Part I: Enzyme replacement versus neurotrophic factor viral vector-mediated gene therapy of Parkinson’s disease, Part II: The effects of orally dosed tolcapone and entacapone on dopamine metabolism in the dorsal striatum and nucleus accumbens in rats

Part I: Parkinson’s disease is a slowly progressive neurodegenerative disorder in which particularly the dopaminergic neurons of the substantia nigra pars compacta degenerate and die. Current conventional treatment is based on restraining symptoms but it has no effect on the progression of the disease. Gene therapy research has focused on the possibility of restoring the lost brain function by at least two means: substitution of critical enzymes needed for the synthesis of dopamine and slowing down the progression of the disease by supporting the functions of the remaining nigral dopaminergic neurons by neurotrophic factors. The striatal levels of enzymes such as tyrosine hydroxylase, dopadecarboxylase and GTP-CH1 are decreased as the disease progresses. By replacing one or all of the enzymes, dopamine levels in the striatum may be restored to normal and behavioral impairments caused by the disease may be ameliorated especially in the later stages of the disease. The neurotrophic factors glial cell derived neurotrophic factor (GDNF) and neurturin have shown to protect and restore functions of dopaminergic cell somas and terminals as well as improve behavior in animal lesion models. This therapy may be best suited at the early stages of the disease when there are more dopaminergic neurons for neurotrophic factors to reach. Viral vector-mediated gene transfer provides a tool to deliver proteins with complex structures into specific brain locations and provides long-term protein over-expression. Part II: The aim of our study was to investigate the effects of two orally dosed COMT inhibitors entacapone (10 and 30 mg/kg) and tolcapone (10 and 30 mg/kg) with a subsequent administration of a peripheral dopadecarboxylase inhibitor carbidopa (30 mg/kg) and L- dopa (30 mg/kg) on dopamine and its metabolite levels in the dorsal striatum and nucleus accumbens of freely moving rats using dual-probe in vivo microdialysis. Earlier similarly designed studies have only been conducted in the dorsal striatum. We also confirmed the result of earlier ex vivo studies regarding the effects of intraperitoneally dosed tolcapone (30 mg/kg) and entacapone (30 mg/kg) on striatal and hepatic COMT activity. The results obtained from the dorsal striatum were generally in line with earlier studies, where tolcapone tended to increase dopamine and DOPAC levels and decrease HVA levels. Entacapone tended to keep striatal dopamine and HVA levels elevated longer than in controls and also tended to elevate the levels of DOPAC. Surprisingly in the nucleus accumbens, dopamine levels after either dose of entacapone or tolcapone were not elevated. Accumbal DOPAC levels, especially in the tolcapone 30 mg/kg group, were elevated nearly to the same extent as measured in the dorsal striatum. Entacapone 10 mg/kg elevated accumbal HVA levels more than the dose of 30 mg/kg and the effect was more pronounced in the nucleus accumbens than in the dorsal striatum. This suggests that entacapone 30 mg/kg has minor central effects. Also our ex vivo study results obtained from the dorsal striatum suggest that entacapone 30 mg/kg has minor and transient central effects, even though central HVA levels were not suppressed below those of the control group in either brain area in the microdialysis study. Both entacapone and tolcapone suppressed hepatic COMT activity more than striatal COMT activity. Tolcapone was more effective than entacapone in the dorsal striatum. The differences between dopamine and its metabolite levels in the dorsal striatum and nucleus accumbens may be due to different properties of the two brain areas.

Vem vänder vindarna? – Vem tänder stjärnorna? Några metodiska grepp i analysen av Eva Dahlgrens rocktexter

Abstract (Vem vänder vindarna ? – Vem tänder stjärnorna? Methodological choices in the analysis of Eva Dahlgren’s rock lyrics): This article deals with some methods I have found useful in analyzing the lyrics in rock music, particularly the lyrics by the Swedish singer songwriter Eva Dahlgren (born 1960). The article is based on my doctoral thesis in progress, dealing with the relationship between the lyrics (in particular the “I” of the lyrics), and the public persona of Eva Dahlgren, as well as the process of "doing Eva Dahlgren" (the constructing of her artist persona). I take my starting point in the lyrics of Dahlgren’s big hit "Vem tänder stjärnorna" (Dahlgren 1991). First, I discuss the themes of the lyrics, mostly the spiritual or religious themes. Second, I present and discuss the methods in my own work. The first method is inspired by conversational analysis, and is based on a transcription of the performed lyrics, with the aim of grasping the dialogues between the words and the music, more specifically Dahlgren’s use of voice. My other methods are related to my aim to describe Dahlgren’s public persona, and the construction of “Eva Dahlgren”. I have used concepts and models developed by the musicologist Laura Ahonen and literary scholar Karin Strand, in an effort to describe the many levels in Dahlgren’s (performed) “I” as well as the different actors in the process of shaping and reshaping images of Eva Dahlgren.

Att skapa en helhet av fragment Om översättningen av kohesiva element i Sjóns Stålnatt

Abstract (Creating a whole from fragments. On the translation of cohesive elements in Sjón's Steelnight): In this paper, I discuss the Swedish translation of the Icelandic writer Sjón’s debut novel Steelnight: a story (in Swedish Stålnatt – en berättelse). Steelnight is a fragmented novel which is located at the border between poetry and prose. At the beginning of the story, the writer introduces two main plots (with subplots). At first glance, it may seem as though the plots do not share much in common. However, a closer analysis of the text reveals that there are striking parallels between the plots which are created partly by the writer’s use of cohesive elements. Thus, despite the fragmented style, the writer creates cohesion in the text by using stylistic means such as repetition of certain nouns and adjectives and by a frequent use of personal and demonstrative pronouns. This use of cohesive elements creates a challenge for the translator.

Biosynthesis of valine and isoleucine in plants I. Formation of α-acetolactate in Phaseolus radiatus

1. 1. The presence of an enzyme system in plants catalyzing the formation of α-acetolactate from pyruvate has been demonstrated; the system in green gram (Phaseolus radiatus) has been partially purified and its characteristics have been studied.2. Free acetaldehyde is formed as a product of the reaction and so the reaction is mainly diverted towards the formation of acetoin. 3. The system requires thiamine pyrophosphate and a divalent metal ion (Mn2+ or Mg2+) for maximum activity. The optimum pH is around 6.0 and the optimum temperature is 60°. 4. The system is very labile in absence of pyruvate, Mn2+ and DPT. 5. The Km values for pyruvate, Mn2+, Mg2+ and DPT are 3·10−2 M. 5·10−5 M, 2·10−5 M, and e·10−6 M respectively. The activation energy is 3540 cal/mole. 6. The enzyme is strongly inhibited by p-chloromercuribenzoate and the inhibition can be reversed partially by 2-mercaptoethanol, BAL or cysteine. Heavy metals, such as Hg2+ and Ag+, are inhibitory but l-valine does not inhibit the reaction.

Stabilisation and characterisation of N,N′-dibenzylidene-o-phenylenediamine as a copper(I) perchlorate complex

QUITE OFTEN, metal ions profoundly affect the condensation of carbonyl compounds with primary amines to form Schiff bases as well as their subsequent reactions[I-4]. Condensation of benzaldehyde with o-phenylenediamine (opd) in glacial acetic acid[5] or in absolute alcohol[6] gives benzimidazole derivative, 1-benzyl-2-phenylbenzimidazole (bpbi). In this reaction, the Schiff base N,N'-dibenzylidene-o-phenylenedianfme (dbpd) has been postulated as an intermediate, which cyclises to give bpbi. It was found that the reaction of opd in presence of copperO1) perchlorate with benzaldehyde gave dbpd complex of copper(l) perchlorate instead of bpbi.

Ironi som forskningsobjekt. Är det möjligt att forska i det som finns mellan raderna?

Abstract (Irony as object of research: Is it possible to explore what is between the lines?): The main concern of this article is the interpretation of irony: how is it brought about and how can it be investigated? The method applied is based on authentic texts and their elicited interpretations − a method referred to in this article response analysis. Interpretation of irony in the approach taken is seen as being crucially dependent on the notion of coherence. A text is perceived as being coherent if it (a) makes sense and if it(b) hangs together. Incoherent texts can result in an ironic interpretation; however, the incoherence must also be perceived as being intentional, and intentionality in turn is a sign of the edge of the ironist. Ironic interpretation is defined as a combination of five factors: (1) an ironic edge that (2) reflects the intention of the ironist, and (3) has a target and (4) a victim too. Essential to irony is its fifth factor, the fact that one or more of these four factors must be inferred from co(n)text. This definition of irony is crucial in distinguishing irony from non-irony, and it also helps to discern the differences as well as the similarities between irony and related phenomena.

Att tolka namn i tiden. Om det socioonomastiska greppet

Abstract (The socio-onomastic approach and translation): The article adopts an onomastic perspective on the translation, and highlights the challenges posed by the given names. The newer socio-onomastic research has drawn attention to the emotive, appealing, ideological and integrative functions of the names, showing strong links with both the period and with society. In the article this is exemplified with ship names from the nineteenth century, which partly reflect classicism (Argo, Hercules, Juno, Neptunus) and national romanticism (Aallotar, Aino, Sampo, Wellamo). A special challenge is posed by the transparent names that evoke the actual words used, such as Penningdraken ('Money Dragon'), a ship that brought big money, and Människoätaren ('The man killer'), a ship where many sailors lost their lives. Names raise time-bound and culture-bound associations and the translator should be able to interpret the names as an embodiment of the society and the culture from which they originate.

Undervisning i forskningsetik

Abstract (Teaching in research ethics): The aim of this paper is to discuss teaching in research ethics. According to the guidelines issued by the National Advisory Board on Research Ethics in Finland (2002) the units providing researcher training have a duty to include good scientific practice and research ethics in this training. Various kinds of materials are needed in teaching in research ethics. One of them is fiction, which has appeared to be helpful in discussions of ethic problems. A number of examples taken from Finnish and Swedish fiction are discussed by referring to the above mentioned guidelines. The presentation is based on a chiasm, i.e. it goes from good scientific practice to fiction and further from fiction to teaching in research ethics.

Spectrophotometric and potentiometric investigations of copper (II)-ethanolamine complexes - Part I. Monoethanolamine

Spectrophotometric and potentiometric investigations have been carried out on copper-monoethanolamine complexes. Job plots at 920, 760 and 620 mµ have indicated the formation of CuA++, CuA2/++ and CuA3 ++. The$$\bar n - pA$$ curves have been obtained by a slight modification of the method of corresponding solutions and by pH measurements. The$$\bar n$$ vs. pA curves obtained at different metal concentrations coincide indicating the formation of mononuclear complexes. Experiments conducted with 0·1. 0·2, 0·5 and 1·0 M monoethanolammonium ion indicate the formation of mononuclear hydroxy complexes above pH 6. The nature of E m vs pA curves is closely analogous to that of$$\bar n$$ vs. pA curves. Absorption spectra taken at pH 9·8 with different amounts of monoethanolamine has given evidence for the formation of (CuA3OH·A)+.$$\bar n - pA$$ curves have been analyzed and the values ofβ 1, 1,β 1, 2 andβ 1, 3 have been obtained. Curves showing the distribution of complexes and the absorption curves of the individual complexes (CuA++, CuA2/++, and CuA3/++) have been calculated.

Synthetic investigations in the sesamin group - Part I. Synthesis of samin, a degradation product of sesamolin

Ethylα-bromovinylacetate (VII) was condensed with the sodio derivative of ethyl piperonoylacetate (VIII) to give diethylα-vinyl-α′-piperonoylsuccinate (IX). The latter on reduction with lithium aluminium hydride furnished the triol (X), which underwent smooth cyclisation with 1% ethanolic hydrogen chloride to 2-(3′, -methylenedioxyphenyl)-hydroxymethyl-4-vinyltetrahydrofuran (XIa). The structure of XIa was established by Oppenauer oxidation to an aldehyde. Ozonolysis of XIa afforded samin (I).

Inhomogeneous Structures in Holographic Superfluids I

We begin an investigation of inhomogeneous structures in holographic superfluids. As a first example, we study domain wall like defects in the 3+1 dimensional Einstein-Maxwell-Higgs theory, which was developed as a dual model for a holographic superconductor. In [1], we reported on such "dark solitons" in holographic superfluids. In this work, we present an extensive numerical study of their properties, working in the probe limit. We construct dark solitons for two possible condensing operators, and find that both of them share common features with their standard superfluid counterparts. However, both are characterized by two distinct coherence length scales (one for order parameter, one for charge condensate). We study the relative charge depletion factor and find that solitons in the two different condensates have very distinct depletion characteristics. We also study quasiparticle excitations above the holographic superfluid, and find that the scale of the excitations is comparable to the soliton coherence length scales.

Studies on the enzyme hydrolysing flavin mononucleotide in plants: I. Partial purification and properties of the enzyme from Phaseolus radiatus

The partial purification of the enzyme hydrolysing FMN from extracts of greengram seeds (Phaseolus radiatus) is described. The procedures, which entailed precipitation of inert material by manganous sulfate and protamine sulfate treatment, fractional precipitation with alcohol and chromatography on CM-cellulose, afforded preparations whose specific activity was 200 times that of the initial crude extract. The preparation was comparatively specific for FMN. It also hydrolysed, to a much smaller extent, β-glycerophosphate, p-nitrophenyl phosphate and 5′-nucleotides. The differential effects of ions on the FMN and β-glycerophosphate hydrolysing activities are discussed.

Studies on the enzyme hydrolysing flavin mononucleotide in plants. I. Partial purification and properties of the enzyme from Phaseolus radiatus

The partial purification of the enzyme hydrolysing FMN from extracts of greengram seeds (Phaseolus radiatus) is described. The procedures, which entailed precipitation of inert material by manganous sulfate and protamine sulfate treatment, fractional precipitation with alcohol and chromatography on CM-cellulose, afforded preparations whose specific activity was 200 times that of the initial crude extract. The preparation was comparatively specific for FMN. It also hydrolysed, to a much smaller extent, β-glycerophosphate, p-nitrophenyl phosphate and 5′-nucleotides. The differential effects of ions on the FMN and β-glycerophosphate hydrolysing activities are discussed.

Studies in the sandalwood-oil series. I. The structure, synthesis, and configuration of the lactone of tricycloekasantalic acid

The structure, synthesis, and configuration of the lactone of tricycloekasantalic acid have been described. It has been shown that in the formation of this lactone (XII) from the acids (I) or (II) a rearrangement is involved.