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Studies on intrinsic and extrinsic sources of variability in pharmacokinetics and pharmacodynamics

Popular Abstract in Swedish Variabilitet i ett läkemedels farmakokinetiska (hur ett läkemedel omsätts i kroppen) och farmakodynamiska (vilken effekt ett läkemedel har) egenskaper kan resultera i att olika individer som erhållit samma dos av ett läkemedel får olika effekter av läkemedel. Biverkningar eller utebliven effekt kan innebära allvarliga konsekvenser för den enskilda individen. VariabiliteVariability in pharmacokinetic and pharmacodynamic parameters between individuals can be due to intrinsic and extrinsic factors. In this thesis three different areas regarding sources of variability have been investigated. 1. Formulation properties as an extrinsic source of variability. Lipophilic substances often have poor oral bioavailability and high inter- and intraindividual variability. High

Traditional versus agricultural lifestyle among Shuar women of the Ecuadorian Amazon: Effects on leptin levels

Leptin is a key biological marker related to energy balance and development of diabetes and cardiovascular diseases. Its levels are increased in populations with a high degree of the metabolic syndrome. Life history of evolution has, however, largely taken place under the ecological context of hunting and gathering. In this study, we explored whether the first steps of transition to sedentary agri

Contribution of known and unknown susceptibility genes to early-onset diabetes in scandinavia: evidence for heterogeneity.

In an attempt to identify novel susceptibility genes predisposing to early-onset diabetes (EOD), we performed a genome-wide scan using 433 markers in 222 individuals (119 with diabetes) from 29 Scandinavian families with ≥2 members with onset of diabetes ≤45 years. The highest nonparametric linkage (NPL) score, 2.7 (P < 0.01), was observed on chromosome 1p (D1S473/D1S438). Six other regions on chr

Efficacy and safety of a new combination of calcipotriol and betamethasone dipropionate (once or twice daily) compared to calcipotriol (twice daily) in the treatment of psoriasis vulgaris: a randomized, double-blind, vehicle-controlled clinical trial.

Background Calcipotriol and betamethasone dipropionate are both widely used, effective treatments for psoriasis. Vitamin D analogues and topical corticosteroids have different mechanisms of action in the treatment of psoriasis. A new vehicle has been developed in order to contain both calcipotriol (50 micro g g-1) and betamethasone dipropionate (0.5 mg g-1) in an ointment form. By using calcipotri

Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition

Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. Its aetiology may involve dietary antioxidant micronutrients such as carotenoids and tocopherols. The objective of this study was to determine the association of plasma levels of seven common carotenoids, their total plasma concentration, retinol and alpha- and gamma-tocopherol, with the risk of gastric ade

In-plane visibility of lesions using breast tomosynthesis and digital mammography

Purpose: The purpose of this work was to evaluate the visibility of simulated lesions in 2D digital mammography (DM) and breast tomosynthesis (BT) images of patients. Methods: Images of the same women were acquired on both a DM system (Mammomat Novation, Siemens Healthcare, Erlangen, Germany) and a BT prototype system adapted from the same type of DM system. Using the geometrical properties of the

Crystallographic Studies of Ternary Chalcogenides and Organic Semiconductors

X-ray diffraction methods have been used to study the crystal structure of different compounds, both organic and inorganic. The inorganic compounds were all synthesized by solid state reactions. A new compound, Re4As6S3, was synthesized and its structure was solved by Rietveld methods. Re4As6S3 is a cluster compound described by a

Molecular Structure and Packing of Platinum(II) Complexes with S-donor Ligands in the Solid State An X-ray Crystallographic Study

Popular Abstract in Swedish All materia består av atomer. Avhandlingen du just nu läser är uppbyggd av atomer; till och med du själv är uppbyggd av atomer. En kemist är intresserad av vilka atomer som hänger ihop för att bilda molekyler och hur dessa molekyler kan sammanfogas till fasta material. Man kan likna det vid att molekylerna är en byggsten som då de sammanfogas bildar en byggnadskonstruktHow do molecules arrange themselves in a crystal? It is today not possible to definite predict the three-dimensional packing arrangement of molecules in the crystalline solid state. The aim of the work presented in this thesis has been to gain more knowledge of what principles that govern molecular packing. Platinum(II) complexes have been chosen as model system since these compounds are stable,

Epidemiology and clinical manifestations of Lyme borreliosis.

Popular Abstract in Swedish Det har nu gått 20 år sedan ett utbrott av ledinflammation (arthrit), i Connecticut, USA, satte forskarna på spåret till den sjukdomsbild som vi idag kallar fästingöverförd borreliainfektion och det är snart 15 år sedan man lyckades isolera bakterien som orsakar sjukdomen, Borrelia burgdorferi. Symptomen på sjukdomen har visserligen varit kända sedan sekelskiftet men he

Dietary Intakes of Individual Flavanols and Flavonols Are Inversely Associated with Incident Type 2 Diabetes in European Populations

Dietary flavanols and flavonols, flavonoid subclasses, have been recently associated with a lower risk of type 2 diabetes (T2D) in Europe. Even within the same subclass, flavonoids may differ considerably in bioavailability and bioactivity. We aimed to examine the association between individual flavanol and flavonol intakes and risk of developing T2D across European countries. The European Prospec

Two-step in vitro antibody affinity maturation enables estradiol-17β assays with more than 10-fold higher sensitivity.

Immunoassays for haptens depend on competitive hapten-anti-hapten reactions, and consequently their sensitivities are significantly influenced by the affinities of anti-hapten antibodies. Thus, genetically engineered antibodies, which have much higher affinities than native antibodies, should increase assay sensitivities. Here, we created a mutated single-chain Fv fragment (scFv) against estradiol

Risk of thromboembolic diseases in men with prostate cancer: results from the population-based PCBaSe Sweden

Background Cancer is associated with an increased risk of thromboembolic diseases, but data on the association between prostate cancer and thromboembolic diseases are scarce. We investigated the risk of thromboembolic disease in men with prostate cancer who were receiving endocrine treatment, curative treatment, or surveillance. Methods We analysed data from PCBaSe Sweden, a database based on the

FTO genetic variants, dietary intake and body mass index: insights from 177 330 individuals.

FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from

Degenerative changes at the lumbar spine-implications for bone mineral density measurement in elderly women.

Degenerative changes of the lumbar spine may lead to misinterpretation of bone mineral density (BMD) measurements and cause underdiagnosis of osteoporosis. This longitudinal study of 1,044 women, 75 years at inclusion and followed for 10 years, shows that identification of apparent degenerative changes on the dual energy X-ray absorptiometry (DXA) scan can increase the proportion diagnosed. INTR

Apolipoprotein(a) Genetic Sequence Variants Associated With Systemic Atherosclerosis and Coronary Atherosclerotic Burden But Not With Venous Thromboembolism

Objectives The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene (LPA) on vascular diseases with different atherosclerotic and thrombotic components. Background It is unclear whether the LPA variants rs10455872 and rs3798220, which correlate with lipoprotein(a) levels and coronary artery disease (CAD), confer susceptibility predominantly via atherosclerosis

Perceptions of genetic research and testing among members of families with an increased risk of malignant melanoma

Background: Several melanoma susceptibility genes have been identified. As part of the international genetic research programme of the GenoMEL consortiums research on genetic mutations in melanoma families, the aim of this study was to examine family members' views about their risk of melanoma, gene testing and genetic research. Methods: Self-report data were gathered using online and paper-based

Atopy is a risk factor for respiratory symptoms in COPD patients: results from the EUROSCOP study

Background: The pathogenesis of COPD is complex and remains poorly understood. The European Respiratory Society Study on Chronic Obstructive Pulmonary Disease (EUROSCOP) investigated long-term effects of budesonide; 18% of the COPD participants were atopic. So far effects of atopy on the long-term course of COPD have not been elucidated. Methods: Factors related to the presence of atopy (positive

Development and validation of a new automatic algorithm for quantification of left ventricular volumes and function in gated myocardial perfusion SPECT using cardiac magnetic resonance as reference standard.

BACKGROUND: By gating image acquisition in myocardial perfusion SPECT (MPS) to ECG, left ventricular (LV) volumes and function can be determined. Several previous studies have shown that existing MPS software packages underestimate LV volumes compared to cardiac magnetic resonance (CMR). The aim of this study was therefore to develop a new LV segmentation algorithm for gated MPS using CMR as refer

A randomized controlled study comparing pain experience between a newly designed needle with a thin tip and a standard needle for oocyte aspiration

Background: Ultrasound-guided transvaginal oocyte retrieval is often performed under local anaesthesia on an outpatient basis. The objective of this study was to compare the overall pain experience of a newly designed reduced needle (RN) compared with a thicker standard needle (SN). Methods: A prospective, randomized, multi-centre study was performed at four different clinics from June to December