Acute toxicity of paraherquamide and its potential as an anthelmintic.

Paraherquamide, an oxindole alkaloid metabolite of Penicillium paraherquei and P charlesii, is a new anthelmintic with potential broad-spectrum use. In initial trials, it had an excellent safety profile in cattle and sheep at doses efficacious against a dozen or more helminths, but recently it produced unexpected and severe toxicosis in dogs at doses far below those that were safe in the ruminants. To provide data on which to build rational safety tests in the future, we tested the acute toxicity of paraherquamide administered PO to male CD-1 mice and compared its profile with the most potent anthelmintic known, ivermectin. The estimated doses lethal to 50% of a group of mice were 14.9 and 29.5 mg/kg of body weight for paraherquamide and ivermectin, respectively. The no-effect doses were 5.6 and 18.0 mg/kg for paraherquamide and ivermectin, respectively. Signs of intoxication in paraherquamide-treated mice, if they developed, emanated within 30 minutes of administration, irrespective of dose, and consisted of either mild depression with complete recovery or a 5- to 10-minute period of breathing difficulty followed by respiratory failure and death by 1 hour after treatment. Gross necropsy findings in paraherquamide-treated mice that died in the high-dose group were normal. Ivermectin-related toxicity was slower and more predictable, taking place over a 3-day period, with dose-dependent signs of intoxication consisting of tremors, ataxia, recumbency, coma, and death. Necropsy of ivermectin-treated mice that died in the high-dose group revealed dehydration, a condition most likely resulting from the coma-induced state.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunohistochemical staining and radionuclide imaging of canine tumors, using a monoclonal antibody recognizing a synthetic carbohydrate antigen

The in vitro and in vivo binding of a monoclonal antibody (MAB) that recognizes a tumor-associated carbohydrate antigen was studied in dogs. Monoclonal antibody 155H.7 was raised in response to innoculation of mice with beta-galactose(1-3)beta N-acetylgalactosamine conjugated to human serum albumin. Avidin-biotin-complex immunohistochemical staining of cryostat sections of normal and neoplastic canine tissue specimens revealed heterogenous binding of MAB 155H.7 to the cells of many canine mammary and lung carcinomas and homogenous staining of many sarcomas, including osteogenic sarcoma. In addition, there was variable staining of a variety of normal tissues including some ductual epithelium, peripheral nerve fibers, and some endothelial cells and fibroblasts. Immunoscintigraphy with 131I-labeled MAB 155H.7 was used to study the in vivo distribution of the antibody. The 131I-labeled MAB 155H.7 was administered to 1 clinically normal dog, 7 dogs with osteogenic sarcoma, 1 dog with undifferentiated sarcoma, and 2 dogs with mammary tumor. Scintigraphy revealed concentration of radioactivity in 8 of 10 tumor sites within 24 hours after MAB administration. The ratio of 131I in tumor sites to 131I in the surrounding normal tissues, compared with the similar ratio of 99mTc-labeled erythrocytes ranged from 1.1 to 4.3, in tumor vs normal tissue with a mean value of 2, confirming tumor localization of the radiolabeled MAB in excess of that associated with enhanced tumor vascularization.     

A herpesvirus-type agent associated with skin lesions of green sea turtles in aquaculture.

Nine successive groups of green sea turtles (Chelonia mydas) were observed in aquaculture during the posthatchling period. During the first 6 months of growth, each group underwent an epizootic of skin lesions, named gray-patch disease. Two types of skin lesions are associated with gray-patch disease: papules and, more characteristically, spreading gray patches which appear 7 to 8 weeks after hatching. In both types of lesions, intranuclear inclusions are found in keratinocytes in the malpighian layer of the epidermis. Electron microscopic examination of scrapings from lesions and biopsies revealed many viral particles, with features characteristic of the herpesvirus group. Transmission of gray-patch disease is possible with bacteria-free preparations of viral particles.     

Hyperlipasemia in 6 dogs with pancreatic or hepatic neoplasia: evidence for tumor lipase production

Abstract: A marked increase in serum pancreatic lipase (PL) activity with minimal concurrent increase in serum α-amylase activity was observed in 6 dogs with pancreatic or hepatic neoplasia. Serum PL activity ranged from 5410 U/L to 42,900 U/L, 11 to 93 times the upper reference limit for our laboratory. Neoplasms included pancreatic adenocarcinoma (n=3), endocrine carcinoma (n=2), and hepatic carcinoma of unknown origin (n=1). Tumor tissue and normal canine pancreatic tissue were stained histochemically with diastase periodic acid-Schiff to demonstrate zymogen granule content, and immunohistochemically with human monoclonal antibody for PL. Normal canine pancreatic tissue stained positive for both zymogen granule content and PL. Five of the 6 tumors stained positive for zymogen granule content, and 2 of the 6 tumors stained positive for PL. Together, the his-tochemical and immunohistochemical staining patterns suggested tumor PL production in 5 of the 6 dogs. Marked, unexplained hyperlipasemia may be a noninvasive indicator and biochemical marker for neoplasia of the pancreas and liver in dogs.     

Evaluation of platelet additive solution for prolonging storage of functional canine platelet concentrate

Objective

To assess storage lesion development, platelet function, and bacterial growth in canine platelet concentrates (PCs) stored in a platelet additive solution (PAS) or a plasma control at 4°C for 21 days.

Design

Prospective, ex vivo, experimental controlled study.

Setting

University veterinary teaching hospital.

Animals

Ten units of canine PCs collected from blood bank donations.

Interventions

The PCs were separated into 2 bags, 1 containing 100% plasma and the other containing 35% plasma and 65% of a PAS (Plasma-Lyte A), and stored at 4°C for 21 days. At days 0, 7, 14, and 21, PCs were analyzed for the presence of swirling, aggregate formation, platelet counts, platelet indices, glucose, lactate, lactate dehydrogenase, Pvco ₂, Pvo ₂, aggregation via light aggregometry, activation percentages using flow cytometry, and bacterial growth.

Measurements and main results

Cold-stored PCs in both PAS and plasma control maintained mean pH >6.8 and mean lactate <9.0 mmol/L over 21 days, with no difference in glucose utilization. Swirl was maintained in both solutions for most days (76/80 combined total samples), with no difference in aggregate formation between solutions. The Pvco ₂ was higher in plasma on all days (P < 0.001), with no difference in Pvo ₂. Platelet indices did not reflect significant storage lesion development in either solution. Lactate dehydrogenase did not differ between solutions but did increase from day 7 to day 21. Mean maximal aggregation percentage was reduced overall but with no significant difference between solutions. The only observed difference in mean activation percentage between solutions was in PAS on day 7, which was significantly higher than plasma (P < 0.05). No bacterial growth occurred during storage.

Conclusions

Cold storage in PAS and plasma allowed PCs to be stored for up to 21 days with minimal storage lesion development, maintenance of platelet function, limited platelet activation, and no bacterial growth within stored bags.     

Magnetic Anomalies over Iceland

An aeromagnetic survey of Iceland reveals broad anomalies of large amplitude over zones of recent volcanic activity. The source of the anomalies is ascribed to large masses of basalt that have been coherently remagnetized by intrusive heating. A simple correlation of the Icelandic anomalies with those of the ocean floor therefore appears unjustified.