Long noncoding RNA KCNQ1OT1 promotes proliferation, migration, and invasion in maxillary sinus squamous cell carcinoma by regulating miR-204/EphA7 axis.

Long noncoding RNAs have been demonstrated to contribute to the development and progression of various cancers. However, the underlying regulatory mechanisms of KCNQ1OT1 in tumorigenesis of maxillary sinus squamous cell carcinoma (MSSCC) remain unknown. Herein, we found that KCNQ1OT1 expression was markedly upregulated in MSSCC tissues and MSSCC cell line (IMC-3) by using quantitative reverse transcription-polymerase chain reaction. Loss-of-function experiments revealed that the deletion of KCNQ1OT1 inhibited cell proliferation, migration, and invasion. Moreover, we confirmed KCNQ1OT1 could directly interact with miR-204 by bioinformatic prediction and dual luciferase assay, and miR-204 inhibitor markedly reversed MSSCC tumor phenotypes induced by shKCNQ1OT1. Finally, we demonstrated that KCNQ1OT1/miR-204 facilitated MSSCC progression by regulating Eph receptor A7 (EphA7). Taken together, these results revealed a novel regulatory mechanism KCNQ1OT1/miR-204/EphA7 axis, which could provide a new understanding of MSSCC tumorigenesis and develop potential targets for MSSCC therapy.

Xylitol nasal irrigation in the treatment of chronic rhinosinusitis.

OBJECTIVE: To evaluate the efficacy of xylitol nasal irrigation (XNI) treatment on chronic rhinosinusitis (CRS) and to investigate the effect of XNI on nasal nitric oxide (NO) and inducible nitric oxide synthase (iNOS) mRNA in maxillary sinus. MATERIALS AND METHODS: Patients with CRS were enrolled and symptoms were assessed by Visual Analog Scale (VAS) and Sino-Nasal Outcome Test 22 (SNOT-22). Nasal NO and iNOS mRNA in the right maxillary sinus were also examined. Then, they were treated with XNI (XNI group) or saline nasal irrigation (SNI, SNI group) for 30days, after which their symptoms were reassessed using VAS and SNOT-22, and nasal NO and iNOS mRNA in the right maxillary sinus were also reexamined. RESULTS: Twenty-five out of 30 patients completed this study. The scores of VAS and SNOT-22 were all reduced significantly after XNI treatment, but not after SNI. The concentrations of nasal NO and iNOS mRNA in the right maxillary sinus were increased significantly in XNI group. However, significant changes were not found after SNI treatment. Furthermore, there were statistical differences in the assessments of VAS and SNOT-22 and the contents of nasal NO and iNOS mRNA in the right maxillary sinus between two groups. CONCLUSIONS: XNI results in greater improvement of symptoms of CRS and greater enhancement of nasal NO and iNOS mRNA in maxillary sinus as compared to SNI.

Differential protein expression in the secretory fluids of maxillary sinusitis and maxillary retention cyst.

Both maxillary sinusitis (MS) and maxillary retention cyst (MRC) involve the maxillary sinus and show similar clinical features. Clinically, differentiating between MS and MRC is sometimes difficult in asymptomatic patients, despite their quite different pathogenic behaviors. To identify differential protein expressions in the secretory fluids of MS and MRC, 25 cases of asymptomatic MS and 15 cases of asymptomatic MRC were examined pathologically in this study. All patients underwent routine endoscopic sinus surgery or modified Caldwell-Luc procedure and the sinus mucosal specimens obtained during these procedures with the approval of the Institutional Review Board. Their secretory fluids were analyzed via immunoprecipitation-based high-performance liquid chromatography (IP-HPLC) using 25 types of antiserum, including inflammatory cytokines, antimicrobial proteins, and mucosal protective proteins. In the histological examinations, MS and MRC showed similar features in the secretory columnar epithelial lining and thick submucosal connective tissue, both of which contained few inflammatory cells infiltrates. The IP-HPLC analysis revealed that TNFα, IL-1, -8, MMP-3, -10, α1-antitrypsin, cathepsin C, lysozyme, lactoferrin, ß-defensin-1, -3, LL-37, mucocidin, and mucin-1 were more intensely expressed in MS than in MRC; whereas IgA, cystatin A, and proline-rich proteins were more strongly expressed in MRC than in MS. These data indicate that the secretory fluid of MS is indicative of a more robust inflammatory reaction to certain bacteria compared to that of MRC, while the secretory fluid of MRC contains more abundant mucosal protective proteins compared to that of MS. Taken together, the IP-HPLC analysis of MS and MRC secretory fluid revealed that MRC showed a weaker inflammatory reaction but a stronger mucosal protective function than MS.

A new Strategy to Improve Drug Delivery to the Maxillary Sinuses: The Frequency Sweep Acoustic Airflow.

PURPOSE: Enhancement of intranasal sinus deposition involves nebulization of a drug superimposed by an acoustic airflow. We investigated the impact of fixed frequency versus frequency sweep acoustic airflow on the improvement of aerosolized drug penetration into maxillary sinuses. METHODS: Fixed frequency and frequency sweep acoustic airflow were generated using a nebulizing system of variable frequency. The effect of sweep cycle and intensity variation was studied on the intranasal sinus deposition. We used a nasal replica created from CT scans using 3D printing. Sodium fluoride and gentamicin were chosen as markers. RESULTS: Studies performed using fixed frequency acoustic airflow showed that each of maxillary sinuses of the nasal replica required specific frequency for the optimal aerosol deposition. Intranasal sinus drug deposition experiments under the effect of the frequency sweep acoustic airflow showed an optimal aerosol deposition into both maxillary sinus of the nasal replica. Studies on the effect of the duration of the sweep cycle showed that the shorter the cycle the better the deposition. CONCLUSIONS: We demonstrate the benefit of frequency sweep acoustic airflow on drug deposition into maxillary sinuses. However further in vivo studies have to be conducted since delivery rates cannot be obviously determined from a nasal replica.

Inflammation and remodelling patterns in early stage chronic rhinosinusitis.

BACKGROUND: A distinct set of inflammatory and remodelling factors have been found elevated in chronic rhinosinusitis. OBJECTIVE: The investigation of their expression in early stage disease may reveal early events in this common disease. METHODS: Sinonasal mucosal samples from nine patients with early stage CRSsNP were taken from the inferior and middle turbinates, the uncinate process, maxillary sinus, anterior ethmoid, bulla ethmoidalis and the posterior ethmoid and measured for TGF-beta 1 and it's receptors, MPO protein as well as pro-inflammatory cytokines (TNF-alpha and IL-1beta) and the Th1 cell signature (IFN-gamma and T-bet). As outcome parameter for TGF-beta signalling collagen deposition was analysed. Inferior turbinates from patients undergoing (rhino-) septoplasty were collected as controls. RESULTS: TGF-beta 1 protein concentrations were significantly increased in the maxillary sinuses (P = 0.006), the uncinate process (P = 0.01), the anterior ethmoid including the bulla ethmoidalis (P = 0.005) and the posterior ethmoid (P = 0.037) when compared to the inferior and middle turbinates. Collagen deposition was significantly increased in the maxillary sinus when compared to the inferior turbinates (P = 0.008). In contrast, mRNA for TGF-beta receptors, Th1 related markers (IFN-gamma and T-bet), pro-inflammatory cytokines (IL-1 beta and TNF-alpha), and MPO protein as neutrophil marker were expressed at all locations but showed no significant differences between the various locations. TGF-beta 1 mRNA expression in inferior turbinates of CRSsNP was significantly higher when compared to inferior turbinates of controls (P = 0.017). The pro-inflammatory cytokines and Th1-related cytokines did not show an upregulation in inferior turbinates of CRSsNP when compared to controls. CONCLUSIONS: In early stage chronic sinus disease, TGF-beta protein is expressed in significantly higher concentrations within the paranasal sinuses when compared to turbinates, whereas pro-inflammatory, neutrophilic and Th1 markers did not show any difference. These findings suggest that TGF-beta plays a central role in the initiation of CRSsNP, and represents a major target for further research and future intervention.

Maxillary sinus floor elevation using a tissue-engineered bone with rhBMP-2-loaded porous calcium phosphate cement scaffold and bone marrow stromal cells in rabbits.

The aim of this study was to evaluate the effects of maxillary sinus floor elevation by a tissue-engineered bone complex with recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded porous calcium phosphate cement (CPC) scaffold and bone marrow stromal cells (bMSCs) in rabbits. bMSCs were cultured and osteogenically induced. The osteoblastic differentiation of expanded bMSCs was detected by alkaline phosphatase activity, and calcium deposits in vitro. Thirty-six rabbits were randomly allocated into week 2, 4 and 8 observation groups. At each time point, 24 maxillary sinus floor elevation surgeries in 12 rabbits were performed bilaterally and randomly implanted by (1) CPC materials alone (group A, n = 6), (2) rhBMP-2/CPC composite materials alone (group B, n = 6), (3) CPC/bMSCs complex (group C, n = 6) and (4) rhBMP-2/CPC/bMSCs complex (group D, n = 6). As for maxillary sinus floor elevation, rhBMP-2-loaded CPC could promote new bone formation as compared to CPC, while addition of bMSCs could further enhance its new bone formation and maturity significantly, as detected by histological findings, and fluorochrome labeling. Our data suggested that rhBMP-2/CPC possessed excellent osteoinductive ability, while combining with bMSCs could further promote new bone formation and maturation in maxillary sinus elevation.

Comparison of CGRP distributions in the maxillary sinus and trigeminal ganglion between elderly dentulous and edentulous humans.

Thickening of the Schneiderian membrane (SM, mucosa of the maxillary sinus) appears in the paranasal sinus. Information on SM thickening is available for patients receiving sinus lift treatments, which is a risk factor for SM excretory dysfunction. However, more information is needed on the structure of the SM and the relationship between the maxilla sinus and palatine with the alveolar bone and the SM for dental implant treatment in the human maxilla. One hundred twenty-six sides of the maxilla from 71 cadavers were subjected to cone-beam CT (CBCT) analysis and macroscopic and immunohistochemical observations in this study. A thickened SM was mainly observed in the middle region of the basal layer of the maxillary sinus (MS). Strong calcitonin gene-related peptide (CGRP)-positive reactions were observed in the alveolar bone, oral mucosa, mucosa of the maxillary sinus, and trigeminal ganglion (TG) cells in dentulous samples compared with edentulous samples. TG cells play important roles in delivering CGRP through axons to the mucosal gland and in regulating the maxilla-related thickening of the SM. These data could help determine CGRP functions in the mucosal gland and bone formation between dentulous and edentulous samples and indicate that CGRP may pass from the TG to the maxillary sinus glands.

A biodegradable gelatin-based nanostructured sponge with space maintenance to enhance long-term osteogenesis in maxillary sinus augmentation.

The search for bone substitutes that are biodegradable, ensure space maintenance, and have osteogenic predictability, is ongoing in the field of sinus augmentation. We thus compared the bone regeneration potential of nanostructured sponges (NS-Sponge) with that of collagen-stabilized inorganic bovine bones (BO-Collagen), gelatin sponges (Gelatin), and blood clots (Cont) in sinus augmentation of rabbits. NS-Sponge was prepared by thermally induced phase separation with porogen leaching techniques. All the materials were non-hemolytic and cytocompatible. The porous and nanofibrous NS-Sponge showed better dimensional stability to support cell growth and osteogenic differentiation. In vivo, the sinus membrane collapsed in Cont and Gelatin, while BO-Collagen and NS-Sponge maintained the elevated height as assessed by come-beam computed tomography. Limited bone regeneration was observed in Cont and Gelatin. In the entire implanted area, histological analysis revealed a higher percentage of new bone area at 4 weeks of BO-Collagen treatment; however, a significantly greater increase in new bone area was observed after 12 weeks of NS-Sponge treatment. The 12-week remnant NS-Sponge material was significantly lower than the 4-week remnant material. Overall, NS-Sponge may be highly recommended for sinus augmentation, as it exhibits numerous advantages, including excellent operability, clear imaging characteristics, space maintenance, biodegradability, and superior osteogenic potential.

Photosensitizer With Illumination Enhances In Vivo Antitumor Effect of Anti-ROBO1 Immunotoxin on Maxillary Sinus Squamous Cell Carcinoma.

BACKGROUND/AIM: Head and neck squamous cell carcinoma (HNSCC) is one of the most common types of cancer worldwide. Our study focused on the axon guidance receptor roundabout guidance receptor 1 (ROBO1) as a target for monoclonal antibody therapy of HNSCC. We previously showed that saporin-conjugated anti-ROBO1 (B5209B) immunotoxin (IT-ROBO1) enhanced cytotoxic effects on HNSCC cells in combination with the photosensitizer aluminum phthalocyanine disulphonate (AlPcS2a) and illumination. We examined the effects of this combination therapy in a mouse xenograft model. MATERIALS AND METHODS: IT-ROBO1 was intraperitoneally administered to HSQ-89 (derived from Japanese maxillary sinus squamous carcinoma, RCB0789; RIKEN, Tsukuba, Japan) xenografted mice. After 3 days, AlPcS2a was injected subcutaneously around the tumor and the area was illuminated at 650 nm for 30 min. The growth of the tumor was evaluated and the effects on the tumor were examined. RESULTS: Pronounced anti-tumor effects were elicited by the administration of IT-ROBO1 and AlPcS2a with light illumination on tumor size and pathological characteristics. CONCLUSION: The results showed that photosensitizer treatment with illumination robustly enhanced the antitumor effect of the IT-ROBO1 immunotoxin.

Immunopathology of chronic rhinosinusitis in young children.

OBJECTIVE: Previous investigation demonstrated predominantly lymphocytic inflammation in sinus mucosa of young children with chronic rhinosinusitis (CRS) rather than eosinophilic inflammation typical of adult CRS. Immunohistopathological study was undertaken to define further the cellular response in pediatric CRS. STUDY DESIGN: Maxillary mucosal biopsies from children and adults with CRS were stained for CD3 (T lymphocytes), CD4 (helper T lymphocytes), CD8 (cytotoxic T lymphocytes), CD20 (B lymphocytes), CD68 (monocytes/macrophages), CD56 (natural killer cells), kappa and lambda (plasma cells), and myeloperoxidase (MPO; neutrophils). RESULTS: Nineteen children with CRS (median age, 3.0 years; range, 1.4-8.2 years) had more CD8+, MPO+, and CD68+ cells (P < or = .03) and a trend toward more CD3+ and CD4+ cells (P = .06) in their epithelium and more CD20+, kappa+ and lambda+, MPO+, and CD68+ cells (P < or = .05) and a trend toward more CD4+ cells (P = .06) in their submucosa compared with adult control subjects. Immunostains from children with positive sinus cultures were similar to those with negative cultures except for more MPO+ cells in the submucosa (P = .04). CONCLUSION: The inflammatory response of young children with CRS is characterized by a mixed lymphocyte population, macrophages, and neutrophils. Differences between pediatric and adult CRS suggest differing pathogenic mechanisms or progression in the inflammatory response with protracted disease.

Hsa_circRNA_33287 promotes the osteogenic differentiation of maxillary sinus membrane stem cells via miR-214-3p/Runx3.

BACKGROUND: Circular RNAs (circRNAs) comprise a novel class of noncoding RNAs that play important roles in a variety of diseases. However, the mechanism by which circRNAs regulate the osteogenic differentiation of maxillary sinus membrane stem cells (MSMSCs) remains largely unclear. METHODS: Microarray analysis was used to explore the expression profiles of circRNAs during the osteogenic differentiation of normal and BMP2 induced-MSMSCs. CircRNA_33287 was identified by agarose electrophoresis, quantitative real-time PCR (qRT-PCR), and western blotting. The function of circRNA_33287 was assessed by loss- and gain-of-function techniques and Alizarin red staining. Potential miRNA binding sites for circRNA_33287, and the target genes of miR-214-3p, were predicted by using online bioinformatics analysis tools. The relationships among the regulatory roles played by circRNA_33287, miR-214-3p, and Runt-related transcription factor 3 (Runx3), during the osteogenic differentiation of MSMSCs were verified by use of the dual luciferase reporter assay, qRT-PCR, and western blotting techniques, respectively. In addition, the molecular sponge potential of circRNA_33287 for miRNA was assessed via in vivo ectopic bone formation and a histological analysis performed after hematoxylin and eosin staining. RESULTS: Expression of circRNA_33287 was confirmed to be up-regulated during the osteogenic differentiation of MSMSCS. Overexpression and silencing of circRNA_33287 increased and decreased the expression levels of key markers of osteogenesis, respectively, including Runx2, OSX, and ALP. Furthermore, circRNA_33287 acted as a molecular sponge for miR-214-3p, which regulated Runx3 expression by targeting its 3'UTR. Moreover, circRNA_33287 protected Runx3 from miR-214-3p-mediated suppression. In addition, circRNA_33287 was shown to increase ectopic bone formation in vivo and displayed the strongest ability to stimulate bone formation when co-transfected with a miR-214-3p inhibitor. CONCLUSION: The novel pathway circRNA_33287/miR-214-3p/Runx3 was found to play a role in regulating the osteoblastic differentiation of MSMSCs in the posterior maxilla.

Toward smart Nebulization: Engineering acoustic airflow to penetrate maxillary sinuses in chronic rhinosinusitis.

Treating chronic rhinosinusitis (CRS) by nebulization requires an airflow capable to deliver medication to deep target sites beyond the nasal valve. Fixed frequency acoustic airflow technology is currently available, mainly as post-surgical therapy, but still have not been able to realize the full potential of direct nose to paranasal sinuses delivery. Reported herein are the application of frequency sweep acoustic airflow and the optimization of its frequency range, sweep cycle duration and intensity. The resonant frequencies of the model's maxillary sinuses can be estimated using the Helmholtz resonator theory. Results indicated a resonant frequency of 479 Hz for the right maxillary sinus and one of 849 Hz for the left maxillary sinus. The highest intrasinus deposition within the experiments are from sweep cycle duration of 1 s, intensity of 80 dB, and frequency range of 100-850 Hz. The optimal range of frequency determined from experiments is in good agreement with the corresponding frequency range obtained from the Helmholtz resonator theory. Results reveal a significantly enhanced maxillary sinus drug deposition. This technique affords the potential of treating CRS.

[Diffusion of methylene blue in the human maxillary sinus mucosa].

The coefficient of diffusion of methylene blue in pathologically changed human maxillary sinus mucosa in vitro has been estimated for the first time. The mean value of the diffusion coefficient is (4.8 +/- 2.9) x 10(-7) cm2/s. The method is based on the registration of the dynamics of reflectance of tissue samples under the action of the dye. The diffusion coefficient has been estimated by approximation of experimental data in the framework of the model presented.

[Unusual nasal clinical entities]. / Entidades clínicas nasales inusuales.

Three cases of rare entities in nasal pathology are reported. Two of them are high-grade lymphomas (T/NK type), with nasal blockage as the first symptom. Clinical course and treatment response are described. The third case refers to an infrequent benign nasal entity called angiocentric eosinophilic fibrosis. Its aetiology and management remains rather uncertain nowadays.

Understanding the mechanisms underlying pulsating aerosol delivery to the maxillary sinus: In vitro tests and computational simulations.

BACKGROUND: Pulsating aerosol delivery has been demonstrated in depositing medications into paranasal sinuses. However, its mechanisms are not fully understood. Influences of the nasal anatomy and sound frequency on intrasinus delivery are not yet clear. OBJECTIVES: This study aimed to gain a better understanding of the mechanisms for enhanced intrasinus delivery with pulsating sound. Specifically, effects of the pulsation frequency, ostium size, and sinus shape on the intrasinus dosage and resonance frequency would be examined. METHODS AND MATERIALS: Both experiments and computational modeling were conducted to understand the pulsating aerosol delivery in both idealized (two-bottle) and realistic nose-sinus models. A computational model of intrasinus pulsation delivery was developed using COMSOL and was cross-validated with both experimental and theoretical results. RESULTS: In contrast to previous studies, seemingly erratic relations between the intrasinus dosage and ostium diameter were observed in experiments, which suggested a more complicated particle transport mechanism. Improved agreement was achieved when grouping the ostium size and sinus volume into the resonance frequency, and therefore, validated the hypothesis that intrasinus deposition strongly depends on the resonance frequency. Extensive computational simulations revealed that the deposition was highest at the resonance frequency and decreased gradually at off-resonance frequencies. The resonance frequency depended on the ostium and sinus morphology, but was independent of the nasal cavity. CONCLUSION: Results of this study verified the hypothesis of resonance being the mechanism for enhanced particle deposition in the maxillary sinus. A better knowledge of the relationship between sinus dosages, pulsating frequency, and nasal morphometry is essential for improving the design of intrasinus delivery devices.

Tolerance and pharmacokinetics of a ciprofloxacin-coated sinus stent in a preclinical model.

BACKGROUND: Chronic rhinosinusitis (CRS) is often associated with persistent bacterial infection despite the use of systemic antibiotics. Topically administered antibiotics are an alternative strategy, but require effective local concentrations, prolonged mucosal contact time, minor systemic absorption, and minimal depletion. The objectives of the current study were to analyze the in vitro release rate and in vivo drug delivery tolerance and pharmacokinetics of a ciprofloxacin-coated sinus stent (CSS). METHODS: The CSS (2 mg) was created from biodegradable poly-D/L-lactic acid. After analyzing in vitro release profile, CSSs were placed unilaterally in maxillary sinuses of 16 rabbits via dorsal sinusotomy. Animals were euthanized between 1 and 3 weeks postoperatively. Ciprofloxacin concentrations in the sinus tissue and plasmas were assessed using high-performance liquid chromatography. Radiological and histological evaluations were performed. RESULTS: In the in vitro release profile, an initial burst release was observed over the first 24 hours, followed by sustained release through the 14-day time point. In the rabbit model, ciprofloxacin was continuously released from the stent up to 3 weeks at doses >50 ng/mL. Histologic examination found no evidence of inflammation, epithelial ulceration, or bony reaction upon euthanization of the animals at 21 days. Computed tomography also demonstrated no signs of mucosal edema or opacification in the sinus. CONCLUSION: The CSS was safe in this preclinical model and sustained release was observed in both the in vitro and in vivo analyses. The innovative stent design coated with ciprofloxacin may provide a unique therapeutic strategy for chronic rhinosinusitis (CRS).

Maxillary Sinus Floor Augmentation Using Xenograft: Gene Expression and Histologic Analysis.

PURPOSE: Many histologic and histomorphometric studies as well as systematic reviews have shown the clinical success of the use of anorganic bovine bone (ABB, Bio-Oss) in maxillary sinus floor augmentation (MSFA). The molecular processes involved in bone healing are, however, still unknown. The aims of this study were to explore gene expression associated with bone remodeling and inflammation in MSFA sites. MATERIALS AND METHODS: The mRNA expression levels of runt related transcription factor 2 (RUNX2), receptor activator of NF-kB ligand (RANKL), osteoprotegerin (OPG), matrix metallopeptidase 9 (MMP-9), tartrate-resistance acid phosphatase (TRAP), and interleukin-1beta (IL-1ß), as well as the ratio of RANKL/OPG were compared between alveolar bone of a group after MSFA with ABB and a maxillary posterior edentulous bone group. Twenty-one bone samples were collected at the time of implant placement after 6 months of MSFA or tooth extraction. Fourteen bone samples from the MSFA group and from the maxillary posterior edentulous bone without MSFA group were taken to analyze gene expression by real-time reverse transcription polymerase chain reaction (RT-PCR). Seven bone samples from the MSFA group were used for histologic analysis. RESULTS: Real time RT-PCR revealed no statistically significant difference in gene expression level of RUNX2, RANKL, OPG, MMP-9, TRAP, and IL-1ß, or in the ratio of RANKL/OPG. Histology showed bone-lining cells at the edge and osteocyte inside newly formed bone. Residual grafted particles were in close contact with new bone. CONCLUSION: After a healing period of 6 months, ABB particles did not have an effect on the expression of genes associated with bone remodeling and inflammation. In addition, histologic evidence supports that ABB particles are replaced by new bone formation and do not affect bone healing.

Significance of the Immunohistochemical Expression of Bone Morphogenetic Protein-4 in Bone Maturation after Maxillary Sinus Grafting in Humans.

BACKGROUND: Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-ß (TGFß) protein superfamily and are known to be involved in bone and cartilage formation. Within this family, BMP-4 is one of the most studied members. It has been shown to induce osteogenic differentiation of osteoblasts and osteoprogenitor cells in vitro, but the intimate processes in which this protein promotes and regulates osseous repair still remains unclear. PURPOSE: To assess whether the native cellular immunohistochemical expression of BMP-4 correlates with the maturation of bone samples obtained at 6 months after maxillary sinus augmentation. MATERIALS AND METHODS: Histopathological and histomorphometrical analyses were performed in all the samples, which were obtained from a total of 58 patients. Immunohistochemical expression of BMP-4 was analyzed in 30 core biopsies obtained from maxillary sinuses grafted with a combination of anorganic bovine bone and autogenous cortical bone [1:1] (AB-group), and 18 biopsies from maxillary sinuses grafted solely with a cortico-cancellous particulate allograft (M-group), all of them after a 6-month healing period. Also, 10 biopsies of native pristine bone were obtained and used as control group (C-group). RESULTS: Mild to moderate immunohistochemical expression of native granular BMP-4 was present in 56.8% (31.0% AB-group, 22.4% M-group, and 3.4% C-group) (p = 0.000, chi-square) of the specimens analyzed. BMP-4 expression was primarily located in the cytoplasm of osteoblasts, osteoclasts, and epithelial cells of the schneiderian membrane. Whereas significant differences were observed in the proportion of mineralized tissue and cellularity between sinuses grafted with anorganic bovine bone, allograft, or nongrafted sinuses, there were no statistically significant differences in the cellular expression of BMP-4 among groups. CONCLUSION: Our findings suggest that the native expression of BMP-4 appears to be associated with normal bone homeostasis and reparation in grafted and nongrafted maxillary sites.

Recent Advances on Nitric Oxide in the Upper Airways.

Exhaled nitric oxide (NO) originates from the upper airways, and takes action, to varying extents, in regulation, protection and defense, as well as in noxious processes. Nitric oxide retains important functions in a wide range of physiological and pathophysiological processes of the human body, including vaso-regulation, antimicrobial activity, neurotransmission and respiration. This review article reports the ongoing investigations regarding the source, biology and relevance of NO within upper respiratory tract. In addition, we discuss the role of NO, originating from nasal and paranasal sinuses, in inflammatory disorders such as allergic rhinitis, sinusitis, primary ciliary dyskinesia, and cystic fibrosis.