcinogen. This study was designed to investigate the carcinogenicity of UDMH in the gastrointestinal tract in a rat model. We wanted to observe if there were any changes in tissue zinc levels and tissue copper zinc superoxide dismutase (CuZnSOD) enzyme activity during the carcinogenic process, and to compare these values with those of control rats in the medium- and long-term. Six-week-old Wistar rats were given a subcutaneous injection of UDMH (30mg/kg body wt) twice a week for 20 weeks, and sacrificed after 5 and 9 months of treatment. Tissue zinc levels showed a significant decrease (p<0.05) in the large intestine at 9 months, whereas in the stomach and small intestine there were no significant changes at 5 and 9 months. Tissue CuZnSOD enzyme activity in the stomach, small intestine and large intestine showed no significant decrease at 5 and 9 months as compared to controls. Histologically, the large intestine was normal at 9 months. This study suggests that UDMH administered at the above dosage was not carcinogenic in this model.

Total synthesis of (+)-rishirilide B: development and application of general processes for enantioselective oxidative dearomatization of resorcinol derivatives.

A concise synthesis of (+)-rishirilide B (2) is described. This is the first synthesis to be reported for the (+)-enantiomer of rishirilide B (2) as found in nature. The strategy accentuates the valuable combination of a method for o-quinone methide coupling with a method for enantioselective resorcinol dearomatization, which provides a densely functionalized chiral building block. The convergent synthesis illustrates several improvements and refinements to these methods and their supporting chemistries. Among these is the in situ generation of PhI[OTMS]OTf. Combination of this oxidant with phenol 31 constitutes the first example of a diastereoselective oxidative dearomatization of a resorcinol displaying a 2-alkyl substituent. In addition, the preparation of the cyclic sulfone 34 is reported. As a new dimethide precursor expressing a readily cleavable O-benzyl residue, sulfone 34 should prove useful in future endeavors. A protocol using the aluminum amide of dimethylhydrazine for opening and cleavage of a [1,4]-dioxan-2-one is also described. This procedure unmasks the hydroxy dione 36 by jettisoning the chiral directing group. Regioselective O-carbamylation of the 1,3-dione 36 enables the transformation of the remaining carbonyl into the alpha-hydroxy carboxylic acid found in 2. The total synthesis of (+)-rishirilide B (2) requires 15 pots from benzaldehyde 17 and 13 pots from benzaldehyde 32. The final product emerges in yields of 12.5% and 20.3% from compounds 17 and 32, respectively. The longest linear sequence requires eight chromatographies. Important observations leading to the development of the principle asymmetric method are described within the context of the total synthesis.

Lack of prevention of large intestinal cancer by VPS, an extract of Coriolus versicolor mushroom.

Cancer prevention studies were conducted with VPS, a hot water extract of the Coriolus versicolor (CV) mushroom, in female Swiss mice. The extract was administered in the diet for life to the animals. Three groups of mice received the following treatments: a). 1,2-dimethylhydrazine dihydrochloride (1,2-DMH) was administered as 10 weekly subcutaneous injections of 20 microg/g body weight, starting at 9 weeks of age; b). VPS was given at a 2% dose level starting at 7 weeks of age followed by 1,2-DMH, as described in group a; c). 1,2-DMH was administered as described in group a followed by VPS at a 2% dose level starting at 21 weeks of age. The number of animals with large intestinal tumors and the total number of these tumors were: a). 30,321; b). 29,359; and c). 28,415. These differences are not statistically significant. Because extracts of the CV mushroom are used by cancer patients as nutritional supplements in the U.S., and particularly in the Orient, the present negative result should caution its users.