Evaluation of post-operative complications after mastectomy performed without perioperative antimicrobial prophylaxis in dogs.

BACKGROUND: Mastectomy is the most common procedure for treatment of mammary tumours. Dogs undergoing mastectomy have a risk of developing surgical site infections (SSI) and other postoperative complications. However, potential risk factors associated with such complications have been sparsely investigated. Thus, the objective of this retrospective study was to determine the incidence of, and identify risk factors for, SSI and non-SSI postoperative complications after mastectomy performed without perioperative antimicrobial prophylaxis in privately owned otherwise clinically healthy dogs. RESULTS: Medical records were reviewed retrospectively for 135 client-owned female dogs, 10-35 kg in weight and three to 10 years of age, which had undergone mastectomy due to mammary tumours at three referral animal hospitals in Sweden over a 3-year period. Twelve (8.9%) dogs developed SSI, and 21 dogs (17.1%) dogs suffered a non-SSI postoperative complication. The incidence of SSI and all complications (SSI and non-SSI) were higher in dogs that had two to three (SSI: P = 0.036 and all complications: P = 0.0039) and four to five (SSI and all complications: P = 0.038) mammary glands excised, compared to dogs that had one mammary gland excised. The incidence of SSI was 1.7% (n = 1/60) in dogs that had one gland removed. The incidence of non-SSI postoperative complications was higher in dogs with a higher body weight (P = 0.02). CONCLUSIONS: The incidence of SSI was lower than or similar to previously reported incidences of SSI in dog populations that have undergone tumour excisional surgery, despite the fact that dogs in the present study had not received perioperative antibiotics. Dogs that had two or more glands excised had an increased risk of developing SSI and non-SSI complications compared to dogs that had one gland excised. Furthermore, higher BW was associated with an increased risk of non-SSI complications. Results from the study indicate that routine use of perioperative antibiotics in tumour excisional surgery can be questioned, at least in single gland mastectomy in otherwise clinically healthy dogs.

Heavy metal concentrations in female wild mink (Neovison vison) in Sweden: Sources of variation and associations with internal organ weights.

The American mink is an invasive species in Sweden, and it is legally hunted all year. Therefore, the mink is well suited as a sentinel species for environmental monitoring. In the present study female mink (n = 91) from 6 different areas in Sweden were analyzed for the concentrations of silver, cadmium, mercury and lead in liver tissue using inductively coupled plasma mass spectrometry. The wet concentrations in liver tissue were 42.6 ± 52.7 ng/g for silver, 99.5 ± 100 ng/g for cadmium, 652 ± 537 ng/g for mercury, and 196 ± 401 ng/g for lead (expressed as mean ± standard deviation). There were associations between the sample area and the concentrations of silver, lead, and mercury. The concentrations of lead and cadmium varied with season of capture and lead, cadmium, and mercury were positively associated with increasing age. Relative liver weight was positively associated with concentrations of mercury and negatively associated with lead and cadmium. Relative kidney weight was negatively associated with lead concentrations. In summary, it is of importance to take age and season of capture into account when assessing levels of heavy metals in wild mink. Also, liver and kidneys seem to be potential targets for heavy metal toxicity in wild female mink in Sweden. Environ Toxicol Chem 2017;36:2030-2035. © 2016 The Authors. Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc. on behalf of SETAC.

Environmental pollutants and dysregulation of male puberty--a comparison among species.

The scientific literature on altered onset of puberty predominantly involves studies on females. This paper reviews current knowledge on the role of environmental pollutants in dysregulation of male puberty in humans, laboratory rodents and farm animals. The methods used to determine the onset of puberty are well developed in humans and farm animals, and standardized across studies in humans. In laboratory rodents standardized external morphological endpoints are used. There is an increasing weight of evidence from epidemiological studies in humans, as well as from experiments in animals, indicating that environmental pollutants dysregulate puberty in males. Most data are from studies on "classical" persistent environmental pollutants. Assessing the effect of multichemical environmental pollution on dysregulation of puberty in humans is more challenging; further solid epidemiological data would likely contribute most to our understanding, especially if combined with systematically collected field-data from selected wildlife.

Morphology and morphometry of the reproductive organs in prepubertal and postpubertal male pigs exposed to di(2-ethylhexyl) phthalate before puberty: Precocious development of bulbourethral glands.

In a split-litter design experiment, male piglets were exposed orally three times weekly to 300 mg/kg of di(2-ethylhexyl) phthalate (DEHP) or placebo between three and seven weeks of age. The effects on the reproductive organs were examined immediately after the exposure at seven weeks of age in one sub-group, and postpuberally at nine months of age in the other. Morphological features of testes were unaffected at either age group; there were no differences (p>0.05) between the treatments in number of Sertoli cells (as identified by immunostaining with GATA-4 antibodies), percent area of Leydig cells (as detected by 3beta-hydroxysteroid dehydrogenase histochemistry), or incidence of germinal epithelial lesions (histopathology of H&E-stained (hematoxylin and eosin) sections). Three of the seven DEHP-treated animals in seven-week-old group had bulbourethral glands at a stage of maturation far more advanced than that of controls. While there were no obvious differences in the cellular composition between the treatment groups in nine-month-old animals, the bulbourethral glands were heavier (p<0.05) in DEHP-treated boars. Collectively, these features indicate that adolescent exposure to DEHP induces precocious maturity of bulbourethral glands in pigs with persistent effects lasting into adulthood.

Pharmacokinetics of the adrenocorticolytic compounds 3-methylsulphonyl-DDE and o,p'-DDD (mitotane) in Minipigs.

The pharmacokinetics of the adrenocorticolytic drug candidate 3-Methylsulphonyl-DDE (3-MeSO2-DDE) and the anticancer drug o,p'-DDD (mitotane) were studied in Göttingen minipigs. The animals were given 3-MeSO2-DDE or o,p'-DDD as single oral doses (30 mg/kg). Concentrations in plasma and subcutaneous fat were measured by gas chromatography at different time points during 180 days. Maximal plasma concentrations appeared within 24 h for both compounds, but were about 2 times higher for 3-MeSO2DDE. o,p'-DDD plasma concentrations declined rapidly to low levels during 4 days. 3-MeSO2-DDE also decreased rapidly, but remained at high concentrations throughout the study. In fat, 3-MeSO2-DDE reached about 25-fold higher levels than o,p'-DDD at 30 days, and both substances were eliminated slowly from this tissue. 3-MeSO2-DDE liver concentrations were about 18-fold higher than those in plasma at 180 days. In contrast, o,p'-DDD liver and plasma levels were about equal at 180 days. o,p'-DDD had roughly 45 times larger CL/F than 3-MeSO2-DDE, confirming that the elimination of this compound was more rapid. Both compounds were characterised by their localisation and retention in fat tissue, and the individual size of the fat stores clearly determined the plasma concentrations. It is concluded that although 3-MeSO2-DDE is an interesting candidate for therapeutic use due to its potential characteristics to specifically target adrenocortical tumour cells the slow elimination of the compound might make it challenging to design appropriate dosage regimes.

Does exposure to di(2-ethylhexyl) phthalate in pre-pubertal boars affect semen quality post-puberty?

Di(2-ethylhexyl) phthalate (DEHP), a plastic softener used in polyvinyl chloride (PVC) products, has been ascribed to have toxic effects on animal reproduction. The present study aimed at determining potential late effects of pre-pubertal oral exposure to DEHP on semen quality in young pigs. Ten pairs of cross-bred male siblings were used. One brother in each pair became, at random, the test animal while the other acted as control. Test males were exposed to 300 mg/kg body weight (bw) of DEHP administered orally three times a week from 3 to 7 weeks of age. The control group was given placebo (water). Semen analyses started when the boars reached 6 months of age, with semen collected twice weekly, until animals were 9 months of age. Semen was evaluated for ejaculate volume, sperm concentration, total sperm count, sperm motility, sperm morphology (including presence of cells other than spermatozoa) and sperm plasma membrane integrity. Total sperm motility tended to be lower while local motility was higher in the DEHP-exposed group compared with controls (p = 0.07) when assessed by computer-assisted sperm analysis. The DEHP-exposed group had a significantly (p < 0.05) lower percentage of spermatozoa with tailless, defective heads (at 7-8 months of age) and double-folded tails (at 6-7, 7-8 and 6-9 months of age), compared with controls (albeit always under 5%). In summary, there were no obvious adverse effects of early oral exposure to 300 mg/kg bw of DEHP on sperm output and sperm quality in post-pubertal young boars.

Early post-natal exposure to low dose oral di(2ethylhexyl) phthalate affects the peripheral LH-concentration in plasma, but does not affect mating behavior in the post-pubertal boar.

In a split-litter design experiment, boars were exposed orally three times weekly to 300 mg/kg of di(2-ethylhexyl) phthalate (DEHP) between 3 and 7 weeks of age. Post-puberty, i.e. at 6 months of age the effects on endocrinology and mating behavior were examined. The response to stimulation with a synthetic GnRH-analogue at 9 months of age resulted initially in lower concentration of LH in the exposed animals, compared to the control animals. We did not find any effects of DEHP on the mating behavior. Also, the effects of DEHP during the treatment period on the plasma concentrations of testosterone, oestradiol and LH were examined. During the exposure period there was a transient decrease in plasma concentrations of LH in the control group, which did not occur in the boars exposed to DEHP. The data suggest that DEHP in low repeated oral doses causes lasting effects on the hypothalamus-pituitary-gonadal axis.

Delayed effects on plasma concentration of testosterone and testicular morphology by intramuscular low-dose di(2-ethylhexyl)phthalate or oestradiol benzoate in the prepubertal boar.

The immediate and delayed effects of prepubertal exposure to di(2-ethylhexyl)phthalate (DEHP) or oestradiol benzoate on the plasma concentrations of testosterone, oestradiol and LH, as well as testicular morphology were examined in prepubertal boars. In a split litter design experiment, prepubertal boars were intramuscularly exposed to DEHP, oestradiol or vehicle during five weeks, starting at six weeks of age. The dose of DEHP was 50mg/kg of bodyweight twice weekly, which is in the same range as recently used oral doses in rodents. Oestradiol-benzoate was administered at 0.25mg/kg of bodyweight twice weekly. One set of animals was examined immediately after the exposure, and the other set was examined at an age of 7.5 months. During the exposure period concentrations of LH in plasma were lower (p=0.02) in the oestradiol-treated animals than in the control group. In the group exposed to oestradiol, the relative to the body weight of the testicles tended to be lower (p=0.07) than control immediately after five weeks of exposure, and the relative to the body weight of the seminal vesicles tended to be lower (p=0.05) than control at 7.5 months of age. In the DEHP-exposed group an elevated (p=0.005) concentration of testosterone and increased (p=0.04) area of the Leydig cells in the testicles compared to the control group were seen at 7.5 months of age. These data suggest that DEHP early in life causes delayed effects on the reproductive system in the adult.

Kinetics of orally administered di(2-ethylhexyl) phthalate and its metabolite, mono(2-ethylhexyl) phthalate, in male pigs.

Di(2-ethylhexyl) phthalate (DEHP) is used as a plastic softener in the polymer industry and is widespread in medical devices. DEHP has been incriminated as an endocrine-disrupting chemical, and the effects of DEHP in various species have included disturbances in the reproductive system. The effects of the chemical have varied, depending upon exposure routes and species. This study was performed in order to characterise the kinetics of DEHP and its metabolite mono(2-ethylhexyl) phthalate (MEHP) in the young male pig, an omnivore model-species for research in reproductive toxicology. Eight pigs were given 1000 mg DEHP/kg bodyweight by oral gavage. The concentrations of DEHP and MEHP were then measured in the plasma and tissues of the pigs at different time points after administration. There was no consistent rise above contamination levels of concentrations of DEHP in the plasma of the pigs. However, the metabolite MEHP reached the systemic blood circulation. The half-life of MEHP in the systemic blood circulation was calculated to be 6.3 h. Absorption from the intestine was biphasic in six of the eight pigs and the mono-exponential elimination-phase started 16 h after the after the administration of DEHP. To conclude, MEHP consistently reaches the systemic circulation in the pig when DEHP is administered orally. The kinetic pattern of the parent substance on the other hand is more difficult to characterise.