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Tox path 2008-2009

Tox path 2008-2009

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Published by: vetpathforum on Jun 03, 2010
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2008Isoproterenol-induced Cardiotoxicity in Sprague-Dawley Rats: Correlation of Reversible andIrreversible Myocardial Injury with Release of Cardiac Troponin T (cTnT) and Roles of iNOS inMyocardial Injury
A Type I response, potential reversible myocardial alterations associated with slightincreases in serum cTnT. The second type of response. irreversible myocyte alterations, together withsignificant increases in serum
cTnT. By 48hrsThere was interstial fibrosis cTnT was in normal levels.Increases in iNOS immunoreactivity correlated with thelesion severity. These findings suggest that low doses of Iso exert complex effects on the myocardiumand that the generation of NO through increased expression of iNOS could be an important factor in the pathogenesis of myocyte injury.
Fibro-osseous (FOL) and Degenerative Joint Lesions in Female Outbred NIH Black Swiss MiceNIH Black Swiss mice (Cr;NIH BL[SJ)
revealed a high inc ~dence of fibro-osseouslesions (POL; 89%)and degenerative joint lesions (90%). FOL in female Black Swiss was often accompanied by reproductive-tract lesions, including ovarian atrophy and uterine cervical dysplasia with hydrometra
Summary of Chemically Induced Pulmonary Lesions in the National Toxicology Program (NTP)Toxicology and Carcinogenesis Studies
The lung is the second most common target site of neoplasia of chemicals tested by the National Toxicology Program (NTP). The most commonly induced lung tumorswere alveolar/bronchiolar (A/B) adenoma and/or carcinoma for both species (rats and mice). The liver was the most common primary site of origin of metastatic lesions to the lungs of mice; however, skin wasmost often the primary site of origin of metastatic lesions to the lungs of rats. site of origin of metastaticlesions to the lungs of mice; however, skin was most often the primary site of origin of metastatic lesionsto the lungs of rats. In summary, AJB adenoma and carcinoma were the most frequently diagnosedchemically induced tumors in the lungs of both rats and mice.
Spontaneous and Age-Related Testicular Findings in Beagle Dogs
Hypospermatogenesis,characterized by randomly scattered missing spermatids and/or spermatocytes within seminiferoustubules, was observed in 75% of dogsAtrophy/hypoplasia of seminiferoustubules, Retained spermatids, multinucleate giant cells, intracytoplasmic vacuoles (presumably in Sertolicells), and swollen spermatocytes were common findings of minimal severity. If evaluationofspermatogenesis is critical, the incidental findings can be minimized by using males over twelvemonths of age.
Characterization of Age- and Gender-related Changes in the Spleen and Thymus from ControlCynomolgus Macaques Used in Toxicity Studies
The thymus had a trend toward increased interlobular fat infiltration with increasing age in both males and females. Thymic delineation of the cortex andmedulla was significantly decreased in the seven-to-fifteen-years age group for males only. The cortex-to-medulla ratio was significantly lower only in males in the seven-to-fifteen-years age group. B
Histopathology of the Urinary Bladders of Cynomolgus Monkeys Treated with PPAR Agonists
Theurinary bladder in the monkey has two very distinctive features that are not seen in rodents, dogs, or humans. The first of these is the presence of eosinophilic granules. Second, the monkey bladder has awide range in the number of mononuclear inflammatory cells normally present in the submucosa andurothelium.
Systemic Inflammatory Response Syndrome in Nonhuman Primates Culminating in MultipleOrgan Failure, Acute Lung Injury, and Disseminated Intravascular Coagulation
The systemic inflammatory response syndrome (SIRS) is a clinicopathological manifestation of overexuberant acute-phase inflammation caused by infectious or noninfectious etiologies. The diagnosisof SIRS should be considered when evaluating nonhuman primate (NHP) cases ofMOP manifesting withhistological evidence of vascular leakage.
2009Carcinogenic Effects of MGP-7 and BjajP on the Hamster Cheek Pouch
The short-term study showed that B[a]P induced p53 protein accumulation, indicative of genotoxicdamage, as well as increased cell proliferation, hyperplasia, and inflammation, which is usually associatedwith promotional activity. In contrast, the MGP-7 presented only marginal p53 accumulation andinduction of BrdU incorporation. In the long-term experiments, all the animals treated with B[a]P had a100% incidence of squamous cell carcinoma (SCC). MGP-7 showed only weak hyperplasia and a low proliferation rate and accumulation of p53 protein through long-term treatment.
Spontaneous Cardiomyopathy in Cynomolgus Monkeys (Macaca Fascicularis)
Microscopically, theapical to mid-ventricular myocardium to subendocardium had foci of cardiomyocyte disarray withcytoplasmic pallor to stippling and karyomegaly, vacuolization of the perimyseal connective tissue, ameshwork of fibrous tissue that concentrated around medium-sized blood vessels and dissected betweenor less often replaced affected cardiomyocytes; and a minimal, predominantly macrophage infiltrate. Thefeatures were reminiscent of chronic eatecholamine-induced experimental cardiomyopathy in monkeys.
Histopathological Features of Capillaria hepatica Infection in Laboratory Rabbits
Capillaria hepotica is a nematode parasite of wild rodents and other mammals. Large granulomas(macrogranulomas) were evident in portal areas and involved the bile ducts. Macrogranulomas containedcollections of characteristic C. hepatica eggs, macrophages, eosinophils, and lymphocytes. Smallgranulomas (microgranulomas), characterized by epithelioid macrophages surrounded by lymphocytesand eosinophils, were also identified. C. hepotica eggs were also observed in the lumina of the bile ductsand gall bladder. No adult C. hepatica worms were identified.Life cycle:After ingestion by the definitive (i.e., final) host, the embryonated egg containing the infective first-stagelarva (L1) hatches in the small intestine or The released L1 larva penetrates the intestinal mucosa and passes to the liver via the portal or mesenteric veins. The L1 larvae are found in the liver at day 2/3 post-infection. All the moults of the larval stages occur in the liver: L1 to L2 (160 to220 urn long) at day 3-7 post-infection; L2 to L3 (270 to670 urn long) at four or five days post-infection; and L3 to L4 (1100 to3600 um long) at seven to sixteen days after infection. The moulting of the L4 larva to produce the maleor femaleL5 larva occurs at eighteen to twenty days post-infectionThe fertilized adult female wormmoves through a syncytium of host liver cells depositing clusters of uncleaved eggs; these eggssubsequently become enclosed by the host in localized granulomas (macrogranulomas)
Strain-related Differences in Urine Composition of Male
Rats of Potential Relevance to Urolithiasis HSD rats had significantly higher urine calcium than SD or WI rals, primarily as calcium phosphate-containing precipitate. When compared to SD rats, HSD rats hadlower urine volume, higher urine protein, and a comparable (week 4) to lower (week13) burden of MgNH4PO4 aggregates. Relative to WI rats, HSD rats had higher urine protein and magnesium andlower serum and urine citrate. Overall, the susceptibility to urolithiasis in male rats was
Phytol-induced Hepatotoxicity in Mice
Phytanic acid is a branched-chain, saturated fatty acid present inhigh concentrations in dairy products and ruminant fat. Some other dietary fats contain lower levels of  phytol, which is readily converted to phytanic acid after absorption. Phytanic acid is a peroxisome proliferator binding thenuclear transcription factor peroxisome proliferator-activated receptor a (PPA.Rre) to induce expressionof genes encoding enzymes of fatty acid oxidation in peroxisomes and mitochondria. Administration of dietary phytol (0.5% or 1%) to normal mice for twelve to eighteen days caused consistent PPARrc-mediated responses, such as lower body weights, higher liver weights, peroxisome proliferation,increased catalase expression, and hepatocellular hypertrophy and hyperplasia. Female mice fed 0.5%
 phytol and male and female mice fed 1% phytol exhibited midzonal hepatocellularnecrosis, periportalhepatocellular fatty vacuolation, and corresponding increases in liver levels of the phytol metabolites phytanic acid and pristanic acid. These results suggestthat phytol may cause selective
midzonal hepatocellular necrosis
in mice, an uncommon pattern of hepatotoxie injury, and that the greater suscept ibility of female mice may reflect a lower capacity tooxidize phytanic acid because of their intrinsically lower hepatie expression of sterol carrier protein-x(SCP-x) males have 5X.
Cardiac Valvular Pathology:
Comparative Pathology and Animal Models of Acquired Cardiac Valvular Disease.Mouse: Spontaneous valve disease has been described in the Swiss CD-i mouse. The alterationwas usually on the free edge of the leaf. The pulmonic valve was commonly affected. In the rat, theincidence was greatest in the mitral valve. In the Dog, The condition is referred to as myxomatousatrioventricular valvular degeneration, chronic valvular fibrosis, or endocardiosismost common in themitral valve, inflammation is rare, Hemorrhage and mineralization may be present, No valvular disease in populations of laboratory nonhuman primates has not been reported. rheumatic heart disease in rats isassociated with streptococcal M protein. Carcinoid heart disease occurs in most patients with carcinoidsyndrome, a metastatic neoplasm of serotonin-producing gastrointestinal endocrine cells, and ischaracterized by fibrous thickening of cardiac valves. [LDLr(-/-)ApoB(l00/l00)] develop aortic valvecalcification. Watanabe rabbits and diet-induced hypercholesterolemic and atheroscleroticmodels in wild-type rabbits. Valvular disease, primarily aortic valvular stenosis, has been described.
Evaluation of Subchronic Toxicity of Pet Food Contaminated with Melamine and Cyanuric Acid inRats:
food contained significant levels of cyanuric acid and melamine in a ratio of 1:6.8. Rats fed the dietof 50%–100% for three months exhibited elevated serum BUN and creatinine, as well as dose-dependentmelamine/cyanuric acid crystal-induced nephrotoxicity. In
conclusion, the combination ratio of cyanuricacid to melamine
and the acidic urine content were two factors that, upon repeated
exposure, determinedthe severity of the nephrotoxicity. Numerous MC crystals of various sizes were mixed with the necroticcell debris in both proximal and distal renal tubules. Slight
to severe inflammatory cell infiltration wasaccompanied by
renal tubular dilation and epithelial cell regeneration with
interstitial fibrosis.
Dietary Fat–Influenced Development of Colon Neoplasia in Apc
Mice Exposed toBenzo(a)pyrene:
Consumption of well-done red meat and saturated fats
rich in polycyclic aromatichydrocarbons may be one of the causative
factors for sporadic colon cancer.
is a mutant mousewith multiple intestinal neoplasias. It has a mutated adenomatous polyposis coli (Apc), a tumor-suppressor gene, similar to that in patients with familial adenomatous polyposis. Apc
mouse mimics therapid development of adenomatous polyps that affect humans. Among the
several environmentaltoxicants, benzo(a)pyrene (B[a]P), a polycyclic
aromatic hydrocarbon (PAH) compound, has generatedthe most
interest, as this chemical is formed in red meat cooked at high
temperatures. Treatment consistedof 50 and
100 µg B(a)P/kg body weight dissolved in peanut or coconut
oil (representatives of unsaturatedand saturated fats, respectively. An increased
 prevalence of adenomas in colons of mice that ingestedB(a)P
through saturated dietary fat compared to unsaturated fat and
The Metrial Gland in the Rat and Its Similarities to Granular Cell Tumors (
Tol Pat l 
2009; 37; 474)Metrial glands are normal structures located in the mesometrial triangle of the pregnant rat uterus fromgestational day (GD) 8 through termination of pregnancy.
Metrial glands are composed of a dynamicmixed cell population of granulated metrial gland (GMG) cells, endometrial stromal cells,trophoblasts, blood vessels, and fibroblasts.
GMG cells are approximately 40 um in diameter and have

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