Genetic Factors in the Regulation of Striatal and Extrastriatal Dopamine D2 Receptor Expression

Positron emission tomography (PET) studies on healthy individuals have revealed a marked interindividual variability in striatal dopamine D2 receptor density that can be partly accounted for by genetic factors. The examination of the extrastriatal lowdensity D2 receptor populations has been impeded by the lack of suitable tracers. However, the quantification of these D2 receptor populations is now feasible with recently developed PET radioligands. The objective of this thesis was to study brain neurobiological correlates of common functional genetic variants residing in candidate genes relevant for D2 receptor functioning. For this purpose, healthy subjects were studied with PET imaging using [₁₁C]raclopride and [₁₁C]FLB457 as radioligands. The candidate genes examined in this work were the human D2 receptor gene (DRD2) and the catechol-Omethyltransferase gene (COMT). The region-specific genotypic influences were explored by comparing D2 receptor binding properties in the striatum, the cortex and the thalamus. As an additional study objective, the relationship between cortical D2 receptor density and a cognitive phenotype i.e. verbal memory and learning was assessed. The main finding of this study was that DRD2 C957T genotype altered markedly D2 receptor density in the cortex and the thalamus whereas in the striatum the C957T genotype affected D2 receptor affinity, but not density. Furthermore, the A1 allele of the DRD2-related TaqIA polymorphism showed increased cortical and thalamic D2 receptor density, but had the opposite effect on striatal D2 receptor density. The DRD2 –141C Ins/Del or the COMT Val158Met genotypes did not change D2 receptor binding properties. Finally, unlike previously reported, cortical D2 receptor density did not show any significant correlation with verbal memory function. The results of this study suggest that the C957T and the TaqIA genotypes have region-specific neurobiological correlates in brain dopamine D2 receptor availability in vivo. The biological mechanisms underlying these findings are unclear, but they may be related to the region-specific regulation of dopamine neurotranssion, gene/receptor expression and epigenesis. These findings contribute to the understanding of the genetic regulation of dopamine and D2 receptor-related brain functions in vivo in man. In addition, the results provide potentially useful endophenotypes for genetic research on psychiatric and neurological disorders.

THE APPLICATION OF AUTOMATED CORRELATION OPTIMIZED WARPING TO THE QUALITY EVALUATION OF Radix Puerariae thomsonii: CORRECTING RETENTION TIME SHIFT IN THE CHROMATOGRAPHIC FINGERPRINTS

The application of automated correlation optimized warping (ACOW) to the correction of retention time shift in the chromatographic fingerprints of Radix Puerariae thomsonii (RPT) was investigated. Twenty-seven samples were extracted from 9 batches of RPT products. The fingerprints of the 27 samples were established by the HPLC method. Because there is a retention time shift in the established fingerprints, the quality of these samples cannot be correctly evaluated by using similarity estimation and principal component analysis (PCA). Thus, the ACOW method was used to align these fingerprints. In the ACOW procedure, the warping parameters, which have a significant influence on the alignment result, were optimized by an automated algorithm. After correcting the retention time shift, the quality of these RPT samples was correctly evaluated by similarity estimation and PCA. It is demonstrated that ACOW is a practical method for aligning the chromatographic fingerprints of RPT. The combination of ACOW, similarity estimation, and PCA is shown to be a promising method for evaluating the quality of Traditional Chinese Medicine.

Evaluation of group electronegativities and hardness (softness) of group 14 elements and containing functional groups through density functional theory and correlation with NMR spectra data

Quantum Chemical calculations for group 14 elements of Periodic Table (C, Si, Ge, Sn, Pb) and their functional groups have been carried out using Density Functional Theory (DFT) based reactivity descriptors such as group electronegativities, hardness and softness. DFT calculations were performed for a large series of tetracoordinated Sn compounds of the CH3SnRR'X type, where X is a halogen and R and R' are alkyl, halogenated alkyl, alkoxy, or alkyl thio groups. The results were interpreted in terms of calculated electronegativity and hardness of the SnRR'X groups, applying a methodology previously developed by Geerlings and coworkers (J. Phys. Chem. 1993, 97, 1826). These calculations allowed to see the regularities concerning the influence of the nature of organic groups RR' and inorganic group X on electronegativities and hardness of the SnRR'X groups; in this case, it was found a very good correlation between the electronegativity of the fragment and experimental 119Sn chemical shifts, a property that sensitively reflects the change in the valence electronic structure of molecules. This work was complemented with the study of some compounds of the EX and ER types, where E= C, Si, Ge, Sn and R= CH3, H, which was performed to study the influence that the central atom has on the electronegativity and hardness of molecules, or whether these properties are mainly affected for the type of ligand bound to the central atom. All these calculations were performed using the B3PW91 functional together with the 6-311++G** basis set level for H, C, Si, Ge, F, Cl and Br atoms and the 3-21G for Sn and I atoms.

Analysis of electricity distribution network operation business models and capitalization of control room functions with DMS

Electricity distribution network operation (NO) models are challenged as they are expected to continue to undergo changes during the coming decades in the fairly developed and regulated Nordic electricity market. Network asset managers are to adapt to competitive technoeconomical business models regarding the operation of increasingly intelligent distribution networks. Factors driving the changes for new business models within network operation include: increased investments in distributed automation (DA), regulative frameworks for annual profit limits and quality through outage cost, increasing end-customer demands, climatic changes and increasing use of data system tools, such as Distribution Management System (DMS). The doctoral thesis addresses the questions a) whether there exist conditions and qualifications for competitive markets within electricity distribution network operation and b) if so, identification of limitations and required business mechanisms. This doctoral thesis aims to provide an analytical business framework, primarily for electric utilities, for evaluation and development purposes of dedicated network operation models to meet future market dynamics within network operation. In the thesis, the generic build-up of a business model has been addressed through the use of the strategicbusiness hierarchy levels of mission, vision and strategy for definition of the strategic direction of the business followed by the planning, management and process execution levels of enterprisestrategy execution. Research questions within electricity distribution network operation are addressed at the specified hierarchy levels. The results of the research represent interdisciplinary findings in the areas of electrical engineering and production economics. The main scientific contributions include further development of the extended transaction cost economics (TCE) for government decisions within electricity networks and validation of the usability of the methodology for the electricity distribution industry. Moreover, DMS benefit evaluations in the thesis based on the outage cost calculations propose theoretical maximum benefits of DMS applications equalling roughly 25% of the annual outage costs and 10% of the respective operative costs in the case electric utility. Hence, the annual measurable theoretical benefits from the use of DMS applications are considerable. The theoretical results in the thesis are generally validated by surveys and questionnaires.

On the development of object functions and restrictions for shapes made with a turret punch press

This study presents the information required to describe the machine and device resources in the turret punch press environment which are needed for the development of the analysing method for automated production. The description of product and device resources and their interconnectedness is the starting point for method comparison the development of expenses, production planning and the performance of optimisation. The manufacturing method cannot be optimized unless the variables and their interdependence are known. Sheet metal parts in particular may then become remarkably complex, and their automatic manufacture may be difficult or, with some automatic equipment, even impossible if not know manufacturing properties. This thesis consists of three main elements, which constitute the triangulation. In the first phase of triangulation, the manufacture occuring on a turret punch press is examined in order to find the factors that affect the efficiency of production. In the second phase of triangulation, the manufacturability of products on turret punch presses is examined through a set of laboratory tests. The third phase oftriangulation involves an examination of five industry parts. The main key findings of this study are: all possible efficiency in high automation level machining cannot be achieved unless the raw materials used in production and the dependencies of the machine and tools are well known. Machine-specific manufacturability factors for turret punch presses were not taken into account in the industrial case samples. On the grounds of the performed tests and industrial case samples, the designer of a sheet metal product can directly influence the machining time, material loss, energy consumption and the number of tools required on a turret punch press by making decisions in the way presented in the hypothesis of thisstudy. The sheet metal parts to be produced can be optimised to bemanufactured on a turret punch press when the material to be used and the kinds of machine and tool options available are known. This provides in-depth knowledge of the machine and tool properties machine and tool-specifically. None of the optimisation starting points described here is a separate entity; instead, they are all connected to each other.

Classification, comorbidity, heredity, and risk factors of female sexual dysfunctions

Female sexual dysfunctions, including desire, arousal, orgasm and pain problems, have been shown to be highly prevalent among women around the world. The etiology of these dysfunctions is unclear but associations with health, age, psychological problems, and relationship factors have been identified. Genetic effects explain individual variation in orgasm function to some extent but until now quantitative behavior genetic analyses have not been applied to other sexual functions. In addition, behavior genetics can be applied to exploring the cause of any observed comorbidity between the dysfunctions. Discovering more about the etiology of the dysfunctions may further improve the classification systems which are currently under intense debate. The aims of the present thesis were to evaluate the psychometric properties of a Finnish-language version of a commonly used questionnaire for measuring female sexual function, the Female Sexual Function Index (FSFI), in order to investigate prevalence, comorbidity, and classification, and to explore the balance of genetic and environmental factors in the etiology as well as the associations of a number of biopsychosocial factors with female sexual functions. Female sexual functions were studied through survey methods in a population based sample of Finnish twins and their female siblings. There were two waves of data collection. The first data collection targeted 5,000 female twins aged 33–43 years and the second 7,680 female twins aged 18–33 and their over 18–year-old female siblings (n = 3,983). There was no overlap between the data collections. The combined overall response rate for both data collections was 53% (n = 8,868), with a better response rate in the second (57%) compared to the first (45%). In order to measure female sexual function, the FSFI was used. It includes 19 items which measure female sexual function during the previous four weeks in six subdomains; desire, subjective arousal, lubrication, orgasm, sexual satisfaction, and pain. In line with earlier research in clinical populations, a six factor solution of the Finnish-language version of the FSFI received supported. The internal consistencies of the scales were good to excellent. Some questions about how to avoid overestimating the prevalence of extreme dysfunctions due to women being allocated the score of zero if they had had no sexual activity during the preceding four weeks were raised. The prevalence of female sexual dysfunctions per se ranged from 11% for lubrication dysfunction to 55% for desire dysfunction. The prevalence rates for sexual dysfunction with concomitant sexual distress, in other words, sexual disorders were notably lower ranging from 7% for lubrication disorder to 23% for desire disorder. The comorbidity between the dysfunctions was substantial most notably between arousal and lubrication dysfunction even if these two dysfunctions showed distinct patterns of associations with the other dysfunctions. Genetic influences on individual variation in the six subdomains of FSFI were modest but significant ranging from 3–11% for additive genetic effects and 5–18% for nonadditive genetic effects. The rest of the variation in sexual functions was explained by nonshared environmental influences. A correlated factor model, including additive and nonadditive genetic effects and nonshared environmental effects had the best fit. All in all, every correlation between the genetic factors was significant except between lubrication and pain. All correlations between the nonshared environment factors were significant showing that there is a substantial overlap in genetic and nonshared environmental influences between the dysfunctions. In general, psychological problems, poor satisfaction with the relationship, sexual distress, and poor partner compatibility were associated with more sexual dysfunctions. Age was confounded with relationship length but had over and above relationship length a negative effect on desire and sexual satisfaction and a positive effect on orgasm and pain functions. Alcohol consumption in general was associated with better desire, arousal, lubrication, and orgasm function. Women pregnant with their first child had fewer pain problems than nulliparous nonpregnant women. Multiparous pregnant women had more orgasm problems compared to multiparous nonpregnant women. Having children was associated with less orgasm and pain problems. The conclusions were that desire, subjective arousal, lubrication, orgasm, sexual satisfaction, and pain are separate entities that have distinct associations with a number of different biopsychosocial factors. However, there is also considerable comorbidity between the dysfunctions which are explained by overlap in additive genetic, nonadditive genetic and nonshared environmental influences. Sexual dysfunctions are highly prevalent and are not always associated with sexual distress and this relationship might be moderated by a good relationship and compatibility with partner. Regarding classification, the results supports separate diagnoses for subjective arousal and genital arousal as well as the inclusion of pain under sexual dysfunctions.

Quasiconformal mappings and inequalities involving special functions

This PhD thesis in Mathematics belongs to the field of Geometric Function Theory. The thesis consists of four original papers. The topic studied deals with quasiconformal mappings and their distortion theory in Euclidean n-dimensional spaces. This theory has its roots in the pioneering papers of F. W. Gehring and J. Väisälä published in the early 1960’s and it has been studied by many mathematicians thereafter. In the first paper we refine the known bounds for the so-called Mori constant and also estimate the distortion in the hyperbolic metric. The second paper deals with radial functions which are simple examples of quasiconformal mappings. These radial functions lead us to the study of the so-called p-angular distance which has been studied recently e.g. by L. Maligranda and S. Dragomir. In the third paper we study a class of functions of a real variable studied by P. Lindqvist in an influential paper. This leads one to study parametrized analogues of classical trigonometric and hyperbolic functions which for the parameter value p = 2 coincide with the classical functions. Gaussian hypergeometric functions have an important role in the study of these special functions. Several new inequalities and identities involving p-analogues of these functions are also given. In the fourth paper we study the generalized complete elliptic integrals, modular functions and some related functions. We find the upper and lower bounds of these functions, and those bounds are given in a simple form. This theory has a long history which goes back two centuries and includes names such as A. M. Legendre, C. Jacobi, C. F. Gauss. Modular functions also occur in the study of quasiconformal mappings. Conformal invariants, such as the modulus of a curve family, are often applied in quasiconformal mapping theory. The invariants can be sometimes expressed in terms of special conformal mappings. This fact explains why special functions often occur in this theory.

Cognitive Functions After Traumatic Brain Injury. A 30-year Follow-up Study

Many cognitive deficits after TBI (traumatic brain injury) are well known, such as memory and concentration problems, as well as reduced information-processing speed. What happens to patients and cognitive functioning after immediate recovery is poorly known. Cognitive functioning is flexible and may be influenced by genetic, psychological and environmental factors decades after TBI. The general aim of this thesis was to describe the long-term cognitive course after TBI, to find variables that may contribute to it, and how the cognitive functions after TBI are associated with specific medical factors and reduced survival. The original study group consisted of 192 patients with TBI who were originally assessed with the Mild Deterioration Battery (MDB) on average two years after the injury, during the years 1966 – 1972. During a 30-year follow-up, we studied the risks for reduced survival, and the mortality of the patients was compared with the general population using the Standardized Mortality Ratio (SMR). Sixty-one patients were re-assessed during 1998-2000. These patients were evaluated with the MDB, computerized testing, and with various other neuropsychological methods for attention and executive functions. Apolipoprotein-E (ApoE) genotyping and magnetic resonance imaging (MRI) based on volumetric analysis of the hippocampus and lateral ventricles were performed. Depressive symptoms were evaluated with the short form of the Beck depression inventory. The cognitive performance at follow-up was compared with a control group that was similar to the study group in regard to age and education. The cognitive outcome of the patients with TBI varied after three decades. The majority of the patients showed a decline in their cognitive level, the rest either improved or stayed at the same level. Male gender and higher age at injury were significant risk factors for the decline. Whereas most cognitive domains declined during the follow-up, semantic memory behaved in the opposite way, showing recovery after TBI. In the follow-up assessment, the memory decline and impairments in the set-shifting domain of executive functions were associated with MRI-volumetric measures, whereas reduction in information-processing speed was not associated with the MRI measures. The presence of local contusions was only weakly associated with cognitive functions. Only few cognitive methods for attention were capable of discriminating TBI patients with and without depressive symptoms. On the other hand, most complex attentional tests were sensitive enough to discriminate TBI patients (non-depressive) from controls. This means that complex attention functions, mediated by the frontal lobes, are relatively independent of depressive symptoms post-TBI. The presence of ApoE4 was associated with different kinds of memory processes including verbal and visual episodic memory, semantic memory and verbal working memory, depending on the length of time since TBI. Many other cognitive processes were not affected by the presence of ApoE4. Age at injury and poor vocational outcome were independent risk factors for reduced survival in the multivariate analysis. Late mortality was higher among younger subjects (age < 40 years at death) compared with the general population which should be borne in mind when assessing the need for rehabilitation services and long-term follow-up after TBI.

NADPH-Dependent Thioredoxin System In Regulation of Chloroplast Functions

Photosynthesis, the process in which carbon dioxide is converted into sugars using the energy of sunlight, is vital for heterotrophic life on Earth. In plants, photosynthesis takes place in specific organelles called chloroplasts. During chloroplast biogenesis, light is a prerequisite for the development of functional photosynthetic structures. In addition to photosynthesis, a number of other metabolic processes such as nitrogen assimilation, the biosynthesis of fatty acids, amino acids, vitamins, and hormones are localized to plant chloroplasts. The biosynthetic pathways in chloroplasts are tightly regulated, and especially the reduction/oxidation (redox) signals play important roles in controlling many developmental and metabolic processes in chloroplasts. Thioredoxins are universal regulatory proteins that mediate redox signals in chloroplasts. They are able to modify the structure and function of their target proteins by reduction of disulfide bonds. Oxidized thioredoxins are restored via the action of thioredoxin reductases. Two thioredoxin reductase systems exist in plant chloroplasts, the NADPHdependent thioredoxin reductase C (NTRC) and ferredoxin-thioredoxin reductase (FTR). The ferredoxin-thioredoxin system that is linked to photosynthetic light reactions is involved in light-activation of chloroplast proteins. NADPH can be produced via both the photosynthetic electron transfer reactions in light, and in darkness via the pentose phosphate pathway. These different pathways of NADPH production enable the regulation of diverse metabolic pathways in chloroplasts by the NADPH-dependent thioredoxin system. In this thesis, the role of NADPH-dependent thioredoxin system in the redox-control of chloroplast development and metabolism was studied by characterization of Arabidopsis thaliana T-DNA insertion lines of NTRC gene (ntrc) and by identification of chloroplast proteins regulated by NTRC. The ntrc plants showed the strongest visible phenotypes when grown under short 8-h photoperiod. This indicates that i) chloroplast NADPH-dependent thioredoxin system is non-redundant to ferredoxinthioredoxin system and that ii) NTRC particularly controls the chloroplast processes that are easily imbalanced in daily light/dark rhythms with short day and long night. I identified four processes and the redox-regulated proteins therein that are potentially regulated by NTRC; i) chloroplast development, ii) starch biosynthesis, iii) aromatic amino acid biosynthesis and iv) detoxification of H₂O₂. Such regulation can be achieved directly by modulating the redox state of intramolecular or intermolecular disulfide bridges of enzymes, or by protecting enzymes from oxidation in conjunction with 2-cysteine peroxiredoxins. This thesis work also demonstrated that the enzymatic antioxidant systems in chloroplasts, ascorbate peroxidases, superoxide dismutase and NTRC-dependent 2-cysteine peroxiredoxins are tightly linked up to prevent the detrimental accumulation of reactive oxygen species in plants.

Creating possibilities for collective creativity : Brokerage Functions in Practice-Based Innovation

In the network era, creative achievements like innovations are more and more often created in interaction among different actors. The complexity of today‘s problems transcends the individual human mind, requiring not only individual but also collective creativity. In collective creativity, it is impossible to trace the source of new ideas to an individual. Instead, creative activity emerges from the collaboration and contribution of many individuals, thereby blurring the contribution of specific individuals in creating ideas. Collective creativity is often associated with diversity of knowledge, skills, experiences and perspectives. Collaboration between diverse actors thus triggers creativity and gives possibilities for collective creativity. This dissertation investigates collective creativity in the context of practice-based innovation. Practice-based innovation processes are triggered by problem setting in a practical context and conducted in non-linear processes utilising scientific and practical knowledge production and creation in cross-disciplinary innovation networks. In these networks diversity or distances between innovation actors are essential. Innovation potential may be found in exploiting different kinds of distances. This dissertation presents different kinds of distances, such as cognitive, functional and organisational which could be considered as sources of creativity and thus innovation. However, formation and functioning of these kinds of innovation networks can be problematic. Distances between innovating actors may be so great that a special interpretation function is needed – that is, brokerage. This dissertation defines factors that enhance collective creativity in practice-based innovation and especially in the fuzzy front end phase of innovation processes. The first objective of this dissertation is to study individual and collective creativity at the employee level and identify those factors that support individual and collective creativity in the organisation. The second objective is to study how organisations use external knowledge to support collective creativity in their innovation processes in open multi-actor innovation. The third objective is to define how brokerage functions create possibilities for collective creativity especially in the context of practice-based innovation. The research objectives have been studied through five substudies using a case-study strategy. Each substudy highlights various aspects of creativity and collective creativity. The empirical data consist of materials from innovation projects arranged in the Lahti region, Finland, or materials from the development of innovation methods in the Lahti region. The Lahti region has been chosen as the research context because the innovation policy of the region emphasises especially the promotion of practice-based innovations. The results of this dissertation indicate that all possibilities of collective creativity are not utilised in internal operations of organisations. The dissertation introduces several factors that could support collective creativity in organisations. However, creativity as a social construct is understood and experienced differently in different organisations, and these differences should be taken into account when supporting creativity in organisations. The increasing complexity of most potential innovations requires collaborative creative efforts that often exceed the boundaries of the organisation and call for the involvement of external expertise. In practice-based innovation different distances are considered as sources of creativity. This dissertation gives practical implications on how it is possible to exploit different kinds of distances knowingly. It underlines especially the importance of brokerage functions in open, practice-based innovation in order to create possibilities for collective creativity. As a contribution of this dissertation, a model of brokerage functions in practice-based innovation is formulated. According to the model, the results and success of brokerage functions are based on the context of brokerage as well as the roles, tasks, skills and capabilities of brokers. The brokerage functions in practice-based innovation are also possible to divide into social and cognitive brokerage.

The Forms and Functions of Multilingual Practices in Early Modern School Drama from the King‟s School, Canterbury

Käsittelen tutkimuksessani monikielisyyden ilmenemistä Canterburyn katedraalikoulun oppilaiden 1600-luvun loppupuoliskolla esittämissä näytelmissä, jotka löytyvät käsikirjoituksesta Lit.Ms.E41 (Canterburyn katedraalin arkisto). Tämä käsikirjoitus sisältää puheita ja näytelmiä, joiden kielinä ovat englanti, latina ja vähemmissä määrin myös kreikka. Useissa näytelmissä esiintyy koodinvaihtoa näiden kielten välillä, ja tutkielmassani selvitän, millaisia syntaktisia ilmenemismuotoja ja pragmaattisia merkityksiä koodinvaihdolla on. Teoreettinen viitekehykseni on yhdistelmä filologista ja lingvististä lähestymistapaa. Olen sisällyttänyt tutkielmaani aiemman koodinvaihdon tutkimuksen lisäksi Brownin ja Levinsonin kohteliaisuusteorian, jonka avulla erityisesti puhujien välisiin sosiaalisiin suhteisiin liittyviä koodinvaihdon funktioita voidaan luokitella. Koska historiallinen koodinvaihto on tutkimusaiheena vielä melko tuore, käsittelen perusteellisesti erilaisia metodologisia ratkaisuja. Valitsemani metodi yhdistää perinteisen filologisen lähiluvun pragmaattiseen analyysiin, jonka kautta työssäni vaikuttavat muun muassa rationaalisuuden ja empatian käsitteet. Analyysini perusteella kävi ilmi, että erityisen yleinen koodinvaihdon funktio on mahdollistaa intertekstuaalisuus, jolla edelleen voidaan ilmaista esimerkiksi solidaarisuutta eli sosiaalista läheisyyttä tai loukata puhuteltavaa. Solidaarisuus oli myös ilman intertekstuaalisuutta yleinen koodinvaihdon funktio. Näiden lisäksi koodinvaihdon funktioita olivat muun muassa kasvoja uhkaavat teot, eufemismit, stilistiset efektit sekä diskurssin avustaminen. Syntaktisten ilmenemismuotojen osalta keskeisin havainto oli, että koodinvaihdon ja lainaamisen erottaminen ei ole tarpeellista tai edes kannattavaa kaikissa tilanteissa. Lisäksi voitiin todeta, että valittu metodi soveltui hyvin aineiston analysoimiseen, ja sitä tulisi soveltaa mahdollisuuksien mukaan laajempaan materiaaliin sekä muiden pragmaattisten ilmiöiden tutkimiseen.

TR(i)P, TR(i)P, hooray : new functions for TRPC2 and TRPC3

Kalciumjonen påverkar många aspekter av cellbiologi, från fertiliseringen av äggcellen till tillväxt och differentiering av alla typer av celler. Störningar i hur kalciumjonerna transporteras in och friges i cellerna kan ha stor betydelse för hur sjukdomar framskrider. På grund av detta är det viktigt att studera hur kalciumtransportörer såsom kalciumkanaler fungerar och hur de påverkar cellernas funktioner. I avhandlingen har klassiska transient receptorpotential (TRPC) katjonkanaler studerats. Dessa kanaler är permeabla för kalcium och aktiveras nedströms av G-proteinkopplade receptorer. Resultaten som presenteras i avhandlingen visar på nya funktioner för TRPC2- och TRPC3-kanalerna. Utöver TRPC3-kanalens roll i plasmamembranen, där den medverkar i receptorreglerat kalciuminflöde, tyder våra resultat på att TRPC3 har en potentiell intracellulär roll. Vid överuttryck av kanalen lokaliserade kanalen till endoplasmatiska nätverket där kanalen friger intracellulärt kalcium. TRPC2 har en viktig funktion i möss där kanalen reglerar hur djuret reagerar på feromoner. Våra resultat tyder på att TRPC2 är involverad i autokrin sfingosin-1-fosfat (S1P)-signalering. S1P som produceras i cellerna transporterades ut från cellerna varpå det aktiverade S1P2-receptorer på plasmamembranen. Diacylglycerol som bildas som en följd av aktivering av S1P2-receptorn aktiverade i sin tur inflöde av extracellulärt kalcium. Våra resultat indikerar att TRPC2 är kanalen som förmedlar detta kalciuminflöde. I sköldkörtelceller studerades nedströms effekter för TRPC2. Kanalen reglerade negativt cAMP-produktionen i cellerna vilket hämmar extracellulärt signalreglerat kinas 1/2 (ERK1/2). När uttrycket för TRPC2 minskades i cellerna, ökades produktionen av cAMP och fosforyleringen av ERK1/2, vilket resulterade i ökat uttryck för receptorn för sköldkörtelstimulerande hormon. Slutligen, presenterar vi resultat som tyder på att TRPC2 är viktigt för sekretion av prekursorn till sköldkörtelhormon.

Influence of distal ileum exclusion on hepatic and renal functions in presence of extrahepatic cholestasis

OBJECTIVE: To verify whether the ileal exclusion interferes with liver and kidney functional changes secondary to extrahepatic cholestasis.METHODS: We studied 24 rats, divided into three groups with eight individuals each: Group 1 (control), Group 2 (ligation of the hepatic duct combined with internal biliary drainage), and Group 3 (bile duct ligation combined with internal biliary drainage and exclusion of the terminal ileum). Animals in Group 1 (control) underwent sham laparotomy. The animals of groups 2 and 3 underwent ligation and section of the hepatic duct and were kept in cholestasis for four weeks. Next, they underwent an internal biliary bypass. In Group 3, besides the biliary-enteric bypass, we associated the exclusion of the last ten centimeters of the terminal ileum and carried out an ileocolic anastomosis. After four weeks of monitoring, blood was collected from all animals of the three groups for liver and kidney biochemical evaluation (albumin, ALT, AST, direct and indirect bilirubin, alkaline phosphatase, cGT, creatinine and urea).RESULTS: there were increased values of ALT, AST, direct bilirubin, cGT, creatinine and urea in rats from Group 3 (p < 0.05).CONCLUSION: ileal exclusion worsened liver and kidney functions in the murine model of extrahepatic cholestasis, being disadvantageous as therapeutic procedure for cholestatic disorders.

Correlation between the Alvarado Scale and the macroscopic aspect of the appendix in patients with appendicitis

Objective: To evaluate the possible association between the scale of Alvarado (EA) and macroscopic appearance (MA) of the appendix in patients with acute appendicitis.Methods: after receiving the diagnosis of acute appendicitis, EA data were collected. During appendectomy, MA data were collected. Data from patients without appendicitis were excluded. The Spearman correlation test was used to compare EA with Appendix MA (p < 0.05). Other variables were represented by simple frequency. The confidence interval (CI) of 95% was calculated for the correlation test.Results: Data were collected from 67 consecutive patients. The mean age was 37.1 ± 12.5 years and 77.6% of patients were male. The Spearman correlation test used for EA and MA was + 0.77 (95% CI 0.65-0.85, p < 0.0001).Conclusion: although correlation was not perfect, our data indicate that a high score on the scale of Alvarado in patients with appendicitis is correlated with advanced stages of the inflammatory process of acute appendicitis.

Correlation between the oropharyngo-laryngoscopic findings and the severity of obstructive sleep apnea

Objective: To correlate anatomical and functional changes of the oral cavity, pharynx and larynx to the severity of obstructive sleep apnea syndrome (OSAS). Methods : We conducted a cross-sectional study of 66 patients of both genders, aged between 21 and 59 years old with complaints of snoring and / or apnea. All underwent full clinical evaluation, including physical examination, nasolarybgoscopy and polisonography. We classified individuals into groups by the value of the apnea-hypopnea index (AHI), calculated measures of association and analyzed differences by the Kruskal-Wallis and chi-square tests. Results : all patients with obesity type 2 had OSAS. We found a relationship between the uvula projection during nasoendoscopy and OSAS (OR: 4.9; p-value: 0.008; CI: 1.25-22.9). In addition, there was a major strength of association between the circular shape of the pharynx and the presence of moderate or severe OSAS (OR: 9.4, p-value: 0.002), although the CI was wide (1.80-53.13). The septal deviation and lower turbinate hypertrophy were the most frequent nasal alterations, however unrelated to gravity. Nasal obstruction was four times more common in patients without daytime sleepiness. The other craniofacial anatomical changes were not predictors for the occurrence of OSAS. Conclusion : oral, pharyngeal and laryngeal disorders participate in the pathophysiology of OSAS. The completion of the endoscopic examination is of great value to the evaluation of these patients.