Cabergoline treatment at dry-off facilitated the remodelling and the lactoferrin immunoprotection of the mammary tissue in dairy cows

ObjectivesIn ruminants, the early phase of drying-off is a period of intense mammary gland involution that is due, in part, to dramatic decline prolactin (PRL) release. The speed at which the bovine mammary gland involutes following the abrupt cessation of lactation is also directly related to the risk of new intramammary infections. Thus, strategies to hasten involution following dry-off could have implications in preventing mastitis and optimizing mammary tissue regenerative processes.Materials and methodsTo assess the effect of prolactin inhibition by cabergoline on mammary gland involution, 14 Holstein dairy cows were injected with a single i.m. administration of 5.6 mg cabergoline (n=7) or placebo (n=7) within 4 hours after the last milking before the drying off at the day of drying-off (D0). Mammary secretion samples were collected using a teat-cannula once during lactation (D-6) and at D1, D2, D3, D4, D8 and D14 after the drying-off. The mammary secretion samples were used for lactoferrin and zymography analyses to detect the activity of enzymes such as MMP, matrix metalloproteinases involved in the remodelling of mammary tissue during involution. Mammary epithelial cells (MEC) were also purified from mammary secretions after centrifugation andimmunocytochemical binding in order to evaluate the MEC exfoliation. Mammary biopsy samples were collected one week before drying-off (D-6), at D1 and at D8 and used for lactoferrin immunochemistry and zymography analyses.ResultsThe activity of MMP9 increased after drying-off in mammary secretions (P < 0.001). Cabergoline increased the activity of MMP9 (1.7 fold, P < 0.05) in mammary secretions and MMP-2 in mammary tissue after drying-off (1.4 fold, P ≤ 0.01). MEC concentration progressively increased in mammary secretions after drying-off (P < 0.01). Cabergoline induced an increase in MEC concentration (P =0.04). Lactoferrin content progressively increased in mammary secretions during involution. The rise of lactoferrin content in mammary secretions was significant starting at D4 in the cabergoline treated cows (P ≤0.05) whereas it only happened at D8 in controls (P < 0.05). Overall, cabergoline treatment increased lactoferrin content of mammary secretions (P = 0.10). The total lactoferrin immunostaining in the mammary tissue increased after drying-off (P < 0.05). Compared with during lactation, this increase was observed at D1 and D8, respectively for cabergoline treated cows and control cows (P <0.05).ConclusionsOur results indicate that cabergoline treatment was efficient to enhance the extracellular matrix mammary remodeling, and the MEC exfoliation from the mammary epithelium and also hasten the udder immunoprotection by lactoferrin and therefore facilitates the drying-off

Cabergoline treatment at dry-off accelerated mammary involution as indicated by mammary secretion composition changes in dairy cows

In ruminants, the early phase of drying-off is a period of mammary gland involution that is marked by the cessation of prolactin (PRL) release. The speed at which the bovine mammary gland involutes following the abrupt cessation of lactation is directly related to the risk of new intramammary infections.ObjectivesOur aim was to assess the effect of PRL inhibition by cabergoline on the speed of the mammary gland involution, through analysis of the changes of mammary secretion composition.Materials and methodsFourteen Holstein dairy cows were injected with a single i.m. administration of 5.6 mg cabergoline (n=7) (Velactis ®, Ceva Sante Animale) or placebo (n=7) at the first day of dryingoff (D0). Mammary secretion samples were collected using a teat-cannula once during lactation (D-6) and at D1, D2, D3, D4, D8 and D14 after the drying-off. The mammary secretion samples were used for milk fat, lactose, true protein, alpha-lactalbumin and SCC analysis. Mammary biopsy samples were collected one week before drying-off (D-6), at D1 and at D8 and used for RNA extraction and RT-PCR analyses.ResultsAs expected, SCC progressively increased whereas lactose content decreased in mammary secretions after drying-off (P < 0.001). The increase in SCC was 2.4 fold higher in cabergoline treated cows than in control cows (P < 0.01). The decrease of lactose content in mammary secretions progressively decreased during involution and was associated with paralleled change in GLUT-1 mRNA level coding the main glucose transporter in the udder. These decreases were faster in cabergoline treated cows compared to controls with lower lactose content in cabergoline treated cows already by D1 than in controls (P < 0.05) and significant decrease in GLUT-1 mRNA levels at D1 and D8 respectively for cabergoline and control treatments compared to D-6 (P ≤ 0.05). Cabergoline treatment tended to increase fat content at D3 after drying-off (P < 0.10). No significant effects of cabergoline treatment were observed both in true protein and in alpha-lactalbumin contents in mammary secretions or in alphalactalbumin and kappa-casein mRNA levels in mammary tissues.ConclusionsThe changes in lactose, SCC and fat in mammary secretions and GLUT-1 mRNA level in the udder, indicate that cabergoline treatment was efficient to hasten the mammary gland involution without affecting milk protein synthesis in the mammary tissue. Cabergoline could facilitate dairy management at the time of dry-off

Prolactin-inhibitor cabergoline hastened the mammary involution during drying-off in dairy cows

In ruminants, the early phase of drying-off is a period of mammary gland involution that is marked by the cessation of prolactin (PRL) release. The analysis of the changes of mammary secretion composition can provide valuable information about the speed of the mammary involution. To assess the effect of PRL inhibition by cabergoline on mammary gland involution, 14 Holstein dairy cows were injected with a single i.m. administration of 5.6 mg cabergoline (n = 7) or placebo (n = 7) at the first day of drying-off (D0). Mammary biopsy samples were collected one week before drying-off (D-6), at D1 and at D8 and used for RNA extraction and RT-PCR analyses. Mammary secretion samples were collected using a teat-cannula once during lactation (D-6) and at D1, D2, D3, D4, D8 and D14 after the drying-off. The mammary secretion samples were used for milk fat, lactose, true protein, a-lactalbumin, lactoferrin and citrate analysis. The decrease in lactose content of mammary secretions seemed to be faster in cabergoline treated cows compared to controls, demonstrated by lower levels of lactose in cabergoline treated cows already by D1 than in control cows (P < 0.05). Cabergoline treatment tended to increase fat content at D3 after drying-off (P < 0.10), whereas an increase in fat content was only observed at D4 in the control group. The rise of lactoferrin was significant starting at D4 in the cabergoline treated cows whereas it only happened at D8 in controls, and overall there was a tendency towards greater lactoferrin content in cabergoline treated cows (P = 0.10). Cabergoline did not seem to alter citrate content. However, the decrease in lactoferrin/citrate ratio happened faster in cabergoline treated cows compared to controls on D1 (P = 0.01). No significant effects of cabergoline treatment were observed both in true protein and in a-lactalbumin contents in mammary secretions or in a-lactalbumin and k-casein mRNA levels in mammary tissues. These changes in lactose, lactoferrin, lactoferrin/citrate ratio and fat, indicate that cabergoline treatment was efficient to hasten the mammary gland involution without affecting milk synthesis in the mammary tissue

Cabergoline treatment at dry-off accelerated mammary involution as indicated by mammary secretion composition changes in dairy cows

In ruminants, the early phase of drying-off is a period of mammary gland involution that is marked by the cessation of prolactin (PRL) release. The speed at which the bovine mammary gland involutes following the abrupt cessation of lactation is directly related to the risk of new intramammary infections.[br/] Objectives[br/] Our aim was to assess the effect of PRL inhibition by cabergoline on the speed of the mammary gland involution, through analysis of the changes of mammary secretion composition.[br/] Materials and methods[br/] Fourteen Holstein dairy cows were injected with a single i.m. administration of 5.6 mg cabergoline (n=7) (Velactis ®, Ceva Sante Animale) or placebo (n=7) at the first day of dryingoff (D0). Mammary secretion samples were collected using a teat-cannula once during lactation (D-6) and at D1, D2, D3, D4, D8 and D14 after the drying-off. The mammary secretion samples were used for milk fat, lactose, true protein, alpha-lactalbumin and SCC analysis. Mammary biopsy samples were collected one week before drying-off (D-6), at D1 and at D8 and used for RNA extraction and RT-PCR analyses.[br/] Results[br/] As expected, SCC progressively increased whereas lactose content decreased in mammary secretions after drying-off (P < 0.001). The increase in SCC was 2.4 fold higher in cabergoline treated cows than in control cows (P < 0.01). The decrease of lactose content in mammary secretions progressively decreased during involution and was associated with paralleled change in GLUT-1 mRNA level coding the main glucose transporter in the udder. These decreases were faster in cabergoline treated cows compared to controls with lower lactose content in cabergoline treated cows already by D1 than in controls (P < 0.05) and significant decrease in GLUT-1 mRNA levels at D1 and D8 respectively for cabergoline and control treatments compared to D-6 (P ≤ 0.05). Cabergoline treatment tended to increase fat content at D3 after drying-off (P < 0.10). No significant effects of cabergoline treatment were observed both in true protein and in alpha-lactalbumin contents in mammary secretions or in alphalactalbumin and kappa-casein mRNA levels in mammary tissues.[br/] Conclusions[br/] The changes in lactose, SCC and fat in mammary secretions and GLUT-1 mRNA level in the udder, indicate that cabergoline treatment was efficient to hasten the mammary gland involution without affecting milk protein synthesis in the mammary tissue. Cabergoline could facilitate dairy management at the time of dry-off

Inhibiting prolactin by cabergoline accelerates mammary gland remodeling during the early dry period in dairy cows

The inhibition of prolactin release using cabergoline, a dopamine agonist, is an effective strategy to accelerate the changes in mammary secretion composition after drying-off. The objective of this study was to determine how cabergoline may affect mammary tissue remodeling during early involution. Holstein dairy cows were treated with either a single i.m. administration of 5.6 mg of cabergoline (Velactis, Ceva Santé Animale, Libourne, France, n = 7) or placebo (n = 7) at the time of drying-off. Mammary biopsy samples were collected 1 wk before drying-off (d -6), after 30 h of milk accumulation (d 1), and again 8 d following drying-off (d 8) to determine changes in gene expression, lactoferrin content, and cell turnover. Blood and mammary secretion samples were collected at d -6 and again at d 1, 2, 3, 4, 8, and 14 following the abrupt cessation of lactation to evaluate indicators of blood-milk barrier integrity and other markers of mammary tissue remodeling. Cabergoline induced less SLC2A1, BAX, CAPN2, and IGFBP5 mRNA expression. In contrast, cabergoline did not modify changes in cell proliferation and apoptosis. Following the cessation of lactation, changes in mammary secretion composition (Na(+) and K(+)) and blood lactose concentrations were indicative of a loss in the blood-milk barrier function in both treatment groups. Cabergoline treatment affected only Na(+) and K(+) concentrations at d 1, suggesting a moderate increase in tight junction permeability. The increase in the activity of MMP9 and in mammary epithelial cell concentration in mammary secretions was greater in cabergoline-treated cows than in control cows, suggesting more mammary tissue remodeling. The increase in lactoferrin immunostaining in the mammary tissue occurred earlier for cabergoline-treated cows than for control cows, and was essentially localized in the stroma. Changes in some key markers of mammary involution suggest that cabergoline accelerates mammary gland remodeling. Thus, a single injection of cabergoline after the last milking would facilitate drying-off by enhancing mammary gland involution

Cabergoline treatment at dry-off facilitated the remodelling and the lactoferrin immunoprotection of the mammary tissue in dairy cows

Objectives[br/] In ruminants, the early phase of drying-off is a period of intense mammary gland involution that is due, in part, to dramatic decline prolactin (PRL) release. The speed at which the bovine mammary gland involutes following the abrupt cessation of lactation is also directly related to the risk of new intramammary infections. Thus, strategies to hasten involution following dry-off could have implications in preventing mastitis and optimizing mammary tissue regenerative processes.[br/] Materials and methods[br/] To assess the effect of prolactin inhibition by cabergoline on mammary gland involution, 14 Holstein dairy cows were injected with a single i.m. administration of 5.6 mg cabergoline (n=7) or placebo (n=7) within 4 hours after the last milking before the drying off at the day of drying-off (D0). Mammary secretion samples were collected using a teat-cannula once during lactation (D-6) and at D1, D2, D3, D4, D8 and D14 after the drying-off. The mammary secretion samples were used for lactoferrin and zymography analyses to detect the activity of enzymes such as MMP, matrix metalloproteinases involved in the remodelling of mammary tissue during involution. Mammary epithelial cells (MEC) were also purified from mammary secretions after centrifugation and immunocytochemical binding in order to evaluate the MEC exfoliation. Mammary biopsy samples were collected one week before drying-off (D-6), at D1 and at D8 and used for lactoferrin immunochemistry and zymography analyses.[br/] Results[br/] The activity of MMP9 increased after drying-off in mammary secretions (P < 0.001). Cabergoline increased the activity of MMP9 (1.7 fold, P < 0.05) in mammary secretions and MMP-2 in mammary tissue after drying-off (1.4 fold, P ≤ 0.01). MEC concentration progressively increased in mammary secretions after drying-off (P < 0.01). Cabergoline induced an increase in MEC concentration (P =0.04). Lactoferrin content progressively increased in mammary secretions during involution. The rise of lactoferrin content in mammary secretions was significant starting at D4 in the cabergoline treated cows (P ≤0.05) whereas it only happened at D8 in controls (P < 0.05). Overall, cabergoline treatment increased lactoferrin content of mammary secretions (P = 0.10). The total lactoferrin immunostaining in the mammary tissue increased after drying-off (P < 0.05). Compared with during lactation, this increase was observed at D1 and D8, respectively for cabergoline treated cows and control cows (P <0.05).[br/] Conclusions[br/] Our results indicate that cabergoline treatment was efficient to enhance the extracellular matrix mammary remodeling, and the MEC exfoliation from the mammary epithelium and also hasten the udder immunoprotection by lactoferrin and therefore facilitates the drying-off

Impact of the First Wave of COVID-19 on Pediatric Oncology and Hematology: A Report from the French Society of Pediatric Oncology

Data regarding coronavirus disease 2019 (COVID-19) description are still limited in pediatric oncology. The French society of pediatric oncology (SFCE) initiated a study to better describe COVID-19 in patients followed in French pediatric oncology and hematology wards. All patients diagnosed with COVID-19 and followed in a SFCE center were enrolled. Data from medical records were analyzed for all patients enrolled up to the end of May 2020. Data were available for 37 patients. Thirty-one were children under 18 years of age. Nineteen patients were female. Seventeen patients had a solid tumor, 16 had a hematological malignancy and four recently underwent hematopoietic stem cell transplantation (HSCT) for non-oncological conditions. Twenty-eight patients presented symptoms, most often with fever, cough, rhinorrhea and asthenia. Ground-glass opacities were the most frequent radiological finding with abnormalities mostly bilateral and peripherally distributed. Twenty-four patients received chemotherapy a month prior to COVID-19 diagnosis. Most patients did not require hospitalization. Three patients required oxygen at the time of diagnosis. In total, five patients were admitted in an intensive care unit because of COVID-19 and one died from the disease. Children and young adults treated for a cancer and/or with a HSCT may be at risk for severe COVID-19 and should be closely monitored