Ethnopharmacological survey of different uses of seven medicinal plants from Mali, (West Africa) in the regions Doila, Kolokani and Siby

An ethnopharmacological survey was carried out to collect information on the use of seven medicinal plants in rural areas in the nearby regions of Bamako, Mali. The plants were Opilia celtidifolia, Anthocleista djalonensis, Erythrina senegalensis, Heliotropium indicum, Trichilia emetica, Piliostigma thonningii and Cochlospermum tinctorium About 50 medical indications were reported for the use of these plants in traditional medicine. The most frequent ailments reported were malaria, abdominal pain and dermatitis. The highest number of usages was reported for the treatment of malaria (22%). The majority of the remedies were prepared from freshly collected plant material from the wild and from a single species only. They were mainly taken orally, but some applications were prepared with a mixture of plants or ingredients such as honey, sugar, salt, ginger and pepper. Decoction of the leaves was the main form of preparation (65%) and leaf powder was mostly used for the preparation of infusions (13%). The part of the plants most frequently used was the leaves. There was a high degree of informant consensus for the species and their medicinal indications between the healers interviewed. The results of this study showed that people are still dependent on medicinal plants in these rural areas of Mali

Polysaccharides from the South African medicinal plant Artemisia afra: Structure and activity studies

Artemisia afra (Jacq. Ex. Willd), is an indigenous plant in South Africa and other parts of the African continent, where it is used as traditional medicine mostly for respiratory conditions. The objective of this study was to investigate the structural features of the polysaccharides from the leaves of this plant, as well as the biological activities of the polysaccharide fractions against the complement assay. Leaves of Artemisia afra were extracted sequentially with organic solvents (dichloromethane and methanol), 50% aqueous ethanol, and water at 50 and 100 °C respectively. The polysaccharide extracts were fractionated by ion exchange chromatography and the resulting fractions were tested for biological activity against the complement fixation assay. Active fractions were further fractionated using gel filtration. Monosaccharide compositions and linkage analyses were determined for the relevant fractions. Polysaccharides were shown to be of the pectin type, and largely contain arabinogalactan, rhamnogalacturonan and homogalacturonan structural features. The presence of arabinogalactan type II features as suggested by methylation analysis was further confirmed by the ready precipitation of the relevant polysaccharides with the Yariv reagent. An unusual feature of some of these polysaccharides was the presence of relatively high levels of xylose as one of its monosaccharide constituents. Purified polysaccharide fractions were shown to possess higher biological activity than the selected standard in the complement assay. Digestion of these polysaccharides with an endo-polygalacturonase enzyme resulted in polymers with lower molecular weights as expected, but still with biological activity which exceeded that of the standard. Thus on the basis of these studies it may be suggested that immunomodulating properties probably contribute significantly to the health-promoting effects of this medicinal plant

Latest development in the medicinal treatment of dogs presumptively diagnosed with granulomatous meningoencephalitis

Granulomatous meningoencephalitis (GME) is a non-suppurative inflammatory disease that affects the central nervous system (CNS) of dogs. It is characterized histologically by the formation of large perivascular cuffs of mononuclear cells in the parenchyma and meninges of the brain and/or spinal cord. GME can affect any breed or age, however, young to middle-aged dogs, females and small purebreds such as toy and terrier breeds and Poodles tend to be overrepresented. Clinical and neurological symptoms of GME often have an acute and rapidly progressive onset, which will be fatal if left untreated. Based on morphological and clinical neurologic abnormalities, three forms of GME have been described; disseminated/multifocal, focal and ocular/ophthalmic form. Clinical signs vary greatly because they reflect the arrangement and location of the CNS lesion. The aetiopathogenesis of the disease remains unknown, although immunemediated mechanism is suspected. GME can only be definitely diagnosed by brain biopsy or post mortem histopathological evaluation of brain tissue. It is therefore commonly referred to as meningoencephalitis of unknown aetiology (MUE), which comprises all canine CNS inflammatory diseases for which there are no histopathological confirmation and no infectious cause have been identified. High dose, long-term immunosuppression has been proven to be the key to a successful therapy. Corticosteroids (primarily prednisone) have been the mainstay of treatment, but due to significant adverse effects, high possibility of relapse and short survival times, new and more effective treatment protocols have been suggested. More recently, supplemental immunosuppressive drugs have been employed in an attempt to prolong survival times and increase the quality of life. A review of azathioprine, cyclosporine, cytosine arabinoside, lomustine, leflunomide and procarbazine as adjunctive immunomodulatory agents is provided in this thesis. Also included in this thesis are case reports of 9 dogs presumptively diagnosed with GME. Their treatment regimes are different, but a common denominator is that more than one supplemental immunomodulatory drug was used. All dogs are still alive and 8/9 dogs are without any medications and living a symptom free life. Even though the results of these case reports are inadequate to be considered as scientific data, it opens up possibilities of a more favourable long-term outcome

Metabolic Engineering des Valinsyntheseweges in Corynebacterium glutamicum : Analyse und Modellierung

The functionality of the intracellular reaction network in a Corynebacterium glutamicum valine production strain was investigated with special focus on the valine / leucine biosynthesis pathway. The aim was to gain a quantitative understanding of the behaviour of the reaction network. The methods required to do so were developed, and enzyme targets for the further optimisation of the investigated strain were identified. The intracellular metabolite concentrations were observed during a transient state by performing a glucose stimulus experiment. A mathematical model describing the in vivo reaction dynamics of the valine / leucine pathway was developed and a metabolic control analysis was performed based on the data from the stimulus experiment and the dynamic model. The thermodynamic driving forces in the valine / leucine pathway were analysed. The optimal procedure for the stimulus experiment with respect to obtaining a useful data set for the modelling and analysis was identified. Samples were taken at sub-second intervals and the concentrations of 26 metabolites from the valine / leucine pathway and the central metabolism were measured. A very fast response to the stimulus was observed in most intracellular metabolites with for example a 3-fold increase in the pyruvate concentration within one second. The connectivities of the metabolites around the ketoisovalerate branchpoint were investigated using a time series analysis. The kinetic model consisted of a system of differential equations defined by setting up material balances on the metabolites. The model can simulate the concentrations and fluxes in the valine and leucine pathway accurately during the transient state. The implementation of a model selection criterion based on the second law of thermodynamics was demonstrated to be essential for the identification of realistic and unique models. Other, alternative methods of setting up a kinetic model were also investigated. The alternative models included a mechanistic model of the valine / leucine pathway and a large linlog model of the whole metabolism of the strain. The mechanistic model was not capable of simulating the measured concentrations due to the limitations of its elasticities. The instability of the whole cell model made it inappropriate for a metabolic control analysis and further interpretation. However, the simulation of the whole metabolism of the strain provides a proof of concept for the whole cell modelling approach and shows in which direction metabolic modelling will develop in the future. Both data driven and model based methods were used to analyse the control hierarchy in the valine / leucine pathway. In addition, predictions of the effect of changes in the enzyme levels were made based on the model. In an optimisation study the enzyme levels were optimised with respect to the valine flux. Based on the acquired understanding of the behaviour of the reaction network the following targets for further strain development were identified: 1. Overexpression of the valine translocase 2. Implementation of an inhibition resistant AHAS enzyme and possibly further overexpression. 3. Removal of the overexpression of the gene coding for DHAD on the plasmid to save the cell the burden of overproducing this enzyme which has negligible influence on the valine flux. 4. Modification of the central carbon metabolism to increase pyruvate availability. The identification of the targets for strain development demonstrates the usefulness of a kinetic model in metabolic engineering and in the general understanding of metabolic control. The concentration data and the kinetic model were used to analyse the thermodynamic driving force, i.e. the reaction affinity, in the valine / leucine pathway. The concept of a reaction resistance was introduced to relate the driving force to reaction rate in analogy with Ohm’s law. This provided a new angle of analysing metabolic networks. The linear relation between reaction rate and affinity which apply for uni-uni reactions can not be assumed to be valid for bi-bi reactions operating far from equilibrium. The theory of metabolic control analysis was extended to include also the reaction potential and the reaction resistance. Reactions far from equilibrium are controlled almost entirely through the changes in the resistance while reactions closer to equilibrium are also affected by changes in the affinity.Untersucht wurde die Funktionalität des intrazellulären Reaktionsnetzwerks eines Corynebacterium glutamicum Valin-Produktionsstamms, wobei insbesondere der Valin-Leucin-Biosyntheseweg in den Blick genommen wurde. Ziel war es, ein quantitatives Verständnis über das Verhalten des Reaktionsnetzwerks zu erlangen. Die dazu benötigten Methoden wurden entwickelt und die Enzym-Targets zur weiteren Optimierung des untersuchten Stamms identifiziert. Die intrazellulären Metabolitkonzentrationen wurden nach Anregung durch einen Substratstimulus im Übergangszustand eines Glukosestimulusexperiment festgestellt. Ein mathematisches Modell, das die Reaktionsdynamik des Valin-Leucin-Synthesewegs in vivo beschreibt, wurde entwickelt und eine metabolische Kontrollanalyse basierend auf den Daten des Stimulusexperiments und des dynamischen Modells durchgeführt. Die thermodynamischen Antriebskräfte im Valin-Leucin-Syntheseweg wurden analysiert. Das optimale Verfahren für das Stimulusexperiment zur Erfassung eines nützlichen Datensatzes für die Modellierung und Analyse wurde festgelegt. Es wurden Proben in Subsekundenintervallen genommen und Konzentrationen von 26 Metaboliten aus dem Valin-Leucin-Syntheseweg und des Zentralstoffwechsels gemessen. Eine sehr schnelle Reaktion auf den Stimulus wurde bei den meisten intrazellulären Metaboliten beobachtet, wie zum Beispiel ein dreifacher Anstieg der Pyruvat-Konzentration innerhalb einer Sekunde. Die Konnektivitäten der Metaboliten um den Verzweigungspunkt Ketoisovalerat wurden mithilfe einer Zeitreihenanalyse untersucht. Das kinetische Model bestand aus einem Differentialgleichungsmodell, das durch die Aufstellung von Materialbilanzen der Metaboliten definiert wurde. Das Modell kann die Konzentrationen und Flüsse im Valin-Leucin-Syntheseweg während des Übergangszustandes genau simulieren. Die Verwendung eines Modellselektionskriteriums auf der Basis des zweiten Hauptsatzes der Thermodynamik zur Identifizierung von realistischen und eindeutigen Modellen erwies sich als entscheidend. Andere alternative Methoden zur Aufstellung eines kinetischen Modells sind ebenfalls untersucht worden. Diese alternativen Methoden bestanden aus einem mechanistischen Modell des Valin-Leucin-Synthesewegs und einem großen Linlog-Modell des gesamten Stoffwechsels des Stammes. Das mechanistische Modell war aufgrund seiner begrenzten Elastizitäten nicht in der Lage die gemessenen Konzentrationen zu simulieren. Die Instabilität des gesamten Zellmodells machte dieses für eine metabolische Kontrollanalyse und weitere Interpretationen unbrauchbar. Die Simulation des gesamten Stoffwechsels des Stammes liefert jedoch einen Proof-of Concept für den gesamten Zellmodellierungsansatz und zeigt, in welche Richtung sich die metabolische Modellierung in Zukunft entwickeln wird. Sowohl die datengestützten als auch die modellbasierten Methoden wurden verwendet, um die Kontrollhierarchie im Valin-Leucin-Syntheseweg zu analysieren. Außerdem wurden auf der Basis des Modells Vorhersagen über die Auswirkungen bei Änderungen der Enzymlevels getroffen. In einer Optimierungsstudie wurden die Enzymlevels im Hinblick auf den Valinfluss optimiert. Auf der Basis des erlangten Verständnisses im Hinblick auf das Verhalten des Reaktionsnetzwerkes wurden die folgenden Ziele zur weiteren Stammentwicklung formuliert: 1. Überexpression von Valin Translokase 2. Verwendung eines inhibierungsresistenten AHAS-Enzyms und möglicherweise einer weiteren Überexpression. 3. Entfernung der Überexpression der Genkodierung für DHAD auf dem Plasmid, um die Zelle von der Überproduktion des Enzyms zu entlasten, da es einen geringfügigen Einfluß auf den Valinfluss hat. 4. Modifizierung des Zentralstoffwechsels zur Erhöhung der Verfügbarkeit von Pyruvat. Die Bestimmung der Ziele für die Stammentwicklung zeigt die Nützlichkeit eines kinetischen Modells im Bereich Metabolic Engineering und für das allgemeine Verständnis der metabolischen Kontrolle. Die Konzentrationswerte und das kinetische Modell wurden eingesetzt, um die thermodynamische Antriebskraft, d.h. die Reaktionsaffinität, im Valin-Leucin-Syntheseweg zu analysieren. Das Konzept des Reaktionswiderstandes wurde verwendet, um die Antriebskraft mit der Reaktionsgeschwindigkeit analog dem Ohmschen Gesetz in Beziehung zu setzen. Dies schaffte einen neuen Blickwinkel hinsichtlich der Analyse von metabolischen Netzwerken. Die lineare Beziehung zwischen der Reaktionsgeschwindigkeit und der Affinität, die für uni-uni-Reaktionen gilt, besitzt für die fern des Gleichgewichts ablaufenden bi-bi-Reaktionen keine Gültigkeit. Die Theorie der metabolischen Kontrollanalyse wurde erweitert, um das Reaktionspotential und den Reaktionswiderstand berücksichtigen zu können. Reaktionen fern des Gleichgewichtes werden fast ausschließlich durch Veränderungen des Widerstandes kontrolliert, während Reaktionen nahe dem Gleichgewicht auch von Veränderungen der Affinität betroffen sind

Fra soldat til krigsfange : behandlingen av svenske krigsfanger i Norge og norske krigsfanger i Sverige i årene 1808-1809

I forsvarstradisjonen blir det lagt stor vekt på strategi og taktikk, krigens forløp, soldatenes stillinger etc, men med en gang soldater fra et bestemt regiment blir tatt til fange, hører vi ikke noe mer om disse soldatene. Krigen fortsetter og de forsvinner ut av historien. Det virker som de krysser en slags grense fra å være en del av militærhistorien til å bli en del av samfunnshistorien. I krigen mellom Norge og Sverige i 1808-1809 ble til sammen ca. 1200 soldater tatt til fange. Napoleon mente at krigsfangene ikke lenger tilhørte det landet de kjempet for, men det landet som hadde avvæpnet dem. Men hvilken behandling fikk de? Oberst Henrik Angell har i ettertid påstått at de norske krigsfangene fikk dårligere behandling i Sverige enn de svenske krigsfangene fikk i Norge, og denne studien tar for seg om dette stemmer eller ikke

Metabolic Engineering of the Valine Pathway in Corynebacterium glutamicum\textit{Corynebacterium glutamicum} - Analysis and Modelling

The functionality of the intracellular reaction network in a $\textit{Corynebacterium glutamicum}$ valine production strain was investigated with special focus on the valine / leucine biosynthesis pathway. The aim was to gain a quantitative understanding of the behaviour of the reaction network. The methods required to do so were developed, and enzyme targets for the further optimisation of the investigated strain were identified. The intracellular metabolite concentrations were observed during a transient state by performing a glucose stimulus experiment. A mathematical model describing the in vivo reaction dynamics of the valine / leucine pathway was developed and a metabolic control analysis was performed based on the data from the stimulus experiment and the dynamic model. The thermodynamic driving forces in the valine / leucine pathway were analysed. The optimal procedure for the stimulus experiment with respect to obtaining a useful data set for the modelling and analysis was identified. Samples were taken at sub-second intervals and the concentrations of 26 metabolites from the valine / leucine pathway and the central metabolism were measured. A very fast response to the stimulus was observed in most intracellular metabolites with for example a 3-fold increase in the pyruvate concentration within one second. The connectivities of the metabolites around the ketoisovalerate branchpoint were investigated using a time series analysis. The difference in metabolite levels and stimulus reaction at two different physiological states was demonstrated. The kinetic model consisted of a system of differential equations defined by setting up material balances on the metabolites. Splines were used to represent the unbalanced metabolites in the reaction system and the reaction rate equations were defined using linlog kinetics. The model can simulate the concentrations and fluxes in the valine and leucine pathway accurately during the transient state. The implementation of a model selection criterion based on the second law of thermodynamics was demonstrated to be essential for the identification of realistic and unique models. Large differences between the enzyme properties determined in vitro and those determined in vivo by the model were observed with the in vivo maximal rates being almost an order of magnitude larger than the in vitro maximal rates. The transamination of ketoisovalerate to valine is carried out mainly by the Transaminase B enzyme with the Transaminase C enzyme playing a minor role. The availability of the cofactors NADP and NADPH has only modest influence on the flux through the valine pathway while the influence of NAD and NADH on the flux through the leucine pathway is negligible. Other, alternative methods of setting up a kinetic model were also investigated. The alternative models included a mechanistic model of the valine / leucine pathway and a large linlog model of the whole metabolism of the strain. The mechanistic model was not capable of simulating the measured concentrations due to the limitations of its elasticities. The instability of the whole cell model made it inappropriate for a metabolic control analysis and further interpretation. However, the simulation of the whole metabolism of the strain provides a proof of concept for the whole cell modelling approach and shows in which direction metabolic modelling will develop in the future. Both data driven and model based methods were used to analyse the control hierarchy in the valine / leucine pathway. In addition, predictions of the effect of changes in the enzyme levels were made based on the model. In an optimisation study the enzyme levels were optimised with respect to the valine flux. Based on the acquired understanding of the behaviour of the reaction network the following targets for further strain development were identified: [...

Elderberry and Elderflower Extracts, Phenolic Compounds, and Metabolites and Their Effect on Complement, RAW 264.7 Macrophages and Dendritic Cells

Modulation of complement activity and inhibition of nitric oxide (NO) production by macrophages and dendritic cells may have therapeutic value in inflammatory diseases. Elderberry and elderflower extracts, constituents, and metabolites were investigated for their effects on the complement system, and on NO production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages and murine dendritic D2SC/I cells. The EtOH crude extracts from elderberry and elderflower and the isolated anthocyanins and procyanidins possessed strong complement fixating activity and strong inhibitory activity on NO production in RAW cells and dendritic cells. Phenolic compounds in the range of 0.1–100 µM showed a dose-dependent inhibition of NO production, with quercetin, rutin, and kaempferol as the most potent ones. Among the metabolites, caffeic acid and 3,4-dihydroxyphenylacetic acid showed the strongest inhibitory effects on NO production in both cell lines, without having cytotoxic effect. Only 4-methylcatechol was cytotoxic at the highest tested concentration (100 µM). Elderberry and elderflower constituents may possess inflammatory modulating activity, which increases their nutritional value

Effect of Phenolic Compounds from Elderflowers on Glucose- and Fatty Acid Uptake in Human Myotubes and HepG2-Cells

Type 2 diabetes (T2D) is manifested by progressive metabolic impairments in tissues such as skeletal muscle and liver, and these tissues become less responsive to insulin, leading to hyperglycemia. In the present study, stimulation of glucose and oleic acid uptake by elderflower extracts, constituents and metabolites were tested in vitro using the HepG2 hepatocellular liver carcinoma cell line and human skeletal muscle cells. Among the crude extracts, the 96% EtOH extract showed the highest increase in glucose and oleic acid uptake in human skeletal muscle cells and HepG2-cells. The flavonoids and phenolic acids contained therein were potent stimulators of glucose and fatty acid uptake in a dose-dependent manner. Most of the phenolic constituents and several of the metabolites showed high antioxidant activity and showed considerably higher α-amylase and α-glucosidase inhibition than acarbose. Elderflower might therefore be valuable as a functional food against diabetes

Effects of lichen heteroglycans on proliferation and IL-10 secretion by rat spleen cells and IL-10 and TNF-alpha secretion by rat peritoneal macrophages in vitro

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldFour polysaccharides Pc-1, Pc-2, Pc-3 and Pc-4 were isolated from water and alkali extracts of the lichen Peltigera canina using ethanol fractionation, gel filtration and preparative HP-GPC. The monosaccharide composition was determined by methanolysis and GC and showed mannose and galactose as the predominating structural units. The mean M(r) was determined by HP-GPC. The heteroglycans were tested for in vitro immunomodulating activities and showed mitogenic activity in rat spleen cell proliferation assay and stimulated IL-10 secretion. In rat peritoneal macrophages, the heteroglycans stimulated TNF-alpha secretion, but not IL-10 secretion. These results indicate that the polysaccharides influence cells of the immune system both from the innate and the adaptive systems