Chicken antibodies, commonly referred to as IgY, have several properties that make them suitable for oral treatment of infections and there is essentially no risk for development of resistance. The overall aims of this thesis were to investigate Anti-Pseudomonas IgY as prophylaxis against infections with Pseudomonas aeruginosa for cystic fibrosis (CF) patients and to characterize the antibody treatment. We found that Anti-Pseudomonas IgY has affinity for P. aeruginosa flagellin, the major component of the flagellum. This is important since the flagellum is required for host invasion and establishment of infection. Flagellin induces inflammation. The main cause of morbidity and mortality among CF patients is chronic colonization of the airways with P. aeruginosa. We have studied prophylactic treatment of 17 Swedish CF patients with Anti-Pseudomonas IgY for up to twelve years. The results were compared with a control group of 23 Danish CF patients. Patients treated with IgY had 2.3 P. aeruginosa positive cultures/100 treatment months vs. 7.0 cultures/100 treatment months in the control group (p=0.028), and the time from inclusion to the first recolonization was significantly longer in the IgY-treated group (p=0.012). Lung function was preserved and patients treated with IgY had good nutritional status at the end of the study. Furthermore, other bacteria have not emerged instead of P. aeruginosa. Freeze-drying of IgY and the content of IgY preparations for oral use was investigated. Besides IgY, 26 egg yolk proteins were identified. Some of the proteins are known to have antimicrobial and immunostimulatory effects, and could have a positive additive effect to IgY treatment. Cholesterol levels were low. Conclusion: Anti-Pseudomonas IgY is a promising complement in the prevention of Pseudomonas aeruginosa infections in CF patients, partly explained by the fact that IgY binds to flagellin. / Felatkigt ISBN ändrat: Tidigare 978-91-554-7477-5 nu 978-91-554-7478-2

Fler unga människor än någonsin är idag överviktiga och stress och stressrelaterade symptom drabbar idag allt fler unga. Därför är det viktigt att unga människor får kunskaper om hur de på bästa sätt kan ta hand om sig själva.  Syftet med detta arbete är att undersöka hur elever som läser gymnasiets kurs Idrott och hälsa A ser på den hälsoundervisning de får. Detta är relevant för alla som arbetar som idrott och hälsa lärare för att kunna hitta en jämkning mellan kursplan och elevernas tankar och förkunskaper.  Genom intervjuer och fokusintervjuer kom jag fram till att eleverna vill lära sig mer om stress och hur man hanterar stress samt om kost. Eleverna tycker däremot att idrottsläraren inte är rätt person att lära ut kunskaper om tobak.

<p>Fler unga människor än någonsin är idag överviktiga och stress och stressrelaterade symptom drabbar idag allt fler unga. Därför är det viktigt att unga människor får kunskaper om hur de på bästa sätt kan ta hand om sig själva.</p><p> Syftet med detta arbete är att undersöka hur elever som läser gymnasiets kurs Idrott och hälsa A ser på den hälsoundervisning de får.</p><p>Detta är relevant för alla som arbetar som idrott och hälsa lärare för att kunna hitta en jämkning mellan kursplan och elevernas tankar och förkunskaper.</p><p> Genom intervjuer och fokusintervjuer kom jag fram till att eleverna vill lära sig mer om stress och hur man hanterar stress samt om kost. Eleverna tycker däremot att idrottsläraren inte är rätt person att lära ut kunskaper om tobak.</p>

Waran används sedan 60 år som blodförtunnande läkemedel för att förebygga eller förhindra progress av blodproppssjukdom. I Sverige behandlas årligen cirka 1 % av befolkningen med waran. I Östergötland uppskattas antal waranpatienter till cirka 3000. Waran hämmar enzymet VKORC1 som ansvarar för vitamin K omsättningen i kroppen. Vitamin K behövs som kofaktor för flera koagulationsfaktorer. Behandling med waran är förenad med en svår balansgång och kräver en noggrann dosering. Stora skillnader i dosbehov mellan olika individer, beroende på ärftliga och miljöfaktorer, gör waran till ett svårhanterligt läkemedel. För låg dos medför otillräcklig effekt och därmed risk för minskat skydd mot blodproppssjukdom. För hög dos leder till allvarliga blödningskomplikationer. Uppskattningsvis 1 – 3 % livshotande blödningsfall registreras årligen efter waranbehandling. Därför måste behandlingen kontrolleras noga med analys av protrombinkomplex (PK) och dosjusteringar göras med ledning av resultaten. Två olika metoder finns att använda för mätning av PK. I Norden och i Japan används Owrens metod (utvecklat i Norge under 40- och 50-talet av Paul Owren). I de flesta andra länder används Quickmetoden (utvecklat i USA under 30-talet av Armand Quick). Den senare metoden är förenad med stora variationer mellan olika analyslaboratorier. I Norden, däremot, där Owrens metod används finns det ofta bra överensstämmelse mellan olika laboratorier i PK-resultat. Beroende på vilken PK-metod som används, kan samma patient få olika warandoser vilket ökar risker för under- eller överbehandling. Vi har i samarbete med flera sjukhus och antikoagulationsmottagningar (AK-mottagningar) i sydöstra Sverige studerat dels mekanismerna bakom skillnader i warandos mellan olika patienter, och dels tittat varför de olika PK-metoder skiljer sig så mycket som de gör. I studien har vi identifierat genetiska varianter av enzymet VKORC1. Av de undersökta patienter som gick på waran under längre tid, har vi identifierat en grupp som markant skiljde sig från de övriga. Denna grupp hade warandoser som var betydligt lägre än de övriga. När vi kartlade deras arvsmassa, fann vi att lågdospatienterna hade genvarianten VKORC1*2. Dessutom hade patienter med denna variant svårigheter att få stabila PK-värden. De gjorde också fler besök på AK-mottagningar än andra patienter. Vi har därför konstaterat att en del av de problem som är förenade med waranbehnadlingen kan förklaras av VKORC1*2 varianten. Vetskap om denna variant skulle troligen underlätta behandlingen framför allt under inledningsfasen då patienter med VKORC1*2 riskerar blödningar på grund av överdosering. Vi har identifierat att provförspädning enligt Owrens metod är nödvändig för harmonisering av PK-resultatet mellan olika länder. Quickmetoden använder inte förspädning av patientprov till skillnad från Owrens metod. När vi modifierade en Quickmetod genom att förspäda prover enligt Owrens metod noterade vi en bra överensstämmelse mellan de två olika metoderna. Däremot var resultatet sämre utan provförspädning. Vi anser att Quickmetoder kan uppnå lika bra resultat som Owrens metod om prover förspäds som i Owrens metod. Det skulle gynna patienter som reser mellan olika regioner eller länder och leda till en bättre övervakning av waranbehandling internationellt. I studien har dessutom en metod för mätning av waran i blodet utvecklats. Metoden som är den enda i sitt slag i Norden ger möjlighet att studera hur läkemedlet beter sig i kroppen. Vi har med denna metod kunnat upptäcka patienter som har onormala nedbrytningar av waran. / Warfarin was introduced more than 60 years ago and is used worldwide for the prophylaxis of arterial and venous thromboembolism in primary and secondary prevention. The drug is orally administered as a racemic mixture of (R)- and (S)-enantiomers. The (S)-form is mainly responsible for the anticoagulant effect and is metabolised by CYP2C9 enzyme in the liver microsomes. Warfarin exerts its pharmacological action by inhibiting the key enzyme (VKORC1) that regenerates vitamin K from an oxidised state to a reduced form. The latter is a cofactor for the post-translational modification of a number of proteins including coagulation factors II, VII, IX and X. The vitamin K-dependent modification provides these factors with the calcium-binding ability they require for the interaction with cell membranes of their target cells such as platelets. Warfarin is monitored by measuring prothrombin time (PT) expressed as INR. Two main methods exist for PT analysis. The Owren method is used mainly in the Nordic and Baltic countries, in Japan, whereas the Quick method is employed in most other countries. Warfarin management is associated with some complications. Unlike many other drugs the dose for a given patient cannot be estimated beforehand, dose-response relationship is not predictable, and the prevention of thrombosis must be balanced against the risk of bleeding. Furthermore, the different PT methods used to monitor the drug are sometimes not in agreement and show significant discrepancies in results. In an attempt to clarify the mechanisms influencing the inter-individual variations in warfarin therapy and to detect the factors that contribute to differences between PT methods, studies were conducted in collaboration with hospitals and anticoagulation clinics in the south-eastern region of Sweden. First, a stereo-specific HPLC method for measurement of warfarin enantiomers was developed and validated. With this method, the levels of plasma warfarin following its oral administration can be studied and evaluated. Abnormal clearance in some patients can be detected, and patient compliance can be verified. Furthermore, differing ratios of (S)- and (R)-isomers can be identified. The impact of common VKORC1 polymorphisms on warfarin therapy was investigated. This study has shown that the VKORC1*2 haplotype is an important genetic determinant for warfarin dosage and is associated with difficulties in attaining and retaining therapeutic PT-INR. Further, significant differences in warfarin S/R-ratio was detected between patients with VKORC1*2 and VKORC1*3 or VKORC1*4 variants. This difference was not coupled with CYP2C9 genotype. The effects of predilution of patient plasma samples, sources of thromboplastin and deficient plasma on between PT methods agreement were studied. This study has revealed that sample predilution according to the Owren method is to be preferred for the harmonisation of PT results. Undiluted samples, in contrast, according to the Quick method have shown reduced correlation between two different thromboplastin reagents. Sources of thromboplastin and deficient plasma were only of minor importance.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2006. / Härtill 5 uppsatser.

<p>Analysis of M-components is an important part of the diagnosis of monoclonal gammopathies and for the evaluation of disease response during treatment. In this project, two widely used electrophoresis methods and their corresponding immunotyping method were compared to evaluate the sensitivity of each method for the detection of small M-components. The project included 30 plasma samples from patients with identified M-components; 10 samples containing each IgG, IgA and IgM, respectively. All samples were diluted with normal EDTA plasma to achieve M-components of 5,00g/L. The samples were then serially diluted to achieve M-component concentrations of; 5,00, 2,50, 1,25, 0,63, 0,31 and 0,16g/L. All 180 samples were analysed with agarose gel electrophoresis and capillary electrophoresis. The dilutions above and below the detection level of each method were then analysed with immunofixation and immunosubtraction. The results showed good agreement between agarose gel electrophoresis and capillary electrophoresis in the highest concentrations of IgG and IgM. With agarose gel electrophoresis, IgA was detected in the same location as transferrin and the lowest concentration detected were therefore 1,25g/L. Besides the samples containing IgG, immunofixation was the most sensitive method.</p>

<p>Haematology instruments using optical and fluorescence techniques have improved the platelet count in domestic animals. There are still some difficulties present, especially when counting cat thrombocytes due to their ability to aggregate and the occurrence of large platelets.</p><p>The objective of this study was to evaluate and compare the platelet count, mean platelet volume and platelet crit in dogs, horses and cats on Advia 2120 and Sysmex XT-2000iV.</p><p>Fresh blood samples from 64 dogs, 40 horses and 39 cats with various medical conditions were analysed on both instruments. Manual blood smears of all feline samples were scrutiniously analysed to evaluate the aggregation warning flag from Advia.</p><p>There was good agreement between the instruments for the optical platelet count in dogs and cats. Slightly higher values were reported from Advia. Samples from horses presented poor correlations for all studied parameters. Platelet clumps appeared in 70% of the 37 scrutinized feline blood smears, while 46% of the samples generated aggregation warning flags from the Advia instrument.</p><p>Advia and Sysmex showed good agreement for platelet counts in blood from dogs and cats. Mean platelet volume and platelet crit need further evaluation before conclusions can be made concerning their clinical relevance. The sensitivity of the platelet aggregation warning flag from the Advia instument needs further elevation.</p>

<p>Mantle cell lymphoma (MCL) is a non-Hodgkin B-cell lymphoma with very bad prognosis. The genetic hallmark of MCL, is the translocation t(11;14)(q13;q32) which leads to overexpression of cyclin D1, a D-type cyclin that is not usually expressed at high levels in normal B lymphocytes.</p><p> </p><p>Previous studies indicate that cannabinoid receptors are expressed in lymphoma and have shown that lymphoma cell death is induced as a result of exposure to cannabinoids (ligands).</p><p> </p><p>The aim of this diploma work was to combined cytostatics with the cannabinoid receptor ligand R (+)-Methanandmide (R-MA). Our data suggest that combination treatment with cytostatics and R-MA induces synergistic effects in most cases.</p>

<p>The insulin-like 3 peptide is autocrine/paracrine insulin-related hormone with a size of approximately 6kDa [1]. It mediates through a leucine richG-coupled receptor named LGR8. INSL3 is mainly expressed in human Leydig cells and is directly responsible for migration of the testis during the pre-natal period in maledevelopment. [2]</p><p>INSL3 mRNA has recently been verified in human platelets whereas no mRNA has been detected for LGR8 (by Sanofi-Aventis GmbH in Frankfurt,Germany), indicating that INSL3 might be released through paracrine functions at sites of platelet adhesion and aggregation upon a vascular injury.Furthermore, has activated platelets been shown to translate essential proteins upon activation, in a term called “signal-dependent protein synthesis”.The B-Cell lymphoma-3 protein (BCL-3) is an example of such a protein [3], and there is a possibility that INSL3 might be also.</p><p>In this thesis we wanted to detect the relaxin- like peptide 3 hormone (INSL3). (Its function, location and the timeframe of its release, when/if it issecreated in stimulated platelets).The source of platelet-derived INSL3 can be found with Western blotting and Enzyme immunoassay.</p><p>Detection of the insulin-like 3 peptide in human platelets turned out to be a difficult challenge due to the small amount of INSL3 secretion uponplatelet activation; hence the total amount of INSL3 produced might be below detection limit.</p>

<p><strong>Objective</strong><em>:</em> Estimation of glomerular filtration rate (GFR) is an important tool in the diagnosis and management of chronic kidney disease. Today creatinine is the most frequently used marker for kidney function though several studies indicate that cystatin C is a superior marker. The purpose of this study was to validate Abbott Diagnostics turbidimetric cystatin C assay and enzymatic creatinine assay.</p><p><strong>Methods</strong><em>:</em> The validation was performed by studies of CV for the two methods and correlations between the two and other available methods for assessing GFR. The stability of cystatin C at room temperature was also evaluated.</p><p><strong>Results</strong><em>: </em>Both methods showed good precision. The Abbott cystatin C assay generally gave lower values and thereby higher estimated GFRs than the correlated Gentian method. The Abbott enzymatic creatinine assay gave higher values than the correlated Jaffe method. Those results are generally unexpected, but in this study the cause is an automatically applied negative intercept used together with the Jaffe method. Cystatin C showed high stability when stored at room temperature.</p><p><strong>Conclusions</strong><em>:</em> Estimated GFRs tend to differ depending on the choice of method for analyzing cystatin C or creatinine and this study gives an overview of the range of variation. The study also enlightens the need for an international calibrator for the cystatin C methods presented by different manufacturers.</p>