Neutrophil Extracellular Traps and Fibrin in Otitis Media: Analysis of Human and Chinchilla Temporal Bones.

Background: Bacterial resistance in acute otitis can result in bacterial persistence and biofilm formation, triggering chronic and recurrent infections.

Objective: To investigate the middle ear inflammatory response to bacterial infection in human and chinchilla temporal bones.

Design, Setting, And Participants: Six chinchillas underwent intrabullar inoculations with 0.

Pneumococcal PspA and PspC proteins: potential vaccine candidates for experimental otitis media.

Objective: Otitis media is the most commonly diagnosed disease in ambulatory care and Streptococcuspneumoniae continues to be the most common bacterial agent. Bacterial resistance to antibiotics underscores the need for better vaccines. Current pneumococcal conjugate vaccines are modestly protective against otitis media; however, limited serotype coverage and serotype replacement have led to the investigation of pneumococcal proteins as potential vaccine candidates.

Viability and virulence of pneumolysin, pneumococcal surface protein A, and pneumolysin/pneumococcal surface protein A mutants in the ear.

Importance: Understanding how pneumococcal proteins affect the pathology of the middle ear and inner ear is important for the development of new approaches to prevent otitis media and its complications.

Objectives: To determine the viability and virulence of Streptococcus pneumoniae mutants deficient in pneumolysin (Ply-) and pneumococcal surface protein A (PspA-) in the chinchilla middle ear.

Design: Bullae of chinchillas were inoculated bilaterally with wild-type (Wt), Ply-, PspA-, and Ply-/PspA- strains.

Invasive and noninvasive Streptococcus pneumoniae capsule and surface protein diversity following the use of a conjugate vaccine.

The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the United States in 2010 for the prevention of invasive pneumococcal disease (IPD) and otitis media. While many studies have reported its potential efficacy for IPD, not much is known about the epidemiology of noninvasive disease following its introduction. We characterized the capsular types and surface protein genes of noninvasive pediatric pneumococcal isolates collected between 2002 and 2010 (n = 1,058) at Children's of Alabama following the introduction of PCV7 and tested a subset of noninvasive and previously characterized IPD isolates for the presence of the pspA, pspC, and rrgC genes, which encode protection-eliciting proteins.

Panel 4: Recent advances in otitis media in molecular biology, biochemistry, genetics, and animal models.

Background: Otitis media (OM) is the most common childhood bacterial infection and also the leading cause of conductive hearing loss in children. Currently, there is an urgent need for developing novel therapeutic agents for treating OM based on full understanding of molecular pathogenesis in the areas of molecular biology, biochemistry, genetics, and animal model studies in OM.

Objective: To provide a state-of-the-art review concerning recent advances in OM in the areas of molecular biology, biochemistry, genetics, and animal model studies and to discuss the future directions of OM studies in these areas.

Activation of the transforming growth factor beta pathway in bacterial otitis media.

Objectives: Granulation tissue is common in otitis media (OM), yet little is known about the signaling pathways in the formation of granulation tissue in response to infections. In this study, we sought to investigate the activation of the transforming growth factor beta (TGF-beta) signaling pathway in the formation of granulation tissue in response to middle ear pathogens.

Methods: Rat OM models were made by inoculating pneumococcus type 6A or nontypeable Haemophilus influenzae into the middle ear cavity or by obstructing the eustachian tube.

Effect of apolactoferrin on experimental pneumococcal otitis media.

Objective: To find the effect of apolactoferrin administration on the middle and inner ears after experimentally induced pneumococcal otitis media.

Design: Histopathologic and morphometric analysis of the middle and inner ears.

Setting: University of Minnesota, Minneapolis.

A combination antioxidant therapy prevents age-related hearing loss in C57BL/6 mice.

Objective: Age-related hearing loss (ARHL) is characterized by gradual, progressive sensorineural hearing loss, which impairs communication, lending to clinical depression and social withdrawal. There are currently no effective treatments for ARHL. The purpose of this study is to evaluate the potential of a combination antioxidant therapy in preventing ARHL.

Cochlear pathology in human temporal bones with otitis media.

Conclusion: Middle and inner ear interactions in otitis media can lead to cochlear pathology. More severe pathological changes observed in the basal turn of the cochlea are consistent with prevalence of sensorineural hearing loss at higher frequencies in patients with otitis media.

Methods: Of 614 temporal bones with otitis media, 47 with chronic and 35 with purulent otitis media were selected following strict exclusion of subjects with a history of acoustic trauma, head trauma, ototoxic drugs, and other diseases affecting the cochlear labyrinth.

Effect of lipooligosaccharide mutations of Haemophilus influenzae on the middle and inner ears.

Objective: The purpose of this study was to determine the virulence of nontypeable Haemophilus influenzae 2019 (NTHi 2019) and its two lipooligosaccharide (LOS) mutant strains, B29 (gene htrB) and DK1 (gene rfaD), and compare their effect on the middle ear, round window membrane, and inner ear.

Results: Fifteen chinchillas were divided into three equal groups and their bullas inoculated bilaterally with 0.5 ml of 10(2)CFU/ml of parent NTHi 2019, B29 or DK1 mutant strains.

Expression of fibroblast growth factor binding protein in head and neck cancer.

Objectives: To characterize the expression of fibroblast growth factor binding protein (FGF-BP) messenger RNA (mRNA) in head and neck squamous cell carcinoma (HNSCC) and to study the association of FGF-BP with vascularity.

Design: The expression of FGF-BP mRNA in HNSCC was studied in 35 primary and 8 metastatic HNSCC specimens and 7 control tissues using in situ hybridization and reverse transcriptase-polymerase chain reaction (RT-PCR). Microvessels in tumor specimens were identified with endothelial cell markers (von Willebrand factor [vWF] and CD34-specific antibodies).

Virulence of pneumococcal proteins on the inner ear.

Objective: To investigate the effects of the virulence characteristics of specific pneumococcal proteins on the inner ear.

Main Outcome Measures: A histologic comparison of inflammatory cell infiltration and pathologic changes in the round window membrane and inner ear.

Results: Most of the animals inoculated with high-dose pneumolysin or wild-type bacteria showed severe pathologic changes of the inner ears.

The role of inflammatory mediators in the pathogenesis of otitis media and sequelae.

This review deals with the characteristics of various inflammatory mediators identified in the middle ear during otitis media and in cholesteatoma. The role of each inflammatory mediator in the pathogenesis of otitis media and cholesteatoma has been discussed. Further, the relation of each inflammatory mediator to the pathophysiology of the middle and inner ear along with its mechanisms of pathological change has been described.

Ototoxicity after combined platinum and fractionated radiation in a novel guinea pig model.

Purpose: Cis-platinum and radiation in combination are current organ preservation treatment strategies for head and neck cancer. Their individual ototoxicity has been investigated, with recent demonstration of ototoxicity in clinical studies. Currently, no ototoxicity studies have been performed in animals receiving similar schedules of radiation or cis-platinum to those patients with head and neck cancer.

Role of pneumococcal proteins in sensorineural hearing loss due to otitis media.

Hypothesis: Two Streptococcus pneumoniae proteins, pneumococcal surface protein A (PspA) and pneumolysin (Ply), have functional and histopathologic effects on the inner ear.

Background: Temporary or permanent sensorineural hearing loss is known to be a sequela of pneumococcal otitis media. Several pneumococcal proteins such as PspA and Ply have been shown to contribute to the pathogenesis of the middle ear; however, effects of these proteins on the inner ear and hearing loss are unknown.

Up-regulation of macrophage migration inhibitory factor induced by endotoxin in experimental otitis media with effusion in mice.

Conclusion: Injection of endotoxin into the middle ear causes production of macrophage migration inhibitory factor (MIF) in an experimental mouse model of otitis media with effusion (OME). Down-regulation of MIF may become a new approach for the management of OME.

Objective: To determine the role of MIF in OME.

The round window membrane in otitis media: effect of pneumococcal proteins.

Objective: To determine whether mutants of Streptococcus pneumoniae that are deficient in pneumococcal surface protein A (PspA), pneumococcal surface antigen A (PsaA), or pneumolysin (Ply) are less virulent and less likely to penetrate the round window membrane (RWM).

Design: Histopathologic comparison of wild-type S. pneumoniae and its mutants deficient in PspA, PsaA, and Ply.

Peripheral facial nerve regeneration using collagen conduit entubulation in a cat model.

Objectives: Facial nerve (FN) injuries are functionally, psychologically, and financially debilitating. Facial nerve autograft repairs produce significant donor nerve morbidity and functional results that rarely exceed House-Brackmann (HB) grade III over VI. In this study we sought to enhance FN regeneration via collagen conduit entubulation.

Induction of heat shock protein 70 inhibits NF-kappa-B in squamous cell carcinoma.

Objective: To determine the relationship between heat shock proteins (HSPs) and the proinflammatory, anti-apoptosis mediator NF-kappa-B in squamous cell carcinoma.

Study Design And Setting: CA-9-22 cells were exposed to heat stress to induce the production of HSPs. Immunoblot and reporter gene experiments determined the inducibility of HSP production and the activation of cytokine-induced NF-kappa-B.

Pseudomonas aeruginosa lipopolysaccharide induction of keratinocyte proliferation, NF-kappa B, and cyclin D1 is inhibited by indomethacin.

NF-kappaB is activated during acute inflammatory states as well as in other injury response disease states. Several pathologic states in squamous tissue injury response are characterized by increased squamous proliferation. This study was performed to investigate the hypothesis that Pseudomonas aeruginosa LPS is able to activate a proliferative phenotype in squamous cells via NF-kappaB induction and that this NF-kappaB-mediated response may be abrogated with the classic anti-inflammatory agent indomethacin.

Assessment of gene expression in head and neck carcinoma using laser capture microdissection and real-time reverse transcription polymerase chain reaction.

Objectives: To quantify gene expression in tumor cells from human head and neck squamous cell carcinomas (HNSCC) using laser capture microdissection (LCM).

Study Design: Histopathologically identified HNSCC cells were microdissected from frozen sections, RNA was isolated, and vascular endothelial growth factor (VEGF) gene expression was measured by real-time reverse transcriptase polymerase chain reaction (RT-PCR).

Materials And Methods: Two human HNSCC tumor samples and matched normal mucosal biopsies and five human xenograft tumor specimens were harvested, embedded, and frozen in OCT.

Expression of platelet-derived growth factor in the developing cochlea of rats.

Objective: Platelet-derived growth factor (PDGF) is involved in the control of cell proliferation, differentiation and survival in various tissues of vertebrates. However, little is known about the expression of PDGF in the developing cochlea of rodents.

Material And Methods: We examined the expression of PDGF family genes in the developing cochlear tissue of rats using microarrays and tested their role in the proliferation of progenitor hair cells using cellular and molecular biology techniques.