Ricinoleic acid effect on the electrical activity of the small intestine in rabbits.

Using myoelectric recording techniques, we examined the myoelectric effects of castor oil; ricinoleic acid (cis isomer), the active ingredient of castor oil; and ricinelaidic acid (trans isomer) in the small intestine of New Zealand white rabbits. Ricinoleic acid, 2 microgram/kg per min (6mM), was perfused into a distal 12-cm ileal loop. An abnormal myoelectric pattern developed that was similar to the alteration in the electrical activity that has previously been reported for cholera enterotoxin. Castor oil, 0.85 ml/kg, had a similar effect. Ricinelaidic acid, 2 microgram/kg per min, induced no activity. A second preparation consisted of an intraluminal perfusion of ricinoleic acid, 2 microgram/kg per min, into the first section of the duodenum. The abnormal myoelectric pattern was observed in the jejunum and the ileum but not the duodenum. The mean onset time for the development of this altered myoelectric state for all experiments was 3.5 h. These studies suggest that an active motility component in addition to the secretory state exists throughout the small intestine that is exposed to castor oil or ricinoleic acid.

Fluroxene toxicity induced by phenobarbital.

Because of reports of fluroxene toxicity in man, the effect of phenobarbital treatment on the toxicity and metabolism of fluroxene was studied in 9 rhesus monkeys. Six monkeys that were exposed to a mean calculated alveolar fluroxene concentration of 5.8% for 4-hr periods up to a total of 16 hr showed no evidence of toxicity. Two animals were sacrificed after a single 4-hr exposure to obtain control measures of fluroxene metabolites in tissues. Four monkeys that had previously survived received exposures to fluroxene and 3 monkeys that had no exposure to fluroxene died during fluroxene anesthesia after treatment with phenobarbital (mean time, 3 hr). Toxicity was manifested by arterial hypotension, pulmonary edema, and arterial hypoxemia. Phenobarbital treatment enhanced production of fluroxene metabolites, including the highly toxic trifluoroethanol. Concentrations of trifluoroethanol in mixed-expired gas, blood, and urine, and of total nonvolatile fluorine in blood, urine, and tissues of animals treated with phenobarbital were 2 to 10 times as in control animals. The results suggest that the rhesus monkey is a valuable model for the study of fluroxene pharmacology and that inclusion of an enzyme-inducing challenge in the evaluation of potential toxicity of other anesthetics seems warranted.

A combined carcinogen bioassay utilizing both the lung adenoma and skin papilloma protocols.

To test the feasibility of employing a combined lung adenoma/skin papilloma assay for broader detection of chemical carcinogenesis than that realized with either bioassay done separately, four strains of mice, SENCAR, BALB/c, A/J, and ICR-Swiss, were administered carcinogens either by the oral or intraperitoneal (IP) routes. The carcinogens administered were ethyl carbamate (EC), benzo(a)pyrene [B(a)P], N-[4-(5-nitro-2-furyl)thiazolyl]formamide (FANFT), and acrylamide (ACR). Starting 2 weeks later, 1 to 5 micrograms (depending on strain) of 12-O-tetradecanoylphorbol-13-acetate (TPA) in 0.2 mL acetone/mouse was applied three times weekly to the shaved back for 20 weeks. All strains displayed increases in the yield of lung adenomas in response to EC at 32 weeks. B(a)P increased lung adenomas in only the SENCAR and A/J strain. Only the SENCAR and ICR-Swiss mice gave positive responses in the skin. In the SENCAR mice, positive response was seen with all four chemicals, however, FANFT gave an inconsistent response. The ICR-Swiss mice responded with an increased skin papilloma yield only to EC. In a separate experiment involving only SENCAR mice, animals were treated with a single oral dose of diethylnitrosamine (DEN) followed by triweekly application of 1.0 microgram TPA. This treatment resulted in 51/57 animals developing lung adenomas vs. 5/57 in the control animals. No treatment-related skin tumors resulted with DEN. Histopathologically confirmed lesions indicate that the spectrum of chemicals detected in the SENCAR mouse may be broadened using a combined bioassay that examines both lung and skin responses.

Ultrastructural distribution of the M form of creatine phosphokinase in human muscle by immunogold labeling.

Creatine phosphokinase regenerates ATP from ADP using creatine phosphate. Isoenzymes of creatine phosphokinase are bound to certain cellular structures or are compartmentalized in areas of the cell, and this has been used as a basis for defining the role of these isoenzymes in energy metabolism. The M isoenzyme of creatine phosphokinase has been morphologically associated with the M-line of striated muscle in many species. In this present study the ultrastructural distribution and the relative concentration of the M form of creatine phosphokinase in human muscle tissue was determined using immunogold and electron microscopy. The M-line of the sarcomere, comprising only 3-4% of the sarcomere area, was found to contain over 20% of the total M isoenzyme signal of the entire sarcomere. This technique represents a quantitative, ultrastructural method to study the subcellular distribution of this isoenzyme. These data suggest that localized concentrations of M-CPK may be important for normal energy metabolism, and may also serve as a foundation for a better understanding of the relationship between abnormal creatine metabolism and the pathogenesis of neuromuscular disease.

Evaluation of room cleaning procedures in a laboratory animal facility.

Animal room cleaning procedures were developed that could be used routinely and economically in this animal facility. Bacterial samples from the floors of rooms housing rabbits, rats and mice provided a useful way to evaluate the effectiveness of the cleaning procedures, and to determine the in-use effectiveness of disinfectant solutions.

Fatal generalized feline viral rhinotracheitis in a young adult cat.

A 7-month-old cat died following a 17-day illness. Necropsy findings included sharply demarcated lingual ulcers and multifocal necrotic hepatitis. Intranuclear inclusions were found in the lesions, and a herpesvirus was recovered from specimens of liver and tongue. The virus was identified by neutralization with specific antiserum as feline rhinotracheitis virus.

Mycotic pneumonia in mariculture-reared green sea turtles.

Microbiologic examination of 29 juvenile green sea turtles with a buoyancy abnormality revealed pulmonary infection with Sporotrichium sp, Cladosporium sp, and Paecilomyces sp. Histologic examination of the lungs revealed granulomatous lesions containing branching septate hyphae. The diagnosis was mycotic pneumonia.

Poxlike skin lesions in captive caimans.

Three juvenile captive spectacled caimans (Caiman sclerops) had scattered, gray-white, circular, 1- to 3-mm skin lesions. In one caiman, the lesions were particularly prominent on the phalanges, palpebrae, and integument overlying the maxillae and mandible. Digital biopsy revealed large eosinophilic intracytoplasmic inclusions within epithelial cells. Transmission electron microscopy of lesions from the lower jaw revealed viral particles morphologically similar to poxvirus.

Postanesthetic recumbency associated with hyperkalemic periodic paralysis in a quarter horse.

Anesthesia and surgery in a Quarter Horse affected with hyperkalemic periodic paralysis resulted in euthanasia after 7 days of postoperative recumbency. Initial recovery was uneventful after extensive sinus surgery, but within 2 hours, the horse had severe muscle weakness. Plasma electrolyte concentrations were within the normal range during the period of recumbency. There was no clinical or laboratory evidence of severe muscle damage. Despite treatment with acetazolamide, isoproterenol, and intensive nursing, the horse was unable to stand for more than a few seconds and developed severe decubital ulcers. Ultrastructural examination revealed nemaline rods and swollen mitochondria in disrupted myofibers.

Environmental monitoring in a laboratory animal facility.

A study was made of the microbial environmental status of an animal facility. Cultures were made of animal and surgical room floors; the germicidal effectiveness of the phenolic disinfectant-detergent employed in the facility was tested against standard test organisms as well as against other microorganisms isolated from the facility, and killing power of the disinfectant-detergent was evaluated during various steps of the usual cleaning procedures, ie, mops and mop bucket solutions were tested before, during, and after mopping a room. It was found that colony counts for animal rooms cleaned with a chlorhexidine disinfectant were much lower than those cleaned with a phenolic disinfectant. The phenolic disinfectant killed some organisms after 10 min exposure, but no others. Pseudomonads were the most resistant organisms. Contaminated mops and mop bucket solutions appeared responsible for the high counts on floors cleaned with the phenolic disinfectant. Guidelines for achievable levels of cleanliness were suggested.

Intracardial mesotheliomas and a gastric papilloma in a giant grouper, Epinephelus itajara (Lichtenstein).

A giant grouper, Epinephelus itajara (Lichtenstein), was found dead in its tank. The principal necropsy findings consisted of multiple tumors in the ventricle of the heart, a tumor mass in the stomach, and protozoa-like organisms in the heart tumor, bile ducts and kidney collecting ducts. The heart tumors were identified as mesotheliomas the stomach tumor as a papilloma. The morphology of the protozoan-like organisms was similar to that of Rhabdospora thelohani (Languesse).

Spontaneous lower motor neuron disease in rabbits (oryctolagus cuniculus).

Spontaneous neurologic disease was observed in 6 to 8-week-old rabbits. Both males and females from several different litters were affected but all were sired by the same male. Clinically, the disease was characterized initially by posterior weakness and incoordination which progressed to tetraplegia within 3--4 weeks. With light microscopy there was neuronal degeneration and loss within the ventral horns of the spinal cord and brain stem and type-II fiber atrophy of skeletal muscles. Ultrastructurally the neuronal degeneration was characterized by accumulations of 100 A neurofilaments within the perikaryon. These findings are compared to diseases with neurofibrillary accumulation in animals and man.

Urolithiasis in ferrets (Mustela putorius).

Urinary calculi was observed frequently in ferrets which were from a group used for influenza research. They were submitted for necropsy with various clinical signs. The calculi were composed of magnesium ammonium phosphate hexahydrate and were found in the pelvis of the kidney, urinary bladder and urethra. Crystals of undetermined nature occasionally were observed in the kidneys.

Feline myeloproliferative disease. Changing manifestations in the peripheral blood.

A 4 1/2-year-old cat had myeloproliferative disease characterized by severe anemia. Peripheral blood had a profusion of relatively normal-appearing nucleated erythroid cells in all stages of development and a few primitive cells with nucleoli. The term "erythremic myelosis" best described the appearance of the peripheral blood. Two weeks later, the peripheral blood picture was that of regenerative anemia. During the next 2 months the cat made an apparent clinical recovery without treatment, but relapsed 3 months after the initial examination. One-fourth of the cells in circulation at the time of relapse contained nucleoli and appeared identical to those described in reticuloendotheliosis in cats. This transition suggested the progressive development of a greater degree of immaturity of erythroid precusors with time. The use of the term "reticuloendotheliosis" in conjunction with feline myeloproliferative disease was considered and determined inappropriate.

Shigella dysenteriae I enterotoxin: proposed role in pathogenesis of shigellosis.

Bacterial strains of Shigella dysenteriae I (3818-T and 3818-O) and Shigella enterotoxin altered myoelectric activity of the small intestine in New Zealand White rabbits. These agents were compared with activity caused by sterile culture broth or sterile saline. The altered myoelectric activity was characterized by two distinct complexes: repetitive bursts of action potentials (RBAP), characteristic of invasive strains of bacteria, and the migrating action potential complex (MAPC), characteristic of noninvasive bacteria. RBAP activity was the predominant myoelectric complex observed with S. dysenteriae strain 3818-T, an invader and toxin producer; S. dysenteriae strain 3818-O, a noninvader and toxin producer; and by Shigella enterotoxin. MAPC activity was present but was significantly less in all cases. These studies of the small intestine demonstrate an alteration in myoelectric activity characterized principally by RBAP activity indicative of invasion.

Calcium phosphate deposition disease in great danes.

A new clinicopathologic syndrome, possibly familial, in Great Dane dogs, resembles the familial childhood variant of calcium pyrophosphate dihydrate deposit disease in man, except that the mineral deposits were composed of amorphous calcium phosphate or hydroxyapatite rather than pyrophosphate. The syndrome was characterized clinically by paraplegia and incoordination in very young puppies which was caused by concentric constriction of the posterior cervical spinal cord. Canal stenosis resulted from dorsal displacement of the seventh cervical vertebra and deformation of the vertebral articular processes. Mineral deposition in the diarthrodial joints of the axial skeleton could be seen on radiographs of weanling puppies, and the appendicular skeleton became involved as the dogs matured. Periarticular mineralization of the limbs was associated with shorter bones, a thin cortex, abnormal bone curvature, and increased medullary trabeculae. Bone alterations were associated with abnormalities of the growth plate, which had focal areas of cartilage calcification. Soft tissue mineralization, seen in all dogs, was a primary feature of the disease process. Serum calcium concentrations were within the normal range, but serum phosphorus concentrations were decreased.