Astra Zeneca R and D Molndal

Mölndal, Sweden

Astra Zeneca R and D Molndal

Mölndal, Sweden
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Turkiewicz A.,Lund University | Turkiewicz A.,Skåne University Hospital | De Verdier M.G.,Astra Zeneca R and D Molndal | Engstrom G.,Lund University | And 8 more authors.
Rheumatology (United Kingdom) | Year: 2014

Objective: The aim of this study was to estimate the prevalence of frequent knee pain in radiographic, symptomatic and clinically defined knee OA in middle-aged and elderly patients and the proportion that seeks medical care. Methods: In 2007 a random sample of 10 000 56- to 84-year-old residents of Malmö, Sweden, were questioned about knee pain. We classified subjects reporting knee pain with a duration of at least 4 weeks as having frequent knee pain. A random sample of 1300 individuals with frequent knee pain and 650 without were invited for assessment by the ACR clinical knee OA criteria and for bilateral weight-bearing knee radiography. We considered a Kellgren-Lawrence grade ≥2 as radiographic knee OA and that in combination with frequent knee pain as symptomatic knee OA. By linkage with the Skåne Healthcare Register, we determined the proportion of subjects that had consulted for knee OA or pain. Results: The 10 000 subjects had a mean age of 70 years (S.D. 7.6), a mean BMI of 27.1 kg/m2 and 62% were women. The prevalence of frequent knee pain was 25.1% (95% CI 24.1, 26.1), higher in women and similar across age groups. The prevalence of radiographic knee OA was 25.4% while 15.4% had either symptomatic or clinically defined knee OA. Of these, 68.9% consulted a physician for knee OA or pain during 2004-11. Conclusion: Fifteen per cent of middle-aged or elderly individuals have knee OA and symptoms. About one in three of those do not consult a physician. Inefficient care of OA and self-coping may be an explanation. © The Author 2014.

Hansson J.,Lund University | Ericsson A.E.,Astra Zeneca R and D Molndal | Axelson H.,Lund University | Johansson M.E.,Lund University | Johansson M.E.,Skåne University Hospital
European Journal of Histochemistry | Year: 2016

The cellular source for tubular regeneration following kidney injury is a matter of dispute, with reports suggesting a stem or progenitor cells as the regeneration source while linage tracing studies in mice seemingly favor the classical theory, where regeneration is performed by randomly surviving cells. We, and others have previously described a scattered cell population localized to the tubules of human kidney, which increases in number following injury. Here we have characterized the species distribution of these proximal tubular progenitor cells (PTPCs) in kidney tissue from chimpanzee, pig, rat and mouse using a set of human PTPC markers. We detected PTPCs in chimpanzee and pig kidneys, but not in mouse tissue. Also, subjecting mice to the unilateral urethral obstruction model, caused clear signs of tubular injury, but failed to induce the PTPC phenotype in renal tubules. © J. Hansson et al., 2016.

Ronkainen J.,University of Oulu | Ronkainen J.,Karolinska Institutet | Ronkainen J.,Primary Health Care Center | Talley N.J.,University of Newcastle | And 6 more authors.
American Journal of Gastroenterology | Year: 2011

Objectives: Symptomatic gastroesophageal reflux disease (GERD) is associated with a significantly increased risk of esophageal adenocarcinoma, but its natural history in the general population is poorly understood. Whether nonerosive reflux disease (NERD) is a risk factor for Barrett's esophagus (BE), the precursor of esophageal adenocarcinoma, is unknown. Furthermore, quantifying the risk of incident BE in those with untreated reflux esophagitis has not been possible. We aimed, in a prospective follow-up study with endoscopy, to evaluate the risk of BE in a cohort from the Swedish general population (the Kalixanda Study). Methods: Those with endoscopic or histological findings suggestive of GERD and randomly half of those with NERD (n481) were invited for follow-up investigation including endoscopy and a validated symptom questionnaire 5 years after the initial study. Multinomial logistic regression was used to estimate relative risk ratios (RRRs) and 95% confidence intervals (CIs) for change in presentation of GERD. Results: Of the 405 subjects available for inclusion, endoscopy was performed in 284 (response rate 70.1%). The incidence of BE was 9.9/1,000 person-years. Of those with NERD at baseline (n=113), progression to erosive esophagitis was found in 11; 2 developed BE. Erosive esophagitis (n=90) progressed to a more severe grade in 12 and to BE in 8 cases. Erosive esophagitis at baseline was independently associated with BE at follow-up (RRR 5.2; 95% CI 1.2-22.9). Conclusions: Compared with being free of GERD at follow-up, erosive esophagitis is a major risk factor for BE (with a fivefold increased risk) after 5 years in the general population. © 2011 by the American College of Gastroenterology.

Svensson T.,Lund University | Alerstam E.,Lund University | Johansson J.,Astra Zeneca R and D Molndal | Andersson-Engels S.,Lund University
Optics Letters | Year: 2010

We investigate how light samples disordered porous materials such as ceramics and pharmaceutical materials. By combining photon time-of-flight spectroscopy and sensitive laser-based gas sensing, we obtain information on the extent to which light interacts with solid and pore volumes, respectively. Comparison with mercury intrusion por- osimetry shows that light predominantly interacts with the solid. Analysis based on a two-state model does not fully explain observations, revealing a need for refined modeling. Nonetheless, excellent correlation between actual porosity and the porosity experienced by photons demonstrates the potential of nondestructive optical porosimetry based on gas absorption. © 2010 Optical Society of America.

Iyu D.,University of Nottingham | Glenn J.R.,University of Nottingham | White A.E.,University of Nottingham | Fox S.C.,University of Nottingham | And 3 more authors.
Thrombosis and Haemostasis | Year: 2011

P2Y12 receptor antagonists are antithrombotic agents that inhibit platelet function by blocking the effects of adenosine diphosphate (ADP) at P2Y12 receptors. However, some P2Y12 receptor antagonists may affect platelet function through additional mechanisms. It was the objective of this study to investigate the possibility that P2Y12 antagonists inhibit platelet function through interaction with G-protein-coupled receptors other than P2Y12 receptors. We compared the effects of cangrelor, ticagrelor and the prasugrel active metabolite on platelet aggregation and on phosphorylation of vasodilator-stimulated phosphoprotein (VASP). We compared their effects with those of selective IP, EP4 and A2A agonists, which act at Gs-coupled receptors. All three P2Y12 antagonists were strong inhibitors of ADP-induced platelet aggregation but only partial inhibitors of aggregation induced by thrombin receptor activating peptide (TRAP) or the thromboxane A2 mimetic U46619. Further, after removing ADP and its metabolites using apyrase and adenosine deaminase, the P2Y12 antagonists produced only minor additional inhibition of TRAP or U46619-induced aggregation. Conversely, the Gs-coupled receptor agonists always produced strong inhibition of aggregation irrespective of whether ADP was removed. Other experiments using selective receptor agonists and antagonists provided no evidence of any of the P2Y12 antagonists acting through PAR1, TP, IP, EP4, A2A or EP3 receptors. All three P2Y12 antagonists enhanced VASP-phosphorylation to a small and equal extent but the effects were much smaller than those of the IP, EP4 and A2A agonists. The effects of cangrelor, ticagrelor and prasugrel on platelet function are mediated mainly through P2Y12 receptors and not through another G-protein-coupled receptor. © Schattauer 2011.

Bjursell M.,Astra Zeneca R and D Molndal | Admyre T.,Astra Zeneca R and D Molndal | Goransson M.,Astra Zeneca R and D Molndal | Marley A.E.,Astrazeneca | And 3 more authors.
American Journal of Physiology - Endocrinology and Metabolism | Year: 2011

Free fatty acid receptor 2 (Ffar2), also known as GPR43, is activated by short-chain fatty acids (SCFA) and expressed in intestine, adipocytes, and immune cells, suggesting involvement in lipid and immune regulation. In the present study, Ffar2-deficient mice (Ffar2-KO) were given a high-fat diet (HFD) or chow diet and studied with respect to lipid and energy metabolism. On a HFD, Ffar2-KO mice had lower body fat mass and increased lean body mass. The changed body composition was accompanied by improved glucose control and lower HOMA index, indicating improved insulin sensitivity in Ffar2-KO mice. Moreover, the Ffar2-KO mice had higher energy expenditure accompanied by higher core body temperature and increased food intake. The liver weight and content of triglycerides as well as plasma levels of cholesterol were lower in the Ffar2-KO mice fed a HFD. A histological examination unveiled decreased lipid interspersed in brown adipose tissue of the Ffar2-KO mice. Interestingly, no significant differences in white adipose tissue (WAT) cell size were observed, but significantly lower macrophage content was detected in WAT from HFD-fed Ffar2-KO compared with wild-type mice. In conclusion, Ffar2 deficiency protects from HFD-induced obesity and dyslipidemia at least partly via increased energy expenditure. Copyright © 2011 the American Physiological Society.

Nelander H.,Astra Zeneca R and D Molndal | Andersson S.,Astra Zeneca R and D Molndal | Ohlen K.,Astra Zeneca R and D Molndal
Journal of Chromatography A | Year: 2011

The performance of four commercially available cellulose tris(3,5-dimethylphenylcarbamate) based chiral stationary phases (CSPs) was evaluated with parallel high performance liquid chromatography (HPLC) and super critical fluid chromatography (SFC). Retention, enantioselectivity, resolution and efficiency were compared for a set of neutral, basic and acidic compounds having different physico-chemical properties by using different mobile phase conditions. Although the chiral selector is the same in all the four CSPs, a large difference in the ability to retain and resolve enantiomers was observed under the same chromatographic conditions. We believe that this is mainly due to differences in the silica matrix and immobilization techniques used by the different vendors. An extended study of metoprolol and structure analogues gave a deeper understanding of the accessibility of the chiral discriminating interactions and its impact on the resolution of the racemic compounds on the four CSPs studied. Also, a clear difference in enantioselectivity is observed between SFC and LC mode, hydrogen bonding was found to play an important role in the differential binding of the enantiomers to the CSPs. © 2011 Elsevier B.V.

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