This study examined the effects of multiple subcutaneous glucagon injections with or without co-administration of oral glycerol on energy status-related blood metabolites and hormones of Holstein dairy cows in the first 2 wk postpartum. Twenty multiparous cows were fed a dry cow ration supplemented with 6 kg of cracked corn during the dry period to increase the likelihood of developing postpartal fatty liver syndrome. Cows with a body condition score of >or=3.5 points (1- to 5-point scale) were assigned randomly to 1 of 4 treatment groups: saline, glucagon, glycerol, or glucagon plus glycerol. Following treatment, serial blood samples were collected over an 8-h period to determine the effects of glucagon and glycerol on blood metabolites and hormones. Treatment effects were determined by comparing the concentrations of metabolites and hormones during the first 4-h period and the entire 8-h period after treatment administration (time 0) with the concentration of the same compounds at time 0 on d 1, 7, and 13 postpartum. Administration of glucagon alone increased concentrations of plasma glucagon and insulin on d 1, 7, and 13 and increased plasma glucose and decreased plasma nonesterified fatty acids (NEFA) on d 7 and 13 postpartum relative to the saline group. Administration of glycerol alone increased plasma glucose on d 7 and plasma triacylglycerols on d 1 postpartum. Glycerol administration also decreased plasma glucagon and NEFA on d 1, 7, and 13 and plasma beta-hydroxybutyrate (BHBA) on d 1 postpartum relative to the saline group. Administration of glucagon plus glycerol increased and sustained concentrations of plasma glucagon, glucose, and insulin on d 1, 7, and 13 and decreased plasma NEFA on d 1, 7, and 13 and BHBA on d 1 and 7. Early postpartal treatment of dairy cows with glucagon plus glycerol increased plasma glucose and insulin, decreased plasma NEFA and BHBA, and increased secretion of liver NEFA as plasma triacylglycerols. This suggests that glucagon and glycerol, when co-administered, act to decrease the likelihood of metabolism-related syndrome development in dairy cows.

Immunocompromised mouse strains expressing human transgenes are being increasingly used in biomedical research. The genetic modifications in these mice cause various cellular responses, resulting in histologic features unique to each strain. The NSG-SGM3 mouse strain is similar to the commonly used NSG (NOD scid gamma) strain but expresses human transgenes encoding stem cell factor (also known as KIT ligand), granulocyte-macrophage colony-stimulating factor, and interleukin 3. This report describes 3 histopathologic features seen in these mice when they are unmanipulated or after transplantation with human CD34+ hematopoietic stem cells (HSCs), virally transduced hCD34+ HSCs, or a leukemia patient-derived xenograft. The first feature is mast cell hyperplasia: unmanipulated, naïve mice develop periductular pancreatic aggregates of murine mast cells, whereas mice given the aforementioned human cells develop a proliferative infiltrative interstitial pancreatic mast cell hyperplasia but with human mast cells. The second feature is the predisposition of NSG-SGM3 mice given these human cells to develop eosinophil hyperplasia. The third feature, secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS)–like disease, is the most pronounced in both its clinical and histopathologic presentations. As part of this disease, a small number of mice also have histiocytic infiltration of the brain and spinal cord with subsequent neurologic or vestibular signs. The presence of any of these features can confound accurate histopathologic interpretation; therefore, it is important to recognize them as strain characteristics and to differentiate them from what may be experimentally induced in the model being studied.

Objective—To determine the effects of protease inhibitors and holding times and temperatures before processing on the stability of substance P in bovine blood samples. Samples—Blood samples obtained from a healthy 6-month-old calf. Procedures—Blood samples were dispensed into tubes containing exogenous substance P and 1 of 6 degradative enzyme inhibitor treatments: heparin, EDTA, EDTA with 1 of 2 concentrations of aprotinin, or EDTA with 1 of 2 concentrations of a commercially available protease inhibitor cocktail. Plasma was harvested immediately following collection or after 1, 3, 6, 12, or 24 hours of holding at ambient (20.3° to 25.4°C) or ice bath temperatures. Total substance P immunoreactivity was determined with an ELISA; concentrations of the substance P parent molecule, a metabolite composed of the 9 terminal amino acids, and a metabolite composed of the 5 terminal amino acids were determined with liquid chromatography–tandem mass spectrometry. Results—Regarding blood samples processed immediately, no significant differences in substance P concentrations or immunoreactivity were detected among enzyme inhibitor treatments. In blood samples processed at 1 hour of holding, substance P parent molecule concentration was significantly lower for ambient temperature versus ice bath temperature holding conditions; aprotinin was the most effective inhibitor of substance P degradation at the ice bath temperature. The ELISA substance P immunoreactivity was typically lower for blood samples with heparin versus samples with other inhibitors processed at 1 hour of holding in either temperature condition. Conclusions and Clinical Relevance—Results suggested that blood samples should be chilled and plasma harvested within 1 hour after collection to prevent substance P degradation.

We examined the long-term effects of daily subcutaneous injections of 15 mg of glucagon during the first 14 d postpartum with or without coadministration of 400 mL of pure glycerol orally on blood metabolites and hormones and liver composition of Holstein dairy cows during early lactation. Fourteen multiparous cows with body condition score of >or=3.5 points (1-5 point scale) were assigned randomly to one of 4 treatment groups-saline, glucagon, glycerol, or glucagon plus glycerol. Fatty liver syndrome was induced by feeding cows a dry-cow ration supplemented with 6 kg of cracked corn daily during the last 6 wk of the dry period. Compared with saline treatment (n=3), coadministration of glucagon and glycerol (n=4) increased plasma glucose and insulin and decreased plasma nonesterified fatty acid concentrations in both treatment weeks, whereas glucagon alone (n=3) produced similar changes plus a decrease in plasma beta-hydroxybutyrate in the second week only. No significant changes were observed for the glycerol alone treatment (n=4). We conclude that a single daily dose of glycerol for the first 14 d postpartum may potentiate the action of glucagon in the first treatment days to alleviate some symptoms of fatty liver syndrome, such as the increase in plasma nonesterified fatty acids and the decrease in plasma glucose and insulin, in Holstein dairy cows after parturition.

Background As prescriptions for off-label pharmaceutical use and autonomous administration of over-the-counter nutraceuticals become mainstream, thorough assessments of these compounds are warranted. Objective To determine the effects of gemfibrozil, rosiglitazone, metformin, taurine, and vitamin E on body composition, hepatic lipids, and metabolic hormone and blood metabolite concentrations in a healthy, outbred rat cohort. Methods Male Sprague Dawley rats were fed a purified 10 kcal% from fat diet for 56 days and assigned to diet alone (control) or diet plus oral administration of gemfibrozil (34 mg/kg), metformin (500 mg/kg), rosiglitazone (3 mg/kg), taurine (520 mg/kg), or vitamin E (200 mg/kg). Results Rosiglitazone administration resulted in a 56% increase in carcass adiposity, cautioning potential prescriptive off-label use. Taurine supplementation had no adverse effects on evaluated parameters. A modest but significant increase in liver triacylglycerol content was observed with vitamin E supplementation compared with control (Δ 17.2 g triacylglycerol/100 g liver lipid). Conclusions The evaluated pharmaceuticals had effects in a healthy population similar to the reported effects in their target population and the nutraceuticals had minimal effects on the measured physiological parameters.