Expression of programmed cell death protein 1 and programmed cell death ligand 1 in feline injection site fibrosarcomas.

Feline injection site fibrosarcomas represent a unique challenge in veterinary oncology due to their association with injection sites and aggressive behaviour. The study explores the expression of immune checkpoints programmed cell death protein 1 and programmed cell death ligand 1 in the malignancy, aiming to unravel their potential significance in tumour progression. The study included 31, archival diagnostic specimens of feline fibrosarcomas, located in the common injection sites. The programmed cell death protein 1 and programmed cell death ligand 1 expression in tumour cells and tumour infiltrating lymphocytes were assessed by immunohistochemical methods. Programmed cell death protein 1 and programmed cell death ligand 1 expression were observed in 84% and 81% of cases, respectively. In tumour infiltrating lymphocytes the PD-1 expression was observed in 71% of cases. Notably, higher programmed cell death protein 1 expression correlated with tumour grade and heightened inflammation score, suggesting a potential association with tumour aggressiveness. Similarly, programmed cell death ligand 1 expression exhibited a positive correlation with tumour grade and inflammation score. The observed findings suggest a potential role for programmed cell death protein 1 and programmed cell death ligand 1 in tumour progression and immune response within the tumour microenvironment. Moreover, this study contributes to a deeper understanding of feline injection site fibrosarcoma pathogenesis, emphasizing the importance of considering immunological perspectives in developing effective treatment strategies for this challenging condition. Further investigations are warranted to advance our knowledge and refine therapeutic approaches for feline injection site fibrosarcoma management.

Fatigue in Inflammatory Joint Diseases.

Fatigue is a prevalent symptom in various rheumatic diseases, such as rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. It is characterised as a subjective, enduring feeling of generalised tiredness or exhaustion, impacting the patient's life quality and exacerbating disability. The fatigue nature is multifaceted, encompassing physiological, psychological, and social factors, and although the exact cause of inflammatory joint diseases is not fully understood, several factors are believed to contribute to its development. Despite high prevalence and importance, the symptom is often underestimated in clinical practice. Chronic inflammation, commonly associated with rheumatic diseases, has been proposed as a potential contributor to fatigue development. While current treatments effectively target inflammation and reduce disease activity, fatigue remains a persistent problem. Clinical evaluation of rheumatic diseases primarily relies on objective criteria, whereas fatigue, being a subjective symptom, is solely experienced and reported by the patient. Managing fatigue in inflammatory joint diseases involves a multifaceted approach. Identifying and comprehensively assessing the subjective components of fatigue in individual patients is crucial for effectively managing this symptom in everyday clinical practice.

Metallothionein expression in feline injection site fibrosarcomas.

BACKGROUND: Feline injection site fibrosarcoma is an aggressive and infiltrative tumour arising in the background of chronic inflammation. The aim of this study was to evaluate the expression of metallothionein (I-II) in feline injection site fibrosarcomas and to assess its possible relationships with Ki67 index, inflammation score and tumour grade. The study included 40 feline fibrosarcomas, located in the common injection sites (i.e., interscapular area, thigh, flank), constituting archival diagnostic specimens collected between 2019-2020. Tumours were graded histologically according to the newly proposed soft-tissue sarcoma grading system in cats. Immunohistochemistry was performed to evaluate the expression of Ki67 and metallothionein in tumour cells. RESULTS: The cytoplasmic and sometimes nuclear expression of metallothionein was observed in all tumours grade I, 66.67% of tumours grade II and 55% of tumours grade III. The expression of metallothionein was negatively correlated with tumour grade and inflammation score, while the Ki67 index was positively correlated with tumour grade, inflammation score and necrosis score. CONCLUSION: The downregulation of MT expression in feline injection site fibrosarcomas seems to be connected with an increase in the inflammatory infiltration, hence tumour progression. This is the first study describing metallothionein expression in feline injection site fibrosarcomas.

Fatal Acute Heart Failure in the Course of Macrophage Activation Syndrome: Case Report and Literature Review.

Macrophage activation syndrome is a severe and potentially fatal condition in rheumatology. It can involve many different organs and systems, including the cardiovascular system, but heart failure due to its course is a relatively rare occurrence. In the following paper, we present a case of a young woman with newly diagnosed systemic lupus erythematosus who, in the span of two months, developed macrophage activation syndrome and acute heart failure, which caused her death. We analyze potential causes that may have led to that outcome, and present a brief review of the current literature concerning different macrophage groups in the heart and their potential involvement in the development of heart failure.

Cutaneous and Subcutaneous Tumours of Small Pet Mammals-Retrospective Study of 256 Cases (2014-2021).

Since small mammals are gaining popularity as pets in Poland, the number of tumour samples submitted for histopathological examination is quite high. This study was a retrospective analysis of cutaneous and subcutaneous tumours in small pet mammals submitted for histopathology in 2014-2021. The analysis included 256 tumours sampled from 103 guinea pigs, 53 rats, 43 pet rabbits, 21 ferrets, 17 hamsters, 8 degus, 5 African pygmy hedgehogs, 3 Mongolian gerbils and 3 chinchillas. Tumours were diagnosed based on routine histopathology, with additional immunohistochemistry when necessary. The results of this study revealed that the vast majority of cutaneous tumours in guinea pigs were benign, with a predominance of lipoma. Adnexal tumours constituted a significant percentage of cutaneous tumours in guinea pigs (24.3%, with the most common being trichofolliculoma), pet rabbits (46.5%, with the most common being trichoblastoma), ferrets (33.3%, mostly derived from sebaceous glands), hamsters (52.9%, with the most common being trichoepithelioma) and gerbils (66.7%, scent gland epithelioma). Soft tissue sarcomas were a predominant group of tumours in rats (52.8%, with the most common being fibrosarcoma), African pygmy hedgehogs (100%), degus (87.5%) and chinchillas (66.7%). Melanocytic tumours were only sporadically seen in small mammal pets. Mast cell tumours were diagnosed only in ferrets, while epitheliotropic T-cell lymphoma was diagnosed only in a hamster and a degu. In summary, malignant tumours constitute a significant percentage of cutaneous tumours in many species of small mammal pets. Therefore, each cutaneous tumour should be sampled for further cytologic or histopathologic diagnosis.

Effects of Bee Pollen on Growth Performance, Intestinal Microbiota and Histomorphometry in African Catfish.

This study aimed to determine the dietary effects of honeybee pollen (BP) on growth parameters, intestinal microbiota, hepatic histoarchitecture, and intestinal histomorphometry of African catfish Clarias gariepinus juveniles. The feeding experiment was carried out in a recirculating aquaculture system under controlled conditions for 21 days to achieve more than a 10-fold increase in weight in fish from the control group. Fish were fed well-balanced commercial feed without any supplements and served as a reference group (group C) and other diets enriched with varying BP levels as 1% (BP1), 2% (BP2), and 3% (BP3). Results showed a significant (p < 0.05) effect of the dietary BP not only on the growth parameters (such as final body weight: 5.0 g to 6.6−7.5 g, weight gain: 0.23 g/d to 0.31−0.35 g/d, body length: 84.7 mm to 93.8−95.9 mm, and specific growth rate: 11.7%/d to 13.1−13.7%/d, group C vs. experimental groups, respectively) but also on the development of beneficially important gut microbiota, such as lactic acid-producing bacteria. In BP-enriched groups, an average of 45% higher body weight gain was observed compared to those reared in the control group. The histological analysis showed that dietary BP may have a positive effect on the development of the intestinal tract and may enhance the absorption of nutrients with the potential ability to maintain a normal hepatic histoarchitecture of the treated African catfish. The results obtained suggest the optimum level of BP additive to feed for African catfish should be 1%.

Effective Microorganisms (EM) Improve Internal Organ Morphology, Intestinal Morphometry and Serum Biochemical Activity in Japanese Quails under Clostridium perfringens Challenge.

The effect of effective microorganisms (EM) on internal organ morphology, intestinal morphometry, and serum biochemical activity in Japanese quails under Clostridium perfringens challenge was determined. After 30 days of EM addition, one group of quails was orally inoculated with Clostridium perfringens. The second group did not receive EM and was inoculated with C. perfringens. In the gut, EM supplementation reduced the number of lesions, enhanced gut health, and protected the mucosa from pathogenic bacteria. EM showed an anti-inflammatory effect and fewer necrotic lesions in villi. In the internal organs, EM showed a protective effect against a typical lesion of C. perfringens infection. Necrosis and degeneration of the hepatocytes, necrosis of bile ducts, and bile duct proliferation were more severe in the infected group without EM. Morphometric evaluation showed significantly higher villi in the jejunum after EM addition. A greater crypt depth was observed in the C. perfringens group. Biochemical analysis of the blood indicated lower cholesterol on the 12th day of the experiment and between-group differences in total protein, lactate dehydrogenase (LDH), and albumin levels in the EM group. Further studies are needed to improve EM activity against pathologic bacteria as a potential alternative to antibiotics and to develop future natural production systems.

Mutations of p53 Gene in Canine Sweat Gland Carcinomas Probably Associated with UV Radiation.

INTRODUCTION: Apocrine sweat gland carcinomas (ASGCs) are rare malignant skin tumours in dogs and humans. The literature published so far focuses mostly on the clinico-epidemiological aspect of these tumours, but little is known about their pathogenesis. In this study we aimed to determine whether the p53 gene is involved in the carcinogenesis of the apocrine sweat gland in dogs and whether ultraviolet radiation (UV) is related to it. MATERIAL AND METHODS: Forty canine ASGCs were submitted to laser capture microdissection to isolate neoplastic cells, from which DNA was subsequently extracted. PCR amplification and sequencing of p53 exons 2-8 was then performed, followed by computer analysis of the obtained sequences. RESULTS: Sixteen mutations within the p53 gene were found in 13 tumours. The mutations involved C → T, T → C, G → A, and CC → TT transitions, C → G transversion and adenine deletion, which are gene alteration types known to be related to UV radiation in the process of skin carcinogenesis in humans. Six of the thirteen tumour cases displayed the C → T transitions in the same location in exon 4 and three of the thirteen cases displayed T → C in the same location in exon 5. CONCLUSION: The results of the present study indicate both the participation of the p53 gene and the influence of UV radiation in the formation of ASGCs in dogs.

Diagnostic immunohistochemistry for canine cutaneous round cell tumours - retrospective analysis of 60 cases.

INTRODUCTION: Canine cutaneous round cell tumours (CCRCTs) include various benign and malignant neoplastic processes. Due to their similar morphology, the diagnosis of CCRCTs based on histopathological examination alone can be challenging, often necessitating ancillary immunohistochemical (IHC) analysis. This study presents a retrospective analysis of CCRCTs. MATERIALS AND METHODS: This study includes 60 cases of CCRCTs, including 55 solitary and 5 multiple tumours, evaluated immunohistochemically using a basic antibody panel (MHCII, CD18, Iba1, CD3, CD79a, CD20 and mast cell tryptase) and, when appropriate, extended antibody panel (vimentin, desmin, a-SMA, S-100, melan-A and pan-keratin). Additionally, histochemical stainings (May-Grünwald-Giemsa and methyl green pyronine) were performed. RESULTS: IHC analysis using a basic antibody panel revealed 27 cases of histiocytoma, one case of histiocytic sarcoma, 18 cases of cutaneous lymphoma of either T-cell (CD3+) or B-cell (CD79a+) origin, 5 cases of plas-macytoma, and 4 cases of mast cell tumours. The extended antibody panel revealed 2 cases of alveolar rhabdo-myosarcoma, 2 cases of amelanotic melanoma, and one case of glomus tumour. CONCLUSIONS: Both canine cutaneous histiocytoma and cutaneous lymphoma should be considered at the beginning of differential diagnosis for CCRCTs. While most poorly differentiated CCRCTs can be diagnosed immunohis-tochemically using 1-4 basic antibodies, some require a broad antibody panel, including mesenchymal, epithelial, myogenic, and melanocytic markers. The expression of Iba1 is specific for canine cutaneous histiocytic tumours, and more sensitive than CD18. The utility of CD20 in the diagnosis of CCRCTs is limited.

Dirofilaria repens-An etiological factor or an incidental finding in cytologic and histopathologic biopsies from dogs.

Dirofilaria repens is an endemic, zoonotic parasite of carnivores, causing subcutaneous dirofilariasis, which is mostly asymptomatic. The aim of this study was to describe 22 cases of canine subcutaneous dirofilariasis. The cytologic and histopathologic samples were collected from dogs, which presented with various clinical signs such as cutaneous/subcutaneous nodules, hydropericardium, ascites, and lymphadenomegaly. The cytologic or histopathologic examination revealed purulent, pyogranulomatous, granulomatous or eosinophilic dermatitis/panniculitis, and the presence of D repens microfilariae or adults. The microfilariae or adults were also found incidentally in neoplastic cutaneous or subcutaneous tumors and in a sialocele. For the first time, microfilariae were also detected and described in pericardial and abdominal effusions and in enlarged reactive lymph nodes. Although it is well known that D repens can cause dermatitis and panniculitis in dogs, no previous reports of D repens microfilariae in body cavity fluids were found. The role of this parasite in the accumulation of body cavity fluid or in reactive lymphadenomegaly requires further investigation. Due to its zoonotic potential, and apparently underestimated pathogenicity, each case of canine subcutaneous dirofilariasis should be treated.

Influence of long-term, high-dose dexamethasone administration on proliferation and apoptosis in porcine hepatocytes.

The aim of this study was to examine the influence of long-term, high-dose dexamethasone administration on the liver, with particular emphasis on hepatocyte proliferation and apoptosis, using a swine model. The study included 48 large, female Polish breed pigs aged 3months (weighing ca. 30kg) divided into groups I (control; n=24) and II (dexamethasone; n=24) that receiving intra-muscular injections of monosodium phosphate dexamethasone for 29days. The pigs were euthanized on days subsequent to the experiment. Immediately after the euthanasia, the pig livers were sampled, fixed, and processed routinely for histopathology, histochemistry, and immunohistochemistry (for proliferating cell nuclear antigen, Bcl-2, and caspase-3). Apoptosis was visualized by terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL). Dexamethasone administration gradually caused hepatocyte glycogen degeneration and finally lipid degeneration, accompanied by sinusoid and central vein dilatation and nuclear chromatin condensation. The proliferating cell nuclear antigen index, mean number of argyrophilic nucleolar organizer regions and proliferation index of argyrophilic nucleolar organizer regions were lower, while Bcl-2 expression was higher in group II compared with group I. The results from this study suggest that safe high-dose dexamethasone administration time is difficult to establish. Long-term, high-dose dexamethasone administration can cause pronounced morphological changes in hepatocytes by diminishing their transcriptional and proliferation activity but also protects them from apoptosis by potentially affecting Bcl-2 expression.

Prostaglandin E2 exerts the proapoptotic and antiproliferative effects on bovine NK cells.

The aim of this research was to determine whether prostaglandin E2 (PGE2) affects bovine NK cells in respect of their counts, apoptosis and proliferation, and if it does, then which of the PGE2 receptor (EP) subtype(s) mediate(s) these effects. We here report that long-term, but not short-term, exposure of bovine peripheral blood mononuclear cells to PGE2 at 10(-5)M, 10(-6)M and 10(-7)M, but not at 10(-8)M, caused a significant increase in the percentage of early apoptotic cells among NK cell subset. Moreover, PGE2 at 10(-5)M and 10(-6)M, but not at 10(-7)M and 10(-8)M, induced a considerable decrease in the absolute count of NK cells. The magnitude of these effects increased with an increasing concentration of PGE2. The blockade of EP1, EP2, EP3 and EP4 receptors did not prevent the PGE2-induced apoptosis and depletion of NK cells. The results suggest that the proapoptotic effect of PGE2 is secondary in character and the induction of this effect is not mediated through EP receptors. Furthermore, the studies demonstrated that PGE2 at 10(-5)M and 10(-6)M, but not at 10(-7)M and 10(-8)M, highly significantly reduced the percentage of proliferating NK cells. The EP1, EP1/2 and EP3 receptor antagonists were unable to block this effect significantly, whereas the selective blockade of EP4 receptors prevented the PGE2-induced inhibition of NK cells proliferation. These results indicate that PGE2 at certain concentrations may impair the proliferation of NK cells and this effect is mediated via the EP4 receptor.

IκB kinase ß inhibitor, IMD-0354, prevents allergic asthma in a mouse model through inhibition of CD4(+) effector T cell responses in the lung-draining mediastinal lymph nodes.

IκB kinase (IKK) is important for nuclear factor (NF)-κB activation under inflammatory conditions. It has been demonstrated that IMD-0354, i.e. a selective inhibitor of IKKß, inhibited allergic inflammation in a mouse model of ovalbumin (OVA)-induced asthma. The present study attempts to shed light on the involvement of CD4(+) effector (Teff) and regulatory (Treg) T cells in the anti-asthmatic action of IMD-0354. The animals were divided into three groups: vehicle treated, PBS-sensitized/challenged mice (PBS group); vehicle treated, OVA-sensitized/challenged mice (OVA group); and IMD-0354-treated, OVA-sensitized/challenged mice. The analyzed parameters included the absolute counts of Treg cells (Foxp3(+)CD25(+)CD4(+)), activated Teff cells (Foxp3(-)CD25(+)CD4(+)) and resting T cells (CD25(-)CD4(+)) in the mediastinal lymph nodes (MLNs), lungs and peripheral blood. Moreover, lung histopathology was performed to evaluate lung inflammation. It was found that the absolute number of cells in all studied subsets was considerably increased in the MLNs and lungs of mice from OVA group as compared to PBS group. All of these effects were fully prevented by treatment with IMD-0354. Histopathological examination showed that treatment with IMD-0354 protected the lungs from OVA-induced allergic airway inflammation. Our results indicate that IMD-0354 exerts anti-asthmatic action, at least partially, by blocking the activation and clonal expansion of CD4(+) Teff cells in the MLNs, which, consequently, prevents infiltration of the lungs with activated CD4(+) Teff cells. The beneficial effects of IMD-0354 in a mouse model of asthma are not mediated through increased recruitment of Treg cells into the MLNs and lungs and/or local generation of inducible Treg cells.