Molecular alterations in dog pheochromocytomas and paragangliomas

Recently, genetic alterations in the genes encoding succinate dehydrogenase subunit B and D (SDHB and SDHD) were identified in pet dogs that presented with spontaneously arising pheochromocytomas (PCC) and paragangliomas (PGL; together PPGL), suggesting dogs might be an interesting comparative model for the study of human PPGL. To study whether canine PPGL resembled human PPGL, we investigated a series of 50 canine PPGLs by immunohistochemistry to determine the expression of synaptophysin (SYP), tyrosine hydroxylase (TH) and succinate dehydrogenase subunit A (SDHA) and B (SDHB). In parallel, 25 canine PPGLs were screened for mutations in SDHB and SDHD by Sanger sequencing. To detect large chromosomal alterations, single nucleotide polymorphism (SNP) arrays were performed for 11 PPGLs, including cases for which fresh frozen tissue was available. The immunohistochemical markers stained positive in the majority of canine PPGLs. Genetic screening of the canine tumors revealed the previously described variants in four cases; SDHB p.Arg38Gln (n = 1) and SDHD p.Lys122Arg (n = 3). Furthermore, the SNP arrays revealed large chromosomal alterations of which the loss of chromosome 5, partly homologous to human chromosome 1p and chromosome 11, was the most frequent finding (100% of the six cases with chromosomal alterations). In conclusion, canine and human PPGLs show similar genomic alterations, suggestive of common interspecies PPGL-related pathways

Acute mountain sickness.

Acute mountain sickness (AMS) is a clinical syndrome occurring in otherwise healthy normal individuals who ascend rapidly to high altitude. Symptoms develop over a period ofa few hours or days. The usual symptoms include headache, anorexia, nausea, vomiting, lethargy, unsteadiness of gait, undue dyspnoea on moderate exertion and interrupted sleep. AMS is unrelated to physical fitness, sex or age except that young children over two years of age are unduly susceptible. One of the striking features ofAMS is the wide variation in individual susceptibility which is to some extent consistent. Some subjects never experience symptoms at any altitude while others have repeated attacks on ascending to quite modest altitudes. Rapid ascent to altitudes of 2500 to 3000m will produce symptoms in some subjects while after ascent over 23 days to 5000m most subjects will be affected, some to a marked degree. In general, the more rapid the ascent, the higher the altitude reached and the greater the physical exertion involved, the more severe AMS will be. Ifthe subjects stay at the altitude reached there is a tendency for acclimatization to occur and symptoms to remit over 1-7 days

Detemir insulin for the treatment of diabetes mellitus in dogs

To investigate the effects of insulin detemir in dogs with diabetes mellitus

Endothelial dysfunction as predictor of angina recurrence after successful percutaneous coronary intervention using second generation drug eluting stents

Background: The role of endothelial dysfunction in predicting angina recurrence after percutaneous coronary intervention is unknown. Design: We assessed the role of peripheral endothelial dysfunction measured by reactive-hyperaemia peripheral-artery tonometry (RH-PAT) in predicting recurrence of angina after percutaneous coronary intervention. Methods: We enrolled consecutive patients undergoing percutaneous coronary intervention with second-generation drug-eluting stents. RH-PAT was measured at discharge. The endpoint was repeated coronary angiography for angina recurrence and/or evidence of myocardial ischaemia at follow-up. Patients with in-stent restenosis and/or significant de novo stenosis were defined as having angina with obstructed coronary arteries (AOCA); all other patients as having angina with non-obstructed coronary arteries (ANOCA). Results: Among 100 patients (mean age 66.7 \ub1 10.4 years, 80 (80.0%) male, median follow-up 16 (3\u201320) months), AOCA occurred in 14 patients (14%), ANOCA in nine patients (9%). Repeated coronary angiography occurred more frequently among patients in the lower RH-PAT index tertile compared with middle and upper tertiles (14 (41.2%) vs. 6 (18.2%) vs. 3 (9.1%), p = 0.006, respectively). ANOCA was more frequent in the lower RH-PAT index tertile compared with middle and upper tertiles. In the multivariate regression analysis, the RH-PAT index only predicted angina recurrence. The receiver operating characteristic curve of the RH-PAT index to predict the angina recurrence demonstrated an area under the curve of 0.79 (95% confidence interval: 0.69\u20130.89; p < 0.001), with a cut-off value of 1.705, having sensitivity 74% and specificity 70%. Conclusions: Non-invasive assessment of peripheral endothelial dysfunction using RH-PAT might help in the prediction of recurrent angina after percutaneous coronary intervention, thus identifying patients who may need more intense pharmacological treatment and risk factor control

Localization of cannabinoid receptors CB1, CB2, GPR55, and PPARα in the canine gastrointestinal tract

none8noThe endocannabinoid system (ECS) is composed of cannabinoid receptors, their endogenous ligands, and the enzymes involved in endocannabinoid turnover. Modulating the activity of the ECS may influence a variety of physiological and pathophysiological processes. A growing body of evidence indicates that activation of cannabinoid receptors by endogenous, plant-derived, or synthetic cannabinoids may exert beneficial effects on gastrointestinal inflammation and visceral pain. The present ex vivo study aimed to investigate immunohistochemically the distribution of cannabinoid receptors CB1, CB2, G protein-coupled receptor 55 (GPR55), and peroxisome proliferation activation receptor alpha (PPARα) in the canine gastrointestinal tract. CB1 receptor immunoreactivity was observed in the lamina propria and epithelial cells. CB2 receptor immunoreactivity was expressed by lamina propria mast cells and immunocytes, blood vessels, and smooth muscle cells. Faint CB2 receptor immunoreactivity was also observed in neurons and glial cells of the submucosal plexus. GPR55 receptor immunoreactivity was expressed by lamina propria macrophages and smooth muscle cells. PPARα receptor immunoreactivity was expressed by blood vessels, smooth muscle cells, and glial cells of the myenteric plexus. Cannabinoid receptors showed a wide distribution in the gastrointestinal tract of the dog. Since cannabinoid receptors have a protective role in inflammatory bowel disease, the present research provides an anatomical basis supporting the therapeutic use of cannabinoid receptor agonists in relieving motility disorders and visceral hypersensitivity in canine acute or chronic enteropathies.mixedGaliazzo, Giorgia; Giancola, Fiorella; Stanzani, Agnese; Fracassi, Federico; Bernardini, Chiara; Forni, Monica; Pietra, Marco; Chiocchetti, Roberto*Galiazzo, Giorgia; Giancola, Fiorella; Stanzani, Agnese; Fracassi, Federico; Bernardini, Chiara; Forni, Monica; Pietra, Marco; Chiocchetti, Roberto