Helium-oxygen improves Clinical Asthma Scores in children with acute bronchiolitis

Sprague-Dawley rats (n = 32) were fed diets without fiber (control) or containing 1 or 5% chicory extract or 5% inulin for 4 wk; 0.2% cholesterol was added to all diets. Rats fed chicory extract and inulin diets had significantly higher serum high density lipoprotein (HDL) cholesterol and generally lower low density lipoprotein (LDL) cholesterol concentrations, thus significantly greater ratios of HDL/LDL cholesterol compared with the controls (P < 0.05). The serum apolipoprotein B/apolipoprotein A-1 ratio was significantly lower in rats fed diets containing chicory extract or inulin than that in rats fed fiber-free diets, due to significant reductions in apolipoprotein B concentration (P < 0.05). Greater liver lipid and triglyceride concentrations were observed in rats fed chicory extract or inulin diets compared with the controls (P < 0.05). However, liver phospholipid and cholesterol concentrations were not significantly different among groups (P > 0.05). Addition of 5% inulin to the diet resulted in greater cecal weight, whereas both 5% chicory extract and 5% inulin resulted in greater cecal propionic acid concentration compared with the controls (P < 0.05). Rats fed chicory extract and inulin had significantly greater fecal lipid, cholesterol and bile acid excretions than those fed fiber-free diets (P < 0.05). The results of this study suggest that the improved lipid metabolism observed in rats fed chicory extract (mainly inulin component) may be caused by an alteration in the absorption and/or synthesis of cholesterol, which might result from the changes in cecal fermentation, and by an increase in the fecal excretion of lipid, cholesterol and bile acid.     

Metabolic epidemiology of colon cancer. Fecal bile acids and neutral sterols in colon cancer patients and patients with adenomatous polyps

Because of potential significance of bile acids and cholesterol metabolites in the pathogenesis of colon cancer, fecal neutral sterols, and bile acids were determined in patients with colon cancer, adenomatous polyps or other digestive diseases and American or Japanese controls. The fecal excretion of cholesterol, coprostanol, coprostanone, total bile acids, deoxycholic acid, lithocholic acid was higher in patients with colon cancer and patients with adenomatous polyps compared to normal American and Japanese controls as well as patients with other digestive diseases. Patients with other digestive diseases excreted comparable levels of fecal bile acids and cholesterol metabolites compared to normal American controls; Japanese controls excreted reduced levels compared to normal American controls. These findings suggest that possible interactions between bile acids and cholesterol metabolites and colonic epithelial cells may be relevant in colon carcinogenesis.     

Regulation of fecal bile acid excretion in male golden Syrian hamsters fed a cereal-based diet with and without added cholesterol

The objective of these studies was to investigate the comparative physiology and regulation of bile acid metabolism in the male Golden Syrian hamster by measuring the rate of fecal bile acid excretion and bile acid pool size in animals fed a cereal-based diet either alone, or with added cholesterol or cholestyramine. In group-housed hamsters fed only the plain diet fecal bile acid excretion in animals at 6, 10, and 15 weeks of age averaged 11.0, 8.0, and 6.9 mumol/d per 100 g body weight (bw), respectively. Pool size, measured by subtracting from the total amount of bile acid washed out over 12 hours of biliary diversion the amount of bile acid excreted in the stools over the same period, equalled 17.8 mumol/100 g bw in 15-week-old hamsters fed the plain diet. Hence, under basal conditions, these animals turned over about 38% of their bile acid pool daily. In hamsters fed a diet with 3% cholestyramine for 18 days, fecal bile acid excretion averaged 20.6 mumol/d per 100 g bw, and the pool size contracted to 5.8 mumol/100 g bw. In matching animals fed a diet containing 0.12% cholesterol for 30 days, hepatic cholesterol levels increased from 1.9 +/- 0.1 to 12.6 +/- 0.7 mg/g, fecal bile acid excretion increased marginally from 5.8 to 8.0 mumol/day per 100 g bw, while pool size was unchanged (16.6 mumol/100 g bw). When the cholesterol content of the diet was raised to 1.0%, hepatic cholesterol levels reached 66.5 +/- 2.6 mg/g, but bile acid excretion remained at 8 mumol/d per 100 g bw. These data define some of the basal features of bile acid metabolism in the hamster, and substantiate the view that the marked cholesterolemic response of this species may relate partly to a limited ability to convert dietary cholesterol to bile acid.     

Effect of oyster mushroom (Pleurotus ostreatus) on pathological changes in dimethylhydrazine-induced rat colon cancer

The effect of 5% of dried oyster mushroom (Pleurotus ostreatus) in the diet on the dimethylhydrazine (DMH)-induced colon carcinogenesis was studied in male Wistar rats. DMH in a dose of 20 mg/kg of body weight was applied to animals once a week during a period of 12 weeks. Mushroom diet was applied either after treatment with DMH for another 21 weeks or during the whole experiment. Mushroom diet reduced significantly the incidence of lymphoid hyperplasia foci when mushroom was supplemented during the whole experiment. Tumour lesions could be characterized either as carcinoma in situ, or as infiltrating adenocarcinoma. Mushroom diet did not affect significantly the incidence of tumours. Nevertheless, a reduction in total number of tumours was observed in both groups of animals fed mushroom diet. A significant reduction of the number of tumour foci of the type carcinoma in situ was observed in animals fed the oyster mushroom during the whole experiment. Also these animals had the significantly lower number of aberrant crypt foci. Mushroom diet reduced the ornithine decarboxylase activity in the colon and in the liver when oyster mushroom diet was administered during the whole experiment.     

Dietary stearic acid reduces plasma and hepatic cholesterol concentrations without increasing bile acid excretion in cholesterol-fed hamsters

Although there is general agreement that saturated fatty acids elevate plasma cholesterol concentrations, the relative effects of individual fatty acids on cholesterol and bile acid metabolism are less clear. In this study, cholesterol and bile acid responses to diets enriched in different saturated fatty acids were investigated in hamsters. The six diets examined were as follows: 5% fat (g/100 g) enriched in palmitic acid (16:0) with no cholesterol, 5% fat 16:0-enriched, 0.05% cholesterol (wt/wt), and four diets containing 0.05% cholesterol and 15% fat with each diet enriched in lauric (12:0), myristic (14:0), palmitic (16:0), or stearic acid (18:0). Total plasma cholesterol concentration was significantly greater in hamsters fed the 14:0-enriched diet relative to those fed the 18:0-enriched diet (P < 0.05). Both plasma and liver cholesterol concentrations of hamsters fed 18:0 did not differ from those of the group fed no dietary cholesterol. In all instances, differences in total plasma cholesterol were accounted for within the HDL fraction; no significant treatment differences in VLDL or LDL cholesterol were found. Total daily fecal bile acid excretion was higher in hamsters fed the 15% fat 16:0 diet compared with those fed no dietary cholesterol (P < 0.05), but not significantly different from other treatment groups. There was greater deoxycholic acid excretion (P < 0.05) from hamsters fed the 14:0 and 16:0 diets compared with those fed the 18:0-enriched diet. Small intestinal + gallbladder bile acids, an index of pool size, did not differ significantly among the groups. The observed relative hypocholesterolemic effect of stearic acid was not mediated by increased bile acid excretion.     

Enrichment of the more hydrophilic bile acid ursodeoxycholic acid in the fecal water-soluble fraction after feeding to rats with colon polyps

We recently showed that feeding the cytoprotective bile acid ursodeoxycholic acid (UDCA) to rats resulted in significant reduction in polyps and especially cancers, both in number and size (D. L. Earnest et al., Cancer Res., 54: 5071-5074, 1994). Because fecal secondary bile acids [particularly deoxycholic acid (DCA)] are considered to promote formation of colon adenomas and cancer, we have now attempted to find a relationship between polyp reduction and fecal secondary bile acids after feeding UDCA to these rats. We examined the fecal bile acids in rats with polyps and compared them with fecal bile acids in control rats and also determined the bile acid composition in fecal aqueous phase, which is in direct contact with the colon epithelium and may be physiologically more active. Treatment with azoxymethane did not significantly alter fecal bile acid composition in the rats. Cholic acid feeding resulted in greatly increased proportions of DCA (82% of total bile acids versus 18% in control rats). On the other hand, UDCA feeding significantly reduced the proportion of fecal DCA (2% in control rats fed UDCA and 3% in rats also treated with azoxymethane). In control rats, 96% of the bile acids were present in the water-insoluble fraction and 4% in the water-soluble fraction. The major insoluble bile acids included DCA and hyodeoxycholic acid (73% of total bile acids). In contrast, the muricholic acids were concentrated in the soluble fraction (37%). When 0.4% UDCA was added to the diet, lithocholic acid increased in the insoluble fraction (40 versus 1%), but the hydrophilic UDCA and muricholic acids were enriched in the water-soluble fraction (37 and 43%, respectively). Thus, the hydrophobic bile acids were distributed predominantly in the water-insoluble fraction, whereas the hydrophilic bile acids were distributed preferentially in the water-soluble fraction. These data suggest that UDCA may prevent colon tumors and polyps by countering the toxic effect of DCA and enhancing the possible cytoprotective effects of UDCA and muricholic acids in the water-soluble fraction in the feces of rat.     

Accelerating effect of chitosan intake on urinary calcium excretion by rats

The effect of chitosan on calcium (47Ca) metabolism was investigated in rats. The whole-body retention of 47Ca by rats fed on a 5% chitosan diet was significantly decreased when compared with that of rats fed on a cellulose diet, but showed no significant difference from that of rats fed on a fiber-free diet. Although there was no significant difference in the fecal excretion of 47Ca between the chitosan group and the cellulose or fiber-free group, the urinary excretion of 47Ca was significantly increased in the chitosan group when compared with the cellulose group. These results suggest that dietary chitosan would affect the calcium metabolism in animals.     

Fecal characteristics contrasted in the irritable bowel syndrome and diverticular disease

A comparison has been made of the fecal characteristics in controls and patients with the irritable bowel syndrome and diverticular disease. No detectable difference was found in the fecal wet weight, dry weight, or total bile acid excretion in the four groups. A significant increase in the percentage of the water content of the stool was seen in the idiopathic diarrhea group with irritable bowel syndrome. Significantly less magnesium, potassium, and calcium was found in the stools of patients with diverticular disease and a similar trend was noted in patients with the spastic colon. These changes did not relate to the age of the patients. This suggests a common etiology for these disorders. The presence of increased water and primary bile acids in the feces of patients with idiopathic diarrhea suggests that this is a separate entity.     

Retrograded high-amylose corn starch reduces cholic acid excretion from the small bowel in ileostomy subjects

OBJECTIVE: To study the short-term effect of resistant starch (RS) from retrograded high-amylose corn starch (HACS) on the excretion of bile acids and nutrients from the small bowel in humans. DESIGN: Seven healthy ileostomists were given a controlled, constant diet during three days. On days 2 and 3, 100 g/d of one of two test-products--drum-dried ordinary corn starch and autoclaved retrograded HACS, providing 5 and 39 g RS/d, respectively--was given, in random order. Ileostomy effluents were collected for 24 h per day and analysed for wet weight, dry weight, energy, bile acids and nutrients. SETTINGS: In-patient study at the metabolic ward, Department of Clinical Nutrition, Sahlgrenska University Hospital, G?teborg. RESULTS: Consumption of retrograded HACS caused (1) a 42% lower mean excretion of cholic acid (P = 0.024); (2) a 42% lower mean wet weight concentration of bile acids (P < 0.001); (3) a 70% increased excretion of dry weight (P = 0.001); and (4) a 41% increased excretion of energy (P= 0.036) compared with consumption of drum-dried ordinary corn starch. CONCLUSION: The reduced ileal excretion and concentration of cholic acid would be protective regarding colon cancer risk in addition to the increased fermentation substrate provided by RS and other energy-yielding components.     

Colon cancer and diet, with special reference to intakes of fat and fiber

Colon cancer, rare in the past, and in developing populations, currently accounts for 2 to 4% of all deaths in Western populations. Evidence suggests the primary cause to be changes in diet, which affect the bowel milieu intérieur. It is possible that in sophisticated populations, the higher concentrations of fecal bile acids and sterols, and longer transit time, favor the production of potentially carcinogenic metabolites. Of secular changes in diet, evidence suggests that the following may have etiological importance: 1) the fall in intake of fiber-containing foods with its effects on bowel physiology, and 2) the decreased fiber but increased fat intakes, in their respective capacities to raise concentrations of fecal bile acids, sterols, and other noxious substances. For possible prophylaxis against colon cancer, recommendations for a lower fat intake, or a higher intake of fiber-containing foods (apart from fiber ingestion from bran) are extremely unlikely to be adopted. For future research, western populations with considerably lower than average mortality rates, e.g., Seventh Day Adventists, Mormons, the rural Finnish population, as well as developing populations, demand intensive study. Also requiring elucidation are the respective roles of diet and of genetic constitution on concentrations of fecal bile acids, etc., and on transit time, in prone and nonprone populations.     

Gender-related differences in bile acid and sterol metabolism in outbred CD-1 mice fed low- and high-cholesterol diets

These studies were undertaken to determine whether in young adult outbred CD-1 mice there were any gender-related differences in basal bile acid metabolism that might be important in determining how males and females in this species responded to a dietary cholesterol challenge. When fed a plain cereal-based rodent diet without added cholesterol, 3-month-old females, compared with age-matched males, manifested a significantly larger bile acid pool (89.1 vs. 54.1 micromol/100 g body weight), a higher rate of fecal bile acid excretion (13.6 vs. 8.5 micromol/d/100 g body weight), a more efficient level of intestinal cholesterol absorption (41.1% vs. 25. 3%), and a lower rate of hepatic sterol synthesis (338 vs. 847 nmol/h/g). Similar results were found in C57BL/6 and 129Sv inbred mice. In matching groups of CD-1 mice fed a diet containing 1% cholesterol for 21 days, hepatic cholesterol levels increased much more in the females (from 2.4 to 9.1 mg/g) than in the males (from 2. 1 to 5.2 mg/g). This occurred even though the level of stimulation of cholesterol 7-hydroxylase activity in the females (79%) exceeded that in the males (55%), as did the magnitude of the increase in fecal bile acid excretion (females: 262% vs. males: 218%). However, in both sexes, bile acid pool size expanded only modestly and by a comparable degree (females: 19% vs. males: 26%) so that in the cholesterol-fed groups, the pool remained substantially larger in the females than in the males (102.3 vs. 67.6 micromol/100 g body weight). Together, these data demonstrate that while male and female CD-1 mice do not differ qualitatively in the way cholesterol feeding changes their bile acid metabolism, the inherently larger bile acid pool in the female likely facilitates the delivery of significantly more dietary cholesterol to the liver than is the case in males, thereby resulting in higher steady-state hepatic cholesterol levels.     

Chemoprevention of colon cancer by organoselenium compounds and impact of high- or low-fat diets

BACKGROUND: Observational and experimental studies have suggested that dietary supplementation with selenium can inhibit the development of colon cancer. However, many forms of selenium are toxic. Consequently, the development of efficacious compounds with low toxicity has been pursued. PURPOSE: Two synthetic organoselenium compounds, p-methoxy-benzyl selenocyanate (p-methoxy-BSC) and 1,4-phenylenebis(methylene)selenocyanate (p-XSC), were tested for their ability to inhibit colon carcinogenesis in rats that were treated with the carcinogen azoxymethane and fed low- or high-fat diets. METHODS: Groups of 5-week-old male F344 rats (42 animals/ group) were fed either a high-fat diet or a low-fat diet with or without added p-methoxy-BSC (10 or 20 parts per million [ppm]) or p-XSC (20 ppm). Two weeks later, 30 animals in each group received a subcutaneous injection of azoxymethane (15 mg/kg body weight); 1 week later, they received a second injection. The remaining 12 rats in each group received two injections of saline. Three days after the second injection of carcinogen or saline, animals being fed diets with p-methoxy-BSC or p-XSC were switched to corresponding organoselenium-free low- or high-fat diets for the remainder of the study to determine the effects of the selenium compounds on the initiation phase of colon carcinogenesis. At that time, groups of animals that had been maintained on organoselenium-free low- or high-fat diets were switched to diets containing p-methoxy-BSC or p-XSC until the end of the study to determine the effects of these compounds on the postinitiation phase of colon carcinogenesis. All animals were killed during the 38th week after azoxymethane or saline treatment, and histopathologic analysis of the colon tumors was performed. Colon tumor incidence and multiplicity were analyzed statistically. RESULTS: No obvious toxic effects were observed following dietary administration of 10 or 20 ppmp-methoxy-BSC or 20 ppm p-XSC. Administration of 20 ppm p-methoxy-BSC in a high-fat diet during the initiation and postinitiation phases of colon carcinogenesis significantly (statistically) reduced colon tumor incidence; 10 ppmp-methoxy-BSC in a high-fat diet significantly reduced colon tumor incidence but only when it was given during the postinitiation phase. Colon tumor incidence was also significantly reduced when 20 ppm p-XSC was given in a high-fat diet during the initiation phase of colon carcinogenesis. When 20 ppm p-XSC was administered in either a high-fat diet or a low-fat diet during the postinitiation phase, both colon tumor incidence and multiplicity were significantly reduced; the greatest reductions were in animals fed a low-fat diet. CONCLUSIONS: In this model system, p-methoxy-BSC and p-XSC are effective agents for the chemoprevention of colon cancer. The effects of p-XSC were enhanced in animals fed a low-fat diet.     

The effects of various diphosphonates on a rat model of cardiac calciphylaxis

Compartmental analysis of the disappearance curve of serum cholesterol specific activity after an intravenous administration of a tracer does of cholesterol-4-14C was carried out in five patients with resection of the distal small intestine, cecum, and proximal colon. The data fit best a two compartment model in all five cases with the rapidly exchangeable pool of 16.6+/-3.2 g (mean +/- SD, 60% of the mean of 15 normal subjects) and the slowly exchangeable pool of 31.5 +/- 10.9 g (65%). The reduction of the pool sizes was associated with a shorter mean transit time of cholesterol, 22.15 +/- 8.07 days (40%) and increased turnover rate, 2.42 +/- 0.72g/ day (172%). Direct fecal analysis for the neutral sterols and bile acids derived from the exchangeable pool confirmed the turnover rate obtained from the compartmental analysis. The increased fecal excretion was mainly in the bile acid fraction. The study suggests that the ileal and proximal colon resection results in bile acid malabsorption which, in turn, increases hepatic cholesterol and bile acid synthesis. The synthetic rates, however, could not compensate totally for the excretory rate. Therefore, the pool size decreased to a new low steady state of equilibrium.     

Enhancement of experimental colon cancer by genistein

Several phytochemicals and micronutrients that are present in fruits and vegetables are known to exert cancer chemopreventive effects in several organs, including the colon. Among them, the soybean isoflavonoid genistein received much attention due to its potential anticarcinogenic, antiproliferative effects and its potential role in several signal transduction pathways. The present study was designed to investigate the effect of genistein on azoxymethane (AOM)-induced colon carcinogenesis and to study its modulatory role on the levels of activity of 8-isoprostane, cyclooxygenase (COX), and 15-hydroxyprostaglandin F2alpha dehydrogenase (15-PGDH) in the colonic mucosa and colon tumors of male F344 rats. At 5 weeks of age, groups of male F344 rats were fed control (AIN-76A) diet or a diet containing 250 ppm genistein. Beginning 2 weeks later, all animals except those in the vehicle-treated groups were given weekly s.c. injections of AOM (15 mg/kg body weight) for 2 successive weeks. All rats were continued on their respective dietary regimen for 52 weeks after AOM treatment and were then sacrificed. Colon tumors were evaluated histopathologically. Colonic mucosae and tumors were analyzed for COX, 15-PGDH, and 8-isoprostane levels. Administration of genistein significantly increased noninvasive and total adenocarcinoma multiplicity (P < 0.01) in the colon, compared to the control diet, but it had no effect on the colon adenocarcinoma incidence nor on the multiplicity of invasive adenocarcinoma (P > 0.05). Also, genistein significantly inhibited the 15-PGDH activity (>35%) and levels of 8-iosoprostane (50%) in colonic mucosa and in tumors. In contrast, genistein had no significant effect on the COX synthetic activity, as measured by the rate of formation of prostaglandins and thromboxane B2 from [14C]arachidonic acid. The results of this investigation emphasize that the biological effects of genistein may be organ specific, inhibiting cancer development in some sites yet showing no effect or an enhancing effect on the tumorigenesis at other sites, such as the colon. The inhibition of 8-isoprostane levels by genistein indicates its possible antioxidant potential, which is independent of the observed colon tumor enhancement, yet this agent may also possess several biological effects that overshadow its antioxidant potential. The exact mechanism(s) of colon tumor enhancement by genistein remain to be elucidated; it is likely that its colon tumor-enhancing effects may, at least in part, be related to inhibition of prostaglandin catabolic enzyme activities.     

Surgical management of retinal detachments related to coloboma of the choroid

We examined the influence of extruded chickpeas and wheat relative to casein and wheat in a dimethylhydrazine (DMH)-induced colon tumor study in male Sprague-Dawley rats. The three diets, based on a modified AIN76 rodent diet with fat present at 10 g/100 g dry matter (DM), were as follows: casein with wheat starch (Cas/S) as control, casein with wheat (Cas/W) and chickpeas with wheat (CP/W). All diets were fed from 5 wk of age throughout the 28-wk study. At 28 wk, there was a significantly lower incidence of large intestinal tumors in rats fed Cas/W relative to those fed CP/W ( 11 vs. 56%, chi-square test, P = 0.018). The colonic tumor burden (tumors/tumor-bearing animal) was not different in Cas/W-fed and CP/W-fed rats (1 vs. 1.7), but the tumor mass index was significantly lower in the former group (0.22 vs. 1.21, P = 0.026). Rats fed the CP/W diet had significantly lower plasma cholesterol concentration (P < 0.01) than rats fed the other two diets. The cecal contents of rats fed the CP/W diet had significantly greater relative weights (46%, P < 0.05) than those of the Cas/W-fed rats; this was associated with higher concentrations of all short-chain fatty acids. Fecal analyses showed significantly (P < 0.05) higher concentrations of total fat (54%), total steroids (83%) and secondary bile acids (179%) in the CP/W-fed rats relative those fed Cas/W. There were higher concentrations of nitrogen in the feces of CP/W rats relative to the Cas/W-fed rats (84%, P < 0.05), associated with greater fecal weights (67%, P < 0.05). Although wheat and its fibers have been shown to be protective against DMH-induced cancers in rats, this was not the case in this study in which chickpeas (45 g/100 g diet) provided the protein and were an important source of soluble fiber. Elevated fat, secondary bile acid concentrations and/or nitrogenous compounds could be responsible for the increased colon tumorigenesis seen and may reflect a legume effect.     

Breast cancer imaging--what are the optimal modalities?

Different soluble dietary fibers known to alter cholesterol metabolism were fed to golden Syrian hamsters, and their specific impact on lipoproteins, biliary bile acid profile, and fecal sterol excretion was evaluated. Semipurified diets containing 20% fat; 0.12% cholesterol; and 8% of psyllium (PSY); high (hePE) and low (lePE) esterified pectin; or high (hvGG) and low (lvGG) viscous guar gum were fed for 5 wk. Compared to control, PSY caused a significant reduction in plasma cholesterol (2.9 +/- 0.5 vs. 5.5 +/- 0.5 mmol/L), whereas hePE, lePE, hvGG, or lvGG had no apparent effect on plasma lipids. Hepatic total and esterified cholesterol were substantially decreased with PSY, pectin and guar gum, whereby PSY produced the most pronounced effect. Distinctive changes existed in the bile acid profile related to the different fibers. In contrast to pectin and guar gum, PSY caused a significant increase in the cholate:chenodeoxycholate and the glycine:taurine conjugation ratio. Pectin and guar gum did not alter daily fecal neutral sterol excretion while PSY caused a 90% increase due to a higher fecal output. Daily fecal bile acid excretion and total fecal bile acid concentration were significantly increased by PSY, whereas hePE, lePE, hvGG, and lvGG revealed no or only minor effects. Taken together, the disparate hypocholesterolemic effects of PSY, pectin, and guar gum on cholesterol and bile acid metabolism in the hamster are possibly related to different physicochemical properties, e.g., viscosity and susceptibility to fermentation, affecting the fiber-mediated action in the intestine.     

Biliary cholesterol excretion: a novel mechanism that regulates dietary cholesterol absorption

The regulation of dietary cholesterol absorption was examined in C57BL/6 and transgenic mice with liver overexpression of the scavenger receptor BI (SR-BI Tg). In C57BL/6 animals, feeding 0.02 to 1% (wt/wt) dietary cholesterol resulted in a dose-dependent decrease in the percentage of dietary cholesterol absorbed. A plot of total daily mass of dietary cholesterol absorbed versus the percentage by weight of cholesterol in the diet yielded a curve suggesting a saturable process with a Km of 0.4% (wt/wt) and a Vmax of 0.65 mg cholesterol/g body weight per day. Dietary cholesterol suppressed hepatic 3-hydroxy-3-methylglutaryl CoA reductase activity, stimulated cholesterol 7alpha-hydroxylase activity, and enhanced fecal excretion of bile acids, but none of these changes correlated with the percentage of dietary cholesterol absorption. Dietary cholesterol also caused an increase in biliary cholesterol concentration, and in this case the concentration of biliary cholesterol was strongly and inversely correlated with the percentage dietary cholesterol absorption (r = -0.63, P < 0.0001). Biliary cholesterol concentration was also directly correlated with daily cholesterol intake, dietary cholesterol mass absorption, and liver cholesterol ester content. Transgene-induced overexpression of SR-BI resulted in a stimulation of excretion of cholesterol into the bile and suppressed percentage dietary cholesterol absorption. Furthermore, biliary cholesterol levels in SR-BI Tg mice were strongly and inversely correlated with the percentage of dietary cholesterol absorbed (r = -0.99, P < 0.0008). In summary, these results suggest that the excretion of cholesterol into the bile plays an important role in regulating the percentage absorption of dietary cholesterol.     

Influence of diets containing high and low risk factors for colon cancer on early stages of carcinogenesis in human flora-associated (HFA) rats

Germ-free rats colonised with a human intestinal flora were fed diets containing high risk (HR) or low risk (LR) factors for colorectal cancer, and putative biomarkers were evaluated in the colonic mucosa; (i) proliferation, (ii) 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci and (iii) DMH-induced DNA damage. The HR diet was high in fat (45% of calories) and low in calcium and fibre, reflecting levels characteristic of typical western diets. The LR diet was low in fat (<5% of calories), and high in calcium and fibre. The nutrient/energy ratio of the two diets were similar. Mucosal crypt cell proliferation, assessed after microdissection, was higher on the LR diet (mean number of mitoses per crypt was 2.65 on the LR diet, and 1.62 on the HR diet; P < 0.05). Aberrant crypt foci (ACF) were assessed in the mucosa 12 weeks after DMH treatment. On the HR diet there were significantly more small ACF with 1 and 2 crypts per focus, but fewer ACF with 3, 5 and 7 or more crypts per focus. There was no significant difference in total ACF or the total number of crypts. The effect of diet on DNA damage in the colon was assessed in vivo by the comet assay. Animals were fed a HR or LR diet for 12 weeks before treatment with DMH or saline. For carcinogen-treated animals, DNA damage was significantly higher in colon cells from animals on the HR diet. On the LR diet both DNA damage and the induction of small ACF were reduced despite an increase in cell proliferation. The increase in large ACF on the LR diet may be attributable to elevated crypt cell proliferation possibly increasing crypt fission rates.     

Distribution and characterization of enterostatin-like immunoreactivity in human cerebrospinal fluid

The effects of two highly fermentable dietary fibers (guar gum and pectin) on the type and concentrations of cecal polyamines as affected by the intestinal microflora were studied in groups of germ-free (n = 10/group) and conventional rats (n = 6/group). Both germ-free and conventional rats were randomly assigned to one of three treatments as follows: 1) fiber-free control diet, 2) control diet + 10% guar gum and 3) control diet + 10% pectin. In germ-free rats, guar gum and pectin had no effect on cecal polyamine concentrations. Putrescine was confirmed to be the major endogenous polyamine within the gut lumen. In cecal contents of conventional rats, both guar gum and pectin led to the appearance of cadaverine and to elevated putrescine concentrations in comparison with the fiber-free control diet (1.35 +/- 0.15 and 2.27 +/- 0.32, respectively, vs. 0.20 +/- 0.03 micromol/g dry weight, P < 0.05). The cecal cadaverine concentration was higher in pectin- than in guar-fed rats (8.20 +/- 0.89 vs. 1.92 +/- 0.27 micromol/g dry weight, P < 0.05). Counts of total bacteria, bacteroides, fusobacteria and enterobacteria were higher (P < 0.05) in rats fed guar gum and pectin. Bifidobacteria were found exclusively in guar-fed rats. In vitro studies on selected species representing the numerically dominant population groups of the human gut flora (bacteroides, fusobacteria, anaerobic cocci and bifidobacteria) were examined for their ability to synthesize intracellular polyamines. These experiments demonstrated the ability of bacteroides, fusobacteria and anaerobic cocci to synthesize high amounts of putrescine and spermidine. Calculations based on these results suggest that the intestinal microflora are a major source of polyamines in the contents of the large intestine.     

Transcriptional activation of the human c-myc gene by simian virus 40 large T antigen without binding to p53 and RB proteins in the transient expression system

Male adult Wistar rats were randomly divided into four groups in a 2 x 2 factorial design and were fed diets containing cooked-stored polished rice (CSPR), with and without 0.7 g/100 g of Nebacitin [bacitracinneomycin sulfate (2:1, wt/wt)] and with and without 1 g cholesterol/100 g diet. The CSPR diet contained 1.87 g resistant starch/100 g. After 4 wk, arterial blood and liver were collected. Feces were collected during the last 7 d. Rats fed the diet with Nebacitin and cholesterol had higher serum total cholesterol than the rats fed diets without cholesterol. Serum triglyceride concentration was greater in rats fed Nebacitin, regardless of dietary cholesterol concentration. Rats fed the diet with Nebacitin and cholesterol had higher serum LDL cholesterol concentration and liver total cholesterol concentration than rats fed the other three diets. Rats fed the CSPR diet with Nebacitin both with and without cholesterol had a higher fecal resistant starch concentration and excretion and lower serum short-chain fatty acid concentration than rats fed the diets without Nabacitin. Hepatic cholesterol concentration was greater in rats fed Nebacitin only when the diet also contained cholesterol. Therefore, dietary Nebacitin alters lipid metabolism in rats, and some effects are most pronounced in those also fed cholesterol.