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  • 2000-2004  (11)
  • 1
    Electronic Resource
    Electronic Resource
    Pharmacological validation of behavioural measures of akinesia and dyskinesia in a rat model of Parkinson's disease (2002)
    Oxford, UK : Blackwell Science, Ltd
    European journal of neuroscience 15 (2002), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In an attempt to define clinically relevant models of akinesia and dyskinesia in 6-hydroxydopamine (6-OHDA)-lesioned rats, we have examined the effects of drugs with high (l-DOPA) vs. low (bromocriptine) dyskinesiogenic potential in Parkinson's disease on three types of motor performance, namely: (i) abnormal involuntary movements (AIMs) (ii) rotational behaviour, and (iii) spontaneous forelimb use (cylinder test). Rats with unilateral 6-OHDA lesions received single daily i.p. injections of l-DOPA or bromocriptine at therapeutic doses. During 3 weeks of treatment, l-DOPA but not bromocriptine induced increasingly severe AIMs affecting the limb, trunk and orofacial region. Rotational behaviour was induced to a much higher extent by bromocriptine than l-DOPA. In the cylinder test, the two drugs initially improved the performance of the parkinsonian limb to a similar extent. However, l-DOPA-treated animals showed declining levels of performance in this test because the drug-induced AIMs interfered with physiological limb use, and gradually replaced all normal motor activities. l-DOPA-induced axial, limb and orolingual AIM scores were significantly reduced by the acute administration of compounds that have antidyskinetic efficacy in parkinsonian patients and/or nonhuman primates (−91%, yohimbine 10 mg/kg; −19%, naloxone 4–8 mg/kg; −37%, 5-methoxy 5-N,N-dimethyl-tryptamine 2 mg/kg; −30%, clozapine 8 mg/kg; −50%, amantadine 40 mg/kg). l-DOPA-induced rotation was, however, not affected. The present results demonstrate that 6-OHDA-lesioned rats do exhibit motor deficits that share essential functional similarities with parkinsonian akinesia or dyskinesia. Such deficits can be quantified using novel and relatively simple testing procedures, whereas rotometry cannot discriminate between dyskinetic and antiakinetic effects of antiparkinsonian treatments.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.0953-816x.2001.01843.x
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  • 2
    Electronic Resource
    Electronic Resource
    Persistent changes in striatal gene expression induced by long-term l-DOPA treatment in a rat model of Parkinson's disease (2001)
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 14 (2001), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Current knowledge of the molecular changes induced by dopamine denervation and subsequent treatment with l-DOPA is based on studies performed on relatively acute and young animal models of parkinsonism. It is highly warranted to ask how well these models simulate the state of chronic denervation and sustained l-DOPA pharmacotherapy which are typical of advanced Parkinson's disease. This study investigates the effects of time postdenervation and l-dopa treatment duration on the striatal expression of opioid precursor mRNAs and FosB/ΔFosB-related proteins. Unilaterally 6-hydroxydopamine-lesioned rats were treated with therapeutical doses of l-DOPA for one year (long-term group) or a few weeks (short-term group). Age-matched lesioned rats received injections of vehicle or bromocriptine, an antiparkinsonian compound which does not produce dyskinesia when administered de novo. The lesion-induced up-regulation of preproenkephalin mRNA expression persisted at more than one year postlesion, and was unaffected by the pharmacological treatments applied. l-DOPA, but not bromocriptine, induced high striatal levels of FosB/ΔFosB immunoreactivity and prodynorphin mRNA, and these did not differ between short-term and long-term l-DOPA-treated rats. The present data provide the first demonstration that l-DOPA maintains high striatal levels of fosB and prodynorphin gene expression during a prolonged course of treatment, which simulates the clinical practice in Parkinson's disease more closely than the short-treatment paradigms studied thus far.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.0953-816x.2001.01743.x
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  • 3
    Electronic Resource
    Electronic Resource
    Time course of striatal ΔFosB-like immunoreactivity and prodynorphin mRNA levels after discontinuation of chronic dopaminomimetic treatment (2003)
    Oxford, UK : Blackwell Science, Ltd
    European journal of neuroscience 17 (2003), S. 0 
    Details
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: ΔFosB-like proteins are particularly stable transcription factors that accumulate in the brain in response to chronic perturbations. In this study we have compared the time-course of striatal FosB/ΔFosB-like immunoreactivity and prodynorphin mRNA expression after discontinuation of chronic cocaine treatment to intact rats and chronic L-DOPA treatment to unilaterally 6-hydroxydopamine (6-OHDA) lesioned rats. The animals were killed between 3 h and 16 days after the last drug injection. In both treatment paradigms, the drug-induced FosB/ΔFosB immunoreactivity remained significantly elevated in the caudate putamen even at the longest withdrawal period examined. The concomitant upregulation of prodynorphin mRNA, a target of ΔFosB, paralleled the time-course of ΔFosB-like immunoreactivity in the 6-OHDA-lesion/L-DOPA model, but was more transient in animals treated with cocaine. These results suggest that ΔFosB-like proteins have exceptional in vivo stability. In the dopamine-denervated striatum, these proteins may exert sustained effects on the expression of their target genes long after discontinuation of L-DOPA pharmacotherapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1460-9568.2003.02469.x
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  • 4
    Electronic Resource
    Electronic Resource
    Topical treatment with aqueous solutions of rofleponide palmitate and budesonide in a pollen-season model of allergic rhinitis (2004)
    Oxford, UK : Blackwell Science Ltd
    Clinical & experimental allergy 34 (2004), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Rofleponide palmitate is an esterified glucocorticosteroid pro-drug with a promising pre-clinical profile designed to deliver topical airway treatment for allergic rhinitis and asthma in a novel manner. Thus, the rofleponide palmitate pro-drug is designed to provide topical exposure of the mucosa to the inactive lipophilic drug, which would be locally metabolized to the more hydrophilic and readily cleared drug rofleponide.Objective To examine whether rofleponide palmitate affects nasal symptoms and peak inspiratory flow (PIF) in a pollen-season model of allergic rhinitis and to compare any such effects with those of another glucocorticosteroid (i.e., budesonide).Methods During the pollen-free season, 40 patients with strictly seasonal allergic rhinitis received topical nasal spray treatment with an aqueous solution of rofleponide palmitate 400 μg and an aqueous solution of budesonide 128 μg once daily for 10 days in a double-blind, placebo-controlled, and crossover study. After 3 days of drug treatment, individualized allergen challenges were given once daily for 7 days while the treatment continued. The washout periods between each of the challenge series were 2 weeks. Nasal symptoms and PIF were recorded in the morning and evening, as well as 10 and 20 min after each allergen challenge. The mean recordings obtained during the last 3 days of the allergen-challenge series, when symptoms were established and when the treatment had lasted for 8–10 days, were used in the analysis.Results Both active treatments reduced nasal symptoms and improved nasal PIF compared with placebo (P〈0.01–0.001). There was no overall difference in efficacy between rofleponide palmitate 400 μg and budesonide 128 μg.Conclusions Topical treatment with aqueous solutions of rofleponide palmitate attenuates nasal symptoms and improves nasal PIF in allergic rhinitis. The overall efficacy of 400 μg of rofleponide palmitate is similar to that of 128 μg of budesonide in the pollen-season model used in this study.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2222.2004.1965.x
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  • 5
    Electronic Resource
    Electronic Resource
    Nasal challenges with recombinant derivatives of the major birch pollen allergen Bet v 1 induce fewer symptoms and lower mediator release than rBet v 1 wild-type in patients with allergic rhinitis (2002)
    Oxford, UK : Blackwell Science, Ltd
    Clinical & experimental allergy 32 (2002), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Genetic engineering of the major birch pollen allergen (Bet v 1) has led to the generation of recombinant Bet v 1 derivatives with markedly reduced IgE-binding capacity, but with retained T cell activating ability.Objective To compare the mucosal reactivity to rBet v 1 derivatives with rBet v 1 wild-type as basis for new therapeutic strategies for birch pollen allergy based on mucosal tolerance induction.Methods Outside the pollen season, 10 patients with birch pollen allergic rhinitis and mild asthma underwent four nasal challenge-sessions in a randomized, double-blind, and cross-over design, employing increasing doses of rBet v 1 fragment mix, rBet v 1 trimer, rBet v 1 wild-type and diluent (albumin). Nasal lavage fluids (NAL) were collected before the challenge-series as well as 10 min, 4 and 24 h thereafter. Nasal lavage fluid levels of tryptase as well as EPO and ECP were measured as indices of mast cell and eosinophil activity, respectively.Results All 10 patients tolerated the highest accumulated dose, 8.124 µg, when challenged with rBet v 1 trimer, eight with rBet v 1 fragments compared to one when challenged with rBet v 1 wild-type. No late phase reactions were observed. The change in tryptase levels (pre-challenge vs. 10 min) was significantly lower after challenges with rBet v 1 trimer and rBet v 1 fragments than with rBet v 1 wild-type. The change in EPO/ECP concentration pre-challenge versus 4 h post-challenge was lower for rBet v 1 trimer and the change was significantly lower when pre-challenge versus 24 h post-challenge to rBet v 1 fragments and rBet v 1 wild-type was examined.Conclusion The derivatives induced significantly fewer symptoms and lower mast cell and eosinophil activation than rBet v 1 wild-type upon application to the nasal mucosa. They could in the future be candidates for immunotherapy based on mucosal tolerance induction.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2745.2002.01495.x
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  • 6
    Electronic Resource
    Electronic Resource
    Mucosal output of eotaxin in allergic rhinitis and its attenuation by topical glucocorticosteroid treatment (2001)
    Oxford, UK : Blackwell Science, Ltd
    Clinical & experimental allergy 31 (2001), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Eotaxin is a chemokine that attracts and activates eosinophils. The present study examines the occurrence of eotaxin in nasal mucosal surface liquids in patients with seasonal allergic rhinitis without allergen exposure and during repeat allergen challenge with and without topical glucocorticosteroid treatment. The number of subepithelial eosinophils and mucosal outputs of bulk plasma (α2-macroglobulin) and eosinophil cationic protein (ECP) are also examined.Methods Twelve patients underwent daily allergen challenges for 6 days. Separately, 14 patients, who were receiving budesonide and placebo in a parallel group design, also underwent allergen challenge for 6 days. Nasal biopsies were obtained before and 24 h after the allergen challenge series, and lavages were carried out before and 15 min after selected allergen challenges.Results At baseline nasal lavage fluid levels of eotaxin correlated to levels of α2-macroglobulin and ECP. After the first allergen challenge there was a correlation between nasal lavage fluid levels of eotaxin and ECP. Repeat allergen exposure increased the mucosal output of eotaxin (P 〈0.05) and ECP (P 〈0.01) as well as eosinophil numbers (P 〈0.01), but no correlation was found between increased eosinophil numbers and eotaxin. Budesonide reduced eotaxin levels during repeat allergen challenge (P 〈0.05).Conclusions Repeat allergen exposure in allergic rhinitis is associated with increased mucosal output of eotaxin. Topical budesonide attenuates this effect, suggesting the possibility that inhibitory effects on mucosal eotaxin may contribute to anti-eosinophilic actions of topical glucocorticosteroids.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2222.2001.01029.x
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  • 7
    Electronic Resource
    Electronic Resource
    Nasal hyperosmolar challenge with a dry powder of mannitol in patients with allergic rhinitis. Evidence for epithelial cell involvement (2000)
    Oxford BSL : Blackwell Science Ltd
    Clinical & experimental allergy 30 (2000), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The responses to airway hyperosmolar challenges probably involve various inflammatory mediators. However, it is not fully understood which cell type/types are the source of these mediators. Potential cell types include mast cell, epithelial cell and the sensory c-fibre nerve cell.〈section xml:id="abs1-2"〉〈title type="main"〉ObjectiveTo clarify which cell types are involved with the mediator response to hyperosmolarity in the human airway.〈section xml:id="abs1-3"〉〈title type="main"〉MethodsTen healthy subjects, 11 patients with nonactive allergic rhinitis, and nine with active allergic rhinitis were challenged intranasally with mannitol powder, and with sham provocation, on separate days. Symptoms were assessed by visual analogue scales and nasal patency by measuring the nasal peak inspiratory flow (nPIF). Nasal lavage fluid levels of α2-macroglobulin (an index of plasma extravasation), substance P (an index of sensory nerve cell activation), tryptase (an index of mast cell activation) and 15-hydroxyeicosatetraenoic acid (15–HETE, an index of epithelial cell activation) were analysed.〈section xml:id="abs1-4"〉〈title type="main"〉ResultsImmediate, although transient burning was the most prominent symptom in all groups whereas only the patients with active rhinitis experienced a fall in nPIF. Mannitol significantly increased the nasal lavage fluid 15-HETE levels in the allergic patients (P 〈 0.01 vs the sham challenge), but not in the healthy subjects. The increase in 15-HETE correlated with nasal symptoms for itching (rs = 0.65, P = 0.019) and burning (rs = 0.72, P = 0.009). Detectable levels of tryptase was found only in five allergic subjects. Lavage levels of substance P and α2-macroglobulin did not not change.〈section xml:id="abs1-5"〉〈title type="main"〉ConclusionEpithelial cell seems to be involved with the mediator response to airway hyperosmolar challenge. The roles of sensory c-fibre nerve cell and mast cell remained less clear.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2222.2000.00923.x
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  • 8
    Electronic Resource
    Electronic Resource
    Disease perception and social behaviour in persistent rhinitis: a comparison between patients with allergic and nonallergic rhinitis (2004)
    Oxford, UK : Munksgaard International Publishers
    Allergy 59 (2004), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Although the understanding of the pathophysiology and pharmacology of rhinitis has increased within recent years, few studies have examined the impact of rhinitis on patients’ behaviour.Aim:  To compare perennial allergic rhinitis (PAR) and perennial nonallergic rhinitis (PNR) in terms of patients’ perception of their disease and its psychosocial concomitants.Methods:  Thirty-one PAR patients and 32 PNR patients responded to a standard symptom list and were interviewed in-depth regarding their complaints and the impact of rhinitis on their daily lives.Results:  PAR and PNR patients reported similar somatic and psychosocial complaints. In both disease groups the adverse effects of rhinitis were reported to be substantially limiting, particularly in social contacts, the impact appearing to be more severe in the women.Conclusion:  Rhinitis has a severe impact on the daily lives of patients, women reporting more severe psychosocial effects. Disease perception and social adjustment appear to not depend appreciably on whether or not an objective diagnosis of rhinitis can be established.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1398-9995.2003.00331.x
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  • 9
    Electronic Resource
    Electronic Resource
    Symptoms of persistent allergic rhinitis during a full calendar year in house dust mite-sensitive subjects (2004)
    Oxford, UK : Munksgaard International Publishers
    Allergy 59 (2004), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Little is known about the natural course of persistent rhinitis symptoms over a prolonged period.Objective:  To describe the frequency and severity of nasal symptoms and quality of life (QoL) in house dust mite-sensitive persistent rhinitic subjects and to determine if medication use was related to symptoms.Methods:  Rhinitics and controls were telephoned fortnightly for 1 year to monitor symptoms. QoL was measured every 3 months.Results:  Thirty-seven rhinitics and 19 controls completed the study. Total nasal symptom scores (TNSS) were ‘high’ for 65% (95% CI ± 6%) of the year in rhinitic subjects. When TNSS increased by 1, the likelihood of nasal medication use increased by 25% (95% CI: 7–46%). General and specific QoL were worse in rhinitic subjects than controls (P 〈 0.04 and 〈0.0001). Rhinitics with pollen allergy (n = 21) had seasonal variation in the frequency of high nasal symptom scores (P = 0.02).Conclusion:  Nasal symptom scores were consistently high in rhinitics, and their QoL was worse than controls, even in general QoL. An increase in nasal symptom score increased the likelihood of nasal medication use. These findings help to characterize the course of persistent rhinitis over a previously unstudied period of 1 year.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.2003.00420.x
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  • 10
    Electronic Resource
    Electronic Resource
    Association between nasal and bronchial symptoms in subjects with persistent allergic rhinitis (2004)
    Oxford, UK : Munksgaard International Publishers
    Allergy 59 (2004), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  The association between nasal and bronchial symptoms, and the course of bronchial responsiveness and airway inflammation in house dust mite sensitive persistent rhinitis over a prolonged time period has not been thoroughly explored.Objective:  To determine if nasal symptoms were associated with bronchial symptoms in persistent rhinitic subjects, and to assess their bronchial responsiveness and airway inflammation in comparison to nonrhinitic, nonatopic controls. The additional impact of pollen sensitivity on the lower airways in rhinitic subjects was also addressed.Methods:  Rhinitics and controls answered telephone symptom questionnaires once every 2 weeks for 1 year. Every 3 months, exhaled nitric oxide (eNO) and bronchial responsiveness to histamine were measured.Results:  Thirty-seven rhinitics and 19 controls completed the study. High nasal symptom scores in rhinitic subjects were associated with bronchial symptoms (OR = 1.7, 95% CI 1.2–2.5). Bronchial hyper-responsiveness was present in 32.4% of rhinitic subjects on at least one clinical visit during the year. Pollen allergy caused seasonal variation in eNO (P = 0.03).Conclusion:  In persistent rhinitic subjects, high nasal symptom scores were associated with bronchial symptoms, and many subjects experienced bronchial hyper-responsiveness during the year. Persistent rhinitic subjects were more at risk than healthy adults of bronchial symptoms and airway inflammation, which are likely risk factors for asthma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.2003.00419.x
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