The relationship between childhood onset obesity and psychopathology in adulthood.

We administered the Symptom Checklist (Derogatis, 1975; SCL-90-R) to 37 obese subjects in outpatient treatment for obesity. Patients with early onset obesity demonstrated a greater frequency and higher levels of emotional distress and psychiatric symptomatology than patients with late onset obesity. Individuals who developed obesity in childhood showed more psychopathology than those who developed obesity later in life. Overall, these findings support the belief that obesity is characteristically associated with greater internal psychological conflict. These findings further suggest that childhood obesity could serve as a predictor variable for possible future psychological disturbance in obese populations.

Quantitative determination of pentane in exhaled air correlates with colonic inflammation in the rat colitis model.

Oxygen radicals play a key role in inflammation and inflammatory tissue damage. Quantitative determination of pentane, a hydrocarbon generated by membrane lipid peroxidation initiated by oxygen radicals, in expired air has been used as a noninvasive determinant or index of inflammation in various conditions. Herein we report the first examination of the relationship between exhaled pentane and colonic inflammation in a rodent model of colitis. Colitis was induced in rats (n = 33) using the trinitrobenzene-sulfonic acid (TNB) model of colitis. Exhaled air was collected in a closed chamber on randomly selected animals on days 1, 2, 4, 7, 11, 13, 15, 20, and 25 post-TNB treatment, and pentane was assayed by means of gas chromatography. Gross and microscopic evidence of inflammation was compared with exhaled pentane levels. Pentane levels varied from 0.0 to 14.6 nmol/l of air and were significantly increased in TNB-treated rats compared with control rats only on days 7 to 15 after treatment (P < 0.05). Gross inspection showed severe colonic inflammation through the first week (mean score = 4.7 out of a possible 5), persistent inflammation on days 7 to 15 (3.2), and healing and fibrosis from the end of week two until day 25 (1.9 to 0). Histologic evaluation confirmed a progression of inflammation from acute ulceration to chronic inflammation to fibrosis and scarring. We have demonstrated that pentane exhalation is increased after the induction of colonic inflammation, with a seven-day lag time, and returns rapidly to normal as acute inflammation resolves. This suggests that pentane exhalation can be used as a noninvasive measure of colonic inflammation in rodent models of colitis and perhaps clinically in humans.

The effect of mild stress on DMH-induced colorectal cancer.

Epidemiologic studies suggest that certain psychosocial factors increase the risk of cancer. Yet, animal studies suggest that psychosocial stress inhibits the development of chemically induced tumorigenesis. The purpose of this study was to examine the effect of three different chronic mild stressors on the development of dimethylhydrazine (DMH)-induced colorectal carcinoma in rats. Results of this study show that the development of DMH-induced colorectal carcinoma was not significantly inhibited or altered by each individual stress treatment. Additionally, results indicate that mild stressors can induce neurochemical changes commonly associated with stress, without the confounding effects of more aversive stressors that are likely to compromise the nutritional and physiological status of the animal and thereby alter tumor formation.

Sulfasalazine alters the character of dimethylhydrazine-induced colorectal carcinoma in rats.

The etiologic variables involved in the increased incidence of colorectal carcinoma in patients with chronic ulcerative colitis have not been defined. Sulfasalazine is the most commonly used medication in the treatment of ulcerative colitis. It is not known whether the pharmacologic treatment of ulcerative colitis alters the incidence of cancer in man, but a drug related to sulfasalazine has been shown to reduce the incidence of colorectal carcinoma in rats. In this study we examined the effect of sulfasalazine on the development of 1,2-dimethylhydrazine-induced (DMH) colorectal carcinogenesis in rats. Daily oral ingestion of sulfasalazine in doses equivalent to human daily doses resulted in serum salicylate levels in those animals that were comparable to human therapeutic serum salicylate levels. Sulfasalazine administration did not significantly effect the incidence of DMH-induced colorectal tumors. However, sulfasalazine treated animals were found to have significantly smaller tumors and to show a trend towards multiple, flat, sessile, frequently microinvasive tumors compared to the fewer, larger, exophytic tumors observed in animals treated only with DMH. These results demonstrate that in the doses given, sulfasalazine treatment alters the character of DMH-induced colorectal tumors without significantly effecting tumor incidence.

The effect of iron on experimental colorectal carcinogenesis.

The effect of parenteral and oral iron was examined in the rat 1,2 dimethylhydrazine (DMH) colorectal carcinogenesis model in a series of experiments. Parenteral supplementation of iron was found to augment tumor yield (p = 0.012) and oral iron was found to augment tumor incidence (p = 0.03, when control groups were combined). In addition, phytic acid, a significant component of dietary fiber was found to reverse the augmenting effect of oral iron on tumor yield and incidence (p = 0.09 for both). Furthermore, in a short term DMH nuclear toxicity assay, analysis of the karyorrhectic index (KI), there was no difference in the KI between oral iron and phytate dietary groups (p = 0.53 for the left colon and p = 0.2 for the right colon), implying that iron's effect on colorectal tumor induction takes place during the promotional phase of carcinogenesis and not during initiation. These experiments support the epidemiologic observation that dietary iron may augment colorectal cancer risk and that the mechanism by which dietary fiber diminishes colorectal cancer risk may be the chelation of dietary iron by the phytic acid component of dietary fiber.

Effect of activity-stress on experimental rat colon carcinogenesis: early histopathologic changes and colon tumor induction.

The effect of stress on experimental colon carcinogenesis was investigated in the rat by adapting the activity-stress ulcerogenesis model to the 1,2-dimethylhydrazine (DMH) rat colon carcinogenesis model. Activity-stress was applied intermittently (normal housing conditions alternated with activity-stress conditions on an equal time basis) to DMH-injected rats either throughout the experiment (AS-DMH) or following completion of DMH injections (DMH-AS). The AS-DMH treatment was associated with reduced colonic tumor induction compared with controls, as was to a lesser degree with DMH-AS condition. In a separate study, the early histopathologic effects on the colon of a single DMH injection, an activity-stress treatment, or the combination of both DMH and activity-stress treatments were compared with those of controls. Activity-stress moderated DMH-induced increases in colonic epithelial cell proliferation and nuclear hyperchromia when compared with DMH treatment alone. The findings of activity-stress-associated protection on colon tumor induction and the concordance of these results with quantitative early histopathologic alterations demonstrate that in the rat activity-stress exerts a protective influence in colon carcinogenesis. In addition, these results suggest further that risk modifiers of colon cancer can be assessed in short-term studies that quantify early histopathologic alterations.

A comparison of dietary fish oil and corn oil in experimental colorectal carcinogenesis.

Rats fed either fish oil (n = 16) or corn oil (n = 16) in calorically and nutritionally balanced diets were injected with 1,2-dimethylhydrazine, which is a colorectal specific carcinogen; differential colorectal tumor induction was then measured. In addition, plasma peroxide concentrations were measured in rats in each dietary group as well as in a group receiving a low-fat diet, either with or without prior carcinogen treatment (n = 3 for each of the 6 groups). Tumor incidence did not differ between groups fed corn oil and fish oil. Tumor yield in the left colon was significantly lower in rats fed fish oil (p = 0.0499). Total colorectal tumors induced were also fewer in the rats fed fish oil (p = 0.065). Plasma peroxide concentrations were difficult to interpret because of the wide variation within groups. The data on tumor yield in the left colon support the hypothesis that a diet rich in n-3 fatty acids, which are found in fish oil, may be less supportive of colorectal tumor development than a diet rich in n-6 fatty acids, which is found in corn oil. However, the mechanism by which fish oil decreases tumor induction is still unknown.

The effect of dietary milk and calcium on experimental colorectal carcinogenesis.

This investigation was based on an epidemiologic association of milk consumption and decreased intestinal cancer risk. Furthermore, there is also some indirect evidence that calcium supplementation in humans and animals may decrease colon cancer risk and that calcium, by inference, may be the protective factor in milk. In order to investigate these associations in a controlled laboratory setting, dietary supplementation of low fat dried milk (37 g/kg diet; N = 18) and calcium carbonate (40 mg/kg rat/day; N = 17) were compared separately to regular diet controls in the rat-dimethylhydrazine colon carcinogenesis model. The results of this investigation showed that neither milk-supplemented rats nor calcium carbonate-supplemented rats had fewer DMH-induced colorectal (P = .374) or total gastrointestinal tumors (P = .291) than did regular diet controls (N = 10; by analysis of variance [ANOVA]). Milk supplementation did result in a significant decrease in tumor burden when measured by incidence of metastases (P = .035) and of intestinal obstruction (P = .011; by chi-square test), when compared with calcium-supplemented and control rats. Though this implies that milk supplementation provides protection against some aspects of carcinogenesis of the colon, in rats fed low fat diets, this does not appear to be mediated through the calcium content of milk.

The influence of physical activity in 1,2 dimethylhydrazine induced colon carcinogenesis in the rat.

Recent epidemiologic findings indicate that relative risk of colon cancer is augmented with increasing proportion of time spent on sedentary occupations, and reduced with occupations requiring high levels of work-related physical activity. Therefore, the influence of exercise on experimental colon carcinogenesis was investigated. Spontaneous running wheel activity was related to incidence of 1,2 dimethylhydrazine (DMH) colon tumor induction. Colon tumor incidence was significantly reduced in animals that were allowed spontaneous wheel activity throughout the period of DMH tumor induction vs standard housed controls (p less than 0.05), indicating that, in the rat, physical activity protects against colon tumorigenesis. Further comparisons reveal a mild positive association (p = 0.07) between activity and incidence of tumors in the left colon. These results are in accord with epidemiologic findings indicating reduced colon cancer risk with increased physical activity. Possible mechanisms for the protective influence of physical activity on tumorigenesis include reduction in fecal pH, body weight and increased antioxidant enzyme activity. To the extent that epidemiologic associations between colon cancer and activity are inclusive of the multidimensional nature of physical activity, animal models such as that utilized in this experiment can be utilized for investigating the etiologic potential, or strength of association in variables that have been epidemiologically associated with colon cancer risk.

Influence of maturation on activity-stress related pathology in the rat colon.

In the rat, activity-stress (A-S) treatment was related to varying degrees of inflammation, goblet depletion, and erosion of the mucosal wall. Young (aged twenty-eight days), and mature (aged seventy days), rats did not differ significantly in terms of overall thinning of the colon wall, however the incidence of hematuria, hemorrhage at fecal bolus sites, mucosal hyperemia and interstitial compression of the mucosal wall was greater for younger animals. These findings suggest that A-S produces both more severe and more acute colonic pathology in young animals. The use of the A-S paradigm as an appropriate route for inducing psychological stress is discussed in terms of its capacity to evoke a somatic stress response as indicated by stereotypical alterations of structure and function of the gastrointestinal and thymicolymphatic system.