State‐of‐the‐Art‐Review: Immunomodulatory effects of opioids

Objective – To review the immunomodulatory effects of opioids. Data Sources – Original research publications and review articles using the PubMed search engine with the following keywords – opioids, morphine, immuomodulation, and immunosuppression. Veterinary and Human Data Synthesis – Opioids have been shown to modulate the immune system in animal models by affecting both the acquired and innate arms of the immune system. Natural killer cell activity, T‐cell proliferation, antibody production, phagocytic cell function, and cytokine production have all been shown to be affected by opioids. Many of these effects are reversed by opioid antagonists. Opioids have also been shown to induce sepsis in laboratory animals. Opioid administration alters immune parameters in healthy humans at analgesic doses and may increase the risk of infection in some patient populations. Conclusions – While opioids remain the most powerful and widely used analgesics available, their negative effects on the immune system are well established in the laboratory setting. Thoughtful consideration should be given to the use of certain opioids in critically ill patients, especially those with pre‐existing immunocompromise.     

Effects of N‐acetyl‐cysteine and N‐acetyl‐cysteine‐amide Supplementation on In Vitro Matured Porcine Oocytes

This study was conducted to evaluate the effects of different concentrations of the antioxidant N‐acetyl‐cysteine (NAC) supplemented to the maturation medium on porcine embryo development. Concentrations of NAC and its synthetic derivative, NAC‐amide (NACA) were evaluated for effects on nuclear maturation, fertilization success and embryo development. Concentrations of NAC (0, 0.5, 1.0, 1.5, 2.0, 2.5 and 5.0 mm ) were supplemented to maturing oocytes, and embryo development was analysed at 48 and 144 h post‐fertilization. There were no differences among cleavage rates for any of the treatment groups. Blastocyst formation for 1.5 mm NAC (56.5 ± 9.2%) was higher (p < 0.05) than all other supplementations. There were no differences in nuclear maturation or fertilization or in cleavage rates when comparing 1.5 mm NAC and 1.5 mm NACA supplementation to the control. Blastocyst formation for 1.5 mm NAC (44.4 ± 4.7%) and 1.5 mm NACA (46.2 ± 3.4%) supplementation were higher (p < 0.05) than the control (32.1 ± 6.2%) oocytes. These results indicate that supplementing 1.5 mm of NAC or NACA to the oocyte maturation medium increased the percentage of viable embryos reaching the blastocyst stage of development.     

Alterations in lycopene concentration and Z‐isomer content in egg yolk of hens fed all‐E‐isomer‐rich and Z‐isomer‐rich lycopene

Effects of feeding lycopene isomers to laying hens on egg qualities such as lycopene concentration and color of the yolk were investigated. Firstly, to evaluate the dietary transfer of lycopene to egg yolk, (all‐E)‐lycopene–rich diets (lycopene content, 100, 200, or 300 mg/kg diet) were fed to hens for 21 days. Lycopene in egg yolk could be detected after 4 days or more from the start of feeding, and the lycopene concentration increased according to the feed amount and period. Even though most of the dietary lycopene was the all‐E‐isomer, more than 65% of lycopene in egg yolk was present as Z‐isomers. Thus, the effect of lycopene Z‐isomer content in the diet (lycopene content, 200 mg/kg diet; lycopene Z‐isomer content, 35.1% or 61.3%) on egg qualities was investigated. As the Z‐isomer content increased, the lycopene concentration in the egg yolk increased, for example, when fed a diet rich in Z‐isomers (61.3%), the lycopene concentration in the egg yolk was approximately three times higher than when fed the (all‐E)‐lycopene–rich diet for 21 days. The results indicated that Z‐isomers of lycopene had higher bioavailability and/or higher transfer efficiency to the egg yolk than the all‐E‐isomer.     

Insulin‐independent actions of glucagon‐like peptide‐1 in wethers

Insulin‐independent actions of glucagon‐like peptide‐1 (GLP‐1) are not yet clear in ruminants. Four Suffolk mature wethers (60.0 ± 6.7 kg body weight (BW)) were intravenously infused with insulin (0.5 mU/kg BW/min; from 0 to 90 min) and GLP‐1 (0.5 μg/kg BW/min; from 60 to 150 min) with both hormones co‐administered from 60 to 90 min, in a repeated‐measure design under euglycemic clamp for 150 min, to investigate whether GLP‐1 has insulin‐independent actions. Jugular blood samples were taken at 15‐min intervals for plasma hormones and metabolites analysis. Compared to baseline concentrations (at 0 min), insulin infusion decreased (P < 0.05) plasma concentrations of glucagon, non‐esterified fatty acids (NEFA), lactate, nonessential amino acids (NEAA), branched‐chain amino acids (BCAA), total amino acids (TAA) and urea nitrogen (UN). Insulin plus GLP‐1 infusion induced a greater increase (P < 0.05) in plasma concentrations of insulin and triglyceride (TG), but decreased (P < 0.05) glucagon, total cholesterol (T‐Cho), NEAA and UN plasma concentrations. GLP‐1 infusion increased (P < 0.05) NEFA, β‐hydroxybutyrate and TG, but decreased (P < 0.05) glucagon, T‐Cho, NEAA, BCAA and UN plasma concentrations. In conclusion, GLP‐1 exerts extrapancreatic roles in ruminants not only insulin‐independent but probably, in contrast to non‐ruminants, antagonistic to insulin effects.     

Within‐ and across‐breed imputation of high‐density genotypes in dairy and beef cattle from medium‐ and low‐density genotypes

The objective of this study was to evaluate, using three different genotype density panels, the accuracy of imputation from lower‐ to higher‐density genotypes in dairy and beef cattle. High‐density genotypes consisting of 777 962 single‐nucleotide polymorphisms (SNP) were available on 3122 animals comprised of 269, 196, 710, 234, 719, 730 and 264 Angus, Belgian Blue, Charolais, Hereford, Holstein‐Friesian, Limousin and Simmental bulls, respectively. Three different genotype densities were generated: low density (LD; 6501 autosomal SNPs), medium density (50K; 47 770 autosomal SNPs) and high density (HD; 735 151 autosomal SNPs). Imputation from lower‐ to higher‐density genotype platforms was undertaken within and across breeds exploiting population‐wide linkage disequilibrium. The mean allele concordance rate per breed from LD to HD when undertaken using a single breed or multiple breed reference population varied from 0.956 to 0.974 and from 0.947 to 0.967, respectively. The mean allele concordance rate per breed from 50K to HD when undertaken using a single breed or multiple breed reference population varied from 0.987 to 0.994 and from 0.987 to 0.993, respectively. The accuracy of imputation was generally greater when the reference population was solely comprised of the breed to be imputed compared to when the reference population comprised of multiple breeds, although the impact was less when imputing from 50K to HD compared to imputing from LD.     

Ammonia‐oxidizing Archaea in laboratory‐scale activated sludge systems for wastewater of low‐ or high‐ammonium concentration

Ammonia‐oxidizing bacteria (AOB) is known as ammonia‐oxidizer in wastewater treatment systems. However, ammonia‐oxidizing Archaea (AOA) is found from various environments, including wastewater treatment systems. In this study, to investigate the relationships between AOA population and ammonia concentration, AOA was monitored in two laboratory‐scale reactors treating artificial wastewater of different ammonium concentrations by denaturing gradient gel electrophoresis targeting ammonia monooxygenase genes. At day 60 of the operation, AOA populations dominant in each reactor differed, suggesting the importance of influent ammonia concentration in dominant AOA selection.     

Non‐immunosuppressive FTY720‐derivative OSU‐2S mediates reactive oxygen species‐mediated cytotoxicity in canine B‐cell lymphoma

OSU‐2S is a FTY720 (Fingolimod) derivative that lacks immunosuppressive properties but exhibits strong anti‐tumour activity in several haematological and solid tumour models. We have recently shown OSU‐2S to mediate potent cytotoxicity in human mantle cell lymphoma cell lines and primary cells. We report here the pre‐clinical activity of OSU‐2S in spontaneous B‐cell lymphoma of dogs which shares many characteristics of human lymphoma. OSU‐2S mediated apoptosis in canine B‐cell lines and primary B‐cell lymphoma cells obtained from spontaneous lymphoma bearing dogs. OSU‐2S induced reactive oxygen species (ROS) in canine lymphoma cells and inhibition of ROS partially rescued OSU‐2S‐mediated cell death. These studies provide a rational basis for the use of spontaneous lymphoma in pet dogs as a preclinical large animal model for the development of OSU‐2S as small molecule for treating people and dogs with lymphoma.     

Low Occurrence of Extended‐Spectrum β‐lactamase‐Producing Escherichia coli in Finnish Food‐Producing Animals

ESBL/AmpC‐producing Escherichia coli is increasingly isolated from humans and animals worldwide. The occurrence of ESBL/AmpC‐producing E. coli was studied in food‐producing animals in Finland, a country with a low and controlled use of antimicrobials in meat production chain. A total of 648 cattle, 531 pig, 495 broiler and 35 turkey faecal samples were collected from four Finnish slaughterhouses to determine the presence of extended‐spectrum β‐lactamase (ESBL/AmpC)‐producing E. coli. In addition, 260 broiler and 15 turkey samples were screened for carbapenemase‐producing E. coli. Susceptibility to different class of cephalosporins and meropenem was determined with disc diffusion tests according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Determination of ESBL/AmpC production was performed with a combination disc diffusion test according to the recommendations of the European Food Safety Authority (EFSA). Plasmidic bla_ESBL/AmpC genes were characterized by polymerase chain reaction and sequencing. A collection of isolates producing AmpC enzyme but not carrying plasmidic bla_AmpC was analysed by PCR and sequencing for possible chromosomal ampC promoter area mutations. Altogether ESBL/AmpC‐producing E. coli was recovered from five cattle (0.8%), eight pig (1.5%) and 40 broiler samples (8.1%). No ESBL/AmpC‐producing E. coli was found in turkey samples. Carbapenem resistance was not detected. Altogether ESBL/AmpC‐producing E. coli was found on 4 (2.0%), 3 (4.5%) and 14 (25%) cattle, pig and broiler farms, respectively. From cattle samples 3 (27%) bla_CTX‐M‐1 and from broiler samples 13 (33%) bla_CTX‐M‐1 and 22 (55%) bla_CMY‐2 gene‐carrying isolates were detected. In pigs, no plasmidic bla_ESBL/AmpC gene‐carrying isolates were found. In all analysed isolates, the same mutations in the promoter region of chromosomal ampC were detected. The results showed low occurrence of ESBL/AmpC‐producing E. coli in Finnish food‐producing animals. In pigs, plasmidic bla_ESBL/AmpC‐carrying E. coli was not detected at all.     

Bone biomarkers and risk of fracture in two‐ and three‐year‐old Thoroughbreds

The aim of this study was to determine whether bone biomarkers (osteocalcin, PICP, ICTP and CTX‐I) could be used to identify 2‐ and 3‐year‐olds at increased risk of fracture in the subsequent flat racing season. It was concluded that these bone biomarkers cannot be used to identify 2‐ and 3‐year‐olds that sustain a fracture. Whether bone biomarkers have better predictive value in older horses or when measured serially in the same animal remains to be determined.