Cerimetric determination of simvastatin in pharmaceuticals based on redox and complex formation reactions

Two sensitive spectrophotometric methods are described for the determination of simvastatin (SMT) in bulk drug and in tablets. The methods are based on the oxidation of SMT by a measured excess of cerium (IV) in acid medium followed by determination of unreacted oxidant by two different reaction schemes. In one procedure (method A), the residual cerium (IV) is reacted with a fixed concentration of ferroin and the increase in absorbance is measured at 510 nm. The second approach (method B) involves the reduction of the unreacted cerium (IV) with a fixed quantity of iron (II), and the resulting iron (III) is complexed with thiocyanate and the absorbance measured at 470 nm. In both methods, the amount of cerium (IV) reacted corresponds to SMT concentration. The experimental conditions for both methods were optimized. In method A, the absorbance is found to increase linearly with SMT concentration (r = 0.9995) whereas in method B, the same decreased (r = -0.9943). The systems obey Beer's law for 0.6-7.5 and 0.5-5.0 µg mL-1 for method A and method B, respectively. The calculated molar absorptivity values are 2.7 X 10(4) and 1.06 X 10(5) Lmol-1 cm-1, respectively; and the corresponding sandel sensitivity values are 0.0153 and 0.0039µg cm-2, respectively. The limit of detection (LOD) and quantification (LOQ) are reported for both methods. Intra-day and inter-day precision, and accuracy of the methods were established as per the current ICH guidelines. The methods were successfully applied to the determination of SMT in tablets and the results were statistically compared with those of the reference method by applying the Student's t-test and F-test. No interference was observed from the common excipients added to tablets. The accuracy and validity of the methods were further ascertained by performing recovery experiments via standard addition procedure.

Development of research networks : the case of social capital

The aim of this study is to explore how a new concept appears inscientific discussion and research, how it diffuses to other fields and out of the scientific communities, and how the networks are formed around the concept. Text and terminology take the interest of a reader in the digital environment. Texts create networks where the terminology used is dependent on the ideas, viewsand paradigms of the field. This study is based mainly on bibliographic data. Materials for bibliometric studies have been collected from different databases. The databases are also evaluated and their quality and coverage are discussed. The thesauri of those databases that have been selected for a more in depth study have also been evaluated. The material selected has been used to study how long and in which ways an innovative publication, which can be seen as a milestone in a specific field, influences the research. The concept that has been chosen as a topic for this research is Social Capital, because it has been a popular concept in different scientific fields as well as in everyday speech and the media. It seemed to be a `fashion concept´ that appeared in different situations at the Millennium. The growth and diffusion of social capital publications has been studied. The terms connected with social capital in different fields and different stages of the development have also been analyzed. The methods that have been used in this study are growth and diffusion analysis, content analysis, citation analysis, coword analysis and cocitation analysis. One method that can be used tounderstand and to interpret results of these bibliometric studies is to interview some key persons, who are known to have a gatekeeper position in the diffusion of the concept. Thematic interviews with some Finnish researchers and specialists that have influenced the diffusion of social capital into Finnish scientificand social discussions provide background information. iv The Milestone Publications on social capital have been chosen and studied. They give answers to the question "What is Social Capital?" By comparing citations to Milestone Publications with the growth of all social capital publications in a database, we can drawconclusions about the point at which social capital became generally approved `tacit knowledge´. The contribution of the present study lies foremost in understanding the development of network structures around a new concept that has diffused in scientific communities and also outside them. The network means both networks of researchers, networks of publications and networks of concepts that describe the research field. The emphasis has been on the digital environment and onthe socalled information society that we are now living in, but in this transitional stage, the printed publications are still important and widely used in social sciences and humanities. The network formation is affected by social relations and informal contacts that push new ideas. This study also gives new information about using different research methods, like bibliometric methods supported by interviews and content analyses. It is evident that interpretation of bibliometric maps presupposes qualitative information and understanding of the phenomena under study.

Det vårdande samtalet

Syftet med studien är att utgående från ett vårdvetenskapligt perspektiv utveckla en teori för det vårdande samtalet, speciellt som det gestaltar sig i den psykiatriska vårdkontexten. Avsikten är primärt att tillföra den kliniska vårdvetenskapen kunskaper om hur samtal mellan vårdare och patienter kan lindra lidande. Studien tar sin utgångspunkt i ett vårdvetenskapligt perspektiv som har sina rötter i Katie Erikssons caritativa vårdteori. Den metodologiska ansatsen är hermeneutisk. Forskningen har genomförts i form av fem delstudier som publicerats i internationella vetenskapliga tidskrifter. Metoderna som använts är: 1) en fenomenologisk hermeneutisk ansats för att beskriva det vårdande samtalet som det skildras av sjuksköterskor och patienter i intervjuer, 2) kvalitativ forskningssyntes av studier rörande begreppen närvaro, beröring och lyssnande, 3) kvalitativ forskningssyntes av studier rörande begreppen narrativer, berättelser, mening och förståelse, 4) en hermeneutisk ansats inspirerad av Paul Ricoeurs hermeneutik för att undersöka hur psykiatriska patienter i samtal med vårdare berättar om lidande, 5) en hermeneutisk analys av de etiska fundamenten för ett vårdande samtal i ljuset av Paul Ricoeurs etik. Resultaten från de fem delstudierna formar utgångspunkten för en teori för hur ett vårdande samtal kan tolkas. Teorin består av tre aspekter, den relationella, den narrativa, och den etiska, vilka undersökts i delstudierna. I den relationella aspekten kan vårdaren genom att lyssna, beröra och vara med-varande skapa en närvaro. Genom vårdarens gåva av sin närvaro, d v s att vara tillgänglig och till förfogande med hela sitt väsen, visas möjligheten till ett möte med patienten utan roller och inlärda repliker. När patienten kan besvara denna gåva med en inbjudan att dela något av sin värld, skapas en förbindelse i vilken patienten kan dela sitt lidande och sin värld med vårdaren. Den narrativa aspekten gestaltas i samtalet som patientens berättelse om sitt lidande. Lidandeberättelsen tar sin början i den fasad som patienten skyddar sig mot lidande och skam med. Frågan om varför patienten lider banar vägen både för en ny förståelse av fasaden och också för upplevelsen av en vändpunkt när fasadens skydd överges, vilket leder till en upplevelse av mening-i-lidandet. Artikuleringen av berättelsens poäng, mening-med-lidandet innebär dels en ny tolkning och förståelse för de förhållanden som rådde vid berättelsens början, dels de nya preferenser för hur patienten vill leva sitt liv som vuxit fram. Den etiska aspekten gestaltas i en relation som på grund av patientens lidande och vårdarens medlidande är asymmetrisk, men omfattar en ömsesidig respekt. Genom caritas skapar vårdaren ett utrymme där patienten kan (åter)upprätta sin självaktning, autonomi och sitt ansvar och därmed skapa möjligheter för ett gott liv.

On the impact of rigorous approaches on the quality of development

Software systems are expanding and becoming increasingly present in everyday activities. The constantly evolving society demands that they deliver more functionality, are easy to use and work as expected. All these challenges increase the size and complexity of a system. People may not be aware of a presence of a software system, until it malfunctions or even fails to perform. The concept of being able to depend on the software is particularly significant when it comes to the critical systems. At this point quality of a system is regarded as an essential issue, since any deficiencies may lead to considerable money loss or life endangerment. Traditional development methods may not ensure a sufficiently high level of quality. Formal methods, on the other hand, allow us to achieve a high level of rigour and can be applied to develop a complete system or only a critical part of it. Such techniques, applied during system development starting at early design stages, increase the likelihood of obtaining a system that works as required. However, formal methods are sometimes considered difficult to utilise in traditional developments. Therefore, it is important to make them more accessible and reduce the gap between the formal and traditional development methods. This thesis explores the usability of rigorous approaches by giving an insight into formal designs with the use of graphical notation. The understandability of formal modelling is increased due to a compact representation of the development and related design decisions. The central objective of the thesis is to investigate the impact that rigorous approaches have on quality of developments. This means that it is necessary to establish certain techniques for evaluation of rigorous developments. Since we are studying various development settings and methods, specific measurement plans and a set of metrics need to be created for each setting. Our goal is to provide methods for collecting data and record evidence of the applicability of rigorous approaches. This would support the organisations in making decisions about integration of formal methods into their development processes. It is important to control the software development, especially in its initial stages. Therefore, we focus on the specification and modelling phases, as well as related artefacts, e.g. models. These have significant influence on the quality of a final system. Since application of formal methods may increase the complexity of a system, it may impact its maintainability, and thus quality. Our goal is to leverage quality of a system via metrics and measurements, as well as generic refinement patterns, which are applied to a model and a specification. We argue that they can facilitate the process of creating software systems, by e.g. controlling complexity and providing the modelling guidelines. Moreover, we find them as additional mechanisms for quality control and improvement, also for rigorous approaches. The main contribution of this thesis is to provide the metrics and measurements that help in assessing the impact of rigorous approaches on developments. We establish the techniques for the evaluation of certain aspects of quality, which are based on structural, syntactical and process related characteristics of an early-stage development artefacts, i.e. specifications and models. The presented approaches are applied to various case studies. The results of the investigation are juxtaposed with the perception of domain experts. It is our aspiration to promote measurements as an indispensable part of quality control process and a strategy towards the quality improvement.

Spatio-temporal modelling of the duration of the cotton cycle in the State Of Goiás, Brazil

The objective of this work was to develop and validate a mathematical model to estimate the duration of cotton (Gossypium hirsutum L. r. latifolium hutch) cycle in the State of Goiás, Brazil, by applying the method of growing degree-days (GD), and considering, simultaneously, its time-space variation. The model was developed as a linear combination of elevation, latitude, longitude, and Fourier series of time variation. The model parameters were adjusted by using multiple-linear regression to the observed GD accumulated with air temperature in the range of 15°C to 40°C. The minimum and maximum temperature records used to calculate the GD were obtained from 21 meteorological stations, considering data varying from 8 to 20 years of observation. The coefficient of determination, resulting from the comparison between the estimated and calculated GD along the year was 0.84. Model validation was done by comparing estimated and measured crop cycle in the period from cotton germination to the stage when 90 percent of bolls were opened in commercial crop fields. Comparative results showed that the model performed very well, as indicated by the Pearson correlation coefficient of 0.90 and Willmott agreement index of 0.94, resulting in a performance index of 0.85.

Strategic outsourcing of R&D: The location-specific advantages of India to the pharmaceutical industry

Companies are increasingly under pressure to be more efficient both in terms of costs and overall performance and thus, they seek new ways to develop their products and innovate. For pharmaceutical industry it can take several decades to launch a new drug to the markets. Since pharmaceutical industry is one of the most research-intensive industries, is outsourcing one way to enhance the R&D processes of such companies. It is said that outsourcing to offshore locations is vastly more challenging and complicated than any other exporting activity or inter-company relationship that has evoked a lot of discussion. By outsourcing strategically, companies must also thoroughly focus on transaction costs and core competences. Today, the suppliers are looked for beyond national boundaries and furthermore, the location of the outsourcing activity must also be thoroughly considered. Consequently, the purpose of this study is to analyze what is known of strategic outsourcing of pharmaceutical R&D to India. In order to meet the purpose of the study, this study tries to answer three sub-questions set to it: first, what is strategic outsourcing, second, why pharmaceutical companies utilize strategic outsourcing of R&D and last, why pharmaceutical companies select India as the location for outsourcing their R&D. The study is a qualitative study. The purpose of the study was approached by a literature review with systematic elements and sub-questions were analyzed through different relevant theories, such as theory of transaction costs, core competences and location advantages. Applicable academic journal articles were comprehensively included in the study. The data was collected from electronic journal article databases using key words and almost only peer-reviewed, as new as possible articles were included. Also both the reference list of the included articles and article recommendations from professionals generated more articles for inclusion. The data was analyzed through thematization that resulted in themes that illuminate the purpose of the study and sub-questions. As an outcome of the analysis, each of the theory chapters in the study represents one sub-question. The literature used in this study revealed that strategic outsourcing of R&D is increasingly used in pharmaceutical industry and the major motives to practice it has to do with lowering costs, accessing skilled labor, resources and knowledge and enhancing their quality while speeding up the introduction of new drugs. Mainly for the above-mentioned motives India is frequently chosen as the target location for pharma outsourcers. Still, the literature is somewhat incomplete in this complex phenomenon and more research is needed.

First identification of natural infection of Rickettsia rickettsii in the Rhipicephalus sanguineus tick, in the State of Rio de Janeiro

The Brazilian Spotted Fever (BSF) is a zoonotic disease caused by Rickettsia rickettsii and transmitted by ticks of the genus Amblyomma, more frequently, Amblyomma cajennense. The aim of this paper was to report the first molecular detection of R. rickettsii on R. sanguineus naturally infected in Rio de Janeiro, Brazil. Ticks were collected from dogs in a rural region of Resende municipality, Rio de Janeiro State, Brazil (22º30'9.46"S, 44º42'44.29"WO), where occurred five human cases of BSF in 2006. The ticks were identified under a stereoscopic microscope and separated in pools by stages, species and sex. DNA extraction was carried out using QIAamp DNA Mini Kit (QIAGEN®). The DNA was submitted to PCR amplification using 04 set of primers: Rr190.70p/Rr190.602n (OmpA, 532bp), BG1-21/BG2-20 (OmpB, 650bp), Tz15/Tz16 (17 kDa protein-encoding gene, 246bp) and RpCS.877p/RpCS.1258n (gltA, 381bp). PCR products were separated by electrophoresis on 1% agarose gels and visualized under ultraviolet light with ethidium bromide. PCR products of the expected sizes were purified by QIAquick® and sequenced by ABI PRISM®. The generated nucleotide sequences were edited with using Bioedit® software and compared with the corresponding homologous sequences available through GenBank, using Discontiguous Mega Blast (http://www.ncbi.nlm.nih.gov). It was confirmed R. rickettsii by sequencing of the material (GenBank FJ356230). The molecular characterization of R. rickettsii in the tick R. sanguineus emphasizes the role of dogs as carriers of ticks from the environment to home. Moreover, this result suggests that there is a considerable chance for active participation of R. sanguineus as one of tick species in the transmission of R. ricketsii to human being in the Brazilian territory.

Simulerade skoldilemman : redskap för utveckling av reflektionsförmåga?

Syftet med avhandlingen är att studera lärarstuderandes samtal om simulerad skolverksamhet för att söka förstå möjligheter och begränsningar med simulerade dilemman som medierande redskap för reflektion över lärares arbete. Undersökningen är genomförd under seminarier i svensk och finländsk lärarutbildning. Forskningsprocessen består av tre faser; en konstruktionsfas, en prövningsfas och en undersökningsfas. Under konstruktionsfasen producerades simuleringar på basen av en narrativ analys av semistrukturerade intervjuer med nyutbildade lärare. Simuleringarna testades med lärare och lärarstuderande i prövningsfasen. I undersökningsfasen utarbetades reflektionsfrågor och studiens empiriska data samlades in genom videoobservation. Totalt femton samtal filmades vid fem seminarier och tre olika lärosäten, två i Sverige och ett i Svenskfinland. De studerande som förekommer i datamaterialet befann sig i början, mitten och i slutet av sin lärarutbildning. Analysen bygger på Schöns olika reflektionsbegrepp och ett sociokulturellt perspektiv som bygger på den ryska kulturhistoriska skolan. Resultaten visar att de studerande engagerade sig starkt i samtalen i de flesta fall och att engagemanget var relaterat till deras uppfattningar om simuleringens autenticitet. Simuleringarna och reflektionsfrågorna användes både som sekundära och tertiära artefakter. Bland simuleringarnas modaliteter framstod ljudet som den viktigaste för nyanser av förståelse och engagemang och reflektionsfrågorna fungerade som kommunikativt stöd och strukturell scaffolding. När de studerande använde simuleringen för dekontextualisering i en öppen dialog förekom en tertiär dialog, i vilken förhandling av ny mening ägde rum. Kreativ reflektion – att se dilemmat ur olika perspektiv och reciprok reflektion – öppen utmanande dialog förekom flitigt i vilka en didaktiskanalytisk praktikgemenskap skapades. Slutsatserna är att simulerade skoldilemman kan utgöra en potential för lärarstuderandes utveckling av reflektionsförmåga när de används i mindre samtalsgrupper och den didaktiska inramningen relateras till aktuellt kursinnehåll. Om simuleringens innehåll inte upplevs som autentiskt finns dock risk för att förutfattade meningar om lärares arbete förstärks om de inte utmanas av medstuderande eller lärarutbildare.

Seedling growth of fifteen Brazilian tropical tree species differing in successional status

Growth of seedlings of fifteen tropical tree species representative, at the adult stage, of different successional positions, was studied under field conditions. Seedlings were grown in three treatments: full sun (FS), artificial shade imposed by neutral screens (AS) and natural shade imposed by a closed canopy in a Forest Reserve in Southeast Brazil (NS). Most of the studied species survived in both shade treatments, although their growth was severely affected. Decreases in height, internode numbers, dry weight, leaf area, root:shoot ratio (R:S) and increases in leaf mass ratio (LMR), leaf area ratio (LAR) and specific leaf area (SLA) were common responses to shade. Relative growth rates (RGRs) and net assimilation rates (NARs) were consistently lower in the shaded treatments than in full sun. RGR was significantly correlated with NAR in the FS and NS treatments, whereas it was correlated with LAR in the AS treatment. Natural shade had more severe effects than artificial shade on leaf area reduction and RGR. Between-species differences in R:S, LMR, SLA and LAR were not related to the successional status of species. However, there was a tendency for early-successional species to have higher RGRs than late successional ones, regardless of the light environment. Late-successional species also showed less pronounced responses to shade than early ones. The characteristics presented by the late-successional species may be associated with shade tolerance, enabling their persistence under dense canopies.

Pennförare i periferin : österbottniska sockenskrivare 1721-1868

Modern research on literacy, the scriptualization of the administration and the interaction between the governing and the governed as part of the political culture, has brought to the fore the issue of different scripts and their terms. The present dissertation focuses on the parish scribes in the county of Ostrobothnia during the period 1721–1868. The peasantry had been given the right to pay parish scribes in 1624. The parish scribes who were to assist the peasants in connection with the collection of taxes simultaneously supervised the bailiffs who collected the taxes. Their writing skills made the scribes indispensable also in many other contexts. In Ostrobothnia, the peasantry had use for parish scribes, who worked as mediators between Swedish and Finnish, between the oral and the written and vice versa. The aim of this dissertation is on the one hand to explore the recruitment of parish scribes, and on the other to examine the parish scribes as a professional and social group. The parish scribes’ significance for the peasantry in everyday life, local decision-making and in connection with political processes will be analyzed by examining their work and professional activities. The recruitment of parish scribes and has been analyzed as a decision process where different actors were able to influence the election. The parish scribes’ competence requirements and terms of employment have been analyzed. The parish scribes as a professional body or a social group has not previously been explored. The examination of the 154 parish scribes as a professional and social group has been carried out in the form of a collective biography. Parish scribes’ tasks originally consisted of the collection of taxes, but the duties within the parish administration increased in the eighteenth and nineteenth centuries. The private writing assignments consisted of many different documents: bills of sale, probate inventories and estate distributions, wills, land tenancy agreements, life annuity and crofter agreements, promissory notes, auction records and different survey documents. The interaction with state power has been analyzed by examining five political decision-making processes that the peasants actively participated in.

Staircase in mammalian muscle without light chain phosphorylation

In disuse atrophied skeletal muscle, the staircase response is virtually absent and light chain phosphorylation does not occur. The purpose of the present study was to determine if staircase could be restored in atrophied muscle with continued absence of myosin light chain phosphorylation, by reducing what appears to be an otherwise enhanced calcium release. Control (untreated) and sham-operated female Sprague-Dawley rats were compared with animals after 2 weeks of complete inactivity induced by tetrodotoxin (TTX) application to the left sciatic nerve. In situ isometric contractile responses of rat gastrocnemius muscle were analyzed before and after administration of dantrolene sodium (DS), a drug which is known to inhibit Ca2+ release in skeletal muscle. Twitch active force (AF) was attenuated by DS from 2.2 ± 0.2 N, 2.7 ± 0.1 N and 2.4 ± 0.2 N to 0.77 ± 0.2 N, 1.05 ± 0.1 N and 1.01 ± 0.2 N in TTX (N = 5), sham (N = 11) and control (N = 7) muscles, respectively. Following dantrolene treatment, 10 s of 10-Hz stimulation increased AF to 1.32 ± 0.2 N, 1.52 ± 0.1 N and 1.45 ± 0.2 N for the TTX, sham and control groups, respectively, demonstrating a positive staircase response. Regulatory light chain (R-LC) phosphorylation was lower for TTX-treated (5.5 ± 5.5%) than for control (26.1 ± 5.3%) and sham (20.0 ± 5%) groups. There was no significant change from resting levels for any of the groups after DS treatment (P = 0.88). This study shows that treatment with dantrolene permits staircase in atrophied muscle as well as control muscle, by a mechanism which appears to be independent of R-LC phosphorylation.

Relative influence of age, resting heart rate and sedentary life style in short-term analysis of heart rate variability

In order to assess the relative influence of age, resting heart rate (HR) and sedentary life style, heart rate variability (HRV) was studied in two different groups. The young group (YG) consisted of 9 sedentary subjects aged 15 to 20 years (YG-S) and of 9 nonsedentary volunteers (YG-NS) also aged 15 to 20. The elderly sedentary group (ESG) consisted of 16 sedentary subjects aged 39 to 82 years. HRV was assessed using a short-term procedure (5 min). R-R variability was calculated in the time-domain by means of the root mean square successive differences. Frequency-domain HRV was evaluated by power spectrum analysis considering high frequency and low frequency bands. In the YG the effort tolerance was ranked in a bicycle stress test. HR was similar for both groups while ESG showed a reduced HRV compared with YG. Within each group, HRV displayed a negative correlation with HR. Although YG-NS had better effort tolerance than YG-S, their HR and HRV were not significantly different. We conclude that HRV is reduced with increasing HR or age, regardless of life style. The results obtained in our short-term study agree with others of longer duration by showing that age and HR are the main determinants of HRV. Our results do not support the idea that changes in HRV are related to regular physical activity.

Semantic and fuzzy modelling for human behaviour recognition in smart spaces : a case study on ambient assisted living.

Human activity recognition in everyday environments is a critical, but challenging task in Ambient Intelligence applications to achieve proper Ambient Assisted Living, and key challenges still remain to be dealt with to realize robust methods. One of the major limitations of the Ambient Intelligence systems today is the lack of semantic models of those activities on the environment, so that the system can recognize the speci c activity being performed by the user(s) and act accordingly. In this context, this thesis addresses the general problem of knowledge representation in Smart Spaces. The main objective is to develop knowledge-based models, equipped with semantics to learn, infer and monitor human behaviours in Smart Spaces. Moreover, it is easy to recognize that some aspects of this problem have a high degree of uncertainty, and therefore, the developed models must be equipped with mechanisms to manage this type of information. A fuzzy ontology and a semantic hybrid system are presented to allow modelling and recognition of a set of complex real-life scenarios where vagueness and uncertainty are inherent to the human nature of the users that perform it. The handling of uncertain, incomplete and vague data (i.e., missing sensor readings and activity execution variations, since human behaviour is non-deterministic) is approached for the rst time through a fuzzy ontology validated on real-time settings within a hybrid data-driven and knowledgebased architecture. The semantics of activities, sub-activities and real-time object interaction are taken into consideration. The proposed framework consists of two main modules: the low-level sub-activity recognizer and the high-level activity recognizer. The rst module detects sub-activities (i.e., actions or basic activities) that take input data directly from a depth sensor (Kinect). The main contribution of this thesis tackles the second component of the hybrid system, which lays on top of the previous one, in a superior level of abstraction, and acquires the input data from the rst module's output, and executes ontological inference to provide users, activities and their in uence in the environment, with semantics. This component is thus knowledge-based, and a fuzzy ontology was designed to model the high-level activities. Since activity recognition requires context-awareness and the ability to discriminate among activities in di erent environments, the semantic framework allows for modelling common-sense knowledge in the form of a rule-based system that supports expressions close to natural language in the form of fuzzy linguistic labels. The framework advantages have been evaluated with a challenging and new public dataset, CAD-120, achieving an accuracy of 90.1% and 91.1% respectively for low and high-level activities. This entails an improvement over both, entirely data-driven approaches, and merely ontology-based approaches. As an added value, for the system to be su ciently simple and exible to be managed by non-expert users, and thus, facilitate the transfer of research to industry, a development framework composed by a programming toolbox, a hybrid crisp and fuzzy architecture, and graphical models to represent and con gure human behaviour in Smart Spaces, were developed in order to provide the framework with more usability in the nal application. As a result, human behaviour recognition can help assisting people with special needs such as in healthcare, independent elderly living, in remote rehabilitation monitoring, industrial process guideline control, and many other cases. This thesis shows use cases in these areas.

Consequences of cerebroventricular insulin injection on renal sodium handling in rats: effect of inhibition of central nitric oxide synthase

In the present study, we investigated the effects of acute intracerebroventricular (icv) insulin administration on central mechanisms regulating urinary sodium excretion in simultaneously centrally NG-nitro-L-arginine methylester (L-NAME)-injected unanesthetized rats. Male Wistar-Hannover rats were randomly assigned to one of five groups: a) icv 0.15 M NaCl-injected rats (control, N = 10), b) icv dose-response (1.26, 12.6 and 126 ng/3 µL) insulin-injected rats (N = 10), c) rats icv injected with 60 µg L-NAME in combination with NaCl (N = 10) or d) with insulin (N = 10), and e) subcutaneously insulin-injected rats (N = 5). Centrally administered insulin produced an increase in urinary output of sodium (NaCl: 855.6 ± 85.1 Δ%/min; 126 ng insulin: 2055 ± 310.6 Δ%/min; P = 0.005) and potassium (NaCl: 460.4 ± 100 Δ%/min; 126 ng insulin: 669.2 ± 60.8 Δ%/min; P = 0.025). The urinary sodium excretion response to icv 126 ng insulin microinjection was significantly attenuated by combined administration of L-NAME (126 ng insulin: 1935 ± 258.3 Δ%/min; L-NAME + 126 ng insulin: 582.3 ± 69.6 Δ%/min; P = 0.01). Insulin-induced natriuresis occurred by increasing post-proximal sodium excretion, despite an unchanged glomerular filtration rate. Although the rationale for decreased urinary sodium excretion induced by combined icv L-NAME and insulin administration is unknown, it is tempting to suggest that perhaps one of the efferent signals triggered by insulin in the CNS may be nitrergic in nature.

Cystatin C and renal function in pediatric kidney transplant recipients

In clinical practice, the glomerular filtration rate (GFR) is often determined with serum creatinine. However, studies have shown cystatin C to be a better parameter for the diagnosis of impaired renal function. We compared GFR estimated by plasma cystatin C with GFR estimated by serum creatinine in a sample of 50 pediatric renal transplant recipients and 24 healthy children. The correlation between GFR estimated by serum creatinine and by cystatin C was significant (r = 0.75; P < 0.001, Person’s correlation); however, in pediatric kidney transplant recipients, the GFR was 6.7 mL/min lower when determined using cystatin C rather than serum creatinine. Moreover, using GFR estimated by cystatin C we found that 42% of the pediatric kidney transplant recipients had an estimated GFR <60 mL·min-1·1.73 (m²)-1, whereas when GFR was estimated by the serum creatinine formula only 16% of the children had values below this cutoff point indicative of chronic kidney disease (P < 0.001). We conclude that, in pediatric kidney transplant recipients, estimation of GFR yields lower values when cystatin C is used rather than serum creatinine.