The parasitic worm-derived immunomodulator, ES-62 and its drug-like small molecule analogues exhibit therapeutic potential in a model of chronic asthma

Chronic asthma is associated with persistent lung inflammation and long-term remodelling of the airways that have proved refractory to conventional treatments such as steroids, despite their efficacy in controlling acute airway contraction and bronchial inflammation. As its recent dramatic increase in industrialised countries has not been mirrored in developing regions, it has been suggested that helminth infection may protect humans against developing asthma. Consistent with this, ES-62, an immunomodulator secreted by the parasitic worm Acanthocheilonema viteae, can prevent pathology associated with chronic asthma (cellular infiltration of the lungs, particularly neutrophils and mast cells, mucus hyper-production and airway thickening) in an experimental mouse model. Importantly, ES-62 can act even after airway remodelling has been established, arresting pathogenesis and ameliorating the inflammatory flares resulting from repeated exposure to allergen that are a debilitating feature of severe chronic asthma. Moreover, two chemical analogues of ES-62, 11a and 12b mimic its therapeutic actions in restoring levels of regulatory B cells and suppressing neutrophil and mast cell responses. These studies therefore provide a platform for developing ES-62-based drugs, with compounds 11a and 12b representing the first step in the development of a novel class of drugs to combat the hitherto intractable disorder of chronic asthma

The parasitic worm-derived immunomodulator, ES-62 and its drug-like small molecule analogues exhibit therapeutic potential in a model of chronic asthma

Chronic asthma is associated with persistent lung inflammation and long-term remodelling of the airways that have proved refractory to conventional treatments such as steroids, despite their efficacy in controlling acute airway contraction and bronchial inflammation. As its recent dramatic increase in industrialised countries has not been mirrored in developing regions, it has been suggested that helminth infection may protect humans against developing asthma. Consistent with this, ES-62, an immunomodulator secreted by the parasitic worm Acanthocheilonema viteae, can prevent pathology associated with chronic asthma (cellular infiltration of the lungs, particularly neutrophils and mast cells, mucus hyper-production and airway thickening) in an experimental mouse model. Importantly, ES-62 can act even after airway remodelling has been established, arresting pathogenesis and ameliorating the inflammatory flares resulting from repeated exposure to allergen that are a debilitating feature of severe chronic asthma. Moreover, two chemical analogues of ES-62, 11a and 12b mimic its therapeutic actions in restoring levels of regulatory B cells and suppressing neutrophil and mast cell responses. These studies therefore provide a platform for developing ES-62-based drugs, with compounds 11a and 12b representing the first step in the development of a novel class of drugs to combat the hitherto intractable disorder of chronic asthma

Healthy cats tolerate long-term daily feeding of Cannabidiol

Cannabidiol (CBD)-containing products are widely commercially available for companion animals, mirroring popularity in human use. Although data on the safety and efficacy of long-term oral supplementation are increasing in dogs, evidence remains lacking in cats. The purpose of these studies was to address gaps in the knowledge around the long-term suitability and tolerance of a tetrahydrocannabinol (THC)-free CBD distillate in clinically healthy cats. The studies were randomized, blinded, and placebo-controlled. The first study supplemented cats with either a placebo oil (n = 10) or with 4 mg/kg body weight (BW) CBD in placebo oil (n = 9) daily, with a meal, for 4 weeks. The concentration of CBD in plasma was measured over 4 h at d0 (first dose) and again at d14 (after 2 weeks of daily dosing). The second study supplemented cats daily with either placebo oil (n = 10) or 4 mg/kg BW CBD in placebo oil (n = 10) for a period of 26 weeks. A comprehensive suite of physiological health measures was performed throughout the study at baseline (week 0) and after 4, 10, 18, and 26 weeks of feeding, followed by a 4-week washout sample (week 30). Postprandial plasma CBD time course data, at both d0 and d14, showed a peak plasma CBD concentration at 2 h after the dose. This peak was 251 (95% CI: 108.7, 393.4) and 431 (95% CI, 288.7, 573.4) ng/mL CBD at d0 and d14, respectively, and the area under the curve concentration was higher by 91.5 (95% CI, 33.1, 149.9) ng-h/mL after 2 weeks of supplementation (p = 0.002). While in the first study the CBD group displayed increased alanine aminotransferase (ALT; 68.7 (95% CI, 43.23, 109.2) U/L) at week 4 compared to the placebo control group [1.44-fold increase (95% CI, 0.813, 2.54)], statistical equivalence (at 2-fold limits) was found for ALT across the duration of the second, long-term study. All other biochemistry and hematology data showed no clinically significant differences between supplement groups. Data presented here suggest that a THC-free, CBD distillate fed at a dose of 4 mg/kg BW was absorbed into plasma and well tolerated by healthy cats when supplemented over a period of 26 weeks

The use of visual and automatized behavioral markers to assess methodologies: a study case on PIT-tagging in the Alpine newt

peer reviewedBiomarkers are now widely used as tools in various research fields to assess individual integrity. The recent advances in quantification methods of behavioral patterns, such as computerized video-tracking procedures, make them valuable biomarkers. However, the corollary of these novelties is that they remain relatively unknown and unused. In this study, we show that such tools can assess the validity of research methods, such as individual recognition. To demonstrate this we employed as a model a marking method (Passive Integrate Transponders: PIT-tagging) widely used in amphibians. Both detailed visual observations and video-tracking methods were complementary in highlighting components at different behavioral scales: locomotion, feeding, and breeding. We illustrate the scientific and ethical adequacy of the targeted marking method but also suggest that more studies should integrate behavioral analyses. Such biomarkers are a powerful tool to assess conservation concerns when other techniques cannot detect detrimental effects

Genetic growth potential interacts with nutrition on the ability of mice to cope with Heligmosomoides bakeri infection

Artificial selection for improved productivity may reduce an animal's ability to cope with pathogens. Here, we used Roslin mice, uniquely divergently selected for high (ROH) and low (ROL) body weight, to assess interactive effects of differing growth potential and protein nutrition on host resilience and resistance. In a 226 factorial design, ROH and ROL mice were either sham-infected or infected with 250 L3Heligmosomoides bakeri and fed diets with 30, 80, 130, 180, 230 and 280 g crude protein per kg. The infected ROL-30 treatment resulted in clinical disease and was discontinued. In the remaining ROL mice, infection and feeding treatments did not affect growth but infection reduced weight gain in ROH-30, ROH-80 and ROH-130 mice. Although infection resulted in temporarily reduced food intake (anorexia) in both mouse lines, mean food intake over the whole experiment was reduced in ROH mice only. ROH mice excreted more worm eggs and had higher worm burdens, with relatively fewer female worms, than ROL mice. However, these resistance traits were not sensitive to dietary protein. These results support the view that selection for high growth may reduce the ability to cope with pathogens, and that improved protein nutrition may to some extent ameliorate this penalty. © 2009 Cambridge University Press

Image_1_Healthy cats tolerate long-term daily feeding of Cannabidiol.JPEG

Cannabidiol (CBD)-containing products are widely commercially available for companion animals, mirroring popularity in human use. Although data on the safety and efficacy of long-term oral supplementation are increasing in dogs, evidence remains lacking in cats. The purpose of these studies was to address gaps in the knowledge around the long-term suitability and tolerance of a tetrahydrocannabinol (THC)-free CBD distillate in clinically healthy cats. The studies were randomized, blinded, and placebo-controlled. The first study supplemented cats with either a placebo oil (n = 10) or with 4 mg/kg body weight (BW) CBD in placebo oil (n = 9) daily, with a meal, for 4 weeks. The concentration of CBD in plasma was measured over 4 h at d0 (first dose) and again at d14 (after 2 weeks of daily dosing). The second study supplemented cats daily with either placebo oil (n = 10) or 4 mg/kg BW CBD in placebo oil (n = 10) for a period of 26 weeks. A comprehensive suite of physiological health measures was performed throughout the study at baseline (week 0) and after 4, 10, 18, and 26 weeks of feeding, followed by a 4-week washout sample (week 30). Postprandial plasma CBD time course data, at both d0 and d14, showed a peak plasma CBD concentration at 2 h after the dose. This peak was 251 (95% CI: 108.7, 393.4) and 431 (95% CI, 288.7, 573.4) ng/mL CBD at d0 and d14, respectively, and the area under the curve concentration was higher by 91.5 (95% CI, 33.1, 149.9) ng-h/mL after 2 weeks of supplementation (p = 0.002). While in the first study the CBD group displayed increased alanine aminotransferase (ALT; 68.7 (95% CI, 43.23, 109.2) U/L) at week 4 compared to the placebo control group [1.44-fold increase (95% CI, 0.813, 2.54)], statistical equivalence (at 2-fold limits) was found for ALT across the duration of the second, long-term study. All other biochemistry and hematology data showed no clinically significant differences between supplement groups. Data presented here suggest that a THC-free, CBD distillate fed at a dose of 4 mg/kg BW was absorbed into plasma and well tolerated by healthy cats when supplemented over a period of 26 weeks.</p

Table_2_Healthy cats tolerate long-term daily feeding of Cannabidiol.DOCX

Cannabidiol (CBD)-containing products are widely commercially available for companion animals, mirroring popularity in human use. Although data on the safety and efficacy of long-term oral supplementation are increasing in dogs, evidence remains lacking in cats. The purpose of these studies was to address gaps in the knowledge around the long-term suitability and tolerance of a tetrahydrocannabinol (THC)-free CBD distillate in clinically healthy cats. The studies were randomized, blinded, and placebo-controlled. The first study supplemented cats with either a placebo oil (n = 10) or with 4 mg/kg body weight (BW) CBD in placebo oil (n = 9) daily, with a meal, for 4 weeks. The concentration of CBD in plasma was measured over 4 h at d0 (first dose) and again at d14 (after 2 weeks of daily dosing). The second study supplemented cats daily with either placebo oil (n = 10) or 4 mg/kg BW CBD in placebo oil (n = 10) for a period of 26 weeks. A comprehensive suite of physiological health measures was performed throughout the study at baseline (week 0) and after 4, 10, 18, and 26 weeks of feeding, followed by a 4-week washout sample (week 30). Postprandial plasma CBD time course data, at both d0 and d14, showed a peak plasma CBD concentration at 2 h after the dose. This peak was 251 (95% CI: 108.7, 393.4) and 431 (95% CI, 288.7, 573.4) ng/mL CBD at d0 and d14, respectively, and the area under the curve concentration was higher by 91.5 (95% CI, 33.1, 149.9) ng-h/mL after 2 weeks of supplementation (p = 0.002). While in the first study the CBD group displayed increased alanine aminotransferase (ALT; 68.7 (95% CI, 43.23, 109.2) U/L) at week 4 compared to the placebo control group [1.44-fold increase (95% CI, 0.813, 2.54)], statistical equivalence (at 2-fold limits) was found for ALT across the duration of the second, long-term study. All other biochemistry and hematology data showed no clinically significant differences between supplement groups. Data presented here suggest that a THC-free, CBD distillate fed at a dose of 4 mg/kg BW was absorbed into plasma and well tolerated by healthy cats when supplemented over a period of 26 weeks.</p

Image_2_Healthy cats tolerate long-term daily feeding of Cannabidiol.JPEG

Cannabidiol (CBD)-containing products are widely commercially available for companion animals, mirroring popularity in human use. Although data on the safety and efficacy of long-term oral supplementation are increasing in dogs, evidence remains lacking in cats. The purpose of these studies was to address gaps in the knowledge around the long-term suitability and tolerance of a tetrahydrocannabinol (THC)-free CBD distillate in clinically healthy cats. The studies were randomized, blinded, and placebo-controlled. The first study supplemented cats with either a placebo oil (n = 10) or with 4 mg/kg body weight (BW) CBD in placebo oil (n = 9) daily, with a meal, for 4 weeks. The concentration of CBD in plasma was measured over 4 h at d0 (first dose) and again at d14 (after 2 weeks of daily dosing). The second study supplemented cats daily with either placebo oil (n = 10) or 4 mg/kg BW CBD in placebo oil (n = 10) for a period of 26 weeks. A comprehensive suite of physiological health measures was performed throughout the study at baseline (week 0) and after 4, 10, 18, and 26 weeks of feeding, followed by a 4-week washout sample (week 30). Postprandial plasma CBD time course data, at both d0 and d14, showed a peak plasma CBD concentration at 2 h after the dose. This peak was 251 (95% CI: 108.7, 393.4) and 431 (95% CI, 288.7, 573.4) ng/mL CBD at d0 and d14, respectively, and the area under the curve concentration was higher by 91.5 (95% CI, 33.1, 149.9) ng-h/mL after 2 weeks of supplementation (p = 0.002). While in the first study the CBD group displayed increased alanine aminotransferase (ALT; 68.7 (95% CI, 43.23, 109.2) U/L) at week 4 compared to the placebo control group [1.44-fold increase (95% CI, 0.813, 2.54)], statistical equivalence (at 2-fold limits) was found for ALT across the duration of the second, long-term study. All other biochemistry and hematology data showed no clinically significant differences between supplement groups. Data presented here suggest that a THC-free, CBD distillate fed at a dose of 4 mg/kg BW was absorbed into plasma and well tolerated by healthy cats when supplemented over a period of 26 weeks.</p