Synthesis and biological studies on analogs of cyclolinopeptide A with a shortened peptide chain

Continuing our work on the immunosuppressive activity of cyclolinopeptide A (CLA), a cyclic nonapeptide of the sequence: c-(-Leu-Ile-Ile-Leu-Val-Pro-Pro-Phe-Phe), we synthesized a series of 6 linear analogs of CLA, successively shortened at the N-terminus of the peptide chain. Immunosuppressive activity of acetates as well as trifluoroacetates of these peptides was investigated using PFC (humoral immunity) and DTH (cellular immunity) tests. It was found that the immunosuppressive potency of the peptides examined diminishes with shortening of the peptide chain. Octapeptide I with the sequence Ile-Ile-Leu-Val-Pro-Pro-Phe-Phe was found to be the most active of the whole series. The immunosuppressive activity increased again for a tripeptide fragment of CLA of the sequence Pro-Phe-Phe. The immunosuppressive activity of octapeptide probably depends on the suppression of IL-1, IL-6 and TNF production by the cells involved in immune and inflammatory response.     

Differential class III and glibenclamide effects on action potential duration in guinea-pig papillary muscle during normoxia and hypoxia/ischaemia

1. Microelectrode recording techniques were used to study the effects of several potassium channel blockers which are considered to be Class III antiarrhythmic compounds. The effects of (+)-sotalol, UK-66,914, UK-68,798 and E-4031 on action potential duration (APD) were determined in guinea-pig isolated papillary muscles. The compounds were evaluated under normoxic or hypoxic/ischaemic conditions at 36.5 degrees C and compared to glibenclamide, which is considered to be a blocker of ATP-dependent potassium channels. Prolongation of action potential duration at 90% repolarization (APD90) was taken as an indirect measure of potassium channel blockade. 2. Under normoxic conditions, the Class III compounds prolonged APD in a concentration-dependent manner. According to EC15 values, the order of potency of the Class III compounds was found to be UK-68,798 > E-4031 > UK-66,914 > (+)-sotalol. Glibenclamide did not significantly prolong APD90 under normoxic conditions. 3. Perfusion with an experimental hypoxic or ischaemic bathing solution produced qualitatively similar effects on action potentials. Over a period of 20-25 min in either of the experimental solutions, there was a small decrease in action potential amplitude (APA) and a prominent shortening of APD. The ischaemic solution also depolarized the resting membrane potential by about 15 mV. 4. (+)-Sotalol and UK-66,914 did not reverse the shortening of APD induced by perfusion with hypoxic Krebs solution. High concentrations of glibenclamide (10 microM) and UK-68,798 (30 and 60 microM) partially reversed the hypoxia-shortened APD. Glibenclamide was more potent and exhibited a greater time-dependent action than UK-68,798. 5. During experimental ischaemia, the Class III compound E-4031 (10 microM, n = 7) produced small, but significant, increases in the APD90 (11 +/-3 ms after 20 min) which were not clearly time-dependent(14 +/- 4 ms after 30 min). UK-68,798 (10 microM) also produced a small, but insignificant, increase in APD90(12 =/-6 ms at 20 min, n = 4). Higher concentrations of UK-68,798 (30 and 60 microM, n = 4) did not produce a consistently significant increase in APD90 during ischaemia: significance was only attained after 20 min in the presence of 60 microM UK-68,798 (24 +/- 12 ms). However, in marked contrast to the effects of the Class III compounds, glibenclamide (10 microM) produced large time-dependent increases in ischaemic APD90 (34 +/- 11 ms at 7 min, n = 9) which were significant 15 min or more after drug addition(52 +/- 12 ms at 20 min, n = 7; 74 +/- 5 ms at 30 min, n = 6).6. The present microelectrode data suggest that blockers of ATP-dependent potassium channels, such as glibenclamide, might prove to be more effective than Class III compounds against ischaemia-induced shortening of cardiac action potentials.     

Caring for dying children: nurses' experiences

Interviews with 25 nurses in this grounded theory study show that when nurses recognized that a child's death was inevitable, they struggled with both grief distress and moral distress. Their distress occurred within the context of the nurse-patient relationship. Nurses employed a range of strategies to manage their distress. Several conditions facilitated or constrained nurses' strategies, and resulted in far-reaching implications both professionally and personally.     

Structural evolution in gel-derived mullite precursors

The evolution of mullite from organo-metal gel precursors above 700 °C is found to be strongly influenced in both gel pieces and powdered samples by the thermal pretreatment at lower temperatures. Under the present conditions, the optimum preheating temperature was found to be 350 °C, at which temperature an anomalously high concentration was found of an Al species with a characteristic ²⁷Al magic-angle spinning NMR resonance at about 30 ppm. Such Al sites are often described as pentaco-ordinated, but an alternative assignment is considered. The optimum temperature for the formation of this Al site is also optimal for the catalytic formation of aromatic molecules from the residual organic fragments and/or solvent present. Mass spectrometry shows that under the present reaction conditions, these aromatics are thermally stable up to at least 900 °C in air, and the prolonged presence of their decomposition products (CO and water) could facilitate the transformation of the gel to crystalline mullite. The ²⁹Si NMR spectra indicate at least three different Si environments, including one which may arise from the formation of silicon oxycarbide glasses in these gels.     

Effect of ortho- and pyrophosphates on dissolution of Fe,Al, Si,Ca, and organic C in three soils

Phosphate application changes chemical properties of surface soils, consequently influencing crop nutrient availability and pedological process. Sodium ortho- (OP) or pyrophosphate (PP) was equilibrated with three Quebec soils: an Uplands sand (Orthic-Podzol), a St. Bernard loam (Eutric-Cambisol), and a Dalhousie clay (Humic Gleysol) in 0.03 M KClO₄ solution at an initial pH 6.0. Both autoclaved and nonautoclaved soils were used, and dissolution of Fe, Al, Si, Ca and organic C was studied.Concentrations of Fe and Al in OP equilibrated solutions were not detectable. Ca solubility was reduced while dissolution of Si and organic C was increased in the presence of OP. These changes were possibly due to P—Ca precipitates or increased Ca sorption by P, and competition between OP and Si or organic materials for sorption sites. PP enhanced dissolution of Fe, Al, Si and organic C but reduced solubility of Ca. Comparisons showed that PP added to autoclaved soils had greater effects on increasing dissolutions of Fe, Al, Si and organic C and on reducing Ca solubility than OP in both autoclaved and nonautoclaved soils. Autoclaving resulted in greater dissolution of organic C. Dissolved Si with added OP was greater with nonautoclaved soils probably due to more P sorption in the nonautoclaved system, compared with autoclaved soil. Added PP dissolved Fe and Al ions which may ultimately enhance P precipitation by forming less soluble compounds upon hydrolysis of PP to OP.     

Sex attractants for Geometrid and Noctuid moths

Male moths belonging to 17 species of Geometridae and nine species of Noctuidae were captured in traps baited with synthetic chemicals as part of a field screening program. The compounds tested were the C₁₈-C₂₂ homologs of: (1) (3Z,6Z,9Z)-triene hydrocarbons; (2) mixtures containing equal quantities of (3Z,6Z)-cis-9,10-expoxydienes, (3Z,92Z)-cis-6,7-epoxydienes, and (6Z,9Z)-cis-3,4-epoxydienes; (3) (3Z,6Z)-9S,10R-epoxydienes; (4) (3Z,6Z)-9R,10S-epoxydienes; and (5) (3Z,6Z,9Z,11E)-nonadecatetraene. Field captures and electroantennographic assays revealed a high degree of specificity in the responses of many species to the synthetic chemicals. In several species the ability of males to discriminate between the 9S,10R and 9R,10S enantiomers of the monoepoxydiene isomers was clearly shown. Synergists and inhibitors were discovered for several of the reported attractants, some of which were not previously known to have semiochemical activity. The geometrid moths captured includedEpirrhoe sperryi (Herbulot),Mesoleuca ruficillata (Guenée),Triphosa haesitata (Guenée),Metanema inatomaria (Guenée),Prochoerodes transversata (Drury),Cabera erythemaria (Guenée),Synaxis jubararia (Hulst),Dysstroma brunneata ethela (Hulst),Eulithes testata (Linnaeus),Sicya macularia (Harris),Xanthorhoe iduata (Guenée),X. abrasaria aquilonaria (Herrich-Schäffer),X. munitata (Hübner),Itame loricaria (Eversmann),Eupithecia annulata (Hulst),E. rovocastaliata (Packard) andE. satyrata dodata (Taylor). The noctuid moths captured includedBleptina caradrinalis (Guenée),Idia américalis (Guenée),I. aemula (Hübner),Rivula propinqualis (Guenée),Lomanaltes eductalis (Walker),Spargaloma sexpunctata (Grote),Caenurgina distincta (Neumuller),Euclidia cuspidea (Hübner), andZale duplicata (Bethune). Six of the nine noctuid species captured belong to three subfamilies for which sex attractants had not been reported previously. Details for the stereospecific synthesis of (3Z,6Z)-cis-9,10-epoxydienes are also reported.Issued as NRCC No. 24314.     

The Problem of Measurement Model Misspecification in Behavioral and Organizational Research and Some Recommended Solutions.

The purpose of this study was to review the distinction between formative- and reflective-indicator measurement models, articulate a set of criteria for deciding whether measures are formative or reflective, illustrate some commonly researched constructs that have formative indicators, empirically test the effects of measurement model misspecification using a Monte Carlo simulation, and recommend new scale development procedures for latent constructs with formative indicators. Results of the Monte Carlo simulation indicated that measurement model misspecification can inflate unstandardized structural parameter estimates by as much as 400% or deflate them by as much as 80% and lead to Type I or Type II errors of inference, depending on whether the exogenous or the endogenous latent construct is misspecified. Implications of this research are discussed. (PsycINFO Database Record (c) 2011 APA, all rights reserved)