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.
Glutamine has been used to treat canine patients with parvoviral enteritis. However, little is known about the effect of L-alanyl-L-glutamine (Ala-Gln) supplementation in dogs with parvoviral enteritis. The objective of this study was to determine whether Ala-Gln supplementation can improve dog survival and ameliorate clinical signs without adverse effects. We conducted a randomized, double-blind, placebo-controlled clinical trial involving 39 client-owned dogs. The dogs were randomly assigned to two groups and administered either an Ala-Gln solution (Dipeptiven, 0.4 g/kg, n = 20) or an equivalent volume of placebo (n = 19) orally twice daily. Of the 39 dogs, 17 were vaccinated (n = 9 in the Ala-Gln-treated group and n – 9 in the placebo group). All dogs received standard treatment while hospitalized. The dogs were monitored according to a clinical scoring system and evaluated diagnostically daily for 11 days. Survival rates in both groups were quantified using Kaplan‒Meier survival curves and statistically compared using the log-rank test. The total score for clinical signs did not differ between the groups, except on day 2. The survival rates differed significantly (p=0.038). Three Ala-Gln-treated dogs (15.0%) died during the study, whereas eight dogs in the placebo group died (42.1%). No adverse effects were found to be associated with Ala-Gln treatment. Oral administration of Ala-Gln improves survival in dogs with parvoviral enteritis without causing adverse effects.
This study aimed to identify prognostic factors and describe the treatment outcomes of multidrug therapy in dogs with meningoencephalomyelitis of unknown etiology (MUE). A total of 23 dogs diagnosed with MUE were treated with prednisolone in combination with cyclosporine, cytosine arabinoside (CA), leflunomide, and mycophenolate mofetil. Based on the survival time, these dogs were divided into two groups: group A (n = 10), surviving for < 100 days, and group B (n = 13), surviving for > 100 days. Signalment, seizure activity, cerebrospinal fluid (CSF) analysis results, and magnetic resonance (MR) imaging findings were reviewed. Survival studies were conducted to investigate the association of each prognostic factor and treatment with the clinical outcome. There were no significant differences in age, sex, body weight, occurrence of seizures, cell number and protein concentration in the CSF, or location of lesions between groups A and B. Abnormal MR features were more frequently observed in group A than in group B. It was identified that the longest median survival time was administration of multi-drug therapy including CA. In conclusion, abnormal MR features were associated with poor prognosis in dogs with MUE and CA-based multi-drug therapy could be considered the most effective treatment of MUE.
Vitamin K1 (VK1) has been widely used as a coumarin antagonist and for the treatment of hemorrhagic disease in veterinary practice. However, the potential mechanism of adverse reaction after VK1 injection has been not fully elucidated. In this study, two cases of anaphylactic reactions after subcutaneous VK1 injection were presented, and then an experimental study was performed to further characterize the anaphylactic reactions. Two dogs developed anaphylactic reactions after subcutaneous VK1 injections and were promptly treated with antihistamines and glucocorticoids, after which abnormal signs related to anaphylaxis disappeared. Subsequently, a study was undertaken to ascertain the nature of the adverse reactions to subcutaneous VK1 injection. Six healthy laboratory beagle dogs received subcutaneous VK1 administrations once daily for eight days. They were monitored for clinical signs after each injection, and blood samples were collected for the measurement of plasma histamine and immunoglobulin E concentrations using enzyme-linked immunosorbent assay. All six dogs showed mild angioedema after the VK1 injections. The dogs also displayed clinical signs including sneezing, coughing, skin reddening, excess salivation, pawing the ground, and somnolence on days 4, 6, and 8. Plasma histamine and immunoglobulin E concentrations were significantly increased by the repeated injections. In summary, this study describes anaphylactic reactions resulting from subcutaneous VK1 administration in dogs. Clinicians should be aware that the repeated subcutaneous injection of VK1 can trigger an anaphylactic reaction in dogs.
Mesenchymal stem cells (MSCs) has been reported as multipotent progenitor cells that can be expanded rapidly in vitro and differentiated into multiple mesodermal cell type. Human MSCs have been reported to be associated with neural differentiation especially in the cholinergic phenotype in several neural system. In this study, We investigated the ability of MSCs derived human aipose tissue to differentiation into neural cells expressing Islet-1 and further differentiates into cholinergic neurons in cholinergic differentiation media. Immunocytochemistry was performed to detect the expression of Islet-1 and demonstrate characteristic of neurons and cholinergic neurons. Islet-1 was massively detected in the induction stage. Following cholinergic differentiation from Islet-1-expressing MSCs, Cholinergic neuron marker ChAT was higly expressed. Also we examined the neuroprotective effects and neural differentiation of transplanted human adipose tissue-derived mesenchymal stem cells (AT-MSCs) in ischemic stroke. For transplantation, after 3days after MCAO. animal were divided into 2 group: Group A : injected phosphate buffered saline (PBS;5 ㎕ n=10), Group B: transplanted AT-MSCs (5×105 cells, n=10). Each animal received an injection into the right penumbra region (from bregma : AP;-1.3 ㎜, ML;-4.0 ㎜, DV;-5.9 ㎜). In all animals, behavior test were performed at 1, 3, 6, 9, 12, 15 days after MCAO, that was conducted by investigators who were blined to the experimental groups. mNSS test demonstrated that motor, sensory, and balance behavior were impaired after MCAO ischemic insult. Ischemic rats that received AT-MSCs exhibited significantly improved functional performance compared with PBS injected animals and histological analysis revealed that transplanted AT-MSCs expressed marker for neuron. These results suggest that AT-MSCs can be differentiated into neuron especially in cholinergic neuron and may be a potential source of treatment for neurodegenerative disease such as stroke.