The degree of differentiation of mast cell tumours (MCTs) is the most important feature and reflects the morphological characteristics and metastatic potential of the tumour and its likely response to treatment and the prognosis. The aim of this study was to epidemiologically analyse the risk of MCT development in dogs according to breed, age, sex, size and anatomical location of the tumour using the Kiupel grading system. The analysis involved 492 dogs selected based on a histopathological assessment of 2763 canine skin tumours. A logistic regression analysis was performed to determine the odds ratios (ORs) with 95% confidence intervals. Mast cell tumours accounted for 17.8% of all diagnosed canine skin tumours. The highest risk of high-grade MCTs was noted in the Shar-Pei (OR 28.18, P < 0.001) and Weimaraner (OR 6.45, P = 0.023). The highest risk of low-grade MCTs was determined in the Boxer (OR 6.72, P < 0.001), and Pug (OR 6.13, P = 0.027). The scrotum (OR 31.72, P < 0.001), inguinal area (OR 17.69, P < 0.001) and axilla (OR 6.30, P < 0.001) had the highest risk of high-grade MCTs. The risk of high-grade MCTs increased with age and peaked in the oldest dogs, aged 11–16 years (OR 9.55, P < 0.001). A higher risk of low-grade tumours was noted in younger dogs (aged 4–6 years) (OR 8.54, P < 0.001) and females (OR 1.43, P = 0.001). Statistical analysis further revealed a higher risk of both low (OR 3.47, P < 0.001) and high-grade MCTs (OR 1.71, P = 0.006) in medium-sized dogs. This study demonstrated relationships between Kiupel grading system and phenotypic traits, age and location of canine MCTs confirming the complex biological nature of this tumour.

Introduction: Breed predisposition to cutaneous mast cell tumours (MCT) in a population of dogs in Poland affected by various skin tumours was assessed, and the distribution of MCT characteristics such as histological grading, sex, age, and location, in predisposed breeds was evaluated. Material and Methods: The retrospective epidemiological study included 550 dogs affected by cutaneous MCTs with a reference group of 2,557 dogs diagnosed with other skin tumours. Results: A univariable logistic regression analysis was performed to determine the odds ratios (ORs) with 95% confidence intervals. The risk of high-grade MCTs was the highest for Shar-Peis (OR: 26.394) and American Staffordshire Terriers (OR: 2.897). Boxers (OR: 6.619), Labrador Retrievers (OR: 2.630), French Bulldogs (OR: 2.050), Golden Retrievers (OR: 1.949), and American Staffordshire Terriers (OR: 2.592) were mainly affected by low-grade MCTs. The high risk of MCT was calculated to be at the age of 4–6 years for Labrador Retrievers (OR: 2.686) and 7–10 years for Boxers (OR: 2.956) and French Bulldogs (OR: 9.429). MCTs were significantly more often located on the trunk in French Bulldogs (OR: 4.680), American Staffordshire Terriers (OR: 2.520), and Labrador Retrievers (OR: 1.948). There was no statistically significant correlation between gender and the occurrence of MCTs in the breeds. Conclusions: The breed-predicated differences in the clinical course of MCTs suggest a genetic background for the tumours.

The aim of the study was to identify significant relationships between the tumour malignancy grade and dogs’ age, breed, sex, size, and location of mast cell tumours (MCTs). MCTs accounted for 13.27% of all diagnosed canine skin tumours. The highest incidence was recorded among Boxers, Labrador Retrievers, American Staffordshire Terriers, and Golden Retrievers. Statistical analysis revealed significantly higher probability of occurrence of the grade I mast cell tumour in the French Bulldog in the head, neck, torso, and limb regions, the grade-II mast cell tumour in Boxer, Doberman, Dachshund, shepherds, and setters in the scrotal region, and the grade III mast cell tumour in Shar-Pei in the axilla region. In the group of the oldest dogs aged 11-16, there was higher risk of development of MCTs grade II and III. Young dogs (aged 2-3 and 4-6) were found to be more prone to development of MCTs grade I. There was no correlation between MCTs grade and dogs’ sex and size. To the authors’ knowledge this is the first report on statistical relationships between the degree of mast cell tumour malignancy and dogs’ phenotypic traits, age and tumour location. This analysis indicate predilections for development of the particular mast cell tumour malignancy degrees in certain dog breeds, age, and anatomical location

Background: Research has revealed the presence of somatic mutations in mitochondrial DNA (mtDNA) of certain types of tumours. As this has not been studied for canine mast cell tumours, the aim of this study was to identify mutations in the hypervariable region of mtDNA in mast cell tumours in dogs and determine their association with the process of neoplastic transformation. Results: Samples from 17 dogs with histopathologically confirmed mast cell tumours were analysed. The samples consisted of tumour tissues (n = 17), normal tissues (n = 17), and blood (n = 17). Amplicons of the displacement loop (D-loop) were sequenced and the obtained nucleotide sequences were subjected to bioinformatics analyses. Somatic mutations were detected in seven positions of the D-loop nucleotide sequences in 47 % of the dogs, while polymorphisms were identified in 94 % of the dogs. Most of these changes were homoplasmic, while heteroplasmy was detected in two individuals. Six new haplotypes were established as being characteristic for canine mast cell tumours. There was no association between the presence of the mutations and sex, haplotype, or malignancy grade assessed in 3 and 2-grade scales. Conclusions: Differences in the frequency of somatic mutations imply their direct association with the neoplastic transformation. However, their functional consequences and clinical significance are not clear. The mutations may be used for diagnosis and prognosis of canine mast cell tumours in the future.

About 70 million people suffer from epilepsy—a chronic neurodegenerative disease. In most cases, the cause of the disease is unknown, but epilepsy can also develop as the result of a stroke, trauma to the brain, or the use of psychotropic substances. The treatment of epilepsy is mainly based on the administration of anticonvulsants, which the patient must most often use throughout their life. Despite significant progress in research on antiepileptic drugs, about 30% of patients still have drug-resistant epilepsy, which is insensitive to pharmacotherapy used so far. In our recent studies, we have shown that 4-alkyl-5-aryl-1,2,4-triazole-3-thiones act on the voltage-gated sodium channels and exhibit anticonvulsant activity in an MES (maximal electroshock-induced seizure) and 6Hz test in mice. Previous studies have shown their beneficial toxic and pharmacological profile, but their effect on a living organism during chronic use is still unknown. In the presented study, on the basis of the previously conducted tests and the PAMPA (parallel artificial membrane permeability assay) BBB (blood–brain barrier) test, we selected one 1,2,4-triazole-3-thione derivative—TP-315—for further studies aimed at assessing the impact of its chronic use on a living organism. After long-term administration of TP-315 to Albino Swiss mice, its effect on the functional parameters of internal organs was assessed by performing biochemical, morphological, and histopathological examinations. It was also determined whether the tested compound inhibits selected isoforms of the CYP450 enzyme system. On the basis of the conducted tests, it was found that TP-315 does not show nephrotoxic nor hepatotoxic effects and does not cause changes in hematological parameters. In vitro tests showed that TP-315 did not inhibit CYP2B6, CYP2D6, CYP3A4, or CYP3A5 enzymes at the concentration found in the serum of mice subjected to long-term exposure to this compound.

Aim: Identification of mutations and polymorphisms in the cytochrome b gene (Cyb) of mitochondrial DNA (mtDNA) in canine mast cell tumours and determinatiion of their association with the process of neoplastic transformation. Materials and Methods: The samples comprised tumour tissues and blood obtained from 34 dogs of various breeds. Mutations and polymorphisms in the Cyb gene were detected using amplification and sequencing methods. Results: Heteroplasmic mutations were detected at seven positions of mtDNA in 86% of the individuals. Blood and tumour heteroplasmy were recorded at five nucleotide positions of the Cyb gene, whereas tumour heteroplasmy was detected at two positions. Polymorphisms were detected at 14 Cyb gene positions in in the blood of 91% of dogs with mast cell tumours. Conclusion: The presence of numerous mutations and polymorphisms of Cyb in the blood and tumour tissues and the high frequency of heteroplasmy indicate their involvement in the process of neoplastic transformation in dogs.