The effects of acute and chronic hypoxia on cortisol,glucose and lactate concentrations in different populations of three-spined stickleback

The response of individuals from three different populations of three-spined sticklebacks to acute and chronic periods of hypoxia (4.4 kPa DO, 2.2 mg l⁻¹) was tested using measures of whole-body cortisol, glucose and lactate. Although there was no evidence of a neuroendocrine stress response to acute hypoxia, fish from the population least likely to experience hypoxia in their native habitat had the largest response to low oxygen, with significant evidence of anaerobic glycolysis after 2 h of hypoxia. However, there was no measurable effect of a more prolonged period (7 days) of hypoxia on any of the fish in this study, suggesting that they acclimated to this low level of oxygen over time. Between-population differences in the analytes tested were observed in the control fish of the acute hypoxia trial, which had been in the laboratory for 16 days. These differences were not apparent among the control fish in the chronic exposure groups that had been held in the laboratory for 23 days, suggesting that these site-specific trends in physiological status were acclimatory. Overall, the results of this study suggest that local environmental conditions may shape sticklebacks’ general physiological profile as well as influencing their response to hypoxia.     

Subtilomycin: A New Lantibiotic from Bacillus subtilis Strain MMA7 Isolated from the Marine Sponge Haliclona simulans

Bacteriocins are attracting increased attention as an alternative to classic antibiotics in the fight against infectious disease and multidrug resistant pathogens. Bacillus subtilis strain MMA7 isolated from the marine sponge Haliclona simulans displays a broad spectrum antimicrobial activity, which includes Gram-positive and Gram-negative pathogens, as well as several pathogenic Candida species. This activity is in part associated with a newly identified lantibiotic, herein named as subtilomycin. The proposed biosynthetic cluster is composed of six genes, including protein-coding genes for LanB-like dehydratase and LanC-like cyclase modification enzymes, characteristic of the class I lantibiotics. The subtilomycin biosynthetic cluster in B. subtilis strain MMA7 is found in place of the sporulation killing factor (skf) operon, reported in many B. subtilis isolates and involved in a bacterial cannibalistic behaviour intended to delay sporulation. The presence of the subtilomycin biosynthetic cluster appears to be widespread amongst B. subtilis strains isolated from different shallow and deep water marine sponges. Subtilomycin possesses several desirable industrial and pharmaceutical physicochemical properties, including activity over a wide pH range, thermal resistance and water solubility. Additionally, the production of the lantibiotic subtilomycin could be a desirable property should B. subtilis strain MMA7 be employed as a probiotic in aquaculture applications.     

The REFLECT Statement: Methods and Processes of Creating Reporting Guidelines for Randomized Controlled Trials for Livestock and Food Safety by Modifying the CONSORT Statement†

The conduct of randomized controlled trials in livestock with production, health and food‐safety outcomes presents unique challenges that may not be adequately reported in trial reports. The objective of this project was to modify the CONSORT (Consolidated Standards of Reporting Trials) statement to reflect the unique aspects of reporting these livestock trials. A 2‐day consensus meeting was held on 18–19 November 2008 in Chicago, IL, USA, to achieve the objective. Prior to the meeting, a Web‐based survey was conducted to identify issues for discussion. The 24 attendees were biostatisticians, epidemiologists, food‐safety researchers, livestock‐production specialists, journal editors, assistant editors and associate editors. Prior to the meeting, the attendees completed a Web‐based survey indicating which CONSORT statement items may need to be modified to address unique issues for livestock trials. The consensus meeting resulted in the production of the REFLECT (Reporting Guidelines for Randomized Control Trials) statement for livestock and food safety and 22‐item checklist. Fourteen items were modified from the CONSORT checklist and an additional sub‐item was proposed to address challenge trials. The REFLECT statement proposes new terminology, more consistent with common usage in livestock production, to describe study subjects. Evidence was not always available to support modification to or inclusion of an item. The use of the REFLECT statement, which addresses issues unique to livestock trials, should improve the quality of reporting and design for trials reporting production, health and food‐safety outcomes.     

Bioeconomic evaluation of sow longevity and profitability

Sow production indicators, including litter size, litter weight, and the length of time that sows remained in the herd (sow longevity), were used to characterize sow performance and profitability. Sow longevity and production records from 148,568 sows in 32 commercial herds from Central Illinois from January 1995 to May 2001 were analyzed using survival and repeatability models, respectively. The factors studied included sow genetics (32 genetic lines), with eight major lines present in multiple herds, and the combination of herd and year of entry in the herd. The largest difference in longevity between the major genetic lines was approximately one parity. There were differences (P < 0.05) in the instantaneous sow removal rate or hazard from the major lines. These differences constitute evidence that sow longevity could be improved by using replacements from specific genetic lines. The net present value per sow (present value of future cash flows and the present value of the sow) was used to evaluate the effect of sow longevity and production traits on economic returns. Assuming a zero discount rate per parity, genetic lines with longer herd life resulted in greater profit than genetic lines with shorter herd life. This difference was reduced with increasing discount rates and was reversed with high discount rates and low net income per litter. These results suggest that the magnitude of the economic improvement attained through the use of sow genetic lines with longer longevity depends on the economic context under which the evaluation is made.     

A sequential study of experimental infection of pigs with porcine circovirus and porcine parvovirus: immunostaining of cryostat sections and virus isolation

The sequential tissue distribution of virus was investigated using virus isolation and immunofluorescence tests in 1-day-old piglets inoculated with porcine circovirus 2 (PCV2) and/or porcine parvovirus (PPV). Enlarged mesenteric lymph nodes were seen in the pig inoculated with PCV2 alone and killed at 26 days post-inoculation (PI). One of the pigs inoculated with PCV2 and PPV and killed at 21 days PI had an enlarged liver. The pig killed at 26 days PI in this group had enlarged liver, kidneys and heart. Histopathological changes were seen in lymphoid tissues of the pigs inoculated with PCV2 alone and killed at 14 and 26 days PI. Similar, but more severe, lesions were observed in the pigs infected with PCV2 and PPV and killed from 10 days PI onwards. Histological lesions of nephritis, pneumonia and hepatitis were also apparent in these animals. Mild nephritis was also seen in the pigs infected with PPV alone and killed at 14 and 26 days PI. Moderate amounts of PPV antigen were detected in tissues from the pigs inoculated with PPV alone and killed at 14 days PI. Low levels of PCV antigen were detected, mainly in lymphoid tissues, in the pigs inoculated with PCV alone and killed at 14 days PI. Low to moderate amounts of PCV antigen were detected in a wider range of tissues in the pig in this group killed at 26 days PI. In the pigs inoculated with both viruses, PPV antigen was detected in tissues of pigs killed from 3 to 26 days PI with maximal amounts detected between 6 and 14 days PI. PCV2 antigen was detected in low to moderate amounts in the tissues of pigs killed at 14 days PI. Large amounts of PCV2 antigen were detected in most of the tissues from pigs in this group killed between 17 and 26 days PI. Virus isolation results for PCV2 generally correlated well with the results for immunofluorescent staining. PPV was isolated from almost all tissues from pigs inoculated with PCV2 and PPV, a much higher incidence of positive tissues than observed for immunofluorescent staining.     

Farm-level risk factors for the presence of Salmonella in 89 Alberta swine-finishing barns

This study investigated potential risk factors for the presence of Salmonella on 89 Alberta swine-finishing farms with the use of a questionnaire. Salmonella status was regressed on each fixed effect in a logistic mixed regression model, with farm as the random effect. Eleven variables were significant at the 10% level: farm type, number of square feet per pen, number of pigs per pen, source of feed, ration type, dust control measures, cat presence, reported effective mouse-control measures, time required to be away from pigs before visiting the farm, precautions taken when entering or leaving the farm, and reported use of antimicrobials through water. Three factors remained significant at the 5% level in the multivariable analysis: farm type, ration type, and precautions taken when entering or leaving the farm. Finishing barns at multisite operations or individual grow-to-finish farms had a greater risk of the presence of Salmonella at a single visit than did finishing barns at farrow-to-finish farms. The use of pelleted and wet feed was associated with higher odds of the presence of Salmonella than was the use of meal feed. Farms that required their personnel or visitors to shower before entering and before leaving had increased odds of the presence of Salmonella compared with farms that provided boots and coveralls; no significant difference was observed between the latter category and farms that used boot disinfection. Further work is necessary to better understand the effectiveness of all-in/all-out pig management and disinfection practices in reducing the presence of Salmonella in swine and to evaluate the association with certain types of feed.     

Predicting growth in angus bulls: the use of GHRH challenge, insulin-like growth factor-I, and insulin-like growth factor binding proteins

Plasma IGF-I, IGF binding protein-2 (IGFBP-2), and IGFBP-3 were quantified in growing Angus bulls (n = 56) to determine their relationship with postweaning growth and carcass ultrasound measurements. In addition, GH response to GHRH challenge (area-under-the-curve GH [AUC-GH) was determined for each bull as part of a previous study. Blood was collected by jugular venipuncture at the start of a 140-d postweaning growth performance test and at 28 d intervals for plasma IGF-I determination by RIA. Plasma IGFBP-2 and -3 content was measured at the start of the study, on d 70, and d 140 by Western ligand blotting. Individual weights and hip heights were measured every 28 d during the study and carcass longissimus muscle area, intramuscular fat percentage, and carcass backfat were estimated by ultrasound on d 140. Greater plasma IGF-I at the start of the performance test was associated with reduced postweaning ADG and increased longissimus area. Throughout the performance test period, the correlations between plasma IGF-I and hip height were consistently positive, ranging from 0.10 to 0.38, but the correlations between ADG and IGF-I varied from -0.32 to 0.31. Age-adjusted d-1 plasma IGFBP-2 was related to ADG during the performance test, explaining nearly 30% of the variation in ADG. A model combining weaning age, IGFBP-2, and AUC-GH showed a strong relationship with ADG (R2 = 0.40). Plasma IGFBP-2 and -3 were not related to carcass characteristics, and IGFBP-3 was not related to growth rates. This study provides additional evidence for the variable relationship between plasma IGF-I and growth rates in cattle. A significant positive relationship between plasma IGFBP-2, AUC-GH, and postweaning ADG warrants further investigation.     

Pharmacokinetics of ponazuril after administration of a single oral dose to green turtles (Chelonia mydas)

The coccidian protozoan, Caryospora cheloniae, has been associated with severe enteritis and encephalitis in immature farm-raised green turtles (Chelonia mydas) in the Cayman Islands, immature green turtles off the coast of Florida, and immature stranded sea turtles in Australia. An effective anti-coccidial drug that is both orally absorbed and well-distributed throughout the body is needed for treatment of turtles diagnosed with coccidiosis in rehabilitation facilities. Ponazuril is a triazine antiprotozoal drug that is approved in the USA for the treatment of another Apicomplexan, Sarcocystis neurona, and has also been successfully used in the therapy of other coccidian parasites. The objective of this study was to perform an oral dose-ranging pilot study (10–100 mg/kg of body weight ponazuril) in green turtles (N = 9), followed by oral administration of ponazuril at 100 mg/kg body weight (N = 8) to assess its disposition. Another goal of this study was to optimize the method of oral drug administration to green turtles. Plasma ponazuril concentrations were quantified using high performance liquid chromatography (HPLC). Standard compartmental models were fit to the data. Ponazuril was absorbed after oral administration at 100 mg/kg BW, with a maximum plasma concentration of 3.3 µg/ml. Dose-dependent pharmacokinetic parameters only weakly correlated with the dose rate, apparently due to considerable pharmacokinetic variability observed between turtles. Administration of ponazuril in gelatin capsules using a balling gun was deemed the least variable and most successful method of drug administration. Further studies are needed to evaluate the safety and efficacy of ponazuril in sea turtles with coccidiosis.     

Not Drug-like,but Like Drugs: Cnidaria Natural Products

Phylum Cnidaria has been an excellent source of natural products, with thousands of metabolites identified. Many of these have not been screened in bioassays. The aim of this study was to explore the potential of 5600 Cnidaria natural products (after excluding those known to derive from microbial symbionts), using a systematic approach based on chemical space, drug-likeness, predicted toxicity, and virtual screens. Previous drug-likeness measures: the rule-of-five, quantitative estimate of drug-likeness (QED), and relative drug likelihoods (RDL) are based on a relatively small number of molecular properties. We augmented this approach using reference drug and toxin data sets defined for 51 predicted molecular properties. Cnidaria natural products overlap with drugs and toxins in this chemical space, although a multivariate test suggests that there are some differences between the groups. In terms of the established drug-likeness measures, Cnidaria natural products have generally lower QED and RDL scores than drugs, with a higher prevalence of metabolites that exceed at least one rule-of-five threshold. An index of drug-likeness that includes predicted toxicity (ADMET-score), however, found that Cnidaria natural products were more favourable than drugs. A measure of the distance of individual Cnidaria natural products to the centre of the drug distribution in multivariate chemical space was related to RDL, ADMET-score, and the number of rule-of-five exceptions. This multivariate similarity measure was negatively correlated with the QED score for the same metabolite, suggesting that the different approaches capture different aspects of the drug-likeness of individual metabolites. The contrasting of different drug similarity measures can help summarise the range of drug potential in the Cnidaria natural product data set. The most favourable metabolites were around 210–265 Da, quite often sesquiterpenes, with a moderate degree of complexity. Virtual screening against cancer-relevant targets found wide evidence of affinities, with Glide scores <−7 in 19% of the Cnidaria natural products.