Efficacy of using an internal teat sealer to prevent new intramammary infections in nonlactating dairy cattle

OBJECTIVE: To determine whether insertion of an internal teat sealer (ITS) at the end of lactation would prevent development of new intramammary infections (IMIs) during the nonlactating period. DESIGN: Controlled clinical trial. ANIMALS: 939 Holstein-Friesian dairy cows from 16 herds. PROCEDURES: Results of bacteriologic culture of milk samples collected 14 days prior to the end of lactation were used to assign cows to groups (group 1 = negative results for all quarters; group 2 = positive results for > or = 1 quarter). Quarters of cows in group 1 were treated with an ITS or a single intramammary dose of cloxacillin; quarters of cows in group 2 were treated with cloxacillin in conjunction with an ITS or with cloxacillin alone. Milk samples were collected at the end of lactation and within 8 days after calving. RESULTS: Regardless of whether the outcome of interest was new IMIs caused by any pathogens, major pathogens, environmental pathogens, or streptococci other than Streptococcus agalactiae, quarters in group 2 treated with both cloxacillin and an ITS were less likely to develop a new IMI than were quarters treated with cloxacillin alone. For cows in group 1, no significant difference in risk of new IMIs was found between treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that for dairy cattle with an IMI late in the lactation period, intramammary administration of cloxacillin at the end of lactation followed by insertion of an ITS enhanced protection against development of new IMIs, compared with use of cloxacillin alone.     

Crystal structure of a lipid G protein-coupled receptor

The lyso-phospholipid sphingosine 1-phosphate modulates lymphocyte trafficking, endothelial development and integrity, heart rate, and vascular tone and maturation by activating G protein-coupled sphingosine 1-phosphate receptors. Here, we present the crystal structure of the sphingosine 1-phosphate receptor 1 fused to T4-lysozyme (S1P(1)-T4L) in complex with an antagonist sphingolipid mimic. Extracellular access to the binding pocket is occluded by the amino terminus and extracellular loops of the receptor. Access is gained by ligands entering laterally between helices I and VII within the transmembrane region of the receptor. This structure, along with mutagenesis, agonist structure-activity relationship data, and modeling, provides a detailed view of the molecular recognition and requirement for hydrophobic volume that activates S1P(1), resulting in the modulation of immune and stromal cell responses.