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  • Taponen, Suvi (Helsingin yliopisto, 2008)
    Bovine mastitis caused by coagulase-negative staphylococci Mastitis is the most common disease affecting dairy cows, and staphylococci are the most common cause of mastitis. According to Finnish studies, staphylococci are isolated from 36% of clinical and 60% of subclinical mastitis cases. In mastitis diagnostics, staphylococci are divided into coagulase-positive and coagulase-negative based on their ability to coagulate plasma. Majority of staphylococcal mastitis is caused by coagulase-negative staphylococci (CNS). In mastitis diagnostics they are not identified at species level but are treated as a uniform group. Usually they cause subclinical or mildly clinical mastitis, and are considered as harmless bacteria of the normal skin flora. CNS mastitis is most common on the first lactation. It is assumed to cure spontaneously and antimicrobial treatment is not recommended. Although usually subclinical or mildly clinical, CNS mastitis causes increase of milk leucocytes and may decrease the milk quality. CNS mastitis seems to be especially a problem in well managed dairy herds with good udder health. In contrast to the usual assumption that CNS mastitis cures spontaneously, it may persist in the udder throughout the entire lactation. In addition, the CNS species are not necessarily a uniform group but differences between the species in virulence and clinical characteristics may exist. In this dissertation, different aspects of bovine mastitis caused by CNS were studied. The response of CNS mastitis to antimicrobial treatment was investigated, as well as the persistence of CNS intramammary infection when left without antimicrobial treatment. The prevalence of different CNS species in mastitis and on cows skin, and possible differences in clinical characteristics and persistence between CNS species were studied. Species identification was performed based on bacterial phenotype and genotype. Identification using different methods was compared. Majority of CNS mastitis was caused by S. chromogenes or S. simulans. Many other CNS species were isolated from mastitis sporadically. Molecular genetic identification methods based on bacterial genotype proved more reliable than biochemical methods based on bacterial phenotype. In some cases the identification results of genotypic and phenotypic methods disagreed. About half of CNS mastitis detected during lactation persisted without antimicrobial treatment, commonly until the end of lactation. Mastitis caused by penicillin-susceptible CNS cured well, about 90% cured. Of mastitis caused by penicillin-resistant CNS, 60 to 70% cured, although the causing bacteria were susceptible to the antimicrobial used. Most often CNS mastitis was subclinical or mildly clinical. Statistically significant differences in clinical characteristics or persistence between the two most common CNS species were not detected.
  • Simojoki, Heli (Helsingin yliopisto, 2011)
    Coagulase-negative staphylococci (CNS) are the most common bacteria isolated in bovine subclinical mastitis in many countries, and also a frequent cause of clinical mastitis. The most common species isolated are Staphylococcus (S) chromogenes, S. simulans, S. epidermidis, and S. xylosus. One half of the intramammary infections (IMI) caused by CNS persist in the udder. The pathogenesis of IMI caused by CNS is poorly understood. This dissertation focuses on host response in experimental intramammary infection induced by S. chromogenes, S. epidermidis and S. simulans. Model for a mild experimental CNS infection was developed with S. chromogenes (study I). All cows were infected and most developed subclinical mastitis. In study II the innate immune response to S. epidermidis and S. simulans IMI was compared in eight cows using a crossover design. A larger dose of bacteria was used to induce clinical mastitis. All cows became infected and showed mild to moderate clinical signs of mastitis. S. simulans caused a slightly stronger innate immune response than S. epidermidis, with significantly higher concentrations of the interleukins IL-1beta and IL-8 in the milk. The spontaneous elimination rate of the 16 IMIs was 31%, with no difference between species. No significant differences were recorded between infections eliminated spontaneously or remaining persistent, although the response was stronger in IMIs eliminated spontaneously, except the concentration of TNF-α, which remained elevated in persistent infections. Lactoferrin (Lf) is a component of the humoral defence of the host and is present at low concentrations in the milk. The concentration of Lf in milk is high during the dry period, in colostrum, and in mastitic milk. The effect of an inherent, high concentration of Lf in the milk on experimental IMI induced with S. chromogenes was studied in transgenic cows that expressed recombinant human Lf in their milk. Human Lf did not prevent S. chromogenes IMI, but the host response was milder in transgenic cows than in normal cows, and the former eliminated infection faster. Biofilm production has been suggested to promote persistence of IMI. Phenotypic biofilm formation and slime producing ability of CNS isolates from bovine mastitis was investigated in vitro. One-third of mastitis isolates produced biofilm. Slime production was less frequent for isolates of the most common mastitis causing species S. chromogenes and S. simulans compared with S. epidermidis. No association was found between the phenotypic ability to form biofilm and the persistence of IMI or severity of mastitis. Slime production was associated with persistent infections, but only 8% of isolates produced slime.
  • Suojala, Leena (Helsingin yliopisto, 2010)
    Bovine mastitis caused by Escherichia coli remains a problem in many countries despite of improvements in managing and housing of dairy cattle. Cows with compromised immune systems, especially those in early lactation, are particularly susceptible to E. coli intramammary infection. Mastitis caused by E. coli varies from mild, with local signs only, to severe systemic. The severe form of E. coli mastitis is associated with loss of milk production and can result in death of the cow. Intramammary infection caused by E. coli is often eliminated spontaneously as the defense mechanisms of the cow are able to clear the bacteria from the udder. The aims of this thesis were to investigate host response to E. coli mastitis in terms of characteristics of bacteria, effect of antimicrobial and non-antimicrobial treatment, and prophylactic effect of recombinant human lactoferrin expressed in milk. Host response was studied using two consecutive intramammary challenges with E. coli in the same cows at a short interval. All cows became infected, but local signs were significantly milder and disappeared faster after the second challenge. The same pattern was recorded for the indicators of inflammation; the differences being statistically significant for serum and milk haptoglobin, milk serum amyloid A, and white blood cell count. Milk production returned to the pre-challenge level significantly faster after the second challenge. This study revealed a possible carry-over or immunizing effect of the previous intramammary infection by the same pathogen. Broad-spectrum antimicrobials have been widely used for treating E. coli mastitis, although the results of treatment studies have been controversial. In our field study, systemic enrofloxacin treatment did not result in better bacteriological or clinical cure of acute clinical mastitis caused by E. coli than supportive treatment alone. Enrofloxacin treatment did not affect survival of the cows, return of quarter milk production or tissue damage of the affected quarter within three weeks post-treatment; nor did it affect the length of time the cow remained in the herd during the six-month follow-up period. The only positive effect of the enrofloxacin treatment was a higher bacteriological cure 2 days post-treatment. On the contrary, clinical cure on day 2 was lower in the enrofloxacin treated cows. Clinical cure assessed 21 days post-treatment was relatively low in both groups, which probably reflects the severe nature of acute E. coli mastitis. Our study did not support the use of parenteral antimicrobial treatment of clinical E. coli mastitis. In severe cases of coliform mastitis, antimicrobial treatment could, however, still be recommended for safety reasons, as it can increase the elimination of bacteria and prevent possible bacteraemia. Our results indicated also that frequent milking at the acute stage of mastitis might improve the initial clinical cure of E. coli mastitis and decrease inflammation and tissue damage in the infected quarter. Most E. coli isolates belonged to the phylogenetic group A, indicating their commensal nature. Close to 40% of the isolates had at least one virulence gene, but combinations of virulence genes varied greatly, each combination being present mainly in a single isolate. Approximately 30% of the isolates showed resistance to one or more antimicrobials tested, most commonly against ampicillin, streptomycin, tetracycline and sulphonamides. No specific virulence factor, phylogenetic group or resistance to antimicrobials was associated with persistence or severity of disease among mastitis E. coli isolates in our field study. These results indicate that characteristics of bacteria are not likely to affect the clinical course and outcome of E. coli mastitis. In 11% of mastitis cases, the same genotype of E. coli was isolated from the affected quarter three weeks post-treatment as originally, indicating persistence of the same genotype of E. coli in the quarter. Non-antimicrobial treatments, such as lactoferrin, which has antibacterial and lipopolysaccharide neutralizing properties, could be beneficial in the treatment of E. coli mastitis. The efficacy of intramammary lactoferrin was compared with that of systemic enrofloxacin in an experimentally induced E. coli model. No significant differences were found in the clinical signs between cows treated with lactoferrin and those treated with enrofloxacin. The results from this study remained inconclusive. The prophylactic effect of lactoferrin against E. coli mastitis was studied in a new model of using hLf-transgenic cows, which expressed recombinant human lactoferrin in their milk. This was the first study to describe an experimentally induced E. coli mastitis model using transgenic cows. The high concentration of lactoferrin in the milk of the transgenic cows did not protect the cows from E. coli intramammary infection, and all of them became infected. No differences were noted in the bacterial growth, times to bacterial elimination, local signs or in any of the milk or blood inflammatory parameters, except in concentrations of haptoglobin and cortisol in the serum. However, systemic signs were significantly milder in transgenic cows. Prevention of E. coli mastitis relies on decreasing the infection pressure in the environment of the cows and improving the cow comfort and herd management. In E. coli mastitis, the treatment should be as efficient as possible, but novel therapeutic approaches are needed, as the efficacy of the current commonly used antimicrobial treatments is not satisfactory.
  • Ollikainen, Pia (Helsingin yliopisto, 2013)
    Bovine milk is a rich source of nutrients, such as protein, fat, carbohydrate, minerals and vitamins. In addition to the major protein components of casein and whey proteins, milk has low concentrations of compounds with bioactivity, growth factors and insulin. Insulin-like growth factor I (IGF-I) and transforming growth factor-β2 (TGF-β2) are the most studied because of their various growth-promoting activities and the possibility to use them as bioactive supplements in foodstuffs. In the present work heat-stability and separation of IGF-I, TGF-β2 and insulin were studied using ELISA immunoassay. Milk from a dairy farm was heat-treated at 65, 72, 90 or 135⁰C for 15 s using an indirect pilot heating processor. Both IGF-I and TGF-β2 showed good heat stability up to 90⁰C, but at 135⁰C both growth factors had lost most of their immunochemical activity. Heating also activated the latent forms of IGF-I and TGF-β2 to immunoreactive form, which was possible to analyse without any separate pre-treatment. Heat-activation of TGF-β2 was temperature-dependent and at 90⁰C all the TGF-β2 concentration was activated by heat. IGF-I was less sensitive, but at 90⁰C it showed a sharp increase in immunoreactivity. Heating as a pre-treatment method was introduced as a new method to analyse and compare IGF-I concentrations in samples with no or low whey protein concentrations. When heat-treated milks were separated to casein and whey fractions by acid, ultracentrifugation or membrane filtration, the heat-activated immunoreactive form of the growth factor followed the casein fraction and the latent form remained in whey. Bovine insulin was heat stable during pasteurization at 65 and 72⁰C, but lost some of its immunochemical activity at higher temperatures. During membrane filtration a higher share of insulin was concentrated in MF retentate than in UF retentate when compared to IGF-I. An in vitro digestion experiment was performed in order to compare the digestibility of the latent and active forms of TGF-β2. In the adult model TGF-β2 was hydrolysed in gastric phase, but in the infant model a small share of TGF-β2 survived the gastric and duodenal phases. There was no difference in survival or digestibility between the latent or active forms of the growth factor. The digestibility of IGF-I was tested in the infant model and this growth factor was hydrolysed during duodenal phase. The results obtained in this study have great importance when separating and concentrating the growth factors from milk or colostrum. If the separation and concentration is performed from whey, these results show that the heating history of milk has a great effect on the yields. The results also demonstrate that heating as a pre-treatment method and membrane filtration can be used to lead growth factors to different fractions, depending on the intended usage.
  • Markkanen, Jani (2012)
    B-puut ovat yleisesti käytettyjä hakemistopuita. Tutkielmassa tutustutaan B-puiden samanaikaisuudenhallintaan ja elvytykseen erityisesti tietokannanhallintajärjestelmän kannalta. Tehokkaan samanaikaisuudenhallinnan tarjoavan Blink-puun algoritmeista esitellään solmujen poistojen seurantaan ja läpikäydessä rakennemuutoksien viimeistelyyn perustuvat algoritmit. Näistä jälkimmäinen toteutetaan ja sen tehokkuutta arvioidaan kokeellisesti. Kokeellisessa arvioinnissa huomataan, että lisäys- ja poisto-operaatioissa samanaikaisuudenhallinnan kustannus nousee jopa 94 %:iin arvioinnin maksimioperaatiotiheydellä. Samalla maksimioperaatiotiheydellä hakuoperaation samanaikaisuudenhallinta vie alle prosentin kokonaisajasta. Korkea samanaikaisuudenhallinnan kustannus lisäys- ja poisto-operaatioissa johtuu päivitysoperaatioiden U-salpaamasta juurisolmusta. Juurisolmun U-salpaus on usein turhan vahva toimenpide, sillä sitä tarvitaan vain 0,06 % päivitysoperaatioita, kun salpa halutaan korottaa kirjoittamista varten X-salvaksi. Puun juuren ruuhkan helpottamiseksi esitellään algoritmille jatkokehitysideoita, jotka perustuvat juuren U-salpauksen tarpeen harvinaisuuteen ja mahdollisuuteen aloittaa puun läpikäynti aina uudelleen puun juuresta.
  • Nojonen, Kati (2013)
    Denna avhandling behandlar frivilliga substitutionsvårsklienters upplevelser på HAL-(Huume Alkoholi Lääkkeet) polikliniken, som är en enhet vid HNS/ HUCS Kvinnoklinik där vård finns tillgänglig för gravida som har missbruksproblem. Kvinnokliniken är främst ett förlossningssjukhus. HAL-polikliniken erbjuder stöd för de gravida som har missbruksproblem. Läkare, sjuksköterskor/barnmorskor samt socialarbetare jobbar på HAL-polikliniken. Klienterna kan söka sig till HAL-polikliniken antingen själva eller komma med remiss från mödrarådgivningen eller en missbrukarvårdsanstalt. På HAL-polikliniken vårdar man de som har drog, alkohol, medicin – eller blandmissbruk och är gravida. Denna undersökning koncentrerade sig på de kvinnor som är i substitutionsvård, det vill säga de kvinnor, som har haft ett opioidberoende och behandlas med buprenorfin. Genom ett livsloppsperspektiv beskriver avhandlingen informanternas upplevelser om livet före graviditeten, under graviditeten, och vad de gravida kvinnorna önskar och vill i framtiden. I denna pro-gradu intervjuas gravida kvinnor (n=7) i substitutionsvård. Avhandlingen har ett fenomenologiskt forskningsangrepp och syftet med avhandlingen är att lyfta fram kvinnornas upplevelser. Ett annat syfte med avhandlingen är att berättelserna ska vara till hjälp för andra i liknande situation och även i utvecklandet av missbrukarvården. Det transkriberade materialet har jag analyserat med innehållsanalys då olika teman lyfts fram. De centrala slutsatserna var att kvinnorna är nöjda med vården de får på HAL-polikliniken och även övrigt samhälleligt stöd. Kvinnorna upplever att det varit deras egna val att söka vård, vilket de ser som det viktigaste stödet för ett drogfritt liv i fortsättningen. Kvinnorna har även upplevt mycket fördomar vilket leder till att de ser substitutionsvården som sin egna hemlighet som de ogärna talar om. Informanterna i avhandlingen påvisade en rädsla för barnets hälsa och attityden till buprenorfinet var paradoxalt. En upplevelse var att substitutionsvården gav stöd till kvinnorna i ett drogfritt liv men samtidigt upplevde de blivande mödrarna en rädsla för barnets eventuella kommande abstinensbesvär. Det som informanterna i avhandlingen upplevde som bristfälligt var stödet till den blivande fadern i familjen. Mödrarna upplevde att enbart mödrarna togs i beaktande, trots att fädrarna också skulle behövt stöd med att få missbrukarvård innan barnet föds. Avhandlingen påvisar att de kvinnor som deltagit i studien varit nöjda med den vård de fått på HAL-polikliniken men att de känner ett personligt ansvar för det, att de börjat ta droger och även att de slutar ta droger. Det går inte att göra större slutsatser utifrån dessa resultat då det grundar sig på sju informanter men det ger en inblick i hur det kan upplevas att vara gravid i substitutionsvård.
  • Kivelev, Juri (Helsingin yliopisto, 2010)
    Cavernomas are rare neurovascular lesions, encountered in up to 10% of patients harboring vascular abnormalities of the CNS. Cavernomas consist of dilated thin-walled sinusoids or caverns covered by a single layer of endothelium. Due to advancements in neuroradiology, the number of cavernoma patients coming to be evaluated in neurosurgical practice is increasing. In the present work, we summarized our results on the treatment of cavernomas. Particular attention was paid to uncommon locations or insufficiently investigated cavernomas, including 1. Intraventricular cavernomas; 2. Multiple cavernomas; 3. Spinal cavernomas; and 4. Temporal lobe cavernomas. After analyzing the patient series with these lesions, we concluded that: 1. IVCs are characterized by a high tendency to cause repetitive hemorrhages in a short period of time after the first event. In most patients, hemorrhages were not life-threatening. Surgery is indicated when re-bleedings are frequent and the mass-effect causes progressive neurological deterioration. Modern microsurgical techniques allow safe removal of the IVC, but surgery on fourth ventricle cavernomas carries increased risk of postoperative cranial nerve deficits. 2. In MC cases, when the cavernoma bleeds or generates drug-resistant epilepsy, microsurgical removal of the symptomatic lesion is beneficial to patients. In our series, surgical removal of the most active cavernoma usually the biggest lesion with signs of recent hemorrhage - was safe and prevented further bleedings. Epilepsy outcome showed the effectiveness of active treatment of MCs. However, due to the remaining cavernomas, epileptogenic activity can persist postoperatively, frequently necessitating long-term use of antiepileptic drugs. 3. Spinal cavernomas can cause severe neurological deterioration due to low tolerance of the spinal cord to mass-effect with progressive myelopathy. When aggravated by extralesional massive hemorrhage, neurological decline is usually acute and requires immediate treatment. Microsurgical removal of a cavernoma is effective and safe, improving neurological deficits. Sensorimotor deficits and pain improved postoperatively at a high rate, whereas bladder dysfunction remained essentially unchanged, causing social discomfort to patients. 4. Microsurgical removal of temporal lobe cavernomas is beneficial for patents suffering from drug-resistant epilepsy. In our series, 69% of patients with this condition became seizure-free postoperatively. Duration of epilepsy did not correlate with seizure prognosis. The most frequent disabling symptom at follow-up was memory disorder, considered to be the result of a complex interplay between chronic epilepsy and possible damage to the temporal lobe during surgery.
  • Vartiainen, Nuutti (Helsingin yliopisto, 2009)
    Acute pain has substantial survival value because of its protective function in the everyday environment. Instead, chronic pain lacks survival and adaptive function, causes great amount of individual suffering, and consumes the resources of the society due to the treatment costs and loss of production. The treatment of chronic pain has remained challenging because of inadequate understanding of mechanisms working at different levels of the nervous system in the development, modulation, and maintenance of chronic pain. Especially in unclear chronic pain conditions the treatment may be suboptimal because it can not be targeted to the underlying mechanisms. Noninvasive neuroimaging techniques have greatly contributed to our understanding of brain activity associated with pain in healthy individuals. Many previous studies, focusing on brain activations to acute experimental pain in healthy individuals, have consistently demonstrated a widely-distributed network of brain regions that participate in the processing of acute pain. The aim of the present thesis was to employ non-invasive brain imaging to better understand the brain mechanisms in patients suffering from chronic pain. In Study I, we used magnetoencephalography (MEG) to measure cortical responses to painful laser stimulation in healthy individuals for optimization of the stimulus parameters for patient studies. In Studies II and III, we monitored with MEG the cortical processing of touch and acute pain in patients with complex regional pain syndrome (CRPS). We found persisting plastic changes in the hand representation area of the primary somatosensory (SI) cortex, suggesting that chronic pain causes cortical reorganization. Responses in the posterior parietal cortex to both tactile and painful laser stimulation were attenuated, which could be associated with neglect-like symptoms of the patients. The primary motor cortex reactivity to acute pain was reduced in patients who had stronger spontaneous pain and weaker grip strength in the painful hand. The tight coupling between spontaneous pain and motor dysfunction supports the idea that motor rehabilitation is important in CRPS. In Studies IV and V we used MEG and functional magnetic resonance imaging (fMRI) to investigate the central processing of touch and acute pain in patients who suffered from recurrent herpes simplex virus infections and from chronic widespread pain in one side of the body. With MEG, we found plastic changes in the SI cortex, suggesting that many different types of chronic pain may be associated with similar cortical reorganization. With fMRI, we found functional and morphological changes in the central pain circuitry, as an indication of central contribution for the pain. These results show that chronic pain is associated with morphological and functional changes in the brain, and that such changes can be measured with functional imaging.
  • Heikkilä, Heini (Helsingin yliopisto, 2010)
    Aim: So far, most of the cognitive neuroscience studies investigating the development of brain activity in childhood have made comparisons between different age groups and ignored the individual stage of cognitive development. Given the wide variation in the rate of cognitive development, this study argues that chronological age alone cannot explain the developmental changes in brain activity. This study demonstrates how Piaget s theory and information on child s individual stage of development can complement the age-related evaluations of brain oscillatory activity. In addition, the relationship between cognitive development and working memory is investigated. Method: A total of 33 children (17 11-year-olds, 16 14-year-olds) participated in this study. The study consisted of behavioural tests and an EEG experiment. Behavioral tests included two Piagetian tasks (the Volume and Density task, the Pendulum task) and Raven s Standard Progressive Matrices task. During EEG experiment, subjects performed a modified version of the Sternberg s memory search paradigm which consisted of an auditorily presented memory set of 4 words and a probe word following these. The EEG data was analyzed using the event-related desynchronization / synchronization (ERD/ERS) method. The Pendulum task was used to assess the cognitive developmental stage of each subject and to form four groups based on age (11- or 14-year-olds) and cognitive developmental stage (concrete or formal operational stage). Group comparisons between these four groups were performed for the EEG data. Results and conclusions: Both age- and cognitive stage-related differences in brain oscillatory activity were found between the four groups. Importantly, age-related changes similar to those reported by previous studies were found also in this study, but these changes were modified by developmental stage. In addition, the results support a strong link between working memory and cognitive development by demonstrating differences in memory task related brain activity and cognitive developmental stages. Based on these findings it is suggested that in the future, comparisons of development of brain activity should not be based only on age but also on the individual cognitive developmental stage.
  • Laaksonen, Kristina (Helsingin yliopisto, 2012)
    Brain plasticity and stroke recovery Recovery from stroke is based on the capability of the brain to reorganize its structure and function after lesion. An acute stroke triggers a cascade of time-dependent metabolic and physiological reactions, which enable changes in the organization and function of widespread cortical regions. A wide range of studies, using various functional imaging methods, have thrown light on the reorganizational changes after stroke. However, less is known about the temporal evolution of these changes and their correlation to clinical recovery. In this thesis, different aspects of neurophysiological changes related to sensorimotor recovery were studied in 18 patients with first-ever stroke in the middle cerebral artery territory, affecting upper limb motor function. Follow-up recordings of somatosensory evoked fields (SEF) and spontaneous rhythmic brain activity were performed with whole-head MEG within 1 week (T0), 1 month (T1), and 3 months (T2) after stroke with concomitant evaluation of clinical outcome. MEG suits stroke studies especially well, as it is independent from hemodynamic alterations, and the signals are practically unaffected by morbid tissue. The results indicated that the hand representation in the primary somatosensory cortex (SI) in the affected hemisphere (AH) was transiently enlarged at T1 and returned to normal size concomitantly with clinical improvement of hand function (Study I). Study II showed that the activation in the contralateral secondary somatosensory cortex (cSII) was decreased in the AH at T0 and increased during follow-up. The strength of cSII activation paralleled the recovery of hand function during the 3 months follow-up, suggesting that cSII may be an important region in mediating the somatosensory input to the motor cortex. The results in Study III indicated that afferent-input-modulated motor cortex excitability was increased in the AH in the acute phase after stroke and decreased during follow-up in association with recovery of hand function. Study IV showed that the ~10-Hz oscillations were enhanced in the AH at T1 and T2. Moreover, pathological perilesional low-frequency oscillations were detected in 7/16 patients at T0, and the low-frequency oscillations persisted for at least 3 months in 4 patients. These 4 patients had a worse clinical outcome at T2 than the rest of the patients. The results indicate that even small lesions can cause widespread neurophysiological changes in the cortical network. Certain brain regions, such as SII, seem to be specifically important for the recovery of hand function. The results underline the importance of parallel recovery of the somatosensory and motor systems for fluent hand function. The most evident neurophysiological changes were observed within 1 month after stroke in parallel with steepest improvement of clinical recovery, suggesting that the first 4 weeks are critical for functional recovery.
  • Rantamäki, Tomi (Helsingin yliopisto, 2006)
    Reduced actions of brain-derived neurotrophic factor (BDNF) are linked to the pathophysiology of depression whereas antidepressants induce BDNF synthesis together with neuroplastic alterations in the brain. Still the molecular mechanisms regulating the effects of antidepressants on BDNF synthesis are largely obscure and it is not well known whether this BDNF induction leads to the signaling of BDNF receptor TrkB in vivo. By using an antibody against autophosphorylated TrkB, we show that pharmacologically diverse antidepressants induce TrkB activity in the rodent anterior cingulate cortex (ACC) and hippocampus (HC). Lithium (Li+), an antimanic and antidepressant-augmenting agent, produces similar changes in TrkB activity in the ACC. ACC and HC are two key brain areas implicated in depression and antidepressant action. Given that clinically used antidepressants and Li+ act in a lag-time manner, it is interesting that the effects of these agents on brain TrkB signaling are observed rapidly after a single drug administration. Antidepressant-regulated TrkB-induction specifically leads to the activation of phospholipase-Cγ1 (PLCγ1) which in turn, and likely in concert with monoaminergic signaling events, induces the phosphorylation of CREB (cAMP related element binding protein). Through the activation of PLCγ1-CREB cascade, antidepressants may regulate synaptic plasticity and the release and synthesis of BDNF itself. Interestingly however, electroconvulsive shock (ECS), among the most potent antidepressant therapy, rapidly reduces TrkB signalling in the rodent prefrontal cortex (PFC) even in situations were endogenous BDNF levels are high. In contrast, ECS induces the ERK (extracellular signal-regulated kinase) neurotrophic pathway in the rodent PFC. The behavioural studies revealed that sustained increase in TrkB signalling is characterized with antidepressant-like behaviour in a rodent model of behavioural despair, the forced swim test (FST). In contrast, basal behaviour of TrkB deficient mice is normal but these mice do not respond to serotonergic antidepressant in the FST. Altogether, the present results provide compelling evidence that chemical antidepressants produce rapid neurotrophic actions through the TrkB-PLCγ1-CREB signaling in the rodent brain and suggest that these changes initiate plastic responses in the neuronal networks implicated in depression.
  • Nevanlinna, Saija (2014)
    Sosiaalisen median hyödyntäminen brandiviestinnässä nähdään kasvavana suuntauksena. Sosiaalisen median käytön yleistyminen on johtanut muutoksiin yritysten liiketoimintaympäristössä. Brandiviestinnän suunnittelun pääpainopiste on siirtynyt perinteisistä markkinointimenetelmistä Internetiin ja sosiaaliseen mediaan. Markkinointiviestiväylän tai -väylien valinnasta on samalla tullut yksi merkittävimmistä yritysten brandiviestintästrategiaa koskevista päätöksistä. Tutkimuksen tavoitteena on selvittää, miten kuluttajat suhtautuvat brandiviestintään ruokablogeissa. Tutkimuksessa tarkastellaan ruokablogien toiminnallisuuden ja käyttökulttuurin sopivuutta brandiviestinnän välineeksi. Brandiviestinnän toimivuuden mittarina käytetään kuluttajien suhtautumista brandiviesteihin. Tutkimuksen lähestymistavaksi valittiin kvalitatiivinen tutkimusmenetelmä. Tutkimusaineiston keräämisessä käytettiin aineistotriangulaatiota. Aineisto kerättiin havainnoimalla ja teemahaastatteluilla. Havainnoinnilla kerätty aineisto koostuu ruokablogien keskustelualustojen kommenteista. Havainnoinnin lisäksi haastateltiin 11 ruokablogin seuraajaa. Aineistosta selvisi, että kuluttajien motiivit seurata ruokablogeja ovat yksilöllisiä. Nämä motiivit vaikuttavat siihen, miten kuluttajat suhtautuvat brandiviestintään ruokablogeissa. Ruokablogien selailu ei ole kuluttajille pelkästään ajanvietettä, vaan niistä etsitään myös tietoa, mielipiteitä, kokemuksia ja tukea ostopäätöksille. Kuluttajat osallistuvat brandiviestintään ruokablogeissa. Blogien brandiviestin arvo perustuu pitkälti kuluttajien omaan toimintaan. Haastateltavat kokivat brandiviestinnän vaikuttavan heidän mielikuviin ja käsityksiin brandista, mikäli heillä ei ollut aiempaa omakohtaista kokemusta brandista. Brandiviestin ja sen lähettäjän tunnistaminen koettiin vaikeaksi. Brandiviestinnän nähtiin olevan olennainen osa ruokablogien sisältöä ja toimintaa. Parhaassa tapauksessa ruokablogit ovat tehokas brandiviestintäväylä. Kuluttajista on tullut yhä pysyvämpi osa yritysten brandiviestintää. Brandiviestintä ja brandimaininnat blogeissa ovat kuluttajien silmissä usein sama asia. Kaikki brandimaininnat nähdään brandin ilmentymänä, mikä tarkoittaa sitä, että ne voivat vaikuttaa kuluttajien mielikuviin brandista. Blogien kautta tapahtuvan brandiviestinnän haasteena on tuottaa mielenkiintoisia brandiviestejä, jotka jäisivät kuluttajien mieliin.
  • Känkänen, Outi (2006)
    Tämä pro gradu –tutkielma on laadullinen tapaustutkimus, jossa tutkitaan brandin rakentamista ja viestintää www-sivuilla relationaalisen viestintänäkemyksen näkökulmasta. Tutkimusaineisto koostuu Internetissä valmiina olevasta aineistosta, Pampersin ja Libero-vaipan www-sivuista. Työn teoreettisen taustan muodostavat relationaalinen viestintämalli (Karvonen 1999), brandin rinnakkaistermin mielikuvan ja mielikuvien syntymallien tarkastelu sekä brandin markkinointi ja markkinointiviestintä www-sivuilla. Tutkimuksen pääpaino ole pelkkien kirjallisten tekstien tai kuvien analysoinnissa, vaan multimedian keinoin www-sivuilla esitetyn brandia ilmentävän representaation (tekstien, kuvien ja äänien yhdistelmä), kokonaisuuden, tarkastelussa. Brandin representaation tarkastelussa tekijä tukeutuu Mitran ja Cohenin (1999) systemaattisen tekstianalyysin yhteydessä esittämiin seikkoihin www-tekstin erityispiirteiden huomioimisesta sekä Janne Seppäsen (2005) määritelmiin representaatiosta ja multimodaalisuudesta ja Minna Tarkan (2000) ajatukseen käyttöliittymästä vuorovaikutteisena kuvana. Yhteistä näille näkökulmille on se, että niissä kuvaruudulla näkyvä aineisto ymmärretään multimedian keinoin järjestetyksi, erilaisten esitystapojen yhdistelmäksi. Tekstin retoriikan ja hypertekstin lukemista koskevien erityispiirteiden sekä näistä syntyvien mahdollisten luentojen ja niiden merkitysten osalta tekijä tukeutuu Sosnoskin (1999) esitykseen konfiguroinnista retorisena analyysitapana. Kokonaisanalyysi koostuu molempien tutkimustapausten, Liberon ja Pampersin www-sivustojen, osalta seuraavista osa-analyyseista: teemoittelusta, www-sivustojen tekstianalyyseistä, brandi-identiteetin kokonaisuuden ja brandiviestinnän analyyseistä sekä sivustoihin liittyvien mahdollisten luentojen retorisesta analyysista. Analyysin tulosten perusteella varsinaiset tuotteet, vaipat, eivät ominaisuuksiltaan ja toiminnallisilta hyödyiltään oleellisesti eroa toisistaan, minkä vuoksi markkinoijat pyrkivät erilaistamaan tuotteitaan muilla tavoilla. Tarkastellut brandit pyrkivät erilaistumaan toisistaan ja muista kilpailijoistaan brandin persoonallisuuden ja siihen liittyvien symbolien, arvoväittämän tunnepohjaisten ja käyttäjän persoonallisuutta ilmaisevien hyötyjen painotusten sekä tavoittelemansa asiakassuhteen avulla. Persoonallisuuden ja asiakassuhteen osalta voisi tiivistää, että Libero vertautuu vanhemman vertaiseen ystävään, Pampers puolestaan asiantuntijaan. Kaksi jokseenkin samanlaista tuotetta edustavaa markkinoijaa voi erilaistaa tuotteensa viestinnässään mielikuvien avulla, brandia rakentamalla. Brandin www-sivujen lukijat kokevat brandin henkilökohtaisesti. Brandiin liittyvällä näkökulmien ja merkitysten moninaisuudella on yhtymäkohta relationaaliseen viestintänäkemykseen ja relationaaliseen näkemykseen mielikuvista: samoin kuin Karvonen (1999) esittää järviesimerkillään, miten eri ihmiset antavat järvelle eri merkityksiä omasta näkökulmastaan ja todellisuudestaan käsin, myös www-sivujen elementtien synnyttämien erilaisten mielikuvien perusteella syntyvät mahdolliset näkökulmat tai tulkinnat antavat www-sivulle ja brandille erilaisia merkityksiä. Eri osapuolet suhteutuvat brandiin perspektiivisesti vain rajallisessa suhteessa, minkä perusteella kullekin brandista syntyvä merkitys edustaa yksipuolista ymmärrystä. Jos olisi mahdollista kerätä kaikkien osallisten käsitykset yhteen, voisi tarkastella kohteen, brandin, ”todellisuutta”, joka siten edustaisi mahdollisimman monipuolista ymmärrystä. Samasta asiasta, esimerkiksi lasten vaipoista merkityksineen, voidaan siis puhua hyvin monilla toisistaan eroavilla tavoilla.
  • Känkänen, Outi (Helsingin yliopisto, 2006)
    Tämä pro gradu –tutkielma on laadullinen tapaustutkimus, jossa tutkitaan brandin rakentamista ja viestintää www-sivuilla relationaalisen viestintänäkemyksen näkökulmasta. Tutkimusaineisto koostuu Internetissä valmiina olevasta aineistosta, Pampersin ja Libero-vaipan www-sivuista. Työn teoreettisen taustan muodostavat relationaalinen viestintämalli (Karvonen 1999), brandin rinnakkaistermin mielikuvan ja mielikuvien syntymallien tarkastelu sekä brandin markkinointi ja markkinointiviestintä www-sivuilla. Tutkimuksen pääpaino ole pelkkien kirjallisten tekstien tai kuvien analysoinnissa, vaan multimedian keinoin www-sivuilla esitetyn brandia ilmentävän representaation (tekstien, kuvien ja äänien yhdistelmä), kokonaisuuden, tarkastelussa. Brandin representaation tarkastelussa tekijä tukeutuu Mitran ja Cohenin (1999) systemaattisen tekstianalyysin yhteydessä esittämiin seikkoihin www-tekstin erityispiirteiden huomioimisesta sekä Janne Seppäsen (2005) määritelmiin representaatiosta ja multimodaalisuudesta ja Minna Tarkan (2000) ajatukseen käyttöliittymästä vuorovaikutteisena kuvana. Yhteistä näille näkökulmille on se, että niissä kuvaruudulla näkyvä aineisto ymmärretään multimedian keinoin järjestetyksi, erilaisten esitystapojen yhdistelmäksi. Tekstin retoriikan ja hypertekstin lukemista koskevien erityispiirteiden sekä näistä syntyvien mahdollisten luentojen ja niiden merkitysten osalta tekijä tukeutuu Sosnoskin (1999) esitykseen konfiguroinnista retorisena analyysitapana. Kokonaisanalyysi koostuu molempien tutkimustapausten, Liberon ja Pampersin www-sivustojen, osalta seuraavista osa-analyyseista: teemoittelusta, www-sivustojen tekstianalyyseistä, brandi-identiteetin kokonaisuuden ja brandiviestinnän analyyseistä sekä sivustoihin liittyvien mahdollisten luentojen retorisesta analyysista. Analyysin tulosten perusteella varsinaiset tuotteet, vaipat, eivät ominaisuuksiltaan ja toiminnallisilta hyödyiltään oleellisesti eroa toisistaan, minkä vuoksi markkinoijat pyrkivät erilaistamaan tuotteitaan muilla tavoilla. Tarkastellut brandit pyrkivät erilaistumaan toisistaan ja muista kilpailijoistaan brandin persoonallisuuden ja siihen liittyvien symbolien, arvoväittämän tunnepohjaisten ja käyttäjän persoonallisuutta ilmaisevien hyötyjen painotusten sekä tavoittelemansa asiakassuhteen avulla. Persoonallisuuden ja asiakassuhteen osalta voisi tiivistää, että Libero vertautuu vanhemman vertaiseen ystävään, Pampers puolestaan asiantuntijaan. Kaksi jokseenkin samanlaista tuotetta edustavaa markkinoijaa voi erilaistaa tuotteensa viestinnässään mielikuvien avulla, brandia rakentamalla. Brandin www-sivujen lukijat kokevat brandin henkilökohtaisesti. Brandiin liittyvällä näkökulmien ja merkitysten moninaisuudella on yhtymäkohta relationaaliseen viestintänäkemykseen ja relationaaliseen näkemykseen mielikuvista: samoin kuin Karvonen (1999) esittää järviesimerkillään, miten eri ihmiset antavat järvelle eri merkityksiä omasta näkökulmastaan ja todellisuudestaan käsin, myös www-sivujen elementtien synnyttämien erilaisten mielikuvien perusteella syntyvät mahdolliset näkökulmat tai tulkinnat antavat www-sivulle ja brandille erilaisia merkityksiä. Eri osapuolet suhteutuvat brandiin perspektiivisesti vain rajallisessa suhteessa, minkä perusteella kullekin brandista syntyvä merkitys edustaa yksipuolista ymmärrystä. Jos olisi mahdollista kerätä kaikkien osallisten käsitykset yhteen, voisi tarkastella kohteen, brandin, ”todellisuutta”, joka siten edustaisi mahdollisimman monipuolista ymmärrystä. Samasta asiasta, esimerkiksi lasten vaipoista merkityksineen, voidaan siis puhua hyvin monilla toisistaan eroavilla tavoilla.
  • Puolamäki, Kai (Helsingin yliopisto, 2001)
  • Eerola, Hannaleena (Helsingin yliopisto, 2001)