Evaluation of White Striping prevalence and predisposing factors in broilers at slaughter

White striping ( WS: ) is an alteration of breast and thigh muscles of broiler chickens characterized by the presence of white striations parallel to the direction of muscle fibers. This study was performed to evaluate the prevalence and the predisposing factors to WS in commercial broilers of different weight reared in northern Italy. Fifty seven broiler flocks, including animals of medium- and heavy-weight, were grossly evaluated at slaughter for the presence of WS. For each flock, breeding data (mean BW at slaughter, ADG, sex, color of skin and fat, genetic line, age, antibiotic treatment, and prevalence of deep pectoral myopathy) were collected and statistically analyzed to assess their correlation with WS. Histology of breast fillets affected by different grades of WS was performed to evaluate potential differences between medium- and heavy-weight broilers. The overall prevalence of WS in medium- and heavy-weight broilers (mean BW 2.59 \ub1 0.13 kg and 3.64 \ub1 0.34 kg, respectively) was 70.2 \ub1 7.9% and 82.51 \ub1 8.5%, respectively, while the percentage of severe WS was 13.3 \ub1 7.1% and 25.7 \ub1 12.8%, respectively. A strong correlation was found between presence of WS, BW at slaughter, and ADG (Pearson correlation = 0.69, P < 0.01; Pearson correlation = 0.67, P < 0.01). WS also closely correlated with the prevalence of deep pectoral myopathy (Spearman's Rho slaughterhouse 1 = 0.74, Spearman's Rho slaughterhouse 2 = 0.51, P < 0.01). No correlation was found between genetics or sanitary status of the flock and WS. Histology confirmed that breasts with WS lesions were affected by a polyphasic degenerative and necrotizing myopathy, and that the lesions, as expected, were more severe in heavy-weight broilers. In conclusion, WS is a major concern in commercial meat poultry reared in Italy, affecting more severely heavier broilers, and it is mainly related to the BW and ADG of animals

Dose and batch-dependent hepatobiliary toxicity of 10 nm silver nanoparticles

Silver nanoparticles (AgNPs) are widely used because of their antimicrobial properties in medical devices and in a variety of consumer products. The extensive use of AgNPs raises concerns about their potential toxicity, although it is still difficult to draw definite conclusions about their toxicity based on published data. Our preliminary studies performed to compare the effect of the AgNPs size (10-40-100 nm) on toxicity, demonstrated that the smallest AgNPs determine the most severe toxicological effects. In order to best investigate the impact of physicochemical characteristics of 10 nm AgNPs on toxicity, we compare three different batches of 10 nm AgNPs slightly different in size distribution (Batch A: 8.8±1.7 nm; Batch B: 9.4±1.7 nm; Batch C: 10.0±1.8 nm). Mice were intravenously treated with two doses (5 and 10 mg/kg) of the 3 AgNPs. 24 hours after the treatment, mice were euthanized and underwent complete necropsy. Tissues were collected for histopathological examination and total silver content was determined in tissues by inductively coupled plasma mass spectrometry (ICP-MS). All batches induced severe hepatobiliary lesions, i.e. marked hepatocellular necrosis and massive hemorrhage of the gall bladder. The toxicity was dose-dependent and interestingly, the toxic effects were more severe in mice treated with batches A and B that contained smaller AgNPs. Since the total silver mass concentration was similar, the observed batch-dependent toxicity suggest that even subtle differences in size may contribute to relevant changes in the toxicological outcomes, confirming the fundamental involvement of physicochemical features with respect to toxicity

Localization of Helicobacter spp. in the fundic mucosa of laboratory Beagle dogs: an ultrastructural study

In dogs Helicobacter spp. are found in all gastric regions usually localized in the surface mucus, gastric glands and parietal cells. The aim of this study was to detail the distribution of Helicobacter spp. in the fundic mucosa of asymptomatic Beagle dogs and their intracellular localization within parietal cells, in order to evaluate species-specific pathogenetic effects on gastric cells. The presence of Helicobacter spp. was investigated by immunohistochemistry, TEM, and PCR in the fundic mucosa of six Beagle dogs. Helicobacter spp. were found in all dogs examined, and H. bizzozeronii and H. felis were identified by PCR and confirmed by TEM. In the lumen of the fundic glands, co-localization was common. H. bizzozeronii was present in larger numbers than H. felis in both intraluminal and intraparietal localization. The amounts of H. bizzozeronii were similar in superficial and basal portions of the glands. H. felis was predominantly localized in the superficial portions of gastric glands but almost absent from the base. Within parietal cells, most Helicobacter organisms were intracanalicular, but intact and degenerate Helicobacter organisms were also visualized free in the cytoplasm or in secondary lysosomes. No specific degenerative lesions were found in infected parietal cells. Helicobacter organisms were also observed within macrophages in the lamina propria. In conclusion, there is a differential distribution of H. bizzozeronii and H. felis in the fundic mucosa of Beagle dogs, and their intracellular localization in parietal cells and macrophages suggests novel pathogenic scenarios for the development of immune response and maintenance of chronic gastritis in dogs

Tissue distribution and acute toxicity of silver after single intravenous administration in mice: nano-specific and size-dependent effects

Background: Silver nanoparticles (AgNPs) are an important class of nanomaterials used as antimicrobial agents for a wide range of medical and industrial applications. However toxicity of AgNPs and impact of their physicochemical characteristics in in vivo models still need to be comprehensively characterized. The aim of this study was to investigate the effect of size and coating on tissue distribution and toxicity of AgNPs after intravenous administration in mice, and compare the results with those obtained after silver acetate administration. Methods: Male CD-1(ICR) mice were intravenously injected with AgNPs of different sizes (10 nm, 40 nm, 100 nm), citrate-or polyvinylpyrrolidone-coated, at a single dose of 10 mg/kg bw. An equivalent dose of silver ions was administered as silver acetate. Mice were euthanized 24 h after the treatment, and silver quantification by ICP-MS and histopathology were performed on spleen, liver, lungs, kidneys, brain, and blood. Results: For all particle sizes, regardless of their coating, the highest silver concentrations were found in the spleen and liver, followed by lung, kidney, and brain. Silver concentrations were significantly higher in the spleen, lung, kidney, brain, and blood of mice treated with 10 nm AgNPs than those treated with larger particles. Relevant toxic effects (midzonal hepatocellular necrosis, gall bladder hemorrhage) were found in mice treated with 10 nm AgNPs, while in mice treated with 40 nm and 100 nm AgNPs lesions were milder or negligible, respectively. In mice treated with silver acetate, silver concentrations were significantly lower in the spleen and lung, and higher in the kidney than in mice treated with 10 nm AgNPs, and a different target organ of toxicity was identified (kidney). Conclusions: Administration of the smallest (10 nm) nanoparticles resulted in enhanced silver tissue distribution and overt hepatobiliary toxicity compared to larger ones (40 and 100 nm), while coating had no relevant impact. Distinct patterns of tissue distribution and toxicity were observed after silver acetate administration. It is concluded that if AgNPs become systemically available, they behave differently from ionic silver, exerting distinct and size-dependent effects, strictly related to the nanoparticulate form

Surgical complications following sentinel lymph node biopsy guided by γ‐probe and methylene blue in 113 tumour‐bearing dogs

Sentinel lymph node biopsy (SLNB) is an accepted veterinary surgical procedure given the impact of early detection of nodal metastases on staging of several canine malignancies. This study aims at reporting the incidence and risk factors for surgical complications of SLNB in tumour-bearing dogs. A total of 113 client-owned dogs that underwent tumour excision and SLNB guided by γ-probing and blue dye were retrospectively enrolled. Recorded variables included: signalment, location and number of extirpated lymphocenters and nodes, time for SLNB, histopathological status of excised nodes. Incidence of SLNB complications was calculated. They were classified as minor and major based on severity and required treatment, and as short-term (0–30 days) and long-term (31–90 days). Univariate analysis with generalized linear model with binomial error estimated the association between variables and incidence of SLNB complications. Significance was set at 5%. Median overall time for SLNB was 25 min. Surgeons excised one node in 38% of dogs and multiple nodes in 62% of cases, belonging to one (62%) or multiple (38%) lymphocenters. Metastases were detected in 45% of nodes. No intraoperative complications occurred. The overall incidence of postoperative complications of SLNB was 21,24%, the majority of which (91.67%) were minor. Only increasing dogs' weight was associated with an increased incidence of SLNB complications (p = .00976). Sentinel lymphadenectomy was associated with a relatively low incidence of complications, most of which were self-limiting. The low morbidity and previously reported impact on staging of SLNB justify its implementation to collect data for prognostic studies

The chemerin/CMKLR1 axis regulates intestinal graft-versus-host disease

: Gastrointestinal graft-versus-host disease (GvHD) is a major cause of mortality and morbidity following allogeneic bone marrow transplantation (allo-BMT). Chemerin is a chemotactic protein that recruits leukocytes to inflamed tissues by interacting with ChemR23/CMKLR1, a chemotactic receptor expressed by leukocytes, including macrophages. During acute GvHD, chemerin plasma levels were strongly increased in allo-BM-transplanted mice. The role of the chemerin/CMKLR1 axis in GvHD was investigated using Cmklr1-KO mice. WT mice transplanted with an allogeneic graft from Cmklr1-KO donors (t-KO) had worse survival and more severe GvHD. Histological analysis demonstrated that the gastrointestinal tract was the organ mostly affected by GvHD in t-KO mice. The severe colitis of t-KO mice was characterized by massive neutrophil infiltration and tissue damage associated with bacterial translocation and exacerbated inflammation. Similarly, Cmklr1-KO recipient mice showed increased intestinal pathology in both allogeneic transplant and dextran sulfate sodium-induced colitis. Notably, the adoptive transfer of WT monocytes into t-KO mice mitigated GvHD manifestations by decreasing gut inflammation and T cell activation. In patients, higher chemerin serum levels were predictive of GvHD development. Overall, these results suggest that CMKLR1/chemerin may be a protective pathway for the control of intestinal inflammation and tissue damage in GvHD

TRPM7 kinase activity is essential for T cell colonization and alloreactivity in the gut

The melastatin-like transient-receptor-potential-7 protein (TRPM7), harbouring a cation channel and a serine/threonine kinase, has been implicated in thymopoiesis and cytokine expression. Here we show, by analysing TRPM7 kinase-dead mutant (Trpm7 R/R) mice, that the enzymatic activity of the receptor is not essential for thymopoiesis, but is required for CD103 transcription and gut-homing of intra-epithelial lymphocytes. Defective T cell gut colonization reduces MHCII expression in intestinal epithelial cells. Mechanistically, TRPM7 kinase activity controls TGF-β-induced CD103 expression and pro-inflammatory T helper 17, but not regulatory T, cell differentiation by modulating SMAD2. Notably, we find that the TRPM7 kinase activity promotes gut colonization by alloreactive T cells in acute graft-versus-host disease. Thus, our results unravel a function of TRPM7 kinase in T cell activity and suggest a therapeutic potential of kinase inhibitors in averting acute graft-versus-host disease

GADD45β loss ablates innate immunosuppression in cancer

T cell exclusion from the tumour microenvironment (TME) is a major barrier to overcoming immune escape. Here we identify a myeloid-intrinsic mechanism governed by the NF-κB effector molecule GADD45β that restricts tumour-associated inflammation and T cell trafficking into tumours. In various models of solid cancers refractory to immunotherapies, including hepatocellular carcinoma (HCC) and ovarian adenocarcinoma, Gadd45b inhibition in myeloid cells restored activation of pro-inflammatory tumour-associated macrophages (TAM) and intratumoural immune infiltration, thereby diminishing oncogenesis. Our results provide a basis to interpret clinical evidence that elevated expression of GADD45B confers poor clinical outcomes in most human cancers. Further, they suggest a therapeutic target in GADD45β for re-programming TAM to overcome immunosuppression and T cell exclusion from the TME

Caecal coccidiosis in commercial male turkeys

An outbreak of coccidiosis with high mortality is reported in 30-day-old commercial turkeys. Grossly, a severe typhlitis with a large fibrino-necrotic core was present. Large numbers of oocysts were observed in caecal smears. The location and the severity of the lesions and the oocyst morphology were strongly suggestive of Eimeria adenoeides infection. This species has already been reported in turkey flocks in Italy, but it is rarely responsible for clinical coccidiosis and severe lesions with high mortality. Other caecal parasitic infections are considered in differential diagnosis

IL-1R8 as Pathoimmunological Marker for Severity of Canine Chronic Enteropathy

Chronic enteropathy (CE) is a severe multifactorial gastrointestinal disease that affects dogs and is driven by poorly characterized inflammatory pathways. Imbalance of pro-inflammatory response regulators, including IL-1R8, may be due to different factors, among which the infection with Helicobacteraceae is known to lead to a vicious circle in which excessive pro-inflammatory signaling and gastrointestinal injury reinforce each other and boost the disease. We investigated the expression of IL-1R8 in large intestine biopsies of dogs with or without clinical signs of CE and with previously assessed enterohepatic Helicobacter spp. colonization status by mean of quantitative real-time PCR. Our study revealed that IL-1R8 is downregulated in both acutely (p = 0.0074) and chronically (p = 0.0159) CE affected dogs compared to healthy controls. The data also showed that IL-1R8 expression tends to decrease with colonization by Helicobacter spp. Interestingly, a negative correlation was detected between the level of expression of IL-1R8 and the severity of macroscopic lesions identified by endoscopy and the crypt hyperplasia score. We further compared the expression levels between males and females and found no statistically significant difference between the two groups. No significant difference was observed in IL-1R8 expression profiles with the age of the animals either. Interestingly, an association was uncovered between IL-1R8 expression level and dog breed. Together, our data advance knowledge on gastrointestinal pathoimmunology in dogs and highlight the potential utilization of IL-1R8 as a diagnostic, prognostic and therapeutic biomarker for canine chronic enteropathy