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Biomedical subjects

B P Stuart

Publications and source records attributed to B P Stuart.

At least 19 recordsLinked to original sources

Tumors in long-term rat studies associated with microchip animal identification devices.

Tumors surrounding implanted microchip animal identification devices were noted in two separate chronic toxicity/oncogenicity studies using F344 rats. The tumors occurred at a low incidence rate (approximately 1 percent), but did result in the early sacrifice of most affected animals, due to tumor size and occasional metastases. No sex-related trends were noted. All tumors occurred during the second year of the studies, were located in the subcutaneous dorsal thoracic area (the site of microchip implantation) and contained embedded microchip devices. All were mesenchymal in origin and consisted of the following types, listed in order of frequency: malignant schwannoma, fibrosarcoma, anaplastic sarcoma, and histiocytic sarcoma. The following diagnostic techniques were employed: light microscopy, scanning electron microscopy, and immunohistochemistry. The mechanism of carcinogenicity appeared to be that of foreign-body induced tumorigenesis.

Animal Identification Systems↗

Renaut bodies in the sciatic nerve of beagle dogs.

182 control Beagle dogs from 23 historical studies (14 chronic, 9 subchronic) were reviewed histologically for the presence of Renaut bodies in the sciatic nerve. Renaut bodies were found in 36.1 percent of the subchronic-study dogs and in 46.4 percent of the chronic-study dogs. The Renaut bodies most often resided in the distal sections of the sciatic nerve, specifically in the tibial branch as it traversed the knee joint in situ. There was no sex predilection. Renaut bodies were located predominately in the endoneurium, in the center of the nerve sections. There was no associated axonal degeneration, reactive gliosis, or encapsulation. The Renaut bodies were characterized as large (20 to 500 microns diameter in cross section), well-demarcated elliptical structures with an onion-skin arrangement of loosely textured, filamentous strands intermixed with sparse numbers of dark spindle-shaped nuclei. Occasionally the core displayed a more dense, intensely eosinophilic arrangement of fibers. Histochemical results included: positive acidic alcian blue, Gomori's trichrome, and Verhoeff Van Gieson's; and negative Periodic-acid Schiff, Congo Red, and Luxol fast blue/cresyl violet. Immunohistochemical results included: positive vimentin and collagen (subtypes I, II, and VI); and negative NSE, S-100, GFAP, amyloid A component, desmin, alpha-sarcomeric actin, pancytokeratin, EMA, and von Willebrand factor. Transmission electron microscopy revealed loosely arrayed, circumferentially oriented collagen fibers intermixed with varying amounts of amorphous substance and finely fibrillar material. Most of the cells comprising the Renaut body were identified as fibroblasts. No nerve fibers entered or left the Renaut body, and nearby nerves appeared to be normal structurally. Based on this characterization of Renaut bodies and in conjunction with the past literature, Renaut bodies appear to have little or no pathological significance, but rather are suggestive of a physiological adaptation in response to mechanical stress imposed on nerves.

Animals↗

Electronic imaging system incorporating a hand-held fundus camera for canine ophthalmology.

An electronic imaging system incorporating a hand-held fundus camera was used to collect images of the canine ocular fundus. The electronic imaging system comprised a hand-held fundus camera, an IBM personal computer (PC 350), Microsoft Windows NT 4.0, Adobe Photoshop, and a color printer (Tektronix Phaser 550) and was used to store, edit, and print the images captured by the fundus camera. Hand-held fundus cameras are essential for use in canine ophthalmology. The Nidek NM-100 hand-held fundus camera digitalizes images, enabling their direct transfer into reports and their storage on writeable CDs.

Animals↗

Electrophysiology and pathology evaluation of the Yucatan pig as a non-rodent animal model for regulatory and mechanistic toxicology studies.

Six male and six female Yucatan pigs were utilized to investigate the feasibility of this species as a non-rodent model for routine regulatory and mechanistic toxicology studies. This study evaluated disease surveillance and computerized electrophysiology, along with possible gross and micropathology changes. Two pigs were used as sentinel animals to evaluate the microbiological status of the vendor upon arrival; the other pigs were maintained as biomonitors and to provide baseline clinical chemistry, urinalysis, pathology and electrophysiology data. The electrophysiology tests conducted included electrocardiography (ECG), electroretinography (ERG) and quantitative electroencephalography (qEEG), which achieved consistent baseline values with acceptable intrasubject variation. Tissue cholinesterase and histochemical staining were done to determine their suitability for testing cholinesterase compounds. Evaluation of the serum chemistry profile demonstrated increased CPK and LDH, which was likely associated with slight haemolysis or minor subclinical muscle stress during handling. There were no additional clinical chemistry changes or findings in haematology, urinalysis parameters or gross pathology. Micropathology found an absence of background lesions which would interfere with routine toxicology studies, except for a mild rhinitis. The aetiological agent was identified by electron microscopy as being consistent with inclusion body rhinitis of swine, previously unreported in miniature swine. This would most notably interfere with inhalation studies. The anatomical and physiological similarities of the Yucatan pig, along with its ability to accept the performance of electrophysiology tests allow this species to be considered as a suitable model for organ system testing in toxicology studies.

Animals↗

Comparative kinetic analysis of cholinesterase methods in rat and human erythrocytes and plasma.

A kinetic analysis of the substitution of 6,6'-dithiodinicotinic acid (DTNA) for 5,5'-dithiobis-2-nitrobenzoic acid (DTNB) for the determination of rat and human erythrocyte acetylcholinesterase (AChE; EC 3.1.1.7) and plasma butyrylcholinesterase (BuChE; EC 3.1.1.8) is presented. Increasing concentrations of DTNB, but not DTNA, significantly increased Km for the substrate acetylthiocholine but had little or no effect on Vmax for rat or human AChE. The coupling agent DTNA was more efficient than DTNB, as demonstrated by the higher Vmax/Km ratio for the former. DTNB, more so than DTNA, caused linear mixed-type inhibition of rat AChE. Poor precision was observed for the DTNB versus DTNA method. Reagent blanks were a significant component of rat, but not human, AChE activity. The use of DTNA in place of DTNB is recommended for quantitative mechanistic investigations of cholinesterases. The most practical aspect of the DTNA method is that it can be adapted to automated instruments which can monitor the change in absorbance at 340 nm, away from the hemoglobin peak.

Acetylcholinesterase↗

Evidence of chemical stimulation of hepatic metabolism by an experimental acetanilide (FOE 5043) indirectly mediating reductions in circulating thyroid hormone levels in the male rat.

N-(4-Fluorophenyl)-N-(1-methylethyl)-2-[[5-(trifluoromethyl)-1,3, 4-thiadiazol-2-yl]oxy]acetamide (FOE 5043) is a new acetanilide-type herbicide undergoing regulatory testing. Previous work in this laboratory suggested that FOE 5043-induced reductions in serum thyroxine (T4) levels were mediated via an extrathyroidal site of action. The possibility that the alterations in circulating T4 levels were due to chemical induction of hepatic thyroid hormone metabolism was investigated. Treatment with FOE 5043 at a rate of 1000 ppm as a dietary admixture was found to significantly increase the clearance of [125I]T4 from the serum, suggesting an enhanced excretion of the hormone. In the liver, the activity of hepatic uridine glucuronosyl transferase, a major pathway of thyroid hormone biotransformation in the rat, increased in a statistically significant and dose-dependent manner; conversely, hepatic 5'-monodeiodinase activity trended downward with dose. Bile flow as well as the hepatic uptake and biliary excretion of [125I]T4 were increased following exposure to FOE 5043. Thyroidal function, as measured by the discharge of iodide ion in response to perchlorate, and pituitary function, as measured by the capacity of the pituitary to secrete thyrotropin in response to an exogenous challenge by hypothalamic thyrotropin releasing hormone, were both unchanged from the controlled response. These data suggest that the functional status of the thyroid and pituitary glands has not been altered by treatment with FOE 5043 and that reductions in circulating levels of T4 are being mediated indirectly through an increase in the biotransformation and excretion of thyroid hormone in the liver.

Acetamides↗

Extrathyroidally mediated changes in circulating thyroid hormone concentrations in the male rat following administration of an experimental oxyacetamide (FOE 5043).

Evidence of increased hepatic metabolizing capacity coupled with reductions in serum thyroxine (T4) levels were noted in the rat during preliminary toxicity studies with FOE 5043, an oxyacetamide with herbicidal properties. These findings were consistent with reports in the literature suggesting that declines in T4 as a result of exposure to various classes of chemicals may be mediated extrathyroidally, such as through chemical induction of hepatic thyroid hormone metabolism. To examine this question with respect to FOE 5043, male rats were surgically thyroidectomized and provided thyroid hormone replacement therapy via implanted osmotic minipumps capable of maintaining a T4/triiodothyronine (T3) serum concentration for approximately 4 weeks at a level comparable to that of euthyroid controls. Seven days after minipump implantation, thyroidectomized + T4/T3 (TX + T4/T3) and nonthyroidectomized intact rats (NTX) were fed diets containing 0, 25, 1000, or 3000 ppm FOE 5043 for up to 3 weeks. Dose-related and equivalent declines in total and free serum T4 levels in both TX + T4/T3 and NTX rats were measured at Weeks 1, 2, and 3. Alterations in thyrotropin, total, free, and reverse serum T3 levels were also noted in both TX and NTX animals; however, a compound-related trend was difficult to discern and, when compared to the T4 response, the changes were markedly less consistent with respect to both time and dose. Additionally, dose-related increases in absolute and relative liver weights were measured in both TX + T4/T3 and NTX animals. As the only source of thyroid hormone in the TX + T4/T3 animals was that provided by the pump, these data suggest that FOE 5043-induced alterations in serum thyroid hormone levels, most notably T4, are being mediated indirectly, possibly as a result of increased hepatic metabolism, rather than through a direct effect on the thyroid gland.

Acetamides↗

Neuromuscular hamartoma (benign "Triton" tumour) in a mouse.

Histological examination of a 22-month-old CD-1 mouse revealed a threefold enlargement of the right trigeminal ganglion. This change was due to the presence of well-differentiated striated muscle fibers intermingling with nerves and ganglion cells. The number of ganglionic Schwann cells was also increased as demonstrated by their positive S-100 protein staining. In addition, slight interstitial mononuclear cell infiltration and fibrosis were observed. The myocytes, which stained positive for myoglobin and desmin, and the proliferated Schwann cells did not show any signs of cellular or nuclear atypia. The lesion was diagnosed as "neuromuscular hamartoma (benign "Triton" tumor)" reflecting the capability of either Schwann cells or neural crest derived precursor cells to differentiate into various other cell types.

Animals↗

Coccidiosis in swine.

It is clear that although the clinical history, pathologic lesions, and endogenous stage life cycle of I. suis are well understood, the epidemiology of this parasite is not understood or is misunderstood. Consequently, treatment of individual piglets and prophylactic use of coccidiostats in sows have not been consistently rewarding. The best control at present is achieved through use of extensive sanitation, particularly steam cleaning. The incidence of clinical coccidiosis in piglets continues to be a major component (approximately 20 per cent) in the differential etiology of scours in baby pigs.

Animals↗

Prevalence of oocysts of Isospora suis and Eimeria spp from sows on farms with and without a history of neonatal coccidiosis.

Oocysts of Isospora suis were not found in any of 77 fecal samples from sows on farms with a history of neonatal coccidiosis. Oocysts of Isospora suis were found in 1 of 172 fecal samples from farms without a history of neonatal coccidiosis. Oocysts of Eimeria spp were found in 81.8% of the sows from farms with a history of neonatal coccidiosis and in 94.8% of the sows from farms without a history of neonatal coccidiosis. Oocysts of Isospora spp from birds were encountered as a pseudoparasite in several fecal samples.

Animals↗

Paralysis in swine due to focal symmetrical poliomalacia: possible selenium toxicosis.

A paralytic disease in swine was observed on three farms located in the same geographical area of Georgia. Postmortem examinations revealed the paralysis to be related to spinal poliomalacia. Feed collected from two of the affected farms was used in a feeding study, and the paralytic condition was reproduced. In pigs from both the feeding trial and field cases, the poliomyelomalacia was characterized by focal, symmetrical lesions located in the cervical and lumbar intumescences. Selenium was detected in the feed at levels ranging from 19 to 24 ppm.

Animal Feed↗

Coccidiosis in swine: a search for extraintestinal stages of Isospora suis.

Clinical coccidiosis in swine is associated with Isospora suis infection of piglets. The endogenous life cycle of I suis in piglets occurs within the superficial epithelium of the small intestine. Extraintestinal stages of I suis were not demonstrated in tissues of experimentally infected piglets or mice. Feeding these tissues to previously uninfected piglets did not result in oocyst shedding of consequence. Extraintestinal stages do not seem to occur in piglets with I suis as in some other Isospora species.

Animals↗

Acute aflatoxicosis in swine: clinical pathology, histopathology, and electron microscopy.

Feeder pigs weighing 12 to 15 kg each were given a single oral dose of aflatoxin, 1.2 mg/kg of body weight. Liver-specific serum enzyme activities were compared with gross, microscopic, and ultrastructural hepatic changes in individual pigs euthanatized at 24, 48, and 72 hours after they were given aflatoxin. The greater the morphologic change in liver of the treated pigs, the greater the increase in liver-specific serum enzyme activities. Isocitric dehydrogenase, alkaline phosphatase, sorbitol dehydrogenase, and aspartate aminotransferase activities increased in 6 of 8 treated pigs by 24 hours. Increase in gamma-glutamyl transpeptidase activity was not significant. Microscopic and ultrastructural changes in centrilobular hepatocytes included glycogen deletion, mitochondrial and endoplasmic reticulum swelling, membrane disruption, and nuclear fragmentation at 24 hours. The centrilobular areas had marked extravasation of erythrocytes at 24 hours without basal lamina changes. At 72 hours, the centrilobular hepatocytes had increased lipid vacuoles and acceptable amounts of glycogen. Marked infiltrations of monocytes, plasma cells, and lymphocytes were also present at this time.

Alkaline Phosphatase↗

Coccidiosis in swine: dose and age response to Isospora suis.

Coccidiosis is a disease of the young piglet due to infection with Isospora suis and is characterized by diarrhea which is nonresponsive to antibacterial therapy. There is variable morbidity and mortality. Piglets develop a more severe clinical illness and enteritis when infected with I. suis at one to three days of age than when infected at two weeks of age. Microscopic lesions range from villous atrophy and mild erosion to severe fibrinonecrotic enteritis.

Age Factors↗

High performance liquid chromatographic determination and clearance time of aflatoxin residues in swine tissues.

Liver, kidney, and muscle tissues from swine given a single oral dose of 1.2 mg aflatoxins/kg body weight and from young pigs fed an aflatoxin-contaminated diet (0,400, or 800 ng/g feed) for 10 weeks were analyzed for aflatoxin residues. Extraction was performed according to the method of Stubblefield and Shotwell. Aflatoxin residues were detected by high performance liquid chromatography (HPLC), and residue levels were correlated with withdrawal times. Residues were present in liver and kidney but not muscle by 12 h post-dosing; residues were detected in muscle by after 24 h. Residue levels decreased over the 72 h period in all tissues. No aflatoxin residues were detected in the muscle from any pig 72 h post-dosing or in those pigs fed the 400 ng/g diet, but were present in the muscle of pigs fed the 800 ng/g diet.

Aflatoxins↗