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 literature review, this is the first nephroblastoma occurred at renal papilla in a rat.
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 ultrasonography and radiography confirmed a significant amount of pleural effusion. However, the thoracic radiographs showed no radiopaque nodules or interstitial patterns indicative of thoracic tumors. Thoracentesis was performed to relieve effusion-induced thoracic pressure, yielding a hemorrhagic serosanguinous pleural fluid. The cytological analysis of this fluid revealed mesothelial cells, supporting the clinical diagnosis of mesothelioma in situ. To address the patient’s clinical symptoms, an aggressive management approach was implemented with chest tube placement to address recurrent pleural effusion after initial thoracentesis. During treatment, 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 successfully alleviated dyspnea symptoms and provided symptomatic relief in a patient with mesothelioma in situ.
Hyperoxaluria is a disorder associated with an increased risk of renal stones, one of the most common conditions. For people with hyperoxaluria, there are a limited number of effective therapeutic 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 formation as well as the formation of crystals that had sharp edges. In animal experiments, rats that had been treated with EG showed impaired renal filtration functions, as well as increased deposition 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 by CaOx intratubular crystal deposits with hyperoxaluria dramatically reduces the severity of the disease. 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 administration of OxdC.
Following the previous study, which investigated the pharmacological properties of the Technekitty injection (Tc-99m), the toxicity of a single intravenous administration of the Technekitty injection (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 observation, 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 administered 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, allowing 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 nonclinical 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 veterinary drug in Korea.
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 primary excretory organ. Maximum distribution was confirmed at 1 hour in the small intestine, 6 hours 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.
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 internationally. This shortage has been further exacerbated by the COVID-19 pandemic. Consequently, the importance of resource conservation through effective primate management is increasing. 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 public 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 various countries 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 contribute to the development of strategies for improving methods to prevent the spread of infectious diseases and enhancing quarantine management methods.
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 Veterinary 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 biomarkers, and echocardiographic markers. This is a retrospective study of veterinary practice performed at Chungbuk National University Animal Hospital. The electronic medical record of 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 variables 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 subclinical MMVD stage progression. This is the inaugural exploratory study to concentrate on blood test results, a relatively straightforward and quantifiable test result that can be readily obtained in primary care veterinary clinics, among the factors that may be associated with the progression of subclinical MMVD stages.
Clinical pathology, including hematology and serum chemistry, is an important indicator of biological changes. Animals for inhalation studies are kept in specific chambers and require historical 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 considered the most affected parameter by aging in both sexes based on statistical results. In this study, we presented clinicopathological data from F344 rats for inhalation toxicity studies. We confirmed aging trends in clinicopathological parameters and identified TCHO as the parameter most affected by aging in F344 rats. These results would be helpful for inhalation research using F344 rats.
We investigated the stress-induced changes in the lipid and hormonal concentrations in plasma, including cytochrome P450 (CYP)-derived oxidative stress in the liver, and the anti-stress effect of Korean Red Ginseng (KRG) water extract in mice. Stress induction using restraint increased the levels of corticosterone (CORT), glucose, total cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C) while decreasing in the levels of insulin and high-density lipoprotein-cholesterol (HDL-C), compared with those of unstressed mice. Restraint-stress also increased the generation of reactive oxygen species (ROS) in plasma by 5.4-fold. Moreover, the stress resulted in a 2.8-fold higher production of C-reactive protein (CRP) than the control group. In addition, the catalytic activities of CYP1A2 and CYP3A4 in the liver microsomes were stimulated by 5.5- and 3.8-fold, respectively, and concomitant ROS formation was elevated by 4.3-fold in the liver extract, compared to the normal group. In contrast, the KRG treatment (5, 20, or 50 mg/kg/day) to stress-exposed 3 groups alleviated the increased CORT, TC, LDL-C, ROS, and CRP levels and restored the decreased insulin concentrations. The enhanced each ROS in the plasma and liver, and the CYP enzyme activities were also attenuated in KRG-treated mice in a concentration-dependent manner. In conclusion, these results suggest that KRG ameliorates stress-induced detrimental effects on the plasma and liver of treated mice.
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 intermediates 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. Clinical signs, mean body weight, food consumption, bronchoalveolar lavage fluid (BALF), hematology, blood biochemistry, gross findings, organ weights, and microscopic findings were examined 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.
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 derived from 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 intestinal barrier 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 the intestinal barrier. We examine the effect of BPA on the proliferation and tight junction gene expression 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 increase the significant number of HT-29 cell respectively. Proliferation-related gene and tight junction gene 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.
Inflammatory bowel disease (IBD) is a chronic condition characterized by continuous inflammation of the gastrointestinal tract that varies in intensity over time. IBD is caused by several factors including aberrant gut flora, immunological dysregulation, altered environmental conditions, and genetic variations. However, the pathogenesis of IBD remains unclear. Studies have indicated that an imbalance between T helper 17 (Th17) and regulatory T (Treg) cells contributes significantly to the development of IBD. Intestinal Tregs suppress inflammation and are critical for maintaining tissue homeostasis. Th17 cells are known to play an important role in the development and pathogenesis of IBD and provide non-inflammatory support for the integrity of the intestinal barrier against bacterial and fungal infections. Therefore, the Th17/Treg cell balance is crucial in the pathogenesis of IBD and gut integrity. The microenvironment of the intestinal mucosal immunity is regulated by the secretion of cytokines associated with Th17 cells and Tregs. Several studies have indicated that the gut bacteria contribute to the control of the immune milieu and play a key role in the regulation of Th17 cell development. Intestinal bacteria and cytokines control Th17 cell development. Th17 cells secrete cytokines that regulate the immune microenvironment in the gut mucosa. This review provides an overview of Th17 cells and examines the strategies for treating patients with IBD using Th17 cell-targeted drugs.
This study aimed to investigate the effectiveness of carrageenan (CGN) as an oral immune adjuvant. During the initial research, the inadvertent shallow insertion of an oral gavage needle confirmed CGN’s effect as an adjuvant for esophageal immunization. However, in oral immunization, antibody formation was not observed regardless of CGN’s presence or absence as an adjuvant. Conversely, when bovine serum albumin (used as an antigen) was introduced into the esophagus along with CGN, it resulted in the production of antigen-specific IgG. An exploration was conducted to ascertain whether CGN’s adjuvant effects were associated with prolonging the antigen’s residence time in the esophagus. Upon introducing the antigen into the esophagus without CGN, it was undetectable at two minutes post-introduction. Conversely, when administered with CGN, the antigen remained detectable in the esophagus for up to five minutes post-introduction. To investigate whether this immune response was elicited through mucosal immune mechanisms in the esophagus, the production of IgA, a representative immunoglobulin of mucosal immunity, was assessed. Following esophageal immunization with CGN as an adjuvant, total IgG, IgG1, and IgG2a were detected in serum, while IgA was not detected. These findings suggest that under specific conditions, the esophagus may serve as a site for initiating a novel immune response.
Antimicrobial resistance significantly threatens human and animal health globally, with considerable mortality and economic impact. This study investigated antimicrobial usage in small animal clinics in South Korea, focusing on understanding the trends in prescriptions for therapeutic and preventive purposes. Data were collected from 12 small animal clinics that were analyzed for antimicrobial prescriptions from 2018–2020. A comprehensive dataset was used, including patient signalment, clinical notes, and prescription details, and statistically analyzed using SPSS software. The results indicated that most antimicrobials (93.1%) were prescribed for the treatment of infectious diseases, with a smaller portion (6.9%) used for preventive measures, such as surgery. High prescription rates were observed for the treatment of cutaneous and otological diseases, which may reflect common diseases in companion animals. The study highlighted a higher prescription rate for adult age groups, possibly because of the higher prevalence in those groups. Overall, this study provides valuable insights into common prescription patterns in veterinary practice and underscores the need for more stringent antimicrobial stewardship to curb the rise of antimicrobial resistance. This suggests that ongoing surveillance and education on appropriate antimicrobial use are crucial for optimizing treatment outcomes and minimizing the development of resistance.
The functional roles of plant extracts have been investigated for the treatment of various diseases including subfertility. Recent studies have highlighted the benefits of ashwagandha extract (AE) in enhancing sperm production, boosting testosterone levels, and lowering reactive oxygen species (ROS) levels in mammals. The current study is to examine the effects of the addition of AE to liquid boar semen on sperm quality during storage and its potential application in assisted reproductive technology. A hot water extract of ashwagandha was prepared from the dried powder of ashwagandha roots. Boar spermatozoa were stored in Beltsville thawing solution (BTS) at 17℃ for 5 days, with various concentrations of AE (1–50 mg/mL). During storage, motility, viability, acrosomal integrity and ROS of boar spermatozoa were examined. The results have shown that sperm stored in BTS with varying quantities of AE ranging from 1–20 mg/mL exhibited higher motility compared to those without AE (control) or with 50 mg/mL AE for 5 days. Similarly, sperm viability was better maintained in sperm treated with 1–20 mg/mL AE. Moreover, sperm stored in BTS with AE led to significantly higher acrosomal integrity and chromatin stability rates than sperm stored without AE. Notably, intracellular ROS levels significantly decreased in sperm stored in BTS with AE. Particularly, spermatozoa stored at 10 mg/mL AE exhibited an effective reduction in ROS during storage. These findings suggest the potential role of AE as an additive during sperm storage maintains sperm quality and can be used during subfertility treatment in both animals and humans.
Traditional medicine and herbal remedies are gaining popularity worldwide, comprising a significant portion of healthcare research, advancements, and market demand. Growing scientific evidence supports their substantial efficacy as pharmaceutical ingredients and dietary supplements in preventive healthcare. When developing pharmaceuticals, it is crucial to ensure that ingredients are free from side effects and toxicity in order to prioritize safety. Geckos, known as shou gong, are a diverse group of lizards that are widely utilized for treating various diseases in Korean Medicine. This study was conducted to assess the potential acute toxicity of a water extract Gekko gecko by a single oral dose in Sprague-Dawley rats. Twenty rats of each sex were randomly assigned to four groups (5 rats each). Test articles were administrated once by oral gavage to rats at dose levels of 0, 500, 1,000, or 2,000 mg/kg body weight. Mortality, changes of body weight, and clinical signs of gross observation were monitored for 14 days after dosing. At the end of a 14-day observation period, all animals were sacrificed and complete macroscopic and hematological examinations were performed. There was no dead animal or test article-related effect on clinical signs, body weight, or gross finding. Other specific changes were not found between control and treated groups in hematology. Results showed no adverse effect at a dose of 500, 1,000, or 2,000 mg/kg in rats. The minimal lethal dose was considered to be over 2,000 mg/kg body weight in rats.
Drug-induced liver injury (DILI) is considered to be a significant cause of drug wastage. To mitigate clinical DILI risks, assessing drugs using human liver models is crucial since animal studies may fall short due to species-specific liver pathway variations. Cell-based preclinical hepatotoxicity testing is often pertinent. In the present study, cells from a human liver cancer line (HepG2 and HepaRG) were cultured in both formats of 2D and 3D spheroids to explore their responses to drugs. Liver-specific marker expressions across cell lines and culture formats were also examined to assess disparities in DILI marker expressions. After treating each cell with the drugs, cytotoxicity and liver injury markers aspartate aminotransferase and alanine aminotransferase were increased. In addition, liver specific markers albumin and urea decreased in a drug concentration-dependent manner. These findings were consistent with drug sensitivity. Additionally, mRNA expression levels of cytochrome P450 enzymes (CYPs) involved in hepatocellular drug metabolism were compared following treatment with enzyme inducers. CYP1A2 and CYP2C9 were not epxressed in HepG2 cells. HepaRG cells exhibited significantly increased expression of CYP1A2, 2C9, and 3A4 post-treatment. Notably, enzyme expression was notably higher in 3D cultures than in 2D cultures. Collectively, these findings suggest that HepaRG cells and 3D cultures hold promise for evaluating DILI during early-stage drug development.
Caprine cryptosporidiosis mainly occurs in young goats, with morbidity rates of 80%–100% and mortality over 50% in goat kids. However, limited research has been conducted on the impact of Cryptosporidium parvum, a diarrhea-causing pathogen, on the intestinal microbiota of goat kids. In this study, 16S rRNA-based metataxonomic analysis was performed to compare the microbial diversity and abundance of the gut microbiota between C. parvum-infected and uninfected goat kids. In total, 12 goat fecal samples were collected, including seven naturally C. parvum-infected and five uninfected goats from Chungcheongbuk-do, Korea. After amplification of the V3–V4 hypervariable region of the bacterial 16S rRNA, high-throughput sequencing was performed. The results showed differences in the microbial composition between C. parvum-infected and uninfected groups based on beta diversity. Firmicutes and Bacteroidetes were the most dominant phyla in both groups. However, no significant difference was observed in the Bacteroidetes/Firmicutes ratio between the two groups. Compared with the uninfected group, the C. parvum-infected group showed significantly higher abundances of Tyzzerella nexillis, Lactobacillus johnsonii, Butyricicoccus pullicaecorum, Enterococcus raffinosus, Enterococcus faecalis, and Negativicoccus massiliensis, and significantly reduced abundances of Aerococcus vaginalis, Faecalicoccus pleomorphus, Oribacterium parvum, and Coprococcus comes. These findings indicate that C. parvum infection, which is associated with diarrhea in neonatal goats, induces alterations in the caprine gut microbiota.
This study was conducted to collect the patents of microbiome-based treatment technology for pets. An electronic search for microbiome or probiotics in brain nervous system disease was studied using the WINTELIPS database. Patent Cooperation Treaty of Korea, Japan, the EU, the US, and China that were registered by October 31, 2022 were selected in this study. A total of 206 patents were included for final analysis. Since 2016, patent activity has shown an explosive increase in recent years. China is the leading market in this technology field, and Korea has the second-highest market share. To provide the groundwork for the next research and development, we examined the industrial trend of microbiome for brain nervous system diseases in this study using an analysis of patents that have been applied for and registered up to this point. Looking at the overall patent trends by year in the technology field related to treating of brain and nervous system diseases using the microbiome, there was a tendency to repeat increasing and decreasing trends. However, considering 2021 and 2022, which have undisclosed sections, it can be seen that patent activity has tended to increase explosively in recent years, starting in 2016. If related studies use the patent analysis data constructed in this way strategically, it is expected that it will lead to patent registration and the development of new products, ultimately contributing to the revitalization of the companion animal industry.
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease by John Cunningham virus (JC virus) infection in oligodendrocytes. The radiographic and clinical features, along with the identification JC in cerebrospinal fluid polymerase chain reaction, are sufficient for the diagnosis of PML in immunodeficiency. However, it is difficult to suspect PML without the patient history of immunodeficiency. A 32-year-old man presented with headache for a month without any medical history. Based on clinical and image features, the differential diagnoses included demyelinating lesion and neoplasms. Microscopically, biopsy specimen showed multifocal demyelinating and degenerative white matter, consistent with PML. Oligodendrocytes cells with increased nuclei and plum-colored inclusions were admixed with perivascular lymphocytic and histiocytic infiltration, and loss of myelin. Atypical astrocytes had large or multiple nuclei. After brain biopsy, human immunodeficiency virus infection was confirmed by serum chemiluminescent immunoassay. It is unlikely that PML would be considered without the information of immunosuppression. Therefore, it is very important to be aware of the histological features of PML.