| 1. |
- Butler, Stephen H., et al.
(författare)
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Predictors of severe pain in a cohort of 5271 individuals with self-reported neuropathic pain
- 2013
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Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 154:1, s. 141-146
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Tidskriftsartikel (refereegranskat)abstract
- The influence of pain descriptors and mechanical hypersensitivity on pain severity in neuropathic pain has not been well researched and is poorly understood. The aim of this study was to determine the relationship between pain severity and other factors describing chronic neuropathic pain in a large cohort of patients with self-reported neuropathic pain potentially recruited as subjects for a Phase IIa study. A questionnaire specific to the study parameters covering demographics and pain characteristics was sent to potential participants. Overall, 9185 questionnaires were returned from potential subjects who self-reported neuropathic pain. Adjusted odds ratios with 95% confidence intervals were used as a measure of association. These were estimated by unconditional logistic regression. Pain descriptors in the questionnaire were: burning, shooting, shocking, and aching. The presence of self-reported allodynia and hyperalgesia was strongly indicative of both moderate and severe pain, with a significant interaction of both factors in moderate and severe pain. Having 3 or 4 pain descriptors was also strongly indicative of both moderate and severe pain. Female gender, age, and history of serious mental disorders were found to be weaker indicators of both moderate and severe pain. Given the large and varied population with many neuropathic pain diagnoses in the study, the findings are not likely to be merely chance, but are likely to reflect important relationships between pain severity and other factors in those who suffer from chronic neuropathic pain.
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| 2. |
- Johansson, Cecilia, et al.
(författare)
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Adenoviruses Use Lactoferrin as a Bridge for CAR-Independent Binding to and Infection of Epithelial Cells.
- 2007
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Ingår i: Journal of Virology. - : American Society for Microbiology. - 1098-5514 .- 0022-538X. ; 81:2, s. 954-963
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Tidskriftsartikel (refereegranskat)abstract
- Most adenoviruses bind to the coxsackie- and adenovirus receptor (CAR). Surprisingly, CAR is not expressed apically on polarized cells and is thus not easily available to viruses. Consequently, alternative mechanisms for entry of coxsackievirus and adenovirus into cells have been suggested. We have found that tear fluid promotes adenovirus infection, and we have identified human lactoferrin (HLf) as the tear fluid component responsible for this effect. HLf alone was found to promote binding of adenovirus to epithelial cells in a dose-dependent manner and also infection of epithelial cells by adenovirus. HLf was also found to promote gene delivery from an adenovirus-based vector. The mechanism takes place at the binding stage and functions independently of CAR. Thus, we have identified a novel binding mechanism whereby adenovirus hijacks HLf, a component of the innate immune system, and uses it as a bridge for attachment to host cells.
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| 3. |
- Wadell, Cecilia, 1969-
(författare)
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Nasal Drug Delivery : In Vitro Studies on Factors Influencing Permeability and Implications on Absorption
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Nasal delivery is a feasible alternative to oral or parenteral administration for some drugs because of the high permeability of the nasal epithelium, rapid drug absorption across this membrane and avoidance of hepatic first-pass metabolism. The main objective of this thesis was to investigate factors influencing the permeability of the nasal mucosa to various compounds and to evaluate implications for drug absorption via the nasal route. Porcine nasal mucosa mounted in an Ussing chamber system was established as an in vitro model, and glucose, insulin, lidocaine, mannitol, melagatran, nicotine, PEG 4000, propranolol, sumatriptan, verapamil, vinblastine and an aminodiether were used as model compounds. The pharmacokinetics of melagatran and propiomazine were investigated in absorption studies in rats, and the influence of the enhancers SDS and EDTA on melagatran absorption was evaluated and compared with in vitro permeability data. The expression of P-glycoprotein in porcine nasal mucosa was investigated and compared with that in human nasal epithelial biopsies using the Western Blot technique.The results demonstrated that the Ussing chamber model using porcine nasal mucosa has potential as a tool for evaluating mechanisms of nasal absorption and predicting the in vivo effects of absorption enhancers. Moreover, porcine nasal mucosa is comparable to human nasal mucosa in its morphology and P-glycoprotein expression. The in vitro permeability data were found to weakly correlate with literature data on human absorption after nasal administration of the corresponding compounds. In vivo absorption studies of the sedative propiomazine demonstrated that nasal administration of this drug offers an interesting alternative to the oral formulation currently on the market, since the absorption was rapid and the bioavailability was promising. The bioavailability of melagatran in rats was moderate but variable, and responded to the addition of enhancers. Finally, the establishment and characterisation of an in vitro method for prediction of nasal drug absorption, and the investigation of factors influencing nasal membrane permeability and absorption offer substantial contributions for nasal drug delivery.
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