Health and immune traits of Basque and Large White pigs housed in a conventional or enriched environment

Since decades, production traits such as growth rate, feed efficiency or body composition have been drastically increased in pigs by genetic selection. Whether this selection impacted animal robustness is still unclear. In this study, we compared Large White (LW) pigs, a breed submitted to intense genetic selection for production traits, and Basque (B) pigs, a local rustic breed, reared in two different housing environments (conventional v. enriched). Adaptation to housing conditions among each breed was evaluated at the level of endocrine and immune traits. These are known to be impacted by housing conditions and breed; however, the interaction effects between genotype and environment are less described. Animals (20 per breed and housing environment) entered the experiment at 35 kg of live weight. Levels of cortisol, acute-phase inflammatory proteins, immunoglobulins and hydrogen peroxide, blood formula, lymphocyte proliferation and in-vitro cytokine expression were measured at ∼115 kg of live weight. Animals were checked for skin injuries during the growing period. At slaughter, at the average live weight of 145 kg, carcasses were examined for pathological conditions of the respiratory tract. The major result was that the two breeds exhibited differences in response to the housing environment. Among the 24 sanitary, endocrine or immune traits investigated, the housing conditions affected eight variables in both breeds (salivary cortisol at 0700 and 1900 h, severity of pneumonia at slaughter) or only in B pigs (severe skin lesions) or LW pigs (salivary cortisol at 1500 h, granulocyte numbers and lymphocyte/granulocyte ratio and lymphocyte proliferation). These observations strengthen the hypothesis that selection for high meat production level might be associated with an increased susceptibility of animals to environmental stressors.     

A mechanism for rapid neurosteroidal regulation of parenting behaviour

While systemic steroid hormones are known to regulate reproductive behaviour, the actual mechanisms of steroidal regulation remain largely unknown. Steroidogenic enzyme activity can rapidly modulate social behaviour by influencing neurosteroid production. In fish, the enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD) synthesizes 11-ketotestosterone (KT, a potent teleost androgen) and deactivates cortisol (the primary teleost glucocorticoid), and both of these steroid hormones can regulate behaviour. Here, we investigated the role of neurosteroidogenesis in regulating parenting in a haremic bidirectionally hermaphroditic fish, Lythrypnus dalli, where males provide all requisite parental care. Using an in vitro assay, we found that an 11β-HSD inhibitor, carbenoxolone (CBX), reduced brain and testicular KT synthesis by 90% or more. We modulated neurosteroid levels in parenting males via intracerebroventricular injection of CBX. Within only 20 min, CBX transiently eliminated parenting behaviour, but not other social behaviour, suggesting an enzymatic mechanism for rapid neurosteroidal regulation of parenting. Consistent with our proposed mechanism, elevating KT levels rescued parenting when paired with CBX, while cortisol alone did not affect parenting. Females paired with the experimental males opportunistically consumed unattended eggs, which reduced male reproductive success by 15%, but some females also exhibited parenting behaviour and these females had elevated brain KT. Brain KT levels appear to regulate the expression of parenting behaviour as a result of changes in neural 11β-HSD activity.     

Lack of glucose and hsp70 responses in haddock Melanogrammus aeglefinus (L.) subjected to handling and heat shock

Juvenile haddock Melanogrammus aeglefinus ( c. 39 g) were exposed to either a handling stressor (1 min out of water) or heat shock (increase from 10 to 15° C for 1 h), and plasma cortisol, plasma glucose and gill hsp70 levels were determined before, and at 1, 3, 6, 12, 24 and 48 h post-stress. The pattern of cortisol increase was similar following both stressors, with levels increasing by 25-fold at 1 h post-stress, but returning to pre-stress levels (2–5 ng ml⁻¹) by 3 h. In contrast, neither handling nor heat shock caused an increase in plasma glucose levels. Although gill hsp70 was detected, presumably constitutive levels, in both control and heat shocked groups, there were not significant changes in gill hsp70 levels after exposure to heat shock. The lack of glucose and hsp70 responses to these typical stressors is consistent with previous studies on Atlantic cod Gadus morhua , and suggests that the stress physiology of Gadidae differs from the 'typical' teleost.     

Echocardiographic Findings in Patients With Normocalcemic Primary Hyperparathyroidism Compared With Findings in Hypercalcemic Primary Hyperparathyroid Patients and Control Subjects

ObjectiveThere are no data regarding echocardiographic parameters in patients with normocalcemic primary hyperparathyroidism (NCPHPT). We compared the echocardiographic findings in postmenopausal women with NCPHPT with those in patients with hypercalcemic primary hyperparathyroidism (PHPT) and controls.MethodsSeventeen consecutive Caucasian postmenopausal women with NCPHPT were compared with 20 women with hypercalcemic PHPT and 20 controls. Obesity, diabetes, kidney failure, and previous cardiovascular diseases were considered exclusion criteria. Each patient underwent biochemical evaluation, bone mineral density scan, and echocardiographic measurements. Patients with parathyroid disorders underwent kidney ultrasound evaluation.ResultsPatients with PHPT had significantly higher mean total serum calcium, ionized calcium, 24-hour urinary calcium, and parathyroid hormone and lower mean phosphorus levels compared with those in the controls (all P < .05). The only differences between patients with NCPHPT and PHPT were significantly lower mean total serum calcium, ionized calcium, and 24-hour urinary calcium and higher phosphorus levels in patients with NCPHPT (all P < .05). The only biochemical difference between patients with NCPHPT and the controls was a higher level of mean parathyroid hormone in patients with NCPHPT. There were no differences in cardiovascular risk factors between patients with NCPHPT and PHPT and the controls. Hypertension was the most frequent cardiovascular risk factor, diagnosed in 65% of patients with PHPT. This high prevalence was not statistically significant compared with that observed in patients with NCPHPT (59%) and in the controls (30%). Echocardiography parameters were not different between patients with NCPHPT and PHPT and the controls when subdivided according to the presence of hypertension (ANOVA followed by Bonferroni correction).ConclusionIn a population with a low cardiovascular risk, we found no differences in cardiovascular risk factors and echocardiographic parameters between patients with NCPHPT and PHPT and the controls.     

Effects of softness of bedding materials upon overnight excretion of urinary catecholamines and sleep quality in warm environmental conditions

The purpose of this study was to investigate whether, when subjects were living in a moderately warm environment: (1) the softness of clothing worn during the daytime could influence the subjects’ preference in the evening for the softness of clothing and a face towel; and (2) the softness of bedding materials could modulate their nocturnal body temperature, overnight urinary catecholamine excretion, and sleep quality. Six females were tested during the luteal phase of their menstrual cycles. The experiment was conducted over three consecutive days and nights in a climatic chamber controlled at 28 ± 0.2 °C and 50% RH during the evening (from 19:30 to 21:30 h) and at 29 ± 0.2 °C and 50% RH during the sleep period (from 22:30 to 07:00 h). The first night was for adaptation to the experimental chamber. Five different sets of clothing and bedding were used; these were identical except for the softness/hardness of the materials used (due to treatment with fabric softener or starch), and material softness decreased in the order: Type A (softest)?>?Type B > Type C > Type D > Type E (hardest). There were two phases to the experiment, conducted in random order. In one phase, subjects wore “soft type” (Type B) T-shirt and shorts in the daytime and, in the other phase, “hard type” (Type D/E) T-shirt and shorts. In both phases, subjects were asked at 21:30 h to select a T-shirt and a face towel which they felt would be most comfortable to use. At night, they slept on bedding (a mattress cover, a pillowcase and a covering blanket) which was of the same degree of softness as the T-shirt and shorts that had been worn in the daytime in that phase. Rectal temperature, skin temperatures at seven sites, and body movement were measured during sleep, an overnight urine sample was taken for measurement of urinary excretion of adrenaline and noradrenaline, and subjective sleep quality was assessed on being woken the following morning. The main results were as follows: (1) T-shirt preference in the evening showed large inter-individual variation but did not differ significantly between the two phases (when “hard type” or “soft type” clothing had been worn during the daytime). The preferred texture of the face towel was softer than that of the T-shirt, the difference in softness between the chosen face towel and T-shirt being significant (p < 0.05 and p < 0.10, respectively, when having worn “soft type” and “hard type” clothing in the daytime). (2) Rectal temperature and mean skin temperature were not significantly different when sleeping with “soft type” (Type B) and “hard type” (Type D/E) bedding materials. (3) Overnight secretions of urinary adrenaline and noradrenaline were significantly less with “soft type” than “hard type” (p < 0.01 and p < 0.05 for adrenaline and noradrenaline, respectively) bedding. (4) When sleeping with “soft type” bedding materials, five out of the six subjects showed less body movements during the sleep period and reported that they had slept better. These results suggest that, in a moderately warm environment, bedding materials with a softer texture might be more comfortable to the subject (due to less tactile stimulation of the skin, which results in neurophysiological relaxation) and provide them with better sleep quality.     

Could protein content of Urinary Extracellular Vesicles be useful to detect Cirrhosis in Alcoholic Liver Disease?

Alcohol abuse has a high impact on the mortality and morbidity related to a great number of diseases and is responsible for the development of alcoholic liver disease (ALD). It remains challenging to detect and evaluate its severity, which is crucial for prognosis. In this work, we studied if urinary EVs (uEVs) could serve in diagnose and evaluate cirrhosis in ALD. To this purpose, uEVs characterization by cryo-electron microscopy (Cryo-EM), Nanoparticle Tracking Analysis (NTA) and Western blotting (WB) was performed in a cohort of 21 controls and 21 cirrhotic patients. Then, proteomics of uEVs was carried out in a second cohort of 6 controls and 8 patients in order to identify new putative biomarkers for cirrhosis in ALD. Interestingly, uEVs concentration, size and protein composition were altered in cirrhotic patients. From a total of 1304 proteins identified in uEVs, 90 of them were found to be altered in cirrhotic patients. The results suggest that uEVs could be considered as a tool and a supplier of new biomarkers for cirrhosis in ALD, whose application would be especially relevant in chronic patients. Yet, further research is necessary to obtain more relevant result in clinical terms.     

Differentially expressed glycoproteins in pre- and post-digital rectal examination urine samples for detecting aggressive prostate cancer

Urinary glycoproteins associated with aggressive prostate cancer (AG-PCa) were previously reported using post-digital rectal examination (DRE) urine specimens. To explore the potential of using pre-DRE urine specimens for detecting AG-PCa, we compared glycoproteins between pre- and post-DRE urine specimens, verified the previously identified post-DRE AG-PCa-associated urinary glycoproteins in pre-DRE urine specimens, and explored potential new glycoproteins for AG-PCa detection in pre-DRE urine specimens. Quantitative glycoproteomic data were acquired for 154 pre-DRE urine specimens from 41 patients with no cancer at biopsy, 48 patients with non-AG-PCa (Gleason score = 6), and 65 patients with AG-PCa (Gleason score 7 or above). Compared to glycopeptides from the post-DRE urine data, humoral immunity-related proteins were enriched in pre-DRE urine samples, whereas cell mediated immune response proteins were enriched in post-DRE urine samples. Analyses of AG-PCa-associated glycoproteins from pre-DRE urine revealed that the three urinary glycoproteins, prostate-specific antigen (PSA), prostatic acid phosphatase (ACPP), and CD97 antigen (CD97) that were previously identified in post-DRE urine samples, were also observed as AG-PCa associated glycoproteins in pre-DRE urine. In addition, we identified three new glycoproteins, fibrillin 1 (FBN1), vitronectin (VTN), and hemicentin 2 (HMCN2), to be potentially associated with AG-PCa in pre-DRE urine specimens. In summary, glycoprotein profiles differ between pre- and post-DRE urine specimens. The identified AG-PCa-associated glycoproteins may be further evaluated in large cohort of pre-DRE urine specimens for detecting clinically significant PCa.     

Design,synthesis, and biological evaluation of a novel series of peripheral-selective noradrenaline reuptake inhibitors – Part 3

Peripheral-selective inhibition of noradrenaline reuptake is a novel mechanism for the treatment of stress urinary incontinence to overcome adverse effects associated with central action. Here, we describe our medicinal chemistry approach to discover a novel series of highly potent, peripheral-selective, and orally available noradrenaline reuptake inhibitors with a low multidrug resistance protein 1 (MDR1) efflux ratio by cyclization of an amide moiety and introduction of an acidic group. We observed that the MDR1 efflux ratio was correlated with the pK_a value of the acidic moiety. The resulting compound 9 exhibited favorable PK profiles, probably because of the effect of intramolecular hydrogen bond, which was supported by a its single-crystal structure. The compound 9, 1-{[(6S,7R)-7-(4-chloro-3-fluorophenyl)-1,4-oxazepan-6-yl]methyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid hydrochloride, which exhibited peripheral NET-selective inhibition at tested doses in rats by oral administration, increased urethral resistance in a dose-dependent manner.     

Correlated response to selection for litter size environmental variability in rabbits’ resilience

Resilience is the ability of an animal to return soon to its initial productivity after facing diverse environmental challenges. This trait is directly related to animal welfare and it plays a key role in fluctuations of livestock productivity. A divergent selection experiment for environmental variance of litter size has been performed successfully in rabbits over ten generations. The objective of this study was to analyse resilience indicators of stress and disease in the divergent lines of this experiment. The high line showed a lower survival rate at birth than the low line (−4.1%). After correcting by litter size, the difference was −3.2%. Involuntary culling rate was higher in the high than in the low line (+12.4%). Before vaccination against viral haemorrhagic disease or myxomatosis, concentration of lymphocytes, C-reactive protein (CRP), complement C3, serum bilirubin, triglycerides and cholesterol were higher in the high line than in the low line (difference between lines +4.5%, +5.6 µg/ml, +4.6 mg/ml, +7.9 mmol/l, +0.3 mmol/l and +0.4 mmol/l). Immunological and biochemical responses to the two vaccines were similar. After vaccination, the percentage of lymphocytes and CRP concentration were higher in the low line than in the high one (difference between lines +4.0% and +13.1 µg/ml). The low line also showed a higher increment in bilirubin and triglycerides than the high line (+14.2 v. +8.7 mmol/l for bilirubin and +0.11 v. +0.01 mmol/l for triglycerides); these results would agree with the protective role of bilirubin and triglycerides against the larger inflammatory response found in this line. In relation to stress, the high line had higher basal concentration of cortisol than the low line (+0.2ng/ml); the difference between lines increased more than threefold after the injection of ACTH 1 to 24, the increase being greater in the high line (+0.9 ng/ml) than in the low line (+0.4 ng/ml). Selection for divergent environmental variability of litter size leads to dams with different culling rate for reproductive causes and different kits’ neonatal survival. These associations suggest that the observed fitness differences are related to differences in the inflammatory response and the corticotrope response to stress, which are two important components of physiological adaptation to environmental aggressions.