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| 5. |
- Cardell, L O, et al.
(författare)
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Genes regulating molecular and cellular functions in noninfectious nonallergic rhinitis.
- 2009
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 64:9, s. 1301-8
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Tidskriftsartikel (refereegranskat)abstract
- Chronic noninfectious, nonallergic rhinitis (NINAR) is a complex syndrome with a principally unknown pathophysiology. New technology has made it possible to examine differentially expressed genes and according to network theory, genes connected by their function that might have key roles in the disease.
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| 10. |
- Berglof, A, et al.
(författare)
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Association of bronchopneumonia with sinusitis due to Bordetella bronchiseptica in an experimental rabbit model
- 2000
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Ingår i: American journal of rhinology. - : SAGE Publications. - 1050-6586 .- 1539-6290. ; 14:2, s. 125-130
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Tidskriftsartikel (refereegranskat)abstract
- An animal model for rhinogenic sinusitis was developed in rabbits naturally colonized with Bordetella bronchiseptica. It was found that ostial occlusion predisposes the sinus to invasion with this opportunistic bacterium and subsequent sinusitis as a result of reduced local host defense. In addition to the inflammatory lesions in the sinus, bronchitis and pneumonia were found in 84% of the experimental rabbits, suggesting that ostial dysfunction can also contribute to infectious disease of the lower respiratory tract. In such a model it is possible to study the significance of asymptomatic carriage of potential pathogens after ostial occlusion.
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| 15. |
- Erlandsson, A C, et al.
(författare)
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Herpes simplex virus type 1 infection and glucocorticoid treatment regulate viral yield, glucocorticoid receptor and NF-kappaB levels.
- 2002
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Ingår i: The Journal of endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 175:1, s. 165-76
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Tidskriftsartikel (refereegranskat)abstract
- The interplay between the endocrine and immune systems has come into focus in recent years with the insight that endocrine parameters may affect susceptibility to both auto-immune and infectious diseases. Our interest in immunoendocrine regulation led us to investigate the effects of glucocorticoids on Herpes simplex virus type 1 (HSV-1) infections. Glucocorticoids used to treat inflammatory conditions are not yet recommended for HSV-1 therapy, since they have been reported to prolong viral shedding both in vivo and in vitro. Here we report that glucocorticoids did not alter the viral yield in human gingival fibroblast (HGF) cell culture when glucocorticoid treatment and viral infection occured simultaneously, but the viral yield increased when cells were treated with the glucocorticoid dexamethasone (dex) prior to viral infection. We found that viral infection in our primary cell system increased NF-kappaB levels and DNA binding. In addition, the amount of glucocorticoid receptor (GR) increased following viral infection, and HSV-1 infection as such could induce glucocorticoid-driven transcription of a reporter gene in human embryo kidney (HEK) 293 cells stably transfected with GR. Dex treatment did not affect HSV-1-induced binding of p65 to an NF-kappaB element in an electrophoretic mobility shift assay, and acyclovir was still efficient as an anti-viral drug in the presence of dex. Further studies of the observed effects of HSV-1 infection and glucocorticoid treatment on GR and NF-kappaB regulation could give insights into the immunoendocrine mechanisms important for defence and therapy against viral infections.
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| 18. |
- Forsgren, K, et al.
(författare)
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Effects of surgery on mucosal pathologic changes following experimental sinusitis in rabbit
- 1998
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Ingår i: The Annals of otology, rhinology, and laryngology. - : SAGE Publications. - 0003-4894 .- 1943-572X. ; 107:2, s. 155-163
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Tidskriftsartikel (refereegranskat)abstract
- In the present investigation, the regenerative capacity of the infected maxillary sinus mucosa following surgical procedures was studied in a rabbit model. Sinusitis was induced by occluding the ostium with and without the addition of Staphylococcus aureus or Bacteroides fragilis, or by provoking a prolonged bacterial infection with both pathogens. The surgical procedures performed were 1) widening of the natural sinus ostium (middle meatal antrostomy; MMA) and 2) removal of sinus mucosa without ostial interference (modified radical operation; MRO). The histologic features of the entire nose-sinus complex were studied, graded semiquantitatively, and compared with findings in untreated sinusitis, or after surgery only. Whereas MMA and MRO both led to a decrease of the inflammatory features of the sinus mucosa in induced sinusitis, persistent local histopathology was observed in the ostial region following MMA surgery. This indicates the importance of local pathologic changes resulting from interactions of bacterial colonization, inflammation, and surgery in chronic sinusitis.
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| 19. |
- FORSGREN, K, et al.
(författare)
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Endoscopic and Caldwell-Luc approaches in chronic maxillary sinusitis: a comparative histopathologic study on preoperative and postoperative mucosal morphology
- 1995
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Ingår i: The Annals of otology, rhinology, and laryngology. - : SAGE Publications. - 0003-4894 .- 1943-572X. ; 104:5, s. 350-357
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present investigation was to study the histopathologic mucosal changes occurring in chronic maxillary sinusitis both preoperative and postoperative to functional endoscopic sinus (FES) surgery and the Caldwell-Luc (C-L) operation. Correlations were also sought between the histopathologic parameters and endoscopic findings, as well as patient symptoms. Sixty sinuses with the FES surgery and 55 sinuses with the C-L procedure were studied. The histologic parameters were graded semiquantitatively and compared preoperatively and postoperatively. The C-L operation reduced almost all parameters, whereas after the FES operation only edema and inflammatory cells were significantly reduced. Fibrosis increased postoperatively with both methods. The number of inflammatory cells was closely correlated to a thickened antral mucosa and to purulent secretion. No valid correlations were found when comparing histology with patient symptoms. All in all, histologic considerations suggest that asthmatic patients with severe sinonasal polyposis might benefit from the C-L procedure.
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| 24. |
- Georen, SK, et al.
(författare)
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Timing-dependent effects of restraint stress on eosinophilic airway inflammation in mice
- 2008
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Ingår i: Neuroimmunomodulation. - : S. Karger AG. - 1423-0216 .- 1021-7401. ; 15:3, s. 157-164
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> Chronicstress has been proposed to aggravate allergic inflammation, whereas acute stress may have functional beneficial effects. The aim of this study was to investigate the influence of timing of single short restraint stress (RST) in a model of eosinophilic airway inflammation. <i>Methods:</i> The airways of ovalbumin (OVA)-sensitized mice were exposed to an intranasal OVA challenge. RST was applied in two different ways; either 2 h before (pre-stress) or after (post-stress) the OVA challenge, respectively, or as a combination of stress before and after (double-stress) the OVA challenge. One group of mice was also treated with metyrapone (ME) prior to a pre-stress challenge. The inflammatory cell response was evaluated in bronchoalveolar lavage fluid (BALF), lung and nasal tissue, as well as bone marrow. <i>Result:</i> RST applied prior to the OVA challenge (pre-stress) inhibited OVA-induced airway inflammation in BALF and lung tissue, and reduced nasal histopathology compared to unstressed mice. Given as post-stress or double-stress, RST did not affect the inflammation in BALF, lungs or nasal tissue. Pre-treatment with ME prevented the pre-challenge stress evoked decrease in inflammation in BALF and lungs. <i>Conclusion:</i> Effects of RST on eosinophilic airway inflammation appear to be strongly dependent on timing and, as could be judged from the ME inhibition pattern, also corticosterone dependent. Hypothalamic-pituitary-adrenal axis activation probably influences eosinophilic inflammation through specific sequences of compartmental activation and thereby timing effects are evident on cellular recruitment pattern during the allergic reaction.
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| 25. |
- Harmenberg, JG, et al.
(författare)
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ME-609: a treatment for recurrent herpes simplex virus infections
- 2003
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Ingår i: Antiviral chemistry & chemotherapy. - : SAGE Publications. - 0956-3202 .- 2040-2066. ; 14:4, s. 205-15
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Tidskriftsartikel (refereegranskat)abstract
- Studies in conventional murine models of HSV infection use immunologically naive animals. These models thus mimic primary infections rather than recurrent infections in humans. We have, therefore, used a newly developed mouse model that more closely mimics recurrent HSV infection in humans. In this model, the mice are infected, and zosteriform HSV-1 infection develops in the presence of a primed immune response using adoptive transfer of immunity (ATI) as we have described previously. Using the ATI mouse model, it has been shown that a more beneficial therapy for recurrent mucocutaneous HSV infection could be achieved by controlling both the viral replication and the inflammatory response to the virus. Topical treatment was initiated in this model at the time of first occurrence of symptoms and was given three times daily for 4 days. Topical treatment with ME-609 (which contains 5% acyclovir and 1% hydrocortisone) in the ATI mouse model was substantially more efficacious than 5% Zovirax® cream, 1% hydrocortisone or no treatment, respectively. The beneficial properties of ME-609 were also found to be superior to those of Zovirax cream when tested in the standard guinea pig model, representing a primary HSV infection. ME-609 represents a novel treatment principle of recurrent HSV infections and the present paper summarizes the preclinical and early clinical experience of ME-609.
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| 29. |
- Henriksson, G, et al.
(författare)
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Effects of topical budesonide treatment on glucocorticoid receptor mRNA down-regulation and cytokine patterns in nasal polyps
- 2001
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Ingår i: American journal of rhinology. - : SAGE Publications. - 1050-6586 .- 1539-6290. ; 15:1, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- The effects of a topically applied corticosteroid, budesonide, on the expression of glucocorticoid receptor (CR) mRNA and regulation of pro-inflammatory cytokine patterns in patients with nasal polyps were evaluated. All patients were eligible for surgical polypectomy, and a majority of them had been treated with nasal steroids. Patients were given 400 μg b.i.d. (group A, n = 11), 200 μg bid. (group B, n = 10), or no treatment (group C, n = 15) during two months before polypectomy. Morning serum cortisol was analyzed on the day of surgery. Surgically removed polyps were taken for analysis of GR mRNA expression by solution hybridization. Remaining tissue was cryostat-sectioned, whereafter quantification of the cytokines interleukin 1β, interleukin 2, interleukin 4, interleukin 5, interleukin 6, interleukin 10, tumor necrosis factor a, and interferon γ was made by immunohistochemistry and digitized image analysis. No significant differences among the three groups were found for any of the parameters investigated. Conclusion: nasal polyps do not respond with down-regulation of CR mRNA or cytokines following topical corticosteroid treatment. The proposed corticosteroid resistance may be inherent, or induced by a change of local tissue bioavailability.
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| 30. |
- Henriksson, G, et al.
(författare)
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Expression of P-glycoprotein 170 in nasal mucosa may be increased with topical steroids
- 1997
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Ingår i: American journal of rhinology. - : SAGE Publications. - 1050-6586 .- 1539-6290. ; 11:4, s. 317-321
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Tidskriftsartikel (refereegranskat)abstract
- The synthesis of P-glycoprotein 170 (P-gp), a “multidrug resistance” protein capable of extruding various drugs including 11-OH steroids from human cells, can be upregulated by certain glucocorticosteroids. This study demonstrates the presence of P-gp in the columnar surface epithelium and in glandular acini of healthy nasal mucosa with immunohistochemical technique. Furthermore, nasal polyps from 5 of 17 patients treated with clinical doses of a topical nasal steroid, budesonide, appear to show a stronger staining intensity for P-gp than polyps from 13 untreated patients. This suggests the possibility of local P-gp gene induction by topical glucocorticoid treatment. Upregulation of P-gp synthesis appears as a new possible cause of relative resistance to topical steroid medication in patients with nasal inflammatory disease.
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| 33. |
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| 34. |
- Holmström, Mats, et al.
(författare)
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Current perspectives on the treatment of nasal polyposis : a Swedish opinion report
- 2002
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 122:7, s. 736-744
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Tidskriftsartikel (refereegranskat)abstract
- This Swedish study group has examined the current knowledge of nasal polyposis with emphasis on different treatment modalities. Polyposis is a multifactorial disease that exists for decades in the majority of cases. Different types of treatment must be considered, focusing on the underlying disease. However, as we only know the specific origin of polyposis in a minority of cases, treatment is usually symptomatic. When making a thorough evaluation of different treatment strategies, it is obvious that there is a real need for more controlled treatment studies which would make the scientific ground more stable when it comes to suggesting medical, surgical or combined treatments.
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| 45. |
- Lekander, M, et al.
(författare)
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Cytokine inhibition after glucocorticoid exposure in healthy men with low versus high basal cortisol levels
- 2009
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Ingår i: Neuroimmunomodulation. - : S. Karger AG. - 1423-0216 .- 1021-7401. ; 16:4, s. 245-250
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Tidskriftsartikel (refereegranskat)abstract
- <i>Objective:</i> The balance between glucocorticoid (GC) release and GC sensitivity in target cells is believed to be important to maintain homeostasis in the neuroendocrine control of inflammation. We investigated the impact of in vivo exposure to adrenocorticotropic hormone (ACTH) and dexamethasone (DEX) on GC sensitivity measured in vitro in healthy individuals with high versus low baseline cortisol levels. <i>Methods:</i>136 healthy male volunteers were screened twice and sorted according to their 24-hour urinary free cortisol (UFC) excretion. The 10 individuals with the highest UFC (290 ± 87 nmol/24 h) and the 10 with the lowest UFC (168 ± 34 nmol/24 h) were further tested. Measurements were performed at baseline, after a low dose (0.5 μg/1.73 m<sup>2</sup>) of ACTH challenge and after 2 weeks’ exposure to DEX (0.1 mg twice daily). GC sensitivity was assessed in vitro as the ability of DEX to inhibit lipopolysaccharide-stimulated production of the cytokines interleukin 1-β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in a whole-blood assay. <i>Results:</i>After exposure to DEX in vivo<i>,</i> inhibition of IL-6 and TNF-α decreased. Also<i>, </i>after DEX in vivo, low-cortisol men showed lower inhibition of IL-1β and IL-6, both compared to the high-cortisol group and their own baseline levels. <i>Conclusion:</i> A downregulation of GC sensitivity in leukocytes after exposure to an exogenous GC seems to occur most strongly in men with low cortisol levels.
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| 46. |
- Ljung, Thomas, 1961-, et al.
(författare)
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Central and peripheral glucocorticoid receptor function in abdominal obesity.
- 2002
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Ingår i: Journal of endocrinological investigation. - 0391-4097 .- 1720-8386. ; 25:3, s. 229-35
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Tidskriftsartikel (refereegranskat)abstract
- Abdominal obesity seems to be associated with a moderately deranged feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis where central glucocorticoid receptors (GR) are involved. Therefore, functions of central and peripheral GR were compared in this study. Furthermore, since trinucleotide repeats in early exons of steroid hormone receptor genes influence transcription, and therefore may influence receptor density, this was also studied. Ten middle-aged men, 5 with abdominal obesity and 5 controls, were studied. The suppression of dexamethasone (dex) on serum cortisol was used in dose-response tests to assess the function of central GR. Abdominal adipose tissue biopsies were incubated and exposed to cortisol in different concentrations, and the function of the peripheral GR assayed as induction of lipoprotein lipase (LPL) activity. Aberrant expansion of exonic trinucleotide repeats in the first coding exon of the GR gene was studied by sequencing of genomic DNA. Results showed that men with abdominal obesity showed less inhibition of serum cortisol by dex, particularly at lower concentrations, while in the controls cortisol secretion was inhibited in an apparent dose-response manner. LPL activity in adipose tissue was lower in abdominal obese men than in controls. However, the sensitivity to cortisol was not different between the groups. There was no evidence for expansion of trinucleotide repeats. These results suggest that the central GR and the peripheral GR in adipose tissue exhibit functional differences in abdominal obesity.
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| 47. |
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| 48. |
- Mosges, R, et al.
(författare)
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Why do we treat allergies with antibiotics?
- 2006
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Ingår i: Current opinion in allergy and clinical immunology. - : Ovid Technologies (Wolters Kluwer Health). - 1528-4050. ; 6:3, s. 144-145
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Tidskriftsartikel (refereegranskat)
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