A blinded, placebo-controlled study of the efficacy of borage seed oil and fish oil in the management of canine atopy.

Twenty-one dogs with atopy were entered into a blinded, placebo-controlled study lasting eight weeks. They were randomly divided into three groups and were all given supplementary oils orally once daily. The dogs in groups A and B were given borage seed oil and fish oil in combination (Viacutan; Boehringer Ingelheim Vetmedica) to provide 176 mg/kg or 88 mg/kg borage seed oil respectively. The dogs in group C were given 204 mg/kg olive oil as a placebo. They were all re-examined after four and eight weeks and scored for pruritus, erythema, oedema, alopecia and self-excoriation. After eight weeks the scores for erythema and self-excoriation, and the total score for the dogs in group A, and the total score for the dogs in group B were significantly reduced (P < 0.05). The dogs in group C showed no significant improvement.

Expression and characterization of four recombinant human dihydrodiol dehydrogenase isoforms: oxidation of trans-7, 8-dihydroxy-7,8-dihydrobenzo[a]pyrene to the activated o-quinone metabolite benzo[a]pyrene-7,8-dione.

The bioactivation of polycyclic aromatic hydrocarbons (PAHs) to their ultimate carcinogenic forms proceeds via the formation of proximate carcinogen trans-dihydrodiols. Previous studies demonstrated that rat liver 3 alpha-hydroxysteroid dehydrogenase/dihydrodiol dehydrogenase (3 alpha-HSD/DD), a member of the aldo-keto reductase (AKR) superfamily, oxidizes PAH trans-dihydrodiols to redox-cycling o-quinones. Multiple closely related AKRs exist in human liver; however, it is unclear which, if any, participate in PAH activation by catalyzing the NADP+ -dependent oxidation of PAH trans-dihydrodiols. In this study, cDNAs encoding four human DD isoforms were isolated from HepG2 cells using isoform-selective RT-PCR. The recombinant proteins were overexpressed in Escherichia coli, purified to homogeneity, and kinetically characterized. Calculation of KM and kcat values of each isoform for model substrates revealed that they possessed enzymatic activities assigned to native human liver DD1, DD2, DD4, and type 2 3alpha-HSD (DDX) proteins. The ability of human DDs to oxidize the potent proximate carcinogen (+/-)-trans-7,8-dihydroxy-7, 8-dihydrobenzo[a]pyrene (BP-diol) was then examined. A reverse phase HPLC radiochemical assay demonstrated that all four isoforms oxidize (+/-)-BP-diol in the following rank order: DD2 > DD1 > DD4 > DDX. Each DD consumed the entire racemic BP-diol mixture, indicating that both the minor (+)-S,S- and major (-)-R,R-stereoisomers formed in vivo are substrates. First-order decay plots showed that DD1 and DD2 displayed preferences for one of the stereoisomers, and circular dichroism spectroscopy indicated that this isomer was the (+)-7S, 8S-enantiomer. The products of these reactions were trapped as either glycine or thiol ether conjugates of benzo[a]pyrene-7,8-dione (BPQ), indicating that the initial oxidation product was the reactive BPQ. Thus, human liver possesses multiple AKRs which contribute to PAH activation by catalyzing the NADP+-dependent oxidation of PAH trans-dihydrodiols to redox-active o-quinones.

A comparison of evening primrose oil and sunflower oil for the management of papulocrustous dermatitis in cats.

Eleven cats with papulocrustous dermatitis were randomly assigned to one of two groups and supplemented with either evening primrose oil or sunflower oil for 12 weeks. Clinical scores were assessed at intervals of three weeks and blood samples were taken for the analysis of plasma and erythrocyte fatty acid concentrations. The cats in both groups improved during the period of treatment and the concentration of linoleic acid in erythrocyte phospholipid increased in the cats fed evening primrose oil. Six weeks after the supplement was withdrawn the cats fed evening primrose oil had deteriorated less than those fed sunflower oil.

Effect of varying proportions of evening primrose oil and fish oil on cats with crusting dermatosis ('miliary dermatitis')

Fourteen cats with crusting dermatoses ('miliary dermatitis') were supplemented with various combinations of evening primrose oil and fish oil. The cutaneous signs improved when the cats were supplemented with either evening primrose oil alone or with a combination of evening primrose oil and fish oil. Fish oil alone was unable to maintain the remission and the cutaneous signs deteriorated. The subsequent administration of a combination of the two oils resulted in a resolution of the dermatosis.

Management of feline miliary dermatitis by supplementing the diet with essential fatty acids.

Of eight cats with miliary dermatitis, six showed a good response to treatment with a dietary supplement of essential fatty acids. The analysis of serum fatty acids revealed significant abnormalities in cats with miliary dermatitis compared with normal cats.

The importance of the "bay region" diol-epoxide in 7,12-dimethylbenz[a]anthracene skin tumor initiation and mutagenesis.

The skin tumor-initiating and V79 mutagenic activities of various derivatives of 7,12-dimethylbenz[a]anthracene (DMBA) were investigated to determine what possible cellular metabolite(s) may be responsible for its carcinogenicity and/or mutagenicity. 1-,2-,3-,4- and 5-hydroxyDMBA were found to be essentially inactive as skin tumor initiators whereas 9- and 10-hydroxyDMBA had weak activity. The (+/-)-trans DMBA 8,9- and 5,6-dihydrodiols were also essentially inactive as skin tumor initiators and (+/-)-DMBA 8beta,9alpha-diol-10alpha-11alpha-epoxide had weak skin tumor initiating activity. All of the above tested derivatives of DMBA were essentially inactive as mutagens in the cell-mediated or direct V79 mutagenesis systems. A methyl or fluoro addition to the 1, 2 or 5 positions almost completely blocked the skin tumor initiating and V79 mutagenic activities of DMBA, whereas a fluoro addition to position 11 did not. From our data we suggest that a 'bay region' diol-epoxide may be important in DMBA carcinogenicity and mutagenicity.

A bacteriophage system for screening and study of biologically active polycyclic aromatic hydrocarbons and related compounds.

The usefulness of bacterial viruses for detecting substances that are potentially carcinogenic is reexamined as a model system for screening biologically active polycyclic aromatic hydrocarbons. A modification of the original assay procedure allows one to distinguish between aromatics that can modify the biological activity of infectious nucleic acids directly and those polycyclic aromatic hydrocarbons that require metabolic activation by Escherichia coli enzymes. The effect of chemical modification of several different polycyclic aromatic hydrocarbons, with respect to their biological activity in the phage assay system, is described. Among the 31 different compounds examined, (+/-)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide was the most potent inhibitor of infectious phage nucleic acid. The (+) and (-) isomers of the above racemic mixture did not differ significantly in their capacity to inhibit phage replication.