The ameliorative role of Aloe vera-loaded chitosan nanoparticles on Staphylococcus aureus induced acute lung injury: Targeting TLR/NF-κB signaling pathways.

Background: Acute lung injury (ALI) is a severe condition distinguished by inflammation and impaired gas exchange in the lungs. Staphylococcus aureus, a common bacterium, can cause ALI through its virulence factors. Aloe vera is a medicinal plant that has been traditionally used to treat a variety of illnesses due to its anti-inflammatory properties. Chitosan nanoparticles are biocompatible and totally biodegradable materials that have shown potential in drug delivery systems. Aim: To explore the antibacterial activity of Aloe vera-loaded chitosan nanoparticles (AV-CS-NPs) against S. aureus in vitro and in vivo with advanced techniques. Methods: The antibacterial efficacy of AV-CS-NPs was evaluated through a broth microdilution assay. In addition, the impact of AV-CS-NPs on S. aureus-induced ALI in rats was examined by analyzing the expression of genes linked to inflammation, oxidative stress, and apoptosis. Furthermore, rat lung tissue was scanned histologically. The rats were divided into three groups: control, ALI, and treatment with AV-CS-NPs. Results: The AV-CS-NPs that were prepared exhibited clustered semispherical and spherical forms, having an average particle size of approximately 60 nm. These nanoparticles displayed a diverse structure with an uneven distribution of particle sizes. The maximum entrapment efficiency of 95.5% ± 1.25% was achieved. The obtained findings revealed that The minimum inhibitory concentration and minimum bactericidal concentration values were determined to be 5 and 10 ug/ml, respectively, indicating the potent bactericidal effect of the NPs. Also, S. aureus infected rats explored upregulation in the mRNA expression of TLR2 and TLR4 compared to healthy control groups. AV-CS-NP treatment reverses the case where there was repression in mRNA expression of TLR2 and TLR4 compared to S. aureus-treated rats. Conclusion: These NPs can serve as potential candidates for the development of alternative antimicrobial agents.

Mogroside V ameliorates broiler pulmonary inflammation via modulating lung microbiota and rectifying Th17/Treg dysregulation in lipopolysaccharides-induced lung injury.

The dysbiosis of lung microbiota and inflammatory factors play a crucial role in the occurrence of lipopolysaccharides (LPS)-induced lung injury. Recently, mogroside V (MGV) has received increasing attention due to its potential health benefits in pneumonia, but its complex mechanism needs further experimental elucidation. In this study, we established an LPS-induced chicken lung injury model to investigate the protective effect of MGV on LPS-induced acute lung injury in broiler and its related mechanisms. A total of 192 one-day-old white-finned broilers were randomly assigned into 4 groups with 6 replicates: 1) control group: basal diet (d 1-44), saline (d 43); 2) LPS group: basal diet (d 1-44), LPS (d 43); 3) MGV group: basal diet + 0.2% MGV (d 1-44), saline (d 43); 4) MGV-LPS group: basal diet + 0.2% MGV (d 1-44), LPS (d 43). The results showed that pathological examination showed that lung tissue inflammation infiltration was reduced after MGV treatment. In addition, MGV can promote the balance of Th17 and Treg cell cytokines, significantly inhibit the expression of proinflammatory cytokines (IL-1ß (P < 0.01), IL-6 (P < 0.001), IL-17F (P < 0.05)), and decrease immunosuppressive target expression (PD-L1 (P < 0.01), PD-1 (P < 0.001), RORα (P < 0.001)), activating the immune system. Furthermore, 16S rRNA sequencing analysis showed that MGV treatment could increase the abundance of beneficial bacteria in the lung and reduce the abundance of bacteria associated with inflammation. Generally, MGV intervention has a preventive effect on the pathological damage induced by lipopolysaccharides. Its mechanism is related to inhibiting the inflammatory response, regulating the Th17/Treg balance, and maintaining the stability of lung microbiota.

Oleocanthal alleviated lipopolysaccharide-induced acute lung injury in chickens by inhibiting TLR4/NF-κB pathway activation.

This study aimed to investigate the ameliorative effect of oleocanthal (OC) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in chickens and its possible mechanisms. In total, 20 chickens were randomly divided into 4 groups: control (CON) group, LPS group, LPS + OC group, and OC group. LPS + OC and OC groups were intragastrically administered a 5 mg/kg·d OC dose for 7 d. On d 8, the LPS group and LPS + OC group were intratracheally administered 2 mg/kg LPS for 12 h. It was found that OC ameliorated the pathological morphology and significantly suppressed apoptosis after OC treatment in LPS-induced ALI chicken (P < 0.01). Antioxidant capacity was higher in the LPS + OC group compared with the LPS group (P < 0.01). OC downregulated the related genes and proteins expression of toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) pathway in LPS group (P < 0.01). In conclusion, OC supplementation can alleviate LPS-induced ALI in chickens by suppressing apoptosis, enhancing lung antioxidant capacities and inhibiting TLR4/NF-κB pathway activation.

Fatal acute lung injury after balloon valvuloplasty in a dog with pulmonary stenosis.

A one-year-old French Bulldog was referred for the management of a severe form of pulmonary valve stenosis (PS) complicated by right-sided congestive heart failure. Echocardiography showed severe valvular PS with right ventricular concentric hypertrophy, dilatation and severe right atrial enlargement. A pulmonary balloon valvuloplasty (PBV) was performed with a balloon-to-pulmonary annulus ratio of 1.36. Echocardiography immediately after PBV showed a significant reduction in right atrial and ventricular size, improved opening and mobility of the pulmonary valve leaflets, and a 75% reduction in the pulmonary pressure gradient from 158 mmHg pre-operative to 40 mmHg post-operative. The dog recovered well from anesthesia, but 2 h later, it suddenly showed severe respiratory distress. Focus cardiac ultrasound showed increased left cardiac size with echocardiographic signs of high left ventricular filling pressure. Bedside lung ultrasound showed diffuse numerous-to-confluent B lines, compatible with a severe alveolar-interstitial syndrome. The dog was treated with furosemide, helmet continuous positive airway pressure, and then mechanical ventilation but without success. At post-mortem evaluation, histological examination of the lung showed diffuse, severe broncho-alveolar edema with mixed leukocyte, fibrin, and red blood cell infiltrate. Moreover, severe congestion and multifocal alveolar hemorrhages were evident. All findings were compatible with fatal acute lung injury after PBV secondary to pulmonary reperfusion-ischemia injury and increased pulmonary capillary hydrostatic pressure. Based on the present case, acute lung injury should be considered as a rare but serious complication of PBV.

Effect of intrabronchial platelet rich plasma on the exercise-induced pulmonary hemorrhage endoscopic score in thoroughbred racehorses using furosemide: a preliminary study / [Efeito da instilação intrabronquial de plasma rico em plaquetas no escore endoscópico da hemorragia pulmonar induzida por exercício em cavalos Puro-Sangue Inglês de corrida e usuários de furosemida: um estudo preliminar]

The high prevalence of exercise-induced pulmonary hemorrhage (EIPH) in athletic horses constitutes to be a challenge to the racing industry and a source of major concern to animal welfare. Both experimental and clinical evidence indicate that the use of autologous platelet-rich plasma (PRP) is a promising effector of repair in a variety of pulmonary conditions. The present study evaluated the effect of intrabronchial instillation of PRP on EIPH endoscopic scores from 37 Thoroughbred racehorses. Inclusion criteria were for animals to be EIPH-positive in, at least, two consecutive post-exercise endoscopic exams and to receive 250mg of furosemide IV four hours before racing. Animals were randomly assigned into 3 groups: placebo, control, and PRP instillation. All 37 Thoroughbred racehorses included had EIPH endoscopic scores pre- and post- treatment compared by statistical analysis. The bleeding score from the group receiving PRP was significantly lower than in the control and placebo groups. No adverse effects were observed in any animal during or after the experiment. It was possible to conclude that the intrabronchial instillation of autologous PRP was effective in reducing EIPH scores in racehorses receiving furosemide and that this bioproduct can be considered as a promising coadjuvant in controlling EIPH in athletic horses.(AU)

A alta prevalência de hemorragia pulmonar induzida por exercício (HPIE) em cavalos atletas é um desafio de longa data para a indústria de corridas, além de figurar como grande preocupação sobre o bem-estar animal. As evidências experimentais e clínicas indicam que o uso do plasma rico em plaquetas (PRP) de fonte autógena é promissor na terapêutica de diversas lesões pulmonares. O presente estudo objetivou avaliar as mudanças após corrida no escore endoscópico de HPIE de 37 cavalos Puro-Sangue Inglês que receberam instilação intrabronquial de PRP autólogo. Os animais selecionados eram HPIE-positivos em, ao menos, dois exames endoscópicos consecutivos e recebiam 250mg de furosemida IV administrado quatro horas antes de cada corrida. Na comparação dos escores endoscópicos pré e pós-tratamento, verificou-se que o escore de HPIE do grupo tratado com PRP foi significantemente menor que o dos grupos controle e placebo. Nenhum efeito adverso foi observado nos animais durante ou após o experimento. Concluiu-se que a instilação intrabronquial de PRP autólogo foi efetiva na redução do escore de HPIE de cavalos de corrida usuários de furosemida e que este bioproduto pode ser considerado uma alternativa promissora no controle de HPIE em cavalos atletas.(AU)

Pulmonary complications in dogs with acute presentation of pancreatitis.

BACKGROUND: In humans, respiratory complications in patients with acute pancreatitis (AP) are a common life-threatening comorbidity. Since possible lung impairment has not been individually evaluated in canine AP, the aims of the present study were to: (1) describe the prevalence, types and severity of pulmonary complications in dogs with acute presentation of AP, and (2) evaluate their association with mortality. AP diagnosis was based on compatible clinical and laboratory parameters, abnormal canine pancreatic-lipase test, and positive abdominal ultrasound within 48 h from admission. The canine acute pancreatitis severity score (CAPS) was calculated for each dog at admission. Arterial blood gas analysis and thoracic radiography were performed at admission. Thoracic radiography was classified on the basis of pulmonary pattern (normal, interstitial or alveolar) and a modified lung injury score (mLIS) was applied to the ventrodorsal projections for each dog. VetALI/VetARDS were diagnosed using current veterinary consensus. Dogs were divided into non-survivors or survivors (hospital discharge). Clinical, radiological and blood gas parameters collected at presentation were compared between survivors and non-survivors and associated with mortality. RESULTS: This prospective cohort study included twenty-six client-owned dogs with AP. Twelve out of twenty-six dogs (46%) died or were euthanized. At admission, thirteen dogs showed respiratory distress at physical examination, which was associated with death (P < 0.001). Radiographic abnormalities were found in twenty-one dogs: alveolar (n = 11) and interstitial pattern (n = 10). Radiographic alterations and mLIS score were both associated with death (P = 0.02 and P = 0.0023). The results of the arterial blood-gas evaluation showed that non-survivors had lower PaCO2 and HCO3- levels, and higher A-a gradient than survivors (P = 0.0014, P = 0.019 and P = 0.004, respectively). Specifically, three dogs had aspiration pneumonia, and VetALI was diagnosed in nine dogs (34.6%), and no dogs met the criteria for VetARDS. The presence of VetALI was associated with mortality (P < 0.001). CONCLUSIONS: As with humans, possible lung impairments, such as VetALI, should be investigated in dogs with acute presentation of pancreatitis.

Sevoflurane reduces inflammatory factor expression, increases viability and inhibits apoptosis of lung cells in acute lung injury by microRNA-34a-3p upregulation and STAT1 downregulation.

OBJECTIVE: Evidence has shown that sevoflurane plays a protective role in acute lung injury (ALI) due to its anti-inflammatory and apoptotic-regulating activity. Nevertheless, the mechanism of sevoflurane is still not completely understood. This study intends to discuss the mechanism of sevoflurane on ALI and the possible mechanisms involved. METHODS: ALI model of rats was established through intravenous injection of endotoxin lipopolysaccharide. microRNA-34a-3p (miR-34a-3p) and signal transducers and activators of transcription 1 (STAT1) expression in lung tissues of ALI rats were detected. The optimal inhaled concentration of sevoflurane was screened, and then the modeled rats were injected with miR-34a-3p inhibitors, overexpressed STAT1 and inhaled 1.0 Minimum Alveolar Concentration (MAC) sevoflurane to determine mean arterial pressure (MAP) of rats, wet weight/dry weight ratio and myeloperoxidase (MPO) activity, oxidative stress- and inflammation-related factors in lung tissues of rats, along with lung cell viability and apoptosis. RESULTS: MiR-34a-3p was downregulated while STAT1 was upregulated in ALI rats. Sevoflurane of 1.0 MAC was selected as the optimal inhalation concentration. Sevoflurane (1.0 MAC) increased MAP at T3 and reduced MPO activity, alleviated pathological damage, suppressed apoptosis, oxidative stress and inflammation, and induced cell viability in lung tissues of ALI rats. Down-regulated miR-34a-3p or up-regulated STAT reversed the functions of sevoflurane (1.0 MAC) on ALI rats. CONCLUSION: Collectively, we demonstrate that sevoflurane reduces inflammatory factor expression, increases lung cell viability and inhibits lung cell apoptosis in ALI through upregulation of miR-34a-3p and downregulation of STAT1, which provides new clues for ALI treatment.

Baicalin alleviated APEC-induced acute lung injury in chicken by inhibiting NF-κB pathway activation.

Bacterial pneumonia is a leading cause of death in the animal husbandry. Acute lung injury (ALI), most often seen as a part of systemic inflammatory process, characterized by progressive hypoxemia, edema, and neutrophil accumulation in the lung. Baicalin has been reported to inhibit inflammatory response, but its role in ALI remains unknown. The purpose of our study was to determine the protective effect and possible mechanism of baicalin against avian pathogenic Escherichia coli (APEC)-induced ALI in chicken. Chickens were conditioned with baicalin 1 week before intratracheally instilled with APEC. Then, chickens were sacrificed by CO2 inhalation 12 h later and the lung tissues were collected for examining histopathological changes, wet/dry (W/D) ratio, myeloperoxidase (MPO) activity, levels of pro-inflammatory cytokines and activation of NF-κB signaling pathway. The results showed that pre-treatment of chickens with baicalin significantly alleviated the death rate, histopathological changes in lung tissues. The W/D ratio, MPO activity and production of cytokines, such as IL-1ß, TNF-α, IL-6 of lung tissues were also decreased following treatment with baicalin. Furthermore, the mechanism responsible for these effects was attributed to the inhibitory effect of baicalin on nuclear factor-κB (NF-κB) signaling activation. These data thus support the application of baicalin as a potential medicine for the treatment of E. coli-induced ALI by regulating NF-κB signaling pathway.

Heme scavenging reduces pulmonary endoplasmic reticulum stress, fibrosis, and emphysema.

Pulmonary fibrosis and emphysema are irreversible chronic events after inhalation injury. However, the mechanism(s) involved in their development remain poorly understood. Higher levels of plasma and lung heme have been recorded in acute lung injury associated with several insults. Here, we provide the molecular basis for heme-induced chronic lung injury. We found elevated plasma heme in chronic obstructive pulmonary disease (COPD) (GOLD stage 4) patients and also in a ferret model of COPD secondary to chronic cigarette smoke inhalation. Next, we developed a rodent model of chronic lung injury, where we exposed C57BL/6 mice to the halogen gas, bromine (Br2) (400 ppm, 30 minutes), and returned them to room air resulting in combined airway fibrosis and emphysematous phenotype, as indicated by high collagen deposition in the peribronchial spaces, increased lung hydroxyproline concentrations, and alveolar septal damage. These mice also had elevated pulmonary endoplasmic reticulum (ER) stress as seen in COPD patients; the pharmacological or genetic diminution of ER stress in mice attenuated Br2-induced lung changes. Finally, treating mice with the heme-scavenging protein, hemopexin, reduced plasma heme, ER stress, airway fibrosis, and emphysema. This is the first study to our knowledge to report elevated heme in COPD patients and establishes heme scavenging as a potential therapy after inhalation injury.

Retrospective evaluation of the prevalence, risk factors, management, outcome, and necropsy findings of acute lung injury and acute respiratory distress syndrome in dogs and cats: 29 cases (2011-2013).

OBJECTIVE: To determine the prevalence and risk factors for veterinary acute lung injury (VetALI) and veterinary acute respiratory distress syndrome (VetARDS), assess mechanical ventilation settings and patient outcomes, and to evaluate the relationship of clinical diagnoses with necropsy findings. DESIGN: Retrospective study. SETTING: University teaching hospital. ANIMALS: Twenty-four dogs and 5 cats with a clinical diagnosis of VetALI or VetARDS. Control population includes 24 dogs and 5 cats with a clinical diagnosis of respiratory disease other than VetALI or VetARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: VetALI and VetARDS were diagnosed in 3.2% of dogs and 1.3% of cats presenting to the ICU. Systemic inflammatory response syndrome was the most common inciting condition (16/24 dogs, 2/5 cats), followed by vomiting and subsequent aspiration of gastric contents (9/24 dogs), sepsis (5/24 dogs, 3/5 cats), multiple transfusions (4/24 dogs), trauma (3/24 dogs), and adverse drug reactions (1/24 dogs, 1/5 cats).  None of these conditions were found to be significantly associated with a risk of development of VetALI or VetARDS when compared to controls. Twelve dogs (50%) and 4 cats (80%) underwent mechanical ventilation for a median duration of 18 hours in dogs (range: 6-174 h) and 15.5 hours in cats (range: 6-91 h). Overall, 3/29 patients survived to discharge including 2/24 dogs and 1/5 cats. Necropsy results were available for 8/22 dogs and 3/4 cats. A total of 6/8 dogs (75%) dogs and 3/3 (100%) cats met the histopathologic criteria for diagnosis of VetALI or VetARDS. CONCLUSIONS: VetALI and VetARDS can cause life-threatening respiratory distress in dogs and cats necessitating mechanical ventilation in 50% of dogs and 80% of cats in this study. These diseases are associated with a poor clinical outcome and a high rate of humane euthanasia.

Incidence of acute lung injury in dogs receiving transfusions.

OBJECTIVE: To document the existence and incidence of acute lung injury (ie, veterinary acute lung injury [VetALI] per the 2007 consensus definition) in a population of client-owned dogs receiving transfusions for various clinical reasons. DESIGN: Prospective observational study. ANIMALS: 54 client-owned dogs. PROCEDURES: Arterial blood gas analysis was performed for dogs receiving a transfusion (blood and plasma products) at 0 to 12 hours before and 24 to 48 hours after transfusion; dogs also underwent thoracic radiography 0 to 24 hours before and 24 to 48 hours after transfusion. The ratio of PaO2 to fraction of inspired oxygen (FIO2) was calculated. Dogs with posttransfusion radiographic signs of pulmonary infiltrates, a PaO2:FIO2 ratio < 300, or clinical signs of respiratory compromise were suspected of having VetALI and underwent echocardiography to exclude left-sided heart failure. The incidence of VetALI was calculated, and χ(2) tests were used to compare the incidence in study dogs with the historical reported incidence of acute respiratory distress syndrome (ARDS) in ill dogs (not receiving transfusions) and transfusion-related acute lung injury (TRALI) in humans. RESULTS: The incidence of VetALI (2/54 [3.7%]; 95% confidence interval, 0% to 8.73%) in study dogs was significantly less than the reported incidence of TRALI in humans (25%) and not significantly different from the reported incidence of ARDS in ill dogs (10%). CONCLUSIONS AND CLINICAL RELEVANCE: VetALI occurred in dogs that received transfusions at a frequency similar to that previously reported for ARDS in ill dogs that did not receive transfusions.

Respiratory complications in critical illness of small animals.

The percentage of emergency patients with respiratory problems treated at veterinary emergency and critical care facilities is poorly defined. Regardless of whether an animal has a primary lung disease or develops a secondary lung disease during hospitalization, acute respiratory distress syndrome (ARDS) is a common sequela to the failing lung. ARDS is a frequent sequela to sepsis, systemic inflammatory response (SIRS), and disseminated intravascular coagulation and is frequently the pulmonary manifestation of multiple organ dysfunction syndrome (MODS). ARDS, acute lung injury, SIRS, sepsis, and MODS are serious syndromes with grave consequences. Understanding the pathophysiology and consequences of these syndromes is imperative to early recognition.

Systemic inflammatory response syndrome in nonhuman primates culminating in multiple organ failure, acute lung injury, and disseminated intravascular coagulation.

The systemic inflammatory response syndrome (SIRS) is a clinicopathological manifestation of overexuberant acute-phase inflammation caused by infectious or noninfectious etiologies. The systemic release of pro-inflammatory cytokines, chemokines, and lipid and vasoactive mediators induces endothelial damage and microvascular thrombosis, potentially culminating in disseminated intravascular coagulation (DIC), acute respiratory distress syndrome (ARDS), and multiple organ dysfunction (MOD) or failure (MOF). We present five cases in the pig-tailed macaque and olive baboon where SIRS resulted in MOF, ARDS, DIC, and the Waterhouse-Friderichsen syndrome; each with gross and histological elements manifested as edema, deposition of fibrin, hemorrhage, and thrombosis. In the described cases, SIRS was the end-common pathway for multiple risk factors that parallel those documented in humans: major surgery, obstetric complications, and infection. The diagnosis of SIRS should be considered when evaluating nonhuman primate (NHP) cases of MOF manifesting with histological evidence of vascular leakage. Experimental manipulation of NHP models may be complicated by SIRS and accompanying rapid clinical decompensation. Such adverse events may compromise toxicological studies and should be avoided when possible.

A novel Respiratory Health Score (RHS) supports a role of acute lung damage and pig breed in the course of an Actinobacillus pleuropneumoniae infection.

BACKGROUND: Bacterial lung infections are a major cause of economic losses in the pig industry; they are responsible for approximately 50% of the antibiotics used in pigs and, therefore, also present an increasing concern to consumer protection agencies. In response to this changing market we investigated the feasibility of an old approach aimed at the breeding selection of more resistant pigs. As a first step in this direction we applied a new respiratory health score system to study the susceptibility of four different pig breeding lines (German Landrace, Piétrain, Hampshire, Large White) towards the respiratory tract pathogen Actinobacillus (A.) pleuropneumoniae. RESULTS: A controlled experimental aerosol infection with an A. pleuropneumoniae serotype 7 isolate was performed using 106 weaning pigs of defined breeding lines from the breeds German Landrace, Piétrain, Hamphire, and Large White. Pigs were clinically assessed on days 4 and 20 post infection following a novel scoring system, the Respiratory Health Score (RHS), which combines clinical, sonographic and radiographic examination results. The ranking on day 4 was significantly correlated with the ranking based on the pathomorphological Lung Lesion Score (LLS; Spearman Rank Correlation Coefficient of 0.86 [p < 0.0001]). Based on their RHS pigs were assigned to the different quartiles independent of the breeding line. The RHS-based rankings of pigs on day 4 and on day 20 were highly correlated (Spearman Rank Correlation Coefficient of 0.82 [p < 0.0001]) independent of the breeding line. Pigs of the Hampshire line were predominantly found in the lowest scoring quartile (47.6%) and absent in the highest scoring quartile. In contrast, pigs of the German Landrace and Piétrain breeding lines were predominantly found in the highest scoring quartile (32.3% and 35.7%, respectively). CONCLUSION: These results demonstrate that the RHS obtained from live pigs shows a highly significant correlation to the lung lesion score considered as a "gold standard". The correlation of the ranking at days 4 and 20 post infection implies that the course of disease is highly dependent on the acute lung damage. The different severity of signs among the tested pig breeding lines clearly suggests a genetic difference in the susceptibility of pigs to A. pleuropneumoniae infection.