Rioprostil prevents gastric bleeding induced by nonsteroidal antiinflammatory drugs in dogs and arthritic rats.

Gastrointestinal irritation is the most significant side effect in patients chronically taking nonsteroidal antiinflammatory drugs (NSAID) for treatment of arthritic conditions. Rioprostil, a primary alcohol prostaglandin E1 analog, prevents gastric bleeding induced by several NSAID in a rat model of arthritis that is similar in many aspects to human rheumatoid arthritis. Daily oral dosing of rioprostil (50 micrograms/kg BID for 15 days) did not influence the course of the adjuvant disease in rats or alter the antiinflammatory or analgesic effect of the NSAID. In a 13 week efficacy study in dogs, rioprostil (40-60 micrograms/kg, PO) completely prevented gastric hemorrhagic lesions induced by daily administration of aspirin.

Spontaneous lesions in the sternums of growing rats.

Pathologic examination of sternums from young growing rats revealed a number of skeletal lesions involving both cartilage and bone elements. Degeneration or aseptic necrosis of the intersternebral cartilage was a frequent finding in most rats that were examined either at 130 or 180 days of age. Thickening of the sternal cortices and trabeculae containing prominent cement lines were less frequently occurring lesions in these sternums. These changes were absent in rats of 70 days of age. The etiology of the lesions is not understood, although several factors may be incriminated.

Three types of cytoplasmic granules in cardiac muscle cells of cynomolgus monkeys (Macaca fascicularis).

Ceroid, lipofuscin, and hyaline-type intracytoplasmic granules found in cardiac muscle cells of cynomolgus monkeys were studied using histologic, histochemical, and fluorescent microscopic techniques. The studies indicated that the ceroid granules contained an insoluble lipid as well as a component that was stainable with Luxol fast blue and Mallory's phloxine stain for hyaline. Lipofuscin granules had staining reactions characteristic of the classical age-related pigment. Hyaline granules were devoid of lipid component and were distinctly different from either ceroid or lipofuscin. All three types of granules were located at the poles of cardiac muscle cell nuclei.

An unusual case of generalized ceroid-lipofuscinosis in a cynomolgus monkey.

Histologic, histochemical, and electron microscopic studies of generalized ceroid-lipofuscinosis in a cynomolgus monkey are presented. Histologically, a wide variety of tissue cells contained numerous bright eosinophilic intracytoplasmic granules that varied in size from 0.5 micron to 4.0 microns in diameter. Histochemically, the granules gave a weakly positive reaction with periodic acid-Schiff and for lipids. They were weakly acid fast and capable of emitting autofluorescence. Ultrastructurally, the granules were single unit membrane-bound, and contained dense osmiophilic material with frequent concentric or fingerprint-type lamellar formation. The granules were different than hemofuscin, iron, and bilirubin. Tinctorially the granules were unique--they were bright red with hematoxylin and eosin and, thus, differed from typical age-related lipofuscin pigment.

Testicular toxicity induced by oral administration of SC-32855, A 1,4-benzodiazepine, in the dog.

A 1,4-benzodiazepine, SC-32855, was administered orally once daily at doses of 30, 100, and 300 mg/kg for two weeks to adult Beagle dogs (1/sex/dose). The 300 mg/kg animals were sacrificed in extremis on day three after showing extreme signs of CNS depression. At necropsy, the testes of the 100 mg/kg male weighed considerably less than those of the control. The testicular weights of the 30 and 300 mg/kg animals were comparable to the weight of the control testes. Histopathologic evaluation of the testes of the 100 mg/kg male revealed degenerative and necrotic changes in the seminiferous tubules and cytoplasmic vacuolation in Leydig cells. In the 30 and 300 mg/kg animals, degenerative and necrotic changes were restricted to the seminiferous tubules.

Preliminary studies of the mode of action of arildone, a novel antiviral agent.

Arildone (also known as Win 38020), a novel aryl diketone, inhibited replication of herpes simplex virus type 2 in tissue culture by interfering with an event that occurs prior to 6 h postinfection. The inhibition could be partially reversed by washing. Although the exact mechanism of action is unknown, neither viral deoxyribonucleic acid nor viral proteins were synthesized in the presence of arildone.

Cell-to-cell attachments and associations in tumors induced by CELO virus or virus-transformed cells in hamsters.

Cell-to-cell attachments or associations in expermentally induced sarcoma of chicken embryo lethal orphan virus (avian adenovirus) origin were studied in hamsters by electron microscopic examination. In many instances, the neoplastic cells seemed to be held together either by desmosome-like structures or an "interlocking" of their apposing plasma membranes. Less frequently, the cells were attached by button-like projections between the cell surfaces. Only rarely, interdigitation occurred between filopodial processes of cell surface of adjoining cells.

Morphology of tumours induced in hamsters by CELO virus, tumour tissue, and tumour cells grown in culture.

Tumours in hamsters, induced by the chicken-embryo-lethal-orphan (CELO) virus, by tumour tissue transplants, or by tumour cells grown in culture, were well circumscribed solid tumours and covered by a thin capsule-like structure. All were fibrosarcomata. However, tumours produced by the 3 inocula exhibited the following histological differences. Neoplasms induced by CELO virus were generally less differentiated and were composed of cells with polygonal or oval nuclei and indistinct cytoplasmic boundaries. Numerous multinucleated bizarre giant cells were found. Those produced by tumour tissue transplants were more differentiated and were composed of spindle shaped cells with abundant collagen fibre formation. Neoplasms induced by tumour cells grown in culture were generally undifferentiated with many mitotic figures and contained numerous giant cells.Cells from tumours induced by CELO virus or tumour transplants produced similar morphologies when cultured in vitro. The cell cultures consisted of large cells with oval or rounded large nuclei and prominent nucleoli. Multinucleated giant cells, cells in mitosis, and a disorganized growth pattern were also characteristic of the cell cultures. However, mitosis and a piling-up of cells occurred more frequently with cell cultures derived from the CELO virus-induced tumour.