Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.775
Filtrar
1.
Am J Respir Cell Mol Biol ; 63(5): 707-709, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32857620
2.
Sci Rep ; 10(1): 10568, 2020 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-32601278

RESUMO

Topical intra-nasal sprays are amongst the most commonly prescribed therapeutic options for sinonasal diseases in humans. However, inconsistency and ambiguity in instructions show a lack of definitive knowledge on best spray use techniques. In this study, we have identified a new usage strategy for nasal sprays available over-the-counter, that registers an average 8-fold improvement in topical delivery of drugs at diseased sites, when compared to prevalent spray techniques. The protocol involves re-orienting the spray axis to harness inertial motion of particulates and has been developed using computational fluid dynamics simulations of respiratory airflow and droplet transport in medical imaging-based digital models. Simulated dose in representative models is validated through in vitro spray measurements in 3D-printed anatomic replicas using the gamma scintigraphy technique. This work breaks new ground in proposing an alternative user-friendly strategy that can significantly enhance topical delivery inside human nose. While these findings can eventually translate into personalized spray usage instructions and hence merit a change in nasal standard-of-care, this study also demonstrates how relatively simple engineering analysis tools can revolutionize everyday healthcare. Finally, with respiratory mucosa as the initial coronavirus infection site, our findings are relevant to intra-nasal vaccines that are in-development, to mitigate the COVID-19 pandemic.


Assuntos
Administração por Inalação , Administração Intranasal/métodos , Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Sistemas de Liberação de Medicamentos/métodos , Sprays Nasais , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Simulação por Computador , Infecções por Coronavirus/virologia , Humanos , Hidrodinâmica , Cavidade Nasal/anatomia & histologia , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/virologia , Nebulizadores e Vaporizadores , Seios Paranasais/efeitos dos fármacos , Seios Paranasais/virologia , Pneumonia Viral/virologia , Vacinas Virais/administração & dosagem
3.
Toxicol Lett ; 333: 33-41, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32687961

RESUMO

Recent studies have revealed that increased reactive oxidative stress (ROS) induced by particulate matter (PM) affects tight junction (TJ) functions; however, the molecular mechanisms underlying this effect have not been evaluated fully. Cultured human epithelial cells obtained from inferior turbinate tissues were exposed to an urban PM (UPM) standard reference material (SRM 1648a). Intracellular ROS level and expression of proinflammatory cytokines and TJ proteins were examined. Expression level of phosphorylated (p)-Akt, p38, p65 were compared between exposed and unexposed cells. Cells were pretreated with the ROS scavenger N-acetylcysteine (NAC) or Akt inhibitor MK-2206 before exposure to determine whether the changes in cellular ROS and TJ protein expression could be reversed. Exposure to UPM significantly increased ROS levels and inflammatory cytokine expression levels, and decreased expression of TJ proteins zonula occludins (ZO)-1, occludin, claudin-1, and E-cadherin. UPM exposure increased p-Akt, p-p38, and p65 expression levels, and NAC pretreatment reversed these effects. Akt inhibition decreased UPM-induced ROS formation and p38 and p65 protein phosphorylation, and restored the decreased ZO-1 and E-cadherin expression. Akt inhibition and ROS scavenging may provide targets for maintaining epithelial integrity by restoring decreased TJ protein expression during exposure to UPM.


Assuntos
Poluentes Atmosféricos/toxicidade , Células Epiteliais/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Mucosa Nasal/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Material Particulado/toxicidade , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas de Junções Íntimas/metabolismo , Acetilcisteína/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Células Epiteliais/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/metabolismo , Estresse Oxidativo/genética , Transdução de Sinais , Proteínas de Junções Íntimas/genética , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , Conchas Nasais/efeitos dos fármacos , Conchas Nasais/metabolismo , Urbanização
4.
Am J Otolaryngol ; 41(4): 102561, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32504853

RESUMO

OBJECTIVE: Levitra, a phosphodiesterase-5 (PDE5) inhibitor, is the trade name of vardenafil. It is applied to treatment of erectile dysfunction. PDE5 inhibitors dilate the penile blood vessels and cause prolonged erections. However, the effects of Levitra on human nasal mucosa are not yet fully explored. MATERIALS AND METHODS: We examined the effectiveness of Levitra on human nasal mucosa directly in vitro by testing: 1) effect on human nasal mucosa resting tension; 2) effect on contraction caused by 10-6 M methoxamine as a sympathetic mimetic; 3) effect of the drugs on electrically induced human nasal mucosa contractions. RESULTS: The results showed that addition of methoxamine to the incubation medium caused the nasal mucosa to contract in a dose-dependent manner. Addition of Levitra at doses of 10-4 M elicited a significant relaxation response to 10-6 M methoxamine-induced mucosa strip contraction. Levitra could not inhibit electrical field stimulation-induced spike contraction and had a minimal effect on the basal tension of nasal mucosa as the concentration increased. CONCLUSION: This study indicated that high concentrations of Levitra had a significant spasmolytic effect by antagonizing α-adrenoceptors. Moreover, nasal obstruction might not be relieved in patients suffering from erectile dysfunction and stuffy noses who were concomitant using α-adrenergic agonist and Levitra.


Assuntos
Reposicionamento de Medicamentos , Contração Isométrica/efeitos dos fármacos , Mucosa Nasal/efeitos dos fármacos , Parassimpatolíticos , Inibidores da Fosfodiesterase 5/farmacologia , Dicloridrato de Vardenafila/farmacologia , Relação Dose-Resposta a Droga , Disfunção Erétil/tratamento farmacológico , Humanos , Técnicas In Vitro , Masculino , Metoxamina/farmacologia , Obstrução Nasal/diagnóstico por imagem , Inibidores da Fosfodiesterase 5/uso terapêutico , Simpatomiméticos/farmacologia , Dicloridrato de Vardenafila/uso terapêutico
5.
Int Arch Allergy Immunol ; 181(5): 385-394, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32259823

RESUMO

BACKGROUND: Drug-free viscous nasal applications have been shown to reduce nasal symptoms in individuals with seasonal allergic rhinitis (SAR). Nascum®-Plus (NP), a commercially available thixotropic gel, has been designed to reduce dryness and soreness of the nasal mucosa and prevent the absorption of small particles. OBJECTIVES: The aim of this study was to assess the efficacy of single-dose NP in treating nasal symptoms and secretion during challenge in an allergen challenge chamber (ACC). Furthermore, the effect of this treatment on biomarkers and immune cells of the allergic cascade were measured. METHODS: This open-label, cross-over, sequence-randomized, monocentric trial randomized 18 adults with SAR and a positive skin prick test reaction to Dactylis glomerata pollen to receive NP or no treatment during two 4-h ACC sessions 3 weeks apart. On Day 1, 9 subjects were challenged for 4 h with treatment, the other 9 without treatment, and vice versa on Day 22. Nasal lavage fluid and nasal filter eluate samples were obtained pre, 2, and 18 h post challenge in the ACC. RESULTS: NP significantly reduced nasal symptoms, assessed by total nasal symptom score (p < 0.001), and minimized nasal secretion (p = 0.047), while no significant effect on biomarkers and immune cells in the nasal fluid was observed. The treatment was safe and well-tolerated. CONCLUSIONS: The physical barrier built by NP nasal gel can be safely applied in patients with allergic rhinitis. It reduces allergic nasal symptoms and secretion, but application of a single dose does not affect local inflammatory biomarkers.


Assuntos
Óleo de Rícino/administração & dosagem , Mucosa Nasal/efeitos dos fármacos , Rinite Alérgica Sazonal/imunologia , Rinite Alérgica Sazonal/prevenção & controle , Dióxido de Silício/administração & dosagem , Administração Intranasal , Adulto , Biomarcadores , Coloides , Feminino , Géis , Humanos , Inflamação/imunologia , Inflamação/prevenção & controle , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/imunologia
6.
PLoS One ; 15(2): e0228463, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32027689

RESUMO

Infection with Brucella abortus causes contagious zoonosis, brucellosis, and leads to abortion in animals and chronic illness in humans. Chitosan nanoparticles (CNs), biocompatible and nontoxic polymers, acts as a mucosal adjuvant. In our previous study, B. abortus malate dehydrogenase (Mdh) was loaded in CNs, and it induced high production of pro-inflammatory cytokines in THP-1 cells and systemic IgA in BALB/C mice. In this study, the time-series gene expression analysis of nasal-associated lymphoid tissue (NALT) was performed to identify the mechanism by which Mdh affect the target site of nasal immunization. We showed that intranasal immunization of CNs-Mdh reduced cell viability of epithelial cells and muscle cells at first 1 h, then induced cellular movement of immune cells such as granulocytes, neutrophils and lymphocytes at 6h, and activated IL-6 signaling pathway at 12h within NALT. These activation of immune cells also promoted signaling pathway for high-mobility group box 1 protein (HMGB1), followed by the maturation of DCs required for mucosal immunity. The CNs also triggered the response to other organism and inflammatory response, showing it is immune-enhancing adjuvant. The ELISA showed that significant production of specific IgA was detected in the fecal excretions and genital secretions from the CNs-Mdh-immunized group after 2 weeks-post immunization. Collectively, these results suggest that B. abortus Mdh-loaded CNs triggers activation of HMGB1, IL-6 and DCs maturation signaling within NALT and induce production of systemic IgG and IgA.


Assuntos
Formação de Anticorpos/fisiologia , Brucella abortus/imunologia , Brucelose/prevenção & controle , Imunização/métodos , Tecido Linfoide/imunologia , Malato Desidrogenase/imunologia , Administração Intranasal , Animais , Formação de Anticorpos/efeitos dos fármacos , Brucella abortus/metabolismo , Brucelose/imunologia , Quitosana/administração & dosagem , Quitosana/química , Quitosana/imunologia , Quitosana/farmacologia , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Feminino , Imunidade nas Mucosas/efeitos dos fármacos , Imunogenicidade da Vacina , Tecido Linfoide/efeitos dos fármacos , Malato Desidrogenase/administração & dosagem , Malato Desidrogenase/metabolismo , Malato Desidrogenase/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/administração & dosagem , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/imunologia
7.
Environ Int ; 137: 105506, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32044442

RESUMO

BACKGROUND: Diesel engine exhaust (DEE) exposure causes lung cancer, but the molecular mechanisms by which this occurs are not well understood. OBJECTIVES: To assess transcriptomic alterations in nasal epithelium of DEE-exposed factory workers to better understand the cellular and molecular effects of DEE. METHODS: Nasal epithelial brushings were obtained from 41 diesel engine factory workers exposed to relatively high levels of DEE (17.2-105.4 µg/m3), and 38 unexposed workers from factories without DEE exposure. mRNA was profiled for gene expression using Affymetrix microarrays. Linear modeling was used to identify differentially expressed genes associated with DEE exposure and interaction effects with current smoking status. Pathway enrichment among differentially expressed genes was assessed using EnrichR. Gene Set Enrichment Analysis (GSEA) was used to compare gene expression patterns between datasets. RESULTS: 225 genes had expression associated with DEE exposure after adjusting for smoking status (FDR q < 0.25) and were enriched for genes in pathways related to oxidative stress response, cell cycle pathways such as MAPK/ERK, protein modification, and transmembrane transport. Genes up-regulated in DEE-exposed individuals were enriched among the genes most up-regulated by cigarette smoking in a previously reported bronchial airway smoking dataset. We also found that the DEE signature was enriched among the genes most altered in two previous studies of the effects of acute DEE on PBMC gene expression. An exposure-response relationship was demonstrated between air levels of elemental carbon and the first principal component of the DEE signature. CONCLUSIONS: A gene expression signature was identified for workers occupationally exposed to DEE that was altered in an exposure-dependent manner and had some overlap with the effects of smoking and the effects of acute DEE exposure. This is the first study of gene expression in nasal epithelial cells of workers heavily exposed to DEE and provides new insights into the molecular alterations that occur with DEE exposure.


Assuntos
Mucosa Nasal , Exposição Ocupacional , Transcriptoma , Emissões de Veículos , Humanos , Leucócitos Mononucleares , Mucosa Nasal/efeitos dos fármacos , Emissões de Veículos/toxicidade
8.
Arch Immunol Ther Exp (Warsz) ; 68(1): 6, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32076842

RESUMO

Allergic rhinitis (AR) is an IgE-mediated inflammation which causes olfactory dysfunction. Antihistamines have been widely used to treat AR while few studies have investigated the effect of antihistamines on improving the sense of smell. In addition, the underlying mechanisms are not well elucidated. We established the ovalbumin (OVA)-induced allergic rhinitis rat model and administrated desloratadine to AR rats. The AR symptoms, serum level of OVA-specific IgE and IL-17, and expression of IL-4, IL-5 and IL-13 in nasal mucosa were measured. The olfactory dysfunction was monitored by buried food test and the expression of GluR1 was measured. Desloratadine treatment alleviated AR symptoms, decreased serum level of OVA-specific IgE and IL-17 in AR rats. Desloratadine decreased IL-4, IL-5, and IL-13 expression in nasal mucosa of AR rats. Desloratadine ameliorated olfactory dysfunction in AR rats and decreased GluR1 expression in AR rats. Desloratadine treatment alleviated AR symptoms and ameliorated olfactory dysfunction in AR rats. The expression of AMPA receptor subunit GluR1 in olfactory bulb was associated with olfactory disorder.


Assuntos
Antagonistas dos Receptores Histamínicos H1 não Sedativos/uso terapêutico , Loratadina/análogos & derivados , Transtornos do Olfato/tratamento farmacológico , Receptores de AMPA/metabolismo , Rinite Alérgica/tratamento farmacológico , Animais , Modelos Animais de Doenças , Imunoglobulina E/sangue , Interleucinas/metabolismo , Loratadina/uso terapêutico , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/metabolismo , Transtornos do Olfato/etiologia , Transtornos do Olfato/fisiopatologia , Bulbo Olfatório/efeitos dos fármacos , Bulbo Olfatório/metabolismo , Ovalbumina/toxicidade , Ratos , Ratos Sprague-Dawley , Receptores de AMPA/genética , Rinite Alérgica/induzido quimicamente , Rinite Alérgica/fisiopatologia
9.
Cell Immunol ; 351: 104035, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32051090

RESUMO

BACKGROUND: Piper nigrum L. (Piperaceae) is commonly used as a spice and traditional medicine in many countries. It has been reported to have anti-oxidant, anti-bacterial, anti-tumor, anti-mutagenic, anti-diabetic, and anti-inflammatory properties. However, the protective role of P. nigrum on epithelial function of upper respiratory tract injury in an allergic rhinitis (AR) mouse model has been unclear. This study aims to investigate the effects of P. nigrum fruit extract (PNE) on the nasal epithelial barrier function of the upper respiratory tract in an ovalbumin (OVA)-induced AR model. METHODS: AR mouse model was established by intraperitoneal injection with 200 µL saline containing 50 µg OVA adsorbed to 1 mg aluminum hydroxide, and intranasal challenge with 20 µL per nostril of 1 mg/ml OVA. Besides, mice were orally administrated once daily with PNE and dexamethasone (Dex) in 13 days. The nasal symptoms, inflammatory cells, OVA-specific immunoglobulins, cytokines, nasal histopathology, and immunohistochemistry were evaluated. RESULTS: The PNE oral administrations inhibited allergic responses via reduction of OVA-specific antibodies levels and mast cells histamine release, accordingly, the nasal symptoms in the early-phase reaction were also clearly ameliorated. In both nasal lavage fluid and nasal tissue, PNE suppressed the inflammatory cells accumulation, specifically with eosinophils. The intravenous Evans blue injection illustrated the epithelial permeability reduction of nasal mucosa layer in PNE-treated mice. Also; PNE treatments protected the epithelium integrity by preventing the epithelial shedding from nasal mucosa; as a result of enhancing the strong expression of the E-cadherin tight junction protein in cell-to-cell junctions, as well as inhibiting the degraded levels of zonula occludens-1 (ZO-1) and occludin into the nasal cavity. Additionally, PNE protected against nasal epithelial barrier dysfunction via enhancing the expression of Nrf2 activated form which led to increasing synthesis of the anti-inflammation enzyme HO-1. CONCLUSIONS: These obtained results suggest that PNE has a promising strategy for epithelial barrier stabilization in allergic rhinitis treatment.


Assuntos
Heme Oxigenase-1/metabolismo , Proteínas de Membrana/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Mucosa Nasal/efeitos dos fármacos , Extratos Vegetais/farmacologia , Rinite Alérgica/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mucosa Nasal/metabolismo , Ovalbumina/toxicidade , Piper nigrum , Rinite Alérgica/induzido quimicamente , Transdução de Sinais/efeitos dos fármacos
10.
Int J Mol Sci ; 21(2)2020 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-31940884

RESUMO

Nasal mucosa injury can be caused by trauma, radiotherapy, chronic infection such as sinusitis, and post sinus surgery. The rate of healing and its treatment are important in the recovery of patients especially in post sinus surgery, which introduces new injuries. In this review, the current knowledge in terms of the mechanism underlying nasal wound healing was initially discussed. The currently available treatment options for enhancement of wound healing following sinus surgery were discussed and these had included intravenous antibiotics or steroids, various nasal sprays, and nasal packing. In addition, emerging alternative therapies in nasal mucosa wound healing such as herbal medicine and the advancement of regenerative medicine therapies such as stem cells and their byproducts were also discussed. Despite the various available treatment options for wound healing in nasal mucosa, rigorous strong evidence of their efficacy is gravely warranted in order to recommend them as part of the treatment modality.


Assuntos
Mucosa Nasal/lesões , Doenças dos Seios Paranasais/cirurgia , Complicações Pós-Operatórias/tratamento farmacológico , Administração Oral , Antibacterianos/uso terapêutico , Terapias Complementares , Endoscopia/efeitos adversos , Humanos , Mucosa Nasal/efeitos dos fármacos , Sprays Nasais , Esteroides/uso terapêutico , Cicatrização/efeitos dos fármacos
12.
Int Forum Allergy Rhinol ; 10(1): 59-68, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610615

RESUMO

BACKGROUND: Nasal irrigation (NI) is commonly used to treat several sinonasal diseases, including chronic rhinosinusitis with nasal polyps (CRSwNP); however, the effects of NI on the sinonasal epithelium are not fully known. The aim of this study was to investigate the effects of commonly used NI solutions on epithelial mucociliary and barrier functionality in primary cultured human nasal epithelial cells (HNECs). METHODS: HNECs from control subjects and patients with CRSwNP were established as air-liquid interface (ALI) cultures. Differentiated cultures were treated with different NI solutions, including isotonic 0.9% and hypertonic 3.0% saline, isotonic and hypertonic seawater, and Ringer lactate solution. The changes in ciliary beat frequency (CBF), numbers of ciliated and goblet cells, and cytotoxicity were measured. Epithelial barrier functionality was assessed by measuring the transepithelial electric resistance (TER), paracellular flux, and expression of tight junction protein zonula occludens-1 (ZO-1) and occludin. RESULTS: Isotonic saline, isotonic seawater, and Ringer lactate solutions did not affect epithelial mucociliary and barrier function in either control or CRSwNP-derived ALI cultures; however, hypertonic saline induced a significant disruption of these cell functions in both cultures. Hypertonic seawater caused a transient decrease of CBF and TER in CRSwNP-derived ALI cultures, in contrast to inducing an obvious mucociliary and barrier dysfunction and cytotoxicity in control ALI cultures. CONCLUSION: Although isotonic NI solutions appear to not affect epithelial mucociliary and barrier function in control and CRSwNP-derived ALI cultures, hypertonic saline and seawater solutions damaged sinonasal epithelial cells in ALI cultures. The safety and efficacy of these solutions requires further investigation.


Assuntos
Células Epiteliais/efeitos dos fármacos , Mucosa Nasal/efeitos dos fármacos , Solução Salina/farmacologia , Água do Mar/efeitos adversos , Células Cultivadas , Doença Crônica , Células Epiteliais/fisiologia , Humanos , Depuração Mucociliar/efeitos dos fármacos , Lavagem Nasal/efeitos adversos , Mucosa Nasal/patologia , Mucosa Nasal/fisiopatologia , Pólipos Nasais/patologia , Pólipos Nasais/terapia , Rinite/patologia , Rinite/terapia , Lactato de Ringer/farmacologia , Solução Salina/química , Água do Mar/química , Sinusite/patologia , Sinusite/terapia , Junções Íntimas/efeitos dos fármacos
13.
J Ethnopharmacol ; 248: 112262, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31585162

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia ordosica Krasch. (AOK) has been used for rheumatic arthritis, cold headache, sore throat, etc. in traditional Chinese/Mongolian medicine and is used for nasosinusitis by local Mongolian "barefoot" doctors. Up to now, their mechanisms are still unclear. AIM: To evaluate the in vivo anti-inflammatory and allergic rhinitis (AR) alleviating effect as well as in vitro antimicrobial activities of AOK extracts to verify its ethno-medicinal claims. MATERIALS AND METHODS: Crude extracts (methanol/95%-ethanol/ethyl acetate) of AOK root/stem/leaf and fractions (petroleum ether/ethyl acetate/n-butanol/aqueous) of AOK root extract were prepared. Xylene-induced ear swelling model in mouse and ovalbumin (OVA)-induced AR model in guinea pig were established. Ear swelling degrees of mice were measured. The numbers of rubbing movement and sneezes of guinea pigs were counted to evaluate the symptoms of AR. The serum levels of histamine, INF-γ, IL-2/4/10, and VCAM-1 were measured by ELISA assay. The histological changes of nasal mucosa were investigated by light microscope after H&E staining. Antimicrobial activities of AOK extracts were also tested. LC-MS/MS analysis was performed to characterize the constituents of active extract and molecular docking was conducted to predict the biological mechanism. RESULTS: In ear-swelling model, extract (100.00 mg/kg) from the ethyl acetate layer of 95% ethanol (100.00 mg/kg) showed better swelling inhibition in mice than positive control (dexamethasone, 191.91 mg/kg). In AR model, extract from the ethyl acetate layer of 95% ethanol significantly alleviated the AR symptoms in guinea pigs, decreased the serum levels of histamine, INF-γ, IL-2/4/10, and VCAM-1, and reduced the infiltration of eosinophil in nasal mucosa. For Staphylococcus aureus, the ethyl acetate extract of AOK stem showed the highest inhibition (MIC=1.25 mg/mL), for Escherichia coli, n-butanol layer of 95% ethanol extract of AOK root showed the highest inhibition (MIC=15.00 mg/mL), for Candida glabrata, 95%-ethyl acetate extract of AOK leaf showed the best inhibition (MIC=0.064 mg/mL), while ethyl acetate and n-butanol layers showed similar inhibition on MRSA (MIC=7.50 mg/mL). LC-MS/MS characterization showed that dicaffeoylquinic acids account for more than 30% of ethyl acetate layer of AOK extract. Dicaffeoylquinic acids bind with histamine-1 receptor with high affinities and interesting modes. CONCLUSIONS: Extracts from AOK had interesting anti-inflammatory activity in mice, alleviating effect against OVA-induced AR in guinea pigs, and antimicrobial activities in vitro, which support the ethno-medicinal use of it. The main constituents in ethyl acetate layer of AOK root extract are dicaffeoylquinic acids and could bind with histamine-1 receptor well. These findings highlighted the importance of natural product chemistry study of AOK.


Assuntos
Antialérgicos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Artemisia , Extratos Vegetais/uso terapêutico , Rinite Alérgica/tratamento farmacológico , Sinusite/tratamento farmacológico , Alérgenos , Animais , Antialérgicos/farmacologia , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/farmacologia , Candida glabrata/efeitos dos fármacos , Candida glabrata/crescimento & desenvolvimento , Citocinas/imunologia , Edema/induzido quimicamente , Edema/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Cobaias , Masculino , Medicina Tradicional Chinesa , Medicina Tradicional da Mongólia , Camundongos , Simulação de Acoplamento Molecular , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/patologia , Ovalbumina , Extratos Vegetais/farmacologia , Receptores Histamínicos H1/metabolismo , Rinite Alérgica/imunologia , Rinite Alérgica/patologia , Sinusite/imunologia , Sinusite/patologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Xilenos
14.
J Asthma ; 57(1): 71-78, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30489179

RESUMO

Background: The anti-immunoglobulin E monoclonal antibody, omalizumab, is used to treat severe asthma and has the potential to ameliorate airway inflammation. However, the effect of omalizumab in ameliorating upper airway inflammation has not been fully elucidated. Objective: We investigated the association of upper and lower airway inflammation with the response to omalizumab treatment. Methods: We used the Global Evaluation of Treatment Effectiveness to assess the efficacy of omalizumab in treating 16 patients with severe asthma. We also investigated the symptom score, short-acting ß-agonist inhaler use, pulmonary function, biomarkers, computed tomography scans, and nasal mucosa pathology at omalizumab initiation and after four months of treatment. Results: When the fraction of exhaled nitric oxide (FeNO) and the percentage of sputum eosinophil were used as indicators of lower airway inflammation, positive correlations were found between CD20 B-cell, mast cell, and eosinophil counts in the nasal mucosa. Improved asthma symptoms were observed in 12 of the 16 severe asthma cases. The FeNO and eosinophil levels in the nasal tissue, prior to the administration of omalizumab were predictors of the response to asthma treatment. Conclusions: These findings suggest heterogeneity among people with severe asthma. In addition, the phenotype associated with response to omalizumab, leading to improvement in asthma symptoms, comprises upper airway eosinophilia and high FeNO levels.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Eosinófilos/imunologia , Mucosa Nasal/imunologia , Omalizumab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiasmáticos/farmacologia , Asma/diagnóstico , Asma/imunologia , Linfócitos B/imunologia , Eosinófilos/efeitos dos fármacos , Expiração , Feminino , Humanos , Contagem de Leucócitos , Masculino , Mastócitos/imunologia , Pessoa de Meia-Idade , Mucosa Nasal/citologia , Mucosa Nasal/efeitos dos fármacos , Óxido Nítrico/análise , Omalizumab/farmacologia , Prognóstico , Índice de Gravidade de Doença , Escarro/citologia , Escarro/imunologia , Resultado do Tratamento
15.
Chem Biol Interact ; 315: 108874, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31669322

RESUMO

Allergic rhinitis (AR) is a type I hypersensitivity immune response and is a common chronic allergic respiratory disorder characterized by one or more nasal symptoms. Despite many studies on AR therapy, the drugs of treatment for AR remain limited in effect. In the present study, we aimed to elucidate the effects of saikosaponin A (SSA) on nasal inflammation, T helper (Th)2 and Th17 cytokines, retinoic acid-related orphan nuclear receptor (ROR)-γt, signal transducer and activator of transcription (STAT)3, and nuclear factor (NF)-κB signalings in ovalbumin (OVA)-induced AR mice model. OVA-induced AR mice exhibited increase in nasal symptoms, histological alteration, OVA-specific immunoglobulin (Ig)E/IgG1, ROR-γt, STAT3 and NF-κB signalings. However, the administration of SSA significantly decreased allergic symptoms including nasal rubbing and sneezing. Additionally, histological alterations such as mucosa layer thickness, goblet cell hyperplasia, eosinophils and mast cell infiltration in nasal tissues dramatically improved by treatment with SSA. Also, SSA treatment decreased the levels of OVA-specific IgE/IgG1 in serum and the levels of Th2 and Th17 cytokines such as interleukin (IL)-6 and IL-17 in nasal lavage fluid (NALF). Moreover, SSA inhibited the activation of transcription factor ROR-γt, STAT3 and phosphorylated STAT3 in both NALF and lung. Futher, SSA could also significantly inhibit the expressions of NF-κB p65 and phosphorylated NF-κB p65 in NALF and lung. These present results suggested that SSA may attenuate OVA-induced allergic rhinitis through regulating the expression of IL-6/ROR-γt/STAT3/IL-17/NF-κB signaling. The results indicate that SSA may be used as a therapeutic candidate for allergic rhinitis disease.


Assuntos
Inflamação/tratamento farmacológico , Inflamação/metabolismo , Mucosa Nasal/efeitos dos fármacos , Ácido Oleanólico/análogos & derivados , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica/metabolismo , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Imunoglobulina E/metabolismo , Imunoglobulina G/metabolismo , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Mucosa Nasal/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Ácido Oleanólico/farmacologia , Ovalbumina/farmacologia , Rinite Alérgica/induzido quimicamente , Fator de Transcrição STAT3/metabolismo , Células Th17/efeitos dos fármacos , Células Th17/metabolismo , Células Th2/efeitos dos fármacos , Células Th2/metabolismo
16.
Eur J Clin Microbiol Infect Dis ; 39(2): 333-338, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31720943

RESUMO

This study surveys the clinical relevance of the nasal Staphylococcus aureus colonization status on intensive care unit (ICU)-acquired S. aureus infections and compares molecular characteristics of isolates from the nose and infectious sites. The 390 patients included comprised 278 non-carriers and 112 carriers. Among the carriers, 56 were decolonized with mupirocin. Decolonization was verified through a second (negative) culture. Spa typing and virulence gene profiling were performed for all isolates. Twenty six S. aureus infections were detected in the carriage group and 20 in the non-carriage group. Eighteen of these 26 (69.2%) infections were among carriers, and 8 of these 26 (30.8%) infections occurred among decolonized carriers (p = 0.02). Overall, 31/112 (27.7%) of the colonized patients and 25/46 (60.1%) of infection were due to methicillin-resistant S. aureus (MRSA). The highest frequency virulence genes were sea and hlg (both 100%) in nasal isolates and sea, hlg, fnb, and clf (100%) for infectious isolates. t030 was the most abundant spa type overall. S. aureus carriers were more likely to develop S. aureus infection compared with decolonized and non-carrying patients. The sources of ICU S. aureus infection appear to be exogenous mostly, and a predominant clone (spa type 030) plays an important role. We confirm that nasal mupirocin treatment prevents ICU infections even when there is an increased prevalence of nosocomial MRSA.


Assuntos
Antibacterianos/administração & dosagem , Portador Sadio/microbiologia , Mupirocina/administração & dosagem , Mucosa Nasal/microbiologia , Infecções Estafilocócicas/prevenção & controle , Staphylococcus aureus/efeitos dos fármacos , Técnicas de Tipagem Bacteriana , Portador Sadio/prevenção & controle , Humanos , Unidades de Terapia Intensiva , Irã (Geográfico) , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Mucosa Nasal/efeitos dos fármacos , Prevalência , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/classificação , Staphylococcus aureus/isolamento & purificação , Fatores de Virulência/genética
17.
Int Immunopharmacol ; 78: 106058, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31835084

RESUMO

The G protein-coupled estrogen receptor (GPER) specific agonist G-1 has therapeutic effects in patients with allergic diseases, but any role for G-1 as a therapy for inflammation associated with allergic rhinitis (AR) remains unclear. The structure of the environmental hormone nonylphenol (NP) is very similar to that of estrogen; it binds to the estrogen receptor to produce estrogen-like effects and thus may also bind to the membrane GPER. We explored whether NP administration would reduce the effects of G-1 on AR, the interactions between the two materials, and their mechanisms of action using a murine model of AR. Mice were randomly assigned into control, AR, G-1, and G-1 + NP groups (n = 10/group). AR nasal symptoms were scored. Eosinophils in nasal mucosa were counted after staining with hematoxylin and eosin. Serum ovalbumin (OVA)-specific IgE was determined by ELISA. The proportions of splenic Th1, Th2, and Treg cells were determined by flow cytometry. The expression of transcription factors unique to Th1, Th2, Treg cells and cytokine levels in nasal mucosa were evaluated by real-time PCR and cytometric bead arrays. AR nasal symptoms, including sneezing, nasal scratching, eosinophil infiltration of nasal mucosa, and serum IgE, were reduced in G-1 group. After injection, Th2 cells proportions, Th2-immune response-related cytokines (IL-4, IL-5, and IL-13), and a Th2 cell-specific transcription factor (GATA-3) were significantly decreased in G-1 group. Treg immune response was enhanced (as reflected by Treg cell, IL-10, and Foxp3 levels). The levels of all of these were significantly increased after adding NP, and the Treg immune response was significantly decreased. These results indicate that G-1 attenuated the nasal symptoms, serum OVA-specific IgE, and Th2 cell immune response, whereas it enhanced Treg immune response, in mice with AR. Adding NP weakened these therapeutic effects.


Assuntos
Ciclopentanos/farmacologia , Disruptores Endócrinos/farmacologia , Fenóis/farmacologia , Quinolinas/farmacologia , Receptores Acoplados a Proteínas-G/agonistas , Rinite Alérgica/tratamento farmacológico , Animais , Ciclopentanos/uso terapêutico , Modelos Animais de Doenças , Interações Medicamentosas , Estrogênios/imunologia , Estrogênios/metabolismo , Feminino , Humanos , Camundongos , Mucosa Nasal/citologia , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/imunologia , Ovalbumina/imunologia , Quinolinas/uso terapêutico , Receptores Estrogênicos/imunologia , Receptores Estrogênicos/metabolismo , Receptores Acoplados a Proteínas-G/imunologia , Receptores Acoplados a Proteínas-G/metabolismo , Rinite Alérgica/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia
18.
HNO ; 68(1): 8-13, 2020 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-31511908

RESUMO

BACKGROUND: While an abundant number of studies concerning tobacco smoke and chewing tobacco show carcinogenic potential, there is little data on the consequences of snuff, especially on the cellular level. Therefore, the mutagenic effect of snuff is difficult to estimate and the WHO assessment of snuff being not carcinogenic is based on very limited data. OBJECTIVES: This paper investigates the potential cytotoxic and genotoxic effects of snuff on human lymphocytes and nasal mucosa cells. MATERIALS AND METHODS: Two types of snuff were used: one without menthol and one with a high degree of menthol. The necessary nasal mucosa cells and lymphocytes were collected from 10 subjects undergoing nasal obstruction surgery and incubated for one hour with a snuff-DMSO mixture (range 0.01-2000 µg/ml). Methods included the trypan blue test, the comet assay, and the micronucleus test. RESULTS: The trypan blue test showed no decrease in cell viability for either cell type. The comet assay revealed a significant increase in the Olive Tail Moment for lymphocytes starting at 100 µg/ml and at 1000 µg/ml for nasal mucosa cells. There was no significant increase in micronuclei according to the micronucleus test. No differences between these two types of tobacco were observed. CONCLUSION: The present study demonstrated genotoxic damage, such as DNA strand breaks, which may be repaired, but no non-repairable elevated micronuclei. The present findings cast doubts on the WHO assessment that snuff is not carcinogenic. However, for a sound assessment of the risk potential of snuff, further research on various genotoxic endpoints in human cells is warranted.


Assuntos
Linfócitos , Mucosa Nasal , Tabaco sem Fumaça , Ensaio Cometa , Dano ao DNA , Humanos , Linfócitos/efeitos dos fármacos , Mucosa Nasal/efeitos dos fármacos , Tabaco sem Fumaça/efeitos adversos
19.
Int J Med Sci ; 16(12): 1631-1641, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31839751

RESUMO

Epithelial-mesenchymal transition (EMT) has been reported to occur in eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP). Among the cytokines that cause EMT, high mobility group box 1 (HMGB1) has been shown to give rise to EMT in airway epithelial cells. However, the mechanism of HMGB1-induced EMT in ECRSwNP is unknown. We explored the mechanism and possible inhibitor. Immunohistochemistry (IHC), immunofluorescence (IF), and western blot assay were used to detect the expression and location of HMGB1, peroxisome proliferator-activated receptor-γ (PPAR-γ), and EMT markers in eighteen ECRSwNP and twelve normal nasal mucosa tissues. Epithelial cells isolated from ECRSwNP were cultured with various doses of recombinant human HMGB1 (rhHMGB1) to study the expression of PPAR-γ, and EMT markers. Additionally, the ligand of PPAR-γ was incubated with epithelial cells to interfere with the effects of lipopolysaccharide (LPS) or rhHMGB1 to explore the effect on expression of HMGB1 and EMT markers. These results suggest that HMGB1 was highly expressed in ECRSwNP compared with its expression in control tissues, and EMT was also found highly in ECRSwNP compared with control tissues. Moreover, the cytoplasmic accumulation of HMGB1 in ECRSwNP was obvious compared with normal tissues. We also found dose-dependent induction by rhHMGB1 of up-regulation of N-cadherin and vimentin and down-regulation of ZO-1 and E-cadherin in epithelial cells isolated from ECRSwNP. The agonist of PPAR-γ not only reduced release of HMGB1 induced by LPS, but also reversed the EMT. The protective role of PPAR-γ also appeared in cells that had been incubated with rhHMGB1. In the current study, we discovered that the agonist of PPAR-γ has a potential role in inhibited HMGB1-induced EMT in ECRSwNP. The agonist of PPAR-γ may contribute to inhabit epithelial cells to become mesenchymal-like cells which play an important role in the pathogenesis of ECRSwNP.


Assuntos
Proteína HMGB1/genética , Pólipos Nasais/genética , PPAR gama/genética , Rinite/genética , Sinusite/genética , Caderinas/genética , Células Epiteliais/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Proteína HMGB1/farmacologia , Humanos , Ligantes , NF-kappa B/genética , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/patologia , Pólipos Nasais/complicações , PPAR gama/antagonistas & inibidores , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Rinite/complicações , Rinite/patologia , Transdução de Sinais/efeitos dos fármacos , Sinusite/complicações , Sinusite/patologia , Vimentina/genética , Proteína da Zônula de Oclusão-1/genética
20.
Braz. j. otorhinolaryngol. (Impr.) ; 85(6): 746-752, Nov.-Dec. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1055505

RESUMO

Abstract Introduction: The use of saline irrigation for nasal washes is a well established procedure in the treatment of sinonasal inflammation and infection. In addition to saline solutions, Ringer's lactate is also an efficient option for nasal washes and humidification. Objective: To assess the comfort, humidification and tolerance regarding stinging sensation, provided by sodium chloride nasal gel at the concentrations of 4.5 mg/g and 6.0 mg/g through questionnaires answered by the patients. Methods: A total of 60 patients, 56 females, aged between 22 and 66 years old (mean age of 47) and 4 males, aged between 36 and 66 years (mean age of 49), were included in the study for a period of 17 days (±2 days) treatment. The patients were monitored by a general practitioner throughout the study period. They were instructed to apply each product in both nostrils twice a day during a 7-day period (±2 days). The patients were evaluated prior to the use of the first product at visit 0 (V0), after 7 days of treatment (±2 days) at visit 1 (V1), after 3 days of product discontinuation at visit 2 (V2) and after 7 days (±2 days) of treatment with the second product, in visit 3 (V3). Results: A significant difference (5% significance) was observed regarding comfort and stinging sensation between the two different concentrations; comfort was higher and stinging was lower with the 6.0 mg/g concentration gel. No difference in humidification was observed between the two treatments. Conclusion: Ringer's lactate at the concentration of 6.0 mg/g was superior to that at 4.5 mg/g for parameters comfort and stinging sensation. No statistical difference was observed between the two products regarding nasal humidification.


Resumo Introdução: O uso de soluções salinas para lavagem nasal está consagrado no tratamento de quadros inflamatórios e infecciosos nasossinusais. Além das soluções salinas, o ringer lactato é uma importante opção tanto para lavagem quanto para a hidratação nasal. Objetivo: Avaliar a tolerabilidade (ardência e conforto) e umidificação do produto gel nasal cloreto de sódio 4,5 mg/g em relação ao ringer lactato 6,0 mg/g, por meio de questionários respondidos pelos pacientes. Método: Foram incluídos 60 pacientes, 56 mulheres (22-66 anos; média: 47 anos) e quatro homens (36-66 anos; média: 49 anos) foram incluídos no estudo de 17 dias (± 2 dias) de tratamento. Os pacientes foram supervisionados por um clínico geral durante todo o período do estudo. Os pacientes usaram os produtos com uma borrifada em cada narina duas vezes ao dia, durante sete dias (± 2 dias). As formulações foram avaliadas antes do uso do primeiro produto na visita 0 (V0), após sete dias (± 2 dias) de tratamento na visita 1 (V1), após três dias de interrupção do primeiro tratamento na visita 2 (V2) e após sete dias (± 2 dias) de uso do segundo produto na visita 3 (V3). Resultados: Foi observada diferença significante para o conforto das vias nasais, (significância de 5%), na comparação entre os tratamentos nos atributos de conforto e ardência. O conforto das vias nasais foi superior e a ardência inferior para o gel nasal ringer lactato 6,0 mg/g em comparação ao gel cloreto de sódio 4,5 mg/g. Não foi observada diferença significante para a umidificação entre os tratamentos. Conclusão: O gel ringer lactato 6,0 mg/g foi superior ao produto gel cloreto de sódio 4,5 mg/g nos quesitos conforto e ardência. Não foi observada diferença estatisticamente significante entre os tratamentos em relação à umidificação das vias nasais.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Cloreto de Sódio/administração & dosagem , Doenças Nasais/tratamento farmacológico , Lactato de Ringer/administração & dosagem , Mucosa Nasal/efeitos dos fármacos , Método Simples-Cego , Líquido da Lavagem Nasal , Géis , Umidade , Mucosa Nasal/fisiopatologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA