Search

Objective: To present the clinical signs and treatment methods for atypical tumor‐like meibomitis in two dogs. Animals Studied: A 4‐year‐old castrated‐male Coton de Tulear (Case 1) and a 6‐year‐old spayed‐female Maltese dog (Case 2). Procedure: Full ophthalmic examination revealed a well‐circumscribed, firm, and raised solitary mass on the upper eyelid of the left (Case 1) and right eye (Case 2). Case 1 showed a recurrent mass with a diameter of 2–3 mm, which was excised by the referring veterinarian. The possibility of meibomian gland involvement was suggested histopathologically. Case 2 had a history of blepharitis treated with systemic corticosteroids 4 years ago. Results: Topical and systemic antibiotics and anti‐inflammatory drugs were administered to reduce inflammation and prevent secondary infections. In Case 1, the mass appeared static at the beginning of medication; however, after stopping antibiotics while tapering steroids, the mass increased in size and was associated with suppurative discharge. In Case 2, the mass continued to grow despite treatment, showing a similar infection pattern. Cytological examination revealed neutrophilic inflammation with cocci infection, and bacterial culture confirmed the presence of Staphylococcus pseudintermedius in both cases. When steroid administration was stopped and antibiotic administration was initiated according to the results of the antibiotic susceptibility test, the mass rapidly decreased in size and completely disappeared. There was no recurrence on follow‐up. Conclusions: A unilateral antibiotic‐responsive tumor‐like solitary mass on the upper eyelid resolved without surgical treatment. Medical treatment must be considered when treating atypical eyelid masses, and the use of appropriate antibiotics through antibiotic susceptibility testing is important. [ABSTRACT FROM AUTHOR]

Background: Evaluating regeneration is essential for the classification and differential diagnosis of anemia in dogs. Early detection of regeneration is challenging in anemic dogs. Objectives: This study assessed the value of immature reticulocyte fraction (IRF) in differentiating preregenerative anemia (PRA) from nonregenerative anemia (NRA) in dogs. Animals: Ninety‐four dogs: 49 controls and 45 with anemia. Methods: Case‐control study. Fractions of low‐, medium‐ (MFR), and high‐fluorescence reticulocytes (HFR), were measured using the ADVIA 2120i hematology analyzer. The IRF was calculated as the sum of percentages of MFR and HFR. Data from dogs with regenerative anemia (RA, n = 19), PRA (n = 11), and NRA (n = 15) were retrospectively analyzed. The value of IRF was compared with reticulocyte production index (RPI) using the receiver operating characteristic (ROC) curve. Results: The median of IRF was significantly higher in dogs with RA (46.5%; range, 40.9‐53.6%; P <.001) and PRA (40.6%; range, 27.7‐47.1%; P =.01) than in controls (22.1%; range, 16.9‐29.3%). The IRF in dogs with PRA showed no difference compared to dogs with RA (P >.99) but was higher than dogs with NRA (18.7%; range, 8.8‐24%; P =.00). The area under the ROC curve of IRF was superior to that of RPI (0.897 vs 0.818, P =.00) in differentiating dogs with PRA from NRA. Conclusions and Clinical Importance: The IRF is a reliable variable for detecting early regeneration in anemic dogs without reticulocytosis. The study suggests that the measurement of IRF could be useful in classifying anemic dogs. [ABSTRACT FROM AUTHOR]

Background: Serum uromodulin concentration has been described as a novel biomarker of chronic kidney disease (CKD) in humans but not dogs. Objective: To evaluate the serum uromodulin concentration in dogs with CKD and assess its diagnostic performance in distinguishing dogs with CKD from healthy dogs. Animals: Forty‐nine dogs with CKD (International Renal Interest Society [IRIS] Stage 1, n = 23; Stage 2, n = 20; Stage 3‐4, n = 6) and 25 healthy controls. Methods: Prospective, observational study. Serum uromodulin concentration was measured using a canine‐specific enzyme‐linked immunosorbent assay (ELISA), and its correlation with conventional renal markers was analyzed. Results: Serum uromodulin concentrations were significantly lower in the CKD group than in the control group (P <.001), but no significant difference was observed among stages of CKD. A negative correlation was observed between serum uromodulin concentration and conventional renal markers (blood urea nitrogen concentration, r = −.60, P <.0001; serum creatinine concentration, r = −.46, P <.0001; serum symmetric dimethylarginine concentration [SDMA], r = −.65, P <.0001). In receiver operating characteristic analysis, the area under the curve (AUC) of uromodulin (AUC, 0.97; 95% confidence interval [CI], 0.94‐1.00) was higher than that of SDMA (AUC, 0.87; 95% CI, 0.79‐0.95) for CKD diagnosis (P =.01). The AUC of uromodulin (AUC, 0.95; 95% CI, 0.89‐1.00) also was higher than that of SDMA (AUC, 0.72; 95% CI, 0.58‐0.87) in distinguishing dogs with Stage 1 CKD from controls (P =.001). Conclusions and Clinical Importance: Serum uromodulin concentration is decreased in dogs with CKD. Thus, serum uromodulin may be a valuable diagnostic marker for CKD in dogs, particularly in identifying early‐stage CKD. [ABSTRACT FROM AUTHOR]

Little is known about the transcriptional regulation of tumor angiogenesis, and tumor ECs (tECs) remain poorly characterized. Here, we studied the expression pattern of the transcription factor Sox17 in the [...]

Metformin, a drug for type 2 diabetes mellitus, has shown therapeutic effects for various cancers. However, it had no beneficial effects on the survival rate of human malignant mesothelioma (HMM) patients. The present study was performed to elucidate the underlying mechanism of metformin resistance in HMM cells. Glucose‐starved HMM cells had enhanced resistance to metformin, demonstrated by decreased apoptosis and autophagy and increased cell survival. These cells showed abnormalities in mitochondria, such as decreased ATP synthesis, morphological elongation, altered mitochondrial permeability transition pore and hyperpolarization of mitochondrial membrane potential (MMP). Intriguingly, Mdr1 was significantly upregulated in mitochondria but not in cell membrane. The upregulated mitochondrial Mdr1 was reversed by treatment with carbonyl cyanide m‐chlorophenyl hydrazone, an MMP depolarization inducer. Furthermore, apoptosis and autophagy were increased in multidrug resistance protein 1 knockout HMM cells cultured under glucose starvation with metformin treatment. The data suggest that mitochondrial Mdr1 plays a critical role in the chemoresistance to metformin in HMM cells, which could be a potential target for improving its therapeutic efficacy. This study illustrated that glucose‐deficient conditions facilitated resistance to metformin in human malignant mesothelioma (HMM) cells through Mdr1 increasing in defected mitochondria. It also increased through mitochondrial membrane potential hyperpolarization and mitochondrial dysfunction rescued glucose‐starved HMM cells as a result of metformin treatment. [ABSTRACT FROM AUTHOR]

Patients with advanced urothelial carcinoma (UC) generally have poor prognoses due to therapeutic resistance. Furthermore, there are limited treatment options for advanced UC. Therefore, novel or effective chemotherapeutic agents are needed to improve patient survival. The present study was conducted to investigate the effect of temozolomide (TMZ) on UC cells so as to identify a potential method to overcome therapeutic resistance. TMZ is an alkylating agent with a target different from that of other anticancer drugs used to treat UC, such as cisplatin. TMZ enhanced the autophagic response and senescence, which was mediated via the p53 and p21 pathways. Inhibiting the autophagic response using chloroquine synergistically augmented the cytotoxic effect of TMZ on UC cells. TMZ significantly reduced the invasiveness of UC cells. Notably, the abundance of side population fraction was also significantly reduced following TMZ treatment. Considering that side population fraction is known to confer therapeutic resistance, it is noteworthy that the TMZ treatment markedly decreased side population fraction. Altogether, TMZ may have the potential to be applied as a part of an alternative treatment strategy to reduce the malignancy of UC cells. [ABSTRACT FROM AUTHOR]

Cancer-associated fibroblasts (CAFs) are an abundant component of the tumor microenvironment and have distinct features from normal fibroblasts (NFs). However, the discriminative nature of heterogeneous CAFs under glucose starvation remains unknown. In this study, we investigated the changes in the mitochondrial calcium concentration and relevant intracellular machinery in CAFs under glucose-deficient conditions. Xenografted tumor masses were dissected into multiple pieces and subjected to the CAF isolation using magnetically activated cell sorting (MACS). NFs were separated from the normal lung and skin. Under glucose starvation, CAFs from the tumor mass exhibited heterogeneity in cell proliferation, ATP production and calcium concentration. Compared to NFs, mitochondrial calcium concentration was significantly higher in glucose-starved CAFs with upregulation of mitochondrial calcium uniporter (MCU) that led to enhancement of ATP production and cell growth. Intriguingly, treatment of glucose-starved CAFs with oligomycin increased apoptosis by disrupted calcium homeostasis following overactivation of the mPTP. Moreover, oligomycin-induced apoptosis was mitigated by calcium chelation. This study demonstrated that the discriminative calcium influx to mitochondria through MCU coordinated cell growth and apoptosis in glucose-starved CAFs but not in NFs. • CAFs from a tumor mass are heterogeneous under the glucose deficient condition. • CAFs survive under glucose deficient condition by activation of TGF-β and calcium. • Calcium influx to mitochondria is critical for survival of glucose-deficient CAFs. • MCU in CAFs could be a feasible target for the development of anticancer drugs. [ABSTRACT FROM AUTHOR]

Abstract: Increased permeability of the brain–blood barrier (BBB) in the piriform cortex (PC) has been reported in various animal models of temporal lobe epilepsy. Since BBB disruption induced by epileptogenic insult has not fully clarified, we attempted to determine whether changes in BBB-related molecules are associated with vasogenic edema in the PC. One day after status epilepticus (SE), PC neurons and astrocytes showed a pyknotic nucleus and shrunken cytoplasm accompanied by vasogenic edema. At this time point, SMI-71 (an endothelial barrier antigen) immunoreactivity had decreased in the PC. Prior to vasogenic edema formation (12h after SE), dystrophin immunoreactivity disappeared within astrocytes, while the change in glial fibrillary acidic protein immunoreactivity was negligible. However, glucose transporter-1 (an endothelial cell marker) had increased at 12h after SE. These findings indicate that dysfunction of dystrophin induced by SE may result in endothelial and astroglial damage with BBB breakdown and increase vascular permeability, leading to vasogenic edema that is involved in pathogenesis of epileptogenesis. [ABSTRACT FROM AUTHOR]

Importance: Kidney disease is prevalent among veterinary species, including zoo animals; however, investigations into this condition in striped skunks ( Mephitis mephitis ) are scarce. Diagnostic tools for kidney diseases in this species also remain limited., Objective: This study aimed to assess the utility of symmetric dimethylarginine as a biomarker for kidney disease in captive striped skunks in Korea., Methods: This retrospective study analysed 11 striped skunks housed at the Everland Zoo between 2017 and 2021. Blood samples were collected during health checks. Kidney function was assessed through blood analysis and diagnostic ultrasound, with necropsies conducted on deceased animals. Symmetric dimethylarginine levels were measured in 27 plasma samples collected from 11 skunks., Results: Over the study period, seven skunks were diagnosed with kidney disease. Analysis of 27 blood samples revealed a concurrent increase in SDMA levels with concentrations of blood urea nitrogen and blood creatinine. In 3 of the 7 skunks with kidney disease, symmetric dimethylarginine exceeded 14 µg/dL prior to the elevation of blood urea nitrogen and blood creatinine above the upper reference limit., Conclusions and Relevance: To our knowledge, this is the first study investigating symmetric dimethylarginine in captive striped skunks in Korea. Our findings suggest that symmetric dimethylarginine may serve as an early and consistent biomarker for renal dysfunction in striped skunks. Further studies with larger clinical sample size from striped skunks are needed to validate the clinical utility of blood symmetric dimethylarginine concentration., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Korean Society of Veterinary Science.)

A 12-year-old, spayed female, Maltese dog with a round and firm mass on the dorsal part of the left rear paw and a cervical mass was brought to the clinic. The paw mass was contiguous to the adjacent tendon; it was composed of neoplastic mesenchymal cells and had scattered foci of calcification with chondroid differentiation microscopically. The neoplastic cells were positive for vimentin and S100, but negative for desmin and smooth muscle actin. Microscopic features and immunohistochemistry results were consistent with calcifying aponeurotic fibroma (CAF). The cervical mass was composed of polygonal cells forming acini with marked anisocytosis and anisokaryosis and diagnosed as thyroid follicular carcinoma. No recurrence or metastasis occurred during follow-up. To the best of our knowledge, this is the first case of canine CAF with features identical to its human counterparts. Key clinical message: This report describes the rare case of calcifying aponeurotic fibroma on the paw in a dog. This is apparently the first case in the veterinary literature with identical clinical and pathological features to the human counterpart., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Atopic dermatitis (AD) is a common skin disorder difficult to be treated with medication. This study investigated the potential of ovalicin extracted from Cordyceps militaris for the treatment of AD using in vitro and in vivo models. We found that, in canine macrophage cell line DH82, lipopolysaccharide (LPS) upregulated the expression of genes associated with inflammation and pruritic responses through activating calcium and interleukin-31 (IL-31) signaling, and the upregulation could be suppressed by ovalicin, with an effect significantly stronger than dexamethasone. Ovalicin also reduced the expression of IL-31 downstream genes, including JAK2 (Janus kinase 2), TRPV1 (transient receptor potential vanilloid receptor-1), and HRH2 (histamine receptor H2). Ovalicin significantly alleviated the allergic symptoms in the AD mouse model. Histologically, the number of macrophages and mast cells infiltrated in the dermis was significantly reduced by ovalicin treatment. In the skin tissue of AD mice, reduction of IL-31 receptor was observed in the ovalicin treated group compared to the group without ovalicin treatment. To our knowledge, this is the first study to elucidate the anti-atopic mechanism of ovalicin, which could be an alternative to steroidal drugs commonly used for AD treatment.

Background: Quantitation of urine protein is important in dogs with chronic kidney disease. Various analyzers are used to measure urine protein-to-creatinine ratios (UPCR)., Objectives: This study aimed to compare the UPCR obtained by three types of analyzers (automated wet chemistry analyzer, in-house dry chemistry analyzer, and dipstick reading device) and investigate whether the differences could affect clinical decision process., Methods: Urine samples were collected from 115 dogs. UPCR values were obtained using three analyzers. Bland-Altman and Passing Bablok tests were used to analyze agreement between the UPCR values. Urine samples were classified as normal or proteinuria based on the UPCR values obtained by each analyzer and concordance in the classification evaluated with Cohen's kappa coefficient., Results: Passing and Bablok regression showed that there were proportional as well as constant difference between UPCR values obtained by a dipstick reading device and those obtained by the other analyzers. The concordance in the classification of proteinuria was very high (κ = 0.82) between the automated wet chemistry analyzer and in-house dry chemistry analyzer, while the dipstick reading device showed moderate concordance with the automated wet chemistry analyzer (κ = 0.52) and in-house dry chemistry analyzer (κ = 0.53)., Conclusions: Although the urine dipstick test is simple and a widely used point-of-care test, our results indicate that UPCR values obtained by the dipstick test are not appropriate for clinical use. Inter-instrumental variability may affect clinical decision process based on UPCR values and should be emphasized in veterinary practice., Competing Interests: The authors declare no conflicts of interest., (© 2021 The Korean Society of Veterinary Science.)