Towards a better energy efficiency through a systems approach in an industrial forklift

The purpose of this study is to improve the potential energy recovery to electric energy in an electrohydraulic forklift system. The initial achieved result for energy saving ratio after structural optimization is 40 %. Component optimization is applied to the tested drive which consists of a DTC controlled electric servo motor directly running a reversible hydraulic pump. According to the study the energy efficiency and the energy recovery from the electro-hydraulic forklift system can be increased by 11 % units. New ideas and directions of further research were obtained during the study.

Aurinkovoimalaitoksen mitoittaminen suunnitteilla olevaan kerrostaloon

Aurinkopaneelien ja inverttereiden hinnat ovat laskeneet viime vuosina, joten au-rinkosähköstä on tullut kannattava sähköntuotantomuoto kiinteistöille. Tässä kandidaatintyössä kerrotaan, kuinka arvioida suunnitteilla olevan rakennuksen peruskuormaa aurinkopaneeleiden asennuksen näkökulmasta. Voimalaitoksen sijoituskohde sijaitsee Järvenpäässä. Kohteessa on 69 huoneistoa 8 kerroksessa ja yhteiset tilat 9. kerroksessa. Voimalaitoksen kannattavuutta tutkitaan simuloimalla tuotantoja ja arvioimalla kulutusta. Tuotantoja simuloidaan HOMER-ohjelmistolla. Rakennuksen kulutusta arvioidaan suunnittelijoilta saatujen tietojen perusteella, ja vanhempien samankaltaisten kohteiden kulutusten perusteella, jotka saadaan Nuuka-portaalista. Saaduista tuloksista huomataan, että nykyisillä sähkönhinnoilla aurinkopaneelit ovat kannattava investointi, vaikka sähköä tuotettaisiin hieman ylimääräistä, joten paneelit voidaan mitoittaa hieman kulutusta suuremmaksi. Takaisinmaksuaika on noin 20 vuotta. Tulokset ovat linjassa vanhempien tutkimusten kanssa. Tuloksista huomataan, myös että paneeleita jakamalla eri ilmansuuntiin saadaan tuotannon huipputeho pienemmäksi ja samalla tuotanto jakautumaan laajemmalle ajanjaksolle. Paneelien hintojen laskettua on kannattavaa asentaa paneeleja epäedullisempiin suuntiin, täten saadaan tuotantoa ajoitettua mahdollisesti paremmin kulutus-ta vastaavaksi. Mitoituksen voi tarkistaa rakennuksen valmistuttua, sillä raken-nuksesta tullaan mittaamaan paneeleiden tuottama sähkö ja kohteen kiinteistösähkönkulutus.

Opistorakennusten energiatehokkuuden parantaminen

Tämän diplomityön tavoitteena on selvittää Kymenlaakson Opiston energiatehokkuuden parantamista ja tutkia onko olemassa selvästi taloudellisempi sekä ekologisempi tapa kattaa Opiston lämmitystarve verrattuna nykyisin käytössä olevaan kaukolämpöön. Työn teoriaosuudessa tehdään katsaus rakennusten energiatehokkuuteen vaikuttaviin seikkoihin, lähienergian tuotantoon ja energiatehokkuuden parantamiseen liittyvään lainsäädäntöön ja säädöksiin. Useasta rakennuksesta koostuva kansanopisto tarjoaa mielenkiintoisen pohjan selvitystyölle ja suuri lämmitystehontarve yhdistettynä monille saneerauskohteille tyypillisiin ahtaisiin teknisiin tiloihin asettaa rajoituksia lämmitysjärjestelmän suunnittelulle. Soveltavassa osuudessa määritellään reunaehdot mahdolliselle kaukolämmön korvaavalle lämmitysratkaisulle. Tutkitaan vesistölämmön hyödyntämisen mahdollisuutta ja lasketaan aurinkosähkön ja -lämmön tuotantopotentiaalia. Maalämpöjärjestelmän mitoituksessa ja taloudellisessa vertailussa käytettiin apuna maalämpöjärjestelmiä toimittavia yrityksiä. Työssä saatujen tulosten perusteella maalämpöjärjestelmä on taloudellisesti kannattava isossa kohteessa, tosin järjestelmän asennukseen liittyy ahtaiden tilojen johdosta ongelmia. Maalämpö on myös selvästi ekologisempi, kuin nykyisin käytössä oleva kaukolämpö. Aurinkosähkön tuotannolle on Kymenlaakson Opistolla hyvä potentiaali ja sähkön tuotanto kohtaa hyvin sähkön käytön.

Variable-speed-drive-based detection methods for problems in fluid handling systems

Fluid handling systems account for a significant share of the global consumption of electrical energy. They also suffer from problems, which reduce their energy efficiency and increase life-cycle costs. Detecting or predicting these problems in time can make fluid handling systems more environmentally and economically sustainable to operate. In this Master’s Thesis, significant problems in fluid systems were studied and possibilities to develop variable-speed-drive-based detection methods for them was discussed. A literature review was conducted to find significant problems occurring in fluid handling systems containing pumps, fans and compressors. To find case examples for evaluating the feasibility of variable-speed-drive-based methods, queries were sent to industrial companies. As a result of this, the possibility to detect heat exchanger fouling with a variable-speed drive was analysed with data from three industrial cases. It was found that a mass flow rate estimate, which can be generated with a variable speed drive, can be used together with temperature measurements to monitor a heat exchanger’s thermal performance. Secondly, it was found that the fouling-related increase in the pressure drop of a heat exchanger can be monitored with a variable speed drive. Lastly, for systems where the flow device is speed controlled with by a pressure measurement, it was concluded that increasing rotational speed can be interpreted as progressing fouling in the heat exchanger.

Vuotovesien merkitys jätevesihuollossa

Yleisimmät viemäröintijärjestelmät ovat erillisviemäröinti ja sekaviemäröinti. Erillisviemä-röinnissä jäte- ja hulevedet johdetaan omissa verkostoissa. Sekaviemäröinnissä kaikki viemä-röitävät vedet virtaavat samassa verkostossa. Vuotoveden osuus jätevesiviemäriverkostossa virtaavasta jätevedestä on keskimäärin yli 30 prosenttia. Vuotovesiselvityksen avulla pyritään selvittämään vuotoveden esiintymisalueet ja mahdolliset vuotokohteet. Mallintamalla laadittu selvitys tarjoaa mahdollisuuden tarkastella verkostoa kokonaisuutena ja erilaisissa käyttötilan-teissa. Tämä työ perustuu Joensuun kantakaupungin viemäriverkostosta mallintamalla laadit-tuun vuotovesiselvitykseen. Työssä on tarkoitus selvittää vuotovesistä aiheutuvan lisäener-giantarpeen ja kasvihuonekaasupäästöjen kasvua sekä pohtia verkoston omistussuhteiden, sään ääri-ilmiöiden ja taajuusmuuttajien vaikutuksia vuotovesien hallintaan. Lisäksi selvitetään voidaanko tuloksista tehdä valtakunnallisia yleistyksiä. Joensuun viemäriverkostossa jätevesien pumppaukseen käytetystä energiasta noin 43 prosent-tia kuluu vuotovesien pumppaukseen. Siitä aiheutuu vuosittain 480 MWh:n lisäenergiantarve, joka johtaa 106 tonnin hiilidioksidipäästöihin. Lisäenergiantarpeesta aiheutuva hiilidioksidi-päästö on pieni liikenteen aiheuttamaan päästöön verrattuna. Saneerauksilla voidaan saavuttaa 60 prosentin vähennys vuotovesimäärään. Tavoitteeksi tulisi asettaa keskusta-alueella olevien sekaviemäreiden korvaaminen erillisviemäreillä esimerkiksi lähimmän 10 vuoden aikana ja vuotovesimäärän yleinen vähentäminen koko verkoston alueella. Ilmastonmuutoksen myötä yleistyvät rankkasateet lisäävät vuotovesimäärää etenkin sekaviemäröidyillä alueilla. Tämä korostaa sekaviemäröidyn verkoston korjaustoimenpiteiden tärkeyttä. Taajuusmuuttajien yleistyvä käyttö tasaa haitallisia virtaamapiikkejä. Optimaaliseksi säädetty pyörimisnopeus pienentää merkittävästi pumppujen energiankulutusta. Työstä saadut tulokset ovat valtakun-nallisella tasolla suuntaa antavia. Tarkemmat yleistykset vaativat useista erikokoisista verkos-toista tehtyjen vuotovesiselvitystulosten analysointia.

Localization of the mechanism of pH-dependent non- photochemical fluorescence quenching in thylakoid membranes

Higher plants have evolved a well-conserved set of photoprotective mechanisms, collectively designated Non-Photochemical Quenching of chlorophyll fluorescence (qN), to deal with the inhibitory absorption of excess light energy by the photosystems. Their main contribution originates from safe thermal deactivation of excited states promoted by a highly-energized thylakoid membrane, detected via lumen acidification. The precise origins of this energy- or LlpH-dependent quenching (qE), arising from either decreased energy transfer efficiency in PSII antennae (~ Young & Frank, 1996; Gilmore & Yamamoto, 1992; Ruban et aI., 1992), from alternative electron transfer pathways in PSII reaction centres (~ Schreiber & Neubauer, 1990; Thompson &Brudvig, 1988; Klimov et aI., 1977), or from both (Wagner et aI., 1996; Walters & Horton, 1993), are a source of considerable controversy. In this study, the origins of qE were investigated in spinach thylakoids using a combination of fluorescence spectroscopic techniques: Pulse Amplitude Modulated (PAM) fluorimetry, pump-probe fluorimetry for the measurement of PSII absorption crosssections, and picosecond fluorescence decay curves fit to a kinetic model for PSII. Quenching by qE (,..,600/0 of maximal fluorescence, Fm) was light-induced in circulating samples and the resulting pH gradient maintained during a dark delay by the lumenacidifying capabilities of thylakoid membrane H+ ATPases. Results for qE were compared to those for the addition of a known antenna quencher, 5-hydroxy-1,4naphthoquinone (5-0H-NQ), titrated to achieve the same degree of Fm quenching as for qE. Quenching of the minimal fluorescence yield, F0' was clear (8 to 130/0) during formation of qE, indicative of classical antenna quenching (Butler, 1984), although the degree was significantly less than that achieved by addition of 5-0H-NQ. Although qE induction resulted in an overall increase in absorption cross-section, unlike the decrease expected for antenna quenchers like the quinone, a larger increase in crosssection was observed when qE induction was attempted in thylakoids with collapsed pH gradients (uncoupled by nigericin), in the absence of xanthophyll cycle operation (inhibited by DTT), or in the absence of quenching (LlpH not maintained in the dark due to omission of ATP). Fluorescence decay curves exhibited a similar disparity between qE-quenched and 5-0H-NQ-quenched thylakoids, although both sets showed accelerated kinetics in the fastest decay components at both F0 and Fm. In addition, the kinetics of dark-adapted thylakoids were nearly identical to those in qEquenched samples at F0' both accelerated in comparison with thylakoids in which the redox poise of the Oxygen-Evolving Complex was randomized by exposure to low levels of background light (which allowed appropriate comparison with F0 yields from quenched samples). When modelled with the Reversible Radical Pair model for PSII (Schatz et aI., 1988), quinone quenching could be sufficiently described by increasing only the rate constant for decay in the antenna (as in Vasil'ev et aI., 1998), whereas modelling of data from qE-quenched thylakoids required changes in both the antenna rate constant and in rate constants for the reaction centre. The clear differences between qE and 5-0H-NQ quenching demonstrated that qE could not have its origins in the antenna alone, but is rather accompanied by reaction centre quenching. Defined mechanisms of reaction centre quenching are discussed, also in relation to the observed post-quenching depression in Fm associated with photoinhibition.

Investigations in flow injection analysis (FIA): conventional FIA determination of chloride in water; sequential injection (SI)-FIA determination of mercury in water

Flow injection analysis (FIA) was applied to the determination of both chloride ion and mercury in water. Conventional FIA was employed for the chloride study. Investigations of the Fe3 +/Hg(SCN)2/CI-,450 nm spectrophotometric system for chloride determination led to the discovery of an absorbance in the 250-260 nm region when Hg(SCN)2 and CI- are combined in solution, in the absence of iron(III). Employing an in-house FIA system, absorbance observed at 254 nm exhibited a linear relation from essentially 0 - 2000 Jlg ml- 1 injected chloride. This linear range spanning three orders of magnitude is superior to the Fe3+/Hg(SCN)2/CI- system currently employed by laboratories worldwide. The detection limit obtainable with the proposed method was determin~d to be 0.16 Jlg ml- 1 and the relative standard deviation was determined to be 3.5 % over the concentration range of 0-200 Jig ml- 1. Other halogen ions were found to interfere with chloride determination at 254 nm whereas cations did not interfere. This system was successfully applied to the determination of chloride ion in laboratory water. Sequential injection (SI)-FIA was employed for mercury determination in water with the PSA Galahad mercury amalgamation, and Merlin mercury fluorescence detection systems. Initial mercury in air determinations involved injections of mercury saturated air directly into the Galahad whereas mercury in water determinations involved solution delivery via peristaltic pump to a gas/liquid separator, after reduction by stannous chloride. A series of changes were made to the internal hardware and valving systems of the Galahad mercury preconcentrator. Sequential injection solution delivery replaced the continuous peristaltic pump system and computer control was implemented to control and integrate all aspects of solution delivery, sample preconcentration and signal processing. Detection limits currently obtainable with this system are 0.1 ng ml-1 HgO.

Examining and describing professional development and continuing education in the personal training and fitness industry : sites and issues of disconnect

The following phenomenologically oriented study examines and describes the relevance and effectiveness of professional development and continuing education programs for real-world situations of personal trainers. The participants were personal trainers, facility managers, and persons involved in the accreditation process. Data collection took place in 3 phases. The first phase consisted of the participants completing the PUMP Questionnaire, followed by focus groups with personal trainers and interviews with managers. The study's 3 data sets required reduction via a content analysis by question, content analysis by existential categories, and further thematic analysis using the lived relation existential dimension. The discussion contains the salient sites and issues of disconnect between clients, personal trainers, and facility managers and how they might affect the personal training experience. The intergenerational disconnect emphasized between Boomers as clients and Millennials as personal trainers requires further exploration and dialogue and underscores the need for different approaches to content and delivery of professional development and continuing education experiences for personal trainers and managers of fitness facilities.

Letter written by John Bentley, Sept. 26, 1813.

Transcript [original spelling and grammar retained]: Sacketts Harbour 26th Sept. 1813. Dear wife. From this you are informed that I am in health at this Date. When I last wrote to you I some expected to go upon and expedition but to us unknown we sat out and went up the Lake 3 Days Landed at Oswego The British Fleet appeared off, and we returned and saw our fleet upon our return, I think that our Regt. going was only a maneuver to get the Fleet out that our Fleet might come a threat[?] of them We expect to embark immediately into Canada as preparations are making to convey us over to them we are anxious to commence an action with them. Troops are daily coming in to the Harbour to take the Stand in our absence, we shall not be here 3 days before we try their[?] Powder. they are daily defecting[?] to us from Canada very fearful of the consequence of our Resisting[?] of them…our Fleet is now out and has been for 6 or 7 days. The Lake Erie fleet has done great things. I hope ours will be as successful. I think that our Generals are waiting to hear from them as every thing is ready[?] of to embark various opinions reflecting were we shall attack them some say at Kingston others at Montreal and others at Prescot—Mr. William Butler and D[?]…are well and in Spirits, Sergt Daniel White is very hearty for him, M. Samuel C[?] is well and in good health Benjm Thompson is well Charles Bryant is well [?] is well Eben[?] Smith is very much plagued with the Rheumatik Disease[?] he……… his limbs very often for being Crippled[?] he is at the Hospital I often visit it to see the sick Jacob Barnes is at the Hospital but recovering fast been very sick. Luther Gregory is at the Hospital and on the recovery, Sergt. L[?] & Smith are well, Henry ………[?] is well, very healthy have not more die here than 3…[?]to the best of my knowledge. I will make a few remarks upon the place it abounds in Lime Rock more than Thomaston and not every person to my knowledge burn it, and in the whole Town not but one Pump that supplies the Towns People and Soldiers and a ………[?] of such a Lake of water the Lake water is good for drinking but the water near the Shore is exposed to all kind of filth being thrown into it. The officers with whom I have been with have used me kindly and I get quietly by them. The Lieut. Downer who recruits at Thomaston tell me he has thots[?] of Leaving the army if so I must say I am greatly sorry as he was my ……[?] friend although he Left us and went in a northern Company it is a Company……………[?]worthy an officer as he proves to be, I cannot get any higher than a Sergeant or Quarter Master Sergeant which I may have without any friends at Thomaston assisting me. I am a Sergeant and Sergeant Daniel White is expecting[?] to be a Quarter Master Sergeant, and a number of his friends from Thomaston have went to their Major for him in the 9th Regt Major….[?] and he expects to obtain a Commission as I ……[?] expect to be promoted and it died away he will have the Laugh upon me, I wish that My Friend Dawes would[?] put the question to Col. Foot? to write to our Col. E.W. Ripley if he has …[?]in the …[?]taken by him and others of my …[?] friends[?]. I expect to come home this winter without fail. I remain your Loving Husband till Death. John Bentley for Betsey Bentley Thomaston P.S. The next Letter will be ……[?]to Mr. Dawes[?] and shall write as soon as our Fleet arrives or if we are ordered off tomorrow shall write before I leave this Place. I have understood that many letters have been ……[?]to me. I have received only 2 from Mary, one from Mr. Dawes, one from William Thompson and have answered them please to write……[?]to S. Harbour.

Modulation of epithelial sodium channel (ENaC) expression in mouse lung infected with Pseudomonas aeruginosa

Affiliation: André Dagenais: Centre hospitalier de l'Université de Montréal/ Hôtel-Dieu, Département de médecine, Université de Montréal. Yves Berthiaume: Médecine et spécialités médicales, Faculté de médecine

Développement d’un système d’administration de l’anesthésie en boucle fermée

En salle d’opération, les tâches de l’anesthésiste sont nombreuses. Alors que l’utilisation de nouveaux outils technologiques l’informe plus fidèlement sur ce qui se passe pour son patient, ces outils font que ses tâches deviennent plus exigeantes. En vue de diminuer cette charge de travail, nous avons considérer l’administration automatique d’agents anesthésiques en se servant de contrôle en boucle fermée. À cette fin, nous avons développé un système d’administration d’un agent anesthésique (le propofol) visant à maintenir à un niveau optimal la perte de conscience du patient pendant toute la durée d’une chirurgie. Le système comprend un ordinateur, un moniteur d’anesthésie et une pompe de perfusion. L’ordinateur est doté d’un algorithme de contrôle qui, à partir d’un indice (Bispectral IndexTM ou BIS) fournit par le moniteur d’anesthésie détermine le taux d’infusion de l’agent anesthésiant. Au départ, l’anesthésiste choisit une valeur cible pour la variable de contrôle BIS et l’algorithme, basé sur système expert, calcule les doses de perfusion de propofol de sorte que la valeur mesurée de BIS se rapproche le plus possible de la valeur cible établie. Comme interface-utilisateur pour un nouveau moniteur d’anesthésie, quatre sortes d’affichage ont été considérés: purement numérique, purement graphique, un mélange entre graphique et numérique et un affichage graphique intégré (soit bidimensionnel). À partir de 20 scenarios différents où des paramètres normaux et anormaux en anesthésie étaient présentés à des anesthésistes et des résidents, l’étude des temps de réaction, de l’exactitude des réponses et de la convivialité (évaluée par le NASA-TLX) a montré qu’un affichage qui combine des éléments graphiques et numériques était le meilleur choix comme interface du système. Une étude clinique a été réalisée pour comparer le comportement du système d’administration de propofol en boucle fermée comparativement à une anesthésie contrôlée de façon manuelle et conventionnelle où le BIS était aussi utilisé. Suite à l’approbation du comité d’éthique et le consentement de personnes ayant à subir des chirurgies générales et orthopédiques, 40 patients ont été distribués également et aléatoirement soit dans le Groupe contrôle, soit dans le Groupe boucle fermée. Après l’induction manuelle de propofol (1.5 mg/kg), le contrôle en boucle fermée a été déclenché pour maintenir l’anesthésie à une cible de BIS fixée à 45. Dans l’autre groupe, le propofol a été administré à l’aide d’une pompe de perfusion et l’anesthésiste avait aussi à garder manuellement l’indice BIS le plus proche possible de 45. En fonction du BIS mesuré, la performance du contrôle exercé a été définie comme excellente pendant les moments où la valeur du BIS mesurée se situait à ±10% de la valeur cible, bonne si comprise de ±10% à ±20%, faible si comprise de ±20% à ±30% ou inadéquate lorsque >±30%. Dans le Groupe boucle fermée, le système a montré un contrôle excellent durant 55% du temps total de l’intervention, un bon contrôle durant 29% du temps et faible que pendant 9% du temps. Le temps depuis l’arrêt de la perfusion jusqu’à l’extubation est de 9 ± 3.7 min. Dans le Groupe contrôle, un contrôle excellent, bon, et faible a été enregistré durant 33%, 33% et 15% du temps respectivement et les doses ont été changées manuellement par l’anesthésiste en moyenne 9.5±4 fois par h. L’extubation a été accomplie après 11.9 ± 3.3 min de l’arrêt de la perfusion. Dans le Groupe boucle fermée, un contrôle excellent a été obtenu plus longtemps au cours des interventions (P<0.0001) et un contrôle inadéquat moins longtemps (P=0.001) que dans le Groupe contrôle. Le système en boucle fermée d’administration de propofol permet donc de maintenir plus facilement l’anesthésie au voisinage d’une cible choisie que l’administration manuelle.

Évaluation d’une intervention infirmière Motivationnelle Selon les Stades de Changement (MSSC) sur des comportements d’auto-soins chez des patients insuffisants cardiaques

L’insuffisance cardiaque (IC), une maladie chronique caractérisée par un mauvais fonctionnement du muscle cardiaque, entraîne des symptômes comme l’essoufflement, l’œdème et la fatigue. L’IC nécessite l’adoption de comportements d’auto-soins pour prévenir les épisodes de décompensation. Le but de cette recherche est d’évaluer l’intervention infirmière motivationnelle selon les stades de changements (MSSC) sur les comportements d’auto-soins chez des patients IC. Afin de guider l’intervention MSSC, la théorie spécifique aux auto-soins chez les patients IC de Riegel et Dickson (2008) a été retenue ainsi que le modèle d’intervention de Bédard et al. (2006) combinant le modèle transthéorique (Prochaska & DiClemente, 1984) et l’entrevue motivationnelle (Miller & Rollnick, 2006). Il s’agit d’un devis expérimental randomisé (pré et post-test) avec groupe contrôle (N = 15/groupe). Les patients du groupe contrôle ont reçu les soins usuels et les patients du groupe intervention (GI) ont reçu l’intervention MSSC durant trois entretiens. Les mesures de résultats ont été collectées à un mois suite à la randomisation par une assistante de recherche aveugle à la randomisation. L’effet de l’intervention a été évalué par des analyses de covariance sur cinq mesures de résultats : la réalisation et la gestion (générale et spécifique à l’IC) des auto-soins, la confiance aux auto-soins (générale et spécifique à l’IC) et la conviction. L’acceptabilité et la faisabilité ont été évaluées. Les résultats indiquent un effet significatif sur la mesure de confiance à effectuer les auto-soins spécifiques à l’IC. La majorité des participants du GI ont progressé dans leurs stades de changement. Ces résultats soulignent le potentiel de cette approche pour favoriser l’adoption des auto-soins mais une étude à plus large échelle est proposée afin d’évaluer l’effet de cette approche dans un essai clinique randomisé.

Recherche sur les effets de l'analgésie périopératoire optimale (RAPO) sur la douleur et la fonction après chirurgie de la main

Essai cinique randomisé

Contribution of tachykinin and kinin receptors in central autonomic control of blood pressure and behavioural activity in hypertensive rats

This work aims at studing the role of tachykinin NK-3 receptor (R) and kinin B1R in central autonomic regulation of blood pressure (BP) and to determine whether the B1R is overexpressed and functional in rat models of hypertension by measuring the effect of a B1R agonist on behavioural activity. Assumptions: (1) NK-3R located in the ventral tegmental area (VTA) modulates the mesolimbic dopaminergic system and has a tonic activity in hypertension; (2) B1R is overexpressed in the brain of hypertensive rats and has a tonic activity, which contributes to hypertension via a dopamine mechanism; (3) the inhibition of NK-3R and B1R with selective antagonists, reduces central dopaminergic hyperactivity and reverses hypertension. A model of genetic hypertension and a model of experimental hypertension were used: spontaneously hypertensive rats (SHR, 16 weeks) and Wistar-Kyoto (WKY) rats infused for 14 days with angiotensin II (Ang II) (200 ng / kg / min, subcutaneous (s.c.) with Alzet mini pump). The age-matched untreated WKY rats served as common controls. In the first study (article # 1), the cardiovascular response in SHR was evaluated following intracebroventricular (i.c.v.) and/or intra-VTA injection of an agonist (senktide) and antagonists (SB222200 and R-820) of NK-3R. These responses have also been characterized using selective dopamine antagonists DA-D1R (SCH23390), DA-D2R (raclopride) or non-selective dopamine DA-D2R (haloperidol). Also the VTA has been destroyed by ibotenic acid. The pressor response induced by senktide and the anti-hypertensive response induced by SB222200 or R-820 were more pronounced by intra-VTA. These responses were prevented by pre-treatment with raclopride and haloperidol. The lesion of the VTA has prevented the pressor response relayed by senktide (i.c.v.) and the anti-hypertensive effect of R-820 (i.c.v.). In addition, SB222200 (intra-VTA) prevented the pressor response of senktide (i.c.v.) and conversely, senktide (i.c.v.) prevented the antihypertensive effect of SB222200 (intra-VTA). The second study (article # 2) showed that the B1R antagonist (SSR240612) administered by gavage or i.c.v. reverses hypertension in both models. This anti-hypertensive effect was prevented by raclopride and haloperidol. In contrast, the two B1R antagonists (R-715 and R-954) injected s.c., which do not cross the blood-brain barrier reduced weakly blood pressure in hypertensive rats. In the third study (article # 3), the i.c.v. injection of a selective kinin B1R agonist Sar[DPhe8][des-Arg9]BK caused behavioural responses in SHR and Ang II-treated rats and had no effect in control WKY rats . The responses elicited by B1R agonist were blocked by an antagonist of NK-1 (RP67580), an antagonist of NMDA glutamate receptor (DL-AP5), an inhibitor of nitric oxide synthase (NOS) (L -NNA) as well as raclopride and SCH23390.The responses were modestly affected by the inhibitor of inducible NOS (iNOS). The B1R mRNA (measured by RT-PCR) was significantly increased in the hypothalamus, the VTA and the nucleus accumbens of hypertensive animals (SHR and treated with Ang II) compared with control rats. These neuropharmacological studies suggest that: (1) the NK-3R from the VTA is involved in the maintenance of hypertension in SHR by increasing DA transmission in the midbrain; (2) the B1R in SHR and Ang II-treated rats contributes to hypertension via a central mechanism involving DA-D2R; (3) the central B1R increases locomotor activity and nocifensive behaviours via the release of substance P (NK-1), DA and nitric oxide in both rat models of hypertension. Thus, the brain tachykinin NK-3R and kinin B1R represent potential therapeutic targets for the treatment of hypertension. The modulation of the mesolimbic/mesocortical dopaminergic pathway by these receptors suggests their involvement in other physiological functions (pleasure, motor activity, coordination of the response to stress) and pathophysiology (anxiety, depression).

Troubles du rythme cardiaque dans les modèles murins transgéniques

Thèse en cotutelle avec Université de Nantes - Pays de La Loire - France (2005-2010)