Elevation of circulating serotonin improves calcium dynamics in the peripartum dairy cow.

Hypocalcemia is a metabolic disorder that affects dairy cows during the transition from pregnancy to lactation. Twelve multiparous Holstein cows and twelve multiparous Jersey cows were intravenously infused daily for approximately 7 days prepartum with either saline or 1.0mg/kg bodyweight of the immediate precursor to serotonin synthesis, 5hydroxy-l-tryptophan (5-HTP). On infusion days, blood was collected before, after, and at 2, 4, and 8h postinfusion. Blood and urine were collected daily before the infusion period, for 14 days postpartum and on day 30 postpartum. Milk was collected daily during the postpartum period. Feed intake and milk yield were unaffected by 5-HTP infusion postpartum. Cows infused with 5-HTP had elevated circulating serotonin concentrations prepartum. Infusion with 5-HTP induced a transient hypocalcemia in Jersey cows prepartum, but not in any other treatment. Holstein cows infused with saline had the highest milk calcium on the day of and day after parturition. Postpartum, circulating total calcium tended to be elevated, and urine deoxypyridinoline (DPD) concentrations were elevated in Holstein cows infused with 5-HTP. Overall, Jerseys had higher urine DPD concentrations postpartum when compared with Holsteins. Taken together, these data warrant further investigation of the potential therapeutic benefit of 5-HTP administration prepartum for prevention of hypocalcemia. Further research should focus on delineation of mechanisms associated with 5-HTP infusion that control calcium homeostasis during the peripartum period in Holstein and Jersey cows.

Serotonin (5-HT) affects expression of liver metabolic enzymes and mammary gland glucose transporters during the transition from pregnancy to lactation.

The aim of this experiment was to demonstrate the ability of feeding serotonin (5-HT; 5-hydroxytryptamine) precursors to increase 5-HT production during the transition from pregnancy to lactation and the effects this has on maternal energy metabolism in the liver and mammary gland. Pregnant rats (n = 45) were fed one of three diets: I) control (CON), II) CON supplemented with 0.2% 5-hydroxytryptophan (5-HTP) or III) CON supplemented with 1.35% L-tryptophan (L-TRP), beginning on d13 of pregnancy through d9 of lactation (d9). Serum (pre and post-partum), milk (daily), liver and mammary gland tissue (d9) were collected. Serum 5-HT was increased in the 5-HTP fed dams beginning on d20 of gestation and remained elevated through d9, while it was only increased on d9 in the L-TRP fed dams. 5-HT levels were increased in mammary gland and liver of both groups. Additionally, 5-HTP fed dams had serum and milk glucose levels similar to the CON, while L-TRP had decreased serum (d9) and milk glucose (all dates evaluated). Feeding 5-HTP resulted in increased mRNA expression of key gluconeogenic and glycolytic enzymes in liver and glucose transporters 1 and 8 (GLUT-1, -8) in the mammary gland. We demonstrated the location of GLUT-8 in the mammary gland both in the epithelial and vascular endothelial cells. Finally, phosphorylated 5' AMP-activated protein kinase (pAMPK), a known regulator of intracellular energy status, was elevated in mammary glands of 5-HTP fed dams. Our results suggest that increasing 5-HT production during the transition from pregnancy to lactation increases mRNA expression of enzymes involved in energy metabolism in the liver, and mRNA abundance and distribution of glucose transporters within the mammary gland. This suggests the possibility that 5-HT may be involved in regulating energy metabolism during the transition from pregnancy to lactation.

Comparison of inhibitory effects of glucosamine and mannosamine on bovine articular cartilage degradation in vitro.

OBJECTIVE: To compare the inhibitory effects of glucosamine and mannosamine on articular cartilage degradation and the effects on chondrocyte viability in vitro. SAMPLE POPULATION: Bovine articular cartilage explants. PROCEDURES: Explants were cultured in commercial medium for 48 hours. Cartilage was exposed to medium containing 10% fetal bovine serum, 10 microg of lipopolysaccharide/mL, and 0.5, 1.0, 2.5, 5.0, and 10.0 mg of glucosamine or mannosamine/mL for 24 hours. Nitric oxide (NO) production (nitrite concentration) and proteoglycan (PG) release (PG concentration) in media were measured. Cartilage extracts were analyzed via zymography to detect gelatinolytic activity. At the end of the experiment, explants were assessed for chondrocyte viability. RESULTS: Addition of lipopolysaccharide resulted in increased NO production and PG release, but no increase in gelatinolytic activity, compared with controls. Glucosamine and mannosamine at concentrations as low as 0.5 mg/mL inhibited NO production. Glucosamine inhibited PG release at a minimum concentration of 1.0 mg/mL, whereas mannosamine inhibited PG release at a concentration of 0.5 mg/mL. Concentrations of glucosamine < or = 5.0 mg/mL did not adversely affect chondrocyte viability; however, at a concentration of 10.0 mg/mL, cell death was evident. Mannosamine had a toxic effect at a concentration of 5.0 mg/mL and was associated with pronounced chondrocyte death at a concentration of 10.0 mg/mL. CONCLUSIONS AND CLINICAL RELEVANCE: Glucosamine and mannosamine inhibit selected indices of bovine articular cartilage degradation at concentrations that do not affect chondrocyte viability. The potential for cytotoxic effects at higher concentrations underscores the importance of establishing appropriate dosage regimens for these aminomonosaccharides.

Serum concentrations of keratan sulfate, osteocalcin, and pyridinoline crosslinks after oral administration of glucosamine to standardbred horses during race training.

OBJECTIVE: To determine the effects of orally administered glucosamine on concentrations of markers of bone and cartilage metabolism in Standardbred horses during race training. ANIMALS: Twenty 16- to 20-month-old Standardbreds beginning race training. PROCEDURE: Horses were randomly assigned to 2 groups. One group received glucosamine hydrochloride (4 g, PO, q 12 h), and the second (control) group received glucose (4 g, PO, q 12 h). Serum samples were obtained prior to onset of the study (baseline) and at regular intervals for 48 weeks for determination of concentrations of keratan sulfate (KS), osteocalcin (OC), and pyridinoline crosslinks (PYD). RESULTS: Osteocalcin concentrations changed significantly with time; mean serum concentrations were significantly higher than baseline values for samples obtained at 24 to 48 weeks after onset of the study. Although a significant effect of time was observed for mean concentration of KS, concentrations did not differ significantly from baseline values at any time during the study when groups were analyzed separately. However, pooled analysis revealed significant increases of mean serum KS concentration at weeks 24 and 30. Significant changes in serum PYD concentrations were not detected. Oral administration of glucosamine did not significantly affect serum concentrations of any of the markers. CONCLUSIONS AND CLINICAL RELEVANCE: Increased serum OC in clinically normal Standardbreds during race training may reflect bone formation that accompanies adaptive remodeling of the appendicular skeleton. For these experimental conditions, glucosamine did not appear to exert a detectable influence on serum concentrations of these 3 markers of connective tissue metabolism.