| 1. |
- Greiff, Lennart, et al.
(författare)
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Effects of topical platelet activating factor on the guinea-pig tracheobronchial mucosa in vivo
- 1997
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 160:4, s. 387-391
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Tidskriftsartikel (refereegranskat)abstract
- Platelet activating factor (PAF) has been reported to produce a variety of airway effects including epithelial damage and increased airway-lung absorption of hydrophilic tracers. The present study examines effects of PAF on the guinea-pig tracheobronchial mucosa in vivo. Vehicle with and without PAF (4.0 and 8.0 nmol) was superfused onto the tracheobronchial mucosa. The levels of 125I-albumin, previously given intravenously, were determined in tracheobronchial lavage fluids as an index of mucosal exudation of plasma. The mucosa was also examined by scanning electron microscopy. In separate animals, 99mTc-DTPA (a low molecular weight, 492 Da, hydrophilic tracer) was superfused onto the mucosal surface through an oro-tracheal catheter, together with vehicle or PAF (8.0 nmol). A gamma camera determined the disappearance rate of 99mTc-DTPA from the airways as an index of mucosal absorption. PAF produced dose-dependent mucosal exudation of plasma up to 20-fold greater than control (P < 0.001). However, PAF did not damage the epithelium and the absorption ability of the airway mucosa was unaffected. The results, in contrast to previous reports, suggest that PAF may not readily damage the airway mucosa even at large exudative doses of the agent. The present finding support the view that the plasticity of the epithelial junctions allows the creation of valve-like paracellular pathways for unidirectional clearance of extravasated plasma into the airway lumen. We suggest that endogenous PAF may participate in first line respiratory defence reactions by causing lumenal entry of bulk plasma without harming the epithelium.
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| 2. |
- Greiff, Lennart, et al.
(författare)
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Effects of hydrogen peroxide on the guinea-pig tracheobronchial mucosa in vivo
- 1999
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Ingår i: Acta Physiologica Scandinavica. - : Wiley. - 0001-6772 .- 1365-201X. ; 165:4, s. 415-420
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Tidskriftsartikel (refereegranskat)abstract
- Lumenal entry of plasma (mucosal exudation) is a key feature of airway inflammation. In airways challenged with histamine-type mediators and allergen the mucosal exudation response occurs without causing epithelial derangement and without increased airway absorption. In contrast, reactive oxygen metabolites may cause mucosal damage. In this study, involving guinea-pig airways, we have examined effects of H2O2 on airway exudation and absorption in vivo. Vehicle or H2O2 (0.1 and 0.5 M) was superfused onto the tracheobronchial mucosal surface through an oro-tracheal catheter. 125I-albumin, given intravenously, was determined in tracheobronchial tissue and in lavage fluids 10 min after challenge as an index of mucosal exudation of plasma. The tracheobronchial mucosa was also examined by scanning electron microscopy. In separate animals, 99mTc-DTPA was superfused 20 min after vehicle or H2O2 (0.1 and 0.5 M) had been given. A gamma camera determined the disappearance rate of 99mTc-DTPA from the airways as an index of airway absorption. The high dose of H2O2 (0.5 M) produced epithelial damage, increased the absorption of 99mTc-DTPA (P < 0.001), and increased the exudation of plasma (P < 0.001). Notably, it appeared that all extravasated plasma had entered the airway lumen within 10 min. These data demonstrate that H2O2 differs from exudative autacoids such as histamine by causing both epithelial damage and plasma exudation responses. These data also agree with the view that the epithelial lining determines the rate of absorption and is responsible for the valve-like function that allows lumenal entry of extravasated bulk plasma without any increased inward perviousness.
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| 3. |
- Persson, Carl, et al.
(författare)
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Unbalanced research
- 2001
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Ingår i: Trends in Pharmacological Sciences. - 0165-6147. ; 22:10, s. 538-541
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Lindén, Ola, et al.
(författare)
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Chemorefractory rhabdomyosarcoma treated with radiotherapy, bevacizumab, statins and surgery and maintenance with bevacizumab and chemotherapy.
- 2008
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Ingår i: Onkologie. - : S. Karger AG. - 0378-584X .- 1423-0240. ; 31:7, s. 391-393
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Rhabdomyosarcoma is a rare disease in children and young adults, usually responsive to chemotherapy. Here we report on a patient with chemorefractory disease, treated in an unconventional approach. CASE REPORT: A young woman presented with an embryonal rhabdomyosarcoma of the retromaxillary space. She exhibited progressive disease to two chemotherapy regimens. The patient started hyperfractionated radiotherapy that due to lack of response was changed to 3 Gy fractions once daily to a total absorbed dose of 53 Gy. The therapeutic predicament led us to add bevacizumab and hydroxymethylglutaryl-CoA reductase inhibitors (statins), for which some experimental support could be found. RESULTS: The tumour responded clearly, and a radical R0 resection followed. The patient was treated postoperatively with bevacizumab and chemotherapy. The combined treatment was accompanied by side effects such as mucositis grade IV, impaired healing of the mandibulotomy as well as a prominent cystitis. Side effects subsided following treatment with hyperbaric oxygen. CONCLUSION: Rhabdomyosarcoma refractory to chemotherapy may respond to radiotherapy and the addition of bevacizumab and statins. Although the contribution of the adjuncts is unclear, the unexpected tumour control in this case may help in decision-making in similar cases and may encourage the investigation of these adjuncts in protocols.
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| 5. |
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| 6. |
- Persson, Carl, et al.
(författare)
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Obalanserad medicinsk forskning
- 2001
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Ingår i: Läkartidningen. - 0023-7205. ; 98:34, s. 3580-3586
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Tidskriftsartikel (refereegranskat)
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| 7. |
- Andersson, Morgan, et al.
(författare)
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Barrier-enforcing measures as treatment principle in allergic rhinitis: a systematic review
- 2014
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Ingår i: Current Medical Research and Opinion. - : Informa Healthcare. - 1473-4877 .- 0300-7995. ; 30:6, s. 1131-1137
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Forskningsöversikt (refereegranskat)abstract
- Background and objectives Barrier-enforcing measures have been suggested as treatment options for allergic rhinitis. This review identifies and describes the literature on the subject. Methods Relevant publications were searched for in the PubMed database (search entries: 'allergic rhinitis' and 'treatment'). The evaluation comprised condition (seasonal or perennial allergic rhinitis), type of intervention, duration of treatment, study design, peer review status or not, number of test subjects, type of allergen exposure, and outcome in terms of effects or not on nasal symptoms of allergic rhinitis. Results Fifteen studies were either identified in the PubMed database search or from the reference lists of identified publications. Seven were placebo-controlled, randomized, and peer-reviewed, and symptom-reducing effects were reported by all of these reports. Limitations of this review reflect that the remainder of the studies had inferior designs, particularly lack of placebo control. Conclusions Barrier-enforcing measures as achieved by nasal administrations of cellulose powder and microemulsions, respectively, have symptom-reducing effects in allergic rhinitis.
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| 8. |
- Mårtensson, Anders, et al.
(författare)
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Nasal administration of a probiotic assemblage in allergic rhinitis: A randomised placebo-controlled crossover trial
- 2022
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222 .- 0954-7894. ; 52:6, s. 774-783
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Tidskriftsartikel (refereegranskat)abstract
- Background: Topical probiotics have been suggested as a treatment option for allergic rhinitis, as they may skew the immune response towards a beneficial type-1 non-allergic profile. So far observations in man have exclusively involved oral intake. The aim of this study was to examine whether a topical/nasal administration of a probiotic assemblage (PA) affects quality of life, symptoms and signs of allergic rhinitis in a nasal allergen challenge (NAC) model.Methods: In a placebo-controlled and crossover design, 24 patients with seasonal allergic rhinitis were randomised to topical/nasal administration with a PA of Lactobacillus rhamnosus SP1, Lactobacillus paracasei 101/37 and Lactococcus lactis L1A or placebo for 3 weeks. Participants and investigators were blind to treatment allocation. The last week of each treatment period was combined with a NAC series. Efficacy variables were "Mini-Rhinoconjunctivitis Quality of Life Questionnaire" (Mini-RQLQ), "Total Nasal Symptom Score" (TNSS), "Peak Nasal Inspiratory Flow" (PNIF) and "Fractional Exhaled Nitric Oxide" (FeNO). In addition, to assess whether or not the PA produced any pro-inflammatory effect per se, soluble analytes were monitored in nasal lavage fluids. Finally, bacterial cultures, sampled using swabs from the middle nasal meatus, were assessed for the presence of the PA by MALDI-TOF analysis.Results: Administration of the PA did not produce any nasal symptoms (cf. placebo). An innate immune response was discerned within the PA run (cf. baseline), but no change in nasal lavage fluid levels of cytokines/mediators was observed cf. placebo except for IL-17/IL-17A (a minor increase in the PA run). Administration of the PA did neither affect Mini-RQLQ, TNSS, PNIF nor FeNO. No evidence of persistent colonization was observed.Conclusions: Topical/nasal administration of a PA comprising Lactobacillus rhamnosus SP1, Lactobacillus paracasei 101/37 and Lactococcus lactis L1A, while likely evoking a minor innate immune response yet being safe, does not affect quality of life, symptoms or signs of allergic rhinitis.
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| 9. |
- Ahlström-Emanuelsson, Cecilia, et al.
(författare)
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Establishing a model of seasonal allergic rhinitis and demonstrating dose-response to a topical glucocorticosteroid
- 2002
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Ingår i: Annals of Allergy, Asthma & Immunology. - 1081-1206. ; 89:2, s. 159-165
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Tidskriftsartikel (refereegranskat)abstract
- Background: Symptoms of seasonal allergic rhinitis may vary greatly. Hence, for research purposes, there is a need for disease-like models of allergic rhinitis. In a preliminary study, involving 7 days' challenge with allergen, promising symptom consistency was obtained and dose-response to a glucocorticosteroid could, in part, be demonstrated. Objective: To establish this model of seasonal allergic rhinitis and test the hypothesis that mometasone furoate is more potent than budesonide as an antirhinitis drug. Methods: Thirty-eight patients with seasonal allergic rhinitis received treatment with spray-formulations of placebo, budesonide 64 kg, budesonide 256 mug, and mometasone furoate 200 mug in a double-blind, crossover design. After 3 days' treatment, individualized nasal allergen-challenges were administered daily for 7 days while the treatment continued. Nasal symptoms and peak inspiratory flow (PIF) were recorded. Results: During the last 3 days of allergen challenge without active treatment, consistent around-the-clock symptoms were recorded and recordings during these days were used in the analysis. With few exceptions the active treatments reduced nasal symptoms and improved nasal PIF (P values <0.001 to 0.05). Budesonide caused dose-dependent improvements in evening symptoms, morning nasal PIF, and nasal PIF recorded 10 minutes after allergen-challenge (P values <0.05). Budesonide 256 mug produced greater improvement than mometasone furoate 200 mug for nasal PIF 10 minutes after allergen-challenge (P < 0.05). Conclusion: The present allergen challenge method, producing consistent symptoms and nasal PIF data, emerges as a model of seasonal allergic rhinitis well suited for exploring potency and efficacy of drug intervention. The present data do not support the view that mometasone furoate is a more potent antirhinitis drug than budesonide.
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| 10. |
- Korsgren, Magnus, et al.
(författare)
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Clinical efficacy and pharmacokinetic profiles of intranasal and oral cetirizine in a repeated allergen challenge model of allergic rhinitis.
- 2007
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Ingår i: Annals of Allergy, Asthma & Immunology. - 1081-1206. ; 98:4, s. 316-321
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Tidskriftsartikel (refereegranskat)abstract
- Background: Intranasal and oral antihistamines are effective in treating allergic rhinitis. Studies comparing these routes of administration of an antihistamine regarding efficacy and pharmacokinetic profile are lacking. Objective: To compare topical and oral routes of administration of cetirizine regarding efficacy, plasma exudation, and systemic drug levels in a repeated allergen challenge model of allergic rhinitis. Methods: Oral cetirizine dihydrochloride, 10 mg once daily, and topical cetirizine dinitrate in a dose corresponding to 4.4 mg of the dihydrochloride salt twice daily were given to grass pollen-sensitive individuals for 12 days in a double-blind, placebo-controlled, crossover design. Timothy grass pollen allergen challenges were given once daily for 7 days using a nasal spray device. Nasal symptoms and peak inspiratory flow were recorded in the morning, 10 minutes after allergen challenge, and in the evening. The pharmacokinetics of the treatments was monitored in 8 patients. The remaining 28 patients were challenged topically with histamine 12 and 24 hours after the final topical and oral cetirizine doses, respectively. Nasal lavage levels of alpha(2)-macroglobulin were determined to evaluate histamine-induced mucosal plasma exudation. Results: During the last 3 days of the repeated allergen challenge model, chronic symptoms were established. Both treatments reduced symptoms 10 minutes after allergen challenge (P < .001 vs placebo). Neither treatment reduced morning and evening symptoms or nasal peak inspiratory flow. Topical, but not oral, cetirizine reduced histamine-induced plasma exudation (P < .01 vs placebo) when systemic drug levels were similar in the 2 treatment regimens. Conclusions: Topical and oral cetirizine reduced acute nasal symptoms produced by allergen challenges in patients with established chronic symptoms. There were also antihistaminic effects of topical cetirizine not related to systemic drug levels.
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