Effect of Experimental Ostertagia Ostertagi Infection or Chronic Pentagastrin Treatment on Abomasal Pathophysiology and Morphology of Goats.

European-type mixed-breed goat kids were infected with Ostertagia ostertagi or were given chronic pentagastrin treatment. Selected clinicopathological parameters and fecal egg counts were monitored throughout the study. At necropsy the abomasal physical parameters were recorded and tissue samples were saved for parasite recovery, quantitative and qualitative light microscopy and transmission and scanning electron microscopy. Serum pepsinogen and gastrin immunoreactivity increased in parasitized animals. The increase was associated with the tissue phase of the parasitic development. Pentagastrin did not alter pepsinogen or gastrin immunoreactivity. All 8 infected animals had patent infection, and approximately 5% establishment of the infective dose of 15,000 O ostertagi was achieved. The majority of the recovered parasites were adult and approximately 60% of them were female. At the time of necropsy the O ostertagi-infected animals had increased abomasal pH and the abomasa of the parasitized and the pentagastrin-treated animals had slightly increased weight. The abomasal mucosa of infected animals had umbilicated, white, raised nodules as has been described in bovine ostertagiasis. Pentagastrin-treated animals had prominent fundic folds. The light microscopic morphology of infected goats was similar to that of the bovine disease. There was a significant increase in the abomasal mucosal thickness, primarily due to the proliferation of mucous cells. The majority of the proliferating mucous cells contained sialoor sulfomucins. In pentagastrin-treated animals only slight thickening of the mucosa occurred. The transmission electron microscopic findings in parasitized animals were similar to bovine ostertagiasis, although there was no striking separation of the lateral plasmalemmata. In pentagastrin-treated animals the parietal cells appeared active and had abundant intracytoplasmic canaliculi lined by long microvilli. Scanning electron microscopy revealed marked surface alterations in hypertrophic parasitized abomasa, while control and pentagastrin treated animals had morphology similar to other mammals. Goats infected with O ostertagi developed a hypertrophic abomasitis. Hormonal factors appeared to be associated with the development of abomasal changes. Pentagastrin did not have a significant effect on the caprine abomasum. Slight subcellular changes and slight hyperplastic changes occurred

Az Egyetemes Postaegyesület és az Egyesült Nemzetek Szervezetének kapcsolata

INST: L_08

Egy szakmai projekt sikeres megvalósulása a Fecskefészek Evangélikus Óvodában

Nem ismer

Estrogen-related receptor gamma is a key regulator of muscle mitochondrial activity and oxidative capacity

Estrogen-related receptor γ (ERRγ), a member of the ERR family of orphan nuclear hormone receptors, was described to play a role a critical role in the perinatal switch to oxidative metabolism in the myocardium. In addition to the heart, ERRγ is expressed in tissues and cell types that have a high metabolic activity. We show that ERRγ regulates the expression of genes regulating oxidative phosphorylation, fatty acid oxidation, angiogenesis and skeletal muscle fiber type and contractile function. Further, we wanted to understand the functional consequence of ERRγ expression in skeletal muscle. Transgenic mice expressing a VP16ERRγ under the regulation of the muscle creatine kinase promoter, demonstrate an increase in exercise capacity as compared to their wildtype littermates. Despite a decrease in muscle size, mitochondrial function, as assessed by activity of key mitochondrial enzymes, was increased in these mice. Further, the peak oxidative capacity was higher in the transgenics, and the mice were able to maintain a lower respiratory exchange ratio under this exercise regimen. In contrast, mice lacking one copy of ERRγ, have a decrease in exercise capacity and muscle mitochondrial function. Interestingly, it was observed that increased ERRγ in muscle appears to generate a gene expression profile that is similar to that of “red oxidative fiber type”. We demonstrate that a small molecule agonist of ERRbeta/gamma can increase mitochondrial function in mouse myotubes. Our data indicate that ERRγ plays an important role in causing a shift toward slow twitch muscle and oxidative metabolism in skeletal muscle, and concomitantly, a greater capacity for endurance exercise. Thus, the activation of this nuclear receptor provides a potential node for therapeutic intervention for diseases such as obesity, which is associated with reduced oxidative metabolism and a lower type I fiber content in skeletal muscle

Investigation of Correlation between safety biomarkers in serum, histopathological examination and toxicogenomics

This article addresses the issue of miscorrelation between hepatic injury biomarkers and histopathological findings in the drug development context. Our studies indicate that the use of toxicogenomics can aid in the drug development decision-making process associated with such miscorrelated data. BLZ945 was developed as a Colony-Stimulating Factor 1 Receptor (CSF-1R) inhibitor. Treatment of BLZ945 in rats and monkeys increased serum alanine aminotransferase (ALT) and aspartate transaminase (AST). However, liver hypertrophy was the only histopathological liver finding in rats, and there was no change in the livers of monkeys. Longer treatment of BLZ945 in rats for 6 weeks caused up to 6-fold elevation of ALT, yet hepatocyte necrosis was not detected microscopically. Toxicogenomic profiling of liver samples demonstrated that the genes associated with early response to liver injury, apoptosis/necrosis, inflammation, oxidative stress, and metabolic enzymes were upregulated. Studies are ongoing to evaluate the mechanisms underlying BL945-induced ALT and AST elevation

Meeting report: Spontaneous Lesions and Diseases in Wild, Captive-Bred, and Zoo-Housed Nonhuman Primates and in Nonhuman Primate Species Used for Drug Safety Studies

The combination of loss of habitat, human population encroachment, and increased demand of select species for biomedical research has expanded the list of emerging diseases. There remains a need for knowledge and expertise in understanding background findings as related to the age, source, strain, and disease status of nonhuman primates. In particular, for safety/biomedical studies, a broader understanding and documentation of lesions would help clarify background from treatment related findings. A workshop and mini-symposium on spontaneous lesions and diseases in nonhuman primates were sponsored by the concurrent Annual Meetings of the American College of Veterinary Pathologists and the American Society for Veterinary Clinical Pathology held December 3-4, 2011 in Nashville, TN. The first session had presentations from Drs. Linda Lowenstine and Richard Montali, pathologists with extensive experience in wild and zoo populations of nonhuman primates, which was followed by presentations of 20 unique case studies of rare or newly observed spontaneous lesions in nonhuman primate species. The mini-symposium concentrated on background and spontaneous lesions in nonhuman primate species used for drug safety studies, and included presentations on incidence and range of spontaneous findings in cynomolgus macaques; lesions in the urogenital system of macaques; gastrointestinal lesions and pathogens in macaques and marmosets; age-associated lesions in rhesus macaques; and effects of Plasmodium infection on drug development. Both sessions were heavily attended by meeting participants that included students, pathology trainees, and experienced pathologists from academia and industry with an interest in spontaneous diseases of nonhuman primates