ABSTRACT
Sphingolipids such as ceramide and sphingosine-1-phosphate have recently attracted intense research interests because of their functional roles as signaling molecules in many important physiological processes, such as growth arrest, apoptosis, and inflammatory responses, and cell proliferation, vascular maturation and trafficking of lymphocytes. The well-defined modular structures of ceramides and related glycosylceramides are ideally amenable to library formation for medicinal chemistry investigation. We have developed divergent synthetic routes to all eight phytosphingosine stereoisomers and then proceeded to prepare phytosphingosine-based ceramide library composed of more than 500 compounds.
Subject(s)
Ceramides/chemical synthesis , Sphingosine/analogs & derivatives , Ceramides/chemistry , Chromatography, Liquid , Chromatography, Thin Layer , Combinatorial Chemistry Techniques , Magnetic Resonance Spectroscopy , Molecular Structure , Spectrometry, Mass, Electrospray Ionization , Sphingosine/chemical synthesis , Sphingosine/chemistry , StereoisomerismABSTRACT
Two 60+-membered libraries of alpha-galactosylceramides have been prepared by reactions between activated ester resins and two core, fully deprotected galactosylated sphingoid bases. The libraries were evaluated for their ability to stimulate CD1d-restricted NKT cells, using in vitro stimulation of a murine NKT cell hybridoma line and for their ability to induce the expansion of NKT cells from peripheral blood mononuclear cells (PBMC) of a normal human subject. Our results showed that many compounds constructed on a C18-phytosphingosine base had significant stimulatory activity in both assays. Because no product purification was required, this approach is particularly attractive as a method for rapid synthesis of large libraries of potential immunomodulatory glycosylceramides.
Subject(s)
Combinatorial Chemistry Techniques , Galactosylceramides/immunology , Galactosylceramides/pharmacology , Killer Cells, Natural/drug effects , Leukocytes, Mononuclear/drug effects , Lymphocyte Activation/drug effects , Animals , Galactose/chemistry , Galactosylceramides/chemical synthesis , Humans , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/metabolism , Lymphocyte Activation/physiology , Mice , Models, Chemical , Resins, Synthetic/chemistry , Sphingolipids/chemistry , Sphingosine/analogs & derivatives , Sphingosine/chemistry , Sphingosine/immunology , Sphingosine/metabolismABSTRACT
PURPOSE: To evaluate an emergency department's use of a mental health triage and mental health crisis counsellor for persons presenting with mental health concerns. METHOD: Mixed method (qualitative and quantitative), multiple measures. RESULTS: Significant pre- and post-intervention reductions for wait time, security incidents and hospital admissions were found. Follow ups with a community agency, medications and a psychiatrist increased post-intervention, while follow ups with detox decreased post-intervention. CONCLUSIONS: The qualitative and quantitative findings are congruent with other studies supporting the use of properly implemented mental health triage and crisis counsellors to improve the care of persons with mental health concerns.
Subject(s)
Emergency Services, Psychiatric , Mental Disorders , Triage , Adolescent , Adult , Aged , Counseling , Data Collection , Female , Focus Groups , Humans , Male , Middle Aged , OntarioABSTRACT
PROBLEM: People with mental illness are twice as likely to smoke than people without a mental illness. METHODS: Data were collected through interviews with individuals who smoke and have been diagnosed with schizophrenia (N = 100). The research design included a descriptive, correlational design that described and examined the relationships among psychiatric symptoms, medication side effects, and reasons for smoking; and a qualitative analysis of the subjective experience of smoking. FINDINGS: A positive relationship was found between the age of onset of smoking and the onset of schizophrenia. Subjects reported they smoked primarily for sedative effects and control of negative symptoms of schizophrenia. Subjects also reported smoking related to addiction. Most indicated they would like to quit smoking or at least cut down on the number of cigarettes. CONCLUSIONS: Among people with schizophrenia, the motivation to smoke is related to their schizophrenia.
