Comparative analysis of primer sets for the assessment of clonality in feline lymphomas.

Introduction: Lymphomas are among the most important and common malignant tumors in cats. Differentiating lymphomas from reactive lymphoid proliferations can be challenging, so additional tools such as clonality assessment by PCR are important in diagnosis finding. Several PCR assays have been developed to assess clonality in feline lymphomas. For T-cell lymphomas TRG (T-cell receptor gamma) genes are the preferred target whereas for B-cell lymphomas most primer sets target immunoglobulin heavy chain (IGH) genes. Here we compare commonly used diagnostic primer sets for the assessment of clonality in feline lymphomas under controlled conditions (i.e., identical sample set, PCR setup, amplicon detection system). Methods: Formalin-fixed and paraffin-embedded samples from 31 feline T-cell lymphomas, 29 B-cell lymphomas, and 11 non-neoplastic controls were analyzed by PCR combined with capillary electrophoresis. Results and discussion: We show that the combination of the primer sets published by Weiss et al. and Mochizuki et al. provided the best results for T-cell clonality, i.e., correctly assigns most populations as clonal or polyclonal. For B-cell clonality, the combination of the primer sets by Mochizuki et al. and Rout et al. gave the best results when omitting the Kde gene rearrangement due to its low specificity. This study rigorously evaluated various primer sets under uniform experimental conditions to improve accuracy of lymphoma diagnostic and provides a recommendation for achieving the highest diagnostic precision in lymphoma clonality analysis.

Hepatocyte integrity depends on c-Jun-controlled proliferation in Schistosoma mansoni infected mice.

Schistosomiasis is a parasitic disease affecting more than 250 million people worldwide. The transcription factor c-Jun, which is induced in S. mansoni infection-associated liver disease, can promote hepatocyte survival but can also trigger hepatocellular carcinogenesis. We aimed to analyze the hepatic role of c-Jun following S. mansoni infection. We adopted a hepatocyte-specific c-Jun knockout mouse model (Alb-Cre/c-Jun loxP) and analyzed liver tissue and serum samples by quantitative real-time PCR array, western blotting, immunohistochemistry, hydroxyproline quantification, and functional analyses. Hepatocyte-specific c-Jun knockout (c-JunΔli) was confirmed by immunohistochemistry and western blotting. Infection with S. mansoni induced elevated aminotransferase-serum levels in c-JunΔli mice. Of note, hepatic Cyclin D1 expression was induced in infected c-Junf/f control mice but to a lower extent in c-JunΔli mice. S. mansoni soluble egg antigen-induced proliferation in a human hepatoma cell line was diminished by inhibition of c-Jun signaling. Markers for apoptosis, oxidative stress, ER stress, inflammation, autophagy, DNA-damage, and fibrosis were not altered in S. mansoni infected c-JunΔli mice compared to infected c-Junf/f controls. Enhanced liver damage in c-JunΔli mice suggested a protective role of c-Jun. A reduced Cyclin D1 expression and reduced hepatic regeneration could be the reason. In addition, it seems likely that the trends in pathological changes in c-JunΔli mice cumulatively led to a loss of the protective potential being responsible for the increased hepatocyte damage and loss of regenerative ability.

Impact of age on liver damage, inflammation, and molecular signaling pathways in response to femoral fracture and hemorrhage.

Background: Trauma causes disability and mortality globally, leading to fractures and hemorrhagic shock. This can trigger an irregular inflammatory response that damages remote organs, including liver. Aging increases the susceptibility to dysregulated immune responses following trauma, raising the risk of organ damage, infections, and higher morbidity and mortality in elderly patients. This study investigates how aging affects liver inflammation and damage post-trauma. Methods: 24 male C57BL/6J mice were randomly divided into four groups. Twelve young (17-26 weeks) and 12 aged (64-72 weeks) mice were included. Mice further underwent either hemorrhagic shock (trauma/hemorrhage, TH), and femoral fracture (osteotomy) with external fixation (Fx) (THFx, n=6) or sham procedures (n=6). After 24 hours, mice were sacrificed. Liver injury and apoptosis were evaluated using hematoxylin-eosin staining and activated caspase-3 immunostaining. CXCL1 and infiltrating polymorphonuclear leukocytes (PMNL) in the liver were assessed by immunostaining, and concentrations of CXCL1, TNF, IL-1ß, and IL-10 in the liver tissue were determined by ELISA. Gene expression of Tnf, Cxcl1, Il-1ß, and Cxcl2 in the liver tissue was determined by qRT-PCR. Finally, western blot was used to determine protein expression levels of IκBα, Akt, and their phosphorylated forms. Results: THFx caused liver damage and increased presence of active caspase-3-positive cells compared to the corresponding sham group. THFx aged group had more severe liver injury than the young group. CXCL1 and PMNL levels were significantly higher in both aged groups, and THFx caused a greater increase in CXCL and PMNL levels in aged compared to the young group. Pro-inflammatory TNF and IL-1ß levels were elevated in aged groups, further intensified by THFx. Anti-inflammatory IL-10 levels were lower in aged groups. Tnf and Cxcl1 gene expression was enhanced in the aged sham group. Phosphorylation ratio of IκBα was significantly increased in the aged sham group versus young sham group. THFx-induced IκBα phosphorylation in the young group was significantly reduced in the aged THFx group. Akt phosphorylation was significantly reduced in the THFx aged group compared to the THFx young group. Conclusion: The findings indicate that aging may lead to increased vulnerability to liver injury and inflammation following trauma due to dysregulated immune responses.

Age-related exacerbation of lung damage after trauma is associated with increased expression of inflammasome components.

Background: Trauma, a significant global cause of mortality and disability, often leads to fractures and hemorrhagic shock, initiating an exaggerated inflammatory response, which harms distant organs, particularly the lungs. Elderly individuals are more vulnerable to immune dysregulation post-trauma, leading to heightened organ damage, infections, and poor health outcomes. This study investigates the role of NF-κB and inflammasomes in lung damage among aged mice post-trauma. Methods: Twelve male C57BL/6J mice underwent hemorrhagic shock and a femoral fracture (osteotomy) with external fixation (Fx) (trauma/hemorrhage, THFx), while another 12 underwent sham procedures. Mice from young (17-26 weeks) and aged (64-72 weeks) groups (n=6) were included. After 24h, lung injury was assessed by hematoxylin-eosin staining, prosurfactant protein C (SPC) levels, HMGB1, and Muc5ac qRT-PCR. Gene expression of Nlrp3 and Il-1ß, and protein levels of IL-6 and IL-1ß in lung tissue and bronchoalveolar lavage fluid were determined. Levels of lung-infiltrating polymorphonuclear leukocytes (PMNL) and activated caspase-3 expression to assess apoptosis, as well as NLRP3, ASC, and Gasdermin D (GSDMD) to assess the expression of inflammasome components were analyzed via immunostaining. To investigate the role of NF-κB signaling, protein expression of phosphorylated and non-phosphorylated p50 were determined by western blot. Results: Muc5ac, and SPC as lung protective proteins, significantly declined in THFx versus sham. THFx-aged exhibited significantly lower SPC and higher HMGB1 levels versus THFx-young. THFx significantly increased activated caspase-3 versus both sham groups, and THFx-aged had significantly more caspase-3 positive cells versus THFx-young. IL-6 significantly increased in both sham and THFx-aged groups versus corresponding young groups. THFx significantly enhanced PMNL in both groups versus corresponding sham groups. This increase was further heightened in THFx-aged versus THFx-young. Expression of p50 and phosphorylated p50 increased in all aged groups, and THFx-induced p50 phosphorylation significantly increased in THFx-aged versus THFx-young. THFx increased the expression of inflammasome markers IL-1ß, NLRP3, ASC and GSDMD versus sham, and aging further amplified these changes significantly. Conclusion: This study's findings suggest that the aging process exacerbates the excessive inflammatory response and damage to the lung following trauma. The underlying mechanisms are associated with enhanced activation of NF-κB and increased expression of inflammasome components.

Acute Intoxication With Alcohol Reduces Trauma-Induced Proinflammatory Response and Barrier Breakdown in the Lung via the Wnt/ß-Catenin Signaling Pathway.

Background: Trauma is the third leading cause of mortality worldwide. Upon admission, up to 50% of traumatized patients are acutely intoxicated with alcohol, which might lead to aberrant immune responses. An excessive and uncontrolled inflammatory response to injury is associated with damage to trauma-distant organs. We hypothesize that, along with inflammation-induced apoptosis, the activation of the Wnt/ß-catenin signaling pathway would cause breakdown of the lung barrier and the development of lung injury after trauma. It remains unclear whether ethanol intoxication (EI) prior to trauma and hemorrhagic shock will attenuate inflammation and organ injury. Methods: In this study, 14 male C57BL/6J mice were randomly assigned to two groups and exposed either to EtOH or to NaCl as a control by an oral gavage before receiving a femur fracture (Fx) and hemorrhagic shock, followed by resuscitation (THFx). Fourteen sham animals received either EtOH or NaCl and underwent surgical procedures without THFx induction. After 24 h, oil red O staining of fatty vacuoles in the liver was performed. Histological lung injury score (LIS) was assessed to analyze the trauma-induced RLI. Gene expression of Cxcl1, Il-1ß, Muc5ac, Tnf, and Tnfrsf10b as well as CXCL1, IL-1ß, and TNF protein levels in the lung tissue and bronchoalveolar lavage fluid were determined by RT-qPCR, ELISA, and immunohistological analyses. Infiltrating polymorphonuclear leukocytes (PMNLs) were examined via immunostaining. Apoptosis was detected by activated caspase-3 expression in the lung tissue. To confirm active Wnt signaling after trauma, gene expression of Wnt3a and its inhibitor sclerostin (Sost) was determined. Protein expression of A20 and RIPK4 as possible modulators of the Wnt signaling pathway was analyzed via immunofluorescence. Results: Significant fatty changes in the liver confirmed the acute EI. Histopathology and decreased Muc5ac expression revealed an increased lung barrier breakdown and concomitant lung injury after THFx versus sham. EI prior trauma decreased lung injury. THFx increased not only the gene expression of pro-inflammatory markers but also the pulmonary infiltration with PMNL and apoptosis versus sham, while EI prior to THFx reduced those changes significantly. EI increased the THFx-reduced gene expression of Sost and reduced the THFx-induced expression of Wnt3a. While A20, RIPK4, and membranous ß-catenin were significantly reduced after trauma, they were enhanced upon EI. Conclusion: These findings suggest that acute EI alleviates the uncontrolled inflammatory response and lung barrier breakdown after trauma by suppressing the Wnt/ß-catenin signaling pathway.

Benign mixed Müllerian (duct) vaginal tumor in a 12-y-old goat.

In human and veterinary medicine, mixed Müllerian tumors (MMTs) are rarely diagnosed neoplasms of the tubular female genital tract. Although there are case reports of malignant MMTs in various species, benign MMTs have only been described once in a macaque. Here we present a case of benign MMT in a 12-y-old goat, and review the literature on uterine, cervical, and vaginal neoplasia in goats. The doe was presented with vaginal discharge and was euthanized because of the high suspicion of intraabdominal neoplasia. On gross examination, an ulcerated vaginal mass was identified. Histologically, 2 distinct cell populations were present: smooth muscle cells that were well differentiated and positive for alpha-smooth muscle actin, and ciliated columnar epithelial cells that lined ductal structures and had no signs of malignancy. These findings led to the diagnosis of neoplasia of Müllerian origin. Benign MMT should be considered as a differential diagnosis for uterine and vaginal neoplasms in goats.

Gammaherpesvirus Infections in Cattle in Europe.

The genus Macavirus, subfamily Gammaherpesvirinae, comprises ungulate viruses that infect domestic and wild ruminants and swine. They cause asymptomatic latent infections in reservoir hosts and malignant catarrhal fever in susceptible species. Lung, spleen, bronchial lymph node, and tongue were collected from 448 cattle (348 necropsied, 100 slaughtered) in Switzerland, United Kingdom, Finland, Belgium, and Germany to determine their infection with bovine herpesvirus-6 (BoHV-6) and gammaherpesviruses of other ruminants, i.e., ovine herpesvirus-1 and -2, caprine herpesvirus-2, and bison lymphotropic herpesvirus, using quantitative PCR. Only BoHV-6 was detected, with an overall frequency of 32%, ranging between 22% and 42% in the different countries. Infection was detected across all ages, from one day after birth, and was positively correlated with age. There was no evidence of an association with specific disease processes. In positive animals, BoHV-6 was detected in all organs with high frequency, consistently in the lungs or spleen. Viral loads varied substantially. In BoHV-6-positive gravid cows, organs of fetuses tested negative for infection, indicating that the virus is not vertically transmitted. Our results confirm previous data indicating that BoHV-6 is a commensal of domestic cattle not associated with disease processes and confirm that infections with other macaviruses are rare and sporadic.

Systemic versus local adipokine expression differs in a combined obesity and osteoarthritis mouse model.

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage loss and reduced joint function. OA risk factors are age and obesity. Many adipokines are altered by obesity but also OA although systemic adipokine regulation in OA is not always clear. Therefore, metabolic effects of diet-induced obesity on OA development as well as the influence of obesity and OA progression on systemic vs. local adipokine expression in joints were compared. C57Bl/6-mice fed with HFD (high fat diet) or normal diet prior to destabilization of the medial meniscus (DMM) were sacrificed 4/6/8 weeks after surgery. Sera were evaluated for adiponectin, leptin, visfatin, cytokines. Liver grading and staging for non-alcoholic steatohepatitis (NASH) was performed and crown-like structures (CLS) in adipose tissue measured. OA progression was scored histologically. Adipokine-expressing cells and types were evaluated by immunohistochemistry. Time-dependent changes in DMM-progression were reflected by increased systemic adiponectin levels in DMM especially combined with HFD. While HFD increased serum leptin, DMM reduced systemic leptin significantly. OA scores correlated with bodyweight, leptin and hepatic scoring. Locally, increased numbers of adiponectin- and leptin-producing fibroblasts were observed in damaged menisci but visfatin was not changed. Local adipokine expression was independent from systemic levels, suggesting different mechanisms of action.

Atypical myopathy in 2 Bactrian camels.

Atypical myopathy (AM) is an acute seasonal rhabdomyolysis seen primarily in equids, caused by the ingestion of sycamore maple samaras containing hypoglycin A (HGA) and methylenecyclopropyl-glycine (MCPG). Toxic metabolites inhibit acyl-CoA dehydrogenases and enoyl-CoA hydratases, causing selective hyaline degeneration of type I muscle fibers. Two zoo-kept Bactrian camels (Camelus bactrianus) with a fatal course of AM had sudden onset of muscle pain and weakness, recumbency, and dysphagia, accompanied by increased serum creatine kinase activity and detection in serum of HGA, MCPG, and metabolites. Medical treatment was ineffective. At postmortem examination, sycamore maple tree material was found within the first gastric compartment of the 2-y-old gelding. Although musculature was macroscopically normal, histologically, monophasic hyaline degeneration was marked within type I fibers of intercostal and hypoglossal muscles of the gelding, and in neck, tongue, and masticatory muscles of the cow. The ingestion of sycamore maple material can cause AM in Bactrian camels, and trees of the Sapindaceae family should be avoided in enclosures.

Club Cell Protein 16 Attenuates CD16brightCD62dim Immunosuppressive Neutrophils in Damaged Tissue upon Posttraumatic Sepsis-Induced Lung Injury.

BACKGROUND: Recently, identification of immunosuppressive polymorphonuclear leukocytes (PMNL) that were traditionally described as proinflammatory cells emerged in the field of posttraumatic immunity. To understand their local and remote distribution after trauma, PMNL-subsets and the impact of immunomodulatory Club Cell protein (CC)16 that correlates with pulmonary complications were assessed. METHODS: C57BL/6N mice were divided into three groups, receiving isolated blunt chest trauma (TxT), undergoing TxT followed by cecal ligation and puncture (CLP, TxT + CLP) after 24 h, or sham undergoing analgosedation (n = 18/group). Further, each group was subdivided into three groups receiving either no treatment (ctrl) or intratracheal neutralization of CC16 by application of anti-CC16-antibody or application of an unspecific IgG control antibody (n = 6/group). Treatment was set at the time point after TxT. Analyses followed 6 h post-CLP. PMNL were characterized via expression of CD11b, CD16, CD45, CD62L, and Ly6G by flow cytometry in bone marrow (BM), blood, spleen, lung, liver, and bronchoalveolar and peritoneal lavage fluid (BALF and PL). Apoptosis was assessed by activated (cleaved) caspase-3. Results from untreated ctrl and IgG-treated mice were statistically comparable between all corresponding sham, TxT, and TxT + CLP groups. RESULTS: Immature (CD16dimCD62Lbright) PMNL increased significantly in BM, circulation, and spleen after TxT vs. sham and were significantly attenuated in the lungs, BALF, PL, and liver. Classical-shaped (CD16brightCD62Lbright) PMNL increased after TxT vs. sham in peripheral tissue and were significantly attenuated in circulation, proposing a trauma-induced migration of mature or peripheral differentiation of circulating immature PMNL. Immunosuppressive (CD16brightCD62Ldim) PMNL decreased significantly in the lungs and spleen, while they systemically increased after TxT vs. sham. CLP in the TxT + CLP group reduced immunosuppressive PMNL in PL and increased their circulatory rate vs. isolated TxT, showing local reduction in affected tissue and their increase in nonaffected tissue. CC16 neutralization enhanced the fraction of immunosuppressive PMNL following TxT vs. sham and decreased caspase-3 in the lungs post-CLP in the TxT + CLP group, while apoptotic cells in the liver diminished post-TxT. Posttraumatic CC16 neutralization promotes the subset of immunosuppressive PMNL and antagonizes their posttraumatic distribution. CONCLUSION: Since CC16 affects both the distribution of PMNL subsets and apoptosis in tissues after trauma, it may constitute as a novel target to beneficially shape the posttraumatic tissue microenvironment and homeostasis to improving outcomes.

Differential diagnosis for a mandibular mass - a rare case of an odontoameloblastoma in a red deer (Cervus elaphus elaphus).

BACKGROUND: Mandibular masses caused by inflammatory processes due to bacterial infections, most common with Actinomyces bovis, are well known in herbivors. This case represents a rare differential diagnosis to common inflammatory processes which cannot be distinguished from neoplasia without detailed histopathological examination. CASE PRESENTATION: A large unilateral mandibular mass of a free-ranging female adult red deer (Cervus elaphus elaphus) was submitted for pathological examination. The animal had been shot due to its poor body condition. Grossly, the mandibular mass showed gingival ulceration and necrosis. Histologically, irregular strands and islands of odontogenic epithelial cells and a matrix of dentin and osteoid-like material were found, leading to the diagnosis of an odontogenic tumor. Considering the animal's age the tumor was classified as odontoameloblastoma with secondary chronic purulent osteomyelitis. CONCLUSIONS: Odontogenic tumors are rare in domestic and wildlife species and so far have not been reported in red deer. In addition to the more common inflammatory processes of the mandibula and other neoplastic diseases of the oral cavity, odontogenic tumors represent a rare differential diagnosis that must be kept in mind especially when masked by inflammatory lesions.

Echinococcus multilocularis infection in horses in Poland.

A cross-sectional survey was performed to obtain first information on the prevalence of Echinococcus multilocularis infection in slaughter horses from central, eastern and southern Poland, a country with a highly endemic occurrence of this tapeworm in red foxes. White tough nodular lesions being 3-10 mm in size, sharply demarcated and spherically or irregularly shaped were found in 54 of 365 livers examined. Histologically, focal granulomatous necrotizing inflammations and sometimes PAS-positive acellular lamellar structures being characteristic of the E. multilocularis metacestode stage were visible; protoscoleces were not found. E. multilocularis DNA was detected in six of 19 hepatic lesions examined by nested PCR. Our results from molecular and morphological diagnostics suggest an overall prevalence of alveolar echinococcosis between 4.7% and 14.8% in the horse population studied. Horses as dead-end hosts do not play any role in the life cycle of E. multilocularis but may serve as additional sentinel animals in monitoring the environmental contamination with tapeworm eggs.

Schistosoma mansoni eggs induce Wnt/ß-catenin signaling and activate the protooncogene c-Jun in human and hamster colon.

Schistosomiasis (bilharzia) is a neglected tropical disease caused by parasitic flatworms of the genus Schistosoma, with considerable morbidity in parts of the Middle East, South America, Southeast Asia, in sub-Saharan Africa, and particularly also in Europe. The WHO describes an increasing global health burden with more than 290 million people threatened by the disease and a potential to spread into regions with temperate climates like Corsica, France. The aim of our study was to investigate the influence of S. mansoni infection on colorectal carcinogenic signaling pathways in vivo and in vitro. S. mansoni infection, soluble egg antigens (SEA) and the Interleukin-4-inducing principle from S. mansoni eggs induce Wnt/ß-catenin signaling and the protooncogene c-Jun as well as downstream factor Cyclin D1 and markers for DNA-damage, such as Parp1 and γH2a.x in enterocytes. The presence of these characteristic hallmarks of colorectal carcinogenesis was confirmed in colon biopsies from S. mansoni-infected patients demonstrating the clinical relevance of our findings. For the first time it was shown that S. mansoni SEA may be involved in the induction of colorectal carcinoma-associated signaling pathways.

[Uterine serosal inclusion cysts in the dog - case report and literature review of canine uterine cysts]. / Serosazysten am Uterus der Hündin ­ Fallbericht und Literaturübersicht zu kaninen Uteruszysten.

In bitches, uterine cysts are usually associated with pathological conditions. Serosal inclusion cysts of the uterus represent an exception to this rule. These thin-walled cysts develop on the uterine surface and occur either as single or multiple cysts. The cysts lack endocrine activity and usually do not cause clinical symptoms. Their occurrence shows no association to the estrus cycle. Serosal inclusion cysts are mainly found in older multiparous bitches and large breeds are more often affected. Diagnosis of serosal inclusion cysts may be achieved by transabdominal sonography. Differentiation between uterine and ovarian serosal inclusion cysts is possibly challenging as serosal inclusion cysts are often located in the area of the tip of the uterine horn. This report presents the case of a breeding bitch with multiple uterine serosal inclusion cysts detected during caesarean section. The concentrations of estradiol 17ß and progesterone in the cyst fluid corresponded to the blood concentrations of these hormones in a bitch during parturition. The concentrations of total calcium, zinc, copper, and iron in the cyst fluid were below the reference values in canine blood whereas the concentrations of magnesium, phosphorus, sodium, and potassium in the cyst fluid were comparable to pertaining blood levels.

Different experimental multiple trauma models induce comparable inflammation and organ injury.

Multiple injuries appear to be a decisive factor for experimental polytrauma. Therefore, our aim was to compare the inflammatory response and organ damage of five different monotrauma with three multiple trauma models. For this, mice were randomly assigned to 10 groups: Healthy control (Ctrl), Sham, hemorrhagic shock (HS), thoracic trauma (TxT), osteotomy with external fixation (Fx), bilateral soft tissue trauma (bsTT) or laparotomy (Lap); polytrauma I (PT I, TxT + HS + Fx), PT II (TxT + HS + Fx + Lap) and one multi-trauma group (MT, TxT + HS + bsTT + Lap). The inflammatory response and organ damage were quantified at 6 h by analyses of IL-6, IL-1ß, IL-10, CXCL1, SAA1, HMGB1 and organ injury. Systemic IL-6 increased in all mono and multiple trauma groups, while CXCL1 increased only in HS, PT I, PT II and MT vs. control. Local inflammatory response was most prominent in HS, PT I, PT II and MT in the liver. Infiltration of inflammatory cells into lung and liver was significant in all multiple trauma groups vs. controls. Hepatic and pulmonary injury was prominent in HS, PT I, PT II and MT groups. These experimental multiple trauma models closely mimic the early post-traumatic inflammatory response in human. Though, the choice of read-out parameters is very important for therapeutic immune modulatory approaches.

Ethyl Pyruvate Reduces Systemic Leukocyte Activation via Caspase-1 and NF-κB After Blunt Chest Trauma and Haemorrhagic Shock.

Background: Blunt chest (thoracic) trauma (TxT) and haemorrhagic shock with subsequent resuscitation (H/R) induce strong systemic and local inflammatory response, which is closely associated with apoptotic cell loss and subsequently impaired organ function. The underlying mechanisms are not completely understood, therefore, the treatment of patients suffering from TxT+H/R is challenging. In our recent studies, we have demonstrated local anti-inflammatory effects of ethyl pyruvate (EtP) in lung and liver after TxT+H/R. Here, the therapeutic potential of a reperfusion regime with EtP on the early post-traumatic systemic inflammatory response and apoptotic changes after TxT followed by H/R were investigated. Methods: Female Lewis rats underwent TxT followed by haemorrhagic shock (60 min). Resuscitation was performed with own blood transfusion and either lactated Ringers solution (LR) or LR supplemented with EtP (50 mg/kg). Sham group underwent the surgical procedures. After 2 h blood as well as lung and liver tissues were obtained for analyses. Systemic activation of neutrophils (expression of CD11b and CD62L), leukocyte phagocytosis, apoptosis (caspase-3/7 activation), pyroptosis (caspase-1 activation) and NF-κB p65 activity were assessed. p < 0.05 was considered significant. Results: TxT+H/R-induced systemic activation of neutrophils (increased CD11b and reduced CD62L expression) was significantly reduced by EtP. Trauma-induced delayed neutrophil apoptosis was further reduced by EtP reperfusion but remained unaltered in monocytes. Reperfusion with EtP significantly increased the phagocytizing capacity of granulocytes. Trauma-induced inflammasome activation, which was observed in monocytes and not in neutrophils, was significantly reduced by EtP in both cell entities. NF-κB p65 activation, which was increased in neutrophils and monocytes was significantly decreased in monocytes. Conclusion: TxT+H/R-induced systemic activation of both neutrophils and monocytes concomitant with increased systemic inflammation was reduced by a reperfusion with EtP and was associated with a down-regulation of NF-κB p65 activation.

[Listeriosis in a chinchilla herd - a case report]. / Listeriose beim Chinchilla als Bestandsproblem ­ ein Fallbericht.

A 6-year-old female chinchilla from a small colony in residential housing was presented due to lethargy and anorexia. Besides a ketoacidosis diagnosed by urinalysis, sepsis was suspected. Symptomatic treatment did not lead to any improvement, in consequence the animal was euthanized. On the basis of histopathological, immunohistological, and bacteriological examinations an infection with Listeria monocytogenes was diagnosed. The pathogen was also detectable in the feces of 2 other animals of the herd, one of which died and the other survived. The herd was treated with antibiotics following microbiologic sensitivity testing. At the end of the 2-month observation period, 3 out of 7 chinchillas were still alive. The presented case report describes the detection of listeriosis in pet chinchillas, the pathogenesis of the disease, as well as the diagnostic options and therapy.

Reactive mesothelial hyperplasia mimicking mesothelioma in an African green monkey (Chlorocebus aethiops).

A spontaneous reactive mesothelial hyperplasia occurred in a female, 15.7-year-old African green monkey (grivet; Chlorocebus aethiops). At necropsy, massive effusions were found in the abdomen, the thorax, and the pericardium. Additionally, multiple small, beige-gray nodules were detected on the serosal surfaces of the abdominal organs. Histopathologically, the mesothelial cells resembled the epithelioid subtype of a mesothelioma, but no infiltrative or invasive growth could be demonstrated. The mesothelial cells on the thoracis, liver, and intestinal serosa were accompanied by chronic serositis. Mesothelial cells expressed cytokeratin, vimentin, calretinin, desmin, Wilms Tumor 1 (WT-1) protein, and epithelial membrane antigen (EMA). Cells were negative for carcinoembryonic antigen (CEA), cluster of differentiation 15 (CD15), and podoplanin. Ultrastructurally, cells revealed a moderate amount of microvilli of medium length, perinuclear tonofilament bundles, and long desmosomes. In fluorescence in situ hybridization (FISH) for the detection of characteristic gene loss (p16; CDKN2A), NF2, and MTAP, no deletions were detected. No asbestos fibers and no presence of Simian virus 40 antigen (SV40) could be demonstrated.

YARS2 Missense Variant in Belgian Shepherd Dogs with Cardiomyopathy and Juvenile Mortality.

Dog puppy loss by the age of six to eight weeks after normal development is relatively uncommon. Necropsy findings in two spontaneously deceased Belgian Shepherd puppies indicated an abnormal accumulation of material in several organs. A third deceased puppy exhibited mild signs of an inflammation in the central nervous system and an enteritis. The puppies were closely related, raising the suspicion of a genetic cause. Pedigree analysis suggested a monogenic autosomal recessive inheritance. Combined linkage and homozygosity mapping assigned the most likely position of a potential genetic defect to 13 genome segments totaling 82 Mb. The genome of an affected puppy was sequenced and compared to 645 control genomes. Three private protein changing variants were found in the linked and homozygous regions. Targeted genotyping in 96 Belgian Shepherd dogs excluded two of these variants. The remaining variant, YARS2:1054G>A or p.Glu352Lys, was perfectly associated with the phenotype in a cohort of 474 Belgian Shepherd dogs.YARS2 encodes the mitochondrial tyrosyl-tRNA synthetase 2 and the predicted amino acid change replaces a negatively charged and evolutionary conserved glutamate at the surface of the tRNA binding domain of YARS2 with a positively charged lysine. Human patients with loss-of-function variants in YARS2 suffer from myopathy, lactic acidosis, and sideroblastic anemia 2, a disease with clinical similarities to the phenotype of the studied dogs. The carrier frequency was 27.2% in the tested Belgian Shepherd dogs. Our data suggest YARS2:1054G>A as the candidate causative variant for the observed juvenile mortality.