Keith W. Prasse

Eicosanoid synthesis in 7,12-dimethylbenz(a)anthracene-induced mammary carcinomas in Sprague-Dawley rats fed primrose oil, menhaden oil or corn oil diet

The comparative effects of high-fat diets (20%, w/w) on eicosanoid synthesis during mammary tumor promotion in 7,12-dimethylbenz(a)anthracene (DMBA)-induced rats were studied using diets containing 20% primrose oil (PO), 20% menhaden oil (MO) or 20% corn oil (CO). Sprague-Dawley rats fed the PO or MO diet had 21% or 24% fewer adenocarcinomas, respectively, than rats fed the CO diet. Histologically (i.e., mitotic figures, inflammatory cell infiltration and necrosis), the CO-fed rats exhibited the highest frequency of changes within tumors. Plasma fatty acid composition was significantly altered by diet, reflecting the composition of the oils which were being fed. Only the plasma of PO-fed rats contained detectable levels of gamma-linolenic acid (GLA). Arachidonic acid (AA) levels were significantly higher (p<0.05) in PO-fed than in CO- or MO-fed rats. MO-fed rats had significantly higher levels of plasma palmitic acid, while palmitoleic, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids were detected only in MO-fed rats. As expected, linoleic acid (LA) and AA levels were lower (p<0.05) in the MO-fed rats than in PO- or CO-fed groups. The plasma of the CO-fed rats contained significantly higher levels of oleic acid. Eicosanoid synthesis in mammary carcinomas of rats fed the 20%-fat diets was 2–10 times higher than in mammary fat pads of control rats. The synthesis of PGE1 and LTB4 was significantly (p<0.05) higher in PO-fed rats than in CO-fed or MO-fed rats, although PGE values were significantly (p<0.05) higher in CO-fed rats than in Mo or PO groups. The synthesis of eicosanoids in both mammary fat pads and mammary carcinomas of MO-fed rats was lower (p<0.05) than in tissues of rats fed either CO or PO diets due to less AA precursor being fed and/or to competition between n−6 and n−3 fatty acids for cyclooxygenase and lipoxygenase. The ratios of monoenoic to dienoic eicosanoids in both mammary fat pads and mammary carcinomas were higher in the PO group than in the MO or CO groups. These results suggest that inclusion of GLA (PO feeding) or EPA and DHA (MO feeding) in the diet may decrease malignancy by altering eicosanoid profiles.

Cytologie Differentiation of Benign from Malignant Canine Mammary Tumors

Cytologic and histologic examination of 91 canine mammary masses was performed by two cytologists and two histopathologists. Ten important cytologic criteria of malignancy for canine mammary tumors were identified. A cytologic grading system for differentiation of benign from malignant mammary tumors was proposed using these criteria. With this system, approximately one fourth of the malignant mammary tumors were given a concordant cytologic diagnosis. Approximately one-half of the benign masses were given a concordant cytologic diagnosis by the two cytologists. One-half of all the tumors examined were given inconclusive cytologic diagnoses by both cytologists. The cytologic identification of spindle cells did not differentiate complex and mixed mammary tumors from simple tumors. Only five of the animals studied died of mammary cancer, precluding a critical analysis of the cytologic criteria for prediction of cancer mortality.

Effects of dietary primrose oil on mammary tumorigenesis induced by 7,12-dimethylbenz(a) anthracene

The mammary tumor-promoting effect of a high-fat diet containing 20% evening primrose oil (PO) was compared to that of a 20% corn oil (CO) diet. Mammary tumors were induced in female Sprague-Dawley rats using 10 mg (Study 1) and 5 mg (Study 2) 7,12-dimethylbenz(a)anthracene (DMBA). The 10 mg dose of DMBA gave a total mammary tumor incidence of 47% in rats fed the PO diet and 80% for those fed the CO diet. When only adenocarcinomas were counted, the malignant mammary tumor incidences were 41% in rats fed the PO diet and 73% in rats fed the CO diet. In a second study using 5 mg DMBA to induce mammary tumors, total tumor incidences were 50% for PO-fed rats and 63% for those receiving a CO diet. Again, when only adenocarcinomas were counted, tumor incidences were 27% for PO- and 63% for CO-dieted rats. Analysis of plasma fatty acid profiles indicated that animals fed a 20% PO diet showed significant increases in 18∶3 and 20∶4 fatty acids and significant decreases in 16∶0 and 18∶1 compared to animals fed a 20% CO diet. These results indicate that the mammary tumor promoting effect of a diet containing 20% fat can be diminished by substituting PO for CO. Moreover, the promoting effect on mammary cancer by a high-fat diet could be depressed by feeding a source of γ-linolenic acid (GLA).

Hemostatic Indices in Healthy Foals from Birth to One Month of Age

Hemostatic indices were determined in 45 healthy light breed foals, from birth to 1 month of age, and in 20 healthy adult (>2 years of age) light breed horses. Blood samples were obtained from each foal at 4 ages: 1) < 24 hours, 2) 4-7 days, 3) 10-14 days, and 4) 25-30 days. The following hemostatic indices were determined: platelet count; prothrombin and activated partial thromboplastin times; activity concentrations of protein C, antithrombin III, plasminogen, alpha-2 antiplasmin, tissue plasminogen activator, and plasminogen activator inhibitor- 1; plasma protein C antigen and fibrinogen concentrations; and serum fibrin degradation products concentration. Prothrombin and activated partial thromboplastin times were significantly longer at birth than in older foals. The plasma concentrations of the following were significantly lower at birth than in older foals: antithrombin III, plasminogen and tissue plasminogen activator activities, protein C antigen, and fibrinogen. Concentrations of the following were significantly higher at birth than in older foals: protein C and plasminogen activator inhibitor-1 activities and fibrin degradation products. These results indicate that hemostatic indices of neonatal foals differ significantly from those of older foals and adults. With the exceptions of antithrombin III and tissue plasminogen activator activities, all hemostatic indices measured in foals at 1 month of age were equivalent to adult values.

Immunohistochemical Detection of Canine Adenovirus in Paraffin Sections of Liver

An avidin-biotin immunoperoxidase procedure was optimized for detection of canine adenoviral antigens in formalin-fixed, paraffin-embedded liver. Long-term stability of viral antigen was shown by successful demonstration of virus in liver tissue preserved up to six years from dogs with infectious canine hepatitis. This immunohistochemical stain was applied to sections from livers with a wide range of inflammatory lesions. Examination of sections from 53 dogs yielded five livers with small amounts of adenovirus. An additional virus-positive liver was identified from a dog with no hepatic inflammation. Although a cause and effect relationship remains to be determined, these findings suggest a possible connection between canine adenovirus and spontaneous chronic hepatitis.