STUDIES ON THE MECHANISM OF ANTIBACTERIAL ACTION OF 2-METHYL-1,4-NAPHTHOQUINONE

Thioglycolic acid neutralized with sodium carbonate, sodium thioglycolate (Eastman), ethyl mercaptan, cysteine hydrochloride and certain sulfur-containing reducing agents (sodium bisulfite and sodium hydrosulfite) antagonize the antibacterial action of 2-methyl-1,4-naphthoquinone on Escherichia coli in a synthetic medium. Other reducing agents such as stannous chloride, potassium formate and sodium thiosulfate, show no such antagonism. The antibacterial activities of 2-methyl-3-chloro-1,4-naphthoquinone and 2,6-dimethyl-1,4-naphthoquinone are also abolished by excess thioglycolate and cysteine, while that of 2-methyl-3-methoxy-1,4-naphthoquinone with -OCH(3) instead of -Cl or -H in the 3 position on the quinone ring, is not. These findings suggest that the mode of antibacterial action of 2-methyl-1,4-naphthoquinone is by blocking essential enzymes through combination with sulfhydryl groups, or through combination with sulfhydryl groups of essential bacterial metabolites. This combination may take place in the 3-position on the quinone ring. This mode of action is similar to that suggested by other investigators for several antibiotic agents including penicillin. The antibacterial activity of the methoxy quinone, however, even in the presence of sulfhydryl groups, suggests that the foregoing explanation may not be the complete one.     

Measurement of canine IgE using the alpha chain of the human high affinity IgE receptor

In vitro assays for allergen specific immunoglobulin E (IgE) are a convenient and reproducible alternative to intradermal skin testing in dogs. Such tests may be used to support a diagnosis of atopic dermatitis and to define appropriate allergens for immunotherapy. Current in vitro assays rely upon monoclonal or polyclonal antibodies as IgE detection reagents. However, in sera where allergen-specific IgG occurs in great excess, any IgE:IgG cross-reactivity of the detection reagent may result in lowered assay specificity. Therefore, we have developed an assay for canine IgE which uses a recombinant form of the extracellular part of the alpha chain of the human high affinity IgE receptor (FcvarepsilonRIalpha). Biotinylated FcvarepsilonRIalpha shows no significant binding to purified canine IgG, and recognizes a heat labile antibody in serum, with a detection limit of 73-146pg/ml. Comparison of assay signals using the labeled FcvarepsilonRIalpha and a highly specific anti-canine IgE monoclonal antibody (MAb) shows good agreement. The FcvarepsilonRIalpha is therefore a sensitive and specific alternative to polyclonal or monoclonal antibodies for canine serum IgE measurement.     

Childhood IQ's as Predictors of Adult Educational and Occupational Status

IQ's between 3 and 18 years of age were used to predict attained education and occupational status after 26 years of age. By the second grade these predictive correlations approached those that have been obtained with contemporaneous adult IQ's, especially for occupational status. However, they were not high enough for practical purposes requiring long-term prediction for individual normal children.     

COLLATERAL PULMONARY CIRCULATION IN DOGS EXPERIMENTALLY INFECTED WITH DIROFILARIA IMMITIS: ITS ANGIOGRAPHIC EVALUATION*

Collateral pulmonary circulation was evaluated angiographically 11 months after experimental infection of dogs with either 25 or 100 infective larvae of Dirofilaria immitis. In both groups, collateral pulmonary circulation developed from bronchial arteries and esophageal branches of the left gastric artery. Of the four dogs receiving 25 larvae, one had no detectable collateral circulation, one developed collateral pulmonary circulation from the bronchial arteries only, and two had collateral pulmonary circulation from the bronchial arteries and esophageal branches of the left gastric artery. Of the three dogs receiving 100 larvae, all had collateral pulmonary circulation from the bronchial arteries and the esophageal branches of the left gastric artery. Bronchial artery collateral pulmonary circulation was more extensive in the 100-larvae dogs than in the 25-larvae dogs. Collateral pulmonary circulation from the left gastric artery esophageal branches was similar in both dog groups. Angiographically detectable collateral pulmonary circulation developed within the first year of heaertworm infection. In some respects, the extent of collateral pulmonary circulation development was related to the severity of heartworm infection.     

Pilot study to assess the effects of early flea exposure on the development of flea hypersensitivity in cats

This pilot study was to determine if early oral flea exposure reduces the incidence of flea allergy dermatitis (FAD) in cats. Eighteen kittens, assigned to three groups, received no flea exposure, oral flea exposure or flea infestation for 12 weeks. Then all the kittens were exposed continually to fleas for 31 weeks. Sensitization was monitored using intradermal testing (IDT), in vitro measurement of anti-flea saliva immunoglobulin E (IgE) and development of FAD. There was no statistically significant difference between groups in IDT reactions, in vitro data or clinical scores. The development of FAD was not associated with the presence of anti-flea saliva IgE. However, the development of a delayed reaction to flea bite was associated with symptoms after flea exposure. Although not statistically significant, the FAD scores in the oral group were lower than in the controls. Further studies are required to determine the role of oral flea exposure in the development of FAD in cats.     

Late-phase reactions to intradermal testing with Dermatophagoides farinae in healthy dogs and dogs with house dust mite-induced atopic dermatitis

OBJECTIVE: To determine the prevalence of late-phase reactions to intradermal testing with Dermatophagoides farinae in healthy dogs and dogs with atopic dermatitis and an immediate reaction to D farinae. ANIMALS: 6 healthy dogs and 20 dogs with atopic dermatitis and immediate reactions to D farinae. PROCEDURE: ntradermal tests were performed with D farinae at 1:1,000 wt/vol and 1:50,000 wt/vol concentrations, and skin reactivity was evaluated after 0.25, 6, and 24 hours. Serum D farinae-specific IgE antibodies were assayed. Extent of lesions (atopy index) and pruritus (visual analogue scale) were evaluated in dogs with atopic dermatitis. RESULTS: Late-phase reactions were observed in healthy dogs at 6 hours (n = 2 dogs) and 24 hours (1) with the 1:1,000 wt/vol concentration, and at 6 hours (1) and 24 hours (1) with the 1:50,000 wt/vol concentration of allergen. Late-phase reactions in healthy dogs were only observed in dogs with an immediate reaction to D farinae. Late-phase reactions were observed in 11 of 20 dogs with atopic dermatitis at 6 and 24 hours with the 1:1,000 wt/vol concentration and in 10 of 20 at 6 and 24 hours with the 1:50,000 wt/vol concentration of allergen. There was no difference in mean atopy index, mean visual analogue scale of pruritus, or mean serum D farinae-specific IgE concentration of dogs with a late-phase reaction, compared to dogs without a late-phase reaction. CONCLUSIONS AND CLINICAL RELEVANCE: Late-phase reactions may be observed after an immediate reaction to intradermal skin testing in healthy and allergic dogs but are more commonly observed in dogs with atopic dermatitis.     

Antioxidant and prooxidant actions of prenylated and nonprenylated chalcones and flavanones in vitro

Prenylated flavonoids found in hops and beer, i.e., prenylchalcones and prenylflavanones, were examined for their ability to inhibit in vitro oxidation of human low-density lipoprotein (LDL). The oxidation of LDL was assessed by the formation of conjugated dienes and thiobarbituric acid-reactive substances (TBARS) and the loss of tryptophan fluorescence. At concentrations of 5 and 25 microM, all of the prenylchalcones tested inhibited the oxidation of LDL (50 microg protein/ml) induced by 2 microM copper sulfate. The prenylflavanones showed less antioxidant activity than the prenylchalcones, both at 5 and 25 microM. At 25 microM, the nonprenylated chalcone, chalconaringenin (CN), and the nonprenylated flavanone, naringenin (NG), exerted prooxidant effects on LDL oxidation, based on TBARS formation. Xanthohumol (XN), the major prenylchalcone in hops and beer, showed high antioxidant activity in inhibiting LDL oxidation, higher than alpha-tocopherol and the isoflavone genistein but lower than the flavonol quercetin. When combined, XN and alpha-tocopherol completely inhibited copper-mediated LDL oxidation. These findings suggest that prenylchalcones and prenylflavanones found in hops and beer protect human LDL from oxidation and that prenylation antagonizes the prooxidant effects of the chalcone, CN, and the flavanone, NG.