Gintonin upregulates cytokine production and expression of NKp30, NKp44 and NKp44 related to natural killer cell activity on immunosuppressive rat.

The objective of the study is to estimate the potential of gintonin, as an immune enhancing agent through natural killer cell (NK cell) activity in cyclophosphamide (CY)-induced immunosuppressive animals. Accumulated results reveals that, gintonin attenuated CY-induced immunosuppression and it might modulate NK cell activity to boost the immunity.

Serum thymidine kinase 1 protein concentrations and presence of its autoantibody as biomarkers for screening dogs with malignant tumors.

BACKGROUND: An accurate and easily accessible method for diagnosing malignancies in local veterinary clinics has not yet been established. OBJECTIVES: To investigate the usefulness of serum thymidine kinase 1 (TK1) protein and its autoantibody as tumor biomarkers in dogs. ANIMALS: Serum samples from 1702 dogs were collected from local animal hospitals and referral animal medical centers in South Korea. METHODS: TK1 protein OD value and TK1 autoantibody ratio (TK1 autoantibody OD/total IgG OD) in serum samples of dogs classified into healthy controls, group with nontumor disease, group with benign and group with malignant tumors were measured using lateral flow immunochromatographic assay methods. RESULTS: TK1 autoantibody levels were significantly higher in malignant tumor group (median 0.71) than in healthy controls (median 0.34), group with nontumor disease (median 0.34), and group with benign tumor (median 0.32, Welch t test, P < .0001). They were also significantly different among dogs with carcinomas (median 0.77), hematopoietic tumors (median 0.71), and sarcomas (median 0.56) than in healthy controls (median 0.34, post hoc Games-Howell test, P < .0001). In the receiver operating characteristic curve of TK1 protein, AUC was 0.633 (95% CI: 0.592-0.675, P < .0001). The AUC of TK1 autoantibody ratio was 0.758 (95% CI: 0.723-0.793, P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: TK1 autoantibody is a potentially useful biomarker for differentiating between healthy and tumor-bearing dogs, better than TK1 protein measurement. However, both were inadequate when used as single biomarkers for screening dogs to discover occult malignant tumors.

Isolation of multidrug-resistant (MDR) Mycobacterium bovis from a dog in Korea.

A 3-year-old female Miniature Schnauzer dog with a week-long history of generalized intention tremor and progressive weight loss for several months was admitted. Mild anemia, fever, splenomegaly, aseptic cerebral meningitis and systemic lymph nodes enlargement were examined through erythrogram, ultrasonography, computed tomography and magnetic resonance imaging. Mycobacterium bovis was identified via molecular microbiology having the same molecular type as that of isolates from a cattle farm previously identified. However, the dog was raised in a city. The M. bovis had multidrug resistance (MDR)-bearing mutations in both katG and rpoB genes toward first-line antibiotics. To the best of our knowledge, this is the first report describing an MDR M. bovis infection of a dog in Korea.

Evaluation of the Randox and Fuji Dri-Chem vcCRP-P assays of canine C-reactive protein.

In veterinary medicine, measurement of canine C-reactive protein (cCRP) is used widely to detect inflammatory diseases. We evaluated the precision of Randox and Fuji assays for cCRP, as well as accuracy, correlation, and agreement compared to a reference ELISA. Blood samples from 71 client-owned dogs (20 healthy, 51 diseased) were analyzed with the 3 assays. Inter-assay CVs were ~3.5% with both the Randox and Fuji assays. The mean biases were -1.90% for the Randox and -5.93% for the Fuji test; the targeted biases were ~8.5% for both assays. The CV, bias, and observed total error were acceptable for the 2 assays compared to ASVCP recommendations based on biological variation studies. The Spearman correlation coefficient for cCRP concentration compared with the reference ELISA was 0.83 for the Randox test and 0.92 for the Fuji test. Both assays measured cCRP precisely at intermediate and increased concentrations. Correlation with the reference ELISA was good, and both assays could be used to evaluate cCRP concentrations in veterinary practice. However, the assays did not reach analytical agreement; hence the results obtained by these assays are not interchangeable, and serial monitoring of cCRP requires the use of the same assay.

Prevalence of Reticulocytosis in the Absence of Anemia in Dogs with Cardiogenic Pulmonary Edema Due to Myxomatous Mitral Valve Disease: A Retrospective Study.

Myxomatous mitral valve disease (MMVD) is the most common heart disease in small breed dogs. Dogs with MMVD commonly show clinical signs of dyspnea due to cardiogenic pulmonary edema (CPE). Reticulocytosis in the absence of anemia (RAA) is a hematological finding in hypoxic conditions. We aimed to assess the prevalence of RAA in dogs with CPE due to MMVD, and evaluate whether RAA is reversible with amelioration of dyspnea. Twenty-nine client-owned dogs with CPE due to MMVD were included. Dogs who died within 6 weeks of the onset of CPE were included in the non-survival group, while the others comprised the survival group. Of the 21 dogs, RAA was observed in 17 dogs (80.9%). In the RAA group, the absolute reticulocyte count significantly decreased as CPE resolved (p < 0.001). The mean absolute reticulocyte count in the RAA group was 163.90 ± 50.77 on the first measurement and 78.84 ± 25.64 after resolution of CPE. In the RAA group, no significant differences in mean absolute reticulocyte count were observed between the survival and non-survival groups at either the first or second measurement. Our results indicate that RAA occurs in dogs with MMVD-related CPE and can resolve after resolution of CPE.

Perfusion change in benign prostatic hyperplasia before and after castration in a canine model: Contrast enhanced ultrasonography and CT perfusion study.

Hormonal and vascular changes affecting the canine prostate after castration were investigated to identify the effects of hormones and perfusion on the development of benign prostatic hyperplasia (BPH). Concentrations of serum testosterone and estrogen and intraprostatic dihydrotestosterone (DHT) were compared between 5 normal dogs, 6 dogs with mild BPH, and 6 dogs with marked BPH. In addition, prostatic perfusion using contrast-enhanced ultrasonography (CEUS) and CT perfusion (CTP), as well as CT volumes of the prostates were compared. The changes in these values following castration were assessed in 6 dogs with marked BPH. CEUS revealed significantly slower prostatic arterial inflow and relatively faster venous outflow in BPH versus normal prostate. Permeability and blood volume were not significantly different between the groups via CTP. Intraprostatic DHT level was higher in BPH than in normal prostate and decreased significantly following castration, which was accompanied by a rapid decrease in prostatic volume. On CEUS, arterial inflow to the prostate significantly decreased following castration. Blood volume within the prostate decreased significantly by day 60 following castration. Permeability increased significantly during the early phase after castration; however, by day 60 post-castration, all perfusion parameters decreased significantly. Perfusion changes including venous parameters measured by CEUS and blood volume changes measured by CTP, however, did not support the backflow theory postulating that BPH is induced by vascular changes from congested testes. The major etiology for the development of BPH is attributed to be increased levels of DHT rather than vascular changes.

AniScan Using Extracellular Cyclic AMP-Dependent Protein Kinase A as a Serum Biomarker Assay for the Diagnosis of Malignant Tumors in Dogs.

The early detection of tumors improves chances of decreased morbidity and prolonged survival. Serum biomarkers are convenient to use and have several advantages over other approaches, such as accuracy and straightforward protocols. Reliable biomarkers from easily accessible sources are warranted for the development of cost-effective assays for routine screening, particularly in veterinary medicine. Extracellular c-AMP-dependent protein kinase A (ECPKA) is a cytosolic leakage enzyme. The diagnostic accuracy of detecting autoantibodies against ECPKA was found to be higher than that of ECPKA activity from enzymatic assays, which use a complicated method. Here, we investigated the diagnostic significance of measuring serum ECPKA autoantibody levels using an in-house kit (AniScan cancer detection kit; Biattic, Anyang, Korea). We used sera from 550 dogs, including healthy dogs and those with malignant and benign tumors. Serum ECPKA and immunoglobulin G were determined using the AniScan cancer detection kit. ECPKA autoantibody levels were significantly higher (p < 0.01) in malignant tumors than in benign tumors, non-tumor diseases, and healthy controls. On the basis of sensitivity and specificity values, AniScan ECPKA is a rapid and easy-to-use assay that can be applied to screen malignant tumors from benign tumors or other diseases in dogs.

Extracellular cyclic adenosine monophosphate-dependent protein kinase A autoantibody and C-reactive protein as serum biomarkers for diagnosis of cancer in dogs.

Protein kinase A, a cyclic adenosine monophosphate (AMP)-dependent enzyme, normally exists within mammalian cells; however, in cancer cells, it can leak out and be found in the serum. Extracellular cyclic AMP-dependent protein kinase A (ECPKA) has been determined to increase in the serum of cancer-bearing dogs. However, there have been no reports in the veterinary literature on serum ECPKA autoantibody (ECPKA-Ab) expression in dogs with cancer. The aim of this study was to evaluate ECPKA-Ab and C-reactive protein (CRP) as serum biomarkers for cancer in dogs. ECPKA-Ab and CRP levels were detected by an enzyme-linked immunosorbent assay in serum samples from dogs with malignant tumours (n = 167), benign tumours (n = 42), or non-tumour disease (n = 155) and from healthy control dogs (n = 123). ECPKA-Ab and CRP levels were significantly higher in the dogs with malignant tumours than in those with benign tumours or non-tumour diseases, as well as in the healthy controls (P < 0.001, Kruskal-Wallis test). There was a significant positive correlation between the neoplastic index, which was developed using ECPKA-Ab and CRP levels, and the presence of cancer in dogs (P < 0.001); the area under the receiver-operating characteristic curve was estimated to be >0.85 (P < 0.001). In conclusion, ECPKA-Ab is a potential serum biomarker for a broad spectrum of cancers. Combined measurement of CRP and ECPKA-Ab levels in serum improves the sensitivity and accuracy of a diagnosis of cancer in dogs.

First Case of Canine Infection with Hepatozoon canis (Apicomplexa: Haemogregarinidae) in the Republic of Korea.

This report describes a dog infected with Hepatozoon canis, the first canine infection in the Republic of Korea. A 2-year-old intact male Maltese dog presented with anorexia and depression. Physical examinations revealed mild dehydration and hyperthermia (39.8°C), and blood analysis showed pancytopenia. Diff-Quik staining of blood smear specimens showed the presence of ellipsoidal shaped structures (gamonts of H. canis) within a small number of neutrophils. Real-time PCR analysis using whole blood confirmed infection by H. canis. The clinical condition of the dog improved after symptomatic treatment and administration of doxycycline. Although a molecular epidemiologic survey in Korea showed H. canis infection of dogs, to our knowledge this is the first report of a dog infection in Korea molecularly shown to be H. canis.

A rare case of hepatic T-cell rich B-cell lymphoma (TCRBCL) in a juvenile dog.

A 7-month-old castrated male French Bull dog was presented with vomiting, lethargy, anorexia and weight loss of 2 weeks duration. The patient's history and clinical manifestations of suspected hepatopathy were subjected to ultrasonography, radiography, biochemical investigations and cytology of hepatic lesion. The cytologic impression was hepatic lymphoma, which was later confirmed by histopathology. The neoplastic cells were strongly diffusely immunoreactive for PAX5, but not immunoreactive for CD3, and B lymphocyte specific clonal proliferation was detected using by assay of antigen receptor rearrangement. Large numbers of immunoreactive mature non-neoplastic lymphocytes were admixed with the neoplastic cell population. Therefore, the immunohistochemical results were definitively consistent with a T-cell rich B-cell lymphoma (TCRBCL). This is the first description of a hepatic TCRBCL in a juvenile dog showing a poor response to aggressive chemotherapy.

Multicentric epitheliotropic T-cell lymphoma in an African hedgehog (Atelerix albiventris).

A 2-year-old female African hedgehog was presented with a 5-month history of pruritus, and diffuse spine and hair loss. A dermatologic examination revealed erythema, excoriation, scales, and crusting affecting the face, flanks, forelimbs, hindlimbs, and dorsal and ventral abdomen. Fine-needle aspiration was performed and skin biopsies were taken from several lesions for cytologic and histologic evaluation. The aspirates yielded smears characterized by a monomorphic population of medium-sized to large lymphocytes with scant to moderate amounts of clear to moderately basophilic cytoplasm and distinct nucleoli along with a low number of cytoplasmic fragments. On histopathologic examination, there were dense dermal lymphoid infiltrates invading the dermis and a monomorphic population of round cells that had infiltrated the overlying epidermis. Epitheliotropic cutaneous lymphoma was diagnosed based on morphologic features. Additional immunochemical analysis using anti-CD3 and anti-CD79a antibodies revealed strong CD3 expression by the tumor cells, which confirmed epitheliotropic cutaneous T-cell lymphoma. This is the first description of a multicentric pattern of epitheliotropic cutaneous T-cell lymphoma in an African hedgehog.

Central nervous system relapses in 3 dogs with B-cell lymphoma.

This report describes cases of central nervous system (CNS) relapse that occurred during chemotherapy in 3 dogs with lymphoma. Diagnosis was made by a combination of clinical signs and cytology of cerebrospinal fluid. The suspected risk factors, clinical features common to the 3 dogs, and treatment options are discussed.

Topical 0.03% tacrolimus for treatment of pemphigus erythematosus in a Korea Jindo dog.

Topical 0.03% tacrolimus was used for treatment of a Korea Jindo dog diagnosed with pemphigus erythematosus. The dog was slowly improved following application of tacrolimus but did not achieve complete remission until end of this study. No adverse effects on clinical or laboratory parameters were noted during the topical tacrolimus therapy period.

Hypercalcemia and high parathyroid hormone-related peptide concentration in a dog with a complex mammary carcinoma.

A 10-year-old female Dachshund was presented with a history of mammary masses, slight lethargy, polyuria, and polydipsia. Physical examination findings included masses involving the first, second, and fourth mammary glands of the left side. The mandibular, axillary, and right popliteal lymph nodes were mildly enlarged. Serum chemistry results included hypercalcemia (13.9 mg/dL, reference interval 8.0-11.5 mg/dL). Although intact parathyroid hormone (PTH) concentration (1.05 pmol/L) was below the reference interval (2-13 pmol/L), PTH-related protein (PTHrP) concentration was markedly increased (9.40 pmol/L, reference value < 2 pmol/L). The masses were surgically removed, and the histopathologic diagnosis was complex mammary carcinoma. Three weeks after surgery, serum total calcium concentration had decreased to 10.5 mg/dL. Resolution of the hypercalcemia and clinical signs supported a diagnosis of humoral hypercalcemia of malignancy associated with mammary gland carcinoma.

Palliative intravenous cisplatin treatment for concurrent peritoneal and pleural mesothelioma in a dog.

A 10-year-old Maltese dog was presented with abdominal distention and dyspnea. Cytological examination of pleural and peritoneal effusion was suggestive of malignant effusion of glandular origin. Numerous, multifocal, tan to white nodules were disseminated throughout the surface of the abdominal organs and peritoneum at biopsy. Histologically, the tumors were revealed to be an epithelial type of mesothelioma. Neoplastic cells co-expressed cytokeratin and vimentin. Intravenous administration of cisplatin was chosen as the treatment. During treatment, the dog's overall body condition improved and the clinical signs were relieved without significant side effects. The survival time from diagnosis to sudden death by unknown cause was 153 days.