The Angiotensin II Type 1 (AT1) receptor is the main receptor responsible for the effects of the renin-angiotensin system, and its expression pattern is altered in several diseases. [11C]Methyl-Losartan has been developed based on the clinically used AT1 receptor antagonist Losartan. The aim of this work is to characterize the pharmacokinetics, repeatability and reliability of measurements, binding specificity and selectivity of [11C]Methyl-Losartan in rats using in vivo small animal positron emission tomography (PET) imaging, ex vivo biodistribution and in vitro autoradiography methods. Also, we aim to measure the presence of metabolites in the kidney and plasma using high-performance liquid chromatography. We have demonstrated in vivo that [11C]Methyl-Losartan is taken up in the AT1 receptor-rich kidneys and that it is displaceable by selective AT1 receptor antagonists. Using ex vivo biodistribution, we have confirmed these results and demonstrated that [11C]Methyl-Losartan binds selectively to the AT1 receptor over the AT2, Mas and β-adrenergic receptors. In vitro autoradiography results confirmed these renal binding selectivity studies. [11C]Methyl-Losartan was also shown to have one and two C-11 labeled metabolites in the plasma and kidneys, respectively. In conclusion, [11C]Methyl-Losartan is a promising agent for studying the AT1 receptor in rat models with normal and altered AT1 receptor expression using small animal PET imaging.

The Angiotensin II Type 1 (AT1) receptor is the main receptor responsible for the effects of the renin-angiotensin system, and its expression pattern is altered in several diseases. [11C]Methyl-Losartan has been developed based on the clinically used AT1 receptor antagonist Losartan. The aim of this work is to characterize the pharmacokinetics, repeatability and reliability of measurements, binding specificity and selectivity of [11C]Methyl-Losartan in rats using in vivo small animal positron emission tomography (PET) imaging, ex vivo biodistribution and in vitro autoradiography methods. Also, we aim to measure the presence of metabolites in the kidney and plasma using high-performance liquid chromatography. We have demonstrated in vivo that [11C]Methyl-Losartan is taken up in the AT1 receptor-rich kidneys and that it is displaceable by selective AT1 receptor antagonists. Using ex vivo biodistribution, we have confirmed these results and demonstrated that [11C]Methyl-Losartan binds selectively to the AT1 receptor over the AT2, Mas and β-adrenergic receptors. In vitro autoradiography results confirmed these renal binding selectivity studies. [11C]Methyl-Losartan was also shown to have one and two C-11 labeled metabolites in the plasma and kidneys, respectively. In conclusion, [11C]Methyl-Losartan is a promising agent for studying the AT1 receptor in rat models with normal and altered AT1 receptor expression using small animal PET imaging.

Equine Herpesvirus type 1 (EHV-1) is a worldwide threat to the health of horses. It can cause mild respiratory disease, abortions and deaths of newborn foals as well as a potentially fatal neurologic disorder known as Equine Herpesvirus Myeloencephalopathy (EHM). The virus is maintained in populations by stress-induced periodic reactivation of virus in long-term latently infected horses and transmission of the reactivated virus to susceptible individuals. In horses, peripheral blood leukocytes (PBLs) are thought to be an important site for EHV-1 latent genomes. Since the Unfolded Protein Response (UPR) is a cellular response to a variety of stressors that has been linked to reactivation of herpes simplex virus in humans, a virus closely related to EHV-1, I tested the hypothesis that latent EHV-1 relies on the UPR as a pluripotent stress sensor and uses it to reactivate lytic gene expression. Since little work has been done in defining the UPR in horses, I first successfully developed a quantitative real-time polymerase chain reaction (RT-qPCR) assay to detect and quantitate transcripts for selected UPR genes in equine dermal (E.Derm) cells and PBLs. Activation of the UPR was achieved in both cell types using thapsigargin and a difference in gene expression after activation of the UPR in two equine cell types was found. A nested PCR assay to detect and distinguish latent EHV-1 and EHV-4 was evaluated and the sensitivity of the technique to detect EHV-1 was determined. I discovered that the nested PCR technique was not sensitive enough to detect the estimated one latent viral genome in 50,000 PBLs. Lytic EHV-1 infection was characterized by single step growth curve in E.Derm cells and consistent detection of temporal EHV-1 gene expression by RT-qPCR was achieved. The relationship between EHV-1 gene expression and UPR gene expression during lytic infection was investigated. While EHV-1 infection had no effect on UPR gene expression, activation of the UPR appeared to decrease the expression of EHV-1 genes temporarily and reversibly during the first 4 h after infection. Finally, detection of EHV-1 in PBLs from horses presumed to be latently infected by co-cultivation with E. Derm cells permissive to EHV-1 infection was attempted. To detect viral DNA, PBLs were stimulated with thapsigargin or interleukin 2 (IL-2) which was previously reported to induce reactivation of latent EHV-1. I was not able to reproduce previously published experiments of reactivation in vitro of latent EHV-1 by stimulation with IL-2, and virus reactivation did not occur after stimulation of PBLs with thapsigargin. In summary, a RT-qPCR assay to measure the expression of equine UPR genes was developed and activation of the UPR by treatment of E.Derm cells and PBLs with thapsigargin was successfully achieved. A difference in gene expression after activation of the UPR in two equine cell types was found. In contrast to what has been reported for other alphaherpesviruses, there appears to be no, or only little, interaction between the UPR and EHV-1 during viral infection. Detection of latent EHV-1 genomes in PBLs was not achieved by using a nested PCR, as this technique was not sensitive enough to detect the estimated one latent viral genome in 50,000 PBLs. Finally, latent EHV-1 was not detected in presumed latently infected PBLs or reactivated by triggering the UPR in equine PBLs.

Sammanfattning  Bakgrund: Typ 1 diabetes är en av de vanligaste kroniska sjukdomarna bland barn. Målet för all diabetesbehandling hos barn är att normalisera blodsockernivån för att undvika senkomplikationer i vuxen ålder. Eftersom barnet tillbringar en stor del av dagen i skolan så behöver behandlingen fungera bra under skoldagen. År 2008 uppgav barndiabetesteam i Sverige att ca 50 % av alla barn med diabetes i låg- och mellanstadiet inte får ett tillräckligt stöd i sin diabetesbehandling i skolan. En funktion som diabeteskonsulent har testats i Jönköpings läns landsting under två år för att erbjuda kunskaper som skolpersonal behöver angående diabetes.Syfte: Att beskriva diabeteskonsulentens möjlighet att påverka de stöd som barn med typ 1 diabetes får i skolan. Metod: Insamlingen av empirisk data har skett genom intervjuer, enkäter och jämförelse av HbA1c. Resultat: Diabeteskonsulenten upplever att hon har möjlighet att förmedla den kunskap som skolpersonal behöver. De föräldrar vars barn haft besök av diabeteskonsulenten upplever sig mindre ofta vara oroliga över att barnet inte får ett bra stöd i skolan, fler av dessa barn har en huvudansvarig person i skolan samt fler barn har en individuellt informationsplan än de barn som inte haft besök. Funktionen som diabeteskonsulent har inte förändrat den metabola kontrollen under studieperioden.Diskussion: Resultatet av interventionen visar att en diabeteskonsulent kan vara ett framgångsrikt arbetssätt för att förbättra stödet till barn med typ 1 diabetes i skolan. Ytterligare studier behövs för att klargöra i vilka årskurser diabeteskonsulenten gör mest nytta och för att efterhöra skolpersonalens upplevelse av diabeteskonsulentens arbete. / AbstractBackground: Type 1 diabetes is one of the most common chronic diseases in children. The overall goal in treating diabetes is to normalize the blood sugar level, in order to avoid complications in adulthood. Since a child spends a large part of the day at school, the treatment has to work well during the school hours. In 2008, paediatric diabetes team in Sweden reported that about 50% of the children in lower primary school, suffering from diabetes, do not receive sufficient support in their diabetic treatment at school. A function such as diabetes resource nurse has been tested in Jönköping County Council for two years to offer the school staff necessary knowledge about diabetes. Purpose: Describe the diabetes resource nurse possibility to influence the support children with diabetes receive at school. Method: The collection of empirical data was done through interviews, questionnaires and comparison of HbA1c. Results: The diabetes resource nurse feels that she is able to convey the knowledge necessary for the school personnel. Parents whose children have been visited by a diabetes recourse nurse says that they less often fear that their child does not get good support at school, that more of the children have a person in charge in school and that more children have an individual communication plan, compared to parents whose children have not been visited by a diabetes resource nurse. The function of the diabetes resource nurse did not improve the metabolic control during the study period. Discussion: The result of the intervention shows that a diabetes resource nurse can successfully improve the support children with type 1 diabetes receive at school. Further studies are needed to clarify which grades benefits the most from the support of a diabetes resource nurse and inquire the school personnel's experience of the diabetes consultant's work.

Syfte: Att utifrån litteratur beskriva hur sjuksköterskan kan identifiera tecken på depression hos tonåringar med typ 1 diabetes och hur hon kan stödja dessa tonåringar. Metod: En deskriptiv litteraturstudie som baseras på 15 artiklar sökta i databaserna CINAHL och PubMed samt genom manuella sökningar. Huvudresultat: Tecken på depression hos tonåringar med typ 1 diabetes är högt HbA1c-värde, låg frekvens av blodsockerkontroller och lägre livskvalité. Sjuksköterskan kan använda sig av standardiserade mätinstrument för att identifiera tecken på depression hos tonåringar med typ 1 diabetes, till exempel CDI, CES-D, YSR, WHO-5 och VAS. Tonåringar med typ 1 diabetes önskar stödåtgärder i form av skräddarsydda strukturerade undervisningsprogram, roliga aktiviteter och uppföljning via SMS. Sjuksköterskan kan använda sig av gruppintervention, internetbaserade egenvårdsprogram samt be tonåringarna skriva själva om sin diabetes, vilket har visat sig ha positiva effekter på tonåringens välbefinnande. Vårdgivare uppger flera hinder i hanteringen av depression hos diabetespatienter, bland annat otillräcklig utbildning och tidsbrist. Slutsats: Det är viktigt med utbildning för sjuksköterskor inom området tonåringar, typ 1 diabetes och depression. Mer forskning är nödvändigt för att möta kombinationen typ 1 diabetes och depression hos tonåringar. / Aim: To describe according to the literature how the nurse can identify signs of depression in adolescents with type 1 diabetes and how the nurse can support them. Method: A literature study with descriptive design based on 15 scientific articles searched in the databases CINAHL, PubMed and by ancestry approach. Main results: Signs of depression in adolescents with type 1 diabetes are high HbA1c, low frequency of blood glucose monitoring and lower quality of life. The nurse can use standardized questionnaires to identify signs of depression in adolescents with type 1 diabetes, for example CDI, CES-D, YSR, WHO-5 and VAS. Adolescents with type 1 diabetes wish supportive measures such as tailored, structured education programs, fun activities and follow-up by text messaging. The nurse can use group interventions, internet-based self-care programs and ask adolescents to write about their diabetes, because this has positive effects on the adolescent’s well-being. Health care providers report several obstacles in the management of depression in patients with diabetes, among other things inadequate training and lack of time. Conclusion: It is important with training for nurses in the field of adolescents, type 1 diabetes and depression. More research is needed to meet the combination of type 1 diabetes and depression in adolescents.

Syftet med denna litteraturstudie var att beskriva hur föräldrar till barn med diabetes mellitus typ 1 upplever och hanterar sin vardag samt hur de upplever stöd och information från sjukvården. Den design som användes var beskrivande litteraturstudie. De databaser som användes var Cinahl och PubMed och resultatet formades från 15 vetenskapliga artiklar. Det resultat som framkom var att i samband med barnets insjuknande upplevde föräldrar bland annat kaos, ångest, sorg och chock. Föräldrarna fick ta ett stort ansvar över sjukdomen och de använde olika copingstrategier för att kunna hantera detta. Oron för att barnet skulle drabbas av hypoglykemi var stor hos många föräldrar och många var också oroliga över att låta barnet ta ansvar över sin sjukdom. Att kunna få stöd från sjukvården tyckte många föräldrar var viktigt, de sökte också information på andra sätt exempelvis genom föräldragrupper. De 15 vetenskapliga artiklarna kvalitetgranskades, analyserades och sammanställdes. Den slutsats som framkom var att livet förändrades på många olika sätt efter att barnet fått sin diagnos. Detta krävde stort engagemang från föräldrarna då hela familjens liv påverkades. / The purpose of this study was to describe how parents of children with type 1 diabetes mellitus experienced and coped with their everyday lives and how they experienced support and information from health care. The used design was descriptive literature study. The databases used were Cinahl and PubMed and the result was formed from 15 scientific articles. The results that emerged were that in connection with the child got sick the parents experienced including chaos, anxiety, grief and shock. The parents had to take a major responsibility of the disease and used different coping strategies to deal with it. Concern that the child would suffer from hypoglycemia was high among many parents and many were also concerned about letting the child take responsibility over their illness. Many parents found it important to be eligible support from health care professionals, they also examined the information in other ways such as parent groups. The 15 scientific articles quality were examined analyzed and summarized. The conclusion that emerged was that life changed in many different ways after the child received his diagnosis. This required considerable commitment from the parents when the entire family´s lifes were affected.

This study aims to identify the perceived barriers to eye care and to evaluate concerns about vision and eye care among patients with diabetes in the greater New Haven area. A qualitative study applying one-on-one semi-structured interviews and non-participatory observations was conducted to identify the factors that deter diabetics from seeking eye care. Patients were recruited at the Yale Primary Care Center, Diabetes Center and Eye Center, who met the following criteria: 1) have been diagnosed with type 1 or type 2 diabetes and 2) have been referred to an eye center for dilated eye exam and/or treatment. All interviews and discussions were recorded and transcribed. The transcripts were then analyzed to detect recurrent themes. Data collection continued until no new themes emerged. This study showed that lack of awareness and lack of adequate referral to regular diabetic eye exam were viewed as the most common barriers. Many patients had limited awareness that diabetes could affect the eye or lead to blindness. Patients had little knowledge of diabetic retinopathy, or the significance of early screening and intervention. Primary care providers usually emphasized diet and blood sugar control to prevent future complications; diabetic eye care education was not often prioritized. Other barriers included cost, lack of insurance, immobility due to diabetic complications, reluctance to receive medical intervention, and distrust of the services. A strong family history of diabetes and blindness due to diabetes contributed to the awareness of diabetic retinopathy, and as a result motivated patients to seek regular eye care. Raising the awareness of diabetic retinopathy and the risk of vision loss, offering more diabetic eye care education, tracking the status of patients eye exam attendance, and providing adequate eye exam referral to a patient friendly eye clinic may encourage diabetics to attend regular eye exams.

Welche Schrift für welchen Zweck? Lohnt es sich, Fonts zu kaufen? Was sollte man beim Einsatz neuer Schriften beachten? Wie unterscheidet man überhaupt Fonts?

Thesis (Ph. D.)--Cornell University, January, 2007. / Vita. Includes bibliographical references.

Thèse d'exercice : Médecine : Nancy 1 : 2008. / Titre provenant de l'écran-titre.