| 1. |
- Evaldsson, Chamilly, et al.
(författare)
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4-Thiouridine induces dose-dependent reduction of oedema, leucocyte influx and tumour necrosis factor in lung inflammation
- 2009
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 155:2, s. 330-338
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Tidskriftsartikel (refereegranskat)abstract
- Recent reports demonstrate a role for nucleotides as inflammatory modulators. Uridine, for example, reduces oedema formation and leucocyte infiltration in a Sephadex-induced lung inflammation model. Tumour necrosis factor (TNF) concentration was also reduced. Previous in vivo observations indicated that 4-thiouridine might have similar effects on leucocyte infiltration and TNF release. The aim of this study was thus to investigate the effects of 4-thiouridine in greater detail. We used a Sephadex-induced acute lung inflammation model in Sprague-Dawley rats. The dextran beads were instilled intratracheally into the lungs, which were excised and examined after 24 h. Sephadex alone led to massive oedema formation and infiltration of macrophages, neutrophils and eosinophils. Microgranulomas with giant cell formations were clearly visible around the partially degraded beads. A significant increase in bronchoalveolar lavage fluid (BALF) content of TNF and leukotrienes was also seen. 4-Thiouridine co-administration affected all variables investigated in this model, i.e. oedema, microscopic and macroscopic appearance of lung tissue, total leucocyte and differential leucocyte counts in BALF, TNF and leukotrienes C-4 (LTC4), LTD4 and LTE4 in BALF, indicating a reproducible anti-inflammatory effect. In conclusion, we have demonstrated that 4-thiouridine has anti-inflammatory effects similar to those of uridine. To our knowledge, this is the first demonstration of pharmacological 4-thiouridine effects in vivo. The results suggest nucleoside/nucleotide involvement in inflammatory processes, warranting further studies on nucleoside analogues as attractive new alternatives in the treatment of inflammatory diseases.
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| 2. |
- Evaldsson, Chamilly, 1978-, et al.
(författare)
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Anti-inflammatory effects of exogenous uridine in an animal model of lung inflammation.
- 2007
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Ingår i: International Immunopharmacology. - : Elsevier BV. - 1567-5769 .- 1878-1705. ; 7:8, s. 1025-1032
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Tidskriftsartikel (refereegranskat)abstract
- Nucleosides like adenosine, uridine and their nucleotide derivatives (e.g. ATP and UTP) play important roles in many cellular functions, sometimes by acting as signalling molecules through binding to specific P2 nucleotide receptors. P2 receptors are subdivided into P2X and P2Y subfamilies, the latter of which are G-protein coupled receptors. P2Y receptors and nucleoside transporters have been detected in human and rat lungs, where they mediate effects of interest in airway diseases. The aim of this study was to investigate whether uridine has any anti-inflammatory properties in an asthma-like animal model of lung inflammation. The Sephadex-induced lung inflammation model in Sprague-Dawley rats was chosen mainly due to its localised inflammatory response and uridine's limited oral bioavailability. The dextran beads, with or without the addition of uridine, were instilled intratracheally into the lungs, which were excised and examined after 24 h. Sephadex alone led to massive oedema and infiltration of macrophages, neutrophils and eosinophils. Microgranulomas with giant cell formations were clearly visible around the partially degraded beads. Uridine reduced both the oedema and the infiltration of leukocytes significantly, measured as lung wet weight and leukocyte counts in bronchoalveolar lavage fluid, respectively. Uridine appeared to affect the tumour necrosis factor (TNF) levels, although this could not be statistically confirmed due to large variations within the Sephadex control group. We conclude that uridine has anti-inflammatory effects, and that the exact mechanism(s) of action requires further study.
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| 3. |
- Evaldsson, Chamilly, 1978-
(författare)
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Uridine, 4-thiouridine and isomaltitol in an asthma-like model : Anti-inflammatory and modulating effects
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In chronic inflammatory diseases like asthma or rheumatoid arthritis, erroneous and exaggerated accumulation of leukocytes in a tissue inadvertently causes the body harm. Several efficient anti-inflammatory drugs exist, for example corticosteroids and cyclo-oxygenase inhibitors. However, these drugs have potent and diverse effects and often act by inhibiting events subsequent to initiation of the inflammatory response, leading to more or less severe side-effects, especially when used in high doses for long periods of time. For this reason, strategies aimed at early inhibition of recruitment and activation of leukocytes have been suggested as safer and more specific approaches to reduce inflammation.Leukocyte adhesion to activated endothelium is a prerequisite to the following activation and extravasation, and takes place in the initial phase of inflammation. By using a model that allows leukocytes to adhere to tumour necrosis factor (TNF)-activated endothelial cells, thus mimicking aspects of an inflammatory reaction, we found that uridine, 4-thiouridine and isomaltitol could all reduce adhesion. This suggested that they may have anti-inflammatory potential.We therefore tried the three substances in a Sephadex-induced lung inflammation model and found that uridine and 4-thiouridine have several anti-inflammatory effects, such as being able to reduce leukocyte accumulation, decrease TNF protein levels and partly inhibit the oedema induced by Sephadex. Isomaltitol turned out to have immunomodulating, rather than anti-inflammatory, effects, which could be of interest in diseases where inadequate inflammatory responses are a problem.
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| 4. |
- Rahimi, Bahlol, et al.
(författare)
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Organization-wide adoption of computerized provider order entry systems: a study based on diffusion of innovations theory
- 2009
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Ingår i: BMC Medical Informatics and Decision Making. - : Springer Science and Business Media LLC. - 1472-6947. ; 9:52
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Tidskriftsartikel (refereegranskat)abstract
- Background: Computerized provider order entry (CPOE) systems have been introduced to reduce medication errors, increase safety, improve work-flow efficiency, and increase medical service quality at the moment of prescription. Making the impact of CPOE systems more observable may facilitate their adoption by users. We set out to examine factors associated with the adoption of a CPOE system for inter-organizational and intra-organizational care. Methods: The diffusion of innovation theory was used to understand physicians and nurses attitudes and thoughts about implementation and use of the CPOE system. Two online survey questionnaires were distributed to all physicians and nurses using a CPOE system in county-wide healthcare organizations. The number of complete questionnaires analyzed was 134 from 200 nurses (67.0%) and 176 from 741 physicians (23.8%). Data were analyzed using descriptive-analytical statistical methods. Results: More nurses (56.7%) than physicians (31.3%) stated that the CPOE system introduction had worked well in their clinical setting (P andlt; 0.001). Similarly, more physicians (73.9%) than nurses (50.7%) reported that they found the system not adapted to their specific professional practice (P = andlt; 0.001). Also more physicians (25.0%) than nurses (13.4%) stated that they did want to return to the previous system (P = 0.041). We found that in particular the received relative advantages of the CPOE system were estimated to be significantly (P andlt; 0.001) higher among nurses (39.6%) than physicians (16.5%). However, physicians agreements with the compatibility of the CPOE and with its complexity were significantly higher than the nurses (P andlt; 0.001). Conclusions: Qualifications for CPOE adoption as defined by three attributes of diffusion of innovation theory were not satisfied in the study setting. CPOE systems are introduced as a response to the present limitations in paper-based systems. In consequence, user expectations are often high on their relative advantages as well as on a low level of complexity. Building CPOE systems therefore requires designs that can provide rather important additional advantages, e. g. by preventing prescription errors and ultimately improving patient safety and safety of clinical work. The decision-making process leading to the implementation and use of CPOE systems in healthcare therefore has to be improved. As any change in health service settings usually faces resistance, we emphasize that CPOE system designers and healthcare decision-makers should continually collect users feedback about the systems, while not forgetting that it also is necessary to inform the users about the potential benefits involved.
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