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Derivates
Selected AbstractsAntiplasmodiale Thiostreptonderivate , Proteasominhibitoren mit einem dualen Wirkmechanismus,ANGEWANDTE CHEMIE, Issue 19 2010Sebastian Schoof Zwei auf einen Streich: Semisynthetische Derivate des ribosomalen Inhibitors Thiostrepton zeigten bis zu 10-mal höhere antiplasmodiale Aktivität als der Naturstoff. Diese Aktivität konnte mit der selektiven funktionalen Inhibierung des 20S-Proteasoms korreliert werden (siehe Bild). Die Thiostreptonderivate eignen sich als neuartige Antimalariawirkstoffe mit dualem Wirkmechanismus und als Gerüste für die Entwicklung von Proteasominhibitoren. [source] Naturstoffe und ihre biologischen Angriffsziele: proteomische und metabolomische MarkierungsstrategienANGEWANDTE CHEMIE, Issue 15 2010Thomas Böttcher Abstract Das aktivitätsbasierte Protein-Profiling (ABPP) hat sich zu einer ausgereiften Standardmethode für die schnelle, empfindliche und selektive Identifizierung von Enzymaktivitäten und Inhibitoren in Proteomen entwickelt. Mit naturstoffbasierenden Sonden lassen sich die Angriffsziele (targets) vieler bislang uncharakterisierter Moleküle leicht in komplexen Proteomen aufklären und so ihre genaue Funktion und der Wirkmechanismus verstehen. Zum anderen dienen Naturstoffsonden und ihre Derivate als pharmakologische Leitstrukturen, die essenzielle Komponenten in der Zelle hemmen und in biologischen Assays ihre Wirksamkeit zeigen. Da die komplexen regulatorischen Prozesse einer Zelle mehr umfassen als nur Transkription, Translation und Aktivierung, ist es entscheidend, auch die Produkte des aktiven Proteoms , die Metaboliten und Bindungspartner einzelner Enzyme und Proteine , zu identifizieren. Dabei sind Methoden nötig, mit denen sich das chemisch komplexe Metabolom charakterisieren lässt. In den letzten Jahren gab es hierzu eine Reihe interessanter Ansätze, mit denen eine globale Untersuchung von Enzym-Metabolit-Paaren jetzt zum ersten Mal möglich ist. [source] Amide-to-Ester Substitution Allows Fine-Tuning of the Cyclopeptide Conformational Ensemble,ANGEWANDTE CHEMIE, Issue 15 2010Tommaso Cupido Ohne die dreidimensionale Gesamtstruktur zu beeinflussen, hat eine Substitution von Amid- gegen Esterfunktionen im Molekülgerüst deutliche Auswirkungen auf das Konformationsgleichgewicht des RGD-Cyclopeptids Cilengitid und seiner Derivate (siehe Bild; RGD=Arg-Gly-Asp). Die geeignete Substitution stabilisiert die Rezeptor-komplementären Konformationen und verbessert die biologische Aktivität dieses Integrin-Antagonisten. [source] Reversible, nicht metallunterstützte Bindung von Kohlendioxid durch frustrierte Lewis-Paare,ANGEWANDTE CHEMIE, Issue 36 2009Cornelia Seltene Beispiele für die metallfreie Bindung von Kohlendioxid sind frustrierte Lewis-Paare, bestehend aus sperrigen Phosphan- und Borankomponenten, die CO2 reversibel binden. Der Mechanismus der Bildung der CO2 -Derivate 1 und 2 durch nahezu gleichzeitige P-C- und B-O-Bindungsbildung wurde mithilfe quantenchemischer Rechnungen charakterisiert. [source] CLIMATE OSCILLATIONS AS RECORDED IN SVALBARD ICE CORE ,18O RECORDS BETWEEN AD 1200 AND 1997GEOGRAFISKA ANNALER SERIES A: PHYSICAL GEOGRAPHY, Issue 1 2005ELISABETH ISAKSSON ABSTRACT. We apply two different time series analytical tools to ,18O records from two Svalbard ice cores. One ice core is from Lomonosovfonna at 1250 ma.s.l. and the other from Austfonna at 750 m a.s.l. These cores are estimated to cover at least the past 800 years and have been dated using a combination of known reference horizons and glacial modelling. Wavelet analysis reveals low frequency oscillations on the 60,120,year scale on the lower elevation site Austfonna while the higher altitude site on Lomonosovfonna does not reveal such variability throughout the record. The second method, Significant Zero Crossing of Derivates (SiZer) does not resolve the low-frequency periodicity seen in the wavelet analysis. The low-frequency variability resolved by the wavelet analysis is similar to what has been found in various climate records including instrumental temperatures and tree-rings, and has been proposed as the most important oscillation for the observed trends in Arctic air temperatures. [source] Stability and Drug Loading of Spontaneous Vesicles of Comb-Like PEG DerivatesMACROMOLECULAR RAPID COMMUNICATIONS, Issue 5 2007Xiaolin Li Abstract A novel comb-like derivative CPEG- g -cholesterol was prepared by the reaction of cholesteryl chloroformate with hydroxyl groups of CPEG. The TEM and SEM results showed that CPEG-cholesterol spontaneously aggregated vesicles with the membrane thickness of 4.27,±,0.48 nm. Compared with the vesicles formed by comb-like PEG (CPEG), the derivation of cholesteryl chloroformate increased the thickness of vesicle membrane and developed corrugations. The hydrophobic doxorubicin (Dox) was added into the solution of CPEG and CPEG- g -cholesterol to test their vesicle stability. The drug-loaded vesicles of CPEG- g -cholesterol still existed but those of CPEG disappeared, which indicated that stability of vesicles was enhanced by the derived cholesteryl chloroformate. The vesicles were further cross-linked by the reaction between divinyl sulfone (DVS) and the hydroxy groups in the side chains of the CPEG and CPEG- g -cholesterol. Both cross-linked vesicles of CPEG and CPEG- g -cholesterol entrapped considerable hydrophobic Dox in the vesicles membrane. The spontaneous vesicles of CPEG- g -cholesterol and the crosslinked vesicles of CPEG and CPEG- g -cholesterol might have great potential as a cargo of the hydrophobic drug. [source] Reaction Chemistry of 1,4-Benzopyrone Derivates in Non-Equilibrium Low-Temperature PlasmasPLASMA PROCESSES AND POLYMERS, Issue 6 2010Franziska Grzegorzewski Abstract 1,4-Benzopyrone derivates are exposed to different cold gas discharges. Reactions are carried out using different feed gases (argon, oxygen) and excitation sources (radio frequency, microwave) at both atmospheric and low pressure. A structure-dependent degradation upon plasma-chemical reactions can be observed. From contact-angle measurements a strong surface oxidation is suggested. Independent of the source used plasma treatment leads to a significant increase in oxygen content of the samples through newly introduced carbonyl- and carboxyl-functions. This is in agreement to results showing that during thermal food processes oxidative species lead to the formation of characteristic low-molecular weight degradation products. [source] UIII -Induced Reductive Co-Coupling of NO and CO to Form UIV Cyanate and Oxo DerivatesCHEMISTRY - A EUROPEAN JOURNAL, Issue 31 2010Alistair S. CO and NO give NCO and O! Sequential treatment of [U(,-C8H6{SiiPr3 -1,4}2)(,-Cp*)] with CO followed by NO (or vice versa) affords a mixture of the bridging cyanate complex [{U(,-C8H6{SiiPr3 -1,4}2)(,-Cp*)}2(,-OCN)2] and the bridging oxo complex [{U(,-C8H6{SiiPr3 -1,4}2)(,-Cp*)}2(,-O)], both of which have been structurally characterised (see scheme). [source] Glycine Receptors in the Nucleus Accumbens Involved in the Ethanol Intake-Reducing Effect of AcamprosateALCOHOLISM, Issue 1 2010PeiPei Chau Background:, We have previously demonstrated that strychnine-sensitive glycine receptors (GlyRs) in the nucleus accumbens (nAc) and nicotinic acetylcholine receptors (nAChRs) in the ventral tegmental area are involved in mediating ethanol (EtOH)-induced elevation of dopamine in the rat mesolimbic dopamine system. This neuronal circuitry was also demonstrated to mediate dopamine elevation in the nAc after both taurine, an endogenous agonist of GlyRs, and acamprosate, a synthetic derivate of homotaurine. The aim of this study was to investigate whether the EtOH intake-reducing effect of acamprosate involves accumbal GlyRs. Methods:, For this purpose, we used a voluntary EtOH consumption model where EtOH medium- and high-preferring rats were implanted with guide cannulae in the nAc. The animals received daily injections of acamprosate or 0.9% NaCl before accessing a bottle of 6% EtOH and a bottle of water. After 2 days, a microinjection of strychnine or vehicle preceded the daily systemic injection and bottle-access period. Results:, Acamprosate, but not saline, decreased EtOH intake. Pretreatment with Ringer in the nAc did not influence EtOH intake in saline or acamprosate-treated animals. Pretreatment with strychnine had no effect on EtOH intake in saline-treated animals, whereas it completely reversed the EtOH intake-reducing effect of acamprosate. Conclusions:, Based on current and previous results, we suggest that acamprosate primarily interacts with accumbal GlyRs and secondarily with ventral tegmental nAChRs, in a similar manner to that previously observed with EtOH and taurine. The interaction between acamprosate and GlyRs does not only influence dopamine output in the nAc but also EtOH consumption, giving further support for our hypothesis that GlyRs are of importance in EtOH reinforcement. [source] Skin conductance or entropy for detection of non-noxious stimulation during different clinical levels of sedationACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2007A. C. Gjerstad Background:, State entropy (SE) measures electroencephalographic signals, whereas response entropy (RE) also includes frontal electromyographic activity. In the presence of electromyographic activity, the RE index is larger than the SE index, the difference being denoted as RE-, (RE-,= RE , SE). Skin conductance (SC) may be expressed by a slow reacting variable, the mean SC level, the derivate of the mean SC level (D-SC), the number of SC fluctuations (NSCF) or the amplitude of the SC fluctuations (ASCF), which directly shows skin sympathetic nerve activity. The goal of this study was to evaluate whether these SC and entropy variables could differentiate between the responses obtained to load sound stimuli at different sedation levels before the induction of general anaesthesia. Methods:, Twenty women scheduled for gynaecological laparotomy were studied. The modified observer's assessment of alertness sedation (OAAS) was used to classify the patients' hypnotic levels. White sounds (98 dB) were given at OAAS level 5 without propofol, at OAAS levels 4,3 and 3,2 with propofol and at OAAS levels 3,2 and < 2 with propofol and remifentanil. Results:, RE and SE showed a steady decline from OAAS level 5 to level < 2 (P < 0.01). RE-, did not discriminate between any of the OAAS levels (P= NS). The mean SC level discriminated between OAAS levels 4,3 to < 2 (P < 0.01). D-SC discriminated between all the different OAAS levels (P < 0.01). NSCF discriminated between OAAS levels 5 to 3,2 (P < 0.05), but did not discriminate at OAAS level 3,2 between propofol alone or combined with remifentanil, or between OAAS level 3,2 and < 2. ASCF differentiated between OAAS levels 5 and 4 (P < 0.001) and OAAS levels 3,2 and < 2 (P < 0.05) only. Conclusion:, RE, SE and D-SC showed a similar discrimination between sound responses at the different sedation levels. [source] Tuberculosis Caused by Mycobacterium microti in South American CamelidsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 6 2009P. Zanolari Background: Infection with Mycobacterium microti can cause chronic disease in animals and threaten human health through its zoonotic potential. Objective: To describe clinical findings, diagnostic investigations, necropsy, and epidemiology results in South American camelids (SAC) infected with M. microti, member of the Mycobacterium tuberculosis complex. Animals: Eleven SAC with tuberculous lesions. Methods: Description of 10 llamas and 1 alpaca, aged 4,18 years, from 6 herds with a history of wasting and weakness admitted to the Vetsuisse-Faculty of Berne over 8 years. Results: Clinical signs included weight loss, recumbency, and anorexia in late stages of the disease. Respiratory problems were seen in 6 animals of 11. No consistent hematologic abnormalities were identified. Suspect animals were examined in detail by abdominal ultrasonography and thoracic radiology. Abnormal findings such as enlarged mediastinal, mesenteric, or hepatic lymph nodes were seen only in animals with advanced disease. Single comparative intradermal tuberculin test with bovine protein purified derivate (PPD) and avian PPD was negative in all animals. At necropsy, typical tuberculous lesions were found, and confirmed by bacteriological smear and culture, molecular methods, or both. Conclusions and Clinical Importance: Infection caused by M. microti should be considered a differential diagnosis in chronic debilitating disease with or without respiratory signs in SAC. Antemortem confirmation of the diagnosis remains challenging at any stage of infection. Because cases of M. microti infection have been reported in immunocompromized human patients, the zoonotic potential of the organism should be kept in mind when dealing with this disease in SAC. [source] Plasma ADMA concentrations at birth and mechanical ventilation in preterm infants: A prospective pilot studyPEDIATRIC PULMONOLOGY, Issue 12 2008Milan C. Richir MD Abstract Rationale Nitric oxide (NO) produced in the lung is an important mediator of normal lung development, vascular smooth muscle relaxation, and ventilation perfusion matching. NO is synthesized from arginine by the action of NO-synthase (NOS). Asymmetric dimethylarginine (ADMA), an endogenous derivate of arginine, inhibits NOS and is thereby a determinant of NO synthesis. We compared ADMA and arginine levels in preterm infants requiring mechanical ventilation with preterm infants who did not require mechanical ventilation and determined the relation between ADMA and the length of mechanical ventilation in these infants. Methods Thirty preterm infants, mean (SD) gestational age 29.3 (1.7) weeks and birth weight 1,340 (350) gram, of the Neonatal Intensive Care Unit of the VU University Medical Center were included. ADMA and arginine were measured in umbilical cord blood and the length of mechanical ventilation (days) was registered. Results Gestational age and birth weight were significantly smaller in infants requiring mechanical ventilation, but were not significantly correlated with plasma ADMA concentration after birth. Plasma ADMA concentrations were significantly higher in infants who required mechanical ventilation than in infants who did not require mechanical ventilation (1.53,±,0.23 and 1.37,±,0.14 µmol/L, respectively; P,=,0.036). ADMA concentration was significantly related to length of mechanical ventilation (B,=,3.4; 95% CI: 1.1,5.6; P,=,0.006), also after adjustment for gestational age (B,=,2.3; 95% CI: 0.4,4.2; P,=,0.024). Conclusions Preterm infants who require mechanical ventilation have increased ADMA levels compared to non-ventilated preterm infants. ADMA levels at birth are related to the length of mechanical ventilation. An increased ADMA concentration could reduce NO synthesis, which could lead to insufficient gas exchange and, consequently, a longer period of mechanical ventilation. Pediatr. Pulmonol. 2008; 43:1161,1166. © 2008 Wiley-Liss, Inc. [source] Cytokine Changes in Postmenopausal Women Treated with Estrogens: a Placebo-controlled StudyAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 2 2002GÖRAN BERG PROBLEM:,Hormone replacement therapy (HRT) is being increasingly used in postmenopausal women. Sex steroids are known to affect the immune system in several ways, although this is mainly based on clinical observations and experimental studies. METHOD OF STUDY:,We studied the in vivo effects of transdermal estrogens (50 ,g 17 ,-Estradiol/24 hr) on cytokine production in postmenopausal women. A total of 17 women were randomized to either placebo (n=7) or active estrogen therapy (n=10) for 14 weeks, with addition of oral medoxyprogesterone acetate 10 mg daily during the last 2 weeks in both groups. Secretion of the cytokines IFN-,, IL-4, IL-10 and IL-6 in blood mononuclear cells was determined, spontaneously and after stimulation with common vaccination antigens and mitogen, using the cell ELISA technique. RESULTS:,IL-6 production after stimulation with purified protein derivate (PPD) decreased in the estrogen treated group (P < 0.01). Mitogen-induced IL-6 production was reduced in the estrogen treated group in contrast to an increase in the placebo group, leading to a significant difference (P < 0.01) between the groups after 12 weeks of treatment. This difference was eliminated after an addition of progestagens for 2 weeks. No significant changes were noted for IFN-,, IL-4 or IL-10 in relation to estrogen or placebo treatment. CONCLUSIONS:,In the present controlled study, the main in vivo effect of estrogens was a decrease in IL-6 production, indicating a possible beneficial effect of estrogen therapy. [source] Evaluation of imiquimod for the therapy of external genital and anal warts in comparison with destructive therapiesBRITISH JOURNAL OF DERMATOLOGY, Issue 2007H. Schöfer Summary External genital and anal warts (acuminate condyloma) were the first medical indication the topical immune response modifier imiquimod was approved for in 1997. Since then, many placebo controlled randomized clinical trials have demonstrated the efficacy and safety of this synthetic imidazoquinoline derivate for the treatment of different human papillomavirus infections and tumours. Treatment modalities for genital warts (5% cream, three times weekly, minimum duration 4 weeks, control of side-effects) have been optimized and assured by further clinical trials and meta-analyses. For a few years clinical studies focussed on the long-term efficacy of the immunomodulatory therapy (sustained clearance from warts) and most recent studies compared the efficacy of ablative, destructive and imiquimod monotherapy as well as combination therapies. [source] Cyclic fatty acids in sunflower oils during frying of frozen foods with oil replenishment,EUROPEAN JOURNAL OF LIPID SCIENCE AND TECHNOLOGY, Issue 2 2007Antonio Romero Abstract Frying of frozen foods has become popular because it considerably reduces cooking time. Polymers and cyclic fatty acid monomers (CFAM) formed during frying are potentially toxic and therefore their production should be minimized. Twenty discontinuous fryings of different frozen foods were carried out over ten consecutive days, in sunflower oil (SO) and in high-oleic acid sunflower oil (HOSO), by adding fresh oil after each frying to bring the volume of the fryer oil back to 3,L. CFAM methyl ester derivates were hydrogenated, isolated, concentrated and quantified by HPLC using a reverse-phase column, followed by gas chromatography. After 20,fryings, significantly higher contents of polar material, polymers and CFAM (all p,<0.001) were found in SO than in HOSO. Bicyclic compound formation was four times higher in SO (p,<0.001). The fat from the fried potatoes presented a polymer content very similar to that of their corresponding oils. The 100-g rations of the SO-fried potatoes from the 20th frying supply 49 or 15%, respectively, more polymers and CFAM and 1,mg more bicyclic fatty acids than the 100-g rations of HOSO-fried potatoes. Because digestion and absorption of polar material, polymers and CFAM occur, the data clearly show the advantageousness and advisability of frying with HOSO rather than SO. [source] Plant oxylipins: COI1/JAZs/MYC2 as the core jasmonic acid-signalling moduleFEBS JOURNAL, Issue 17 2009Andrea Chini Jasmonic acid (JA) and its derivates, collectively known as jasmonates (JAs), are essential signalling molecules that coordinate the plant response to biotic and abiotic challenges, in addition to several developmental processes. The COI1 F-box and additional SCF modulators have long been known to have a crucial role in the JA-signalling pathway. Downstream JA-dependent transcriptional re-programming is regulated by a cascade of transcription factors and MYC2 plays a major role. Recently, JAZ family proteins have been identified as COI1 targets and repressors of MYC2, defining the ,missing link' in JA signalling. JA,Ile has been proposed to be the active form of the hormone, and COI1 is an essential component of the receptor complex. These recent discoveries have defined the core JA-signalling pathway as the module COI1/JAZs/MYC2. [source] Identification and characterization of a new gene from Variovorax paradoxus Iso1 encoding N -acyl- d -amino acid amidohydrolase responsible for d -amino acid productionFEBS JOURNAL, Issue 19 2002Pei-Hsun Lin An N -acyl- d -amino acid amidohydrolase (N -D-AAase) was identified in cell extracts of a strain, Iso1, isolated from an environment containing N -acetyl- d -methionine. The bacterium was classified as Variovorax paradoxus by phylogenetic analysis. The gene was cloned and sequenced. The gene consisted of a 1467-bp ORF encoding a polypeptide of 488 amino acids. The V. paradoxusN -D-AAase showed significant amino acid similarity to the N -acyl- d -amino acid amidohydrolases of the two eubacteria Alcaligenes xylosoxydans A-6 (44,56% identity), Alcaligenes facelis DA1 (54% identity) and the hyperthermophilic archaeon Pyrococcus abyssi (42% identity). After over-expression of the N -D-AAase protein in Escherichia coli, the enzyme was purified by multistep chromatography. The native molecular mass was 52.8 kDa, which agreed with the predicted molecular mass of 52 798 Da and the enzyme appeared to be a monomer protein by gel-filtration chromatography. A homogenous protein with a specific activity of 516 U·mg,1 was finally obtained. After peptide sequencing by LC/MS/MS, the results were in agreement with the deduced amino acid sequence of the N -D-AAase. The pI of the enzyme was 5.12 and it had an optimal pH and temperature of 7.5 and 50 °C, respectively. After 30 min heat treatment at 45 °C, between pH 6 and pH 8, 80% activity remained. The N -D-AAase had higher hydrolysing activity against N -acetyl- d -amino acid derivates containing d -methionine, d -leucine and d -alanine and against N -chloroacetyl- d -phenylalanine. Importantly, the enzyme does not act on the N -acetyl- l -amino acid derivatives. The enzyme was inhibited by chelating agents and certain metal ions, but was activated by 1 mm of Co2+ and Mg2+. Thus, the N -D-AAase from V. paradoxus can be considered a chiral specific and metal-dependent enzyme. [source] Immunomodulatory therapy for chronic hepatitis B virus infectionFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2005D. Sprengers Abstract Hepatitis B virus (HBV) is one of the most prevalent viral pathogens of man with around 350 million chronically infected patients. It has been postulated that in persistently infected individuals the HBV-specific immune response is too weak to eliminate HBV from all infected hepatocytes, but sufficiently strong to continuously destroy HBV-infected hepatocytes and to induce chronic inflammatory liver disease. The primary aim in the treatment of chronic hepatitis B is to induce sustained disease remission and prevent serious complications like liver failure and/or hepatocellular carcinoma. The recent emergence of drug-resistant HBV mutants and post-treatment relapse as a consequence of nucleoside analogue monotherapy emphasizes that the principal goal should be to stimulate a successful immune response. In this paper we will focus on the immune response to HBV and we will review reported data on immunotherapeutic strategies like immunomodulatory drugs (cytokines and Thymic derivates) and vaccine therapies using currently available recombinant anti-HBV vaccines, lipopeptide-based T cell vaccine and newly developed genetic vaccines. [source] Identification of Acipenseriformes species in tradeJOURNAL OF APPLIED ICHTHYOLOGY, Issue 2008A. Ludwig Summary Sturgeons and paddlefishes (Acipenseridae) are highly endangered freshwater fishes. Their eggs (sold as caviar) are one of the most valuable wildlife products in international trade. Concerns of overharvesting and the conservation status of many of the 27 extant species of Acipenseriformes led to all species being included on the CITES Appendices in 1998. Since then international trade in all products and parts from sturgeon and paddlefish has been regulated. However, despite the controls on trade, unsustainable harvesting continues to threaten many populations. Illegal fishing and trade continues to be a threat to the management of these fish. To enforce the regulation of legal trade and prevention of illegal trade, the development of a uniform identification system for parts and derivates of Acipenseriformes has been identified as an urgent requirement. Ideally this system should be suitable for (i) identification at the species-level of caviar and other products from Acipenseriformes; (ii) population identification; (iii) source identification (wild vs aquaculture); and (iv) determining the age of caviar because strict timeframes govern its international trade. This paper reviews the techniques currently available and their potential to be used in an identification system for Acipenseriformes species and their products in trade. A review of all available identification techniques has shown that there is not a single method that can meet all requirements (see i,iv), and it does not appear to be feasible to develop such a method in the near future therefore the most appropriate methods need to be developed for each. Considering the advantages and disadvantages of all techniques reviewed in this document, the following conclusions can be drawn: (i) for the identification of species, approaches are recommended that target mitochondrial cytochrome b sequences (RFLP, nested PCR or direct sequencing). However, they show limitations for the detection of hybrids (although natural hybrids are rare, the number of artificially produced hybrids in aquaculture is increasing) and for the differentiation of the following closely related species complexes: Acipenser gueldenstaedti,Acipenser baerii,Acipenser persicus,Acipenser naccarii; Acipenser medirostris,Acipenser mikadoi; and Scaphirhynchus albus,Scaphirhynchus plathorhynchus,Scaphirhynchus suttkusi; (ii) the identification of different populations of the same species is currently not feasible because genetic data are incomplete for most populations, and stocking and release programmes, which have become more and more common, often result in a mixture of phenotypes and genotypes, thereby impeding the creation and application of such a population identification system; (iii) source identification based on genetic approaches can be excluded at present because there are no genetic differences between wild and hatchery-raised fish. This is the result of the continuing restocking of natural populations with captive fish and vice versa. However, because rearing (i.e. environmental) conditions are different, methods focusing on differences in water quality or food seem to be more appropriate (for example differences in fatty acid composition). So far, very few studies have been conducted and therefore, source identification methods merit further exploration; and (iv) the age of a product in trade cannot be detected by DNA-based methods and protein profiling is undoubtedly impractical due to hard-to-perform, labour-and cost-intensive methods, which are highly susceptible to protein degradation. Arising from the limits discussed above, the next steps in the development of a uniform sturgeon identification system are proposed to be the following: (i) designation of qualified reference laboratories at national levels in (re-) exporting and importing countries. These should be approved through a standardized testing procedure, for instance a ring test on blind samples. Registered laboratories should be published and disseminated and their accreditations should be subject to certain guarantees regarding quality, economic independence and scientific rigour. Operational procedures have to be determined and standardized among reference laboratories; (ii) establishment of reference collections that are accessible to the reference laboratories containing DNA analyses results and information on the location and availability of tissue samples. This is highly recommended as an important step towards a population identification system and indispensable for a general species identification system; (iii) creation of a website access to the reference collections containing the reference database information about genetic samples, comparable to NCBI, which provides background data: sample location; population information; citation; available genetic data; location of archival storage; currently treated and distributed caviar and status of analysis. This website should also be a forum for the exchange of knowledge on and experiences with identification systems, species and population status information, relevant scientific research, etc.; and (iv) the outcome of the trade identification tests should be made available to the reference laboratories for future reference. The universal caviar labelling system could incorporate an indication of the verification of the consignment. In view of the lack of knowledge and the great need to develop a uniform identification system for Acipenseriformes with regard to the importance of the international caviar trade, further scientific guidance and appropriate research is strongly recommended. Progress should be assessed and exchanged on a regular basis. [source] Platelet lysate promotes in vitro wound scratch closure of human dermal fibroblasts: different roles of cell calcium, P38, ERK and PI3K/AKTJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 8b 2009Elia Ranzato Abstract There is a growing interest for the clinical use of platelet derivates in wound dressing. Platelet beneficial effect is attributed to the release of growth factors and other bioactive substances, though mechanisms are mostly unknown. We studied wound-healing processes of human primary fibroblasts, by exposing cells to a platelet lysate (PL) obtained from blood samples. Crystal violet and tetrazolium salt (MTS) assays showed dose,response increase of cell proliferation and metabolism. In scratch wound and transwell assays, a dose of 20% PL induced a significant increase of wound closure rate at 6 and 24 hrs, and had a strong chemotactic effect. BAPTA-AM, SB203580 and PD98059 caused 100% inhibition of PL effects, whereas wortmannin reduced to about one third the effect of PL on wound healing and abolished the chemotactic response. Confocal imaging showed the induction by PL of serial Ca2+ oscillations in fibroblasts. Data indicate that cell Ca2+ plays a fundamental role in wound healing even without PL, p38 and ERK1/2 are essential for PL effects but are also activated by wounding per se, PI3K is essential for PL effects and its downstream effector Akt is activated only in the presence of PL. In conclusion, PL stimulates fibroblast wound healing through the activation of cell proliferation and motility with different patterns of involvement of different signalling pathways. [source] Inhibition of nitric oxide synthase inhibitors and lipopolysaccharide induced inducible NOS and cyclooxygenase-2 gene expressions by rutin, quercetin, and quercetin pentaacetate in RAW 264.7 macrophagesJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2001Yen-Chou Chen Abstract Several natural flavonoids have been demonstrated to perform some beneficial biological activities, however, higher-effective concentrations and poor-absorptive efficacy in body of flavonoids blocked their practical applications. In the present study, we provided evidences to demonstrate that flavonoids rutin, quercetin, and its acetylated product quercetin pentaacetate were able to be used with nitric oxide synthase (NOS) inhibitors (N -nitro- L -arginine (NLA) or N -nitro- L -arginine methyl ester (L -NAME)) in treatment of lipopolysaccharide (LPS) induced nitric oxide (NO) and prostaglandin E2 (PGE2) productions, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) gene expressions in a mouse macrophage cell line (RAW 264.7). The results showed that rutin, quercetin, and quercetin pentaacetate-inhibited LPS-induced NO production in a concentration-dependent manner without obvious cytotoxic effect on cells by MTT assay using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide as an indicator. Decrease of NO production by flavonoids was consistent with the inhibition on LPS-induced iNOS gene expression by western blotting. However, these compounds were unable to block iNOS enzyme activity by direct and indirect measurement on iNOS enzyme activity. Quercetin pentaacetate showed the obvious inhibition on LPS-induced PGE2 production and COX-2 gene expression and the inhibition was not result of suppression on COX-2 enzyme activity. Previous study demonstrated that decrease of NO production by L -arginine analogs effectively stimulated LPS-induced iNOS gene expression, and proposed that stimulatory effects on iNOS protein by NOS inhibitors might be harmful in treating sepsis. In this study, NLA or L -NAME treatment stimulated significantly on LPS-induced iNOS (but not COX-2) protein in RAW 264.7 cells which was inhibited by these three compounds. Quercetin pentaacetate, but not quercetin and rutin, showed the strong inhibitory activity on PGE2 production and COX-2 protein expression in NLA/LPS or L -NAME/LPS co-treated RAW 264.7 cells. These results indicated that combinatorial treatment of L -arginine analogs and flavonoid derivates, such as quercetin pentaacetate, effectively inhibited LPS-induced NO and PGE2 productions, at the same time, inhibited enhanced expressions of iNOS and COX-2 genes. J. Cell. Biochem. 82: 537,548, 2001. © 2001 Wiley-Liss, Inc. [source] Synthesis of isomeric 2,3,5-trisubstituted perhydropyrrolo[3,4-d]-isoxazole-4,6-diones via 1,3-dipolar cycloaddition reactionsJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 4 2010Hamdi Özkan A series of isoxazolidine derivates (isomeric 2,3,5-trisubstitutedperhydropyrrolo[3,4-d]isoxazole-4,6-diones) used as anti-inflammatory, immunosuppressive, antibacterial agent, and inhibitor for some enzymes were synthesized. These compounds were prepared by 1,3-dipolar cycloaddition of N -methyl maleimide and N -phenyl maleimide with nitrones. Diastereomeric products obtained in this reaction were separated by column chromatography and recrystallized. All compounds synthesized were characterized by elemental analysis and spectroscopic methods (1H NMR, 13C NMR, and FTIR). J. Heterocyclic Chem., (2010). [source] Expression of 3-hydroxyisobutyrate dehydrogenase in cultured neural cellsJOURNAL OF NEUROCHEMISTRY, Issue 4 2008Radovan Murín Abstract The branched-chain amino acids (BCAAs) , isoleucine, leucine, and valine , belong to the limited group of substances transported through the blood,brain barrier. One of the functions they are thought to have in brain is to serve as substrates for meeting parenchymal energy demands. Previous studies have shown the ubiquitous expression of a branched-chain alpha-keto acid dehydrogenase among neural cells. This enzyme catalyzes the initial and rate-limiting step in the irreversible degradative pathway for the carbon skeleton of valine and the other two branched-chain amino acids. Unlike the acyl-CoA derivates in the irreversible part of valine catabolism, 3-hydroxyisobutyrate could be expected to be released from cells by transport across the mitochondrial and plasma membranes. This could indeed be demonstrated for cultured astroglial cells. Therefore, to assess the ability of neural cells to make use of this valine-derived carbon skeleton as a metabolic substrate for the generation of energy, we investigated the expression in cultured neural cells of the enzyme processing this hydroxy acid, 3-hydroxyisobutyrate dehydrogenase (HIBDH). To achieve this, HIBDH was purified from bovine liver to serve as antigen for the production of an antiserum. Affinity-purified antibodies against HIBDH specifically recognized the enzyme in liver and brain homogenates. Immunocytochemistry demonstrated the ubiquitous expression of HIBDH among cultured glial (astroglial, oligodendroglial, microglial, and ependymal cells) and neuronal cells. Using an RT-PCR technique, these findings were corroborated by the detection of HIBDH mRNA in these cells. Furthermore, immunofluorescence double-labeling of astroglial cells with antisera against HIBDH and the mitochondrial marker pyruvate dehydrogenase localized HIBDH to mitochondria. The expression of HIBDH in neural cells demonstrates their potential to utilize valine imported into the brain for the generation of energy. [source] P2Y receptor-activating nucleotides modulate cellular reactive oxygen species production in dissociated hippocampal astrocytes and neurons in culture independent of parallel cytosolic Ca2+ rise and change in mitochondrial potentialJOURNAL OF NEUROSCIENCE RESEARCH, Issue 15 2007Stefan Kahlert Abstract With mixed cultures of hippocampal astrocytes and neurons, we investigated the influence of nucleotides on cytosolic Ca2+ level, generation of reactive oxygen species (ROS), and mitochondrial potential. We employed ATP and four purine/pyrimidine derivates, which are P2Y receptor subtype-preferring agonists. Stimulation with ATP, a P2Y1/2/4 receptor agonist in rat, caused a large cytosolic Ca2+ increase in astrocytes and a considerably smaller Ca2+ response in neighboring neurons. The P2Y1 receptor antagonist MRS2179 completely blocked the ATP-induced Ca2+ response in astrocytes and neurons. Application of ATP significantly reduced the mitochondrial potential in neurons, which was not inhibited by MRS2179. Interestingly, MRS2179 mediated a mitochondrial depolarization without affecting the cytosolic Ca2+ level. Stimulation with UDP, a P2Y6 receptor agonist; UTP, a P2Y2/4 receptor agonist; 2MeSATP, a P2Y1 receptor agonist; or 2MeSADP, a P2Y1/12/13 receptor agonist, evoked significant Ca2+ responses in astrocytes but small Ca2+ responses in neurons. In astrocytes, there was an inverse relationship between the amplitude of the cytosolic Ca2+ peak and the rate of ROS generation in response to nucleotide application. Activation with UDP resulted in the highest ROS generation that we detected, whereas 2MeSADP and 2MeSATP reduced the ROS generation below the basal level. 2MeSADP and UDP caused mitochondrial depolarization of comparable size. Thus, neither in astrocytes nor in neurons did the degree of mitochondrial depolarization correlate with ROS generation. Nucleotides acting via P2Y receptors can modulate ROS generation of hippocampal neurons without acutely changing the cytosolic Ca2+ level. Thus, ROS might function as a signaling molecule upon nucleotide-induced P2Y receptor activation in brain. © 2007 Wiley-Liss, Inc. [source] Characterization of anion-exchange membranes containing pyridinium groupsAICHE JOURNAL, Issue 12 2003Moon-Sung Kang A poly(vinyl chloride) (PVC)/glycidyl methacrylate (GMA)-divinyl benzene (DVB)-based membrane was prepared via monomer sorption, and then pyridium or its derivates (that is, 4-ethyl pyridium, 4-tetrabutyl pyridium) were introduced into the PVC/poly(GMA-DVB) base membrane. The effects of pyridinium anion-exchangeable sites on the water splitting and the electrochemical properties of the membrane were investigated. The electrochemical properties and the water splitting on the anion-exchange membranes were compared with selected commercial membranes containing quaternary ammonium groups. The pyridium membranes showed good electrochemical properties, comparable to those of the commercial membranes, with electrical resistances of less than 3.0 × 10,4 ,·m2 in 0.5 mol dm,3 NaCl and high ionic permselectivities (the transport number of Cl, ions being 0.96). Moreover, water splitting indicated by the proton transport numbers of the membranes containing pyridinium or its derivates, were about two or three orders of magnitude lower than those of the commercial membranes (such as AM-1) at the same current density because the resonance effect in the quaternary pyridinium groups contributed to their molecular stability. [source] Induction of hepatocyte growth factor by fucoidan and fucoidan-derived oligosaccharidesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2008Kazuhiro Fukuta Fucoidan, which is extracted from brown seaweed, is a complex sulphated polysaccharide that is mostly composed of l -fucose and sulphated ester groups. The structural and anionic characteristics of fucoidan are similar to those of heparin. Heparin stimulates production of hepatocyte growth factor (HGF), which has key roles in tissue regeneration. We have shown that fucoidan and fucoidan-derived oligosaccharides have similar ability to stimulate production of HGF as heparin and heparin-derived oligosaccharides. This induction of HGF by heparin or fucoidan and their oligosaccharide derivates occurs primarily at the level of translation, probably via the same mechanism. Fucoidan may thus be useful to protect tissues and organs from various injuries and diseases, via mechanisms involving HGF. [source] Exploring pathways to reduce the distribution of active sites in the Ziegler,Natta polymerization of propyleneJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 17 2007David Ribour Abstract Chemical treatments of classical supported Ziegler,Natta precatalysts were conducted by using additional bulky ligands to attempt to narrow and homogenize the active sites distribution in propylene polymerization. Additions of monodentate ligands such as bis(trimethylsilyl)amide, cyclopentadienyl derivates or triphenylsilanol were seen to slow down the polymerization without modifying the distribute properties of polypropylenes. In the case of multidentate ligands (porphines or biquinolines), in addition to the poisoning of active sites, an extraction of titanium from the catalyst surface is observed. A decrease of both melting point and isotacticity (II%) of polymers using these compounds suggest that the most isospecific titanium sites are first extracted from the MgCl2 -surface. The narrowing of the molecular weight distribution confirms that the highly isospecific sites are the most active sites, producing the higher molecular weight polymers. Moreover, this study shows that the distributed properties of polymers are due to the chemical diversity of the active sites with various steric and electronic environments at the catalyst surface and not to mass transfer limitations. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 3941,3948, 2007 [source] New ligands for the Fe(III)-mediated reverse atom transfer radical polymerization of methyl methacrylateJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 9 2006Gang Wang Abstract A series of (di)picolinic acids and their derivates are investigated as novel complexing tridentate or bidentate ligands in the iron-mediated reverse atom transfer radical polymerization of methyl methacrylate in N,N -dimethylformamide at 100 °C with 2,2,-azobisisobutyrontrile as an initiator. The polymerization rates and polydispersity indices (1.32,1.8) of the resulting polymers are dependent on the structures of the ligands employed. Different iron complexes may be involved in iron-mediated reverse atom transfer radical polymerization, depending on the type of acid used. 1H NMR spectroscopy has been used to study the structure of the resulting polymers. Chain-extension reactions have been performed to further confirm the living nature of this catalytic system. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 2912,2921, 2006 [source] Molecularly imprinted polymer for selective extraction of endocrine disrupters nonylphenol and its ethoxylated derivates from environmental solidsJOURNAL OF SEPARATION SCIENCE, JSS, Issue 13 2008Laura Núñez Abstract Nonylphenol isomers (NP), linear nonylphenol (4-n-NP) and NP short chain ethoxylated derivates (NPEO1 and NPEO2) are degradation products of nonylphenol polyethoxylates, a worldwide used group of surfactants. All of them are considered endocrine disrupters due to their ability to mimic natural estrogens. In this paper, the preparation and evaluation of several 4-n-NP molecularly imprinted polymers (MIPs) for the selective extraction and clean-up of 4-n-NP, NP, NPEO1 and NPEO2 from complex environmental solid samples is described. Among the different combinations tested, a methacrylic acid-based imprinted polymer prepared in toluene provided the better performance for molecularly imprinted SPE (MISPE). Under optimum MISPE conditions, the polymer was able to selectively retain not only linear NP but also the endocrine disruptors NPEO1, NPEO2 and NP with recoveries ranging from 60 to 100%, depending upon the analyte. The developed MISPE procedure was successfully used for the determination of 4-n-NP, NP, NPEO1 and NPEO2 in sediments and sludge samples at concentration levels according to data reported in the literature for incurred samples. Finally, various sludge samples collected at five different sewage treatment plants from Madrid and commercial sludge for agriculture purposes were analysed. The measured concentrations of the different compounds varied from 3.7 to 107.5 mg/kg depending upon the analyte and the sample. [source] Simple enzymatic procedure for l -carnosine synthesis: whole-cell biocatalysis and efficient biocatalyst recyclingMICROBIAL BIOTECHNOLOGY, Issue 1 2010Jan Heyland Summary , -Peptides and their derivates are usually stable to proteolysis and have an increased half-life compared with , -peptides. Recently, , -aminopeptidases were described as a new enzyme class that enabled the enzymatic degradation and formation of , -peptides. As an alternative to the existing chemical synthesis routes, the aim of the present work was to develop a whole-cell biocatalyst for the synthesis and production of , -peptides using this enzymatic activity. For the optimization of the reaction system we chose the commercially relevant ,,, -dipeptide l -carnosine (, -alanine- l -histidine) as model product. We were able to show that different recombinant yeast and bacteria strains, which overexpress a , -peptidase, could be used directly as whole-cell biocatalysts for the synthesis of l -carnosine. By optimizing relevant reaction conditions for the best-performing recombinant Escherichia coli strain, such as pH and substrate concentrations, we obtained high l -carnosine yields of up to 71%. Long-time as well as biocatalyst recycling experiments indicated a high stability of the developed biocatalyst for at least five repeated batches. Application of the recombinant E. coli in a fed-batch process enabled the accumulation of l -carnosine to a concentration of 3.7 g l,1. [source] | ||||||||||||||||||||||