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Item Glioma Mimics: Magnetic Resonance Imaging Characteristics of Granulomas in Dogs(Frontiers, 2019-08-28) Diangelo, Lauren; Cohen-Gadol, Aaron; Heng, Hock Gan; Miller, Margaret A.; Hague, Devon W.; Rossmeisl, John H.; Bentley, R. Timothy; Neurological Surgery, School of MedicineGranulomas can "mimic" gliomas on magnetic resonance imaging (MRI) in human patients. The goal of this retrospective study was to report canine brain granulomas that were consistent with glioma based upon MRI, report their histologic diagnosis, and identify MRI criteria that might be useful to distinguish granuloma from glioma. Ten granulomas, initially suspected to be glioma based on MRI, were ultimately diagnosed as granulomatous meningoencephalomyelitis (n = 5), infectious granulomas (n = 3) or other meningoencephalitis (n = 2). Age was 1.6-15.0 years and two dogs were brachycephalic breeds. MRI characteristics overlapping with glioma included intra-axial, heterogeneous, T2-weighted hyperintense, T1-weighted hypointense to isointense mass lesions with contrast-enhancement. Signals on fluid attenuation inversion recovery, gradient echo and diffusion weighted imaging also matched glioma. Peri-lesional edema and mass effect were toward the high end of findings reported for glioma. MRI characteristics that would be considered unusual for glioma included dural contact (n = 4), T2-hypointensity (n = 2), concomitant meningeal-enhancement (n = 9), and minor changes in the contralateral brain (n = 2). Cerebrospinal fluid analysis revealed albuminocytological dissociation or mild pleocytosis. These cases show that granulomas can "mimic" glioma on canine brain MRI. In individual cases, certain MRI findings may help increase the index of suspicion for granuloma. Lack of pronounced cerebrospinal fluid pleocytosis does not exclude granuloma. Signalment is very useful in the suspicion of glioma, and many of these dogs with granuloma were of ages and breeds in which glioma is less commonly seen.Item Inhibitory Effects of Alpha-Connexin Carboxyl-Terminal Peptide on Canine Mammary Epithelial Cells: A Study on Benign and Malignant Phenotypes(MDPI, 2024-02-18) da Fonseca, Ivone Izabel Mackowiak; Nagamine, Marcia Kazumi; Sato, Ayami; Rossatto, Carlos Alberto, Jr.; Yeh, Elizabeth Shinmay; Dagli, Lucia Zaidan; Pharmacology and Toxicology, School of MedicineMammary cancer is highly prevalent in non-castrated female dogs. Cell-to-cell communication is an important mechanism to maintain homeostasis, and connexins are proteins that assemble to form the communicating gap junctions. In many cancers, communication capacity is reduced; several approaches are being tested in order to increase the communication capacity in cancer cells and, therefore, alter their viability. This study analyzed the effects of the alpha-connexin carboxyl-terminal peptide (αCT1) on canine mammary non-neoplastic and neoplastic epithelial cells. Seven canine epithelial mammary cell lines were used. Among these, one was a normal canine epithelial mammary cell line (LOEC-NMG), two canine mammary adenomas (LOEC-MAd1 and LOEC-MAd2), and four canine mammary adenocarcinomas (LOEC-MCA1, LOEC-MCA2, LOEC-MCA3 and CF41). The αCT1 corresponds to a short Cx43 C-terminal sequence linked to an internalization sequence called the antennapedia. After 24 h of incubation, the medium containing different αCT1 peptide concentrations was added to the cells, and only the culture medium was used for control. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was used to quantify cell viability before treatment and 48, 72, and 96 h after the treatment. Results showed that the normal mammary epithelial cell line (LOEC-NMG) was resistant to treatment with αCT1, which is consistent with a previous study on human mammary cell lines. One of the adenoma cell lines (LOEC-MAd2) was also resistant to treatment with αCT1, although the other (LOEC-MAd1) was susceptible to treatment, mostly at 72 h after treatment. Regarding the four canine adenocarcinoma cell lines, they differ regarding the susceptibility to the treatment with αCT1. Three cell lines, canine mixed adenocarcinoma (LOEC-MCA1), canine complex adenocarcinoma (LOEC-MCA2), and commercial canine mammary adenocarcinoma cell line CF41, were susceptible to treatment with αCT1, while one canine mammary adenocarcinoma cell line (LOEC-MCA3) was resistant to treatment. In most αCT1 treated cell lines, Cx43 was strongly detected in cell membranes by immunofluorescence. We propose that αCT1 restored the cell-to-cell communication capacity of neoplastic cells and induced inhibitory effects on cell viability.Item Intracoronary glucagon-like peptide 1 preferentially augments glucose uptake in ischemic myocardium independent of changes in coronary flow(SAGE, 2012-03) Moberly, Steven P.; Berwick, Zachary C.; Kohr, Meredith; Svendsen, Mark; Mather, Kieren J.; Tune, Johnathan D.; Department of Cellular & Integrative Physiology, IU School of MedicineWe examined the acute dose-dependent effects of intracoronary glucagon-like peptide (GLP)-1 (7-36) on coronary vascular tone, cardiac contractile function and metabolism in normal and ischemic myocardium. Experiments were conducted in open chest, anesthetized dogs at coronary perfusion pressures (CPP) of 100 and 40 mmHg before and during intracoronary GLP-1 (7-36) infusion (10 pmol/L to 1 nmol/L). Isometric tension studies were also conducted in isolated coronary arteries. Cardiac and coronary expression of GLP-1 receptors (GLP-1R) was assessed by Western blot and immunohistochemical analysis. GLP-1R was present in the myocardium and the coronary vasculature. The tension of intact and endothelium-denuded coronary artery rings was unaffected by GLP-1. At normal perfusion pressure (100 mmHg), intracoronary GLP-1 (7-36) (targeting plasma concentration 10 pmol/L to 1 nmol/L) did not affect blood pressure, coronary blood flow or myocardial oxygen consumption (MVO(2)); however, there were modest reductions in cardiac output and stroke volume. In untreated control hearts, reducing CPP to 40 mmHg produced marked reductions in coronary blood flow (0.50 ± 0.10 to 0.17 ± 0.03 mL/min/g; P < 0.001) and MVO(2) (27 ± 2.3 to 15 ± 2.7 μL O(2)/min/g; P < 0.001). At CPP = 40 mmHg, GLP-1 had no effect on coronary blood flow, MVO(2) or regional shortening, but dose-dependently increased myocardial glucose uptake from 0.11 ± 0.02 μmol/min/g at baseline to 0.17 ± 0.04 μmol/min/g at 1 nmol/L GLP-1 (P < 0.001). These data indicate that acute, intracoronary administration of GLP-1 (7-36) preferentially augments glucose metabolism in ischemic myocardium, independent of effects on cardiac contractile function or coronary blood flow.