• Refine Query
  • Source
  • Publication year
  • to
  • Language
  • 248
  • 97
  • 23
  • 12
  • 9
  • 5
  • 5
  • 4
  • 4
  • 2
  • 2
  • 2
  • 2
  • 1
  • 1
  • Tagged with
  • 453
  • 172
  • 51
  • 44
  • 39
  • 34
  • 30
  • 30
  • 29
  • 28
  • 28
  • 26
  • 26
  • 24
  • 24
  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
51

Výroba krytu / Manufacturing of cover

Březina, Stanislav January 2010 (has links)
The graduation theses worked up within the frame of the master study programme M21-P, field of study M-STM, sets up a proposal of the technology of the casing manufacture. The casing will be made of steel plate 11 305.21. In terms of a linear study of the questions of deep drawing and the calculation, drawing in the instrument with blankholder was suggested. The upper ejector is instrumental to the extension of the components. The intermediate product will be a roundel created by scission of the sneet panel of 1 mm size. The average of the intermediate product is 124,7 mm, while series 100 000 pieces a year. In terms of the calculations for the operation of drawing, the hydraulic press ZH 30 with specified forming power was selected.
52

Potentising and application of a Combretum woodii leaf extract with high antibacterial and antioxidant activity

Zishiri, Vincent Kudakwashe 27 July 2005 (has links)
Given the drawbacks associated with the use of antibiotics as feed additives and the imminent banning of its use in the European Union, the aim of this project was to develop an extract that could be used as an alternative feed additive in poultry production. The desired extract preferably had to be rich in antibacterial activity to control proliferation of undesired microorganisms, and antioxidant activity to boost the immune system of the poultry. A number of trial extraction procedures were employed on dried leaf material samples to identify the best extraction method. In preliminary extraction studies, direct extraction was performed on leaf samples from the Lowveld National Botanical Gardens (LNBG) and from University of Pretoria Botanical Garden (UP). The principle aim of preliminary studies was to identify the solvents that extracted high antibacterial and antioxidant activity while also extracting large quantities of material. The secondary objective was to test for differences in activities between samples collected from LNBG and UP. Five extractants of varying polarities; acetone, ethanol, ethylacetate, dichloromethane and hexane were used. Antibacterial activity of all extracts was quantified by a serial dilution microplate technique while bioautography was used in qualitative analysis of the antibacterial active compounds. ATCC strains of Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Enterococcus faecalis were used as test organisms. Qualitative antioxidant activity was determined by using a DPPH assay on TLC plates. Results from preliminary extraction studies showed larger quantities of material were present in extracts from the LNBG sample than in the UP sample. Two major antioxidant compounds (Rf values of 0.85 and 0.35 in EMW solvent system) were seen on DPPH sprayed TLC plates, while bioautography showed the presence of a number antibacterial active compounds in the acetone, ethanol and ethylacetate extracts with Rr values ranging between 0.85 and 0.56 on TLC plates developed in the EMW solvent system. MIC values of the extracts tallied with the results from bioautography. The acetone, ethanol and ethyl acetate extracts had the highest antibacterial activity while the hexane extracts had the lowest activity with average MIC value of 0.55 mg/ml for both the LNBG and UP samples. MIC values as low as 0.04 mg/ml were measured in the acetone and ethylacetate extracts of the LNBG sample against S. aureus and E. faecalis. Based on results from preliminary extraction studies, hexane was identified as a possible pretreatment solvent for application in enrichment procedures, acetone and ethanol were chosen as the main extractants and only the LNBG sample was used for future work. Enrichment procedures were employed along two pathways; the first pathway involved the use of hexane "wash" as a pretreatment procedure prior to extraction with acetone or ethanol. The second pathway involved the use of various mixtures of acetone in water and ethanol in water as extractants. The rationale of using these various ratios was an attempt to identify solvent mixtures that would selectively extract the bioactive components or otherwise selectively remove inactive material. A serial dilution microplate method was used to determine Minimum Inhibitory Concentrations (MICs) and the Trolox Equivalent Antioxidant Capacity (TEAC) assay was used to quantify antioxidant activity of all extracts. The optimal extract was the one developed by pretreatment with a single direct extraction with hexane prior to extraction with acetone. It had a TEAC value of 2.3, an increase in TEAC value of 283% compared to that of the crude acetone extract. The average MIC of the crude acetone extract against ATCC stains of S. aureus, Ps. aeruginosa, E. coli and E. faecalis had dropped from 0.15 mg/ml to 0.08 mg/ml in the optimal extract (an improvement in antibacterial activity of 87.5%). Since the optimal extract is intended for commercial application in poultry production, its antibacterial activity was tested against Campylobacter jejuni, Clostridium perfringens, Salmonella enteritidis, E. coli and multi drug resistant E. coli isolated from chickens. Its in vitro toxicity was ascertained using the brine shrimp assay and the MTT cytotoxicity assay on monkey kidney cells. The optimal extract was effective against Campylobacter jejuni and Clostridium perfringens with MIC values ranging from 40 µ/ml to 80 µ/ml. It was also active against multi-resistant strains of E. coli and Salmonella enteritidis (MIC values of 125 µ/ml for both strains). LC50 results from the brine shrimp assay and the MTT cytotoxicity assay on monkey kidney cells gave values of 863 µ/ml and 226 µ/ml respectively indicating low toxicity. These results meant that though in some cases the MICs of the optimal extract were higher than befitting of typical antibiotics, due to its relatively low toxicity, large quantities of the extract may possibly be feed to achieve the desired activity without causing any toxicity in the poultry. The major antioxidant compound was isolated by silica gel column chromatography. The isolated compound was identified by nuclear magnetic resonance and mass spectroscopy as combretastatin BS (2', 3', 4-trihydroxyl, 3, S, 4'-trimethoxybibenzyl), previously isolated from the seeds of C. kraussii and also from C. woodii leaves. Famakin (2002) showed this compound to be the major antibacterial compound in C. woodii leaves. Combretastatin BS (CBS) demonstrated in vitro cytotoxicity in the MTT assay on monkey kidney cells with an LC50 value of 1 0 µ/ml. In vitro cytotoxicity of CBS could be due to its antimitotic activity. The TEAC value of 7.9 found in this study means that combretastatin BS has about 8 times the antioxidant capacity of vitamin E. This is the first report of the antioxidant activity of any of the combretastatins. Tolerance of broiler chickens to the optimal extract was assessed at clinically inferred doses of 2 mg/kg, Smg/kg and 10 mg/kg . After 21 days of infeed-dosing with the optimal extract, none of the chickens died or showed any behavioral signs of toxicity. There were no statistically significant differences in weight gain between broilers fed the optimal extract and the positive and negative control. There was also no positive correlation between weight gain and amount of the optimal extract incorporated in feed. Although the optimal extract did not result in significant growth promotion relative to the positive and negative control, 2 mg/kg dose regimens showed the best Feed Conversion Ratio (FCR), with a 6.2% improvement compared to the negative control. The positive control was the only other feed regimen to provide a positive FCR with an improvement of 1.73% compared to the negative control. Because purchase of feed could represent up to 80% of costs of broiler production, this is an important finding. If these results can be confirmed, the product may therefore have commercial value. Repetition of the experiment with lower doses of the optimal extract on poultry challenged with bacterial infections is required to confirm the commercial applicability of this product. Copyright / Dissertation (MSc (Paraclinical Science))--University of Pretoria, 2004. / Paraclinical Sciences / unrestricted
53

An Automated Study of Antioxidant Potentials of Polar Extract of Turmeric as Influenced by Ultraviolet Radiation

Alawadi, Nagham Salah 07 May 2016 (has links)
Turmeric polar extract (TPE) was obtained by dielectric-precipitation of turmeric slurry and found to contain three proteins with two in the 10-11 KDa range being dominant. Antioxidative activity and persistence (AP) of TPE (5%, w/v) respectively showed 87% and 85% greater generation of alkoxy- and peroxyl radicals compared the non-redox-active buffer alone showing significant (p<0.05) pro-oxidative behavior. Conversely, purified curcumin (CU) (0.1% w/v) was dramatically antioxidative with AA and AP values of 2,828 and 1,129%, respectively, compared to the blank. However, a combination of the two at the same concentration dropped these values to 590 and 389%, respectively, reflecting dramatic dampening of the efficacy of CU. Ultraviolet radiation significantly modulated the efficacy of CU where UVB (300 nm) exposure gave the highest enhancement when limited to five min. Data showed that turmeric contains highly pro-oxidant polar proteins that significantly dramatically diminishes the beneficial antioxidative efficacy of its principal phytochemical, CU.
54

Determination of Physicochemical and Sensory Properties of Kudzu (Pueraria Lobata) and Potato Starch in Beef Patties, and Thermal Stability of Kudzu Root Extract Isoflavones in Beef Patties

Kumari, Shweta 15 December 2012 (has links)
Kudzu (Pueraria lobata) plant is an edible leguminous vine. This study focused on the utilization of kudzu starch and kudzu root extract in beef patties. We hypothesized that a) physicochemical and sensory properties of beef patties formulated with kudzu starch, is comparable to those of potato starch; b) the kudzu root extract is rich in isoflavones, and isoflavones quantity is not affected during cooking. In Study I, beef patties were formulated using modified commercially available kudzu and potato starch each at 2.0, 4.0 and 6.0% (wt/wt). Starch treated beef patties were compared with respect to change in physical, chemical, color, textural and consumer responses as affected by starch type (kudzu, potato) and starch level (2, 4, 6 %). Additionally starch treated patties were compared to all-beef patties. Kudzu starch treated patties were significantly lower in moisture % (62.7 vs. 64.4), higher in fat % (9.1 vs. 8.3), protein % (26.3 vs. 24.7), hardness (9.3, vs. 6.9 N) and gumminess (3.7 vs. 1.9 N) compared to potato starch treated patties. Starch treated samples were significantly lighter in color and had lower (P <0.05) expressible moisture compared to all-beef patties. Patties with 6% kudzu or potato starch were significantly higher in cooking yield than all-beef patties. No significant difference existed in consumer overall liking scores of kudzu or potato starch treatments and control beef patties with no added starch. The overall liking scores ranged between 5 ‘neither like nor dislike’ and 6 ‘like slightly’ for all samples. In study II, kudzu root extract was prepared, and using HPLC, ten isoflavones were detected with puerarin and daidzein accounting for 95% of the total isoflavones. Beef patties were formulated with kudzu root extract at 0, 1, and 3% (wt/wt), and four isoflavones were detected in uncooked and cooked patties, considering other isoflavones diluted to undetectable levels in patties. Results indicated that cooking did not change the amount of isoflavones in beef patties. This study illustrates the characteristics of kudzu starch compared to conventionally used potato starch in meat model system and verifies the thermal stability of isoflavones in beef patties.
55

Comparison of Methods For Estimating Tissue Components In Mixed Tissue Sample

Liu, Xuerong January 2016 (has links)
No description available.
56

Creeping Bentgrass, Kentucky Bluegrass and Tall Fescue Responses to Plant Growth Stimulants Under Deficit Irrigation

LaBranche, Adrienne Janel 02 May 2005 (has links)
A four-year drought, increasing population and shifting climate has spurred water conservation practices within Virginia. Creeping bentgrass (<i>Agrostis palustris</i> "L93"), Kentucky bluegrass (<i>Poa pratensis </i>"Midnight"), and tall fescue (<i>Festuca arundinacea</i>) Dominion blend were evaluated under deficit irrigation and upon exogenous application of plant growth stimulants (PGS), seaweed extract (SWE) + humic acid (HA), glycinebetaine (GB) and a commercial SWE product (PP). The objectives were to determine crop coefficients (K<sub>c</sub>) for creeping bentgrass fairways and tall fescue home lawns, to determine if PGS application allowed for more water conservation, and to determine if they impacted physiological function and/or root morphology. A preliminary greenhouse experiment was conducted with creeping bentgrass and Kentucky bluegrass irrigated with 100%, 85% and 70% of evapotranspiration (ET). The study determined that an additional deficit irrigation level should be included for the field study and that GB application and 100% and 85% ET irrigation level produced the greatest creeping bentgrass root mass. The two–year field study evaluated creeping bentgrass and tall fescue. Tall fescue home lawns could be irrigated every five days with a K<sub>c</sub> of 0.55 or once a week with a K<sub>c</sub> of 0.70. Creeping bentgrass fairways could be irrigated every four days with a K<sub>c</sub> of 0.85. Glycinebetaine application increased bentgrass rooting after planting and showed osmoprotectant properties. Another greenhouse study evaluated five GB rates on bentgrass and tall fescue. No differences were found between the five rates and concluded that the rate utilized in the field study may be appropriate for turfgrass application. / Master of Science
57

Understanding cryptic schemata in large extract-transform-load systems

Albrecht, Alexander, Naumann, Felix January 2012 (has links)
Extract-Transform-Load (ETL) tools are used for the creation, maintenance, and evolution of data warehouses, data marts, and operational data stores. ETL workflows populate those systems with data from various data sources by specifying and executing a DAG of transformations. Over time, hundreds of individual workflows evolve as new sources and new requirements are integrated into the system. The maintenance and evolution of large-scale ETL systems requires much time and manual effort. A key problem is to understand the meaning of unfamiliar attribute labels in source and target databases and ETL transformations. Hard-to-understand attribute labels lead to frustration and time spent to develop and understand ETL workflows. We present a schema decryption technique to support ETL developers in understanding cryptic schemata of sources, targets, and ETL transformations. For a given ETL system, our recommender-like approach leverages the large number of mapped attribute labels in existing ETL workflows to produce good and meaningful decryptions. In this way we are able to decrypt attribute labels consisting of a number of unfamiliar few-letter abbreviations, such as UNP_PEN_INT, which we can decrypt to UNPAID_PENALTY_INTEREST. We evaluate our schema decryption approach on three real-world repositories of ETL workflows and show that our approach is able to suggest high-quality decryptions for cryptic attribute labels in a given schema. / Extract-Transform-Load (ETL) Tools werden häufig beim Erstellen, der Wartung und der Weiterentwicklung von Data Warehouses, Data Marts und operationalen Datenbanken verwendet. ETL Workflows befüllen diese Systeme mit Daten aus vielen unterschiedlichen Quellsystemen. Ein ETL Workflow besteht aus mehreren Transformationsschritten, die einen DAG-strukturierter Graphen bilden. Mit der Zeit entstehen hunderte individueller ETL Workflows, da neue Datenquellen integriert oder neue Anforderungen umgesetzt werden müssen. Die Wartung und Weiterentwicklung von großen ETL Systemen benötigt viel Zeit und manuelle Arbeit. Ein zentrales Problem ist dabei das Verständnis unbekannter Attributnamen in Quell- und Zieldatenbanken und ETL Transformationen. Schwer verständliche Attributnamen führen zu Frustration und hohen Zeitaufwänden bei der Entwicklung und dem Verständnis von ETL Workflows. Wir präsentieren eine Schema Decryption Technik, die ETL Entwicklern das Verständnis kryptischer Schemata in Quell- und Zieldatenbanken und ETL Transformationen erleichtert. Unser Ansatz berücksichtigt für ein gegebenes ETL System die Vielzahl verknüpfter Attributnamen in den existierenden ETL Workflows. So werden gute und aussagekräftige "Decryptions" gefunden und wir sind in der Lage Attributnamen, die aus unbekannten Abkürzungen bestehen, zu "decrypten". So wird z.B. für den Attributenamen UNP_PEN_INT als Decryption UNPAIN_PENALTY_INTEREST vorgeschlagen. Unser Schema Decryption Ansatz wurde für drei ETL-Repositories evaluiert und es zeigte sich, dass unser Ansatz qualitativ hochwertige Decryptions für kryptische Attributnamen vorschlägt.
58

Estudo de atividade de Phyllanthus amarus L. contra o Schistosoma mansoni linhagem BH / Study of Phyllanthus amarus L. activity Schistosoma mansoni strain BH

Oliveira, Claudineide Nascimento Fernandes de, 1979- 12 August 2018 (has links)
Orientador: Silmara Marques Allegretti / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-12T15:42:28Z (GMT). No. of bitstreams: 1 Oliveira_ClaudineideNascimentoFernandesde_M.pdf: 7853084 bytes, checksum: e21dff7dd2d35d9545d8717dc30fdb79 (MD5) Previous issue date: 2008 / Resumo: A esquistossomose mansonica e uma doenca cronica e debilitante. Estima-se que mais de 200 milhoes de pessoas estejam infectadas no mundo pela doenca, e no Brasil estima-se que existe de 8 a 10 milhoes de pessoas infectadas. O tratamento da esquistossomose e baseado na quimioterapia com o praziquantel, principalmente devido a sua atividade contra todas as especies de Schistosoma patogenicas ao homem. Infelizmente, o uso extensivo e inapropriado desse farmaco pelo mundo, culminou com o aparecimento de esquistossomas tolerantes, gerando uma preocupacao sobre a selecao da resistencia a esse medicamento. Entao, para se controlar a esquistossomose, ha necessidade de se desenvolver novas opções de farmacos, como alternativa ao praziquantel. As plantas medicinais vem sendo aplicadas e testadas como novas alternativas medicamentosas para o tratamento de parasitoses. Este estudo teve por objetivo avaliar a atividade esquistossomicida da planta Phyllanthus amarus L. sobre Schsistosoma mansoni, linhagem BH em camundongos Swiss. Foram testados os extratos hexanico e etanolico nas concentracoes 100, 150 e 250mg/Kg, e a fracao de Lignanas 50 e 100mg/Kg, administrados em dose unica por tubagem esofagica. Os animais foram divididos em dois grupos de acordo com o periodo de tratamento (30 ou 45 dias apos a infeccao para avaliar a acao dos extratos nos vermes jovens e adultos, respectivamente). Foram analisados os seguintes parametros: quantidade/ porcentagem de vermes adultos nas veias mesentericas, porta e nas visceras; proporcao entre machos e femeas; reducao no numero de vermes; reducao no numero de ovos eliminados para o ambiente externo e retidos no tecido intestinal; alteracao no oograma; aspecto visual dos granulomas nas visceras; alteracao no tamanho dos granulomas encontrados no figado. De acordo com os resultados obtidos, o tratamento feito com o extrato etanolico 250mg/Kg no 30° dia de infeccao, foi o que apresentou maior reducao do numero de vermes (63%), e o grupo tratado com o extrato hexanico 100mg/Kg nesse mesmo periodo foi o que apresentou maior quantidade de vermes nas visceras (n=3,1). Ja os tratamentos feitos com o extrato etanolico 100mg/Kg e a fracao de Lignanas 50mg/Kg apos 30 dias de infeccao, conseguiram cessar a postura de ovos, o que fez com que os orgaos desses grupos fossem pouco lesados. Ocorreu ausencia de granulomas nos figados observados histologicamente para o grupo tratado com o extrato etanolico 100mg/Kg. No 45° dia apos a infeccao o grupo tratado com o extrato hexanico 150mg/Kg foi o que apresentou resultado mais significativo, uma vez que ele conseguiu reduzir o numero de ovos imaturos e aumentar o de ovos maduros, indicando que este tratamento alterou a oviposicao do verme. Os resultados obtidos para os extratos hexanico e etanolico e fracao de Lignanas demonstraram potencial atividade nos diferentes parametros avaliados, evidenciando que a planta P. amarus possui efeito contra o S. mansoni linhagem BH. / Abstract: The schistosomiasis is a chronic and debilitating disease. It is estimated more than 200 million people worldwide are infected by the disease, and in Brazil is estimated 8 to 10 million people infected. The treatment of schistosomiasis is based on praziquantel chemotherapy, mainly due to its activity against all species of pathogenic Schistosoma to humans. The inappropriate and extensive use of this drug in the world culminated in the appearance of tolerant worms, generating a concern about the selection of resistance this drug. So, to control schistosomiasis, there is need to develop new options for drugs, as an alternative to the praziquantel. Medicinal plants have been implemented and tested as a new alternative drug for the treatment of parasitic. The objective of this study was to assess the presence of antichistosomal activity of the plant Phyllanthus amarus L. using Schistosoma mansoni infected mice of BH strain. The hexane and ethanolic extracts with 100, 150 and 250mg/Kg, concentrations and the Lignans fraction 50 and 100mg/kg, were administered with single oral dose by esophageal intubation. The animals were divided into two groups according to the treatment period (30 or 45 days after infection to evaluate the effect of the extracts in young and adult worms respectively). Analyzes performed consists in a set of parameters: quantity / percentage of adult worms in the veins mesenteric, port and the viscera; proportion of male and female worms, worms reduction; eggs reduction eliminated environment and retained in the intestinal tissue; change in oograma; visual aspect of granulomas in the viscera; change in the size of granulomas found in the liver. According to the results, the treatment with ethanolic extract 250mg/Kg in 30th days of infection, presented the greatest reduction in the number of worms (63%), and the group treated with the hexane extract 100mg/kg in same period presented the highest number of worms in the viscera (n=3.1). The treatments made with ethanolic extract 100mg/kg and the Lignans fraction 50mg/kg after 30 days of infection managed to stop the egg laying. So that the organs of these groups were slightly injured. There was absence of granulomas in the liver observed histological for the group treated with ethanolic extract 100mg/kg. In the 45th days after infection the group treated with the hexane extract 150mg/Kg presented the most significant result, as to reduced the number of immature eggs, and increased of mature eggs, indicating that this treatment has changed the worm oviposition. The results for the ethanol, hexane extracts and fraction of Lignans demonstrated potential activity in the various parameters measured, suggesting that the plant P. amarus has effect against S.mansoni strain BH. / Mestrado / Mestre em Parasitologia
59

Evaluation of Peanut Skin Extract, Grape Seed Extract, and Grape Seed Extract Fractions to Reduce Populations of Select Foodborne Pathogens

Levy, Jason M. 10 June 2014 (has links)
Grape seed extract (GSE) and peanut skin extract (PSE) are waste products in the wine and peanut industries. Both extracts have high concentrations of polyphenols, known to possess antioxidant and antimicrobial properties. A subcategory of polyphenol is procyanidin, which can be divided into two types, type A and type B. Type A (PSE), contains two single bonds connecting the phenolic groups while type B (GSE), contains one single bond connecting the phenolic groups. The minimum inhibitory concentration (MIC) of the two extracts was evaluated for their antimicrobial effect on Listeria monocytogenes, Staphylococcus aureus, Escherichia coli O157:H7, and Salmonella Typhimurium using the pour plate method. GSE was found to have a significantly lower MIC (p ≤ 0.05) than PSE for L. monocytogenes (GSE=60.60ppm, PSE=not found), S. aureus (GSE=38.63ppm, PSE=51.36ppm), and S. Typhimurium (GSE=45.73ppm, PSE=60.60ppm). There was no significant difference in inhibition of E. coli O157:H7 (GSE=47.44ppm, PSE=51.13ppm). Since GSE, contributed to greater pathogen inhibition, its extract was fractionated into monomer and oligomers components. Growth curves of all four pathogens inoculated in the monomer and oligomer fractions were compared using the BioScreen method. Oligomers inhibited growth of L. monocytogenes, S. aureus, and E. coli O157:H7 while monomers inhibited growth of S. Typhimurium. These results indicate that an extract with type B procyanidins that are high in oligomers may be more effective as antimicrobials. Type B procyanidins have also been shown to prevent bacterial adhesion, as is the case with urinary tract infections, and may aid in the prevention of biofilms. / Master of Science in Life Sciences
60

Étude électrophysiologique des effets du tabac, de sa fumée et de la nicotine sur des neurones dopaminergiques de l’aire tegmentale ventrale in vivo chez le rat, la souris sauvage et la souris β2 KO / An electrophysiological study of the effects of tobacco, its smoke, and nicotine, on ventral tegmental area dopaminergic neurons in vivo in the rat, the wild type mice and the ß2 KO mice

Arib, Ouafa 15 September 2009 (has links)
La nicotine est considérée comme étant la « molécule » addictogène de la cigarette et du tabac. Mais différentes études cliniques, utilisant notamment des substituts nicotiniques, débouchent pratiquement toutes sur une même conclusion : efficacité ne dépassant que de peu celle d’un placebo, et très limitée dans le temps, contrastant avec le pouvoir hautement addictif du tabac, qu'il soit chiqué, prisé ou fumé. Dans ce travail de thèse, nous avons essayé de mettre en évidence le rôle que pourraient avoir certains des autres composés présents dans le tabac ou produits par pyrolyse. Nous avons d’abord utilisé des extraits aqueux de fumée et de tabac pour approcher un aspect global de ce que les fumeurs absorbent chaque fois qu’ils fument une cigarette, nous rapprochant ainsi des conditions physiologiques du fumeur. Puis nous avons choisi un certain nombre de substances. La cotinine, métabolite de la nicotine. L’harmane, une ß-carboline, synthétisée au cours de la combustion et dans l’organisme des fumeurs. La norharmane, une ß-carboline, présente en partie dans le tabac et synthétisée dans la fumée par pyrolyse. La technique utilisée tout au long de ce travail est l’enregistrement électrophysiologique. Cette technique s’applique très bien à l’étude in vivo de différents systèmes neuronaux y compris le système dopaminergique. Nous l’avons utilisée chez le rat, la souris WT et la souris Knockout ß2 (ß2KO). Nous nous sommes intéressés à deux aspects de l’activité cellulaire des neurones dopaminergiques de l’aire tegmentale ventrale : la fréquence de décharge (le firing) et les bouffées (bursts). En parallèle, nous avons conduit des expériences de liaison (binding) sur des cultures de cellules exprimant le récepteur nicotinique α4ß2. Nos résultats les plus significatifs ont montré que : Les bursts sont le plus souvent absents après les injections d’extraits de tabac et de fumée. Cela pourrait, entre autres, impliquer qu’il existe dans le tabac et la fumée des composés autres que la nicotine qui bloquent les effets de la nicotine sur les bursts. Les effets des extraits de tabac et de fumée sur le firing et les bursts ne sont plus présents chez les souris ß2 KO, ce qui implique que l’ensemble des composés du tabac agit essentiellement sur les récepteurs nicotiniques porteurs de la chaine ß2, même si des hypothèses alternatives existent. L’harmane a des effets activateurs très puissants sur le firing des neurones dopaminergiques, et ces effets sont bloqués à 80% par la mécamylamine, ce qui démontre qu’un des principaux composés du tabac et de la fumée autre que la nicotine agit par un mécanisme essentiellement nicotinique. Les expériences de binding confirment que les effets du tabac et de la fumée impliquent les récepteurs nicotiniques d’une façon majeure, mais d’une façon qui diffère légèrement de celle de la nicotine.Les résultats que nous avons obtenus montrent que les effets pharmacologiques du tabac ne se résument pas à ceux de la seule nicotine. Ils peuvent constituer un point de départ pour d’autres travaux, notamment pour étudier de plus près les effets des ß-carbolines. Il est nécessaire d’identifier les types de récepteurs sur lesquels elles se fixent, en utilisant des agonistes et antagonistes de récepteurs aux neurotransmetteurs contrôlant l’activité des neurones dopaminergiques. Des expériences sur des souris transgéniques chez lesquelles différents types de sous-unités de récepteurs nicotiniques ont été supprimés doivent également être envisagées, pour déterminer les mécanismes d’action des composants autres que la nicotine contenus dans le tabac et sa fumée sur les neurones dopaminergiques / Nicotine is generally considered as the sole tobacco addictive compound. However, nicotine replacement therapy studies almost all end with the same conclusion: the effectiveness of nicotine replacement is very limited on the short-term, and hardly exceeds that of placebo on the long-term. In addition, studies dealing with the effects of denicotinized cigarettes have provided evidence that these cigarettes have an addictive potential. In the present work, we tried to determine the behavioral role of some tobacco or smoke compounds other than nicotine at the neuronal level. We first compared the effects of nicotine with those of whole tobacco and smoke extracts, given that these preparations closer mimic the smoking situation than nicotine alone. We then examined the effects of a number of selected tobacco or smoke compounds. Cotinine, a major nicotine metabolite. Harmane and norharmane, two ß-carbolines synthesized in smoke as well as in the body of smokers. The technique used consists in the in vivo recording of the firing rate and bursts of dopamine neurons in the ventral tegmental area after intravenous injections of compounds in rats and mice. This electrophysiological technique is known to be a useful way to investigate the properties of selected compounds. In the case of mice, we used wild type and ß2 KO mice. We also made a series of in vitro experiments investigating the binding properties of the compounds on cells expressing high densities of α4ß2 nicotinic receptors. The main results of our studies are the following: Bursts are absent most of the times after the injection of the extracts. These results suggest that tobacco and smoke extracts contain compounds that inhibit the burst-promoting effects of nicotine. Increased firing is no longer present in ß2 KO mice treated with tobacco or smoke extracts, indicating that tobacco and smoke components, as a whole, primarily acts on nicotinic receptors that carry the ß2 chain, although alternative hypotheses may exist. Harmane very strongly activates the firing of dopaminergic neurons. Up to 80% of this effect is blocked by mecamylamine, demonstrating that that a major component of tobacco and smoke other than nicotine acts primarily through a nicotinic mechanism. The binding experiments confirm that the effects of tobacco and smoke involve nicotinic receptors in a major way, but in a way that slightly differs from that of nicotine. Our results may constitute a new starting point for further work, especially for a closer look at the effects of ß-carbolines. Attempts to identify the types of receptors involved in these effects are needed, using agonists and antagonists of neurotransmitter receptors that control the activity of dopamine neurons. Experiments on transgenic mice with deletion of different types of subunits of nicotinic receptors should also be made, to determine the different mechanisms of action of tobacco and smoke compounds other than nicotine on dopaminergic neurons

Page generated in 0.3449 seconds