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Selected AbstractsEthylene and Propylene Polymerization Using In Situ Supported Me2Si(Ind)2ZrCl2 Catalyst: Experimental and Theoretical StudyMACROMOLECULAR MATERIALS & ENGINEERING, Issue 3 2006Fernando C. Franceschini Abstract Summary: Me2Si(Ind)2ZrCl2 was in situ immobilized onto SMAO and used for ethylene and propylene polymerization in the presence of TEA or TIBA as cocatalyst. The catalytic system Me2Si(Ind)2ZrCl2/SMAO exhibited different behavior depending on the amount and nature of the alkylaluminum employed and on the monomer type. The catalyst activity was nearly 0.4 kg polymer,·,g cat,1,·,h,1 with both cocatalysts for propylene polymerization. Similar activities were observed for ethylene polymerization in the presence of TIBA. When ethylene was polymerized using TEA at an Al/Zr molar ratio of 250, the activity was 10 times higher. Polyethylenes made by in situ supported or homogeneous catalyst systems had practically the same melting point (Tm). On the other hand, poly(propylenes) made using in situ supported catalyst systems had a slightly lower Tm than poly(propylenes) made using homogeneous catalyst systems. The nature and amount of the alkylaluminum also influenced the molar mass. The poly(propylene) molar mass was higher when TIBA was the cocatalyst. The opposite behavior was observed for the polyethylenes. Concerning the alkylaluminum concentration, the molar mass of the polymers decreased as the amount of TEA increased. In the presence of TIBA, the polyethylene's molar mass was almost the same, independent of the alkylaluminum concentration, and the poly(propylene) molar mass increased with increasing amounts of cocatalyst. The deconvolution of the GPC curves showed 2 peaks for the homogeneous system and 3 peaks for the heterogeneous in situ supported system. The only exception was observed when TEA was used at an Al/Zr molar ratio of 500, where the best fit was obtained with 2 peaks. Based on the GPC deconvolution results and on the theoretical modeling, a proposal for the active site structure was made. Molar mass distribution deconvolution of polyethylene prepared with the system Me2Si(Ind)2ZrCl2/SMAO/TIBA with 500 mol/mol of alkylaluminum as cocatalyst. [source] ,Click' Dendritic Phosphines: Design, Synthesis, Application in Suzuki Coupling, and Recycling by NanofiltrationADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 3 2009Michčle Janssen Abstract A new synthetic route towards stable molecular-weight enlarged monodentate phosphine ligands via ,click' chemistry was developed. These ligands were applied in the Pd-catalyzed Suzuki,Miyaura coupling of aryl halides and phenyl boronic acid. The supported systems show very similar activities compared to the unsupported analogues. Moreover, recycling experiments by means of nanofiltration using ceramic nanofiltration membranes demonstrate that these systems can be recovered and reused efficiently. [source] Specificities of proteases for use in leather manufactureJOURNAL OF CHEMICAL TECHNOLOGY & BIOTECHNOLOGY, Issue 3 2006Farhad Foroughi Abstract Proteases are used in leather manufacture in the processes of soaking, unhairing and bating of hides and skins. However proteases can be relatively non-specific in their usage, and for improved efficacy of enzyme biocatalysis within the industry, an analysis of specific activities of enzymes towards skin proteins was undertaken. Most commercial proteases for soaking showed substantial activity against the substrates elastin,Congo Red and Azocoll but little or no activity against keratin,azure and hide powder black. Enzymes used for unhairing in conjunction with 30% of the usual concentration of sulfide to effect chemical unhairing showed moderate activity against all substrates tested (selected as representative of skin proteins), while proteases used in bating showed activity against Azocoll and elastin,Congo Red but had no keratinase activity and little activity against hide powder black. Bating proteases and soaking proteases displayed similar activities at pH 8. Microbes isolated in the screening of organisms from putrefied skins included one fungal and two bacterial isolates whose extracellular enzymes had efficient unhairing activity without the addition of sulfide. Enzyme activities for these proteases included high activity measured against Azocoll with little or no activity against elastin,Congo Red, keratin,azure and hide powder black. Neither elastase nor keratinase activities were determined as being essential for unhairing. Copyright © 2005 Society of Chemical Industry [source] Novel EGF pathway regulators modulate C. elegans healthspan and lifespan via EGF receptor, PLC-,, and IP3R activationAGING CELL, Issue 4 2010Hiroaki Iwasa Summary Improving health of the rapidly growing aging population is a critical medical, social, and economic goal. Identification of genes that modulate healthspan, the period of mid-life vigor that precedes significant functional decline, will be an essential part of the effort to design anti-aging therapies. Because locomotory decline in humans is a major contributor to frailty and loss of independence and because slowing of movement is a conserved feature of aging across phyla, we screened for genetic interventions that extend locomotory healthspan of Caenorhabditis elegans. From a group of 54 genes previously noted to encode secreted proteins similar in sequence to extracellular domains of insulin receptor, we identified two genes for which RNAi knockdown delayed age-associated locomotory decline, conferring a high performance in advanced age phenotype (Hpa). Unexpectedly, we found that hpa-1 and hpa-2 act through the EGF pathway, rather than the insulin signaling pathway, to control systemic healthspan benefits without detectable developmental consequences. Further analysis revealed a potent role of EGF signaling, acting via downstream phospholipase C-,plc-3 and inositol-3-phosphate receptor itr-1, to promote healthy aging associated with low lipofuscin levels, enhanced physical performance, and extended lifespan. This study identifies HPA-1 and HPA-2 as novel negative regulators of EGF signaling and constitutes the first report of EGF signaling as a major pathway for healthy aging. Our data raise the possibility that EGF family members should be investigated for similar activities in higher organisms. [source] Soldiers With Musculoskeletal InjuriesJOURNAL OF NURSING SCHOLARSHIP, Issue 3 2008Bonnie M. Jennings Purpose: To describe Soldiers' (e.g., U.S. Army personnel) perspectives of the effect of musculoskeletal injuries. Design: Data were collected in the summer of 2003 using a prospective survey design. The survey was mailed to active duty Soldiers on modified work plans because of musculoskeletal injuries. These Soldiers were assigned to one Army installation in the US. Methods: Responses to the survey questions were analyzed using descriptive statistics. The numerous handwritten comments were evaluated qualitatively. Findings: Injuries most often involved the back and knees (18% each). At least 47% of the injuries were work related. Injuries interfered with Soldiers' abilities to perform military tasks such as road marching (80%) and organized physical training (69%). Although many respondents indicated they were not experiencing pain, at least some Soldiers reported mild pain for each of 19 anatomic locations. Severe pain was reported most often for the lower back (21%). In their written comments, Soldiers expressed a sense of frustration with their injuries, the healthcare system and providers, and their unit leaders. Conclusions: Healthcare personnel are challenged to better manage Soldiers with musculoskeletal injuries and expedite their return to full duty. Unit leaders are challenged to create work environments that focus on injury prevention and allow injured Soldiers time to heal. Clinical Relevance: The Soldiers in this study were often engaged in physically challenging work or sports activities when injured. Because people outside the Army engage in similar activities (e.g., construction workers, endurance athletes), the findings from this study might be applicable to nonmilitary communities. Additionally, with the number of Reserve and National Guard Soldiers currently on active duty, civilian nurses might be caring for Soldiers with musculoskeletal injuries. [source] Spread of a Terrestrial Tradition in an Arboreal PrimateAMERICAN ANTHROPOLOGIST, Issue 2 2009Fernanda P. Tabacow ABSTRACT We present data on the spread of terrestrial activities in one group of wild northern muriqui monkeys (Brachyteles hypoxanthus). Both males and females consumed fruit, drank, rested, traveled, and socialized terrestrially, but proportionately more males spent significantly more of their time on the ground than females, and females were more likely to engage in terrestrial activities when accompanied by males than when by themselves. Terrestrial activities occurred in both open and closed habitats where arboreal substrates were available and utilized by other individuals engaged in similar activities. Ecological and demographic factors may have stimulated the muriquis' vertical niche expansion, but increases in the frequency and diversity of terrestrial activities, the high proportion of group members that engage in terrestriality, and its diffusion along male-biased social bonds are consistent with the development of a local terrestrial tradition similar to other types of traditions described in other primates. [Key words: terrestriality, ecology, predation, tradition] [source] Effects of phenolic compounds isolated from Rabdosia japonica on B16-F10 melanoma cellsPHYTOTHERAPY RESEARCH, Issue 7 2008Teruhiko Nitoda Abstract Pedalitin isolated from the aerial part of Rabdosia japonica (Labiatae), exhibited cytotoxicity against the murine B16-F10 melanoma cell line with an IC50 of 30 µm (9.5 µg/mL). As the cells were cultured with this flavone, melanin production was not suppressed, but rather enhanced. Quercetin isolated from the same source exhibited similar activities, but rutin showed neither activity. Copyright © 2008 John Wiley & Sons, Ltd. [source] Recombinant decorsin: Dynamics of the RGD recognition sitePROTEIN SCIENCE, Issue 8 2000Andrzej M. Krezel Abstract Decorsin is an antagonist of integrin ,IIb,3 and a potent platelet aggregation inhibitor. A synthetic gene encoding decorsin, originally isolated from the leech Macrobdella decora, was designed, constructed, and expressed in Escherichia coli. The synthetic gene was fused to the stII signal sequence and expressed under the transcriptional control of the E. coli alkaline phosphatase promoter. The protein was purified by size-exclusion filtration of the periplasmic contents followed by reversed-phase high-performance liquid chromatography. Purified recombinant decorsin was found to be indistinguishable from leech-derived decorsin based on amino acid composition, mass spectral analysis, and biological activity assays. Complete sequential assignments of 1H and proton bound 13C resonances were established. Stereospecific assignments of 21 of 25 nondegenerate ,-methylene groups were determined. The RGD adhesion site recognized by integrin receptors was found at the apex of a most exposed hairpin loop. The dynamic behavior of decorsin was analyzed using several independent NMR parameters. Although the loop containing the RGD sequence is the most flexible one in decorsin, the conformation of the RGD site itself is more restricted than in other proteins with similar activities. [source] Dissatisfied with Life but Having a Good Day: Time-use and Well-being of the Unemployed,THE ECONOMIC JOURNAL, Issue 547 2010Andreas Knabe We apply the Day Reconstruction Method to compare unemployed and employed people with respect to their subjective assessment of emotional affects, differences in the composition and duration of activities during the course of a day and their self-reported life satisfaction. Employed persons are more satisfied with their life than the unemployed and report more positive feelings when engaged in similar activities. Weighting these activities with their duration shows, however, that average experienced utility does not differ between the two groups. Although the unemployed feel sadder when engaged in similar activities, they can compensate this by using the time the employed are at work in more enjoyable ways. [source] Alloplasmic effects on mitochondrial transcriptional activity and RNA turnover result in accumulated transcripts of Arabidopsis orfs in cytoplasmic male-sterile Brassica napusTHE PLANT JOURNAL, Issue 4 2005Matti Leino Summary Mitochondrial transcription was investigated in a cytoplasmic male-sterile (CMS) Brassica napus line with rearranged mitochondrial (mt) DNA mostly inherited from Arabidopsis thaliana. The transcript patterns were compared with the corresponding male-fertile progenitors, B. napus and A. thaliana, and a fertility-restored line. Transcriptional activities, gene stoichiometry and transcript steady-state levels were analysed for all protein and rRNA coding genes and for several orfs present in the A. thaliana mitochondrial genome. The transcriptional activities were highly variable when comparing the parental species, while the CMS and restored lines displayed similar activities. For several ribosomal protein genes transcriptional activity was reduced while it was increased for orf139 in comparison with the parental species. The differences in transcriptional activity observed could be related to differences in relative promoter strength, as gene stoichiometry between lines was very limited. Transcript steady-state levels were more homogenous than the transcriptional activities demonstrating RNA turnover as a compensating mechanism. In the CMS line higher transcript abundance and novel transcript patterns in comparison with the parental lines were found for several genes. Of those, the transcripts for orf139, orf240a and orf294 were less abundant in the fertility-restored line. These putative CMS-associated transcripts were mapped by cRT-PCR. In conclusion we show that (mt) DNA from A. thaliana was non-correctly transcribed and processed/degraded in the B. napus nuclear background. Furthermore, the introgressed nuclear A. thaliana DNA in the fertility-restored line contributes to a more rapid degradation of transcripts accumulated from A. thaliana derived orfs in the CMS line. [source] Preparation and in-vitro Evaluation of 4-Benzylsulfanylpyridine-2-carbohydrazides as Potential Antituberculosis AgentsARCHIV DER PHARMAZIE, Issue 7 2009Petra Herzigová Abstract A set of 4-benzylsulfanylpyridine-2-carbohydrazides was synthesized and evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis, non-tuberculous mycobacteria, and multidrug-resistant M. tuberculosis. The activities expressed as the minimum inhibitory concentration (MIC) fall into a range of 2 to 125 ,mol/L, most often 4 to 32 ,mol/L. The results revealed that the substituents on the benzyl moiety do not influence the antimycobacterial efficacy. The substances exhibited similar activities against sensitive and resistant strains of M. tuberculosis. Furthermore, compounds show low antiproliferative effect and cytotoxicity. [source] Working together: neonatal nurse practitioners in practiceACTA PAEDIATRICA, Issue 2 2002ME Redshaw The aim of this study was to examine the relatively new role of neonatal nurse practitioners (NNPs) in the United Kingdom, comparing practice in different types of neonatal units and work undertaken by junior medical staff (JMS). Diary checklists sent to the total population of qualified NNPs in neonatal units (NNUs) and JMS in six regional centres with qualified NNPs were returned from 68 out of 109 qualified NNPs (62%), working in 50 different NNUs and from 25 out of 48 JMS (52%). Direct observations (totalling 263.5 h) were made by an experienced neonatal nurse researcher on 30 different NNPs. Frequencies of activities and specific procedures were compared between groups. Observational measures included type and duration of activity and interactions with other members of staff. NNPs were found to be undertaking a range of activities: in the NNU, which usually involved blood sampling, siting of intravenous cannulae, presenting at ward rounds and teaching. Outside the unit, NNPs attended the delivery suite and the postnatal ward. Significant differences were found in the nature and organization of their work in different types of NNUs. A comparison between NNPs and JMS showed similar activities, with greater direct involvement by NNPs in the NNU and in teaching. The diary data were supported by observations and together these are evidence of current NNP practice. Conclusion: To a large extent there is an overlap in the work of JMS and NNPs in neonatal units, but although the clinical work and areas of activity are similar, there are differences in emphasis and in work organization. [source] Mutagenicity and disinfection by-products in surface drinking water disinfected with peracetic acidENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2002Silvano Monarca Abstract The aims of this research were to study the influence of peracetic acid (PAA) on the formation of mutagens in surface waters used for human consumption and to assess its potential application for the disinfection of drinking water. The results obtained using PAA were compared to those found with sodium hypochlorite (NaClO) and chlorine dioxide (ClO2). The Ames test, root anaphase aberration assay, and root/micronuclei assay in Allium cepa and Tradescantia/micronuclei test were used to evaluate the mutagenicity of disinfected samples. Microbiological tests were also performed, and disinfection by-products (DBPs) were identified using gas chromatography/mass spectrometry (GC/MS). A slight bacterial mutagenicity was found in raw lake and river water, and similar activity was detected in disinfected samples. A plant test revealed genotoxicity in raw river water, and microbiological analysis showed that PAA has bactericidal activity but lower than that of the other disinfectants. The DBPs produced by PAA were mainly carboxylic acids, which are not recognized as mutagenic, whereas the waters treated with the other disinfectants showed the presence of mutagenic/carcinogenic halogenated DBPs. However, additional experiments should be performed with higher concentrations of PAA and using water with higher organic carbon content to better evaluate this disinfectant. [source] The specificity of alcohol dehydrogenase with cis -retinoidsFEBS JOURNAL, Issue 9 2004Activity with 11- cis -retinol, localization in retina Studies in knockout mice support the involvement of alcohol dehydrogenases ADH1 and ADH4 in retinoid metabolism, although kinetics with retinoids are not known for the mouse enzymes. Moreover, a role of alcohol dehydrogenase (ADH) in the eye retinoid interconversions cannot be ascertained due to the lack of information on the kinetics with 11- cis -retinoids. We report here the kinetics of human ADH1B1, ADH1B2, ADH4, and mouse ADH1 and ADH4 with all- trans -, 7- cis -, 9- cis -, 11- cis - and 13- cis -isomers of retinol and retinal. These retinoids are substrates for all enzymes tested, except the 13- cis isomers which are not used by ADH1. In general, human and mouse ADH4 exhibit similar activity, higher than that of ADH1, while mouse ADH1 is more efficient than the homologous human enzymes. All tested ADHs use 11- cis -retinoids efficiently. ADH4 shows much higher kcat/Km values for 11- cis -retinol oxidation than for 11- cis -retinal reduction, a unique property among mammalian ADHs for any alcohol/aldehyde substrate pair. Docking simulations and the kinetic properties of the human ADH4 M141L mutant demonstrated that residue 141, in the middle region of the active site, is essential for such ADH4 specificity. The distinct kinetics of ADH4 with 11- cis -retinol, its wide specificity with retinol isomers and its immunolocalization in several retinal cell layers, including pigment epithelium, support a role of this enzyme in the various retinol oxidations that occur in the retina. Cytosolic ADH4 activity may complement the isomer-specific microsomal enzymes involved in photopigment regeneration and retinoic acid synthesis. [source] Fish venom: pharmacological features and biological significanceFISH AND FISHERIES, Issue 2 2009Gisha Sivan Abstract Nearly 1200 species of marine fish are venomous and they account for two-third of the population of venomous vertebrates. Fish venoms are focused as a potential source of pharmacological agents and physiological tools that have evolved to target vital processes in the human body that appear to have more electivity than many drugs. Fish venoms possess cardiovascular, neuromuscular, oedematic and cytolytic activity. Lethal toxins have been isolated and purified, with some having LD50 values comparable to that of snake venoms. Cardiovascular activity seems to be the dominant effect of fish venoms in experimental models. Piscine venom acts both pre- and post-junctionally to produce depolarization of cell membranes. Studies on cytolytic activity of fish venom found that it produces lysis by forming hydrophilic pores in cell membranes which then result in cell lysis. Almost all fish venoms with neuromuscular activity also possesses cytolytic activity, and it is very likely that the two activities are related. Fish venom is known to induce intense and sustained edematogenic response. As piscine venoms have evolved for the same purpose, they show a number of similarities pharmacologically and it seems likely that most of the biological activities of any given toxin can be traced back to its cytolytic activity. A variety of toxins have been isolated from piscine venom. Although there is a complex balance between the components present in the venom of different fish, all of them seem to share similar activity , functionally and pharmacologically as well as structurally. [source] Synthesis and Evaluation of S - and C(1) -Substituted Analogues of LincomycinHELVETICA CHIMICA ACTA, Issue 2 2009Marie-Pierre Collin Abstract New thioglycosides and C(1) -alkylated thioglycosides (S -ulosides) of lincomycin were synthesized, and their antibiotic activities were determined. The S -aryl and S -arylalkyl analogues 11a,11i were obtained by S -glycosylation of the sulfoxides 7 with arenethiols, or by S -alkylation of the thiol 14 with alkyl bromides. Lincomycin derivatives 27, 32a, 32b, 38a, 38b, 44, and 47 were prepared via Henry reaction or Michael addition of the lincosamine-derived 1-deoxy-1-nitropyranoses 22. The S -alkyl derivatives showed a similar activity and specificity as lincomycin. Lipophilic S -uloside analogues were two- to fourfold less active than the parent antibiotic, whilst the hydrophilic analogues were inactive. [source] Functional analysis of promoter variants in the microsomal triglyceride transfer protein (MTTP) gene,HUMAN MUTATION, Issue 1 2008Diana Rubin Abstract The microsomal triglyceride transfer protein (MTTP) is required for the assembly and secretion of apolipoprotein B (apoB)-containing lipoproteins from the intestine and liver. According to this function, polymorphic sites in the MTTP gene showed associations to low-density lipoprotein (LDL) cholesterol and related traits of the metabolic syndrome. Here we studied the functional impact of common MTTP promoter polymorphisms rs1800804:T>C (,164T>C), rs1800803:A>T (,400A>T), and rs1800591:G>T (,493G>T) using gene-reporter assays in intestinal Caco-2 and liver Huh-7 cells. Significant results were obtained in Huh-7 cells. The common MTTP promoter haplotype ,164T/,400A/,493G showed about two-fold lower activity than the rare haplotype ,164C/,400T/,493T. MTTP promoter mutant constructs ,164T/,400A/,493T and ,164T/,400T/,493T exhibited similar activity than the common haplotype. Activities of mutants ,164C/,400A/,493G and ,164C/,400A/,493T resembled the rare MTTP promoter haplotype. Electrophoretic mobility shift assays (EMSAs) revealed higher binding capacity of the transcriptional factor Sterol regulatory element binding protein1a (SREBP1a) to the ,164T probe in comparison to the ,164C probe. In conclusion, our study indicates that the polymorphism ,164T>C mediates different activities of common MTTP promoter haplotypes via SREBP1a. This suggested that the already described SREBP-dependent modulation of MTTP expression by diet is more effective in ,164T than in ,164C carriers. Hum Mutat 29(1), 123,129, 2008. © 2007 Wiley-Liss, Inc. [source] Secretion of interferon-, by human macrophages demonstrated at the single-cell level after costimulation with interleukin (IL)-12 plus IL-18IMMUNOLOGY, Issue 3 2009Laila Darwich Summary The interferon (IFN)-, component of the immune response plays an essential role in combating infectious and non-infectious diseases. Induction of IFN-, secretion by human T and natural killer (NK) cells through synergistic costimulation with interleukin (IL)-12 and IL-18 in the adaptive immune responses against pathogens is well established, but induction of similar activity in macrophages is still controversial, with doubts largely focusing on contamination of macrophages with NK or T cells in the relevant experiments. The possible contribution of macrophages to the IFN response is, however, an important factor relevant to the pathogenesis of many diseases. To resolve this issue, we analysed the production of IFN-, at the single-cell level by immunohistochemistry and by enzyme-linked immunosorbent spot (ELISPOT) analysis and unequivocally demonstrated that human macrophages derived from monocytes in vitro through stimulation with a combination of IL-12 and IL-18 or with macrophage colony-stimulating factor (M-CSF) were able to produce IFN-, when further stimulated with a combination of IL-12 and IL-18. In addition, naturally activated alveolar macrophages immediately secreted IFN-, upon treatment with IL-12 and IL-18. Therefore, human macrophages in addition to lymphoid cells contribute to the IFN-, response, providing another link between the innate and acquired immune responses. [source] The expression of metastasis suppressor MIM/MTSS1 is regulated by DNA methylationINTERNATIONAL JOURNAL OF CANCER, Issue 10 2006Jochen Utikal Abstract MIM/MTSS1 was initially described as a gene missing in invasive bladder cancer cell lines. Functional analysis revealed that MIM is an actin binding protein involved in the regulation of actin cytoskeleton dynamics. MIM was shown to be sonic hedgehog (Shh) signaling dependent and synergizes with the effects of Gli transcription factors. Overexpression of MIM in cell lines leads to the inhibition of cell proliferation. In this study, we showed that the inhibition of cell growth by MIM is anchorage independent. We identified and cloned the promoter region of MIM and located the main promoter activity to 276 bp of 5, flanking sequence sited within a CpG island. Analysis of DNA methylation using bisulphite sequencing revealed that MIM promoter is methylated in its 5, region in cells and tissue samples with reduced endogenous MIM expression. Using luciferase reporter assay, we demonstrated that nonmethylated MIM promoter has a similar activity in cell lines with different endogenous MIM expression. Inhibition of DNA methylation by 5-Aza-2,-deoxycytidine led to upregulation of MIM expression in a low expressing cell line. In conclusion, we clearly demonstrate here that the expression of metastasis suppressor MIM is regulated by DNA methylation of a CpG island within its promoter region. © 2006 Wiley-Liss, Inc. [source] Structural characterization of cyclic kallidin analogues in DMSO by nuclear magnetic resonance and molecular dynamicsJOURNAL OF PEPTIDE SCIENCE, Issue 1 2005Elisabetta Schievano Abstract The conformational properties in DMSO of two head-to-tail cyclic analogues of kallidin ([Lys0]-bradykinin, KL) as well as those of the corresponding linear peptides were studied by NMR and molecular dynamics (MD) simulations. The modifications in the sequence were introduced at position 6, resulting in the four peptides, [Tyr6]-KL (YKL), [Trp6]-KL (WKL), cyclo-([Tyr6]-KL) (YCKL) and cyclo-([Trp6]-KL) (WCKL). The linear WKL analogue was significantly more potent than kallidin on rat duodenum preparations, whereas YKL was significantly less potent. Both cyclic peptides, YCKL and WCKL displayed similar activity, lower than that of the linear analogues and also of cyclo-KL. The two linear analogues display high conformational flexibility in DMSO. In the predominant conformer, for both peptides, all three X-Pro bonds adopt a trans configuration. Three out of four conformers present in YCKL and WCKL were completely assigned. The configurations at the X-Pro bonds are the same for the two analogues. All cyclic conformers show a cis configuration in at least one X-Pro bond and always opposite configuration for the two consecutive X-Pro bonds. The NOE-restrained MD calculations resulted in the detection of several elements of secondary structure in each of the conformers. Such elements are described and their possible relevance to biological activity is discussed. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd. [source] Antithrombotic properties of a direct thrombin inhibitor with a prolonged half-life and AT-mediated factor Xa inhibitory activityJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 9 2003G. M. T. Vogel Summary., Rebound thrombin generation after successful thrombolysis might be related to (i) too short-term anticoagulant therapy and to (ii) the inability of heparin derivatives to inhibit clot-bound thrombin. To meet these shortcomings, a compound was synthesized, which consists of a pentasaccharide conjugated to a direct thrombin inhibitor. This compound (Org 42675) has a 10 times longer half-life compared with the original half-life of the direct thrombin inhibitor, while the thrombin inhibitory activity is maintained. An extra advantage of this product is the inhibitory activity on thrombin generation via antithrombin III (AT)-mediated factor (F)Xa inhibition. Org 42675 inhibited in vitro clot-bound thrombin with similar activity to the direct thrombin inhibitor argatroban. In experimental models in rats, Org 42675 showed on a molar base similar antithrombotic activity to unfractionated heparin, was more active than argatroban and was more active than fondaparinux sodium (AT-mediated FXa inhibitor) in arterial thrombosis. Finally, Org 42675 was far more active than the three reference compounds in an experimental thrombolysis model in rabbits. These properties of Org 42675, with its FXa and (clot-bound) thrombin inhibitory activity in combination with its long half-life, make this compound a powerful drug that is likely to be effective in the prevention of re-occlusion after successful thrombolysis in man. [source] Panax notoginseng (Burk.) effects on fibrinogen and lipid plasma level in rats fed on a high-fat dietPHYTOTHERAPY RESEARCH, Issue 2 2003A. F. G. Cicero Abstract Several studies have shown that notoginsenoides improve diastolic function in hypertensive subjects, induce the fibrinolytic system in in vitro models and act as antiproliferative agents on vessel leiomyocytes. Our aim was to evaluate their effect on fibrinogen and lipid plasma levels compared with a well-known HMGCoA reductase inhibitor. Seventy Wistar male adult rats on a fat-enriched diet were treated orally with P. notoginseng pulverized root (43,mg/kg/day or 86,mg/kg/day; 20 animals per group), fluvastatin (3,mg/kg/day; 20 animals) or physiological saline (5,mL/kg/day; 10 animals). The ten rats on a normocaloric diet were also treated with 5,mL/kg/day of physiological saline. After a 28-day treatment, the rats were killed and their blood analysed with standard procedures. Treatment with 43,mg/kg/day of P. notoginseng or 3,mg/kg/day of fluvastatin showed similar activity in decreasing total cholesterol (,23.70%, ,19.29%, respectively) and triglycerides (,21.59%, ,18.55%). The most evident effect of P. notoginseng was the reduction of fibrinogenaemia in treated rats compared with the control values (,38.10%; p,<,0.001), no dose-relationship being shown in this effect. Moreover, no significant variation in HDL cholesterol and glucose levels was observed nor did relevant behavioural changes occur in association with the root intake. Besides a moderate, non dose-related decrease in the plasma lipid levels, P. notoginseng appeared to induce a significant reduction in the rat fibrinogenaemia. Copyright © 2003 John Wiley & Sons, Ltd. [source] Reference-independent ERP old/new effects of auditory and visual word recognition memory: Joint extraction of stimulus- and response-locked neuronal generator patternsPSYCHOPHYSIOLOGY, Issue 6 2007Jürgen Kayser Abstract To clarify polarity, topography, and time course of recognition memory ERP old/new effects during matched visual and auditory continuous word recognition tasks, unrestricted temporal PCA jointly analyzed stimulus- and response-locked, reference-free current source densities (31-channel, N=40). Randomization tests provided unbiased statistics for complete factor topographies. Old/new left parietal source effects were complemented by lateral frontocentral sink effects in both modalities, overlapping modality-specific P3 sources 160 ms preresponse. A mid-frontal sink 45 ms postresponse terminated the frontoparietal generator pattern, showed old/new effects consistent with bilateral activation of anterior cingulate and SMA, and preceded similar activity extending posteriorly along the longitudinal fissure. These methods separated old/new stimulus source (preresponse) and response sink (postresponse) effects from motor and modality-specific ERPs. [source] Is the in situ inflammatory reaction an important tool to understand the cellular immune response in American tegumentary leishmaniasis?BRITISH JOURNAL OF DERMATOLOGY, Issue 1 2008F.N. Morgado Summary Background, The study of American tegumentary leishmaniasis (ATL) lesions might contribute to the understanding of the dynamics of the infection. Objectives, To examine the cellular infiltrate of cutaneous ATL lesions and to compare these results with the detection of the parasites and clinical data. Methods, Lesions of 19 patients with ATL were evaluated through immunohistochemical analysis. Results, The lesions presented an inflammatory reaction mainly consisting of T cells and macrophages. Analysis of the expression of nitric oxide synthase type 2 (NOS2) showed that its intensity was directly correlated with the number of CD3+ T cells. We also observed an association between high NOS2 expression and low quantity of parasites, highlighting the importance of NOS2 in the elimination of parasites. Conclusions, The present results suggest that (i) the inflammatory process is intense in cutaneous ATL lesions and maintains a similar activity for several months; (ii) the dynamics of cell infiltration change during this period, with a gradual decrease in CD8+ T cells, probably correlated with a reduction in the parasite number; (iii) neutrophils may participate in the inflammatory process even during later stages of infection; (iv) the relative increase in the number of CD4+ T cells associated with the onset of fibrosis may suggest a participation of these cells in the control of the inflammatory process; and (v) late lesions with tendency for healing usually show focal inflammation. The study of healing lesions might contribute to the understanding of the late steps of the control of the inflammatory process in ATL lesions. [source] Effects of protein kinase C on M-phase promoting factor in early development of fertilized mouse eggsCELL BIOCHEMISTRY AND FUNCTION, Issue 5 2004Bing-zhi Yu Abstract The mechanism of development of mouse fertilized eggs from the one-cell stage to the two-cell stage remains unclear to date. In the present study, we have evaluated protein kinase C (PKC) and M-phase promoting factor (MPF) kinase activity in fertilized mouse eggs treated with a PKC modulator. PKC and MPF activity have similar activity. The two subunits of MPF, p34cdc2 and cyclin B, were shown to be included in the substrates phosphorylated by PKC in fertilized mouse eggs, while PKC modulator affected the electrophoretic mobility shift of cdc2 and cdc25C by dephosphorylation and phosphorylation. These results clearly indicate that PKC may affect the progression of the cell cycle through post-translational modification of MPF activity. Copyright © 2004 John Wiley & Sons, Ltd. [source] | |||||||||||||||||||