• Experimental and Molecular Medicine
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• v.50 no.11
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• pp.1.1-1.10
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• 2018

Bone marrow-derived mesenchymal stem cells (BMMSCs) are used extensively for cardiac repair and interact with immune cells in the damaged heart. Macrophages are known to be modulated by stem cells, and we hypothesized that priming macrophages with BMMSCs would enhance their therapeutic efficacy. Rat bone marrow-derived macrophages (BMDMs) were stimulated by lipopolysaccharide (LPS) with or without coculture with rat BMCs. In the LPS-stimulated BMDMs, induction of the inflammatory marker iNOS was attenuated, and the anti-inflammatory marker Arg1 was markedly upregulated by coculture with BMMSCs. Myocardial infarction (MI) was induced in rats. One group was injected with BMMSCs, and a second group was injected with MIX (a mixture of BMMSCs and BMDMs after coculture). The reduction in cardiac fibrosis was greater in the MIX group than in the BMC group. Cardiac function was improved in the BMMSC group and was substantially improved in the MIX group. Angiogenesis was better in the MIX group, and anti-inflammatory macrophages were more abundant in the MIX group than in the BMMSC group. In the BMMSCs, interferon regulatory factor 5 (IRF5) was exclusively induced by coculture with macrophages. IRF5 knockdown in BMMSCs failed to suppress inflammatory marker induction in the macrophages. In this study, we demonstrated the successful application of BMDMs primed with BMMSCs as an adjuvant to cell therapy for cardiac repair.

• Journal of Veterinary Science
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• v.22 no.5
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• pp.64.1-64.12
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• 2021

Background: Pituitary pars intermedia dysfunction (PPID), a neurodegenerative disease leading to reduced dopamine production, is a common disease in aged horses. The treatment is based on administration of the dopamine agonist pergolide. This drug has been related to valvular fibrosis in humans, but the cardiovascular effect of this drug has not yet been investigated in horses. Objectives: To determine whether pergolide induces valvular disease in horses or affects the cardiac function. Methods: Standard, tissue Doppler (TDE) and two-dimensional speckle tracking (STE) echocardiography were performed in horses with diagnosed PPID based on adrenocorticotropic hormone dosage. Measurements taken in horses treated with pergolide were compared with those from untreated horses with nonparametric t-tests. Furthermore, measurements from follow-up examinations performed at least three months after the initial exam were compared with a Wilcoxon signed rank test for repeated measurements in each group. Results: Twenty-three horses were included. None of the 12 horses under treatment developed valvular regurgitation. Furthermore, no differences in the measurements of the left ventricular systolic or diastolic function could be seen between the group of horses with treatment and those without treatment. Measurements taken in the follow-up exam did not differ compared to those taken in the initial exam in both groups. Conclusions: No changes of the left ventricular function assessed by TDE and STE could be shown in a small population of horses with confirmed PPID. Treatment with pergolide did not affect the ventricular function nor induce valvular disease.

• Korean Journal of Veterinary Service
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• v.44 no.1
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• pp.45-49
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• 2021

A 23-month-old Holstein cattle showed excess salivation and reluctance of walking and suddenly died after forced sudden movements. Grossly, numerous fibrous adhesions were present within cranial abdominal cavity including the reticulum and diaphragm and thoracic cavity involving lungs, pericardial sac, and heart. A perforation made by a 10 cm-long sharp-ended wire was detected in the reticulum. Histopathologically, fibrous suppurative epicarditis and myocardial necrosis were observed. Fibrosis with neovascularization were found in lungs, spleen, and liver. And granulomatous reticulitis was observed. For differential diagnosis, no pathogenic bacteria were detected through microbiological tests and PCR results were also negative for bovine susceptible pathogenic antigens. Based on the gross and histopathological examination, we diagnosed this case as chronic traumatic pericarditis. Cattle are inquisitive and prone to swallow various kinds of metallic foreign bodies since they do not use their lips. Therefore, avoiding ingestion of metallic objects in animal feed and animal areas by careful environmental management of farms is required and farmers should give the adequate minerals and vitamins into the feeds not to lick or shallow foreign bodies in case of mineral deficiency. For veterinary practitioners, physical examination, blood tests, and diagnostic imaging (X-ray and Ultrasonography) are required for an exact diagnosis. Furthermore, placing the magnets in rumen would be effective for prophylactic administrations.

• Clinical and Experimental Pediatrics
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• v.65 no.5
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• pp.230-238
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• 2022

Myocarditis was previously attributed to an epidemic viral infection. Additional harmful reagents, in addition to viruses, play a role in its etiology. Coronavirus disease 2019 (COVID-19) vaccine-induced myocarditis has recently been described, drawing attention to vaccine-induced myocarditis in children and adolescents. Its pathology is based on a series of complex immune responses, including initial innate immune responses in response to viral entry, adaptive immune responses leading to the development of antigen-specific antibodies, and autoimmune responses to cellular injury caused by cardiomyocyte rupture that releases antigens. Chronic inflammation and fibrosis in the myocardium eventually result in cardiac failure. Recent advancements in molecular biology have remarkably increased our understanding of myocarditis. In particular, microRNAs (miRNAs) are a hot topic in terms of the role of new biomarkers and the pathophysiology of myocarditis. Myocarditis has been linked with microRNA-221/222 (miR-221/222), miR-155, miR-10a^*, and miR-590. Despite the lack of clinical trials of miRNA intervention in myocarditis yet, multiple clinical trials of miRNAs in other cardiac diseases have been aggressively conducted to help pave the way for future research, which is bolstered by the success of recently U.S. Food and Drug Administration-approved small-RNA medications. This review presents basic information and recent research that focuses on myocarditis and related miRNAs as a potential novel biomarker and the therapeutics.

• Journal of Veterinary Clinics
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• v.31 no.3
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• pp.258-261
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• 2014

A 4-week-old male piglet being maintained in a research facility was found dead without any previous clinical signs. The piglet had been born from a surrogate mother after somatic nuclear transfer as part of a xenotransplantation study. Ovaries for nuclear transfer were obtained from a private farm outside the research facility. Histopathologically, multifocal to coalescing granulomatous myocarditis was observed in the heart, characterized by infiltration of lymphocytes, macrophages and multinucleated giant cells, and by myocardial necrosis and fibrosis. Lymphoid tissues showed marked lymphoid depletion with infiltration by histiocytes or giant cells. Immunohistochemistry showed PCV-2 antigens in necrotic myocytes, macrophages and multinucleated giant cells in the heart, as well as in macrophages and giant cells in lymphoid depleted areas of lymphoid tissues. Reproductive failure associated with PCV-2 in aborted or stillborn piglets is frequently characterized by myocarditis, and similar lesions were observed in this 4-week-old piglet with PCV-2 infection. The PCV-2 infection in this piglet may have been due to contamination or infection of an ovary from the pig farm.

• Asian-Australasian Journal of Animal Sciences
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• v.19 no.7
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• pp.997-1003
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• 2006

An experiment with twenty crossbred goat kids (male) of 2-3 months old, weighing about 12 kg was conducted to study the effect of feeding formaldehyde treated rape seed oil cake based diet supplemented with molasses on growth rate and histopathological changes of different organs. Goats were randomly divided into four groups of 5 animals each and were individually fed for a period of 120 days. The animals in group I (URC) and II (URCM) were fed concentrate mixture (CM-I) containing untreated rape seed oil cake (30%) while, the animals in group III (TRC) and IV (TRCM) were offered concentrate mixture (CM-II) containing formaldehyde treated rape seed oil cake. Further, molasses as energy source was additionally supplemented with the concentrate mixture at the rate of 8% of concentrate mixture on dry matter basis to animals in group II and IV. All the animals were maintained on roughage (Berseem hay:wheat straw = 2:1) and concentrate in 50:50 ratio. Average daily gain (g/d) of animals in group IV was significantly (p<0.05) higher than that in group I., but at par with group II and III. Feed conversion efficiency was also significantly (p<0.05) higher in group IV (10.14) than group I and II but at par with group III. The growth rate however increased by 50.2% in group IV showing more consistency in maintaining highest growth rate due to better balance of nutrients. At the end of four months of feeding trial, two animals from each group were sacrificed for histopathological study of different organs. Significant histopathological changes in liver, heart, lungs tissue of animals fed untreated rape seed oil cake diet were recorded which were totally absent in the organ of animals fed formaldehyde treated cake. The liver tissue of goats receiving control diet (containing untreated rape seed oil cake) were found to be associated with engorged central vein and blood vessels. Hepatocytes were swollen, pale and degenerated with cellular infiltration and fibrosis of portal areas. The muscles of heart were found to have intermyofibral edema. Emphysema accompanied by dilated and ruptured alveoli was also recorded in lung tissue. However, histopathological examination of various tissues of goats fed formaldehyde treated cake diet did not exhibit any degenerative changes. Additional supplementation of molasses with or without treated cake diet, apparently did not have any significant effect on ameliorating the above degenerative changes.

• Journal of Chest Surgery
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• v.31 no.4
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• pp.346-352
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• 1998

Rheumatic valvulitis produces at least three distinct pathologic changes, the degree varying widely among the patients: fusion of the valve leaflets at the commissures; fusion and shortening of chordae tendinae: and fibrosis of the leaflets with subsequent stiffening, contraction and calcification. The most extensive changes usually are seen in patients with recurrent attacks of rheumatic fever. We studied on outcome of the surgical treatments of rheumatic valvular diseases that have been experienced for 12 years since 1982 at Pusan National University Hospital. The diagnoses were made by rheumatic fever history, echocardiographic findings, gross operative findings and microscopic findings. Total 502 patients were performed surgery for valvular heart diseases and 440 patients of rheumatic origin have bene analysed. There were more female than male patients as 1.3:1, and the mean age was 37.8 years old. 96.3% of them affected to the mitral valve, 19.8% to aortic valve, 16.3% affected to the tricuspid valve. Most of them underwent valve replacement, and valve repair was done in 3.9% of patients. There were 36 hospital deaths(8.2%) mainly from low cardiac output syndrome, and 15 late deaths equally due to embolism and hemorrhage. Follow up was 90.1% completed(2890 patient- year). Linealized rates of late complication events are follows : thromboembolism 1.3% per patient year; anticoagulant related hemorrhage 0.8% per patient year. Overall actuarial survival including hospital mortality was 92.7＋/-2.9% in 1 year, 88.0＋/-4.5% in 5 year, 82.3＋/-7.7% in 10 year. We conclude that the rheumatic disease is still the most frequent and the most important cause of heart valve disease. So more intensive study is needed in spite of the abrupt decreasing rate of rheumatic fever in U.S.A. and other industrial country.

• Radiation Oncology Journal
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• v.22 no.1
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• pp.40-54
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• 2004

Purpose : Captopril (angiotension converting enzyme inhibitor) is known to have a radioproptective effect in the lungs, intestines and skin, but its effect in the heart is unclear. To investigate the radioprotectlve efiect and mechanism of captopril on the heart, the histopathological changes and immunohistochemical stains were compared with radiation alone, and radiation combined with captopril, in the rats. Materials and Methods : The histopathological changes and immunohistochemical stains ($TNF{\alpha}$, $TGF{\beta}1$, PDGF and FGF2) were examined in the radiation alone and the combined captopril and radiation groups, 2 and 8 weeks after irradiation. Each group consisted of 8 to 10 rats (Sprague-Dawley). Irradiation (12.5 Gy) was given to the left hemithorax in a single fraction. Captopril (50 mg/Kg/d) mixed with water, was given orally and continuously from the first week prior to, up to the 8th week of the experiment. Results : In the radiation alone group, the ventricle at 2 weeks after irradiation showed prominent edema (p=0.082) and fibrin deposit (p=0.018) compared to the control group. At 8 weeks, the edema was decreased and fibrosis increased compared to those at 2 weeks. The histopathological changes of the combined group were similar to those of the control group, due to the reduced radiation toxicity at 2 and 8 weeks. The endocardial fibrin deposit (p=0.047) in the atrium, and the interstitial fibrin deposit (p=0.019) and edema (p=0.042) of the ventricle were reduced significantly in the combined group compared to those in the radiation alone group at 2 weeks. The expressions of $TNF-{\alpha}$, $TGF-{\beta}1$, PDGF and FGF-2 in the radiation alone group were more increased than in the control group, especially in the pericardium and endocardium of the atrium at 2 weeks. At 8 weeks, the pericardial $TNF-{\alpha}$ and $TGF-{\beta}1$ in the radiation alone group continuously increased. The expressions of $TNF-{\alpha}$, $TGF-{\beta}1$ and PDGF were decreased in the combined group at 2 weeks. At 8 weeks, the expressions of $TNF-{\alpha}$ in the atrial and ventricular pericardia were markedly reduced (p=0.049, p=0.009). Conclusion : This study revealed that the early heart damage induced by radiation can be reduced by the addition of captopril in a rat model. The expressions of $TNF-{\alpha}$, $TGF-{\beta}1$ and PDGF were further decreased in the combined compared to the radiation alone group at both 2 and 8 weeks. From these results, it may be concluded that these cytokines probably play roles in the radioprotective mechanism of captopril from the radiation-induced heart toxicity, similarly to in other organs.

• Radiation Oncology Journal
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• v.14 no.4
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• pp.281-290
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• 1996

Purpose : Chest irradiation leads to a significant cardiac injury in a number of patients. To prevent, or to reduce the risk of radiation-induced cardiac injury, pentoxifylline(PTX), a haemorrheologic agent that improves the blood flow through small blood capillaries has been employed. Materials and Methods : One hundred and eighty ICR mice were divided into three study groups: control, radiation alone, and radiation-pentoxifylline. Each group was subdivided into 12 subgroups: 1 3, 6 and 10 days and 2, 3, 4, 6, 8, 12, 16 and 20 weeks by observation Period after irradiation. The total 15Gy of radiation was delivered in a single fraction through anterior mediastinal port. Pentoxifylline was injected subcutaneously daily 50mg/kg to the back of the mice from the first day of irradiation throughout the observation period. The mice of each group after a certain observation period were sacrificed and sectioned for histopathologic examination of the heart. Result : The findings of acute radiation-induced carditis i.e., heterophilic infiltration and vacuolization and ballooning of endothelial cells were observed upto 6 weeks and reduced sharply afterwards. The late radiation effects including pericarditis with mononuclear cell infiltration, pericardial fibrosis, endothelial cell changes, myocardial degeneration and fibrosis present from 4 weeks onwards after irradiation but with various degree of severity. The overall process of pathologic changes of radiation-pentoxifylline group was similar to those of radiation alone group but the duration of acute stage was relatively short and the severity of late cardiac toxicity was much lesser compared with those of radiation alone group. Conclusion : Pentoxifylline can effectively reduce the late radiation-induced cardiac injury and reslve the acute effects relatively rapidly.

• Tuberculosis and Respiratory Diseases
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• v.67 no.6
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• pp.528-535
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• 2009

Background: Dust clouds blown by the wind from the arid deserts of Mongolia and Northeast China are known as Asian dust storms. Ambient particulate matter with a diameter <10 ${\mu}m$ ($PM_{10}$) is associated with the exacerbation of respiratory diseases and increased mortality of heart and lung disease patients. The fibrotic effects of $PM_{10}$ of Asian dust to pulmonary fibroblast cells are unknown. This study examined the production of reactive oxygen species (ROS), TGF-${\beta}$, NF-${\kappa}B$, PDGF-$\alpha$ and Fibronectin in fibroblasts exposed to Asian dust particles. Methods: Air samples were collected using a high volume air sampler (Sibata model HV500F) with an air flow of 500 L/min for at least 6 hours. The MRC-5 cells were exposed to 0, 50 and 100 ${\mu}g/mL$ of $PM_{10}$ for 24 hours. ROS was detected by measuring the level of oxidized DCF using FACS. TGF-$\beta$, NF-${\kappa}B$, PDGF-$\alpha$ and fibronectin were detected by western blotting. Results: There was no increase in the ROS, TGF-$\beta$ and PDGF-$\alpha$ levels in the MRC-5 cells exposed to $PM_{10}$. The NF-${\kappa}B$ level was higher in the MRC-5 cells exposed to 50 and 100 ${\mu}g/mL$ of $PM_{10}$ for 24 hours. The fibronectin level in the MRC-5 cells after 24 hours incubation with 50 ${\mu}g/mL$ $PM_{10}$ was significantly higher than the control group ($PM_{10}$ 50 ${\mu}g/mL$ 113.27${\pm}$8.65 of control, p=0.005). Conclusion: $PM_{10}$ from Asian dust increases the activation of NF-${\kappa}B$ and fibronectin expression in MRC-5 fibroblast cells.