Significant Microscopic Lesions Research Articles

Case report

Blister beetle poisoning (cantharidiasis) of horses has been well documented. Primary exposure to blister beetles is through consumption of contaminated lucerne hay. Confirmed cases of bovine cantharidiasis due to natural exposure have not previously been documented in veterinary literature. This report describes four cases of blister beetle poisoning in three dairy herds and one beef herd in New Mexico and Oklahoma, USA, that were reported between 1995 and 1999. Cows in two large dairy herds consumed blister beetles in a total mixed ration containing green chop lucerne. The most significant clinical signs were mass refusal to eat the freshly cut green chop lucerne, although the cows appeared hungry, and the corresponding dramatic decrease in milk production. Cows in a smaller dairy herd and a beef herd consumed large round bales of lucerne hay containing blister beetles. In contrast to cows exposed to the beetles in green chop, feed refusal in these cases was limited to individual cows. Other clinical signs included salivation, bruxism, frequent urination, diarrhoea, reluctance to move, abdominal pain, ataxia and recumbency. Postmortem examination did not reveal significant gross or microscopic lesions. Cantharidin was detected by gas chromatography-mass spectrometry analysis of either urine or feed samples. In addition, blister beetles were found in the lucerne green chop or hay.

Safety and Efficacy of in ovo Administration of Infectious Bursal Disease Viral Vaccines

In ovo vaccination against Marek's disease virus and infectious bursal disease virus (IBDV) in commercial broilers in the United States is common. Little information exists as to the safety and efficacy of intermediate IBDV vaccines given in ovo. Experiments were initiated to determine the safety and efficacy of three commercially available live intermediate IBDV vaccines by in ovo route. Commonly used vaccines were given at 18 days of embryonation to specific-pathogen-free (SPF) broiler embryos (first and second study) or to commercial broiler embryos (third study) that had maternal antibody against IBDV. When any of the antigenic standard vaccines was given at full dose to SPF embryos, embryonic and 3-wk posthatch mortality increased. Vaccines also caused significant microscopic lesions in the bursa of Fabricius at 1 and 3 wk posthatch. In contrast, there was no adverse effect on embryonic or posthatch mortality when vaccines were given at half dose to SPF or commercial broiler embryos. However, significant microscopic lesions were evident at 1 and 3 wk posthatch in the bursae of SPF embryos given the vaccines at half dose. When vaccines were given at half dose to commercial broiler embryos, lesions were evident at 1 but not 3 wk of age. In the third study, in ovo vaccinated chickens were challenged with either a virulent standard (APHIS) or antigenic variant (variant E) IBDV virus at 3 wk of age. All vaccines produced at least 87% protection against the standard and 60% protection against the variant challenge IBDV, as measured by bursal weight to body weight ratios. This study was the first to examine the safety and efficacy of the three commonly used intermediate IBDV vaccines given in ovo in protection against standard and antigenic variant IBDV challenge viruses.

Characterization of inhaled alpha-methylstyrene vapor toxicity for B6C3F1 mice and F344 rats.

alpha-Methylstyrene (AMS) is a chemical intermediate used in the synthesis of specialty polymers and copolymers. Inhalation studies of AMS were conducted because of the lack of toxicity data and the structural similarity of AMS to styrene, a toxic and potentially carcinogenic chemical. Male and female B6C3F1 mice were exposed to 0, 600, 800, or 1000 ppm AMS 6 h/day, 5 days/week, for 12 days. After 1 exposure, 21% (5/24) of female mice were found dead in the 1000-ppm group, 56% (10/18) in the 800-ppm group, and 6% (1/18) in the 600-ppm concentration group. After 12 exposures, relative liver weights were significantly increased and relative spleen weights were significantly decreased in both male and female mice at all concentrations. No microscopic treatment-related lesions were observed. A decrease in hepatic glutathione (GSH) was associated with AMS exposure for 1 and 5 days. Male and female F344 rats were exposed to 0, 600 or 1000 ppm AMS for 12 days. No mortality or sedation occurred in AMS-exposed rats. Relative liver weights were significantly increased in both males and females after 12 exposures to 600 or 1000 ppm. An increased hyaline droplet accumulation was detected in male rats in both concentration groups; no significant microscopic lesions were observed in other tissues examined. Exposure of male and female F344 rats and male NBR rats to 0, 125, 250 or 500 ppm AMS, 6 h/day for 9 days resulted in increased accumulation of hyaline droplets in the renal tubules of male F344 rats in the 250 and 500 ppm concentration groups. Although AMS and styrene are structurally very similar, AMS was considerably less toxic for mice and more toxic for male rats than styrene.

Aborto em vacas na intoxicação experimental pelas favas de Stryphnodendron obovatum (Leg. Mimosoideae)

As favas maduras de Stryphnodendron obovatum Benth. procedentes de Mato Grosso, administradas a sete vacas com 3 a 7 meses de gestação, na dose de 5 g/kg/dia, durante 9 a 26 dias, causaram doença caractrizada por diminuição do apetite, diminuição da atividade ruminal, sialorréia, dificuldade em se levantar, andar desequilibrado, tremores musculares, acentuado emagrecimento e finalmente em 3 das 7 vacas, aborto entre 20 e 30 dias após o início da administração das favas; uma quarta vaca eliminou um feto mumificado 7 meses após o início do experimento. Três vacas deram nascimento a bezerros normais. Nos fetos abortados e nas placentas não foram verificadas lesões macroscópicas ou microscópicas dignas de nota. Os presentes experimentos confirmam as informações obtidas em fazendas do cerrado nos Estados de São Paulo e Mato Grosso sobre a ocorrência de aborto em vacas que ingerem as favas de S. obovatum.

Granulomatous Dermatitis in New Zealand White Rabbits Following 9-Day Repeated Cutaneous Exposure to Methyldimethoxysilane

Male and female New Zealand White rabbits were exposed to 0.0,0.05,0.1, or 0.2 ml/kg of undiluted methyldimethoxysilane (MDMS), corresponding to 43, 85, or 171 mg/kg, applied under occlusive dressing to the clipped dorsal trunk skin for nine doses over an 11 day period. Five animals/group/gender (10/gender in the 85 mg/kg/day group) were euthanized at the end of the exposure period. Five animals/group/gender from the high-dose and control groups were retained for a 2 week recovery period and then euthanized. The only abnormal findings involved the treated skin. Clinical observations included mild to moderate irritation of the treated skin, affecting mainly high-dose group animals euthanized immediately after the exposure period, with females being slightly more sensitive. Significant gross and microscopic lesions were seen in the treated skin of animals receiving 0.1 ml/kg/day and higher. Gross lesions consisted of erythema, ecchymoses, exfoliation, excoriation, fissures, ulceration, and necrosis. Microscopic lesions included hyperkeratosis, acanthosis, congestion, hemorrhage, epidermitis, dermatitis, and ulceration. Dermal fibrosis and prominent granulomatous inflammation, associated with pigmented granular foreign material, was found in the superficial dermis. After the 2 week recovery period, exfoliation was the only gross skin lesion found in high dose group animals. Microscopic skin lesions consisted of marked granulomatous dermatitis and a fibrotic reaction associated with the foreign material, as well as microscopic examination of the skin of recovery group animals revealed scattered electron-dense deposits in the superficial dermis, which were proven, on elemental analysis, to contain silicon, possibly in the form of a polymer from absorbed MDMS or its breakdown products. There were no abnormal clinical pathologic findings in animals euthanized immediately after exposure, but a significant monocytopenia occurred in high-dose-group male rabbits from the recovery group, which may be due to sequentration of circulating monocytes in the skin at the site of granulomatous inflammation.

Immunoglobulin E Responses and Lung Pathology Resulting from Aerosol Exposure of Calves to Respiratory Syncytial Virus and <i>Micropolyspora faeni</i>

Bovine respiratory syncytial virus (BRSV) infection of calves has been associated with a type-I hypersensitivity syndrome not unlike respiratory syncytial virus-associated pulmonary symptomatology in humans. To study the mechanism of pulmonary pathology in calves and define the relationship with both viral-specific IgE response and IgE titers to concurrent aerosol of Micropolyspora faeni (Mf) we subjected groups of calves to inhalation of Mf during acute BRSV infection. The calves were divided into 4 groups: exposed to virus only (group 1); exposed to aerosolized Mf over a 24-day period and then challenged with Mf during BRSV infection (group 2); similarly exposed to aerosolized Mf and then challenged with Mf without BRSV infection (group 3) and exposed to aerosolized Mf, infected with virus but not challenged with Mf (group 4). All calves were followed for appearance of IgE-specific responses to both BRSV and Mf, clinical disease expression, and pulmonary pathology including viral and allergen localization by immunohistology. Our data indicate an association of BRSV-specific IgE with increased development of lung pathology and clinical disease expression and an enhancing effect of aerosolized Mf on induction of virus-specific IgE. The presence of BRSV-specific IgE was solely in calves with the most significant macroscopic and microscopic pneumonic lesions.

Isolation of [formula omitted][formula omitted] subsp. [formula omitted] (LC variant, Y-Goat) from naturally aborted bovine fetuses

Seven strains of Mycoplasma mycoides subsp. mycoides (LC, Y-Goat) were isolated from 4 of 85 (4.7%) cases of bovine abortion. The biochemical characters of all the isolates were homogenous (except for one sucrose negative isolate), but variation in sensitivity to neomycin, kanamycin and streptomycin were noted. The only gross lesions of internal organs in aborted fetuses were congestion of liver and lungs, and hemorrhagic patches on the heart surface. Significant microscopic lesions were encountered in lungs (edema of the interlobular septae, thickened alveolar wall, lymphocytic infiltration, septal hyperplasia and alveolar infiltration with neutrophils and macrophages), liver (mild lymphocytic infiltration in the hepatic triad, hypertrophy of Von-kupffer cells), kidney (degenerative necrosis and desquamation of tubular epithelium, and the marked lymphocytic infiltration in the interstitium), spleen (depleted lymphoid tissues, infiltration of lymphocytes, macrophage and plasma cells in the red pulp) and heart (lymphocytic myocarditis). The observations of this study focus on the role of M. mycoides subsp. mycoides (LC variant) in bovine abortions.

Histopathological evaluation of proliferative liver lesions in rats fed trans-anethole in chronic studies

In a two-year study of rats fed trans-anethole—a flavouring that is Generally Recognized As Safe by the US Food and Drug Administration—a slight increase in proliferative lesions of the liver was observed. These results were reviewed by a Pathology Working Group (PWG) and their findings are detailed here. The increased incidence of non-neoplastic lesions in male and female rats fed 0.25, 0.5 or 1.0% trans-anethole was considered by the PWG to be treatment related. Male and female rats fed 0.25% trans-anethole in their diet (25 to 29 times the postulated maximum human intake) had no significant treatment-related microscopic lesions in the liver, although there was a slight increase in parenchymal cell hyperplasia. Rats fed 0.5% trans-anethole had hepatic changes consistent with those caused by chronic exposure of rodents to compounds with enzyme-inducing activity. Male and female rats fed 1.0% trans-anethole revealed increased incidence and severity of hepatic changes as seen in the mid-dose rats, and a low incidence of hepatocellular neoplasms. These neoplasms were not increased in male rats in any dietary group or in female rats of the low- (0.25%) and mid-dose (0.5%) groups. The slightly increased incidence of hepatocellular neoplasms in the high-dose females is not considered to be of significance to human safety and it is concluded that trans-anethole does not constitute a carcinogenic risk for man. The slightly increased tumour incidence was seen only in the highest dose group of one sex; it has not been observed in studies of mice fed trans-anethole—the metabolism of trans-anethole in the mouse is similar to that in man. The extremely high exposure was associated with other liver changes which may have contributed to the findings.

Peripheral neuropathy associated with dietary riboflavin deficiency in the chicken. I. Light microscopic study.

Chickens fed a riboflavin-deficient diet from hatching had leg weakness and paralysis as early as 12 days of age. Signs worsened through day 16; after 35 days, recovery was evident. Sciatic nerves from affected chickens were enlarged. Significant microscopic lesions were confined to peripheral nerves and included tissue separation (suggesting interstitial edema), Schwann cell swelling, perivascular leukocytic infiltration, and segmental demyelination accompanied by accumulation of osmiophilic debris in Schwann cell cytoplasm. Axon degeneration was present, but was not a primary lesion. Acid phosphatase enzyme activity of Schwann cells was increased in affected nerves. These results demonstrate that dietary riboflavin deficiency causes a demyelinating peripheral neuropathy in young, rapidly growing chickens.

Lesions of experimentally induced Tyzzer's disease in Syrian hamsters, guineapigs, mice and rats.

The relative susceptibilities of C57BL/6NCR and BALB/cANNCR mice, F344/NCR rats, 2/NCR guineapigs and CR:RGH Syrian hamsters to Bacillus piliformis infection were determined by orally inoculating 20 weanling females from each species with suspensions of B. piliformis spores. Animals from each group were sequentially necropsied over 2 week periods to document the lesions produced. No significant gross or microscopic lesions were observed in the BALB mice or the Fischer rats. Gross and microscopic lesions were observed in the livers and intestines of many guineapigs and hamsters killed 3-14 days after inoculation. A large lesion was observed in the left cardiac ventricle of one C57BL mouse 10 days after inoculation. Warthin-Starry silver-stained tissue sections revealed clusters of B. piliformis within the cytoplasm of intestinal epithelial cells, smooth muscle cells, hepatocytes and myocytes bordering foci of necrosis in the intestines, liver and heart.

Comparative toxicology of tetrachlorobiphenyls in mink and rats: II. Pathology

Young female pastel mink and young female Sprague-Dawley rats were injected intraperitoneally on 3 sequential days with 50 mg/kg of either 2,4,2′,4′ tetrachlorobiphenyl (TCB) or 3,4,3′,4′-TCB and sacrificed after 7 days. Two control groups were established for each species; one allowed free access to food, and one pair-fed to the 3,4,3′,4′-TCB-treatment group. Heart blood was collected from each mink immediately after sacrifice. A complete set of tissues was collected from all animals and placed in buffered formalin. The rats displayed no clinical signs of illness following the administration of either congener, nor were there any significant gross or microscopic lesions created in this species. Mink in the 2,4,2′,4′-TCB and control groups remained free of clinical signs and significant gross or microscopic lesions. Mink in the 3,4,3′,4′-TCB group developed anorexia within 48 hr after the initial injection, and depression and melena by Day 4. Necropsy on Day 7 revealed a severe necrotizing enteritis with moderate to marked villus atrophy and fusion in the small intestines of all mink in this treatment group. The epithelial necrosis generally spared the basal one-third of the mucosa, and the deep crypt epithelium was often moderately hyperplastic. The mechanism by which 3,4,3′,4′-TCB causes this unique lesion is unknown.

Cartilage Lesions Associated with Shaky-Leg Lameness in Turkeys

Shaky-leg lameness is a poorly defined, mild to very severe, painful lameness occurring mainly in 10-to-18-week-old fast-growing male turkeys. Since there are no significant gross or microscopic lesions in early or uncomplicated cases, the cause of the lameness is likely soft-tissue (muscle or tendon) pain. A case history of a flock problem of shaky-leg lameness is described, and it is suggested that stiffness and inactivity secondary to footpad dermatitis in these turkeys was responsible for the severe shaky-leg lameness in the flock. The cartilage lesion described is an avascular lesion and appeared to be the result of inactivity rather than the cause of lameness in these turkeys.

Sequential Pathology of Genital Tract in Chickens Experimentally Infected with Mycoplasma gallisepticum

Unsexed day-old White Leghorn chicks hatched from eggs pre-treated with erythromycin were infected via the yolk sac with a 48-hr broth culture of pathogenic Mycoplasma gallisepticum (S6). Fourteen of the 57 experimental female birds had gross lesions in the oviduct, characterized by the presence of grayish-white caseous plugs of various sizes in a segment or throughout the length of the oviduct. Forty-six of the infected female birds had microscopic lesions, detected primarily as mild heterophilic infiltration, lymphocytic aggregates, lymphoid follicles, diffuse lymphocytic infiltration, pleocellular response, or a combination of any of these depending on the stage and extent of infection. The caseous plugs were formed by tissue debris, fibrin, necrotic heterophils, and sometimes a few lymphocytes and macrophages. Changes that accompanied the necrotic exudate were atrophy of the mucosa, hypertrophy of the oviduct wall, or sometimes necrosis of the folds of mucosa. No significant gross and microscopic lesions were detected in ovaries, although 3 of the 33 infected male chickens had histological lesions in the testes. Gross and microscopic changes of mycoplasmosis were also found in the respiratory tract. M. gallisepticum could be consistently reisolated from oviduct(s) up to five weeks PI; thereafter, isolations were intermittent. From the ovaries or testes the organism could be isolated consistently up to one week PI only. Agglutinins were detected in the sera of infected chickens as early as one week PI, when the mean titer was 1:5, and it reached a maximum of 1:128 at six weeks PI. Thereafter the titer gradually declined, but the demonstrable agglutinins were present until 25 weeks PI.

Adrenocortical degeneration in dogs, monkeys, and rats treated with α-(1,4-dioxido-3-methylquinoxalin-2-yl)- n-methylnitrone

The antibacterial compound α-(1,4-dioxido-3-methylquinoxalin-2-yl)- N-methylnitrone (DMNM), which was administered for a maximum period of 90 days, was given orally at 0, 7.5, 15.0 or 22.5 mg/kg/day for dogs; 0, 15, 50 or 100 mg/kg/day for rats; and 35 mg/kg/day for monkeys. Reduced food consumption and weight gain, depression, debility, and deaths occurred starting at doses (mg/kg/day) of 15 in dogs, 35 in monkeys and 50 in rats. Frequent emesis and occasional black, tarry feces were also observed in most treated dogs. Necropsy examinations revealed small, pale adrenal glands in rats given a dose of 50 mg/kg/day and gastrointestinal hemorrhage in dogs administered 15.0 or 22.5 mg/kg/day of DMNM. Microscopically, vacuolar degeneration of the canine, monkey and rat adrenal cortex was seen at all dosages and appeared to progress from the zona reticularis to the zona glomerulosa. In rats treated with 50 mg/kg/day of the drug chronic lesions of adrenal cortical fibrosis, atrophy, and nodular hyperplasia were also detected. The only other significant microscopic lesions consisted of mild testicular atrophy and occasional gastric erosions in dogs treated with 7.5 mg/kg/day of DMNM.

Pathology of Bolivian Hemorrhagic fever in the African green monkey.

Gross and microscopic pathological findings are presented for an African green monkey model of fatal Bolivian hemorrhagic fever. Six animals were inoculated with 1,000 plaque-forming units of Machupo virus, the etiological agent of Bolivian hemorrhagic fever. Five of the monkeys died within 13 days with signs of fever, anorexia, shock, and hemorrhage. The sixth monkey survived until the 24th day and died with signs of central nervous system disease. Gross lesions in the five monkeys that die in the acute stage included hepatic necrosis, necrotic enteritis, bronchopneumonia, and hemorrhages in the subcutis, lungs, intestine, liver, and lymph nodes. Microscopically, necrosis was consistently seen in liver, intestine, skin, oral cavity, and adrenal cortex. Acute thrombosis was observed in four monkeys, in blood vessels of the intestine, lung and choroid of the brain. Gram-negative bacteria were seen in many tissues, suggesting terminal bacteremia. The sixth monkey was emaciated and had bronchopneumonia, but did not have the necrotic hepatic and enteric lesions observed in the other five monkeys. The significant microscopic lesions in this monkey included encephalomyelitis, ganglionitis, and bronchopneumonia.

Hypervitaminosis D in New World Monkeys

Hypervitaminosis D was produced in squirrel monkeys (Saimiri sciureus) and Cebus monkeys (Cebus albifrons) by daily oral administration of 50,000–100,000 IU vitamin D3/day. Similar doses of vitamin D2 did not induce detectable toxicity. The syndrome in the squirrel monkey was characterized by hypercalcemia, hyperphosphatemia, uremia, and death in the absence of significant metastatic calcification or microscopic renal lesions. The Cebus monkeys developed widespread metastatic calcification similar to that reported in other species. Lesions of bone were not seen in either species. These data further support the difference in activities between vitamins D2 and D3 in New World primates and also suggest that the lesions of vitamin D toxicity may vary with dose and duration of illness. The data also indicate that renal failure in this syndrome need not be related to nephrocalcinosis but may represent a direct effect of vitamin D on renal function.