The role of microtubule movement in bidirectional organelle transport

We study the role of microtubule movement in bidirectional organelle transport in Drosophila S2 cells and show that EGFP-tagged peroxisomes in cells serve as sensitive probes of motor induced, noisy cytoskeletal motions. Multiple peroxisomes move in unison over large time windows and show correlations with microtubule tip positions, indicating rapid microtubule fluctuations in the longitudinal direction. We report the first high-resolution measurement of longitudinal microtubule fluctuations performed by tracing such pairs of co-moving peroxisomes. The resulting picture shows that motor-dependent longitudinal microtubule oscillations contribute significantly to cargo movement along microtubules. Thus, contrary to the conventional view, organelle transport cannot be described solely in terms of cargo movement along stationary microtubule tracks, but instead includes a strong contribution from the movement of the tracks.Comment: 24 pages, 5 figure

Inhaliertes PGI2 versus inhaliertes NO bei hypoxisch pulmonaler Vasokonstriktion

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Searching the ideal inhaled vasodilator: From nitric oxide to prostacyclin

Today, the technique to directly administer vasodilators via the airway to treat pulmonary hypertension and to improve pulmonary gas exchange is widely accepted among clinicians. The flood of scientific work focussing on this new therapeutic concept had been initiated by a fundamental new observation by Pepke-Zaba {[}1] and Frostell in 1991 {[}2]: Both scientists reported, that inhalation of exogenous nitric oxide (NO) gas selectively dilates pulmonary vessels without a concomittant systemic vasodilation. No more than another decade ago NO was identified as an important endogenous vasodilator {[}3] while having merely been regarded an environmental pollutant before that time. Although inhaled NO proved to be efficacious, alternatives were sought-after due to NO's potential side-effects. In search for the ideal inhaled vasodilator another group of endogenous mediators - the prostanoids - came into the focus of interest. The evidence for safety and efficacy of inhaled prostanoids is - among a lot of other valuable work - based on a series of experimental and clinical investigations that have been performed or designed at the Institute for Surgical Research under the guidance and mentorship of Prof. Dr. med. Dr. h.c. mult. K. Messmer {[}4-19]. In the following, the current and newly emerging clinical applications of inhaled prostanoids and the experimental data which they are based on, will be reviewed. Copyright (C) 2002 S. Karger AG, Basel

Kinderanästhesie zur Protonenbestrahlung: Medizin fernab der Klinik

Zusammenfassung: Die Betreuung von Kleinkindern für die Protonentherapie stellt fachlich und menschlich hohe Anforderungen an das Anästhesieteam. Das Anästhesiepersonal soll in Kinderanästhesie speziell ausgebildet und erfahren sein, insbesondere da die Kinder sich oft in einem reduzierten Allgemeinzustand befinden. Die Infrastruktur soll gemäß den aktuellen anästhesiologischen Standards eingerichtet sein. Die ständige visuelle Überwachung des sedierten Patienten und das lückenlose Monitoring der Vitaldaten müssen gewährleistet sein. Propofol eignet sich ideal für die Sedierung von Kleinkindern in Spontanatmung für die Protonentherapie. Auch bei repetitiver Gabe über mehrere Wochen wird Propofol sehr gut toleriert. Eine enge Zusammenarbeit zwischen Radioonkologe, Onkologe und Anästhesist ist notwendig, um interkurrent auftretende medizinische Probleme optimal zu behandeln. Die besonderen Belange onkologischer Patienten müssen bei der Therapieplanung berücksichtigt werde

Action du sulfite de sodium sur la concentration en composés organohalogénés et sur l'activité mutagène de solutions chlorées de substances humiques

Cette étude a eu pour but de déterminer l'effet d'un traitement par le sulfite de sodium sur la concentration en composés organohalogénés totaux (TOX) et sur l'activité mutagène de solutions chlorées de substances humiques d'origine aquatique (SHA), après avoir cherché à préciser l'influence du pH et du temps sur la concentration en TOX.Les résultats obtenus à partir d'échantillons chlorés de SHA en absence de chlore résiduel ont permis de mettre en évidence une diminution de la concentration en composés organohalogénés totaux, soit par stockage en milieu neutre ou basique, soit par addition de sulfite de sodium. L'intensité de cette réduction de la concentration en TOX augmente avec le pH, le temps de réaction et la dose de sulfite de sodium introduite.Les résultats obtenus à partir d'échantillons contenant du chlore libre indiquent que seule une déchloration totale avec un excès de sulfite de sodium peut conduire, en milieu neutre, à une diminution de l'activité mutagène et de la concentration en TOX des solutions diluées de SHA. La comparaison des pourcentages d'abattement obtenus sur le paramètre TOX et sur l'activité mutagène indique que la diminution de la génotoxicité par déchloration totale est due à l'action du sulfite sur des composés mutagènes non chlorés ou sur des composés chlorés fortement mutagènes et ne représentant qu'une très faible fraction du TOX.If is a well known tact that mimerous organohalogenated compounds are formed during the chlorination (preoxidation or final disinfection) of drinking water. Some of these compounds have been shown to be mutagenic. Recent studies have suggested that a treatment with oxygenated derivatives of SIV (SO2, NaHSO3 and Na2SO3) could reduce the genotoxicity of chlorinated drinking water.The general aim of Ibis study was to determine the effect of dechlorination treatments on the mutagenic activity of chlorinated drinking water. The following experiments were carried out in order to point out the effect of a treatment with sodium sulfite on the concentration of total organohalogenated compounds (TOX) and on the mutagenic activity of chlorinated dilute solutions of Aquatic Humic Substances (AHS).At first, the affects of pH, sodium sulfite dose and contact time on TOX concentration were investigated. Then, the importance of the dechlorination rate (partial or complete) on TOX concentration and also on the mutagenic activity could be studied.ExperimentalAquatic Humic Substances (natural mixture of fulvic and humic acids) were dissolved in phosphate-buffered ultra-pure water at 5 and 15 mg l-1 concentrations (pH 6.1 and 6.9 respectively). Stock solutions of chlorine were prepared in the laboratory and titrated by iodometry. Chlorination and dechlorination treatments were carried out in headspace-free baffles, at 20± 1 °C in the dark. Residual chlorine was determined by spectrophotometric measurements at 510 nm, following the calorimetric method using N,N-diethylphenylene-1,4-diamine (DPD). To avoid the slow oxidation of Slv into Svl by dissolved oxygen, the sodium sulfite solutions were prepared freshly before use. TOX concentrations were measured using a DOHRMAN DX-20 TOX analyser equipped with a MC-1 microcoulometric cell and with an AD-2 adsorption module. Before analysis, the residual chlorine was neutralized with sodium thiosulfate and samples were acidified to pH 1.4.The mutagenic activity was determined using acetone-dichloromethane extracts (AMBERLITE XAD-8 and XAD-2 resins) of the aqueous samples of chlorinated and dechlorinated solutions of AHS, acidified to pH 2.0 before extraction. The mutagenicity tests were carried out on TA 98 and TA 100 tester strains, following the method described by MARON and AMES (1983).Results-Effect of pH, addition of sodium sulfite and storage time on the TOX concentrationThe experiments carried out with dilute solutions of AHS ([AHS] = 5 mg 1-1; DOC = 2.5 mg Cl-1; pH = 6.1) showed a linear relationship between TOX production and chlorine consumption in the range 0-2.0 mg Cl2 l-1 (fig. 2).15 % of the chlorine demand was incorporated as organic chlorine in molecules.Experiments performed on solutions containing no residual free chlorine showed that organohatogenated compounds could be partially destroyed upon storage at neutral or basic pH (table 1). Reductions in TOX concentrations of 10 % at pH 6.1-8.5 in 24 hours and of 20 % at pH 11.5 in 2 hours were observed. This was enhanced by increasing the storage time.The addition of sodium sulfite (100 µmol l-1) in solutions containing no residual free chlorine significantly reduced the TOX concentration (10 % in 2 hours at pH 6.1-8.5; table 1). This reduction was enhanced by increasing sulfite dose and storage time and by increasing pH (30 % in 2 hours at pH 11.5). Furthermore, at a given pH value and for a reaction time of 2 hours, the decrease in TOX concentration was larger in presence of sulfite.- Effect of a dechlorination treatment on the TOX concentrationAs shown in figure 3, a dechlorination treatment (reduction of the residual free chlorine concentration) with sodium sulfite could significantly reduce the TOX concentration of the dilute solutions of AHS at pH 6.1 only if an excess of the dechlorinating agent was added. This effect was enhanced by increasing the excess of sulfite but nevertheless seemed to be limited (less than 15 % of reduction for the highest doses used; table 2).The free chlorine residuals measured after a 2 hours partial dechlorination confirmed the stoichiometric factor of 1 mole/mole for the reaction between chlorine and sodium sulfite.- Effect of a dechlorination treatment on the mutagenic activity and on the TOX concentrationThe dechlorination treatments were carried out on chlorinated dilute solutions of AHS ([AHS] = 15 mg l-1; DOC 7.5 mg C l-1; pH = 6.9). The TOX concentrations were measured on aqueous solutions and mutagenicity tests were performed on the corresponding acetone-dichloromethane extracts following a solvent exchange (dimethylsulfoxide). The results obtained showed again that only a total dechlorination treatment could reduce the TOX concentration of the aqueous chlorinated solutions and was able to destroy a significant part of the mutagenic activity of the extracts (table 3 and fig. 4).Although the effect of sulfite on TOX concentration seemed limited (less than 7 % reduction for the highest sulfite dose tested), the reduction in the genotoxicity was more important when the excess of sulfite was increased. No correlation between the TOX concentration and the mutagenic activity could be established. The mutagenic compounds destroyed by sodium sulfite do not appear to be organohalogenated ones. If they are, they are present at trace levels and thus are extremely patent and account for a very little part of the TOX concentration

Reverse methanogenesis and respiration in methanotrophic archaea

Anaerobic oxidation of methane (AOM) is catalyzed by anaerobic methane-oxidizing archaea (ANME) via a reverse and modified methanogenesis pathway. Methanogens can also reverse the methanogenesis pathway to oxidize methane, but only during net methane production (i.e., "trace methane oxidation"). In turn, ANME can produce methane, but only during net methane oxidation (i.e., enzymatic back flux). Net AOM is exergonic when coupled to an external electron acceptor such as sulfate (ANME-1, ANME-2abc, and ANME-3), nitrate (ANME-2d), or metal (oxides). In this review, the reversibility of the methanogenesis pathway and essential differences between ANME and methanogens are described by combining published information with domain based (meta)genome comparison of archaeal methanotrophs and selected archaea. These differences include abundances and special structure of methyl coenzyme M reductase and of multiheme cytochromes and the presence of menaquinones or methanophenazines. ANME-2a and ANME-2d can use electron acceptors other than sulfate or nitrate for AOM, respectively. Environmental studies suggest that ANME-2d are also involved in sulfate-dependent AOM. ANME-1 seem to use a different mechanism for disposal of electrons and possibly are less versatile in electron acceptors use than ANME-2. Future research will shed light on the molecular basis of reversal of the methanogenic pathway and electron transfer in different ANME types.The authors thank Stefanie Berger (RU,Nijmegen) for critical reading of the manuscript. This research is supported by the Soehngen Institute of Anaerobic Microbiology (SIAM) Gravitation Grant (024.002.002) of the Netherlands Ministry of Education, Culture and Science and the Netherlands Organisation for Scientific Research (NWO). Mike S. M. Jetten was further supported by ERC AG 339880 Eco-MoM and Alfons J. M. Stams was supported by ERC AG 323009 Novel Anaerobes.info:eu-repo/semantics/publishedVersio

Improved ventricular function during inhalation of PGI(2) aerosol partly relies on enhanced myocardial contractility

Inhaled prostacyclin (PGI(2)) aerosol induces selective pulmonary vasodilation. Further, it improves right ventricular ( RV) function, which may largely rely on pulmonary vasodilation, but also on enhanced myocardial contractility. We investigated the effects of the inhaled PGI(2) analogs epoprostenol (EPO) and iloprost (ILO) on RV function and myocardial contractility in 9 anesthetized pigs receiving aerosolized EPO (25 and 50 ng center dot kg(-1) center dot min(-1)) and, consecutively, ILO (60 ng center dot kg(-1) center dot min(-1)) for 20 min each. We measured pulmonary artery pressure ( PAP), RV ejection fraction (RVEF) and RV end-diastolic-volume (RV-EDV), and left ventricular end-systolic pressure-volume-relation (end-systolic elastance, E-es). EPO and ILO reduced PAP, increased RVEF and reduced RVEDV. E-es was enhanced during all doses tested, which reached statistical significance during EPO25ng and ILO, but not during EPO50ng. PGI(2) aerosol enhances myocardial contractility in healthy pigs, contributing to improve RV function. Copyright (C) 2005 S. Karger AG, Basel