Method for quantifying the Pasteurella multocida antigen adsorbed on aluminum hydroxide adjuvant in swine atrophic rhinitis vaccine.

Swine atrophic rhinitis is a disease caused by Pasteurella multocida and Bordetella bronchiseptica that affects pigs. Inactivated vaccines containing the toxins produced by Pasteurella multocida and Bordetella bronchiseptica have been widely used for the prevention of swine atrophic rhinitis. The efficacy of a vaccine is correlated with the amount of antigen present; however, the protective toxin of P. multocida bound to aluminum hydroxide, which is used as an adjuvant, can hinder the monitoring of the antigen concentration in the vaccine. This study assessed the applicability of a dot immunoassay as an antigen quantification method using monoclonal antibodies. This quantification method was able to detect the antigen with high specificity and sensitivity even when the antigen was bound to the adjuvant, and its application to vaccine products revealed a correlation between the amount of antigen present in the vaccine and the neutralizing antibody titers induced in pigs. The antigen quantification method presented in this study is a simple and sensitive assay capable of quantifying the amount of antigen present in a vaccine that can be used as an alternative quality control measure.

[Research status and prospect of tissue engineering technology in treatment of atrophic rhinitis].

Objective: To review the research progress of the feasibility of a new treatment method for atrophic rhinitis (ATR) based on tissue engineering technology (seed cells, scaffold materials, and growth factors), and provide new ideas for the treatment of ATR. Methods: The literature related to ATR was extensively reviewed. Focusing on the three aspects of seed cells, scaffold materials, and growth factors, the recent research progress of ATR treatment was reviewed, and the future directions of tissue engineering technology to treat ATR were proposed. Results: The pathogenesis and etiology of ATR are still unclear, and the effectiveness of the current treatments are still unsatisfactory. The construction of a cell-scaffold complex with sustained and controlled release of exogenous cytokines is expected to reverse the pathological changes of ATR, promoting the regeneration of normal nasal mucosa and reconstructing the atrophic turbinate. In recent years, the research progress of exosomes, three-dimensional printing, and organoids will promote the development of tissue engineering technology for ATR. Conclusion: Tissue engineering technology can provide a new treatment method for ATR.

Exploring the Mechanism of Yiqi Qingre Ziyin Method in Regulating Neuropeptide Expression for the Treatment of Atrophic Rhinitis.

Atrophic rhinitis (AR) is a chronic disease that causes severe structural changes to the nasal mucosa leading to squamous epithelial metaplasia. However, treatment regarding AR remains a major challenge. We used network pharmacology and molecular docking methods to explore the potential mechanisms of the Yiqi Qingre Ziyin method to modulate neuropeptides in the treatment of AR. The active ingredients of the Yiqi Qingre Ziyin method and their targets of action were obtained from the Traditional Chinese Medicine Systematic Pharmacology Database Analysis Platform (TCMSP). Disease targets for AR were obtained from four databases: GeneCards, PharmGKB, DrugBank, and Online Mendelian Inheritance in Man (OMIM). A total of 59 active ingredients, 39 potential targets, and 76 relevant neuropeptides were obtained after deduplication. We constructed target interaction networks with the STRING database. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the 14 potential target proteins. We used Cytoscape software to construct the "drug-active ingredient-potential target" and "ingredient-target-pathway" networks of the Yiqi Qingre Ziyin method for treating AR. Molecular docking results suggest that dipeptidyl peptidase 4 (DPP4), opioid receptor gene d1 (OPRD1), and opioid receptor m1 (OPRM1) are key targets for the Yiqi Qingre Ziyin method. Therefore, this study proposed a potential mechanism for the treatment of AR by affecting the expression of neuropeptide-related genes (including DPP4, OPRD1, and OPRM1), which may potentially improve the immune microenvironment of the nasal mucosa.

Historia del manejo de rinitis atrófica / The history of the treatment of atrophic rhinitis

La rinitis atrófica es una enfermedad crónica progresiva caracterizada por dilatación anormal de las cavidades nasales con atrofia de la mucosa, submucosa y cornetes nasales subyacentes. Los factores etiopatogénicos aún son desconocidos. Su presentación clínica consiste en congestión nasal paradójica asociado a secreciones viscosas, con presencia de costras secas de mal olor. La higiene nasal con irrigación de alto volumen y baja presión es el estándar de tratamiento médico. El tratamiento quirúrgico busca reducir el tamaño de las cavidades nasales y promover la regeneración de la mucosa nasal así como también su vascularización y lubricación. A lo largo de la historia se han descrito múltiples procedimientos quirúrgicos que han buscado estrechar la cavidad nasal para permitir el paso de aire de forma más fisiológica. Por otra parte, se han propuesto intervenciones radicales como el cierre de las fosas nasales para disminuir los síntomas y mejorar la calidad de vida. En este artículo se resumen los principales manejos y procedimientos propuestos junto con sus resultados y conclusiones. Si bien la mayoría de las técnicas descritas ya no se utilizan en la actualidad, es importante conocerlas ya que aún existen pacientes que fueron sometidos a ellas pudiendo presentar complicaciones y/o efectos adversos.

Atrophic rhinitis is a chronic progressive disease characterized by abnormal dilatation of the nasal cavities with atrophy of the mucosa, nasal submucosa and underlying nasal turbinates. The etiopathogenic factors are still unknown. Its clinical presentation consists of paradoxical nasal congestion associated with viscous secretions, usually with the presence of dry, bad-smelling crusts. Nasal hygiene with high pressure irrigation remains the standard of medical treatment. Surgical treatment seeks to reduce the size of nasal cavities and promote regeneration of nasal mucosa as well as its vascularization and lubrication. Throughout history, multiple surgical procedures have been described that have sought the narrowing of the nasal cavity to allow the passage of air more physiologically. On the other hand, radical interventions have been proposed such as the closure of the nostrils to reduce symptoms and improve quality. This article summarizes the main proposed procedures along with their results and conclusions. Although most of the techniques described are no longer used today, it is important to know them since there are still patients who were subjected to them and may present complications and / or adverse effects.

Successful management of primary atrophic rhinitis by turbinate reconstruction using autologous costal cartilage.

Initial management of primary atrophic rhinitis is conservative, with nasal ointments, saline irrigation, and antibiotics prescribed to relieve symptoms. However, in cases that show no improvement, a surgical approach is considered. Recently, many studies have reported successful surgical outcomes using various nasal implants. However, no study has reported implantation of autologous costal cartilage in PAR patients. We report here the case of a 63-year-old woman diagnosed with PAR that was intractable to medical therapy. Under general anesthesia, bilateral inferior turbinate reconstruction with autologous costal cartilage was successfully performed without any complications. One month after surgery, her symptoms improved dramatically. At the 2-year follow-up, her Sinonasal Outcome Test 25 (SNOT-25) score was 6, down from an initial score of 108. Her OMU CT showed improved sinonasal mucosal thickness and disappearance of thick mucosal secretion compared with preoperative CT image. Although this is a single case experience, it is suggested that turbinate reconstruction using autologous costal cartilage can serve as promising surgical modality for management of atrophic rhinitis.

Influence of Pasteurella multocida Toxin on the differentiation of dendritic cells into osteoclasts.

Dendritic cells (DC) are antigen-presenting cells that connect the innate and adaptive immune system to ensure an efficient immune response during the course of an infection. Recently, DC came into the spotlight as a potential source of osteoclast progenitors, especially under (auto)inflammatory conditions. The virulence factor Pasteurella multocida Toxin (PMT) causes atrophic rhinitis in pigs, a disease characterised by a severe reduction of nasal bone. Our group and others have shown the potential of PMT in mediating differentiation of monocytes/macrophages into bone-resorbing osteoclasts. However, whether DC are target cells for PMT-induced osteoclast differentiation, is currently unknown. Using different murine DC model systems, we investigated the ability of PMT to induce osteoclast formation in DC. Similar to our previous observations in macrophages, PMT was endocytosed by DC and triggered intracellular deamidation of residue Q209 of the Gq alpha subunit. Still, PMT failed to induce prolonged secretion of osteoclastogenic cytokines and osteoclast formation; instead PMT-treated DC secreted interleukin-12 (IL-12), an inhibitor of osteoclastogenesis. In this study, we show that in comparison to bone marrow-derived macrophages, PMT induces maturation of DC through increased expression of the activation markers CD80 and CD86. As maturation of DC prevents their transdifferentiation into osteoclasts, we hypothesize that PMT, a potent osteoclastogenic toxin, fails to trigger osteoclastogenesis in DC due to its effect on DC maturation and IL-12 production.

Is submucosal fat injection effective in atrophic rhinitis? An experimental animal study.

Atrophic rhinitis (AR) is a disease characterized by the extensive dilatation of the nasal cavity and atrophy of the mucosa, submucosa and bone tissue. Its etiological factors are unknown. There is not a satisfying treatment yet and the treatment of the functional impairment in the atrophic cells is still subject to investigation. The objective of this study is to determine at the histopathological level the possible effects of the submucosal fat injection in an experimental model of AR. 12 albino Wistar-Hannover male rats were included in the study. AR was induced with the Pasteurella multocida toxin, which was diluted with saline. As one of the rats died during the study, it was excluded from the evaluation. The right nasal cavities of all rats (11 nasal cavities) were defined as the control group (Group 1). Fat tissue obtained from the abdominal area was injected in the seven left nasal cavities (Group 2). All injections, which were done to the abdominal regions were also done in the left nasal cavities of the remaining four rats, which constituted the sham group (Group 3). After 14 days, all rats were decapitated and the squamous metaplasia and keratinization in the superficial epithelium, degeneration, vacuolar changes in the basal layer, congestion, inflammatory infiltration, vascular proliferation and glandular atrophy in the submucosa are histopathologically classified. The results were analyzed with statistical methods. Although glandular atrophy was significantly regressed in the fat injection group (Group 2) compared to other groups (p < 0.05), the remaining parameters did not show any significant difference among these three groups. The histopathological effect of the fat injection was modest. We concluded that fat injection treatment has no or at the most a very limited effect in the treatment of atrophic rhinitis.

Analyses and treatments of postoperative nasal complications after endonasal transsphenoidal resection of pituitary neoplasms.

In this study, we analyze and discuss the treatments of postoperative nasal complications after endonasal transsphenoidal resection of pituitary neoplasms (PNs). We performed 129 endonasal transsphenoidal resections of PNs and analyzed and treated cases with nasal complications. After endonasal transsphenoidal resection of PNs, there were 26 cases of postoperative nasal complications (20.1%), including nasal hemorrhage (4.8%), cerebrospinal fluid rhinorrhea (6.9%), sphenoid sinusitis (2.3%), atrophic rhinitis (1.6%), olfactory disorder (1.6%), perforation of nasal septum (0.8%), and nasal adhesion (2.3%). All patients clinically recovered after therapy, which included treatment of the cavity through nasal endoscopy, intranasal corticosteroids, and nasal irrigation. We propose that regular nasal endoscopic review, specific nasal medications, and regular nasal irrigation can effectively clear nasal mucosal hyperemia-induced edema and nasal/nasoantral secretions, as well as promote regeneration of nasal mucosa, prevent nasal adhesion, maintain the sinus cavity drainage, and accelerate the recovery of the physiological function of the paranasal sinus. Timely treatment of patients with nasal complications after endonasal transsphenoidal resections of PNs could greatly relieve the clinical symptoms. Nasal cleaning is very beneficial to patients after surgery recovery.

Characteristics of Human Turbinate-Derived Mesenchymal Stem Cells Are Not Affected by Allergic Condition of Donor.

The characteristics of mesenchymal stem cells (MSCs) derived from human turbinates (hTMSCs) have not been investigated in allergic rhinitis. We evaluated the influence of allergic state of the donor on the characteristics, proliferation, and differentiation potential of hTMSCs, compared with hTMSCs derived from non-allergic patients. hTMSCs were isolated from five non-allergic and five allergic patients. The expression of toll-like receptors (TLRs) in hTMSCs was measured by FACS, and cell proliferation was measured using a cell counting kit. Cytokine secretion was analyzed using multiplex immunoassays. The osteogenic, chondrogenic, and adipogenic differentiation potentials of hTMSCs were evaluated by histology and gene expression analysis. In allergic patients, FACS analysis showed that TLR3 and TLR4 were more highly expressed on the surface of hTMSCs than TLR2 and TLR5. The proliferation of hTMSCs was not influenced by the presence of TLR priming. The expression of IL-6, IL-8, IL-12, IP-10, and RANTES was upregulated after the TLR4 priming. The differentiation potential of hTMSCs was not influenced by TLR priming. These characteristics of hTMSCs were similar to those of hTMSCs from non-allergic patients. We conclude that the allergic condition of the donor does not influence TLR expression, proliferation, or immunomodulatory potential of hTMSCs.

Atrophic rhinitis caused by Cedecea davisae with accompanying mucocele.

Atrophic rhinitis is a chronic inflammatory disease characterized by progressive atrophy of nasal mucosa. Cedecea davisae, a rare pathogen, is a new member of Enterobacteriaceae family. In this article, we report a patient with atrophic rhinitis whose culture test revealed Cedecea davisae. The patient was operated due to accompanying posterior ethmoid mucocele. Levofloxacin and nasal irrigation were administered for two months. Significant improvement was observed in patient's complaints and nasal signs at postoperative sixth month. In conclusion, Cedecea davisae has been thought to cause atrophic rhinitis and mucocele in this patient. Patient recovered with simple treatment. These bacteria should be kept in mind as a causative agent for atrophic rhinitis.

Empty nose syndrome.

Empty nose syndrome (ENS) is a rare, late complication of turbinate surgery. The most common clinical symptoms are paradoxical nasal obstruction, nasal dryness and crusting, and a persistent feeling of dyspnea. Little is known about the pathogenesis of ENS, though it is speculated that anatomical changes leading to alterations in local environment, disruption of mucosal cooling, and disruption of neurosensory mechanisms are strongly implicated. The diagnosis is clinical, though often difficult to make due to the poor correlation between subjective and objective findings. Medical therapies include mucosal humidification, irrigations, and emollients. Surgical therapy should be reserved for refractory cases and may involve turbinate reconstruction, most commonly using implantable biomaterials. Ultimately, prevention of this feared complication through turbinate-sparing techniques is essential.

Noncanonical G-protein-dependent modulation of osteoclast differentiation and bone resorption mediated by Pasteurella multocida toxin.

UNLABELLED: Pasteurella multocida toxin (PMT) induces atrophic rhinitis in animals, which is characterized by a degradation of nasal turbinate bones, indicating an effect of the toxin on bone cells such as osteoblasts and osteoclasts. The underlying molecular mechanism of PMT was defined as a persistent activation of heterotrimeric G proteins by deamidation of a specific glutamine residue. Here, we show that PMT acts directly on osteoclast precursor cells such as bone marrow-derived CD14(+) monocytes and RAW246.7 cells to induce osteoclastogenesis as measured by expression of osteoclast-specific markers such as tartrate-resistant acid phosphatase and bone resorption activity. Treatment performed solely with PMT stimulates osteoclast differentiation, showing a receptor activator of nuclear factor-κB ligand (RANKL)-independent action of the toxin. The underlying signal transduction pathway was defined as activation of the heterotrimeric G proteins Gαq/11 leading to the transactivation of Ras and the mitogen-activated protein kinase pathway. Gαq/11 transactivates Ras via its effector phospholipase Cß-protein kinase C (PKC) involving proline-rich tyrosine kinase 2 (Pyk2). PMT-induced activation of the mitogen-activated protein kinase pathway results in stimulation of the osteoclastogenic transcription factors AP-1, NF-κB, and NFATc1. In addition, Ca(2+)-dependent calcineurin activation of NFAT is crucial for PMT-induced osteoclastogenesis. The data not only elucidate a rationale for PMT-dependent bone loss during atrophic rhinitis but also highlight a noncanonical, G-protein-dependent pathway toward bone resorption that is distinct from the RANKL-RANK pathway but mimics it. We define heterotrimeric G proteins as as-yet-underestimated entities/players in the maturation of osteoclasts which might be of pharmacological relevance. IMPORTANCE: Pasteurella multocida toxin (PMT) induces degradation of nasal turbinate bones, leading to the syndrome of atrophic rhinitis. Recently, the molecular mechanism and substrate specificity of PMT were identified. The toxin activates heterotrimeric G proteins by a covalent modification. However, the mechanism by which PMT induces bone degradation is poorly understood. Our report demonstrates a direct effect of PMT on osteoclast precursor cells, leading to maturation of bone-degrading osteoclasts. Interestingly, PMT stimulates osteoclastogenesis independently of the cytokine RANKL, which is a key factor in induction of osteoclast differentiation. This implicates a noncanonical osteoclastogenic signaling pathway induced by PMT. The elucidated Gαq/11-dependent osteoclastogenic signal transduction pathway ends in osteoclastogenic NFAT signaling. The noncanonical, heterotrimeric G protein-dependent osteoclast differentiation process may be of pharmacological relevance, as members of this pathway are highly druggable. In particular, modulation of G protein-coupled receptor activity in osteoclast progenitors by small molecules might be of specific interest.

Rinitis atrófica / Atrophic rhinitis

La rinitis atrófica es una enfermedad crónica y progresiva de etiología desconocida. Se caracteriza por atrofia de la mucosa nasal y hueso subyacente, dilatación anormal de las cavidades nasales, obstrucción nasal paradójica, y formación de secreciones viscosas y costras secas; produciendo fetidez. Sus manifestaciones clínicas más frecuentes son obstrucción nasal, secreción purulenta, costras nasales y mal olor nasal. Se ha separado en dos entidades: primaria y secundaria. El tratamiento es principalmente conservador, y se han propuesto diversas terapias farmacológicas y quirúrgicas. La rinitis atrófica unilateral es una condición infrecuente, con escasos reportes en la literatura científica. Se puede asociar a la desviación septal, por lo que su corrección quirúrgica es una alternativa terapéutica disponible.

Atrophic rhinitis is a chronic disease of unknown etiology. This condition is characterized by progressive nasal mucosal and underlyng bone atrophy, abnormal widening of the nasal cavities, paradoxical nasal congestion and formation of viscid secretions and dried crusts, leading to a characteristic fetor (ozaena). The main clinical manifestations include nasal obstruction, purulent discharge, daily nasal crusting, nasal dryness and foul smell. It has been divided into two separate entities; primary and secondary. Treatment is mostly conservative, although pharmacological and surgical therapies have been proposed. Unilateral atrophic rhinitis is an uncommon condition, with few reports in the scientific literature. It is associated with septum deviation, so surgical correction is one of the therapeutic options available.

Chronic rhinosinusitis in ex-lepromatous leprosy patients with atrophic rhinitis.

AIM: Rhino-sinus mucosal involvement is well documented in untreated lepromatous leprosy, but less understood in ex-leprosy patients (i.e. leprosy patients who have been treated and cured) with atrophic rhinitis. MATERIALS AND METHODS: Rhino-sinus abnormalities were investigated in 13 ex-lepromatous leprosy patients with atrophic rhinitis, using interviews enquiring about sinonasal symptoms, nasal endoscopy, nasal swab culture and computed tomography. Endoscopic sinus surgery had been performed in three patients. The clinical course, computed tomography findings and nasal biopsy results of these three patients were evaluated. RESULTS: All patients had turbinate atrophy and 6 of the 13 (46.2 per cent) had septal perforation. Paranasal sinus involvement was noted in 9 of 12 examined patients (75 per cent). The most commonly affected sinus was the maxillary sinus (in 8 of 12; 66.7 per cent). All three patients treated by endoscopic sinus surgery experienced relapse and required further surgery. Maxillary sinus irrigation was effective for reduction of persistent symptoms such as postnasal discharge and crusts. CONCLUSION: Ex-lepromatous leprosy patients with atrophic rhinitis had various rhino-sinus abnormalities and persistent symptoms. These patients had chronic rhinosinusitis because of underlying atrophic rhinitis. These patients required repeated otolaryngological observations together with combined surgery and conservative treatment.

[The application of helium-neon laser radiation for the combined treatment of the patients with atrophic rhinitis].

The objective of the present study was to improve the efficacy of the treatment of the patients presenting with atrophic rhinitis (ozena) of the upper respiratory tract by the application of helium-neon laser radiation. A total of 120 patients aged from 15 to 53 years were treated based at the Department of Otorhinolaryngology, G.G. Kuvatov Republican Clinical Hospital, Ufa. All these patients underwent routine clinical, roentgenological, microbiological, and rheographic examination. The method for the treatment of atrophic rhinitis is described; it includes the application of helium-neon laser radiation in combination with the administration of the purified preparation of liquid polyvalent Klebsiella bacteriophage. The positive results of the treatment by the proposed method were documented in 90% of the patients.

Rhinoplasty in atrophic rhinitis.

Rhinoplasty in atrophic rhinitis is a difficult surgery because the dorsal skin is adherent to the underlying structures. There is also more chance of postoperative infection. The experience of various types of rhinoplasty in 15 atrophic rhinitis patients is presented here. The patients were from the age group 17 to 35 years. Most of the operations were done under local anaesthesia. Commonest graft used was conchal-cartilage. Bone graft was avoided for augmentation because of its high rate of absorption in atrophic rhinitis. Young's operation was done in 5 patients in one side along with rhinoplasty. Young's operation was done only with skin layer.

Chemosensory function assessed with psychophysical testing and event-related potentials in patients with atrophic rhinitis.

Atrophic rhinitis (AR) is a chronic inflammation of the nose characterized by an atrophy of the nasal mucosa. This is typically associated with an impaired sense of smell and a subjective sensation of poor nasal breathing. The aim of this study is to assess chemosensory function in patients suffering from AR using psychophysical testings and event-related potentials (ERP) responses. A cohort of nine patients was extensively studied. Eight out of nine had secondary AR sequela of a bilateral total inferior turbinectomy whereas one patient had a primary AR. All the patients had a clinical evaluation using Sniffin' Sticks test and a retro-olfaction test and an electrophysiological evaluation based upon ERPs obtained after both olfactory and trigeminal stimuli. All the patients complained of a poor nasal breathing and presented a distortion of the chemosensory function. Actually, the orthonasal psychophysical testing showed that four patients out of nine had anosmia, three out of nine had hyposmia and two out of nine were normosmic. All the patients demonstrated retro-olfaction scores inferior to the normal values. The chemosensory ERP showed that seven patients had no olfactory response whereas six had no trigeminal response. Four patients had neither olfactory nor trigeminal ERP response. In conclusion, this study demonstrates that most patients with AR secondary to a total bilateral inferior turbinectomy have a reduction of the chemosensory function measured objectively by psychophysical testings and ERP [corrected].