Chitosan oligosaccharide as potential therapy of inflammatory bowel disease: therapeutic efficacy and possible mechanisms of action

Inflammatory bowel disease (IBD) results from intestinal epithelial barrier defect and dysregulated mucosal immune response. This study aimed to evaluate the therapeutic potential of chitosan oligosaccharide (COS), a biodegradation product of dietary fiber chitosan, in the treatment of IBD and to elucidate its possible mechanisms of action. Oral administration of COS protected against mortality and intestinal inflammation in a mouse model of acute colitis induced by 5% dextran sulfate sodium (DSS). The most effective dose range of COS was 10-20 mg/kg/day. In addition, nuclear factor kappa B (NF-κB) activation, and levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in colonic tissues were suppressed in mice receiving COS. Similar protective effect of COS against mortality and intestinal inflammation was observed in another mouse model of acute colitis induced by rectal instillation of 4% acetic acid. Importantly, COS administration after colitis induction was effective in ameliorating intestinal inflammation in both acute colitis models induced by 5% DSS and chronic colitis models induced by cycles of 2.5% DSS. In human colonic epithelial cells (T84 cells), COS treatment prevented NF-κB activation, production of TNF-α and IL-6, and loss of epithelial barrier integrity under both lipopolysaccharide (LPS) and TNF-α-stimulated conditions. Furthermore, binding of LPS to T84 cells, and TNF-α and oxidative stress-induced apoptosis of T84 cells were prevented by treatment with COS. These results suggest that COS may be effective in the treatment of IBD through inhibition of NF-κB signaling and apoptosis of intestinal epithelial cells.     

Changes of drug metabolizing enzymes in the liver of male sheep exposed to either cypermethrin or dimethoate

Xenobiotics such as insecticides are metabolized to more or less toxic metabolites by drug-metabolizing enzymes including cytochrome P450 (Cyp P450), cytochrome b5 (Cyp b5), NADPH-cytochrome c reductase (Cyt.c R), N-nitrosdimethylamine-N-demethylase I (NDMA-dI), glutathione (GSH), glutathione s-transferase (GST), and glutathione reductase (GR). Therefore, the present study showed the influence of oral administration of cypermethrin (6 and 12 mg/kg/day) and dimethoate (1.6 and 3.2 mg/kg/day) for 63 consecutive days on the activities of the above mentioned enzymes in the livers of male sheep. Low and high-treatments of sheep with cypermethrin significantly increased the levels of Cyp P450 by 56% and 98%, Cyp b5 by 65% and 80%, GSH by 68% and 74%, and Cyt.c R by 67% and 98%, respectively in a dose-dependent manner. However, low dose of cypermethrin increased the activities of GST and GR by 56% and 91% respectively. In addition, low and high dose-treatments with dimethoate increased the hepatic contents of Cyp P450 by 27% and 40%, GSH by 259% and 132%, whereas NDMA-dI decreased by 27 and 55% respectively, and no change in the content of Cyp b5 and the activity of Cyt.c-R at any given dose of this compound. It is concluded that exposure to cypermethrin and dimethoate significantly changed the hepatic activity of phases I & II drugmetabolizing enzymes in sheep, and these changes are mainly dependent on the administred dose, and also on the type of the tested insecticides. Also, such changes should be considered when therapeutic drugs administered to people exposed to such insecticides.     

The reliability and validity study of the Kinesthetic and Visual Imagery Questionnaire in individuals with Multiple Sclerosis

Objective

Motor imagery (MI) has been recently considered as an adjunct to physical rehabilitation in patients with multiple sclerosis (MS). It is necessary to assess MI abilities and benefits in patients with MS by using a reliable tool. The Kinesthetic and Visual Imagery Questionnaire (KVIQ) was recently developed to assess MI ability in patients with stroke and other disabilities. Considering the different underlying pathologies, the present study aimed to examine the validity and reliability of the KVIQ in MS patients.

Method

Fifteen MS patients were assessed using the KVIQ in 2 sessions (5-14days apart) by the same examiner. In the second session, the participants also completed a revised MI questionnaire (MIQ-R) as the gold standard. Intra-class correlation coefficients (ICCs) were measured to determine test-retest reliability. Spearman''s correlation analysis was performed to assess concurrent validity with the MIQ-R. Furthermore, the internal consistency (Cronbach''s alpha) and factorial structure of the KVIQ were studied.

Results

The test-retest reliability for the KVIQ was good (ICCs: total KVIQ=0.89, visual KVIQ=0.85, and kinesthetic KVIQ=0.93), and the concurrent validity between the KVIQ and MIQ-R was good (r=0.79). The KVIQ had good internal consistency, with high Cronbach''s alpha (alpha=0.84). Factorial analysis showed the bi-factorial structure of the KVIQ, which was explained by visual=57.6% and kinesthetic=32.4%.

Conclusions

The results of the present study revealed that the KVIQ is a valid and reliable tool for assessing MI in MS patients.     

Exposure keratopathy in sedated and ventilated patients

Purpose

The purpose of this study is to determine the frequency of exposure keratopathy in sedated/mechanically ventilated patients in the intensive care unit and its risk factors.

Materials and Methods

This is a prospective cohort study including all patients admitted to an adult intensive care unit department between March and October 2010 who were sedated and mechanically ventilated. Patients were examined by an ophthalmologist 1 to 5 days after commencing ventilation and subsequently every day. Examination included assessment of lid position, conjunctival edema (chemosis), and corneal changes.

Results

Of the 74 patients included in the study, 57% had exposure keratopathy. Fifty-four percent of patients developed chemosis, and 31% of patients developed lagophthalmos. Frequency of exposure keratopathy differed significantly according to degree of chemosis and lagophthalmos (P < .0001); lagophthalmos was also significantly related to chemosis (P < .0001). For lagophthalmos score of 3, the odds ratio of association with higher exposure keratopathy score was 136 (95% confidence interval [CI], 14.97-1242.6); for lagophthalmos score of 2, it was 14.4 (95% CI, 2.67-77.2). For any edema, the odds ratio of association with exposure keratopathy was 5.50 (95% CI, 2.02-15.00).

Conclusion

The frequency of exposure keratopathy in sedated/mechanically ventilated patients is high with lagophthalmos and chemosis as the main risk factors.