Pasteurella multocida activates Rassf1-Hippo-Yap pathway to induce pulmonary epithelial apoptosis.

Pasteurella multocida is an opportunistic zoonotic pathogen that primarily causes fatal respiratory diseases, such as pneumonia and respiratory syndromes. However, the precise mechanistic understanding of how P. multocida disrupts the epithelial barrier in mammalian lung remains largely unknown. In this study, using unbiased RNA-seq analysis, we found that the evolutionarily conserved Hippo-Yap pathway was dysregulated after P. multocida infection. Given the complexity of P. multocida infection associated with lung injury and systemic inflammatory processes, we employed a combination of cell culture models, mouse models, and rabbit models to investigate the dynamics of the Hippo-Yap pathway during P. multocida infection. Our findings reveal that P. multocida infection activates the Hippo-Yap pathway both in vitro and in vivo, by upregulating the upstream factors p-Mst1/2, p-Lats1, and p-Yap, and downregulating the downstream effectors Birc5, Cyr61, and Slug. Conversely, pharmacological inhibition of the Hippo pathway by XMU-MP-1 significantly rescued pulmonary epithelial cell apoptosis in vitro and reduced lung injury, systemic inflammation, and mouse mortality in vivo. Mechanistic studies revealed that P. multocida induced up-regulation of Rassf1 expression, and Rassf1 enhanced Hippo-Yap pathway through phosphorylation. Accordingly, in vitro knockdown of Rassf1 significantly enhanced Yap activity and expression of Yap downstream factors and reduced apoptosis during P. multocida infection. P. multocida-infected rabbit samples also showed overexpression of Rassf1, p-Lats1, and p-Yap, suggesting that P. multocida activates the Rassf1-Hippo-Yap pathway. These results elucidate the pathogenic role of the Rassf1-Hippo-Yap pathway in P. multocida infection and suggest that this pathway has the potential to be a drug target for the treatment of pasteurellosis.

Physical examination and CT to assess thoracic injury in 137 cats presented to UK referral hospitals after trauma.

OBJECTIVES: The aim of the study was to describe clinical examination and thoracic CT (TCT) findings in cats after trauma, and to identify physical examination findings associated with both abnormalities on TCT and the need for therapeutic interventions. METHODS: A multicentre, retrospective, observational study was conducted. Cats admitted to the participating hospitals with a history of blunt trauma and that underwent TCT were eligible. Data were collected on signalment, history, physical examination, TCT findings and subsequent interventions. RESULTS: In total, 137 cats were included. Road traffic accidents (RTAs) were the most frequently reported cause of trauma (69%). Tachypnoea (32%), pale mucous membranes (22%) and dyspnoea (20%) were the most common abnormal findings on thoracic examination. The most frequently identified thoracic pathologies on TCT were atelectasis (34%), pulmonary contusions (33%), pneumothorax (29%) and pleural effusion (20%). Thoracocentesis was the most commonly performed intervention (12%), followed by chest drain placement (7%). A total of 45 (33%) cats had no physical examination abnormalities but did have abnormalities detected on TCT; six of these cats required interventions. Increasing numbers of thoracic abnormalities on clinical examination were associated with increasing likelihood of having abnormal findings on TCT (odds ratio [OR] 2.04, 95% confidence interval [CI] 1.21-3.44, P = 0.008) and of requiring an intervention (OR 1.82, 95% CI 1.32-2.51, P <0.001). CONCLUSIONS AND RELEVANCE: RTAs were the most common reported cause of blunt trauma. Atelectasis, pulmonary contusions and pneumothorax were the most common abnormalities identified on TCT, and thoracic drainage was the most utilised intervention. TCT may be useful in identifying cats with normal thoracic physical examination findings that have significant thoracic pathology, and a high number of abnormal findings on thoracic examination should raise suspicion for both minor and major thoracic pathology. The results of this study can be used to assist in selecting appropriate cases for TCT after blunt trauma.

Effects of inhaled fine particulate matter on the lung injury as well as gut microbiota in broilers.

Fine particulate matter (PM2.5) has been widely regarded as an important environmental risk factor that has widely influenced health of both animals and humans. Lung injury is the main cause of PM2.5 affecting respiratory tract health. Gut microbiota participates in the development of lung injury in many pathological processes. However, there is still unknown the specific effects of PM2.5 on the gut-lung axis in broilers. Thus, we conducted a broiler model based on 3-wk-old male Arbor Acres broiler to explore the underlying mechanism. Our results showed that PM2.5 exposure triggered TLR4 signaling pathway and induced the increase of IL-6, IFN-γ, TNF-α expression as well as the decrease of IL-10 expression in the lung. Inhaled PM2.5 exposure significantly altered the gut microbiota diversity and community. Specifically, PM2.5 exposure decreased α diversity and altered ß diversity of gut microbiota, and reduced the abundance of DTU089, Oscillospirales, Staphylococcus, and increased the Escherichia-Shigella abundance, leading to the increase of gut-derived lipopolysaccharides (LPS). Moreover, PM2.5 significantly disrupted the intestinal epithelial barrier by reducing the expression of muc2 and claudin-1 to increase intestinal permeability, which possibly facilitated the LPS translocation into the blood. Spearman analysis revealed that gut microbiota dysbiosis was positively related to TLR4, TNF-α, and IFN-γ expression in the lung. In summary, our results showed that PM2.5 exposure induced lung injury by causing inflammation and triggering TLR4 signaling pathway, and also induced gut microbiota dysbiosis resulting in the overproduction of gut-derived LPS. And gut microbiota dysbiosis may be associated with lung injury. The above results provide basis data to comprehend the potential role of gut microbiota dysbiosis in the lung injury as well as providing a new regulatory target for alleviating lung injury associated with environmental pollutants.

Chronic heat stress induces lung injury in broiler chickens by disrupting the pulmonary blood-air barrier and activating TLRs/NF-κB signaling pathway.

As an important respiratory organ, the lung is susceptible to damage during heat stress due to the accelerated breathing frequency caused by an increase in environmental temperature. This can affect the growth performance of animals and endanger their health. This study aimed to explore the mechanism of lung tissue damage caused by heat stress. Broilers were randomly divided into a control group (Control) and a heat stress group (HS). The HS group was exposed to 35°C heat stress for 12 h per d from 21-days old, and samples were taken from selected broilers at 28, 35, and 42-days old. The results showed a significant increase in lactate dehydrogenase (LDH) activity in the serum and myeloperoxidase (MPO) activity in the lungs of broiler chickens across all 3 age groups after heat stress (P < 0.01), while the total antioxidant capacity (T-AOC) was significantly enhanced at 35-days old (P < 0.01). Heat stress also led to significant increases in various proinflammatory factors in serum and expression levels of HSP60 and HSP70 in lung tissue. Histopathological results showed congestion and bleeding in lung blood vessels, shedding of pulmonary epithelial cells, and a large amount of inflammatory infiltration in the lungs after heat stress. The mRNA expression of TLRs/NF-κB-related genes showed an upward trend (P < 0.05) after heat stress, while the mRNA expression of MLCK, a gene related to pulmonary blood-air barrier, significantly increased after heat stress, and the expression levels of MLC, ZO-1, and occludin decreased in contrast. This change was also confirmed by Western blotting, indicating that the pulmonary blood-air barrier is damaged after heat stress. Heat stress can cause damage to the lung tissue of broiler chickens by disrupting the integrity of the blood-air barrier and increasing permeability. This effect is further augmented by the activation of TLRs/NF-κB signaling pathways leading to an intensified inflammatory response. As heat stress duration progresses, broiler chickens develop thermotolerance, which gradually mitigates the damaging effects induced by heat stress.

Bacillus subtilis KC1 prevents Mycoplasma gallisepticum-induced lung injury by enhancing intestinal Bifidobacterium animalis and regulating indole metabolism in chickens.

It has been reported that dietary administration of Bacillus subtilis KC1 is effective in alleviating lung injury induced by Mycoplasma gallisepticum (MG) infection in chickens. However, the underlying molecular mechanism of B. subtilis KC1 against MG infection is still unclear. The purpose of this study was to determine whether B. subtilis KC1 could alleviate MG infection-induced lung injury in chickens by regulating their gut microbiota. The results of this study indicate that B. subtilis KC1 supplementation has the potential to alleviate MG infection-induced lung injury as reflected by reduced MG colonization, reduced pathologic changes, and decreased production of pro-inflammatory cytokines. In addition, B. subtilis KC1 supplementation was partially effective in alleviating the gut microbiota disorder caused by MG infection. Importantly, B. subtilis KC1 enriched the beneficial Bifidobacterium animalis in gut and thus reversed indole metabolic dysfunction caused by MG infection. B. subtilis KC1 supplementation increased levels of indole, which enhanced aryl hydrocarbon receptor activation, improving barrier function and alleviating lung inflammation caused by MG. Overall, this study indicates that B. subtilis KC1 has a "gut-lung axis" mechanism that can reduce the severity of MG infection by enriching intestinal B. animalis and regulating indole metabolism.

A succession of pulmonary microbiota in broilers during the growth cycle.

Respiratory health problems in poultry production are frequent and knotty and thus attract the attention of farmers and researchers. The breakthrough of gene sequencing technology has revealed that healthy lungs harbor rich microbiota, whose succession and homeostasis are closely related to lung health status, suggesting a new idea to explore the mechanism of lung injury in broilers with pulmonary microbiota as the entry point. This study aimed to investigate the succession of pulmonary microbiota in healthy broilers during the growth cycle. Fixed and molecular samples were collected from the lungs of healthy broilers at 1, 3, 14, 21, 28, and 42 d of age. Lung tissue morphology was observed by hematoxylin and eosin staining, and the changes in the composition and diversity of pulmonary microbiota were analyzed using 16S rRNA gene sequencing. The results showed that lung index peaked at 3 d, then decreased with age. No significant change was observed in the α diversity of pulmonary microbiota, while the ß diversity changed regularly with age during the broilers' growth cycle. The relative abundance of dominant bacteria of Firmicutes and their subordinate Lactobacillus increased with age, while the abundance of Proteobacteria decreased with age. The correlation analysis between the abundance of differential bacteria and predicted function showed that dominant bacteria of Firmicutes, Proteobacteria and Lactobacillus were significantly correlated with most functional abundance, indicating that they may involve in lung functional development and physiological activities of broilers. Collectively, these findings suggest that the lung has been colonized with abundant microbiota in broilers when they were just hatched, and their composition changed regularly with day age. The dominant bacteria, Firmicutes, Proteobacteria, and Lactobacillus, play crucial roles in lung function development and physiological activities. It paves the way for further research on the mechanism of pulmonary microbiota-mediated lung injury in broilers.

Pulmonary microbiota intervention alleviates fine particulate matter-induced lung inflammation in broilers.

Fine particulate matter (PM2.5) released during the livestock industry endangers the respiratory health of animals. Our previous findings suggested that broilers exposed to PM2.5 exhibited lung inflammation and changes in the pulmonary microbiome. Therefore, this study was to investigate whether the pulmonary microbiota plays a causal role in the pathogenesis of PM2.5-induced lung inflammation. We first used antibiotics to establish a pulmonary microbiota intervention broiler model, which showed a significantly reduced total bacterial load in the lungs without affecting the microbiota composition or structure. Based on it, 45 AA broilers of similar body weight were randomly assigned to three groups: control (CON), PM2.5 (PM), and pulmonary microbiota intervention (ABX-PM). From 21 d of age, broilers in the ABX-PM group were intratracheally instilled with antibiotics once a day for 3 d. Meanwhile, broilers in the other two groups were simultaneously instilled with sterile saline. On 24 and 26 d of age, broilers in the PM and ABX-PM groups were intratracheally instilled with PM2.5 suspension to induce lung inflammation, and broilers in the CON group were simultaneously instilled with sterile saline. The lung histomorphology, inflammatory cytokines' expression levels, lung microbiome, and microbial growth conditions were analyzed to determine the effect of the pulmonary microbiota on PM2.5-induced lung inflammation. Broilers in the PM group showed lung histological injury, while broilers in the ABX-PM group had normal lung histomorphology. Furthermore, microbiota intervention significantly reduced mRNA expression levels of interleukin-1ß, tumor necrosis factor-α, interleukin-6, interleukin-8, toll-like receptor 4 and nuclear factor kappa-B. PM2.5 induced significant changes in the ß diversity and structure of the pulmonary microbiota in the PM group. However, no significant changes in microbiota structure were observed in the ABX-PM group. Moreover, the relative abundance of Enterococcus cecorum in the PM group was significantly higher than that in the CON and ABX-PM groups. And sterile bronchoalveolar lavage fluid from the PM group significantly promoted the growth of E. cecorum, indicating that PM2.5 altered the microbiota's growth condition. In conclusion, pulmonary microbiota can affect PM2.5-induced lung inflammation in broilers. PM2.5 can alter the bacterial growth environment and promote dysbiosis, potentially exacerbating inflammation.

Fine particulate matter (PM2.5) in broiler houses has a negative impact on broiler respiratory tracts, and PM2.5 exposure can induce lung inflammation and cause microbiota dysbiosis. The pulmonary microbiota is involved in maintaining immune homeostasis in the lungs, and a variety of lung diseases exhibit microbiota disturbances. However, the correlation between the pulmonary microbiota and PM2.5-induced lung inflammation is poorly understood. This study aimed to investigate whether the pulmonary microbiota influenced PM2.5-induced lung inflammation. We use antibiotics to reduce the quantity of bacteria in the lungs without destroying their composition. PM2.5 was then used to induce lung inflammation in both untreated and intervened pulmonary microbiota broilers. Compared to untreated microbiota broilers, intervened microbiota broilers had less morphological lung tissue injury and lower inflammatory factor expression levels after PM2.5 exposure. Furthermore, the intervened microbiota broilers' microbiota structure remained normal, while the untreated microbiota broilers showed dysbiosis. This dysbiosis is closely linked to changes in the microbial growth environment due to the inflammatory response. This suggested that the pulmonary microbiota affects PM2.5-induced lung inflammation in broilers. Dysbiosis caused by inflammation that alters the conditions for bacterial growth may exacerbate inflammation.

Hydroxytyrosol mitigates Mycoplasma gallisepticum-induced pulmonary injury through downregulation of the NF-κB/NLRP3/IL-1ß signaling pathway in chicken.

In this study, the anti-inflammatory and antiapoptotic effects of hydroxytyrosol (HT) in Mycoplasma gallisepticum (MG)-infected chicken were investigated, and the underlying molecular mechanisms were explored. The results revealed severe ultrastructural pathological changes after MG infection in the lung tissue of chicken, including inflammatory cell infiltration, thickening of the lung chamber wall, visible cell swelling, mitochondrial cristae rupture, and ribosome shedding. MG possibly activated the nuclear factor κB (NF-κB)/nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/interleukin (IL)-1ß signaling pathway in the lung. However, HT treatment significantly ameliorated MG-induced pathological damage of the lung. HT reduced the magnitude of pulmonary injury after MG infection by reducing apoptosis and releasing the proinflammatory factors. Compared with the MG-infected group, the HT-treated group exhibited significant inhibition of the expression of NF-κB/NLRP3/IL-1ß signaling-pathway-related genes; for example, the expressions of NF-κB, NLRP3, caspase-1, IL-1ß, IL-2, IL-6, IL-18, and TNF-α significantly decreased (P < 0.01 or <0.05). In conclusion, HT effectively inhibited MG-induced inflammatory response and apoptosis and protected the lung by blocking the activation of NF-κB/NLRP3/IL-1ß signaling pathway and reducing the damage caused by MG infection in chicken. This study revealed that HT may be a suitable and effective anti-inflammatory drug against MG infection in chicken.

Change over time and agreement between clinical markers of disease resolution in dogs with aspiration-induced lung injury.

BACKGROUND: There is a lack of consensus regarding which markers of disease resolution to prioritise when assessing treatment response in client-owned dogs with aspiration-induced lung injury. This study describes the change over time and the agreement between the clinical markers used to determine disease resolution. METHODS: Physical examination (PE), owner-reported clinical signs (CS-O), thoracic radiographs (TXR) scores and C-reactive protein (CRP) concentrations were determined at enrolment, after 24, 48 and 72 hours, and after 7, 14 and 28 days. RESULTS: PE scores were significantly improved at 48 hours, while CRP initially increased (24 hours) and then decreased (48 hours). PE, CS-O and CRP significantly improved earlier (7 days) than TXR (14 days). The median number of days to marker normalisation was 7, 9 and 14 for PE, CRP and CS-O, respectively. Marker agreement was excellent/very good at enrolment and fair/poor during disease recovery. LIMITATIONS: Analysis did not control for differences aetiology of aspiration or the lack of standardisation in treatment approach. CONCLUSIONS: PE was the earliest and most consistent marker indicating disease resolution. Serial CRP monitoring (72 hours) may provide an objective marker of early treatment response. Alongside PE normalisation, improvement in CS-O, CRP and TRX may assist in determining disease resolution and guide treatments, including limiting antibiotic exposure in dogs with aspiration-induced lung injury.

Combinational benefit of antihistamines and remdesivir for reducing SARS-CoV-2 replication and alleviating inflammation-induced lung injury in mice.

COVID-19 is an immune-mediated inflammatory disease caused by SARS-CoV-2 infection, the combination of anti-inflammatory and antiviral therapy is predicted to provide clinical benefits. We recently demonstrated that mast cells (MCs) are an essential mediator of SARS-CoV-2-initiated hyperinflammation. We also showed that spike protein-induced MC degranulation initiates alveolar epithelial inflammation for barrier disruption and suggested an off-label use of antihistamines as MC stabilizers to block degranulation and consequently suppress inflammation and prevent lung injury. In this study, we emphasized the essential role of MCs in SARS-CoV-2-induced lung lesions in vivo, and demonstrated the benefits of co-administration of antihistamines and antiviral drug remdesivir in SARS-CoV-2-infected mice. Specifically, SARS-CoV-2 spike protein-induced MC degranulation resulted in alveolar-capillary injury, while pretreatment of pulmonary microvascular endothelial cells with antihistamines prevented adhesion junction disruption; predictably, the combination of antiviral drug remdesivir with the antihistamine loratadine, a histamine receptor 1 (HR1) antagonist, dampened viral replication and inflammation, thereby greatly reducing lung injury. Our findings emphasize the crucial role of MCs in SARS-CoV-2-induced inflammation and lung injury and provide a feasible combination antiviral and anti-inflammatory therapy for COVID-19 treatment.

Protective effect of lithium chloride on pulmonary injury caused by Actinobacillus pleuropneumoniae via inhibition of GSK-3ß-NF-κB-dependent pathway.

Porcine contagious pleuropneumonia (PCP) is a very serious respiratory disease which is difficult to prevent and treat. In this study, the therapeutic effects of lithium chloride (LiCl) on PCP were examined using a mouse model. A mouse model of PCP was established by intranasal infections with Actinobacillus pleuropneumoniae (App). Histopathological analysis was performed by routine paraffin sections and an H-E staining method. The inflammatory factors, TLR4 and CCL2 were analyzed by qPCR. The expression levels of p-p65 and pGSK-3ß were detected using the Western Blot Method. The death rates, clinical symptoms, lung injuries, and levels of TLR-4, IL-1ß, IL-6, TNF-α, and CCL2 were observed to decrease in the App-infected mice treated with LiCl. It was determined that the LiCl treatments had significantly reduced the mortality of the App-infected cells, as well as the expressions of p-p65 and pGSK-3ß. The results of this study indicated that LiCl could improve the pulmonary injuries of mice caused by App via the inhibition of the GSK-3ß-NF-κB-dependent pathways, and may potentially become an effective drug for improving pulmonary injuries caused by PCP.

Levantamento de dados de condenações pulmonares por aspiração de sangue em abate de suínos sob o Serviço de Inspeção Estadual da Bahia entre os anos de 2018 a 2020 / Data Survey on pulmonary condemnatios for blood aspiration in swine slaughter under the Bahia State, Brazil Inspection Service from 2018 to 2020

O presente estudo tem como objetivo descrever os dados das condenações de pulmões por aspiração de sangue em abate de suínos do estado da Bahia, no período de janeiro de 2018 a outubro de 2020, em abatedouros sob fiscalização do Serviço de Inspeção Estadual (SIE). A coleta retrospectiva foi facilitada pela Agência de Defesa Agropecuária da Bahia (ADAB), através da Guia de Trânsito Animal (GTA), e foram coletados dados de 255.834 suínos abatidos em matadouros frigoríficos, localizados em oito municípios. Nos anos de 2018 e 2019, a aspiração de sangue foi a lesão mais encontrada. Em 2018, foram 15,45% (1131/7322) das alterações macroscópicas e 36,48% (1131/3100) das condenações pulmonares, e em 2019, foram 14,75% (1053/7138) e 36,20% (1053/2909), respectivamente. A congestão foi a lesão mais encontrada em 2020, mas não houve diferença considerável com a aspiração de sangue, que foi destaque das condenações pulmonares, com 38,07% (712/1870). Estes dados revelam a frequência de condenação por aspiração de sangue no estado da Bahia e sugerem implementação de treinamentos de manejo não violento para os funcionários dos abatedouros frigoríficos, visto que esse tipo de lesão indica estresse e uma tecnopatia associada à falha na insensibilização e sangria, em razão do animal agonizar enquanto tenta respirar após a incisão no pescoço.

This study aims to analyze data on lung condemnations for blood aspiration in pig slaughter in the state of Bahia, Brazil from january 2018 to october 2020, in slaughterhouses under supervision of the State Inspection Service (SIE). The retrospective collection was facilitated by the Agricultural Defense Agency of Bahia (ADAB), through the Animal Transit Guide (GTA), and data were collected from 255,834 pigs slaughtered in slaughter houses located in eight municipalities. In 2018 and 2019, blood aspiration was the most common lesion. In 2018, it was 15,45% (1131/7322) of macroscopic changes and 36,48% (1131/3100) of lung condemnations, and in 2019, it was 14,75% (1053/7138) and 36,20% (1053/2909), respectively. Congestion was the most common lesion found in 2020, but there was no considerable difference with blood aspiration, which was highlighted in pulmonary condemnations, with 38,07% (712/1870). These data reveal the frequency of condemnations for blood aspiration in the state of Bahia, Brazil and suggest the implementation of training in non-violent management for employees of slaughterhouses, as this type of injury indicates stress and a technopathy as sociated with failure in stunning and bleeding, because the animal agonizes while trying to breathe after the neck incision

Serum sRAGE and sE-selectin levels are useful biomarkers of lung injury and prediction of mortality in calves with perinatal asphyxia.

The objective of the present study was to evaluate the biomarkers specific to lung endothelial and epithelial damage in the determination of lung injury and its severity in calves with perinatal asphyxia and to evaluate their prognostic importance among survivors and non-survivor calves. Ten healthy calves and 20 calves with perinatal asphyxia were enrolled in the study. Clinical examination and laboratory analysis were performed at admission. Serum concentrations of soluble advanced glycation end-product receptor (sRAGE), soluble E-selectin (sE-selectin), clara cell secretory protein (CC16), and soluble intercellular adhesion molecule-1 (sICAM-1) were measured to assess lung injury. Venous pH, sO2, HCO3, and BE of calves with perinatal asphyxia were significantly lower than the healthy calves. sRAGE, sE-selectin, pCO2, and lactate were significantly high in calves with asphyxia. ROC analysis showed that sRAGE, sE-selectin, pCO2, lactate, and respiratory rate were higher while HCO3 and BE were lower in the nonsurvivor calves than survivors. In conclusion, serum sRAGE and sE-selectin concentrations highlight the utility of these biomarkers in determining lung injury in calves with asphyxia. Also, pH, pCO2, lactate, HCO3, BE, and respiratory rate along with serum sRAGE and sE-selectin were useful indicators in the prediction of mortality.

Conventional versus high-flow oxygen therapy in dogs with lower airway injury.

Dogs with lower airway pathology that present in respiratory distress often receive oxygen therapy as the first line of treatment regardless of the underlying cause. Conventional "low-flow" systems deliver oxygen with a maximum flow rate of 15 L/minute. Traditionally, when an animal's respiratory status does not improve with conventional oxygen therapy and treatments for underlying disease, options might be limited to either intubation and mechanical ventilation or humane euthanasia. High-flow oxygen therapy (HFOT) has been gaining popularity in veterinary medicine as an alternative route of oxygen supplementation for animals that require support beyond conventional therapy. High-flow oxygen therapy can supply a mixture of air and oxygen via a heated and humidified circuit. It is user friendly and can be used in an environment in which mechanical ventilation is unavailable. This review article is written for emergency doctors and general practitioners who lack access to mechanical ventilation. This article briefly reviews pertinent respiratory physiology, traditional oxygen supplementation techniques, the physiology of HFOT, and the limited evidence available in veterinary medicine regarding the use of HFOT, its applications, and limitations. Guidelines for the use of HFOT are suggested and HFOT is compared to conventional therapy.

Les chiens avec une pathologie des voies respiratoires inférieures qui présentent une détresse respiratoire reçoivent souvent une oxygénothérapie en première intention, quelle que soit la cause sous-jacente. Les systèmes conventionnels à « faible débit ¼ fournissent de l'oxygène avec un débit maximum de 15 L/minute. Traditionnellement, lorsque l'état respiratoire d'un animal ne s'améliore pas avec l'oxygénothérapie conventionnelle et les traitements de la maladie sous-jacente, les options peuvent se limiter à l'intubation et à la ventilation mécanique ou à l'euthanasie. L'oxygénothérapie à haut débit (HFOT) gagne en popularité en médecine vétérinaire en tant que voie alternative de supplémentation en oxygène pour les animaux qui nécessitent un soutien au-delà de la thérapie conventionnelle. L'oxygénothérapie à haut débit peut fournir un mélange d'air et d'oxygène via un circuit chauffé et humidifié. Il est convivial et peut être utilisé dans un environnement où la ventilation mécanique n'est pas disponible.Cet article de revue est écrit pour les médecins urgentistes et les médecins généralistes qui n'ont pas accès à la ventilation mécanique. L'article passe brièvement en revue la physiologie respiratoire pertinente, les techniques traditionnelles de supplémentation en oxygène, la physiologie de la HFOT et les preuves limitées disponibles en médecine vétérinaire concernant l'utilisation de la HFOT, ses applications et ses limites. Des lignes directrices pour l'utilisation de la HFOT sont suggérées et la HFOT est comparée au traitement conventionnel.(Traduit par Docteur Serge Messier).

H7N9 influenza virus-like particle based on BEVS protects chickens from lethal challenge with highly pathogenic H7N9 avian influenza virus.

H7N9 avian influenza virus poses a dual threat to both poultry industry and public health. Therefore, it is highly urgent to develop an effective vaccine to reduce its pandemic potential. Virus-like particles (VLP) represent an effective approach for pandemic vaccine development. In this study, a recombinant baculovirus co-expressing the HA, NA and M1 genes of the H7N9 virus was constructed for generation of H7N9 VLP. Single immunization of chickens with 15 µg of the VLP or the commercial whole virus inactivated vaccine stimulates high hemagglutination inhibition, virus neutralizing and HA-specific IgY antibodies. Moreover, the antiserum had a good cross-reactivity with H7N9 field strains isolated in different years. Within 14 days after a lethal challenge with highly pathogenic (HP) H7N9 virus, no clinical symptoms and death were observed in the vaccinated chickens, and no virus was recovered from the organs. Compared to the non-vaccinated chickens, H7N9 VLP significantly reduced the proportion of animals shedding virus. Only 30 % of the VLP-vaccinated birds shed virus, whereas virus shedding was detected in 50 % of the chickens immunized with the commercial vaccine. Moreover, both vaccines dramatically alleviated pulmonary lesions caused by HP H7N9 virus, with a greater degree observed for the VLP. Altogether, our results indicated that the H7N9 VLP vaccine candidate confers a complete clinical protection against a lethal challenge with HP H7N9 virus, significantly inhibits virus shedding and abolishes viral replication in chickens. The VLP generated in this study represents a promising alternative strategy for the development of novel H7N9 avian influenza vaccines for chickens.

Bacterial pneumonia in captive wild boars in southern Brazil: etiological and pathological causes

Respiratory diseases are one of the major health issues described in intensive pig production, causing important economic losses. However, there is little information on the prevalence, etiology and clinical-pathological presentation of these diseases in wild boars. For this reason, this work investigated the presence in captive wild boars of pneumonic lesions and bacterial pathogens commonly detected and associated with respiratory diseases in domestic pigs. A total of 226 captive wild boar lungs from two farms were examined in a slaughterhouse in Southern Brazil. The pneumonic lesions were classified as cranioventral, dorsocaudal, and disseminated, and the quantification of lesions was calculated. From the total of 226 lungs, 121 were collected for laboratory examination. Lungs with macroscopic lesions suggestive of pneumonia were collected for histological, bacteriological and molecular analysis. The molecular analysis was performed to detect the presence of Actinobacillus (A.) pleuropneumoniae, Glaesserella (G.) parasuis, Mycoplasma (M.) hyopneumoniae, Mycoplasma (M.) hyorhinis and Streptococcus (S.) suis serotype 2. The percentages of histological lesions and bacterial agents and their association were calculated. Cranioventral consolidation (75.2%) was the most prevalent macroscopic lung lesion, followed by disseminated (21.5%) and dorsocaudal (3.3%) distribution. Microscopically, chronic lesions were the most prevalent, representing 70.2% of the lungs. Moreover, BALT hyperplasia was present in 86.5% of the lungs, suppurative bronchopneumonia in 65.7%, and alveoli infiltrate in 46.8%. Six bacterial pathogens commonly described as agents of pig pneumonia were identified by bacterial or molecular methods: Pasteurella (P.) multocida, S. suis, M. hyopneumoniae, A. pleuropneumoniae, G. parasuis and M. hyorhinis. Twenty-eight different combinations of pathogens were identified in 84 samples (69.4%). The most common combinations were: M. hyopneumoniae and A. pleuropneumoniae (13.1%), M. hyopneumoniae, G. parasuis and M. hyorhinis (10.7%), and M. hyopneumoniae, A. pleuropneumoniae and G. parasuis (8.3%). Additionally, M. hyopneumoniae was the most frequent pathogen detected in this study, representing 58.7% of the samples. The detection of M. hyopneumoniae and M. hyorhinis by PCR was associated with the presence of BALT hyperplasia (P < 0.05) and there was also an association between the detection of M. hyopneumoniae by PCR and suppurative bronchopneumonia (P < 0.05). In addition, a significant association (P < 0.05) between the detection of M. hyopneumoniae and A. pleuropneumoniae by PCR and the histological classification (acute, subacute or chronic lesions) was observed. The results of this study were similar to those observed in slaughtered domestic pigs, although, the detection of opportunist pathogens was less frequent than that usually described in pig pneumonia. The high prevalence of pneumonia in captive wild boars at slaughter and the similar characteristics of pneumonia in captive wild boars and domestic pigs suggest that the close phylogenetic relationship between pigs and wild boars could influence the susceptibility of both species to the colonization of the same pathogens, indicating that captive wild boars raised in confined conditions could be predisposed to respiratory diseases, similar to domestic pigs.(AU)

Diagnosis of pulmonary contusions with point-of-care lung ultrasonography and thoracic radiography compared to thoracic computed tomography in dogs with motor vehicle trauma: 29 cases (2017-2018).

OBJECTIVE: To determine the accuracy of lung ultrasound (LUS) using the Veterinary Bedside Lung Ultrasound Examination (VetBLUE) protocol and 3-view thoracic radiographs (TXR) compared to thoracic computed tomography (TCT) for diagnosing the presence and quantification of pulmonary contusions (PC). DESIGN: Prospective cohort study conducted from February 2017 to June 2018. SETTING: Private emergency and referral center. ANIMALS: Thirty-two dogs having sustained motor vehicle trauma were consecutively enrolled. Three dogs were excluded from statistical analysis. All dogs survived to hospital discharge. INTERVENTIONS: Within 24 hours of sustaining trauma, dogs had LUS, TXR, and TCT performed. Using the VetBLUE protocol, LUS PC were scored according to the presence and number of B-lines and C-lines, indicating extravascular lung water. Thoracic radiographs and TCT were scored for PC in a similar topographical pattern to the VetBLUE protocol. Lung ultrasound and TXR were compared to "gold standard" TCT for the presence and quantification of PC. MEASUREMENTS AND MAIN RESULTS: On TCT, 21 of 29 (72.4%) dogs were positive and 8 of 29 (27.6%) dogs were negative for PC. When LUS was compared to TCT, 19 of 21 dogs were positive for PC (90.5% sensitivity) and 7 of 8 dogs were negative (87.5% specificity) for PC. LUS PC score correlated strongly with TCT PC score (R = 0.8, P < 0.001). When TXR was compared to TCT, 14 of 21 dogs were positive for PC (66.7% sensitivity) and 7 of 8 dogs were negative (87.5% specificity) for PC. TXR PC score correlated strongly with TCT PC score (R = 0.74, P < 0.001). CONCLUSIONS: In this population of dogs with motor vehicle trauma, LUS had high sensitivity for diagnosis of PC when compared to "gold standard" TCT. LUS provides reliable diagnosis of PC after trauma. More patients with PC were identified with LUS than with TXR, and additional studies are warranted to determine whether this increased sensitivity is statistically significant.

Ammonia induce lung tissue injury in broilers by activating NLRP3 inflammasome via Escherichia/Shigella.

Respiratory tract diseases are closely related to atmosphere pollution. Ammonia is one of the harmful pollutants in the atmosphere environment, which has a great threat to human and animal respiratory tract health, but the mechanism of causing diseases is not clear. In this study, broiler lung tissue was used as a model to study the effect of high ammonia on respiratory tract diseases through the relationship between respiratory microflora, NLRP3 inflammasome, and inflammatory factors. For this, we validated the occurrence of lung tissue inflammation under ammonia exposure and detected the lung tissue microbial constituent by 16S rDNA sequencing. Moreover, the relative expression levels of NLRP3 and caspase-1 mRNA and the content of IL-1ß and IL-6 were measured. After 7-D ammonia exposure, the proportion of the phylum Proteobacteria and the genus Escherichia/Shigella in lung tissue was significantly increased, the expression levels of NLRP3 and caspase-1 mRNA were significantly increased, and the content of IL-1ß in lung tissue and serum was higher than that in the control group. In conclusion, high ammonia induced lung tissue inflammation via increasing the proportion of Escherichia/Shigella, activating NLRP3 inflammasome, and promoting IL-1ß release. These findings provided a reference for the prevention and control of respiratory tract diseases in humans and animals caused by ammonia pollution.

Integration of transcriptomics, proteomics and metabolomics identifies biomarkers for pulmonary injury by polyhexamethylene guanidine phosphate (PHMG-p), a humidifier disinfectant, in rats.

Polyhexamethylene guanidine phosphate (PHMG-p) was used as a humidifier disinfectant in Korea. PHMG induced severe pulmonary fibrosis in Koreans. The objective of this study was to elucidate mechanism of pulmonary toxicity caused by PHMG-p in rats using multi-omics analysis. Wistar rats were intratracheally instilled with PHMG-p by single (1.5 mg/kg) administration or 4-week (0.1 mg/kg, 2 times/week) repeated administration. Histopathologic examination was performed with hematoxylin and eosin staining. Alveolar macrophage aggregation and granulomatous inflammation were observed in rats treated with single dose of PHMG-p. Pulmonary fibrosis, chronic inflammation, bronchiol-alveolar fibrosis, and metaplasia of squamous cell were observed in repeated dose group. Next generation sequencing (NGS) was performed for transcriptome profiling after mRNA isolation from bronchiol-alveoli. Bronchiol-alveoli proteomic profiling was performed using an Orbitrap Q-exactive mass spectrometer. Serum and urinary metabolites were determined using 1H-NMR. Among 418 differentially expressed genes (DEGs) and 67 differentially expressed proteins (DEPs), changes of 16 mRNA levels were significantly correlated with changes of their protein levels in both single and repeated dose groups. Remarkable biological processes represented by both DEGs and DEPs were defense response, inflammatory response, response to stress, and immune response. Arginase 1 (Arg1) and lipocalin 2 (Lcn2) were identified to be major regulators for PHMG-p-induced pulmonary toxicity based on merged analysis using DEGs and DEPs. In metabolomics study, 52 metabolites (VIP > 0.5) were determined in serum and urine of single and repeated-dose groups. Glutamate and choline were selected as major metabolites. They were found to be major factors affecting inflammatory response in association with DEGs and DEPs. Arg1 and Lcn2 were suggested to be major gene and protein related to pulmonary damage by PHMG-p while serum or urinary glutamate and choline were endogenous metabolites related to pulmonary damage by PHMG-p.

Ocorrência de alterações pulmonares em bovinos abatidos em abatedouro-frigorífico na cidade de Belém, Pará, Brasil / Pulmonary alterations in bovine abated in slaughterhouse in the city of Belém, Pará, Brazil

A inspeção post mortem de bovinos destinados ao consumo humano, favorece a obtenção de diagnósticos de doenças. As alterações pulmonares são de interesse para a inspeção sanitária, pois são frequentemente encontradas em bovinos abatidos para consumo em estabelecimentos com serviço oficial de inspeção. O objetivo do trabalho foi levantar a ocorrência de alterações pulmonares que podem ter sido ocasionadas pela insensibilização inadequada em bovinos abatidos para consumo em abatedouro-frigorífico localizado em Belém, Estado do Pará. Avaliou-se 5.654 animais, sendo condenados 603 pulmões que corresponderam a 258 (42,78%) condenações por aspiração de conteúdo ruminal; 191 (31,67%) por enfisema e 154 (25,53%) por aspiração de sangue. Os resultados obtidos podem ter sido decorrentes do método de insensibilização utilizado no estabelecimento.