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SIGNALMENT:
10 month old female Beagle dog

TREATMENT PROTOCOL:
17-day oral gavage toxicity study with PNU-171990A (antimuscarinic)

GROSS PATHOLOGY:
High-dose group only: Small and large intestine; distended, fluid-filled lumen and reddened mucosa

LABORATORY RESULTS:
High-dose group only: Decreased albumin and globulin; increased fibrinogen Increased APTT and PT Fecal positive for Clostridium perfringens

What's Your Diagnosis? Provide your possible etiologies in the comment section below. Member login is required to comment.

Normal colon, beagle dog (50x, H&E).

Normal colon, beagle dog (200x, H&E).

Dog treated with PNU-171990 (120 mg/kg/day). Higher magnification of colon. Numerous glands are devoid of an intact epithelium. There is a mild increase in inflammatory cells in the lamina propria.

MORPHOLOGIC DIAGNOSI(E)S AND ETIOLOGY: 

Etiology: PCBs - Aroclor 1254 ingestion

CONTRIBUTOR: Anonymous

CONTRIBUTOR'S COMMENTS: 

Cytology and fecal swab cultures from dogs with diarrhea indicated that affected dogs had clostridial infections. C. perfringens (CP) is known to cause hemorrhagic diarrhea and necrotizing ileitis and colitis in dogs, both of which were observed in dogs from this study. CP is a normal enteric bacterium that maintains a vegetative state in the dog. Certain factors may cause the vegetative CP to undergo enteric sporulation. These factors include stress associated with hospitalization and surgery, changes in intestinal function due to sudden modifications in diet, altered local immunity, intestinal mucosal damage (i.e. parvoviral enteritis), and modified intestinal flora (i.e. antibiotic therapy). It is known that antimuscarinics have numerous well-defined effects on the gastrointestinal tract including decreased gastric acid secretion and gastrointestinal motility. PNU-171990A markedly slows the charcoal transit time in a standard guinea pig model of intestinal motility. Persistent decreases in intestinal motility due to the antimuscarinic effects of PNU-171990A could have resulted in anorexia, alteration of the gut microenvironment and microflora, and opportunistic proliferation of CP. While this hypothesis is reasonable based on the pharmacologic activity of the drug, a review of published dog toxicology studies with antimuscarinic compounds failed to identify a comparable toxicity.