A crash course in systems analysis Priest, S L; Borella, A B
Journal of healthcare information management,
1998-Fall, Letnik:
12, Številka:
3
Journal Article
A simple and effective preparation of phosphinodipeptides, in good overall yields, has been developed. This one pot procedure, allowing the variation of the substituents in α and/or β position to the ...phosphorus atom and also in α position to the nitrogen atom, consists in the addition of alkyl hypophosphites to imines, followed by Michael-addition on acrylates. To show the value of phosphinodipeptides analogs
1 as synthetic intermediates, selective deprotections of the three functional groups are described.
Preparation of phosphinodipeptide analogs as building blocks for pseudopeptides synthesis. A simple and effective preparation of phosphinodipeptides, in good overall yields, has been developed. This one pot procedure, allowing the variation of the substituents in α and/or β position to the phosphorus atom and also in α position to the nitrogen atom, consists in the addition of alkyl hypophosphites to imines, followed by Michael-addition on acrylates.
Neutron capture on ^(209)Bi produces either an isomeric state ^(210m)Bi with a half life of 3×10^6 years, or the ground state ^(210g)Bi which decays with a half life of 5 days to the alpha emitter ...^(210)Po. Therefore the neutron capture cross section ratio ^(209)Bi(n,γ) ^(210m)^(Bi)/^(210g)Bi plays an important role in predicting the short- and long-term radio-toxicity produced by ^(209)Bi under neutron irradiation. This ratio is dependent on the neutron energy. We have measured this ratio for cold neutrons at the cold neutron beam facility of the Budapest Neutron Centre by observing the population of the ground- and the metastable state using high resolution gamma-ray spectroscopy. The same technique hasbeen used at the pulsed white neutron source GELINA of the IRMM, Geel in combination with the neutron time-of-flight technique. Results for the neutron-energy dependent branching ratio will be presented. In addition we performed simulations using a statistical decay code. KCI Citation Count: 0
Excessive release of glutamate, a potent excitatory neurotransmitter, is thought to play an important role in a variety of acute and chronic neurological disorders, suggesting that excitatory amino ...acid antagonists may have broad therapeutic potential in neurology. Here, we describe the synthesis, pharmacological properties and neuroprotective activity of 9-carboxymethyl-imidazo-1-2aindeno1-2epyrazin-4-one-2-carboxylic acid (RPR117824), an original selective AMPA antagonist. RPR117824 can be obtained through a six-step synthesis starting from (1-oxo-indan-4-yl) acetic acid, which has been validated on a gram-scale with an overall yield of 25%. Monosodium or disodium salts of the compound exhibit excellent solubility in saline (> or = 10 g/L), enabling intravenous administration. RPR117824 displays nanomolar affinity (IC(50)=18 nM) for AMPA receptors and competitive inhibition of electrophysiological responses mediated by AMPA receptors heterologously expressed in Xenopus oocytes (K(B)=5 nM) and native receptors in rat brain slices (IC(50)=0.36 microM). In in vivo testing, RPR117824 behaves as a powerful blocker of convulsions induced in mice or rats by supramaximal electroshock or chemoconvulsive agents such as pentylenetetrazole, bicuculline, isoniazide, strychnine, 4-aminopyridine and harmaline with half maximal effective doses ranging from 1.5 to 10 mg/kg following subcutaneous or intraperitoneal administration. In disease models in rats and gerbils, RPR117824 possesses significant neuroprotective activity in global and focal cerebral ischemia, and brain and spinal cord trauma.
S-100β, a gene triplicated in Down Syndrome (DS), is thought to play a role in development of the brain in general, and in the serotonergic neuronal system in particular. We have been studying an ...animal model of DS, based on overexpression of this gene. In the current study, we report on the social behaviors of these animals, both in same-strain and mixed-strain pairings. In addition, as the neuropeptide oxytocin is often thought to be involved in social behaviors, we have looked at oxytocin-containing cells.
In non-social behaviors, such as grooming and line-crossing, the S-100β animals were more active than the CD-1 control animals and showed significantly less social sniffing. In mixed-strain studies, these differences became more pronounced, with the CD-1 animals showing significantly greater levels of sniffing and anogenital sniffing. As well, the CD-1 animals showed more rearing and an increase in line crossings, suggesting a heightened level of vigilance or awareness of novelty. The S-100β animals, conversely, did not appear to respond to the novelty of the CD-1 animals. In mixed pair studies, the S-100β animals more frequently took submissive postures, while the CD-1 animals more frequently took dominant postures, and showed a significant increase in biting the S-100β partner. The S-100β animals showed less rearing, perhaps a further indication that they were inhibited by the CD-1 animals. Analysis of oxytocin-containing neurons showed comparable levels in the supraoptic and paraventricular nuclei of the hypothalamus, but significantly reduced numbers of cells in the bed nucleus of the stria terminalis of the S-100β animals. These results are discussed in terms of oxytocin contributions to socialization and fear responding and the significance of these findings to DS.
The preparation and topical antiinflammatory potencies of a series of halomethyl 17 alpha-(acyloxy)- 11 beta-hydroxy-3-oxoandrosta-1,4-diene-17 beta-carbothioates, carrying combinations of 6 ...alpha-fluoro, 9 alpha-fluoro, 16-methyl, and 16-methylene substituents, are described. Key synthetic stages were the preparation of carbothioic acids and their reaction with dihalomethanes. The carbothioic acids were formed from 17 beta-carboxylic acids by initial reaction with dimethylthiocarbamoyl chloride followed by aminolysis of the resulting rearranged mixed anhydride with diethylamine, or by carboxyl activation with 1,1'-carbonyldiimidazole (CDI) or 2-fluoro-N-methylpyridinium tosylate (FMPT) and reaction with hydrogen sulfide, the choice of reagent being governed by the 17 alpha-substituent. Carboxyl activation with FMPT and reaction with sodium hydrogen selenide led to the halomethyl 16-methyleneandrostane-17 beta-carboselenoate analogues. Anti-inflammatory potencies were measured in humans using the vasoconstriction assay and in rats and mice by a modification the Tonelli croton oil ear assay. Best activities were shown by fluoromethyl and chloromethyl carbothioates with a 17 alpha-propionyloxy group. S-Fluoromethyl 6 alpha, 9 alpha-difluoro-11 beta-hydroxy-16 alpha-methyl-3-oxo-17 alpha- (propionyloxy)androsta-1,4-diene-17 beta-carbothioate (fluticasone propionate, FP) was selected for clinical study as it showed high topical antiinflammatory activity but caused little hypothalamic-pituitary-adrenal suppression after topical or oral administration to rodents.
Serotonin exerts an influence on the prenatal development of rat brain. However, later developmental times may be more applicable to the understanding of the role of serotonin in human developmental ...disorders. Therefore, the current study was undertaken to gain preliminary information on the postnatal effects of serotonin on rat brain development. As the 5-HT1A receptor has been shown to be involved in much of the developmental functions of serotonin, an agonist for this receptor, 8-hydroxy-DPAT (8-OH-DPAT), was used. Neonatal rat pups at three ages (postnatal days, PNDs) 3-10, 10-17 or 17-24) were injected daily with 1 mg/kg 8-OH-DPAT and evaluated for behavioral consequences. The youngest group showed accelerated incisor eruption and eye-opening, a possible consequence of 5-HT1A receptor interactions with epidermal growth factor (EGF). Behaviorally, the animals were more anxious. Animals treated from PND 10-17, showed no change in craniofacial development but showed greater behavioral maturity in measures of spontaneous alternation and activity in the open field. The oldest animals (PND 17-24) showed no behavioral alterations, suggesting that this time length is beyond the critical period for serotonin's influence in brain development.
