Modulation of the hypolipidemic effect of fish oils by dietary fiber in rats: studies with rice and wheat bran

Adult male rats were fed a purified diet containing rice bran or wheat bran with or without a marine fish oil to investigate the possible effects of such dietary combinations on lipid metabolism. Plasma and hepatic triacylglycerols and hepatic lipogenesis were lowered significantly by feeding fish oil with rice bran but not with wheat bran. Plasma cholesterol and hepatic cholesterol synthesis were significantly lower in animals fed fish oil with either bran. Liver microsomal free cholesterol was significantly lower in rats fed rice bran alone than in all other groups. Hepatic low density lipoprotein (LDL) receptor activity was significantly higher in the two groups fed rice bran than in the two groups fed wheat bran. Fish oil significantly decreased hepatic LDL receptor activity and increased hepatic high density lipoprotein (HDL) binding activity with wheat bran but had no significant effects on these parameters when added to the rice bran diet. However, when the data for all groups were pooled, there was a significant negative correlation between hepatic HDL binding activity and LDL receptor activity. Cecal volatile fatty acids were significantly higher in rats fed rice bran, were unaffected by adding fish oil to either bran diet and did not appear to mediate any of the effects of the brans and fish oil on plasma lipids and hepatic lipid metabolism. The combination of rice bran plus fish oil therefore appears to have more beneficial effects on lipid metabolism than wheat bran plus fish oil.     

Comparative effects of dietary wheat bran and its morphological components (aleurone and pericarp-seed coat) on volatile fatty acid concentrations in the rat

Adult male rats were fed on diets containing 100 g dietary fibre/kg either as alpha-cellulose or wheat bran or the pericarp-seed coat or aleurone layers prepared from that bran by sequential milling and air elutriation and electrostatic separation. After 10 d, concentrations of total volatile fatty acids (VFA) in caecal fluid were significantly different between groups and fell in the order: aleurone greater than wheat bran greater than pericarp-seed coat greater than cellulose. This ranking probably reflected the ease of fermentation of fibre polysaccharides by colonic bacteria which also resulted in a considerably higher faecal bacterial mass in the aleurone group. Because of the differences in the volume of caecal digesta, the mass of caecal VFA was considerably the highest in the aleurone group, intermediate with wheat bran and equally low in the pericarp-seed coat and cellulose groups. The diet based on aleurone gave a relatively higher proportion of propionate but with both pericarp-seed coat and wheat bran the contribution of butyrate was raised. VFA concentrations in hepatic portal venous plasma were proportional to caecal concentrations with very high (greater than 3 mM) values being recorded in the aleurone group. The findings are discussed in relation to the apparent susceptibility of the morphological components of wheat bran to fermentation by large bowel bacteria.     

Ultrastructural characteristics of carcinogen-induced nondysplastic changes in tracheal epithelium

Nondysplastic hypotrophic and metaplastic epithelial alterations induced by dimethylbenz(a)anthracene in isogenic tracheal transplants were studied by light and electron microscopy 3--24 months after cessation of a 4-week carcinogen exposure. Hypotrophic epithelium observed at all time points was characterized by the presence of nonciliated cells that adopted either cuboidal or squamous shapes, forming simple or bistratified epithelia. Most of these cells, as well as some metaplastic cells, exhibited features of mucin-secreting cells. The metaplastic epithelia showed nonkeratinizing squamous metaplasia, closely related to transitional metaplasia, and keratinizing squamous metaplasia, which presented either an atrophic or an acanthotic epithelium. Although many of these epithelia showed morphologic features of normal stratified epithelia, several nonkeratinizing squamous metaplasias and acanthotic keratinizing squamous metaplasias exhibited some irregularities, probably representing very early atypical ultrastructural features (ie, perinuclear concentration of tonofilament bundles, the presence of dark and clear basal epithelial cells, interruptions and alterations of the basal lamina). These features were not observed in a group of early squamous metaplasias studied for comparative purposes 2 weeks after cessation of dimethylbenz(a)anthracene exposure, which were characterized by a combination of degenerative phenomena and increased cell proliferation.     

Immunogenicity of recombinant protective antigen and efficacy against aerosol challenge with anthrax

Immunization with a recombinant form of the protective antigen (rPA) from Bacillus anthracis has been carried out with rhesus macaques. Rhesus macaques immunized with 25 mug or more of B. subtilis-expressed rPA bound to alhydrogel had a significantly increased immunoglobulin G (IgG) response to rPA compared with macaques receiving the existing licensed vaccine from the United Kingdom (anthrax vaccine precipitated [AVP]), although the isotype profile was unchanged, with bias towards the IgG1 and IgG2 subclasses. Immune macaque sera from all immunized groups contained toxin-neutralizing antibody and recognized all the domains of PA. While the recognition of the N terminus of PA (domains 1 to 3) was predominant in macaques immunized with the existing vaccines (AVP and the U.S. vaccine anthrax vaccine adsorbed), macaques immunized with rPA recognized the N- and C-terminal domains of PA. Antiserum derived from immunized macaques protected macrophages in vitro against the cytotoxic effects of lethal toxin. Passive transfer of IgG purified from immune macaque serum into naive A/J mice conferred protection against challenge with B. anthracis in a dose-related manner. The protection conferred by passive transfer of 500 mug macaque IgG correlated significantly (P = 0.003; r = 0.4) with the titers of neutralizing antibody in donor macaques. Subsequently, a separate group of rhesus macaques immunized with 50 mug of Escherichia coli-derived rPA adsorbed to alhydrogel was fully protected against a target dose of 200 50% lethal doses of aerosolized B. anthracis. These data provide some preliminary evidence for the existence of immune correlates of protection against anthrax infection in rhesus macaques immunized with rPA.