Background Second-generation antihistamines are H 1 receptor antagonists and may have additional ... more Background Second-generation antihistamines are H 1 receptor antagonists and may have additional anti-inflammatory effects.
RATIONALE: This study aimed to investigate various lifestyle factors and their association with s... more RATIONALE: This study aimed to investigate various lifestyle factors and their association with symptoms of allergic rhinitis in schoolchildren. METHODS: A questionnaire regarding lifestyle factors and allergic rhinitis was distributed to the parents of 7-year-old schoolchildren at every primary school in Ohmi-Hachiman City, Shiga Prefecture, Japan. The International Collaborative Study of Asthma and Allergies in Childhood questionnaire provided information about the prevalence of allergic rhinitis. Following the descriptive statistics, we developed univariate and multivariate logistic regression models to evaluate the association between lifestyle factors and allergic rhinitis. P values <0.05 were considered to indicate statistical significance and Pvalues <0.1 were considered to indicate a tendency. RESULTS: Among the parents of 759 7-year-old children who attended primary school, 640 (84.3%) answered the questionnaire. Of these children, 223 (34.8%) had allergic rhinitis symptoms. Among the lifestyle factors investigated, children who did not participate in any sports activities after school had significantly fewer allergic rhinitis symptoms than those who did (OR50.69, P50.03). Similarly, children whose commuting time to school was less than 30 minutes tended to have fewer allergic rhinitis symptoms than those whose commuting time was 30 minutes or more (OR50.72, P50.07). No significant association between other lifestyle factors (passive smoking, obesity, bedtime, wake-up time, and eating habits) and allergic rhinitis symptoms was found. CONCLUSIONS: Participating in sports activities and commuting were associated with a higher prevalence of allergic rhinitis. Increased exposure to pollen or other outdoor allergens may contribute to these associations.
Peripheral primitive neuroectodermal tumors are highly malignant small cell neoplasms. A 27-year-... more Peripheral primitive neuroectodermal tumors are highly malignant small cell neoplasms. A 27-year-old female presented with a 6-month history of right-sided facial pain and progressive weakness of the facial muscles. She had non-pulsative tinnitus, progressive right hearing loss and facial palsy. T2-weighted MRI showed a heterogeneous hyperintense lesion invading the right internal auditory canal. Surgical removal was performed. Pathological examination showed sheets of small cells with irregular nuclei. Immunohistochemical studies demonstrated positive immunoreactivity for neuron-specific enolase, synaptophysin, chromogranin, vimentin, S-100 protein and p30-32 MIC-2 gene product. The patient was treated with chemotherapy (etoposide, vincristine, adriamycin, ifosfamide and actinomycin D) and radiotherapy. After 65 months of follow-up, the patient presented with cervical metastasis. Radical cervical dissection was performed and the patient was treated with a second course of chemotherapy. At control MRI after 29 months of follow-up the patient showed no signs of local recurrence or distant metastasis.
The aim of the present study was to evaluate the in vivo regulation of cyclooxygenase-2 in nasal ... more The aim of the present study was to evaluate the in vivo regulation of cyclooxygenase-2 in nasal polyps. In total, 65 patients with nasal polyps were randomly (3:1) treated with (n = 51; 33 with asthma) or without (n = 14) oral prednisone and intranasal budesonide for 2 weeks plus intranasal budesonide for 10 additional weeks. Biopsies were obtained at baseline and after 2 and 12 weeks of treatment. All samples were analysed for cyclooxygenase-1 and cyclooxygenase-2 mRNA. Attempts were made to detect cyclooxygenase-2 protein. At baseline, cyclooxygenase-1 and cyclooxygenase-2 expression did not differ between polyps from nonasthmatic and asthmatic patients. Cyclooxygenase-1 mRNA was unchanged by glucocorticoid treatment, while cyclooxygenase-2 mRNA increased in glucocorticoid-treated patients at week 2 compared with baseline and then decreased at week 12. Within subgroups, increased cyclooxygenase-2 mRNA was found at week 2 in polyps from nonasthmatic and asthmatic patients compared with baseline. At week 12, cyclooxygenase-2 expression remained high in nonasthmatics while it decreased in asthmatics. Cyclooxygenase-2 protein was not detected under any circumstances. Glucocorticoid therapy enhances cyclooxygenase-2 expression in vivo in nasal polyps, a finding that does not follow the generally accepted assumption that cyclooxygenase-2 expression is suppressed by glucocorticoids.
Only dynamic studies can elucidate the discrepancies concerning the expression of the inducible C... more Only dynamic studies can elucidate the discrepancies concerning the expression of the inducible COX-2 gene in inflammatory airway diseases. To quantify the expression and spontaneous regulation of COX-1 and COX-2 mRNAs in nasal polyps and nasal mucosa by real-time PCR. Nasal polyps were obtained from 16 aspirin-tolerant patients with asthma/rhinitis (ATAR) and 18 aspirin-intolerant patients with asthma/rhinitis (AIAR) undergoing nasal polypectomy. Nasal mucosa was obtained from 12 subjects undergoing nasal corrective surgery. All specimens were cut into 3 pieces. One was immediately snap-frozen in liquid nitrogen, and the remaining 2 were left at room temperature for 30 or 60 minutes before freezing. Data are presented as medians and 25th to 75th percentiles of 10 6 cDNA molecules/microg total RNA. Baseline COX-2 mRNA levels were significantly lower in both ATAR (0.45; 0.13-1.20; P &amp;amp;amp;amp;lt;.05) and AIAR (0.24; 0.12-0.41; P &amp;amp;amp;amp;lt;.001) nasal polyps than in nasal mucosa (1.35; 0.52-3.90). COX-2 mRNA expression did not change over time in nasal mucosa but increased significantly in ATAR nasal polyps ( P &amp;amp;amp;amp;lt;.05), reaching similar levels to nasal mucosa after 60 minutes. In contrast, COX-2 mRNA showed no significant change over time in AIAR nasal polyps. COX-1 mRNA was higher in nasal polyps than in nasal mucosa, and its expression was not modified over time in any group of patients. These results suggest differential kinetics of COX-2 mRNA between nasal mucosa and nasal polyps. AIAR nasal polyps appear to have a greater abnormality of the COX-2 pathway than ATAR.
Anomalies in the regulation of cyclooxygenase (COX)-1 and -2 have been described in nasal polyps ... more Anomalies in the regulation of cyclooxygenase (COX)-1 and -2 have been described in nasal polyps of aspirin-induced asthma (AIA). Whether these anomalies are specific to nasal polyps or affect all the nasal mucosa (NM) of upper airways is still unclear. The objective of this study was to compare the COX pathway in NM of AIA patients with the NM of control subjects. Fibroblasts were isolated from NM of five AIA patients (AIA-NM) and five control subjects (control-NM). Cells were treated with 10 ng/mL interleukin (IL)-1β for up to 72 h. Prostaglandin E2 (PGE2 ) production was measured by enzyme-linked immunosorbent assay (ELISA), expression of COX-1 protein by Western blot and COX-2 protein by ELISA, Western blot and immunofluorescence techniques. IL-1β increased PGE2 production and COX-1 protein expression in control-NM fibroblasts, but no changes were found in AIA-NM. IL-1β provoked a significant time-dependent increase in COX-2 protein expression in control-NM fibroblasts but had a very mild effect on COX-2 protein expression in AIA-NM. Our data suggest that abnormalities in the COX pathway are not a phenomenon exclusive to nasal-polyp mucosa as they are also present in all the NM of AIA patients. These anomalies may be involved in the pathogenesis of airway inflammation and non-steroidal anti-inflammatory drug intolerance in asthma patients with chronic rhinosinusitis and nasal polyposis.
RationaleEpithelial cells release cytokines such as GM-CSF that contribute to eosinophil inflamma... more RationaleEpithelial cells release cytokines such as GM-CSF that contribute to eosinophil inflammation in allergic rhinitis and nasal polyposis. The aim of this study was to investigate the effect of desloratadine on both GM-CSF secretion and eosinophil survival.
Journal of Pharmacology and Experimental Therapeutics, 2012
Proteasome inhibitors, used in cancer treatment for their proapoptotic effects, have anti-inflamm... more Proteasome inhibitors, used in cancer treatment for their proapoptotic effects, have anti-inflammatory and antifibrotic effects on animal models of various inflammatory and fibrotic diseases. Their effects in cells from patients affected by either inflammatory or fibrotic diseases have been poorly investigated. Nasal polyposis is a chronic inflammatory disease of the sinus mucosa characterized by tissue inflammation and remodeling. We tested the hypothesis that proteasome inhibition of nasal polyp fibroblasts might reduce their proliferation and inflammatory and fibrotic response. Accordingly, we investigated the effect of the proteasome inhibitor Z-Leu-Leu-Leu-B(OH)(2) (MG262) on cell viability and proliferation and on the production of collagen and inflammatory cytokines in nasal polyp and nasal mucosa fibroblasts obtained from surgery specimens. MG262 reduced the viability of nasal mucosa and polyp fibroblasts concentration- and time-dependently, with marked effects after 48 h of treatment. The proteasome inhibitor bortezomib provoked a similar effect. MG262-induced cell death involved loss of mitochondrial membrane potential, caspase-3 and poly(ADP-ribose) polymerase activation, induction of c-Jun phosphorylation, and mitogen-activated protein kinase phosphatase-1 expression. Low concentrations of MG262 provoked growth arrest, inhibited DNA replication and retinoblastoma phosphorylation, and increased expression of the cell cycle inhibitors p21 and p27. MG262 concentration-dependently inhibited basal and transforming growth factor-β-induced collagen mRNA expression and interleukin (IL)-1β-induced production of IL-6, IL-8, monocyte chemoattractant protein-1, regulated on activation normal T cell expressed and secreted, and granulocyte/macrophage colony-stimulating factor in both fibroblast types. MG262 inhibited IL-1β/tumor necrosis factor-α-induced activation of nuclear factor-κB. We conclude that noncytotoxic treatment with MG262 reduces the proliferative, fibrotic, and inflammatory response of nasal fibroblasts, whereas high MG262 concentrations induce apoptosis.
International Archives of Allergy and Immunology, 2014
Fluticasone furoate (FF) is an intranasal corticosteroid indicated for the treatment of allergic ... more Fluticasone furoate (FF) is an intranasal corticosteroid indicated for the treatment of allergic rhinitis (AR). However, the anti-inflammatory effects of FF in the nasal mucosa have yet to be investigated thoroughly. The aim of this study was to investigate the effect of FF on eosinophil survival and cytokine secretion from nasal mucosa epithelial cells. Epithelial cells obtained from nasal mucosa were stimulated with 10% fetal bovine serum (FBS) in the presence of FF (from 10(-12) to 10(-7)M) for 6-24 h. Cytokine [granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6 and IL-8] concentrations in supernatants were measured by ELISA. Peripheral blood eosinophils were incubated for 4 days with epithelial cell secretions in the presence or absence of FF (from 10(-12) to 10(-7)M) and survival was assessed by Trypan blue dye exclusion. Results are expressed as medians of the minimum effective concentration and IC values. FBS stimulated the secretion of GM-CSF, IL-6 and IL-8. FF significantly inhibited GM-CSF (up to 10(-10)M, IC25 = 12.6 pM), IL-6 (up to 10(-10)M, IC25 = 65.8 pM) and IL-8 (up to 10(-11)M, IC25 = 8.6 pM) secretion induced by FBS (n = 8). Epithelial cell secretions induced eosinophil survival from day 1 to day 4 (n = 6). This effect was significantly inhibited by FF (up to 10(-12)M) at day 3 (IC50 = 3.22 nM) and day 4 (IC50 = 1.29 nM). The results obtained in this in vitro model suggest that FF may reduce upper airway eosinophilic inflammation through decreasing cytokine secretion from epithelial cells and reducing eosinophil survival.
Background Second-generation antihistamines are H 1 receptor antagonists and may have additional ... more Background Second-generation antihistamines are H 1 receptor antagonists and may have additional anti-inflammatory effects.
Loss of sense of smell is one of the most frequent complaints in patients with nasal polyposis (N... more Loss of sense of smell is one of the most frequent complaints in patients with nasal polyposis (NP). The aim of this study was to evaluate the impact of asthma and its severity on the sense of smell. Patients with massive NP and healthy controls were included. More than half of patients presented with asthma. Olfactometry by Barcelona Smell Test 24, nasal symptoms score, nasal endoscopy, allergy study, and paranasal sinus CT scan were assessed. NP patients showed a significant impairment in smell detection, identification, and forced choice compared to the control. Asthmatics reported lower scores for detection, identification, and forced choice than non-asthmatic patients. Patients with persistent asthma had an increased impairment of sense of smell on detection, identification, and forced choice than patients with intermittent asthma. No significant differences were found between mild, moderate, and severe persistent asthmatics. Paranasal sinuses opacification was inversely correl...
Background Mucus hyper-secretion is a feature of several airways diseases such as chronic rhinosi... more Background Mucus hyper-secretion is a feature of several airways diseases such as chronic rhinosinusitis, asthma, and cystic fibrosis (CF). Since mucins are major components of mucus, the knowledge of their distribution and regulation in nasal tissues is likely to improve mucus hyper-secretion therapy.
Airway mucus is composed from water, ions, lung secretions, serum protein transudates, antimicrob... more Airway mucus is composed from water, ions, lung secretions, serum protein transudates, antimicrobial proteins and mucus glycoproteins (mucins) (1). Mucins, the major component of mucus, are high-molecular weight proteins extensively glycosylated, synthesized and secreted by epithelial goblet cells and mucous cells of submucosal glands (SMG). To date, 20 human mucin genes (2) have been identified and subdivided into secreted and membrane-tethered mucins.
L. Pujols). 1 Both authors contributed equally to this work with senior responsibilities. a v a i... more L. Pujols). 1 Both authors contributed equally to this work with senior responsibilities. a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / r m e d Respiratory Medicine (2011) 105, 218e225
Background Second-generation antihistamines are H 1 receptor antagonists and may have additional ... more Background Second-generation antihistamines are H 1 receptor antagonists and may have additional anti-inflammatory effects.
RATIONALE: This study aimed to investigate various lifestyle factors and their association with s... more RATIONALE: This study aimed to investigate various lifestyle factors and their association with symptoms of allergic rhinitis in schoolchildren. METHODS: A questionnaire regarding lifestyle factors and allergic rhinitis was distributed to the parents of 7-year-old schoolchildren at every primary school in Ohmi-Hachiman City, Shiga Prefecture, Japan. The International Collaborative Study of Asthma and Allergies in Childhood questionnaire provided information about the prevalence of allergic rhinitis. Following the descriptive statistics, we developed univariate and multivariate logistic regression models to evaluate the association between lifestyle factors and allergic rhinitis. P values <0.05 were considered to indicate statistical significance and Pvalues <0.1 were considered to indicate a tendency. RESULTS: Among the parents of 759 7-year-old children who attended primary school, 640 (84.3%) answered the questionnaire. Of these children, 223 (34.8%) had allergic rhinitis symptoms. Among the lifestyle factors investigated, children who did not participate in any sports activities after school had significantly fewer allergic rhinitis symptoms than those who did (OR50.69, P50.03). Similarly, children whose commuting time to school was less than 30 minutes tended to have fewer allergic rhinitis symptoms than those whose commuting time was 30 minutes or more (OR50.72, P50.07). No significant association between other lifestyle factors (passive smoking, obesity, bedtime, wake-up time, and eating habits) and allergic rhinitis symptoms was found. CONCLUSIONS: Participating in sports activities and commuting were associated with a higher prevalence of allergic rhinitis. Increased exposure to pollen or other outdoor allergens may contribute to these associations.
Peripheral primitive neuroectodermal tumors are highly malignant small cell neoplasms. A 27-year-... more Peripheral primitive neuroectodermal tumors are highly malignant small cell neoplasms. A 27-year-old female presented with a 6-month history of right-sided facial pain and progressive weakness of the facial muscles. She had non-pulsative tinnitus, progressive right hearing loss and facial palsy. T2-weighted MRI showed a heterogeneous hyperintense lesion invading the right internal auditory canal. Surgical removal was performed. Pathological examination showed sheets of small cells with irregular nuclei. Immunohistochemical studies demonstrated positive immunoreactivity for neuron-specific enolase, synaptophysin, chromogranin, vimentin, S-100 protein and p30-32 MIC-2 gene product. The patient was treated with chemotherapy (etoposide, vincristine, adriamycin, ifosfamide and actinomycin D) and radiotherapy. After 65 months of follow-up, the patient presented with cervical metastasis. Radical cervical dissection was performed and the patient was treated with a second course of chemotherapy. At control MRI after 29 months of follow-up the patient showed no signs of local recurrence or distant metastasis.
The aim of the present study was to evaluate the in vivo regulation of cyclooxygenase-2 in nasal ... more The aim of the present study was to evaluate the in vivo regulation of cyclooxygenase-2 in nasal polyps. In total, 65 patients with nasal polyps were randomly (3:1) treated with (n = 51; 33 with asthma) or without (n = 14) oral prednisone and intranasal budesonide for 2 weeks plus intranasal budesonide for 10 additional weeks. Biopsies were obtained at baseline and after 2 and 12 weeks of treatment. All samples were analysed for cyclooxygenase-1 and cyclooxygenase-2 mRNA. Attempts were made to detect cyclooxygenase-2 protein. At baseline, cyclooxygenase-1 and cyclooxygenase-2 expression did not differ between polyps from nonasthmatic and asthmatic patients. Cyclooxygenase-1 mRNA was unchanged by glucocorticoid treatment, while cyclooxygenase-2 mRNA increased in glucocorticoid-treated patients at week 2 compared with baseline and then decreased at week 12. Within subgroups, increased cyclooxygenase-2 mRNA was found at week 2 in polyps from nonasthmatic and asthmatic patients compared with baseline. At week 12, cyclooxygenase-2 expression remained high in nonasthmatics while it decreased in asthmatics. Cyclooxygenase-2 protein was not detected under any circumstances. Glucocorticoid therapy enhances cyclooxygenase-2 expression in vivo in nasal polyps, a finding that does not follow the generally accepted assumption that cyclooxygenase-2 expression is suppressed by glucocorticoids.
Only dynamic studies can elucidate the discrepancies concerning the expression of the inducible C... more Only dynamic studies can elucidate the discrepancies concerning the expression of the inducible COX-2 gene in inflammatory airway diseases. To quantify the expression and spontaneous regulation of COX-1 and COX-2 mRNAs in nasal polyps and nasal mucosa by real-time PCR. Nasal polyps were obtained from 16 aspirin-tolerant patients with asthma/rhinitis (ATAR) and 18 aspirin-intolerant patients with asthma/rhinitis (AIAR) undergoing nasal polypectomy. Nasal mucosa was obtained from 12 subjects undergoing nasal corrective surgery. All specimens were cut into 3 pieces. One was immediately snap-frozen in liquid nitrogen, and the remaining 2 were left at room temperature for 30 or 60 minutes before freezing. Data are presented as medians and 25th to 75th percentiles of 10 6 cDNA molecules/microg total RNA. Baseline COX-2 mRNA levels were significantly lower in both ATAR (0.45; 0.13-1.20; P &amp;amp;amp;amp;lt;.05) and AIAR (0.24; 0.12-0.41; P &amp;amp;amp;amp;lt;.001) nasal polyps than in nasal mucosa (1.35; 0.52-3.90). COX-2 mRNA expression did not change over time in nasal mucosa but increased significantly in ATAR nasal polyps ( P &amp;amp;amp;amp;lt;.05), reaching similar levels to nasal mucosa after 60 minutes. In contrast, COX-2 mRNA showed no significant change over time in AIAR nasal polyps. COX-1 mRNA was higher in nasal polyps than in nasal mucosa, and its expression was not modified over time in any group of patients. These results suggest differential kinetics of COX-2 mRNA between nasal mucosa and nasal polyps. AIAR nasal polyps appear to have a greater abnormality of the COX-2 pathway than ATAR.
Anomalies in the regulation of cyclooxygenase (COX)-1 and -2 have been described in nasal polyps ... more Anomalies in the regulation of cyclooxygenase (COX)-1 and -2 have been described in nasal polyps of aspirin-induced asthma (AIA). Whether these anomalies are specific to nasal polyps or affect all the nasal mucosa (NM) of upper airways is still unclear. The objective of this study was to compare the COX pathway in NM of AIA patients with the NM of control subjects. Fibroblasts were isolated from NM of five AIA patients (AIA-NM) and five control subjects (control-NM). Cells were treated with 10 ng/mL interleukin (IL)-1β for up to 72 h. Prostaglandin E2 (PGE2 ) production was measured by enzyme-linked immunosorbent assay (ELISA), expression of COX-1 protein by Western blot and COX-2 protein by ELISA, Western blot and immunofluorescence techniques. IL-1β increased PGE2 production and COX-1 protein expression in control-NM fibroblasts, but no changes were found in AIA-NM. IL-1β provoked a significant time-dependent increase in COX-2 protein expression in control-NM fibroblasts but had a very mild effect on COX-2 protein expression in AIA-NM. Our data suggest that abnormalities in the COX pathway are not a phenomenon exclusive to nasal-polyp mucosa as they are also present in all the NM of AIA patients. These anomalies may be involved in the pathogenesis of airway inflammation and non-steroidal anti-inflammatory drug intolerance in asthma patients with chronic rhinosinusitis and nasal polyposis.
RationaleEpithelial cells release cytokines such as GM-CSF that contribute to eosinophil inflamma... more RationaleEpithelial cells release cytokines such as GM-CSF that contribute to eosinophil inflammation in allergic rhinitis and nasal polyposis. The aim of this study was to investigate the effect of desloratadine on both GM-CSF secretion and eosinophil survival.
Journal of Pharmacology and Experimental Therapeutics, 2012
Proteasome inhibitors, used in cancer treatment for their proapoptotic effects, have anti-inflamm... more Proteasome inhibitors, used in cancer treatment for their proapoptotic effects, have anti-inflammatory and antifibrotic effects on animal models of various inflammatory and fibrotic diseases. Their effects in cells from patients affected by either inflammatory or fibrotic diseases have been poorly investigated. Nasal polyposis is a chronic inflammatory disease of the sinus mucosa characterized by tissue inflammation and remodeling. We tested the hypothesis that proteasome inhibition of nasal polyp fibroblasts might reduce their proliferation and inflammatory and fibrotic response. Accordingly, we investigated the effect of the proteasome inhibitor Z-Leu-Leu-Leu-B(OH)(2) (MG262) on cell viability and proliferation and on the production of collagen and inflammatory cytokines in nasal polyp and nasal mucosa fibroblasts obtained from surgery specimens. MG262 reduced the viability of nasal mucosa and polyp fibroblasts concentration- and time-dependently, with marked effects after 48 h of treatment. The proteasome inhibitor bortezomib provoked a similar effect. MG262-induced cell death involved loss of mitochondrial membrane potential, caspase-3 and poly(ADP-ribose) polymerase activation, induction of c-Jun phosphorylation, and mitogen-activated protein kinase phosphatase-1 expression. Low concentrations of MG262 provoked growth arrest, inhibited DNA replication and retinoblastoma phosphorylation, and increased expression of the cell cycle inhibitors p21 and p27. MG262 concentration-dependently inhibited basal and transforming growth factor-β-induced collagen mRNA expression and interleukin (IL)-1β-induced production of IL-6, IL-8, monocyte chemoattractant protein-1, regulated on activation normal T cell expressed and secreted, and granulocyte/macrophage colony-stimulating factor in both fibroblast types. MG262 inhibited IL-1β/tumor necrosis factor-α-induced activation of nuclear factor-κB. We conclude that noncytotoxic treatment with MG262 reduces the proliferative, fibrotic, and inflammatory response of nasal fibroblasts, whereas high MG262 concentrations induce apoptosis.
International Archives of Allergy and Immunology, 2014
Fluticasone furoate (FF) is an intranasal corticosteroid indicated for the treatment of allergic ... more Fluticasone furoate (FF) is an intranasal corticosteroid indicated for the treatment of allergic rhinitis (AR). However, the anti-inflammatory effects of FF in the nasal mucosa have yet to be investigated thoroughly. The aim of this study was to investigate the effect of FF on eosinophil survival and cytokine secretion from nasal mucosa epithelial cells. Epithelial cells obtained from nasal mucosa were stimulated with 10% fetal bovine serum (FBS) in the presence of FF (from 10(-12) to 10(-7)M) for 6-24 h. Cytokine [granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6 and IL-8] concentrations in supernatants were measured by ELISA. Peripheral blood eosinophils were incubated for 4 days with epithelial cell secretions in the presence or absence of FF (from 10(-12) to 10(-7)M) and survival was assessed by Trypan blue dye exclusion. Results are expressed as medians of the minimum effective concentration and IC values. FBS stimulated the secretion of GM-CSF, IL-6 and IL-8. FF significantly inhibited GM-CSF (up to 10(-10)M, IC25 = 12.6 pM), IL-6 (up to 10(-10)M, IC25 = 65.8 pM) and IL-8 (up to 10(-11)M, IC25 = 8.6 pM) secretion induced by FBS (n = 8). Epithelial cell secretions induced eosinophil survival from day 1 to day 4 (n = 6). This effect was significantly inhibited by FF (up to 10(-12)M) at day 3 (IC50 = 3.22 nM) and day 4 (IC50 = 1.29 nM). The results obtained in this in vitro model suggest that FF may reduce upper airway eosinophilic inflammation through decreasing cytokine secretion from epithelial cells and reducing eosinophil survival.
Background Second-generation antihistamines are H 1 receptor antagonists and may have additional ... more Background Second-generation antihistamines are H 1 receptor antagonists and may have additional anti-inflammatory effects.
Loss of sense of smell is one of the most frequent complaints in patients with nasal polyposis (N... more Loss of sense of smell is one of the most frequent complaints in patients with nasal polyposis (NP). The aim of this study was to evaluate the impact of asthma and its severity on the sense of smell. Patients with massive NP and healthy controls were included. More than half of patients presented with asthma. Olfactometry by Barcelona Smell Test 24, nasal symptoms score, nasal endoscopy, allergy study, and paranasal sinus CT scan were assessed. NP patients showed a significant impairment in smell detection, identification, and forced choice compared to the control. Asthmatics reported lower scores for detection, identification, and forced choice than non-asthmatic patients. Patients with persistent asthma had an increased impairment of sense of smell on detection, identification, and forced choice than patients with intermittent asthma. No significant differences were found between mild, moderate, and severe persistent asthmatics. Paranasal sinuses opacification was inversely correl...
Background Mucus hyper-secretion is a feature of several airways diseases such as chronic rhinosi... more Background Mucus hyper-secretion is a feature of several airways diseases such as chronic rhinosinusitis, asthma, and cystic fibrosis (CF). Since mucins are major components of mucus, the knowledge of their distribution and regulation in nasal tissues is likely to improve mucus hyper-secretion therapy.
Airway mucus is composed from water, ions, lung secretions, serum protein transudates, antimicrob... more Airway mucus is composed from water, ions, lung secretions, serum protein transudates, antimicrobial proteins and mucus glycoproteins (mucins) (1). Mucins, the major component of mucus, are high-molecular weight proteins extensively glycosylated, synthesized and secreted by epithelial goblet cells and mucous cells of submucosal glands (SMG). To date, 20 human mucin genes (2) have been identified and subdivided into secreted and membrane-tethered mucins.
L. Pujols). 1 Both authors contributed equally to this work with senior responsibilities. a v a i... more L. Pujols). 1 Both authors contributed equally to this work with senior responsibilities. a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / r m e d Respiratory Medicine (2011) 105, 218e225
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