Intestinal tumorigenesis in the Apc1638N mouse treated with aspirin and resistant starch for up to 5 months.

The Apc1638N mouse model, which carries a targeted mutant allele within the adenomatous polyposis (Apc) gene and develops intestinal tumours spontaneously, predominantly in the small bowel, was used to investigate the effects of two potential chemopreventive agents, aspirin and alpha-amylase resistant starch (RS). Heterozygous Apc+/Apc1638N mice were fed semi-purified diets rich in animal fat, animal proteins and sucrose and low in dietary fibre (Western style diets) from approximately 6 weeks up to 6 months of age. Two of the diets contained aspirin (300 mg/kg diet) and two RS (1:1 mixture of raw potato starch: Hylon VII at 200 g/kg diet) in a 2 x 2 factorial design. A fifth treatment group were fed a conventional rodent chow diet. The mice fed the Western style diets became almost three times as fat as the chow-fed mice but this did not affect tumour yield. Treatment with RS resulted in significantly more intestinal tumours whereas aspirin alone had no effect. However, there was a significant aspirin x RS interaction, which suggests that aspirin could prevent the small intestine tumour-enhancing effects of RS in this Apc-driven tumorigenesis model. The possibility that large amounts of purified forms of resistant starch may have adverse effects within the small bowel is a novel observation that requires further investigation since greater intakes of starchy foods (and of RS) are being encouraged as a public health measure in compensation for reduced dietary fat intake. However, it remains possible that any increased risk is restricted to carriers of germline mutations in APC.

Mononuclear phagocyte populations in the transplanted human lung.

BACKGROUND: Dendritic cells (DC) are essential for the development of alloreactivity, however, little has been published regarding the distribution and phenotype of these and related mononuclear cells in human lung transplantation. METHODS: Lung frozen sections were examined for the presence of CD1a+ DC and for mononuclear cells and alveolar macrophages expressing CD11b and CD68. The effects of transplantation and immunosuppression were assessed by comparison of normal transplant transbronchial biopsy specimens to specimens from unused donor lungs; the normal transbronchial biopsy specimens also were compared with those showing rejection or obliterative bronchiolitis. RESULTS: All biopsy specimens, including those with obliterative bronchiolitis, showed a marked depletion of CD1a+ DC in lung allografts. This has not been described previously. In addition, transplantation and immunosuppression reduced alveolar macrophage coexpression of CD68 and CD11b, and this was reversed in acute rejection. CONCLUSION: The roles of pulmonary DC and other mononuclear phagocyte subpopulations need to be further defined, and data from animal models of lung transplantation should be interpreted with caution.

The effect of supplemental dietary fat on plasma cholesterol levels in lovastatin-treated hypercholesterolemic patients.

STUDY OBJECTIVE: A validation study was conducted first to test assumptions about the effect of saturated and unsaturated dietary fat supplements. The second study was conducted to determine the effect on blood cholesterol levels of saturated and unsaturated fat supplements in patients who followed a low-fat diet and were administered lovastatin. DESIGN: Randomized, crossover design, with three periods in the first study and four in the second study, each lasting 6 weeks. SETTING: Cholesterol Research Center. PATIENTS: The first study evaluated adults with total cholesterol levels between 200 and 280 mg/dl (5.172 and 7.241 mmol/L). The second study included adults with low-density lipoprotein (LDL) cholesterol levels above 160 mg/dl (4.138 mmol/L). INTERVENTIONS: Fat supplements with either coconut or canola oil were delivered to patients in oatmeal-raisin cookies. MEASUREMENTS AND MAIN RESULTS: In the validation study, patients' mean prerandomization total cholesterol level of 222 mg/dl was reduced to 213 mg/dl with canola oil and increased to 233 mg/dl with coconut oil cookies (p = 0.0038). In the second study the mean prerandomization total cholesterol level of 214 mg/dl was decreased to 199 mg/dl with canola oil and to 208 mg/dl with coconut oil cookies (p = 0.2342). The LDL cholesterol levels changed in a similar fashion in both studies. CONCLUSIONS: Changes in total and LDL cholesterol levels in the validation study were expected based on established effects of saturated and unsaturated fatty acids, but changes in these levels in lovastatin-cookie study were not expected. They could have occurred because lovastatin reversed the effect of saturated fats and enhanced the effect of unsaturated fats. Alternatively, they may have been due to enhanced bioavailability of lovastatin when administered with a high-fat diet. These findings must be confirmed.