Das Forschungsprojekt bezieht sich auf die Einführung eines Behandlungspfades (BHP) im Bereich der Urologie in einem großen Krankenhaus im Nordwesten von Deutschland. Untersucht wird, welche Auswirkungen die Einführung eines BHP auf die Zufriedenheit der Patienten mit benigner Prostatahyperplasie und die Mitarbeiter des Krankenhauses hat. Dabei werden die klinischen Abläufe im Bereich der Diagnostik und Therapie genau beschrieben. Die Erarbeitung erfolgt durch eine innerbetriebliche Arbeitsgruppe. Der BHP stellt damit eine systematische und strukturierte Steuerung des Behandlungsprozesses dar. Zielsetzung ist dabei die Verringerung der Verweildauer (VwD), Erhöhung der Wirtschaftlichkeit und Verbesserung der Behandlungsqualität. Damit ist der BHP ein geeignetes Instrument, um die Prozesse im Krankenhaus hinsichtlich dieser Aspekte zu optimieren, ohne dass die Mitarbeiter- und Patientenzufriedenheit darunter leidet. Viele Kliniken in Deutschland stehen durch finanziell schwierige Rahmenbedingun-gen unter wirtschaftlichem Druck. Die Einführung eines BHP sollte die Zufrieden-heit der Patienten und der Mitarbeiter nicht außer Acht lassen. Daher muss seine Erarbeitung in einem Krankenhaus auch die Zufriedenheit dieser beiden Gruppen berücksichtigen. Zur Verringerung der VwD soll auch eine verstärkte ambulante Behandlung vor und nach der Versorgung des Patienten auf der Krankenhausstation durch die ambulant tätigen Ärzte im Rahmen einer sektorenübergreifenden Versor-gung durchgeführt werden. Bei der Realisierung wird in Abstimmung mit den nie-dergelassenen Urologen dann aus Gründen der bestehenden Budgettrennung zwi-schen ambulanter und stationären Medizin vereinbart, dass die ambulante Behand-lung im Krankenhaus durch die Krankenhausärzte erbracht wird (vor- und nachstationäre Behandlung). Da gleichzeitig Patienten mit einer anderen urologischen Erkrankung, der malignen Prostatahyperplasie auf denselben Krankenhausstationen behandelt wurden, dienen diese Patienten als zweite Kontrollgruppe (KG). Bei ihnen wird der BHP nicht eingeführt. Es handelt sich um einen Prä-Post-Vergleich vor und nach Einführung des BHP mit einer zweiten KG. Die Mitarbeitergruppen sind bei der Befragung vor und nach der Einführung des BHP identisch. Zum Einsatz kommen zwei standardisierte, z. T. international eingesetzte Fragebogen, die sich mit dem Betriebsklima, der innerbetrieblichen Organisation und der psychosozialen Belastung am Arbeitsplatz beschäftigten. Ein weiterer Fragebogen wird neu entwickelt, um auch Kategorien zu erfassen, die bei der Einführung des BHP tangiert werden. Die Ergebnisse der Patienten- und Mitarbeiterzufriedenheit zeigen in fast allen Seg-menten keine signifikanten Veränderungen nach Einführung des BHP. Eine Verbes-serung der Zufriedenheit der Mitarbeiter kann daher zwar nicht festgestellt werden, aber auch keine Verschlechterung. Insgesamt ist bei der Befragung der Mitarbeiter festzustellen, dass die Belastung bei ihrer Tätigkeit im Krankenhaus sehr hoch ist. Die Patienten werden in zwei Kohorten getrennt befragt: Zum einen handelt es sich hierbei um Patienten mit der Erkrankung der benignen Prostatahyperplasie, bei der in der Postphase der BHP eingeführt wird, und zum anderen um Patienten mit maligner Prostatahyperplasie, die als zweite KG dienen. Die Fragen beziehen sich auf die Behandlung durch die Ärzte, die erlebte Qualität, die Bewertung der Abläufe, der ärztlichen Visiten, der pflegerischen Betreuung so-wie der Information über Organisation und Behandlungsergebnisse. Nach Einfüh-rung des BHP steigt die Zufriedenheit der Patienten mit benigner Prostatahyperplasie an. Es ist deutlich zu erkennen, dass die Patienten durch die Verbesserung der Prozesse profitieren. In der KG zeigt sich ein geringer „Spill-over-Effekt“ mit entsprechend positiver Tendenz. Die Hypothese, dass die Einführung des BHP die allgemeine Zufriedenheit der Patienten signifikant verbessert, wird nicht bestätigt. Dennoch sind bei einzelnen Items signifikant positive Effekte zu erkennen. Deskriptiv ist die Zufriedenheit der Patienten verbessert worden. Auch die Wirtschaftlichkeit kann durch Einführung des BHP verbessert werden. Die Finanzierung der deutschen Krankenhäuser erfolgt durch Fallpauschalen (German Diagnosis Related Groups, G-DRG). Von einer unteren Grenzverweildauer (u-GVwD) bis zu einer oberen Grenzverweildauer (o-GVwD) bleibt die Höhe der Pau-schale konstant. Kann nun die VwD abgesenkt werden, verringern sich mind. die variablen Kosten. Die VwD bei Patienten mit benigner Prostatahyperplasie liegt vor Einführung des BHP im Durchschnitt bei 8,71 Tagen. Nach Einführung sinkt sie auf durchschnittlich 6,5 Tage. Die Veränderung beträgt daher mehr als 26 %. Der Erlös pro Tag steigt von rund 360 € auf rund 457 € an. Die VwD in der KG verändert sich nur geringfügig.

Les progrès dans la compréhension de la biologie osseuse ont permis d’identifier le rôle du système nerveux sensoriel dans la formation osseuse, le remodelage et la régénération tissulaire. Cependant, le rôle précis du système nerveux sensoriel sur la l’ostéogénèse reste encore méconnu. La première partie de ce travail a été d’analyser le rôle des neurones du ganglion de la racine dorsale (DRG) sur la différenciation ostéoblastique des cellules souches mésenchymateuse (MSCs). Pour répondre à cette question, nous avons utilisé une plate-forme microfluidique, qui tente de mimer l’innervation sensorielle du tissu osseux. Dans la seconde partie de cette étude, nous avons cherché à mieux caractériser la sous-population de neurones DRG impliqués dans la régulation directe de la différenciation des MSCs vers le lignage ostéoblastique. En conclusion, l’ensemble des résultats permettent de montrer que: i) les neurones sensoriels ont un effet positif et direct sur la différenciation ostéoblastique des cellules ostéoprogénitrices, ii) la voie de signalisation Wnt/β-caténine est impliquée dans cette transduction du signal; iii) cet effet est principalement régulé par des neurones sensorimoteur, iv) qui peuvent induire la libération locale de facteurs neuroactifs. / Advances in the understanding of bone biology have identified the sensory nervous system as a critical regulator in the orchestration of bone formation, remodeling, and repair. However, the precise role of the sensory nervous system on bone tissue, particularly on osteoprogenitor cells, remains unknown. Firstly, we were interested in clarifying whether dorsal root ganglion (DRG) neurons would be able to induce the osteoblast differentiation by acting directly on mesenchymal stem cells (MSCs). Afterwards, we attempted to understand whether the canonical Wnt signaling pathway could be implicated in the DRG neurons-induced osteoblastogenesis. In the second part of this study, we aimed at better characterizing the subset of DRG neurons involved in the direct regulation of osteoblast differentiation from MSCs. In this work we provide several novel insights: i) we show that sensory neurons have a positive and direct effect on osteoblast differentiation of osteoprogenitor cells, ii) by activating the Wnt/β-catenin signaling pathway; and iii) we suggest that this effect is mainly regulated by sensorimotor neurons, iv) which possibly mediate the local release of neuroactive factors.

Bakgrund och problem: Sedan marknadiseringen av den svenska hälso- och sjukvården har begreppet ersättningsmodeller fått ett ökat utrymme inom välfärdsdebatten. Motivet med marknadiseringen var att öka kostnadseffektiviteten och minska centralstyrningen. Detta innebar att beslut som tidigare fattats på statlig nivå istället hanteras på regional nivå. Regionerna kan därmed självständigt utforma och tillämpa den ersättningsmodellen de anser lämplig. Mer specifikt resulterade detta i att den traditionella anslagsfinansieringen i större utsträckning ersattes av den framväxande DRG-baserade ersättningen. Flertalet studier lyfts fram vilka riktar kritik mot incitamenten de olika ersättningsmodellerna ger upphov till och hur dessa kan anses vara motsägelsefulla mot hälso- och sjukvårdens olika intressenter. Detta resulterade i att flertalet regioner valde att överge den DRG-baserade ersättningsmodellen. Den institutionella teorin förklarar att såväl intressenterna som omgivningen utsätter beslutsfattare inom hälso- och sjukvården för olika former av påtryckningar. Till följd av detta går det att ifrågasätta att beslut om val av ersättningsmodell kan förklaras vara rationellt.  Syfte: Syftet med denna studie är att undersöka hur beslutsfattare, inom hälso- och sjukvården, i regionerna Västmanland, Halland och Jönköpings län upplever och påverkas av påtryckningar vid val av ersättningsmodell.  Metod: Denna studie är komparativ och av kvalitativ art, vilket gör den till en flerfallsstudie. Det empiriska materialet har samlats in via semistrukturerade intervjuer och analyserats med hjälp av den institutionella teorin.  Slutsats: Analysen visar på hur väl den institutionella teorin lyckas fånga och förklara hur beslutsfattandet, vid val av ersättningsmodell, utsätts för påtryckningar härrörande från de institutionella begreppen legitimitet, löskoppling och isomorfism. Utifrån analysen hävdar vi att dessa påtryckningar medför att beslutsfattandet inte kan förklaras vara rationellt. / Background and problem: Since the marketization of Swedish health care the concept of payment systems have gained further attention in the welfare debate. The motive behind the marketization was to increase cost-efficiency and reduce central regulation. This resulted in a transition where decisions traditionally made on state level were instead handled on regional level. The regions can thus decide independently on the structure and choice of payment systems they consider appropriate. More specifically this resulted to a greater extent in a transition from the traditional payment system being replaced by the emergent DRG-based payment system. Several highlighted studies direct their criticism towards the incentives associated with the different payment systems and how these can be perceived contradictory to the different health care stakeholders. This resulted in most of the regions discarding the DRG-based payment system. The institutional theory explains that both the stakeholders and the environment expose decision-makers in the health care sector to various forms of pressure. As a result it can be questioned whether decisions on the choice of payment system can be explained as rational.     Purpose: The purpose of this study is to investigate how decision-makers in health care, in the regions of Västmanland, Halland and Jönköping County, are experiencing and affected by pressures in the choice of payment system.   Method: This study is comparative and of a qualitative nature, which makes it a multiple-case study. The empirical material has been collected via semi-structured interviews and analyzed using institutional theory. Conclusion: The analysis shows how well the institutional theory manages to capture and explain how decision-making, when choosing a payment system, is exposed to pressure derived from the institutional concepts of legitimacy, detachment and isomorphism. Based on the analysis, we claim that these pressures mean that decision-making cannot be explained as rational.

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Made available in DSpace on 2015-05-14T13:00:16Z (GMT). No. of bitstreams: 1 parte1.pdf: 4104748 bytes, checksum: 578975146349baff07079d6c3f9756b6 (MD5) Previous issue date: 2008-08-29 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Snake venoms contain a complex arsenal of protein bio-active components, many of these being neurotoxins (NTXs). These snakes have high neurotoxic activity venom, corresponding to the Elapidae family, which includes coral snakes (Micrurus) whose venom contains circa 90-95% of low molecular mass protein components. Among these, several are postsynaptic neurotoxins or α- NTXs (MM = 6-9 kDa). The Micrurus ibiboboca (Merren, 1820) is a snake of the Elapidae family witch is quite common in the Northeast of Brazil. In spite of the great diversity of species of Micrurus, scarce works involving the nervous system with isolated and pure toxins of those serpents has been developed in level biochemical, pharmacological and electrophysiological. The aim of this study was to purify the toxin Mic6c7NTX of the Micrurus ibiboboca venom, characterize to biochemically and electrophysiologically the toxin Mic6c7NTX in the peripheral nervous system (PNS) of rats, evaluating alterations in the record of the Compound Action Potential (CAP) of the isolate nerve and the toxin activity on the voltage-dependent sodium channels (Nav) in the neurons of the dorsal root ganglion (DRG). The venom was extracted from the Micrurus ibiboboca collected in Paraiba State (Brazil). Initially, electrophysiological tests (current clamp method) using the single sucrose gap technique were accomplished with crude venom (100μg/mL). It was observed that in this concentration the crude venom caused reduction in the CAP amplitude (25%). This neurotoxity led into an intriguing question: what components of the venom would promote to reduction in the excitability of the nerve? Based upon this question, I decided to purify the venom throughout the Liquid Chromatography of the High Performance (HPLC) of the Cation Exchange Chromatography (CIEX) and the Reverse Phase Chromatography (RPC). The molecular mass (MM) of the raw toxin was determined by mass-spectrometry (MALDI-QTOF/ MS) and N-terminal sequence by means of Edman s Degradation. The search for similarity with other toxins was accomplished against proteomic data bank. The CIEX profile showed 19 fractions and the highest peak fraction was used for the second dimension. The toxin Mic6c7NTX obtained by RPC showed elution in 26.7%of the acetonitrile (ACN) and MM 7.047.56Da. The obtained partial N-terminal sequence showed 31 aminoacid residues. The search for similarity of structure and function showed great similarity (65%) with other short chain α-NTXs Australian elapids snakes. The electrophysiological studies (single sucrose gap technique) showed that the toxin Mic6c7NTX (1 μM) reduced the excitability of the isolate nerve similarly to the reduction observed in the crude venom about 21%. Other CAP parameters such as despolarization speed (DSCAP), repolarization time (τCAP) and peak of time (PTCAP) did not show alterations. This suggests that the toxin may be affecting the Nav channels. For the confirmation of that hypothesis experiments were accomplished with whole cell patch-clamp technique in DRG neurons. This results showed that the toxin Mic6c7NTX (1 WM) abolished completely the current of Nav channels sensitive the tetrodotoxin (TTX-S). Also the Nav channels TTX resistant (TTX-R) were investigated in the presence of the Mic6c7NTX toxin previously using TTX (100 nM). This results showed that the toxin Mic6c7NTX (100 nM) abolished completely the current of Nav channels TTX-R and IC50 = 30nM. However, reversion of this blocking was not observed. The present study biochemically and electrophysiologically characterized an α-NTX of the Micrurus ibiboboca elapid snake. Furthermore, it showed a potent toxin with affinity Nav channels TTX-S and TTX-R of the PNS. This is the first α-NTX isolated and identified of the venom from the Micrurus ibiboboca (Merrem, 1820) snake. / As serpentes da família Elapidae possuem uma peçonha com alta atividade neurotóxica e capacidade de letalidade. Fazem parte dessa família as serpentes corais americanas (gênero Micrurus) com suas peçonhas contendo cerca de 90-95% de componentes protéicos, sendo na sua maior parte neurotoxinas com baixa massa molecular (6-8 kDa), podendo ser destacadas as neurotoxinas com ação pós-sinápticas ou α-Neurotoxinas (α-NTX). A Micrurus ibiboboca (Merrem, 1820) é uma serpente da família Elapidae, comum na região Nordeste. Apesar da grande diversidade de espécies do gênero Micrurus sp., escassos trabalhos envolvendo atividade de toxinas isoladas e puras destas peçonhas e sistema nervoso têm sido desenvolvidos em nível bioquímico, farmacológico ou eletrofisiológico. O objetivo desse estudo foi purificar a toxina Mic6c7NTX da peçonha de M. ibiboboca, caracterizar bioquímicamente e investigar com ferramentas eletrofisiológicas a ação da toxina no Sistema Nervoso Periférico (SNP) de ratos avaliando alterações no Potencial de Ação Composto (PAC) do nervo isquiático isolado e a atividade da toxina nos canais para sódio dependentes de voltagem (Nav) em neurônios do gânglio da raiz dorsal (DRG). A peçonha da M. ibiboboca foi extraída de serpentes coletadas no Estado da Paraíba (Brasil). Inicialmente, ensaios eletrofisiológicos com o método de current clamp utilizando a técnica de single sucrose gap foram realizados com a peçonha bruta (100 Wg/mL). Os resultados mostraram que a peçonha bruta nessa concentração promoveu redução na amplitude do PAC (25%). Esse efeito da toxina na excitabilidade do nervo levantou o questionamento: Que componentes da peçonha estariam causando essa diminuição da excitabilidade? A peçonha foi purificada por meio de Cromatografia Líquida de Alta Performance (HPLC), de troca catiônica (CIEX) e fase reversa (RPC). Na sequência, os picos da CIEX foram submetidos à RPC e posteriormente analisados por espectrometria de massas (MALDI-TOF/MS) que detectou a massa molecular da toxina Mic6c7NTX de 7.047,56 Da. Em seguida, foi determinado o seu N-terminal por Degradação de Edman que apresentou 31 resíduos de aminoácidos e serviu de estudo para a bioinformática na busca por similaridade em banco de dados proteômicos com outras toxinas protéicas, demonstrando que a toxina Mic6c7NTX apresentou similaridade (65%) com α-NTXs de cadeia curta de serpentes elapídicas australianas. Posteriormente, foi investigado o efeito da toxina isolada no SNP. Os estudos eletrofisiológicos em single sucrose gap demonstraram que a toxina Mic6c7NTX (1 WM) reduziu a excitabilidade do nervo isolado de forma similar à observada pela peçonha bruta. Não foram observadas alterações significantes em outros parâmetros do PAC, como velocidade de despolarização (VDPAC), tempo de repolarização (τPAC) e tempo de pico (PTPAC), sugerindo que a toxina atuasse num sítio de ligação específico dos [Escreva uma citação do documento ou o 11 canais Nav no SNP. Para a confirmação dessa hipótese foram realizados experimentos de voltage clamp com a técnica de whole cell patch-clamp em cultura primária de neurônios DRG da medula espinhal de ratos. Os resultados mostraram que a toxina Mic6c7NTX (1 WM) aboliu completamente as correntes dos canais Nav sensíveis à tetrodotoxina (TTX-S). Também foi investigado o efeito da toxina sobre a população de canais Nav resistentes à TTX (TTX-R), utilizando previamente TTX (100 nM) para bloquear os canais Nav TTX-S. Os registros com a toxina Mic6c7NTX (100 nM) demonstraram um bloqueio total da corrente nos canais Nav TTX-R dos DRGs e uma IC50 da toxina em torno de 30 nM. Também foi observado que essa toxina se liga aos canais Nav de forma lenta e irreversível. O presente estudo caracterizou bioquímica e eletrofisiologicamente uma α-NTX da serpente elapídica Micrurus ibiboboca. Farmacologicamente, trata-se de uma potente toxina com afinidade aos canais Nav TTX-S e TTX-R do SNP. Essa é a primeira α-NTX isolada e caracterizada da peçonha da serpente Micrurus ibiboboca (Merrem, 1820).

Abstract The aim of this dissertation is to analyse the process of change in management accounting in public-sector health care. The change is examined through the implementation of a nationally homogeneous Diagnosis Related Grouping (DRG) system. The DRG system is used to classify health-care diagnoses into groups for service productisation and pricing. The system has been proposed as a solution for cost accounting and budgeting. The practical motivation of the dissertation is to analyse the embedding of change in organisations´ practises. The theoretical motivation of the dissertation is to extend the investigation of change by analysing the process of implementation of a nationally homogeneous system. The research data comprise 39 interviews conducted between 2006 and 2011 with hospital district representatives, the representatives of the company managing the DRG system, the DRG system supplier, and the representatives of the National Institute for Health and Welfare and the Association of Finnish Local and Regional Authorities. In addition to interviews, the data consists of participative observations, telephone inquiries, and newspaper articles. This dissertation consists of four essays that analyse the data through the lens of two theories: the Actor Network (ANT) and Institutional theory (NIS). The results indicate how the use of multiple theories (ANT ja NIS) as a methodology enriches and extends the insight into the change process in management accounting. For instance, the analysis of the homogeneous use of the DRG system, without investigating the practices of actors by making use of the ANT, the results could have been different in this respect. Especially, this dissertation indicates how important it is that actors’ actions are also examined in the processes of change in the implementation of public-sector management accounting systems. The idea for the DRG system was introduced to Finland almost twenty years ago. However, the results indicate that it has spread very slowly. According to earlier research, an institutional environment is considered to exercise pressure on organisations in order to make them adopt new practices that are homogeneous with other institutional practices. There is indirect pressure in decentralised health care in Finland, though its power for change is weak. This dissertation shows how the decentralisation of responsibilities in large-scale institutions, such as the health-care system in Finland, also slows down and decentralises reforms. As institutional power becomes weaker, the power of organisations to promote things seems to grow stronger, however. / Tiivistelmä Tämän väitöskirjatyön tarkoituksena on analysoida johdon laskentatoimen muutosprosessia julkisen sektorin terveydenhoidossa. Muutosta tarkastellaan kansallisesti yhtenäisen diagnoosiperustaisen ryhmittelyjärjestelmän (Diagnosis Related Grouping, DRG) käyttöönottoprosessin kautta. DRG on järjestelmä, jossa luokitellaan terveydenhoidon diagnoosit ryhmiin palvelujen tuotteistusta ja hinnoittelua varten. Järjestelmää on esitetty ratkaisuna kustannuslaskentaan ja budjetointiin. Väitöskirjatyön käytännön motivaationa on analysoida muutoksen asettumista organisaatioiden käytäntöihin. Väitöskirjatyön teoreettisena motivaationa on laajentaa muutostutkimusta tarkastelemalla kansallisesti yhtenäisen järjestelmän käyttöönottoa. Tutkimuksen aineisto koostuu 39 haastattelusta, joita on kerätty vuosien 2006 ja 2011 välillä. Tutkimuksessa on haastateltu sairaanhoitopiirien henkilökuntaa, DRG-järjestelmän hallinnoiman yhtiön edustajia, järjestelmän toimittajaa, Terveyden ja hyvinvoinnin laitoksen sekä Kuntaliiton edustajia. Aineisto sisältää haastattelujen lisäksi osallistuvaa havainnointia, puhelinkyselyjä sekä lehtiartikkeleita. Tämä väitöskirjatyö koostuu neljästä esseestä, joissa analysoidaan aineistoa kahden eri teorian, toimijaverkostoteorian (ANT) ja institutionaalisen teorian (NIS), avulla. Tulokset tuovat esille, kuinka kahden teorian (ANT ja NIS) metodologinen käyttö rikastuttaa ja laajentaa näkemystä johdon laskentatoimen muutosprosessista. Esimerkiksi analysoitaessa DRG-järjestelmän yhtenäistä käyttöä tutkimatta toimijoiden toimintaa toimijaverkostoteoriaa hyödyntäen, tulokset voisivat tältä osin olla erilaiset. Erityisesti tämä väitöskirjatyö osoittaa, kuinka tärkeää julkisen sektorin johdon laskentajärjestelmien käyttöönoton muutosprosessia tutkittaessa on tutkia myös toimijoiden toimintaa. Idea DRG-järjestelmästä esitettiin Suomessa melkein kaksikymmentä vuotta sitten. Tulokset osoittavat kuitenkin, että sen leviäminen on ollut hyvin hidasta. Aikaisempien tutkimusten mukaan institutionaalisen ympäristön katsotaan painostavan organisaatioita, jotta ne ottaisivat käyttöön uusia menetelmiä, jotka ovat yhdenmukaiset muiden institutionaalisten käytänteiden kanssa. Suomen hajautetussa terveydenhoidossa esitetään epäsuoraa painetta, mutta sen voima muutokseen ei ole vahva. Väitöskirjatyö tuo esille miten suurien instituutioiden, kuten Suomen terveydenhoidon, vastuun hajautuessa myös reformit hidastuvat ja hajautuvat. Institutionaalisten voimien heikentyessä organisaatioiden voima ajaa asioita näyttää kuitenkin vahvistuvan.

The main goal of this Master's Thesis is to form marketing recommendations for maternity hospitals. These marketing recommendations are in the form of marketing mixes, that are designed for individual revealed segments. The theoretical part of my Master's Thesis contains the reason why the maternity hospitals should implement marketing in the present day. Further goal of the theoretical part is to explain why I apply to the area of obstetrics the marketing of services. Further the theoretical part describes specifics of marketing of services, segmentation process, targeting and positioning. There is stated characteristics of the marketing mix in the area of services at the end of the theoretical part. The analytical part is based on written questionnaires inquiry. On the basis of results of questionnaires inquiry is carried out the process of segmentation using statistical programme IBM SPSS Statistics version 21.0. The result of segmentation process is discovering three market segments. These segments show similar characteristics. There is determined attractiveness of revealed segments in the chapter dealing with targeting. Marketing recommendations describe the value of providing services. Marketing recommendations are supplemented with social status of respondents.

<p>Apoptosis is a genetically regulated cell death program, which shows distinct morphological characteristics. It takes place during neuronal development and in some neurodegenerative diseases. During apoptosis, the intracellular proteins are degraded by various caspases, cysteine aspartases, which are regulated by pro- and anti-apoptotic signals. This thesis elucidates the role of anti-apoptotic proteins in nerve cell survival and neurodegeneration. Studies have focused on Bcl-2 family members and Inhibitor of Apoptosis Proteins (IAP).</p><p>XIAP and RIAP-2 are IAP proteins, which are expressed by neurons in the central nervous system. Kainic acid, a glutamate receptor agonist that induces seizures, increased XIAP immunoreactivity in rat hippocampus, whereas RIAP-2 expression in the same time decreased in degenerating neurons. Both XIAP and RIAP-2 were absent in dying neurons indicating that these proteins have a protective role in kainic acid induced neurodegeneration.</p><p>NAIP, another IAP family member, was shown to interact with the calcium binding protein Hippocalcin using the yeast two-hybrid system and immunoprecipitation experiments. Hippocalcin-NAIP interaction increased motoneuron survival in caspase-3 independent and dependent manners.</p><p>The anti-apoptotic Bcl-2 proteins, Bcl-2 and Bcl-x, were studied using cultured neurons and human neuronal progenitor cells. In the progenitor cells, Bcl-2 overexpression enhanced cell survival and induced downregulation of Caspase-2 (ICH-1) and caspase-3 (YAMA/CPP32). These results suggest a novel mechanism for the action of Bcl-2.</p><p>Estrogen was shown to inhibit death of cultured dorsal root ganglion neurons (DRG) after nerve growth factor withdrawal. The hormone increased the levels of Bcl-x, which may explain the known neuroprotective function of estrogen.</p>