D-Pinitol Attenuated Ovalbumin-induced Allergic Rhinitis in Experimental Mice Via Balancing Th1/Th2 Response

Allergic rhinitis (AR) is a complex, chronic immunoinflammatory disorder of the membrane lining of the nasal mucosa. D-Pinitol is considered a cyclic polyol with a potential effect against various allergies. In the present study, we evaluated the anti-allergic effect of pinitol on ovalbumin (OVA)-induced AR model in mice. BALB/c mice were initially sensitized with an intraperitoneal injection of OVA and divided into 5 groups (n=18, in each group) for a treating schedule of distilled water (DW), montelukast (10 mg/kg), and pinitol (5, 10, and 20 mg/kg) through the mouth. Two saline-injected groups were considered as controls by orally administrating DW and pinitol 20. Thereafter, test and control groups were intranasally challenged by OVA and saline, respectively. Our results showed that the OVA challenge caused a marked elevation in AR symptoms like nasal rubbing, sneezing, and discharge which were remarkably diminished using pinitol (10 and 20 mg/kg) and the results were comparable with montelukast. Additionally, increased levels of total and OVA-specific serum Immunoglobulin (Ig) E and IgG1 were significantly attenuated by pinitol as compared to the control group but not the montelukast group. In AR-induced mice, pinitol had significant modulatory effects on representative markers of Th2 (GATA binding protein 3), signal transducer and activator of transcription-6, Interleukins (IL)-4, IL-5, IL-13, suppressors of cytokine signaling 1, Toll-like receptor 4, and myeloid differentiation factor 88), and Type 1 T helper (Th1) immune responses (T-box protein expressed in T cells and Interferon-gamma) as well as the histopathological aberrations induced in the nasal mucosa. In conclusion, Pinitol had potential effects on OVA-induced AR mice through amelioration of nasal symptoms and balancing the Th1/Th2 immune responses during the allergic rhinitis condition.

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The extract of black cumin, licorice, anise, and black tea alleviates OVA-induced allergic rhinitis in mouse via balancing activity of helper T cells in lung

Allergy Asthma & Clinical Immunology ◽

10.1186/s13223-021-00587-6 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Chengsong Liao ◽

Yangyang Han ◽

Zhijing Chen ◽

Huricha Baigude

Keyword(s):

Allergic Rhinitis ◽

Nasal Mucosa ◽

Aqueous Extract ◽

Nigella Sativa ◽

Inflammatory Cells ◽

Serum Levels ◽

Lavage Fluid ◽

Ar Model ◽

Control Group ◽

Black Cumin

Abstract Background A formulation of black cumin (Nigella sativa L.), licorice (Glycyrrhiza glabra L.), anise (Pimpinella anisum L.) and tea (Camellia sinensis (L.) Kuntze) (denoted BLAB tea) is traditionally used to relief allergy reaction including allergic rhinitis. However, little is known about its underlining mechanism of anti-allergic effects. Methods To investigate the anti-allergenic mechanism of BLAB tea, we treated ovalbumin (OVA)-induced allergic rhinitis (AR) model of mice with BLAB tea, and elucidated its possible mechanism of action. Mice in the control group were treated with phosphate-buffered saline only. Subsequently, the infiltration of different inflammatory cells was measured. In addition, histopathological changes in the nasal mucosa, and the levels of allergen-specific cytokines and OVA-specific immunoglobulins were measured. Results The aqueous extract of BLAB significantly alleviated the nasal symptoms and reduced the accumulation of inflammatory cells in the nasal mucosa and nasal lavage fluid of AR model of mice. Conclusion The aqueous extract of BLAB induced the production of Th1 and Treg cytokines and inhibited the release of Th2 cytokines and histamine in nasal mucosa and serum of mice while decreasing the serum levels of OVA-specific IgE, IgG1, and IgG2a. These results suggest the potential of the aqueous extract of BLAB as a treatment option for allergic diseases.

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Apigenin Attenuates Allergic Responses of Ovalbumin-Induced Allergic Rhinitis Through Modulation of Th1/Th2 Responses in Experimental Mice

Dose-Response ◽

10.1177/1559325820904799 ◽

2020 ◽

Vol 18 (1) ◽

pp. 155932582090479 ◽

Cited By ~ 1

Author(s):

Feng Chen ◽

Dongyun He ◽

Bailing Yan

Keyword(s):

Allergic Rhinitis ◽

Messenger Rna ◽

Immunoglobulin E ◽

Elevated Serum ◽

Lavage Fluid ◽

Specific Ige ◽

Cytokine Signaling ◽

Nuclear Factor ◽

Th2 Response ◽

Ifn Γ

Background: Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated immune-inflammatory response mainly affecting nasal mucosa. Apigenin, a flavonoid, has been documented to possess promising anti-allergic potential. Aim: To determine the potential mechanism of action of apigenin against ovalbumin (OVA)-induced AR by assessing various behavioral, biochemical, molecular, and ultrastructural modifications. Materials and Methods: Allergic rhinitis was induced in BALB/c mice (18-22 grams) by sensitizing it with OVA (5%, 500 μL, intraperitoneal [IP] on each consecutive day, for 13 days) followed by intranasal challenge with OVA (5%, 5 μL per nostril on day 21). Animals were treated with either vehicle (distilled water, 10 mg/kg, IP) or apigenin (5, 10, and 20 mg/kg, IP). Results: Intranasal challenge of OVA resulted in significant induction ( P < .05) of AR reflected by an increase in nasal symptoms (sneezing, rubbing, and discharge), which were ameliorated significantly ( P < .05) by apigenin (10 and 20 mg/kg) treatment. It also significantly inhibited ( P < .05) OVA-induced elevated serum histamine, OVA-specific IgE, total IgE, and IgG1 and β-hexosaminidase levels. Ovalbumin-induced increased levels of interleukin (IL)-4, IL-5, IL-13, and interferon (IFN)-γ in nasal lavage fluid were significantly decreased ( P < .05) by apigenin. Ovalbumin-induced alterations in splenic GATA binding protein 3 (ie, erythroid transcription factor) (GATA3), T-box protein expressed in T cells (T-bet), signal transducer and activator of transcription-6 (STAT6), suppressor of cytokine signaling 1 (SOCS1), nuclear factor-kappa B (NF-κB), and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha messenger RNA, as well as protein expressions were significantly inhibited ( P < .05) by apigenin. It also significantly ameliorated ( P < .05) nasal and spleen histopathologic and ultrastructure aberration induced by OVA. Conclusion: Apigenin regulates Th1/Th2 balance via suppression in expressions of Th2 response (IgE, histamine, ILs, GATA3, STAT6, SOCS1, and NF-κB) and activation of Th1 response (IFN-γ and T-bet) to exert its anti-allergic potential in a murine model of OVA-induced AR.

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Comparison of Intranasal Hypertonic Dead Sea Saline Spray and Intranasal Aqueous Triamcinolone Spray in Seasonal Allergic Rhinitis

Ear Nose & Throat Journal ◽

10.1177/014556130508400713 ◽

2005 ◽

Vol 84 (7) ◽

pp. 426-430 ◽

Cited By ~ 38

Author(s):

Scott Cordray ◽

Jim B. Harjo ◽

Linda Miner

Keyword(s):

Allergic Rhinitis ◽

Nasal Mucosa ◽

Seasonal Allergic Rhinitis ◽

Dead Sea ◽

Control Group ◽

Life Questionnaire ◽

Intranasal Corticosteroids ◽

Eye Symptoms ◽

The Dead ◽

Positive Effect

Intranasal corticosteroids are well known to be efficacious in the treatment of allergic rhinitis. Nasal irrigation with saline, including hypertonic saline, has long been recommended for the treatment of sinonasal disease, and it has been shown to have a positive effect on the physiology of the nasal mucosa. Until now, no study of the clinical efficacy of intranasal hypertonic Dead Sea saline as a monotherapy for seasonal allergic rhinitis has been reported. We conducted a prospective, randomized, single-blind, placebo-controlled comparison of intranasal hypertonic Dead Sea saline spray and intranasal aqueous triamcinolone spray in 15 patients with seasonal allergic rhinitis. Results were based on a 7-day regimen. Based on Rhinoconjunctivitis Quality of Life Questionnaire scores, clinically and statistically significant (p < 0.0001) improvements were seen in both active-treatment groups; as expected, the corticosteroid spray was the more effective of the two treatments. No significant improvement occurred in the control group. Our preliminary results not only confirm the efficacy of intranasal corticosteroid therapy in moderate-to-severe allergic rhinitis, they also suggest that the Dead Sea saline solution can be an effective alternative in mild-to-moderate allergic rhinitis, particularly with respect to nasal and eye symptoms. The hypertonicity of the Dead Sea solution may have a positive effect on the physiology of the nasal mucosa by improving mucociliary clearance. In addition, the dominant cation in the Dead Sea solution— magnesium— probably exerts anti-inflammatory effects on the nasal mucosa and on the systemic immune response.

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EPITHELIAL CELLS EXPRESSING TLR-2 LEVEL AND NOSE MUCOSA BIOCENOSIS IN ALLERGIC RHINITIS PATIENTS

Rossiiskii Allergologicheskii ZHurnal ◽

10.36691/rja617 ◽

2013 ◽

Vol 10 (6) ◽

pp. 20-24

Author(s):

Yu A Tyurin ◽

A A Sharifullina ◽

I G Mustafin ◽

R S Fassakhov

Keyword(s):

Allergic Rhinitis ◽

Epithelial Cells ◽

Healthy Volunteers ◽

Nasal Mucosa ◽

Allergic Diseases ◽

Nasal Lavage ◽

Control Group ◽

Healthy Individuals ◽

Local Immunity

Background. Determination of local epithelial cells expressing TLR2 as an indicator of local immunity in allergic rhinitis (AR) patients with opportunistic species of staphylococci nasal mucosa colonization. Methods. Washed epithelium samples obtained from patients with seasonal AR (n=8) aged 19—42 years, and perennial AR (n=15) aged 19 —45 years, as well as a control group (20 patients) aged 19—45 years without allergic diseases were investigated. Epithelial cells expressing TLR2 receptors were determined by flow cytometry. Results. The level of epithelial cells expressing TLR2 receptor in patients with seasonal AR was almost in 1,9 times, in perennial AR group — in 1,7 times lower then in healthy individuals. In patients with perennial AR S. aureus was obtained in 96,0% (CI: 79,5—99,2), in association with Str. pyogenes in 29% (CI: 14,9—49,2), Neisseria spp. — in 63,0% (CI: 42,7—78,8). Seasonal allergic rhinitis was characterized by association of S. aureus and S. hemolyticus (70,0%, 44,4—85,8). Conclusion. Ratio of epithelial cells positive for TLR2 in nasal lavage from patients with AR was lower than in healthy volunteers. Indicators proportion of epithelial cells expressing TLR2 in nasal lavage in patients with seasonal AR during an exacerbation period was significantly reduced (1,7—1,9 times), in comparison with healthy volunteers. In AR patients with increased density of staphylococci strains in nasal mucosa increased local epithelial cells expressing TLR2 in nasal lavage was established.

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Taurine Promotes the Production of CD4+CD25+FOXP3+ Treg Cells through Regulating IL-35/STAT1 Pathway in a Mouse Allergic Rhinitis Model

10.21203/rs.3.rs-113785/v1 ◽

2020 ◽

Author(s):

Jing Zhou ◽

Yi Lu ◽

Wei Wu ◽

Yunhai Feng

Keyword(s):

Allergic Rhinitis ◽

Nasal Mucosa ◽

Goblet Cell ◽

Inflammatory Cytokine ◽

Neutralizing Antibody ◽

Treg Cells ◽

Ar Model ◽

Cytokine Release ◽

Cell Content ◽

Taurine Treatment

Abstract Background: Allergic rhinitis (AR) is one of the most widespread immune conditions worldwide. However, common treatments often present with significant side effects or are cost-prohibitive for much of the population. A plethora of treatments have been used for the treatment of AR including antihistamines, steroids, and immune modulators. Among the treatments which have shown potential for efficacy in treating AR with a minimum of side effects but remains understudied is the conditionally essential amino acid taurine. Taurine has been previously shown to reduce AR symptoms. Here, we examine the role of taurine in modulating T regulatory cells, modulating the cytokine response in AR, and restoring healthy nasal mucosa.Methods: Blood samples from 20 healthy donors and 20 AR patients were compared for CD4+CD25+FoxP3+ T regulatory (Treg) cell population percentage, cytokine release, and STAT1 signaling with and without taurine treatment or IL-35 neutralization. An OVA-induced AR mouse model was administered vehicle, taurine, or taurine plus an IL-35 neutralizing antibody and assayed for sneezing frequency, inflammatory cytokine response, nasal mucosa goblet cell density, and T regulatory cell percentage. CD4+ cells were further examined for cytokine release, STAT1 phosphorylation, and response to an anti-IL-35 antibody with and without a STAT1 inhibitor. Results: Comparison of blood from normal donors and AR patients showed a reduction in CD4+CD25+FoxP3+ Treg cells in AR patients and a strong correlation between Treg percentage and IL-35 release. A similar pattern of Treg suppression was found in untreated AR mice when compared to normal control mice wherein there was a reduction in Treg percentage and a corresponding decrease in IL-35 release. AR mice also demonstrated increased sneezing frequency, an infiltration of goblet cell in nasal mucosa, and a reduction in IL-35 release from CD4+ cells. Conversely, IL-4, IL-5, and IL-13 secretion from CD4+ cells were increased in AR model mice, as was STAT1 phosphorylation. When AR mice were treated with taurine, sneezing frequency and nasal mucosa goblet cell content were reduced while Treg abundance was increased to that of normal mice. Accordingly, IL-35 release was restored, while IL-4, IL-5, and IL-13 secretion from CD4+ cells were suppressed. Likewise, STAT1 phosphorylation was inhibited with taurine treatment. Taurine-treated mice also given an IL-35 neutralizing antibody exhibited AR pathology including frequent sneezing and high nasal goblet cell content while retaining a restoration of Tregs. Furthermore, murine AR model CD4+ cells exposed to recombinant IL-35 responded with a reduction in inflammatory cytokine release and a decrease in STAT1 phosphorylation, mimicking the effect of taurine treatment. Conclusions: Taurine induces release of IL-35 in AR; IL-35 promotes the production of CD4+CD25+FoxP3+ Treg cells via a STAT1-dependent pathway. The restoration of Treg populations by taurine normalizes the inflammatory response, reduces AR symptomology, and reduces histopathologic signs of AR.

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The Effects of Halofuginone on Wound Healing in the Rat Nasal Mucosa

American Journal of Rhinology and Allergy ◽

10.1177/1945892419866312 ◽

2019 ◽

Vol 34 (1) ◽

pp. 9-15 ◽

Cited By ~ 1

Author(s):

Seyit Mehmet Ceylan ◽

Erdal Uysal ◽

Mehmet Sokucu ◽

Efe Sezgin ◽

Mahmut Alper Kanmaz ◽

...

Keyword(s):

Wound Healing ◽

Nasal Mucosa ◽

Goblet Cell ◽

Cell Formation ◽

Treated Group ◽

Potential Effect ◽

The Other ◽

Parasitic Infections ◽

Control Group ◽

Cell Hyperplasia

Background Halofuginone is an alkaloid febrifugine analogue and bioactive molecule that was isolated incidentally from the Dichroa febrifuga plant. The therapeutic efficacy of halofuginone in parasitic infections, scleroderma, inflammation, and fibrosis-related diseases, as well as in some types of cancer, has been previously reported. The effects of halofuginone on nasal mucosal damage are not yet known. Objective The aim of this study was to investigate the potential effect of topically applied halofuginone on wound healing in the mechanically injured nasal mucosa of rats. Methods A unilateral mucosal wound was created in the nasal cavity of 32 rats (aged 4 weeks) using the brushing technique. These rats were randomly divided into 4 groups. Although the control group did not receive an intervention, a dry pad, a saline-impregnated pad, or a pad impregnated with halofuginone were placed in the rats of the other 3 groups and left for 5 minutes. Rats were sacrificed on the 14th day, and a histological examination was performed. The nasal mucosa was assessed via hematoxylin-eosin and Masson’s trichrome staining. Results There were no statistically significant differences in epithelial thickness, inflammation, goblet cell formation, and epithelial disarray values between the halofuginone group and the control group ( P > .05). The subepithelial thickness was significantly decreased in the saline-treated group and the halofuginone-treated group ( P < .05), but a significantly lower level of subepithelial fibrosis was only observed in the halofuginone group compared to the other groups ( P < .05). Conclusions Topical halofuginone administration reduces the development of fibrosis and subepithelial edema after experimentally induced nasal mucosal injury, but it does not exert therapeutic or preventive effects on epithelial damage, inflammation, and goblet cell hyperplasia.

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Prenatal stress, anxiety and depression alter transcripts, proteins and pathways associated with immune responses at the maternal-fetal interface

Biology of Reproduction ◽

10.1093/biolre/ioab232 ◽

2021 ◽

Author(s):

Cristina A Martinez ◽

Ina Marteinsdottir ◽

Ann Josefsson ◽

Gunilla Sydsjö ◽

Elvar Theodorsson ◽

...

Keyword(s):

Immune System ◽

Immune Responses ◽

Psychiatric Symptoms ◽

Anxiety And Depression ◽

Cytokine Signaling ◽

Control Group ◽

Index Group ◽

Immune Related Genes ◽

The Impact ◽

Maternal Fetal Interface

Abstract During pregnancy, the immune system is modified to allow developmental developmental tolerance of the semi-allogeneic fetus and placenta to term. Pregnant women suffering from stress, anxiety and depression show dysfunctions of their immune system that may be responsible for fetal and/or newborn disorders, provided that provided that placental gene regulation is compromised. The present study explored the effects of maternal chronic self-perceived stress, anxiety and depression during pregnancy on the expression of immune related-genes and pathways in term placenta. Pregnancies were clinically monitored with the Beck’s Anxiety Inventory (BAI) and Edinburgh Postnatal Depression Scale (EPDS). A cutoff threshold for BAI/EPDS of 10 divided patients into two groups: Index group (≥10, n = 11) and a Control group (<10, n = 11), whose placentae were sampled at delivery. The placental samples were subjected to RNA-Sequencing, demonstrating that stress, anxiety and depression during pregnancy induced a major downregulation of placental transcripts related to immune processes such as T-cell regulation, interleukin and cytokine signaling or innate immune responses. Expression differences of main immune related genes such as CD46, CD15, CD8α & β ILR7α and CCR4 among others, were found in the index group (P < 0.05). Moreover, the key immune-like pathway involved in humoral and cellular immunity named “Primary immunodeficiency” was significantly downregulated in the index group compared to controls. Our results show that mechanisms ruling immune system functions are compromised at the maternal-fetal interface following self-perceived depressive symptoms and anxiety during pregnancy. These findings may help unveil mechanisms ruling the impact of maternal psychiatric symptoms and lead to new prevention/intervention strategies in complicated pregnancies.

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Potential markers for allergic rhinitis evaluation

Romanian Medical Journal ◽

10.37897/rmj.2016.1.4 ◽

2016 ◽

Vol 63 (1) ◽

pp. 17-19

Author(s):

Adina Zamfir-Chiru-Anton ◽

◽

Dan-Cristian Gheorghe ◽

Keyword(s):

Allergic Rhinitis ◽

Immune Responses ◽

Nasal Mucosa ◽

Inflammatory Cell ◽

Immune Cell ◽

Basilar Membrane ◽

Type I ◽

Local Inflammatory Response ◽

Fundamental Cause ◽

Type I Hypersensitivity

Allergic rhinitis is the result of a permanent/intermitent inflammation of the nasal mucosa, exposed to certain alergens. An immunological reaction is the fundamental cause – a type I hypersensitivity reaction, followed by local inflammatory response and immune cell pooling (eosinophiles, basophiles, Th cells, mast cells) in the nasal mucosa. Matrix metaloproteinases are tissue proteases that degrade extracellular matrix and basilar membrane and modulate immune responses. Our article reviews the part metalloproteinases play in the changes suffered by the nasal mucosa in chronic allergic rhinitis (fibrosis, metaplasia, edema, inflammatory cell infiltration).

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Intralymphatic Administration of Metagonimus yokogawai-Extracted Protein Attenuates Experimental Murine Allergic Rhinitis Model

International Archives of Allergy and Immunology ◽

10.1159/000511532 ◽

2020 ◽

pp. 1-7

Author(s):

Hyung Chae Yang ◽

Eun Jeong Won ◽

Moon-Ju Kim ◽

Chung Man Sung ◽

Joon Haeng Rhee ◽

...

Keyword(s):

Allergic Rhinitis ◽

Lymph Nodes ◽

Therapeutic Effect ◽

Nasal Mucosa ◽

Treated Group ◽

Eosinophil Infiltration ◽

Th2 Response ◽

Cervical Lymph Nodes ◽

Immunological Mechanism ◽

Cytokine Profiles

Objectives: This study aimed to evaluate potential therapeutic effect of Metagonimus yokogawai on the OVA-induced allergic rhinitis model. Methods: OVA-sensitized mice were used to assess potential therapeutic effect of the extract protein of M. yokogawai (My-TP). My-TP was administrated via the intralymphatic route to cervical lymph nodes. The frequencies of sneezing or nasal rubbing were recorded. Histopathologic evaluation was performed for eosinophil infiltrations in the tissues of the nasal mucosa and skin. The mRNA relative expressions of the cytokine profiles including Th1, Th2, Th17, and Treg subsets in the nasal mucosa, cervical lymph nodes, and spleen were analyzed by quantitative real-time reverse-transcriptase polymerase chain reaction. The potential underlying mechanism was investigated by examining cytokine profiles including IL-4 and Treg subsets from lymphocytes of the spleen by flow cytometry. Results: Intralymphatic injection of My-TP reduced allergic symptoms and eosinophil infiltration in the nasal mucosa. My-TP-treated group showed markedly decreased levels of OVA-specific IgE and WBC counts in nasal lavage. My-TP-treated group showed the decreased expression levels of IL-4, while those of IL-10 were increased in both the nasal mucosa. The levels of IFN-γ and IL-17 were also decreased in the nasal mucosa and cervical lymph nodes. The immunological mechanism may involve the downregulation of Th2 response and upregulation of Tregs in the nasal mucosa and cervical lymph nodes. Conclusions: Our results provide the first evidence of potential therapeutic effect of M. yokogawai in OVA-sensitized allergic rhinitis mice, suggesting that a Treg/Th2 reorganization may play a role in clinical course of allergic rhinitis.

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The Comparation of Intraperitoneal Injection and Nasal-only Delivery Allergic Rhinitis Model Challenged With Different Allergen Concentration

American Journal of Rhinology and Allergy ◽

10.1177/1945892418817221 ◽

2019 ◽

Vol 33 (2) ◽

pp. 145-152 ◽

Cited By ~ 16

Author(s):

Ying Wang ◽

Yue Zhou ◽

Yun Zhu ◽

Wenting Yu ◽

Jinghui Wang ◽

...

Keyword(s):

Allergic Rhinitis ◽

Dose Response ◽

Lavage Fluid ◽

Ar Model ◽

Control Group ◽

Response Relationship ◽

Serum Antibodies ◽

Dose Response Relationship ◽

Delivery Model ◽

Allergic Symptoms

Background Predominantly, 2 animal models are used for allergic rhinitis (AR), which are established by intraperitoneal (IP) injection plus local challenge and nasal-only delivery. The differences between these 2 models are not fully understood. Moreover, dose–response relationship to allergens remains unclear. Methods In this study, mice were sensitized by nasal drops (without adjuvant, once daily for 9 weeks) to set up a nasal-only delivery AR model. Five different doses of ovalbumin (OVA) nasal drops were served to explore the dose–response to allergens. Allergic symptoms, serum antibodies (IgE, IgG2a, and IgG1), spleen supernatant and nasal lavage fluid (NALF) cytokines (IL-4, IL-5, and IFN-r), and infiltrated eosinophils of the nasal mucosa were observed. Results The allergic symptoms, serum antibodies, cytokines, and infiltrated eosinophils were significantly higher in the high OVA concentration compared with those of the control group. Different OVA concentrations associated with the severity of allergy. Within a certain concentration range, OVA concentration positively related to the severity of symptoms, IgE antibody level, and Th2 bias. Meanwhile, serum antibodies (IgE and IgG1) and cytokines (IL-4, IL-5 in spleen and IL-4 in NALF) were significantly higher in the classical IP injection group than in the nasal drip groups. Conclusion The IP injection model and the nasal-only delivery model are 2 typical models for AR that causes a different immune response. A positive dose–response relationship in the nasal-only delivery model is observed from 25 mg/mL to 0.025 mg/mL.

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