Do calcium and magnesium deficiencies in reproducing ewes contribute to high lamb mortality?

2020 ◽  
Vol 60 (6) ◽  
pp. 733 ◽  
Author(s):  
Michael A. Friend ◽  
Marie S. Bhanugopan ◽  
Shawn R. McGrath ◽  
Janelle Hocking Edwards ◽  
Serina Hancock ◽  
...  

High lamb mortality continues to be a significant economic and welfare problem within the Australian sheep industry, with 20–30% of lambs born in commercial flocks dying mostly within 3 days of birth. Clinical hypocalcaemia and hypomagnesaemia cause ewe mortality, and, subsequently, either fetal or lamb death, but it is not known whether subclinical deficiencies of calcium (Ca) and magnesium (Mg) compromise lamb survival. This review considers the potential mechanisms through which Ca and Mg deficiencies may influence lamb survival, and factors influencing the risk of deficiency. Pastures grazed by lambing ewes may be marginal in calcium (Ca; <4 g/kg DM) and magnesium (Mg; <0.9 g/kg DM) but also have a high dietary cation–anion difference (>12 meq/100 g DM) and high concentrations of potassium (K; >30 g/kg DM) and nitrogen. In young cereal crops, sodium concentrations are also often low (<0.9 g/kg DM). This combination of minerals and other nutrients creates an imbalance in supply and increases susceptibility to acute Ca (hypocalcaemia) and Mg (hypomagnesaemia) deficiency. Calcium is required for smooth muscle function and has a direct role in uterine contraction, so may influence the duration of parturition. Low Ca and Mg intake both influence insulin release and sensitivity, low Mg results in poor glycaemic control and insulin resistance by impairing both insulin secretion and its action on peripheral tissues, also potentially altering the duration of parturition as well as risk of metabolic disease. Magnesium is also a neuroprotectant that slows the neuronal damage during hypoxia and has been linked with thermogenesis in offspring and increased immunoglobulins in colostrum. These functions indicate potential importance in improving the ease of parturition and improved ability of the newborn lamb to thermoregulate and survive after birth. Subclinical Ca and Mg deficiencies commonly occur in 20% of lambing ewes grazing temperate pastures, so further studies are warranted to investigate whether correction of these deficiencies can improve lamb survival.

2014 ◽  
Vol 54 (6) ◽  
pp. 736 ◽  
Author(s):  
D. J. Brown ◽  
R. M. Jones ◽  
G. N. Hinch

Heritabilities and genetic correlations were estimated between individual and composite autopsy traits for lambs autopsied in the Australian Sheep Cooperative Research Centre information nucleus flocks between 2008 and 2011 (n = 3224). Correlations were also estimated between autopsy categories and the production parameters Yearling greasy-fleece weight and Yearling weight, and the potential survival indicator traits: Lamb ease, Thorax circumference and Crown–rump length. All autopsy trait heritability estimates were low (range 0.01–0.04). For all traits, a higher proportion of the variance was partitioned into the maternal permanent environment than the direct effects (range 0.01–0.12), suggesting that selection based on lamb autopsy results would impart little advantage over the lamb survival trait itself in improving lamb survival. Genetic correlations between Lamb ease and all autopsy traits were positive, indicating that birth trauma is related to all causes of lamb deaths and that Lamb ease may be a useful selection criterion in seedstock flocks to reduce overall mortality. There were also positive genetic correlations between Thorax circumference after adjusting for birthweight and two classes of dystocia, as well as a positive correlation between Thorax circumference and incidences of Starvation mismothering, implying that Thorax circumference may be a useful indirect field measurement to reduce death from these causes. Of concern were the antagonistic genetic correlations estimated between Yearling greasy-fleece weight and a composite trait of All Dystocia classes plus Starvation mismothering (0.27 ± 0.15), implying that selection for increased fleece weight could be having a detrimental effect on overall lamb survival.


Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 896 ◽  
Author(s):  
Günter A. Müller ◽  
Andreas W. Herling ◽  
Susanne Wied ◽  
Timo D. Müller

(1) Background: Acute administration of the cannabinoid receptor 1 (CB1R) inverse agonist Rimonabant (SR141716A) to fed Wistar rats was shown to elicit a rapid and short-lasting elevation of serum free fatty acids. (2) Methods: The effect of Rimonabant on lipolysis in isolated primary rat adipocytes was studied to raise the possibility for direct mechanisms not involving the (hypothalamic) CB1R. (3) Results: Incubation of these cells with Rimonabant-stimulated lipolysis to up to 25% of the maximal isoproterenol effect, which was based on both CB1R-dependent and independent mechanisms. The CB1R-dependent one was already effective at Rimonabant concentrations of less than 1 µM and after short-term incubation, partially additive to β-adrenergic agonists and blocked by insulin and, in part, by adenosine deaminase, but not by propranolol. It was accompanied by protein kinase A (PKA)-mediated association of hormone-sensitive lipase (HSL) with lipid droplets (LD) and dissociation of perilipin-1 from LD. The CB1R-independent stimulation of lipolysis was observed only at Rimonabant concentrations above 1 µM and after long-term incubation and was not affected by insulin. It was recapitulated by a cell-free system reconstituted with rat adipocyte LD and HSL. Rimonabant-induced cell-free lipolysis was not affected by PKA-mediated phosphorylation of LD and HSL, but abrogated by phospholipase digestion or emulsification of the LD. Furthermore, LD isolated from adipocytes and then treated with Rimonabant (>1 µM) were more efficient substrates for exogenously added HSL compared to control LD. The CB1R-independent lipolysis was also demonstrated in primary adipocytes from fed rats which had been treated with a single dose of Rimonabant (30 mg/kg). (4) Conclusions: These data argue for interaction of Rimonabant (at high concentrations) with both the LD surface and the CB1R of primary rat adipocytes, each leading to increased access of HSL to LD in phosphorylation-independent and dependent fashion, respectively. Both mechanisms may lead to direct and acute stimulation of lipolysis at peripheral tissues upon Rimonabant administration and represent targets for future obesity therapy which do not encompass the hypothalamic CB1R.


2020 ◽  
Vol 98 (11) ◽  
Author(s):  
Tom Flinn ◽  
Jessica R Gunn ◽  
Karen L Kind ◽  
Alyce M Swinbourne ◽  
Alice C Weaver ◽  
...  

Abstract High preweaning mortality rates cost the Australian sheep industry an estimated $540 million annually in lost production, with losses significantly greater in twin (≥30%) compared with singleton lambs (≥10%). Previous intensive studies demonstrated that supplementing pregnant ewes with melatonin reduces adverse effects of fetal growth restriction and perinatal hypoxia on the neonatal brain via increased umbilical blood flow, placental efficiency, and antioxidant actions. The current study examined the effects of supplementing ewes with melatonin on the survival of twin Merino lambs under extensive grazing conditions. Pregnant mixed age ewes were implanted with 1 (M1, n = 50) or 2 (M2, n = 53) slow-release melatonin implants (18 mg, Regulin) at gestational days 70 to 90. Control ewes received no supplementation (CTL, n = 54). Ewes were monitored twice daily throughout the lambing period. Lamb survival, weight, and rectal temperature were recorded on the day of birth. Lamb blood samples were taken the following day for serum immunoglobulin G (IgG) analysis. Lamb survival and weight were recorded again at marking (30.6 ± 0.6 d postpartum) and weaning (70.7 ± 0.6 d postpartum). Lamb survival was increased in both melatonin treatments to 3 d postpartum (M1 = 98.0%; M2 = 95.3%; CTL = 83.3%; each P < 0.01), and this improvement was maintained to weaning (M1 = 94.0%; M2 = 92.5%; CTL = 79.6%; each P < 0.01). Melatonin did not affect lamb birthweight, rectal temperature, or growth rate. However, the rates of parturition-related death (dystocia, stillbirth, and birth injury) were greater in CTL lambs than M1 (P = 0.009) and M2 (P = 0.035). This suggests that improved survival is primarily due to melatonin-induced neuroprotection, although further studies are required to clarify the underlying mechanisms. These data provide evidence that supplementing pregnant twin-bearing Merino ewes with melatonin may be a practical strategy to reduce neonatal mortality and improve weaning rates in extensively managed sheep flocks. Although the present data are promising, this study is limited by small sample size and requires further replication.


2008 ◽  
Vol 36 (05) ◽  
pp. 981-988 ◽  
Author(s):  
Elaine Lin ◽  
Yong Wang ◽  
Sangeeta Mehendale ◽  
Shi Sun ◽  
Chong-Zhi Wang ◽  
...  

Hyperglycemia in diabetic conditions may cause oxidative stress in pancreatic ß-cells, leading to their dysfunction and insulin resistance within peripheral tissues. Previous studies suggest that American ginseng berry extract may have hypoglycemic effects, as well as offer antioxidant protection. We examined effects of American ginseng berry extract and ginsenoside Re in a pancreatic ß-cell line, MIN-6, to determine if these two properties are related. Cells were exposed to oxidative stress via hydrogen peroxide incubation and oxidative stress was measured by oxidation of 2′,7′-dichlorofluorescin diacetate. These cells showed a concentration-related response to hydrogen peroxide at 100–500 μM. In acute conditions where cells were treated with the extract for 10 min, we observed reduced oxidant injury suggesting direct scavenging effects. Chronic incubation of cells with the extract for 48 hours also demonstrated attenuation of oxidative stress. At high concentrations, Re showed a mild antioxidant effect in MIN-6 cells. Our insulin release observations also showed that the extract may help to increase insulin secretions from the cells. Our data suggest that the observed ability of ginseng to reduce blood glucose levels may be linked to its antioxidant effects on pancreatic ß-cells.


2011 ◽  
Vol 300 (1) ◽  
pp. C22-C32 ◽  
Author(s):  
Marc Anderson ◽  
Jae Mi Suh ◽  
Eun Young Kim ◽  
Stuart E. Dryer

N-methyl-d-aspartate (NMDA) receptors are essential for normal nervous system function, but their excessive activation can lead to neuronal degeneration. NMDA receptors are also expressed in peripheral tissues, where their properties and significance are not well understood. Here we show that functional NMDA receptors are expressed in podocytes, polarized cells that form an essential component of the glomerular filtration apparatus. Application of NMDA to podocyte cell lines or primary cultures of mouse podocytes evoked macroscopic currents mediated by cation channels, with significant permeability to Ca2+. Podocyte NMDA receptors do not desensitize with prolonged exposure to NMDA. They are blocked by supraphysiological concentrations of external or internal Mg2+and, also, by the prototype antagonists MK-801 and d-2-aminophosphonovaleric acid. NMDA responses in podocytes were strongly potentiated by d-serine, but not by glycine, even at high concentrations. d-Aspartate and l-homocysteate are effective agonists of podocyte NMDA receptors. Surprisingly, l-glutamate and l-aspartate did not evoke robust ionic currents in podocytes, regardless of the concentration or membrane potential at which these amino acids were tested. NMDA application for 2 h caused activation of secondary signals through Erk and Akt pathways and, at higher concentrations, caused activation of RhoA. Exposure to NMDA for 6 h did not cause loss of cultured podocytes but did lead to a reduction in nephrin expression. NMDA receptors that respond to circulating ligands may play a role in regulation of glomerular function or dysfunction, but they are unlikely to be components of a local glutamate signaling system in glomeruli.


2021 ◽  
Vol 22 (8) ◽  
pp. 4238
Author(s):  
Hitoshi Teranishi ◽  
Reiko Hanada

Obesity is now a public health concern. The leading cause of obesity is an energy imbalance between ingested and expended calories. The mechanisms of feeding behavior and energy metabolism are regulated by a complex of various kinds of molecules, including anorexigenic and orexigenic neuropeptides. One of these neuropeptides, neuromedin U (NMU), was isolated in the 1980s, and its specific receptors, NMUR1 and NMUR2, were defined in 2000. A series of subsequent studies has revealed many of the physiological roles of the NMU system, including in feeding behavior, energy expenditure, stress responses, circadian rhythmicity, and inflammation. Particularly over the past decades, many reports have indicated that the NMU system plays an essential and direct role in regulating body weight, feeding behavior, energy metabolism, and insulin secretion, which are tightly linked to obesity pathophysiology. Furthermore, another ligand of NMU receptors, NMS (neuromedin S), was identified in 2005. NMS has physiological functions similar to those of NMU. This review summarizes recent observations of the NMU system in relation to the pathophysiology of obesity in both the central nervous systems and the peripheral tissues.


1981 ◽  
Vol 154 (1) ◽  
pp. 193-198 ◽  
Author(s):  
E G Engleman ◽  
C J Benike ◽  
E Glickman ◽  
R L Evans

Two major subsets of human T lymphocytes that are functionally analogous to the mouse Lyt-2+ and Lyt-2- subsets have been defined by their expression of two thymus-dependent membrane antigens, Leu-2 and Leu-3. Leu-2+,3- cells have suppressor/cytotoxic functions and Leu-2-,3+ cells have helper functions. These studies were designed to determine the effects of adding IgG1 monoclonal anti-Leu-2 and anti-Leu-3 antibodies to the mixed leukocyte reaction (MLR). At high concentrations, each antibody partially inhibited the proliferative response of unseparated T cells and abolished the response of the isolated subset having the appropriate phenotype. An IgG1 monoclonal antibody to HLA-A2 and an IgG2a antibody to Leu-1, a pan-T antigen, failed to inhibited the MLR. These results suggest that the Leu-2 and Leu-3 antigens may have a direct role in the mechanism whereby T cells recognize and respond to alloantigen.


2002 ◽  
Vol 103 (s2002) ◽  
pp. 306S-309S ◽  
Author(s):  
Laura ROSANÒ ◽  
Debora SALANI ◽  
Valeriana DI CASTRO ◽  
Francesca SPINELLA ◽  
Pier Giorgio NATALI ◽  
...  

Endothelin-1 (ET-1) is a potent mitogenic and angiogenic factor for ovarian carcinoma cell lines, which acts selectively through the ETA receptor (ETAR). A previous study demonstrated that ET-1 is present at high concentrations in ovarian cancer ascites, indicating a direct role in the progression and metastasis of ovarian carcinoma. In this study, we investigated whether ET-1 could induce production and activation of tumour-associated proteinases in ovarian carcinoma cells. As demonstrated by ELISA, we found that the secretion of matrix metalloproteinase (MMP)-2 and MMP-9, urokinase-type plasminogen activator and plasminogen activator inhibitor type-1 and -2 was upregulated by ET-1 in a dose-dependent manner in the HEY cell line. In addition, the MMPs in ET-1-treated cells are consistently active, as shown by MMP gelatinase activity assay. Finally, we demonstrated that BQ-123, an antagonist of ETAR, inhibited the ET-1-induced tumour protease secretion and activity, suggesting that ET-1/ETAR may play an important role in the progression and metastasis of ovarian carcinoma, activating multiple proteinase cascades.


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