Catching and killing of airborne SARS-CoV-2 to control spread of COVID-19 by a heated air disinfection system.

Airborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via air-conditioning systems poses a significant threat for the continued escalation of the current coronavirus disease (COVID-19) pandemic. Considering that SARS-CoV-2 cannot tolerate temperatures above 70 °C, here we designed and fabricated efficient filters based on heated nickel (Ni) foam to catch and kill SARS-CoV-2. Virus test results revealed that 99.8% of the aerosolized SARS-CoV-2 was caught and killed by a single pass through a novel Ni-foam-based filter when heated up to 200 °C. In addition, the same filter was also used to catch and kill 99.9% of Bacillus anthracis, an airborne spore. This study paves the way for preventing transmission of SARS-CoV-2 and other highly infectious airborne agents in closed environments.

Evaluation of the dose-response relationship of oral robenacoxib in urate crystal-induced acute stifle synovitis in dogs.

The objective of the study was to establish the dose-response relationship for robenacoxib, a selective cyclooxygenase (COX)-2 inhibitor, in a urate crystal model of acute synovitis. In a randomized partial Latin square design trial, 12 beagle dogs were administered orally single doses of robenacoxib (0.5, 1, 2, 4 and 8 mg/kg), placebo and the positive control meloxicam (0.1 mg/kg), 3 h after injection of sodium urate crystals into a stifle joint. Dogs were assessed for weight bearing on a force plate and by subjective clinical orthopaedic observations. Robenacoxib produced dose-dependent improvement in weight bearing, and decreased pain on palpation and joint swelling, over the dose range 0.5-2 mg/kg with no further increase in effect over the range 2-8 mg/kg. For weight bearing on the force plate, the ED50 of robenacoxib was 0.6-0.8 mg/kg. The onset of action and time to peak effect of robenacoxib were faster (respectively, 2-2.5 h and 3-5 h) than for meloxicam (respectively, 3 h and 6 h). Robenacoxib significantly inhibited COX-2 at all doses, with dose-related activity. Robenacoxib did not inhibit COX-1 over the dose range 0.5-4 mg/kg, but produced transient inhibition at 8 mg/kg. In conclusion, oral administration of robenacoxib over the dose range 0.5-8 mg/kg demonstrated significant analgesic and anti-inflammatory efficacy in dogs.

The novel sodium glucose transporter 2 inhibitor dapagliflozin sustains pancreatic function and preserves islet morphology in obese, diabetic rats.

AIMS: To investigate whether glucose lowering with the selective sodium glucose transporter 2 (SGLT2) inhibitor dapagliflozin would prevent or reduce the decline of pancreatic function and disruption of normal islet morphology. METHODS: Female Zucker diabetic fatty (ZDF) rats, 7-8 weeks old, were placed on high-fat diet. Dapagliflozin (1 mg/kg/day, p.o.) was administered for ∼33 days either from initiation of high-fat diet or when rats were moderately hyperglycaemic. Insulin sensitivity and pancreatic function were evaluated using a hyperglycaemic clamp in anaesthetized animals (n = 5-6); ß-cell function was quantified using the disposition index (DI) to account for insulin resistance compensation. Pancreata from a matched subgroup (n = 7-8) were fixed and ß-cell mass and islet morphology investigated using immunohistochemical methods. RESULTS: Dapagliflozin, administered from initiation of high-fat feeding, reduced the development of hyperglycaemia; after 24 days, blood glucose was 8.6 ± 0.5 vs. 13.3 ± 1.3 mmol/l (p < 0.005 vs. vehicle) and glycated haemoglobin 3.6 ± 0.1 vs. 4.8 ± 0.26% (p < 0.003 vs. vehicle). Dapagliflozin improved insulin sensitivity index: 0.08 ± 0.01 vs. 0.02 ± 0.01 in obese controls (p < 0.03). DI was improved to the level of lean control rats (dapagliflozin 0.29 ± 0.04; obese control 0.15 ± 0.01; lean 0.28 ± 0.01). In dapagliflozin-treated rats, ß-cell mass was less variable and significant improvement in islet morphology was observed compared to vehicle-treated rats, although there was no change in mean ß-cell mass with dapagliflozin. Results were similar when dapagliflozin treatment was initiated when animals were already moderately hyperglycaemic. CONCLUSION: Sustained glucose lowering with dapagliflozin in this model of type 2 diabetes prevented the continued decline in functional adaptation of pancreatic ß-cells.

Lymphocyte blastogenic response to ovalbumin in a model for canine allergy.

Lymphocyte stimulation tests (LST) were performed in five dogs sensitised with ovalbumin (OVA) and seven healthy dogs. In addition, all five OVA-sensitised and two control dogs were tested after two in vivo provocations with OVA-containing eye drops. The isolated cells were suspended in culture media containing OVA and were cultured for up to 12 days. Proliferation was measured as reduction in 5,6-carboxylfluorescein diacetate succinimidyl ester (CFSE) intensity by flow cytometry on days 0, 3, 6, 9 and 12. A cell proliferation index (CPI) for each day and the area under the curve (AUC) of the CPI was calculated for each dog. All OVA-sensitised dogs demonstrated increased erythema after conjunctival OVA application. The presence of OVA-specific lymphocytes was demonstrated in 2/5 OVA-sensitised dogs before and 4/5 after in vivo provocation. Using the AUC, the difference between OVA-sensitised and control dogs was significant in all three LST before in vivo provocation (P<0.05) and borderline significant (P=0.053) in 2/3 LST after provocation. The most significant difference in CPI was observed after 9 days of culture (P=0.001). This pilot study indicates that the LST allows detection of rare antigen specific memory T-cells in dogs previously sensitised to, but not concurrently undergoing challenge by a specific antigen.

Immune dysregulation in flea allergy dermatitis--a model for the immunopathogenesis of allergic dermatitis.

BACKGROUND: Flea allergy dermatitis (FAD) is a common skin disease in dogs and can be induced experimentally. It often coexists with other allergic conditions. So far no studies have investigated the quantitative production of cytokine mRNA in skin biopsies and peripheral blood mononuclear cells (PBMC) in flea allergic dogs. OBJECTIVE: The aim of our study was to improve the understanding of the immunopathogenesis of allergic dermatitis as a response to fleabites. MATERIAL AND METHODS: Allergic and non-allergic dogs were exposed to fleas. Before and after 4 days of flea exposure mRNA was isolated from biopsies and PBMC. Production of chymase, tryptase, IL-4, IL-5, IL-13, TNF-alpha and IFN-gamma mRNA was measured by real-time RT-PCR. The inflammatory infiltrate in the skin was scored semi-quantitatively. The number of eosinophils, mast cells (MC) and IgE+ cells/mm2 was evaluated to complete the picture. RESULTS: FAD was associated with a higher number of MC before flea exposure and with a significant increase of eosinophils after flea exposure as compared to non-allergic dogs. The number of IgE+ cells was higher in allergic dogs before and after flea exposure. In allergic dogs mRNA for most cytokines and proteases tested was higher before flea exposure than after flea exposure. After exposure to fleas an increased mRNA production was only observed in non-allergic dogs. In vitro stimulation with flea antigen resulted in a decreased expression of most cytokines in allergic dogs before flea exposure. In contrast, in PBMC, only increased levels of IL-4 and IL-5 mRNA were observed in allergic dogs before flea exposure. However, after flea exposure and additional stimulation with flea antigen the production of mRNA for all cytokines tested was significantly increased in allergic dogs. CONCLUSION: We demonstrated that the response in biopsies and PBMC is different and that FAD is associated with a TH2 response.

Detection and neutralization of bovine tumor necrosis factor by a monoclonal antibody.

Monoclonal antibodies (MAbs) have been produced which are specific for bovine tumor necrosis factor (TNF). MAb BC9 detects bovine TNF in a radioimmunoassay with a detection limit of 24 pg/ml. BC9 also neutralizes the in vitro biological function of bovine recombinant TNF. The activity of 250 ng TNF/ml was entirely neutralized by 1% ascitic fluid. When ascites was added at a saturating concentration (10% ascitic fluid), up to 25 micrograms TNF per ml was neutralized. The neutralizing effect of BC9 was seen in cytotoxic assays using L929 cells and WEHI 164 clone 13 cells. The cytotoxic activity of supernatants from in vitro activated bovine monocytes was entirely blocked by BC9.

Effect of interferon-gamma on the production of tumor necrosis factor during acute Escherichia coli mastitis.

The effects of recombinant interferon-gamma on the production of tumor necrosis factor in 10 dairy cows with Escherichia coli mastitis were determined. Prophylactic administration of recombinant interferon-gamma prior to the experimental E. coli challenge was effective in modifying the production of endogenous tumor necrosis factor during acute stages of disease. Elevated tumor necrosis factor concentrations were especially evident in cows that developed severe clinical symptoms and eventually died from endotoxemia. These results indicate that both milk and sera tumor necrosis factor concentrations are associated closely with the manifestation of peracute signs of coliform mastitis and are important factors contributing to morbidity and mortality of endotoxic shock. Pretreatment of cows with recombinant interferon-gamma possibly may down-regulate the generation of this potent endogenous inflammatory mediator within infected quarters. Controlling severe inflammation with recombinant interferon-gamma may prevent the tremendous loss in milk production and death that often accompany acute coliform mastitis during the periparturient period.

Prophylactic effects of recombinant bovine interferon-alpha I1 on acute Salmonella typhimurium infection in calves.

The in vivo effects of a single prophylactic dose of recombinant bovine interferon (rBoIFN)-alpha I1 in calves with salmonellosis were investigated, using a Salmonella typhimurium infection model. Treatment with rBoIFN-alpha I1 reduced the degree of septicemia compared with that in control groups, and, in one experiment, using disease of reduced severity, body temperature was lower in treated calves than in controls.

Induction of circulating tumor necrosis factor cannot be demonstrated during septicemic salmonellosis in calves.

The concentration of tumor necrosis factor in the circulation of calves, which were infected with Salmonella typhimurium and exhibited septicemia as indicated by clinical signs and blood culture, was measured with a radioimmunoassay. These levels were compared with those in calves before infection and in other calves that had received an intravenous dose of gram-negative endotoxin. The tumor necrosis factor levels measured in samples taken during septicemia were not different from those in samples from infected nonsepticemic calves or samples from calves before infection. In contrast, the levels of tumor necrosis factor rose rapidly in calves after treatment with endotoxin by intravenous injection.

Successful treatment of traumatic oesophageal rupture with severe cellulitis in a mare.

A five-year-old standardbred mare suffered a cervical oesophageal rupture subsequent to a kick. Marked cellulitis and extensive soft tissue damage resulted. Treatment consisted of creating an oesophageal fistula, local debridement and systemic antibiotics. The mare made a long but successful recovery. Treatment of oesophageal rupture in the horse is discussed.