Intestinal toxicity evaluation of long-circulating and pH-sensitive liposomes loaded with cisplatin.

Cisplatin (CDDP) is a chemotherapeutic agent widely used in several anticancer protocols for instance head and neck, testicle, ovarian, lung and peritoneal carcinomatosis. According to the literature, the use of CDDP is associated with several side effects; among them, we highlighted the mucositis. CDDP, when administered by IP, promoted significant intestinal epithelium alterations in an experimental model. Our research group has proposed that the incorporation of CDDP into long-circulating and pH-sensitive liposomes (SpHL-CDDP) could help to overcome some side effects induced by this drug. Thus, we evaluated signs of intestinal toxicity 24h and 72h after the administration of a single i.p dose of free CDDP or SpHL-CDDP to healthy Swiss mice. Twenty-four hours after administration of free CDDP, the mice showed signs of intestinal toxicity, principally weight loss, increased intestinal permeability associated with a decrease in expression of tight junctions, and histological damage with the presence of inflammatory infiltrates and activation of ERK1/2 and NF-κB. These changes persisted after 72h. While signs of intestinal toxicity were also observed 24h after administration of SpHL-CDDP, after 72h body weight and intestinal permeability of mice in this group were similar to those of mice in the control group. In comparison with the free CDDP treatment group, 72h after treatment mice in the SpHL-CDDP group showed better histological parameters, lower levels of inflammatory infiltrate with increased IL-10 and IgA levels, and less activation of caspase-3, ERK1/2 and NF-κB. These differences could account for the recovery of the intestinal epithelium observed in mice treated with SpHL-CDDP but not in mice treated with free CDDP. In conclusion, here we show that encapsulation of CDDP in SpHL lessens intestinal damage and that, as such, SpHL-CDDP is a promising candidate for clinical use.

Food quality, physical activity, and nutritional follow-up as determinant of weight regain after Roux-en-Y gastric bypass.

OBJECTIVE: Assess the lifestyle habits, including food patterns, of patients who underwent Roux-en-Y gastric bypass (RYGB) and to identify predictive factors in weight loss and regain. METHODS: Obese patients (100) who underwent RYGB from 1998 to 2008 were included. Dietary habits were assessed by using 24 h dietary recall and the Food Frequency Questionnaire. Rates of weight regain and the percentage of excess weight loss (EWL) were calculated. Patients were also asked whether they attended nutritional follow-up visits after the operation and about the type and regularity of physical activities. RESULTS: The mean age was 45.1 ± 9.9 y, and the majority of the patients were women (84%). Mean EWL was 59.1 ± 20.3%. Weight regain was seen in 56% of the patients with 29% of the patients having regained over 10.1% of the minimum weight reached after RYGB. Weight regain increased significantly with time after surgery (up to 2 y: 14.7%; from 2 to 5 y: 69.7%; over 5 y: 84.8%). Poor diet quality characterized by excessive intake of calories, snacks, sweets, and fatty foods was statistically higher among those who regained weight. Sedentary lifestyle and lack of nutritional counseling follow-up were also significantly associated with regaining weight. CONCLUSION: Despite satisfactory results of EWL, the patients did not properly maintain the lost weight, mainly after 5 y postsurgery. Major factors that influenced this weight gain were poor diet quality, sedentary lifestyle, and lack of nutritional counseling follow-up.