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A nephroblastoma at renal papilla in a SpragueDawley rat

Tae-Woo KIM ; Yong-Hoon LEE ; Tae-Kyung KIM ; Hye-Joon PARK ; Mu-Jin LEE ; Sung-Jin PARK ; Laehong JO ; Yong-Seok KIM ; Byeongwoo AHN

Journal of Biomedical and Translational Research.2024;25(4):233-238. doi:10.12729/jbtr.2024.25.4.233

A protruding mass was identified in the papilla of the right kidney of a 10-week-old male Sprague-Dawley rat. Microscopically, the neoplastic tissues were consisted of epithelial elements, where basophilic neoplastic cells displayed a high nucleus-to-cytoplasm ratio and formed tubular growth patterns characterized by small, elongated, or convoluted tubules.Blastemal elements were often arranged in aggregates or nests, composed of tightly packed basophilic polygonal to spindloid primitive cells. The surrounding interstitial tissue appeared loose and myxomatous. Based on these histological features, the diagnosis was nephroblastoma. Nephroblastoma is considered as an embryonic tumor originated from metanephric blastemal elements in the renal cortex and typically displays characteristic triphasic patterns.Also, this tumor seldom arises from or remains localized to the renal pelvis. To our literaturereview, this is the first nephroblastoma occurred at renal papilla in a rat.

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Oral administration of oxalate decarboxylase prevents hyperoxaluria and renal calcium oxalate stone formation in ethylene glycolinduced nephrolithiasis rats

Hwa Young YU ; Junghyun KIM

Journal of Biomedical and Translational Research.2024;25(4):211-219. doi:10.12729/jbtr.2024.25.4.211

Hyperoxaluria is a disorder associated with an increased risk of renal stones, one of the mostcommon conditions. For people with hyperoxaluria, there are a limited number of effectivetherapeutic options. The aim of this study was to examine whether an oxalate-degrading enzyme, oxalate decarboxylase (OxdC), can inhibit crystallization of calcium oxalate (CaOx) in vitro, and whether it can prevent nephrolithiasis caused by CaOx induced by ethylene glycol (EG) in rats. When OxdC was applied at various concentrations to CaOx in vitro, there was a significant reduction in the crystallization of CaOx. The OxdC was found to inhibit crystal for-mation as well as the formation of crystals that had sharp edges. In animal experiments, ratsthat had been treated with EG showed impaired renal filtration functions, as well as increaseddeposition of CaOx crystals and the creation of kidney stones. It has been found that oral administration of OxdC to rats with chronic EG-induced nephrolithiasis that is characterized byCaOx intratubular crystal deposits with hyperoxaluria dramatically reduces the severity of thedisease. The results of this study point to a potential therapeutic approach for treating human hyperoxaluria as well as CaOx nephrolithiasis that could be achieved by the oral administra-tion of OxdC.

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Quarantine procedures for management of infectious diseases in non-human primate

Gyu-Seo BAE ; Bon-Sang KOO ; Eun-Su JEON ; Wan-Kyu LEE

Journal of Biomedical and Translational Research.2024;25(4):169-183. doi:10.12729/jbtr.2024.25.4.169

Non-human primates, due to their high genetic similarity to humans, are used as laboratory animals in biotechnology researches. The growing demand has recently led to a shortage of primate resources, which has become a significant issue both domestically and internation-ally. This shortage has been further exacerbated by the COVID-19 pandemic. Consequently, the importance of resource conservation through effective primate management is increas-ing. This requires the establishment of proper quarantine procedures and infectious disease control. Quarantine is an important process that protects not only animal health but also pub-lic health significance. Non-human primate quarantine procedures were organized in order.We compared the differences in quarantine procedures not only in Korea but also in variouscountries such as the US, EU, and Australia. In addition, the etiology, clinical symptoms, diagnosis, and treatment methods of representative infectious diseases of quarantine concern(tuberculosis, monkeypox, monkey immunodeficiency virus, salmonellosis, and shigellosis) were summarized. A literature review of nonhuman primate quarantine procedures in other countries revealed minimal differences in the basic structure. The quarantine periods were similar around 30 days, but we found some differences in details such as legal requirements, documentation forms, and quarantine authorities. These findings are expected to contributeto the development of strategies for improving methods to prevent the spread of infectious diseases and enhancing quarantine management methods.

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Clinical and cytologic finding of mesothelioma in situ with hemorrhagic malignant pleural effusion in a dog

Donghyun HAN ; Youngmin CHOI ; Dong-In JUNG

Journal of Biomedical and Translational Research.2024;25(4):221-231. doi:10.12729/jbtr.2024.25.4.221

A 17-year-old spayed female Shih Tzu dog, weighing 5.0 kg, presented with frequent coughing and respiratory distress. Blood tests revealed mild thrombocytosis, and thoracic ultra-sonography and radiography confirmed a significant amount of pleural effusion. However,the thoracic radiographs showed no radiopaque nodules or interstitial patterns indicative ofthoracic tumors. Thoracentesis was performed to relieve effusion-induced thoracic pressure, yielding a hemorrhagic serosanguinous pleural fluid. The cytological analysis of this fluid re-vealed mesothelial cells, supporting the clinical diagnosis of mesothelioma in situ. To address the patient’s clinical symptoms, an aggressive management approach was implemented withchest tube placement to address recurrent pleural effusion after initial thoracentesis. Duringtreatment, the patient exhibited stable health and adapted well to daily life. To the best of our knowledge, this is the first reported case of mesothelioma in situ with hemorrhagic malignant pleural effusion in South Korea. Using a chest tube as an aggressive treatment successfullyalleviated dyspnea symptoms and provided symptomatic relief in a patient with mesothelioma in situ.

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Toxicological properties of Technekitty injection (Tc-99m) in diagnosing feline hyperthyroidism

Jae Cheong LIM ; So-Young LEE ; Eun Ha CHO ; Yu Mi JUNG ; Ki Hwan PARK ; Young Uk PARK ; Sung Soo NAM ; Tae Hoon LEE ; Jae Won LEE ; Yiseul CHOI ; Inki LEE ; Yeon CHAE ; Byeong-Teck KANG

Journal of Biomedical and Translational Research.2024;25(4):201-210. doi:10.12729/jbtr.2024.25.4.201

Following the previous study, which investigated the pharmacological properties of the Technekitty injection (Tc-99m), the toxicity of a single intravenous administration of the Technekittyinjection (Tc-99m) and the side effects that may occur at the diagnostic dose were confirmed.The Technekitty injection (Tc-99m) was administered intravenously once at a dose of 0, 0.67, 2.0, and 6.0 mCi/kg to 5 male and female rats per group. Mortality, general symptom obser-vation, and weight measurement were performed for 2 weeks, followed by observation of autopsy findings. There were no deaths, and no statistically significant weight change was observed. No abnormal systemic signs related to the Technekitty injection (Tc-99m) were observed. These results confirmed that Technekitty injection (Tc-99m) can be safely admin-istered intravenously at doses up to 6.0 mCi/kg. Additionally, technetium-99m at an average dose of 2 mCi (74 MBq) has been verified as a diagnostic dose without adverse effects, al-lowing the Technekitty injection (Tc-99m) to be used safely without side effects at this dosage.This study demonstrates that the Technekitty injection (Tc-99m) has a wide safety margin, supporting its potential for clinical application. Moreover, these findings align with the nonclin-ical safety standards for radiopharmaceuticals, reinforcing its utility in veterinary medicine.The Technekitty injection (Tc-99m) is expected to be applicable for clinical diagnosis as a vet-erinary drug in Korea.

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Pharmacological properties of Technekitty injection (Tc-99m) in diagnosing feline hyperthyroidism

Jae Cheong LIM ; So-Young LEE ; Eun Ha CHO ; Yu Mi JUNG ; Ki Hwan PARK ; Young Uk PARK ; Sung Soo NAM ; Tae Hoon LEE ; Jae Won LEE ; Jisu SUN ; Hye Kyung CHUNG ; Yong Jin LEE ; Yeon CHAE ; Byeong-Teck KANG

Journal of Biomedical and Translational Research.2024;25(4):185-199. doi:10.12729/jbtr.2024.25.4.185

Thyroid scanning using technetium-99m ( 99mTc) is the gold standard for diagnosing feline hyperthyroidism. In cats with an overactive thyroid, a thyroid scan is the most appropriate imaging technique to detect and localize any hyperfunctional adenomatous thyroid tissue. In this study, the pharmacological properties of the Technekitty injection (Tc-99m), developed as a diagnostic agent for feline hyperthyroidism using 99mTc as an active ingredient, were tested in FRTL-5 thyroid follicular cell line and ICR mice. The percentage of cell uptake of the Tc-99m in FRTL-5 thyroid cells was 0.182 ± 0.018%, which was about 6 times higher compared to Clone 9 hepatocytes. This uptake decreased by 38.2% due to competitive inhibition by iodine (sodium iodide). In tissue distribution tests by using ICR mice, the highest distribution was observed in the liver, kidneys, spleen, lungs, and femur at 0.083 hours after administration, and this distribution decreased as the compound was excreted through the kidneys, the pri-mary excretory organ. Maximum distribution was confirmed at 1 hour in the small intestine, 6hours in the large intestine, and 2 hours in the thyroid gland. Additionally, the total amount excreted through urine and feces over 48 hours (2 days) was 78.80% of the injected dose, with 37.70% (47.84% of the total excretion) excreted through urine and 41.10% (52.16% of the total excretion) through feces. In conclusion, the Tc-99m has the same mechanism of action, potency, absorption, distribution, metabolism, and excretion characteristics as 99mTc used for feline hyperthyroidism in the United States, Europe, and other countries, because the Technekitty injection (Tc-99m) contains 99mTc as its sole active ingredient. Based on these results, the Technekitty injection (Tc-99m) is expected to be safely used in the clinical diagnosis of feline hyperthyroidism.

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Subchronic inhalation toxicity study of diethylbenzene in Wistar rats

Eun-Sang CHO ; Dae-Sik RHA

Journal of Biomedical and Translational Research.2024;25(3):119-132. doi:10.12729/jbtr.2024.25.3.119

Diethylbenzene (DEB) is a colorless flammable liquid composed of a benzene ring and two ethyl substituents. DEBs mostly exist as a mixture of isomers and are mainly used as inter-mediates and solvents occupationally. Workers may be exposed to DEB inhalation during their occupational activities including manufacturing or processing of materials; however, limited data are available on the risk assessment of DEB mixtures. In this study, male and female Wistar rats were exposed to vapors of a DEB mixture for 13-weeks (6 hr/day, 5 days/ week) at concentrations of 0, 40, 80, and 160 ppm in a whole-body inhalation chamber. Clini-cal signs, mean body weight, food consumption, bronchoalveolar lavage fluid (BALF), hema-tology, blood biochemistry, gross findings, organ weights, and microscopic findings were ex-amined to determine the toxicity of DEB mixture. The exposure concentrations in chambers were 39.48 ± 1.13 ppm, 80.43 ± 2.06 ppm, and 160.20 ± 4.42 ppm for the low, medium, and high dose groups, respectively. No changes related to the test substance were observed, including changes in clinical observation, body weight, food consumption, BALF and blood analysis, necropsy findings, absolute and relative organ weights or histopathological analysis.Based on these results, the NOAEC (no-observed-adverse-effect-concentration) of DEB was defined as 160 ppm under the study conditions.

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Age-dependent change trends of clinicopathological parameters in F344 rats

Mi Ju LEE ; Jeong-Hee HAN ; Minha KIM

Journal of Biomedical and Translational Research.2024;25(3):145-160. doi:10.12729/jbtr.2024.25.3.145

Clinical pathology, including hematology and serum chemistry, is an important indicator ofbiological changes. Animals for inhalation studies are kept in specific chambers and requirehistorical data for accuracy. Age-related characteristics are essential for interpreting experimental results. This study aimed to provide historical clinical pathology data and analyze age-related trends in these parameters. We collected hematological and biochemical parameters from control groups of male and female F344 rats in the 4-, 13-, 26-, and 52-week repeated inhalation toxicity tests. The number of F344 rats from collected control groups were 24, 60, 50, and 25 males and 25, 60, 50, and 25 females in the 4-, 13-, 26-, and 52-week studies, respectively. Mean comparison, correlation analysis and simple linear regression analysis was conducted to reveal age-related trends. Neutrophil count, eosinophil count, neutrophil percentage, monocyte percentage, total protein, albumin, triglyceride, total cholesterol (TCHO) showed increasing trends, whereas lymphocyte count, lymphocyte percent, platelet count, alkaline phosphatase, albumin/globulin ratio, and inorganic phosphate showed decreasing trends in both the mean comparison and regression analyses. TCHO was con-sidered the most affected parameter by aging in both sexes based on statistical results. Inthis study, we presented clinicopathological data from F344 rats for inhalation toxicity studies.We confirmed aging trends in clinicopathological parameters and identified TCHO as theparameter most affected by aging in F344 rats. These results would be helpful for inhalationresearch using F344 rats.

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Comparative analysis of bisphenol A effects on HT-29 cell line and mouse intestinal organoids

Eunju JANG ; Changhwan AHN

Journal of Biomedical and Translational Research.2024;25(3):107-117. doi:10.12729/jbtr.2024.25.3.107

Cell culture is a widely used in vitro tool that enhances our understanding of cell biology, disease mechanisms, drug responses, and the development of tissue engineering. However, there are a number of important drawbacks to conventional two-dimensional (2D) cultures, such as the loss of polarity, altered cell shape, and disruption of cell-extracellular matrix connections. Alternatively, organoids are tissue-engineered, cell-based in vitro models derivedfrom stem cells that can self-organize and differentiate into three-dimensional (3D) structures,recapitulating the morphology and functions of their in vivo counterparts. Bisphenol A (BPA), a ubiquitous industrial chemical, has recently gained recognition as an environmental hazard.Previous research has demonstrated that BPA negatively affects the integrity of the intestinalbarrier by triggering programmed cell death and suppressing cell growth in human colonic epithelial cell lines. However, a 2D-based cellular study cannot represent its exposure to multicellular organs. This work investigates the impact of BPA on the structure and function of theintestinal barrier. We examine the effect of BPA on the proliferation and tight junction geneexpression with two models: the HT-29 colon cancer cell line and an intestine organoid model and morphological changes of intestinal organoid (I/O). The proliferation was increased in a dose-dependent manner with I/O, but at the same concentration, BPA does not increasethe significant number of HT-29 cell respectively. Proliferation-related gene and tight junctiongene expression pattern was similar between HT-29 and I/O other than Claudin-4. Therefore, this study offers a more precise depiction of the functional and morphological alterations caused by BPA in comparison to traditional 2D cell cultures.

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Clinical factors associated with canine subclinical myxomatous mitral valve disease stage progression in South Korea

Isaac YANG ; Kyung-Duk MIN

Journal of Biomedical and Translational Research.2024;25(3):161-167. doi:10.12729/jbtr.2024.25.3.161

Myxomatous mitral valve disease (MMVD) in dogs is a heart disease that is characterized by histopathologic changes in cardiomyocytes, which ultimately result in valve degeneration and blood regurgitation due to structural changes in the heart valves. A number of studies have been conducted with the objective of identifying prognostic factors that may influence the prognosis of dogs with MMVD. Nevertheless, there is a paucity of research examining the factors that predict MMVD stage progression as defined by the American College of Veteri-nary Internal Medicine. The objective of this study was to examine whether there are factors associated with stage progression within one year of diagnosis in dogs diagnosed with subclinical MMVD (stage B1 or B2) using physical examination findings, clinicopathologic bio-markers, and echocardiographic markers. This is a retrospective study of veterinary practiceperformed at Chungbuk National University Animal Hospital. The electronic medical recordof the hospital was searched to obtain clinical records of canine patients diagnosed with subclinical MMVD over an 11-year period. For each patient cohort, a logistic regression analysis was conducted. The variables were initially selected using the backward elimination method, and the optimal logistic regression model was determined by removing the independent vari-ables with the largest variance inflation factor. Among the independent variables examined in this study, heart murmur intensity was identified as a statistically significant predictor of stage progression within one year for subclinical MMVD, a finding that aligns with those of previous studies. No other independent variables were found to be significantly associated with sub-clinical MMVD stage progression. This is the inaugural exploratory study to concentrate onblood test results, a relatively straightforward and quantifiable test result that can be readilyobtained in primary care veterinary clinics, among the factors that may be associated with the progression of subclinical MMVD stages.

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