ABSTRACT
BACKGROUND: Human platelet activation and aggregation is a complex process. To date, many therapies have been developed targeting proteins that mediate this process to prevent unwanted activation. However, the current standard of care for acute coronary syndromes still has limitations, including bleeding risk. OBJECTIVE: To evaluate the protease-activated receptor 4 (PAR4) anionic cluster as a viable antiplatelet target by using a polyclonal antibody (CAN12). METHODS: We used western blotting, aggregation and secretion ex vivo to evaluate the ability of CAN12 to interact with PAR4 and inhibit platelet activation. The effects of CAN12 in vivo were evaluated with the Rose Bengal arterial thrombosis model and two models of hemostasis. RESULTS: CAN12 was able to interact with human PAR4 and delay PAR4 cleavage. In addition, CAN12 inhibited thrombin-induced human platelet aggregation and secretion in a dose-dependent manner. The specificity of CAN12 was agonist-dependent. In vivo, we determined that CAN12 was able to inhibit arterial thrombosis, and, using two independent methods, we found that CAN12 did not influence hemostasis. CONCLUSION: Targeting the extracellular anionic cluster on PAR4 is a viable novel strategy as an antiplatelet therapy.
Subject(s)
Antibodies/pharmacology , Hemostasis/drug effects , Platelet Aggregation Inhibitors/pharmacology , Receptors, Thrombin/drug effects , Thrombosis/prevention & control , Animals , Blotting, Western , HEK293 Cells , Humans , Mice , Mice, Inbred C57BL , Platelet Activation/drug effectsSubject(s)
Child Health Services/organization & administration , Emergency Medical Services/organization & administration , Pediatrics/organization & administration , Child , Child Health Services/standards , Community Health Planning , Emergency Medical Services/standards , Guidelines as Topic , Humans , Pediatrics/standards , United StatesABSTRACT
A children's institution offers a creative program for single mothers and their families--a 24-hour child care facility on the campus that provides residential service for the entire family. Over several months, the staff helps with family problems such as income, housing, abuse and other family dysfunctions and prevention of separation. Though small, the program has experienced success and has operated on a small budget for the last 10 years.
Subject(s)
Child Abuse/prevention & control , Child Welfare , Family Therapy/methods , Residential Treatment/methods , Adult , Child , Child Abuse/psychology , Child Development , Family/psychology , Female , Group Homes , Humans , Male , Social EnvironmentABSTRACT
A rapid method is described for the purification of human tissue inhibitor of metalloproteinases (TIMP) from plasma which involves immuno-affinity chromatography and gel filtration. The purified plasma inhibitor is immunologically identical with the TIMP previously purified from human amniotic fluid, human synovial fluid and human fibroblast culture medium. It is proposed that this inhibitor is identical with the plasma inhibitor previously named 'B1 anticollagenase', although the plasma inhibitor was shown to migrate as a gamma-serum component.
Subject(s)
Blood Proteins/isolation & purification , Enzyme Inhibitors/isolation & purification , Chromatography, Affinity , Chromatography, Gel , Electrophoresis, Polyacrylamide Gel , Enzyme Inhibitors/blood , Enzyme Inhibitors/immunology , Humans , Immunodiffusion , Tissue Inhibitor of MetalloproteinasesABSTRACT
Although the medical treatment of critically ill newborn babies has advanced significantly in recent years, treatment of a family's emotional trauma brought on by the birth of an ill baby is relatively new. The authors examine the ways a family must cope with a sickly infant and suggest how a perinatal social worker can assist the family.
