Investigation into the potential for establishing a self-sustainable wetland ecosystem over pyritic mine tailings

Research was conducted to investigate the potential for ecologically engineering a sustainable wetland ecosystem over pyritic mine tailings to prevent the generation of acid mine drainage. Ecological engineering is technology with the primary goal being the creation of self-sustainable ecological systems. Work involved the design and construction of a pilot-scale wetland system comprising three wetland cells, each covering 100 m2. Approximately forty tonnes of pyritic mine tailings were deposited on the base of the first cell above a synthetic liner, covered with peat, flooded and planted with emergent wetland macrophytes Typha latifolia, Phragmites australis, and Juncus effusus. The second cell was constructed as a conventional free water surface wetland, planted identically, and used as a reference wetland/experimental control. Wetland monitoring to determine long-term sustainability focused on indicators of ecosystem health including ecological, hydrological, physico-chemical, geochemical, and biotic metrics. An integrated assessment was conducted that involved field ecology in addition to ecological risk assessment. The objective of the field ecology study was to use vegetative parameters as ecological indicators for documenting wetlands success or degradation. The goal of the risk assessment was to determine if heavy-metal contamination of the wetland sediments occurred through metal mobilisation from the underlying tailings, and to evaluate if subsequent water column chemistry and biotic metal concentrations were significantly correlated with adverse wetland ecosystem impacts. Data were used to assess heavy metal bioavailability within the system as a function of metal speciation in the wetland sediments. Results indicate hydrology is the most important variable in the design and establishment of the tailings wetland and suggest a wetland cover is an ecologically viable alternative for pyritic tailings which are feasible to flood. Ecological data indicate that in terms of species richness and diversity, the tailings-wetland was exhibiting the ecological characteristics of natural wetlands within two years. Ata indicate that pH and conductivity in the tailings-wetland were not adversely impacted by the acid-generating potential or sulphate concentration of the tailings substrate and its porewater. Similarly, no enhanced seasonal impacts from sulphate or metals in the water column, nor adverse impacts on the final water quality of the outflows, were detected. Mean total metal concentrations in the sediments of the tailings-wetland indicate no significant adverse mobilisation of metals into the peat substrate from the tailings. Correlation analyses indicate a general increase in sediment metal concentration in this wetland with increasing water depth and pH, and a corresponding decrease in the metal concentrations of the water column. Sediment extractions also showed enrichment of Cd, Fe, Pb and Zn in the oxidisable fraction (including sulphides and organic matter) of the tailings-wetland sediments. These data suggest that adsorption and coprecipitation of metals is occurring from the water column of the tailings wetland with organic material at increasing depths under reducing conditions. The long-term control of metal bioavailability in the tailings wetland will likely be related to the presence and continual build-up of organic carbon binding sites in the developing wetland above the tailings. Metal speciation including free-metal ion concentration and the impact of physico-chemical parameters particularly pH and organic matter, were investigated to assess ecotoxicological risk. Results indicate that potentially bioavailable metals (the sum of the exchangeable and reducible fractions) within the tailings wetland are similar to values cited for natural wetlands. Estimated free-metal ion concentrations calculated from geochemical regression models indicate lower free-metal ion concentrations of Cd in the tailings wetland than natural wetlands and slightly higher free-metal ion concentrations of Pb and Zn. Increased concentrations of metals in roots, rhizomes and stems of emergent macrophytes did not occur in the tailings wetland. Even though a substantial number of Typha latifolia plants were found rooting directly into tailings, elevated metals were not found in these plant tissues. Phragmites also did not exhibit elevated metal concentrations in any plant tissues. Typha and Phragmites populations appear to be exhibiting metal-tolerant behaviour. The chemistry of the water column and sediments in Silvermines wetland were also investigated and were much more indicative of a wetland system impacted by heavy metal contamination than the tailings-wetland. Mean Dc, Fe, Mn, Pb and Zn concentrations in the water column and sediments of Silvermines wetlands were substantially higher than in the pilot wetlands and closely approximate concentrations in these matrices contaminated with metals from mining. In addition, mean sulphate concentration in Silvermines wetland was substantially higher and is closer to sulphate concentrations in waters associated with mining. Potentially bioavailable metals were substantially elevated in Silvermines wetland in comparison to the pilot wetlands and higher than those calculated for natural rive sediments. However, Fe oxy-hydroxide concentrations in Silvermines sediments are also much higher than in the pilot wetlands and this significantly impacts the concentration of free-metal ions in the sediment porewater. The free-metal ion concentrations for Pb and Zn indicate that Silvermines wetland is retaining metals and acting as a treatment wetland for drainage emanating from Silvermines tailings dam.

Influences of alternative fuels and EGR on thermodynamic parameters and emissions of a heavy duty engine

Heavy duty Diesel engine, alternative fuels, EGR, exhaust emissions, HC, NOx, FSN

Approximations and asymptotic expansions for sums of heavy-tailed random variables

Magdeburg, Univ., Fak. für Mathematik, Diss., 2015

Approval voting ion dichotomous preferences

The aim of this paper is to find normative foundations of Approval Voting. In order to show that Approval Voting is the only social choice function that satisfies anonymity, neutrality, strategy-proofness and strict monotonicity we rely on an intermediate result which relates strategy-proofness of a social choice function to the properties of Independence of Irrelevant Alternatives and monotonicity of the corresponding social welfare function. Afterwards we characterize Approval Voting by means of strict symmetry, neutrality and strict monotonicity and relate this result to May's Theorem. Finally, we show that it is possible to substitute the property of strict monotonicity by the one efficiency of in the second characterization.

Fitness to drive and cannabis: Validation of two blood THCCOOH thresholds to distinguish occasional users from heavy smokers.

Many studies based on either an experimental or an epidemiological approach, have shown that the ability to drive is impaired when the driver is under the influence of cannabis. Baseline performances of heavy users remain impaired even after several weeks of abstinence. Symptoms of cannabis abuse and dependence are generally considered incompatible with safe driving. Recently, it has been shown that traffic safety can be increased by reporting the long-term unfit drivers to the driver licensing authorities and referring the cases for further medical assessment. Evaluation of the frequency of cannabis use is a prerequisite for a reliable medical assessment of the fitness to drive. In a previous paper we advocated the use of two thresholds based on 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) concentration in whole blood to help to distinguish occasional cannabis users (≤3μg/L) from heavy regular smokers (≥40μg/L). These criteria were established on the basis of results obtained in a controlled cannabis smoking study with placebo, carried out with two groups of young male volunteers; the first group was characterized by a heavy use (≥10 joints/month) while the second group was made up of occasional users smoking at most 1 joint/week. However, to date, these cutoffs have not been adequately assessed under real conditions. Their validity can now be evaluated and confirmed with 146 traffic offenders' real cases in which the whole blood cannabinoid concentrations and the frequency of cannabis use are known. The two thresholds were not challenged by the presence of ethanol (40% of cases) and of other therapeutic and illegal drugs (24%). Thus, we propose the following procedure that can be very useful in the Swiss context but also in other countries with similar traffic policies: if the whole blood THCCOOH concentration is higher than 40μg/L, traffic offenders must be directed first and foremost toward medical assessment of their fitness to drive. This evaluation is not recommended if the THCCOOH concentration is lower than 3μg/L and if the self-rated frequency of cannabis use is less than 1 time/week. A THCCOOH level between these two thresholds cannot be reliably interpreted. In such a case, further medical assessment and follow-up of the fitness to drive are also suggested, but with lower priority.

How Heavy Is A Job?: A Critical Survey of Job Evaluation as a Payment Device.

With salaries subjected to scrutiny more than ever, it is increasingly important that the process by which they are determined be understood and justifiable. Both public and private organisations now routinely rely on so-called “job evaluation” as a means of constructing an appropriate pay-scale and as such it is ever more necessary that we appreciate how this system works and that we recognise its limits. Only with such an understanding of the way in which salaries are set can we hope to have a meaningful discussion of their economic function. This paper aims to expound the details of job evaluation both in theory and in practice, and critically assess its shortcomings. In Section 1 below we describe the job evaluation system and in Section 2 we briefly outline the history and the usage of the system in both the private and the public sector. In Section 3 we theoretically analyse the often unstated but nonetheless implicit assumptions made by practitioners of the art of job evaluation. Section 4 applies the analysis of Section 3 to review a particular and important case study, namely The Senior Salaries Review of the Welsh Assembly 2004. Section 5 concludes.

No healthy heart for heavy drinkers: a population-based study in Switzerland

Background: Low to moderate alcohol consumption has been associated with lower coronary heart disease (CHD) risk, an effect mainly mediated by an increase in HDL-cholesterol levels. However, data on the CHD risk associated with high alcohol consumption are conflicting. Methods: In a population-based study of 5,769 men and women, aged 35-75 years, without cardiovascular disease in Switzerland, last week alcohol consumption was categorized into 0, 1-6, 7-13, 14-20, 21-27, 28-34, 035 drinks/week and into nondrinkers (0 drink/week), moderate (1-13), high (14-34) and very high drinkers (035). Blood pressure, lipids and high sensitivity C-reactive protein (hs-CRP) were measured, and the 10-year CHD risk was calculated according to the Framingham risk score. Results: 73% (n = 4,214) of the participants consumed alcohol; 16% (n = 909) were considered as high drinkers and 2% (n = 119) as very high drinkers. In multivariate analysis, increasing alcohol consumption was associated with higher HDL-cholesterol (from 1.57 ± 0.01 [adjusted mean ± SE] in nondrinkers to 1.88 ± 0.03 mmol/L in very high drinkers); triglycerides (1.17 ± 1.01 to 1.32 ± 1.05 mmol/L), and systolic and diastolic blood pressure rose significantly (127.4 ± 0.4 to 132.2 ± 1.4 and 78.7 ± 0.3 to 81.7 ± 0.9 mm Hg, respectively, all p for trend <0.001). Predicted 10-year CHD risk increased from 4.31 ± 0.10 to 4.90 ± 0.37 (p = 0.03) with increasing alcohol use, with a J-shaped relationship. Conclusion: As measured by the 10-year CHD risk, the protective effect of alcohol consumption disappears in very high drinkers, namely because the beneficial increase in HDL-cholesterol may be blunt by a rise in blood pressure levels.

On the function of proton-gated ion channels ASICs and TRPV1 : a patch-clamp study

AbstractAcidosis is encountered during tissue inflammation and triggers pain in humans. H+-gated ion channels are expressed at high levels in sensory neurons of the peripheral nervous system. Ion channels from two different families present the required pH sensitivity to detect the acidosis associated with peripheral inflammation: Acid-Sensing Ion Channels (ASICs) and the Transient Receptor Potential Vanilloid-1 (TRPV1) channel.ASICs are members of the Degenerin/Epithelial Na+ Channel family of ion channels. Six ASIC subunits have been identified in mammals (ASICla, -lb, -2a, -2b, -3 and -4). ASICs form In-activated voltage-insensitive homo- or heterotrimeric Na+ channels. TRPV1 is a member of the TRP family of ion channels and forms non-selective cation channels that mediate a sustained current. TRPV1 is activated by H+, heat (T>43°C), lipids, capsaicin, voltage and other stimuli. A stimulus can increase TRPV1 response to a different stimulus. For example H+ can shift the capsaicin concentration dependence of TRPV1 to lower values. ASICs and TRPV1 have been shown to be involved in inflammatory pain. Using the patch-clamp technique, we studied different aspects of the function of ASICs and TRPV1 in the physiological context of pain.In the first part of this thesis, we characterize the effect of a temperature increase from 25 to 35°C on the function of ASICs and TRPV1 in transfected CHO cells and primary cultures of rat DRG sensory neurons. ASICs give rise to transient currents while TRPV1 mediates a sustained current. In addition, ASICs and TRPV1 respond to H+ with distinct pH dependences. We assess the relative contribution of ASICs and TRPV1 to H+-evoked electrical signaling in rat DRG neurons and we conclude that ASICs are the most important pH sensors in the pH range 7.4 to 6.0 at 35°C in sensory neurons.ASICs and TRPV1 are expressed in the epithelium lining the lumen of the bladder (urothelium). The Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) is a painful condition associated with a dysfunction of the urothelial barrier and with inflammation. In the second part of this thesis, we show that human urothelial cells -the cell line TEU2 and primary cultures of human bladder urothelium- express functional ASICs but no functional TRPV1 channels. In addition, we show that the levels of ASIC2 and ASIC3 mRNA are increased in the urothelium of patients suffering from BPS/IC. These data suggest that ASICs are involved in the pathology of BPS/IC.Finally, we demonstrate that APETx2 inhibits the sensory neuron specific voltage-dependent Na+ channel Nav1.8. APETx2 was previously shown to inhibit homo- or heterotrimeric ASIC3- containing channels with IC5o from 0.08 to 1 μΜ. We show that APETx2 also inhibits Nav1.8 with an ICsoof «2.6 μΜ. APETx2 reduces the maximal conductance and induces a depolarizing shift in the voltage dependence of activation of Nav1.8. In current-clamp experiments, APETx2 reduces the number of action potentials (APs) evoked by a current ramp. Nav1.8 mediates most of the current during the AP upstroke and has been shown to be an important mediator of inflammatory pain. The fact that APETx2 inhibits two ion channels involved in inflammatory pain suggests that APETx2 or derivatives may represent novel analgesic compounds.RésuméL'acidose tissulaire est observée durant l'inflammation et entraine la douleur chez l'humain. Des canaux ioniques activés par les protons (H+) sont fortement exprimés dans les neurones sensoriels du système nerveux périphérique. De ceux-ci, les Acid-Sensing Ion Channels [ASICs) et Transient Receptor Potential Vanilloid-1 (TRPV1) présentent une sensibilité adéquate à l'acidité pour servir de détecteurs d'acidose.Les ASICs sont membres de la famille Degenerin/Epithelial Na* Channel. Six sous-unités ASIC ont été identifiées chez les mammifères (ASICla, -lb, -2a, -2b, -3 et -4). Les ASICs forment des canaux sélectifs au Na\ insensibles au voltage et activés par les H+. Les canaux fonctionnels sont des homo- ou hétérotrimères de sous-unités ASIC. TRPV1 est un membre de la famille TRP de canaux ioniques. Les canaux TRPV1 sont activés par les H+, la chaleur (T>43°Ç), les lipides, la capsaicine, le voltage et d'autres stimulus. L'activation de TRPV1 entraine un courant soutenu non-sélectif. Un stimulus peut augmenter la réponse de TRPV1 à un autre stimulus. Les H+ peuvent, par exemple, induire un décalage vers des valeurs plus faibles de la courbe de dépendance à la concentration de TRPV1 pour la capsaicine. Il a été démontré que les ASICs et TRPV1 sont impliqués dans la douleur inflammatoire. En utilisant la technique du patch-clamp, nous avons étudié différents aspects de la fonction des ASICs et de TRPV1 dans des contextes associés à la douleur.Dans la première partie de cette thèse, nous caractérisons l'effet d'une augmentation de température de 25 à 35°C sur la fonction des canaux ASICs et TRPV1, dans des cellules CHO transfectées et dans des cultures primaires de neurones sensoriels (DRG) de rat. L'activation des ASICs entraine l'apparition d'un courant transitoire tandis que l'activation de TRPV1 entraine un courant soutenu. De plus, les ASICs et TRPV1 possèdent des dépendances au pH différentes. Nous évaluons la contribution relative des ASICs et de TRPV1 au signalement électrique induit par les H+ et nous concluons que les ASICs sont les senseurs d'acidité les plus importants dans les neurones sensoriels, dans le domaine de pH de 7.4 à 6.0, à température corporelle.Les ASICs et TRPV1 sont exprimés dans l'épithélium recouvrant l'intérieur de la vessie (l'urothélium). Le Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) est une condition médicale douloureuse associée à une dysfonction de la barrière urothéliale et à une inflammation. Dans la seconde partie de cette thèse, nous démontrons que des cellules urothéliales (de la lignée cellulaire TEU2) et des cellules provenant de cultures primaires d'épithéliums de vessies humaines expriment des canaux ASIC fonctionnels mais pas de TRPV1 fonctionnels. De plus, nous montrons que le niveau d'expression de ASIC2 et -3 est augmenté dans l'urothélium de la vessie de patients souffrant de BPS/IC. Ces données suggèrent que les ASICs sont impliqués dans la pathologie BPS/IC.Pour finir, nous démontrons que la toxine APETx2 inhibe le canal spécifique aux neurones sensoriels Nav1.8, un membre de la famille des canaux sodiques dépendants du potentiel. Il a été démontré précédemment que la toxine APETx2 inhibe les canaux contenant une ou plusieurs sous-unités ASIC3 avec un ICso entre 0.08 et 1 μΜ. Nous montrons que la toxine APETx2 inhibe Nav1.8 avec un IC50 de «2.6 μΜ. La toxine APETx2 réduit la conductance maximale et induit un décalage de la dépendance au potentiel de Nav1.8 vers des valeurs plus positives. Dans des expériences de courant imposé sur des neurones sensoriels, la toxine APETx2 réduit le nombre de potentiels d'action induits par une rampe de courant. Nav1.8 est responsable de la majeure partie du courant durant la phase ascendante du potentiel d'action et a été démontré comme étant un médiateur important de la douleur inflammatoire. L'inhibition de deux types de canaux, impliqués dans la douleurs inflammatoire, par la toxine APETx2, suggère que cette dernière ou ses dérivés représentent des composés analgésiques prometteurs.

Aldosterone paradox: differential regulation of ion transport in distal nephron.

The mechanisms through which aldosterone promotes apparently opposite effects like salt reabsorption and K(+) secretion remain poorly understood. The identification, localization, and physiological analysis of ion transport systems in distal nephron have revealed an intricate network of interactions between several players, revealing the complex mechanism behind the aldosterone paradox. We review the mechanisms involved in differential regulation of ion transport that allow the fine tuning of salt and K(+) balance.

Messenger RNA expression of transporter and ion channel genes in undifferentiated and differentiated Caco-2 cells compared to human intestines.

PURPOSE: The purpose of this work was to study the influence of cell differentiation on the mRNA expression of transporters and channels in Caco-2 cells and to assess Caco-2 cells as a model for carrier-mediated drug transport in the intestines. METHOD: Gene mRNA expression was measured using a custom-designed microarray chip with 750 deoxyoligonucleotide probes (70mers). Each oligomer was printed four times on poly-lysine-coated glass slides. Expression profiles were expressed as ratio values between fluorescence intensities of Cy3 and Cy5 dye-labeled cDNA derived from poly(A) + RNA samples of Caco-2 cells and total RNA of human intestines. RESULTS: Significant differences in the mRNA expression profile of transporters and channels were observed upon differentiation of Caco-2 cells from 5 days to 2 weeks in culture, including changes for MAT8, S-protein, and Nramp2. Comparing Caco-2 cells of different passage number revealed few changes in mRNAs except for GLUT3, which was down-regulated 2.4-fold within 13 passage numbers. Caco-2 cells had a similar expression profile when either cultured in flasks or on filters but differed more strongly from human small and large intestine, regardless of the differentiation state of Caco-2 cells. Expression of several genes highly transcribed in small or large intestines differed fourfold or more in Caco-2 cells. CONCLUSIONS: Although Caco-2 cells have proven a suitable model for studying carrier-mediated transport in human intestines, the expression of specific transporter and ion channel genes may differ substantially.

Glutamatergic regulation of mitochondrial ion dynamics in astrocytes

Résumé grand public :Le cerveau se compose de cellules nerveuses appelées neurones et de cellules gliales dont font partie les astrocytes. Les neurones communiquent entre eux par signaux électriques et en libérant des molécules de signalisation comme le glutamate. Les astrocytes ont eux pour charge de capter le glucose depuis le sang circulant dans les vaisseaux sanguins, de le transformer et de le transmettre aux neurones pour qu'ils puissent l'utiliser comme source d'énergie. L'astrocyte peut ensuite utiliser ce glucose de deux façons différentes pour produire de l'énergie : la première s'opère dans des structures appelées mitochondries qui sont capables de produire plus de trente molécules riches en énergie (ATP) à partir d'une seule molécule de glucose ; la seconde possibilité appelée glycolyse peut produire deux molécules d'ATP et un dérivé du glucose appelé lactate. Une théorie couramment débattue propose que lorsque les astrocytes capturent le glutamate libéré par les neurones, ils libèrent en réponse du lactate qui servirait de base énergétique aux neurones. Cependant, ce mécanisme n'envisage pas une augmentation de l'activité des mitochondries des astrocytes, ce qui serait pourtant bien plus efficace pour produire de l'énergie.En utilisant la microscopie par fluorescence, nous avons pu mesurer les changements de concentrations ioniques dans les mitochondries d'astrocytes soumis à une stimulation glutamatergique. Nous avons démontré que les mitochondries des astrocytes manifestent des augmentations spontanées et transitoires de leur concentrations ioniques, dont la fréquence était diminuée au cours d'une stimulation avec du glutamate. Nous avons ensuite montré que la capture de glutamate augmentait la concentration en sodium et acidifiait les mitochondries des astrocytes. En approfondissant ces mécanismes, plusieurs éléments ont suggéré que l'acidification induite diminuerait le potentiel de synthèse d'énergie d'origine mitochondriale et la consommation d'oxygène dans les astrocytes. En résumé, l'ensemble de ces travaux suggère que la signalisation neuronale impliquant le glutamate dicte aux astrocytes de sacrifier temporairement l'efficacité de leur métabolisme énergétique, en diminuant l'activité de leurs mitochondries, afin d'augmenter la disponibilité des ressources énergétiques utiles aux neurones.Résumé :La remarquable efficacité du cerveau à compiler et propager des informations coûte au corps humain 20% de son budget énergétique total. Par conséquent, les mécanismes cellulaires responsables du métabolisme énergétique cérébral se sont adéquatement développés pour répondre aux besoins énergétiques du cerveau. Les dernières découvertes en neuroénergétique tendent à démontrer que le site principal de consommation d'énergie dans le cerveau est situé dans les processus astrocytaires qui entourent les synapses excitatrices. Un nombre croissant de preuves scientifiques a maintenant montré que le transport astrocytaire de glutamate est responsable d'un coût métabolique important qui est majoritairement pris en charge par une augmentation de l'activité glycolytique. Cependant, les astrocytes possèdent également un important métabolisme énergétique de type mitochondrial. Par conséquent, la localisation spatiale des mitochondries à proximité des transporteurs de glutamate suggère l'existence d'un mécanisme régulant le métabolisme énergétique astrocytaire, en particulier le métabolisme mitochondrial.Afin de fournir une explication à ce paradoxe énergétique, nous avons utilisé des techniques d'imagerie par fluorescence pour mesurer les modifications de concentrations ioniques spontanées et évoquées par une stimulation glutamatergique dans des astrocytes corticaux de souris. Nous avons montré que les mitochondries d'astrocytes au repos manifestaient des changements individuels, spontanés et sélectifs de leur potentiel électrique, de leur pH et de leur concentration en sodium. Nous avons trouvé que le glutamate diminuait la fréquence des augmentations spontanées de sodium en diminuant le niveau cellulaire d'ATP. Nous avons ensuite étudié la possibilité d'une régulation du métabolisme mitochondrial astrocytaire par le glutamate. Nous avons montré que le glutamate initie dans la population mitochondriale une augmentation rapide de la concentration en sodium due à l'augmentation cytosolique de sodium. Nous avons également montré que le relâchement neuronal de glutamate induit une acidification mitochondriale dans les astrocytes. Nos résultats ont indiqué que l'acidification induite par le glutamate induit une diminution de la production de radicaux libres et de la consommation d'oxygène par les astrocytes. Ces études ont montré que les mitochondries des astrocytes sont régulées individuellement et adaptent leur activité selon l'environnement intracellulaire. L'adaptation dynamique du métabolisme énergétique mitochondrial opéré par le glutamate permet d'augmenter la quantité d'oxygène disponible et amène au relâchement de lactate, tous deux bénéfiques pour les neurones.Abstract :The remarkable efficiency of the brain to compute and communicate information costs the body 20% of its total energy budget. Therefore, the cellular mechanisms responsible for brain energy metabolism developed adequately to face the energy needs. Recent advances in neuroenergetics tend to indicate that the main site of energy consumption in the brain is the astroglial process ensheating activated excitatory synapses. A large body of evidence has now shown that glutamate uptake by astrocytes surrounding synapses is responsible for a significant metabolic cost, whose metabolic response is apparently mainly glycolytic. However, astrocytes have also a significant mitochondrial oxidative metabolism. Therefore, the location of mitochondria close to glutamate transporters raises the question of the existence of mechanisms for tuning their energy metabolism, in particular their mitochondrial metabolism.To tackle these issues, we used real time imaging techniques to study mitochondrial ionic alterations occurring at resting state and during glutamatergic stimulation of mouse cortical astrocytes. We showed that mitochondria of intact resting astrocytes exhibited individual spontaneous and selective alterations of their electrical potential, pH and Na+ concentration. We found that glutamate decreased the frequency of mitochondrial Na+ transient activity by decreasing the cellular level of ATP. We then investigated a possible link between glutamatergic transmission and mitochondrial metabolism in astrocytes. We showed that glutamate triggered a rapid Na+ concentration increase in the mitochondrial population as a result of plasma-membrane Na+-dependent uptake. We then demonstrated that neuronally released glutamate also induced a mitochondrial acidification in astrocytes. Glutamate induced a pH-mediated and cytoprotective decrease of mitochondrial metabolism that diminished oxygen consumption. Taken together, these studies showed that astrocytes contain mitochondria that are individually regulated and sense the intracellular environment to modulate their own activity. The dynamic regulation of astrocyte mitochondrial energy output operated by glutamate allows increasing oxygen availability and lactate production both being beneficial for neurons.

High frequency of skin reactions in patients with leishmaniasis treated with meglumine antimoniate contaminated with heavy metals: a comparative approach using historical controls

We analyzed data from historical controls treated with meglumine antimoniate to compare the frequency of adverse events observed in patients with cutaneous leishmaniasis treated with the same dose of meglumine antimoniate contaminated with heavy metals in an endemic area of the State of Bahia, Brazil. Group A patients were treated in 2000 with the drug produced by Eurofarma Laboratórios Ltda., São Paulo, Brazil (lot A) and group B patients were treated in 1996 with the reference drug produced by Rhodia Farma Ltda., São Paulo, Brazil (lot B). We observed an unusual higher frequency of skin reactions in group A patients. However, all type of adverse events observed in group A were also observed in group B. The physico-chemical analysis of these lots revealed that lot A had lower pH and higher concentration of total and trivalent antimony, lead, cadmium, and arsenic. Our findings suggest that the skin reactions could be attributed to heavy metal contamination of lot A.

Effects of tetrodotoxin and ion replacements on the short-circuit current induced by Escherichiacoli heat stable enterotoxin across small intestine of the gerbil (Gerbillus cheesmani)

The effects of mucosally added Escherichia coli heat stable enterotoxin (STa 30 ng ml-1) on the basal short-circuit current (Isc in µA cm-2) across stripped and unstripped sheets of jejuna and ilea taken from fed, starved (4 days, water ad lib) and undernourished (50% control food intake for 21 days) gerbil (Gerbillus cheesmani) were investigated. The effect of neurotoxin tetrodotoxin (TTX 10 µM) and the effects of replacing chloride by gluconate or the effects of removing bicarbonate from bathing buffers on the maximum increase in Isc induced by STa were also investigated. The maximum increase in Isc which resulted from the addition of STa were significantly higher in jejuna and ilea taken from starved and undernourished gerbils when compared with the fed control both using stripped and unstripped sheets. In the two regions of the small intestine taken from fed and starved animals TTX reduced the maximum increase in Isc induced by STa across unstripped sheets only. Moreover in jejuna and ilea taken from undernourished gerbils TTX reduced significantly the maximum increase in Isc induced by STa across stripped and unstripped sheets. Replacing chloride by gluconate decreased the maximum increase in Isc induced by STa across jejuna and ilea taken from undernourished gerbils only. Removing bicarbonates from bathing buffer decreased the maximum increase in Isc across the jejuna and ilea taken from starved and undernourished gerbils.