Pilot study of dogs with suppurative and non-suppurative Malassezia otitis: A case series.

BACKGROUND: Rarely, Malassezia otitis presents as a painful, erosive otitis with an otic discharge containing Malassezia and neutrophils on cytology. There are no published reports of this type of suppurative Malassezia otitis (SMO). The role of Malassezia hypersensitivity in otitis is still unknown, and no association has been demonstrated with SMO. We compared Malassezia IgE levels, intradermal test and histology changes in SMO dogs with the more conventional Malassezia otitis (MO) presentation. RESULTS: Three dogs (case 1, case 2 and case 3) were diagnosed with SMO, one dog (case 4) was diagnosed with unilateral MO and unilateral SMO, and one dog (case 5) was diagnosed with MO. Only one case (case 4) with SMO/MO had a positive Intradermal Allergy Test (IDAT) and elevated IgE levels for Malassezia. Histopathology findings from SMO revealed: interface dermatitis (case 1 and 3), lymphocytic dermatitis (case 2) and chronic hyperplastic eosinophilic and lymphoplasmacytic dermatitis (case 4). Histopathology findings from MO showed perivascular dermatitis (case 4 and 5). All the cases were treated successfully. CONCLUSIONS: SMO presents with a distinct clinical phenotype in comparison with conventional MO. No consistent aetiology could be isolated. In these clinical cases it is possible that previous treatments could have influenced the results. More research is needed to understand the possible aetiologies and the pathogenesis of SMO.

Ethyl acetate fraction from Nymphaea hybrida Peck modulates inflammatory responses in LPS-stimulated RAW 264.7 cells and acute inflammation murine models.

ETHNOPHARMACOLOGICAL RELEVANCE: Nymphaea hybrida Peck is used as a traditional medicinal herb for treating pain and inflammatory diseases, and known for its ornamental value and as a hot drink. However, the effects of N. hybrida polar fractions on lipopolysaccharide (LPS)-induced in vitro inflammation model and acute inflammation murine models have yet to be evaluated. AIM OF THE STUDY: The aim of this study was to elucidate the anti-inflammatory effects of N. hybrida ethanol extract (NHE) and its polar fractions: petroleum ether (PE), methylene chloride (MC), ethyl acetate (EA), methanol (ME), and water (WA). The underlying molecular mechanisms of active fraction in LPS-stimulated RAW 264.7 murine macrophages were further investigated. MATERIAL AND METHODS: Fractions with potential anti-inflammatory effects were screened using direct nitric oxide (NO) radical scavenging and cyclooxygenase (COX)-2 inhibition assays in vitro. The anti-inflammatory properties of potential fraction were evaluated in LPS-stimulated RAW264.7 cells, xylene-induced ear edema, carrageenan-induced paw edema and xylene-induced Evans blue exudation of acute inflammation murine models. The regulation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways were investigated using western blotting and immunofluorescence. RESULTS: Compared to other polar fractions, NHE-EA displayed higher phenol and flavonoid content, and exerted greater activity in direct NO radical scavenging and COX-2 inhibition assay in vitro. NHE-EA markedly decreased the levels of inflammatory mediators, NO and prostaglandin E2 (PGE2), by suppressing the over-expression of inducible nitric oxide synthase (iNOS) and COX-2 in LPS-stimulated RAW264.7 cells. The NHE-EA fraction dose-dependently alleviated over-elevation of LPS-associated intracellular calcium and decreased the abnormal secretion of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6, and interferon-γ (IFN-γ). The combination with NHE-EA effectively attenuated the activation and nuclear translocation of NF-κB p65, and the phosphorylation of extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK), and p38 kinases of MAPK pathways. NHE-EA could significantly ameliorate the degree of swelling of the mice ear and paw, the skin exudation of Evans blue and the excessive secretion of inflammatory cytokines. CONCLUSION: Our results demonstrated that NHE-EA was the most active polar fraction of N. hybrida extracts. It inhibited the LPS-associated inflammatory response by blocking the activation of NF-κB and MAPKs pathways in RAW264.7 cells. It also effectively alleviated the inflammatory response of acute inflammation. These results indicated the role of NHE-EA as adjuvants and their potential role in alternative strategy for the treatment of inflammatory diseases.

Morphological and Pathological Findings in the Middle and Inner Ears of Harbour Porpoises (Phocoena phocoena).

Hearing represents the major sense in harbour porpoises (Phocoena phocoena) and impairment of hearing has a great impact on the survival of these animals. In this communication, some anatomical and histological aspects of the tympanoperiotic complex of harbour porpoises are presented. In addition, the ears of 21 incidentally bycaught or stranded freshly dead harbour porpoises of different age groups and sex were investigated histologically. At the entrance to the middle ear cavity, mucosa-associated lymphoid tissue was present that was often hyperplastic in juvenile (9/10) and adult individuals (7/8). Solitary lymphoid follicles were additionally found in the corpus cavernosum and adjacent to the stapedius muscle in single porpoises. The nematode Stenurus minor represented the most common pathogen observed in the middle ear cavity of juvenile and adult harbour porpoises and the parasite was associated with chronic inflammation with metaplastic and hyperplastic epithelial changes. An unusual bone formation at the attachment of the corpus cavernosum to the perioticum was a common finding, even in young individuals. Whether this represents a normal structure or a metaplastic change remains undetermined. Acute haemorrhages in the cochlea and/or the tympanic cavity occurred in all animals and were most likely agonal changes. Single porpoises suffered from purulent otitis media, mycotic otitis media with osteolysis or chronically fractured tympanic bones, likely causing impairment of hearing that may have contributed to by-catch. There was no evidence that stranding in five porpoises was associated with the aural changes. Histological examination of the ears in harbour porpoises is a valuable part of the assessment of their health status. Damage to hearing structures may explain starvation due to impaired ability to catch prey or unusual behaviour such as stranding or entanglement in nets.

Muenke syndrome: Medical and surgical comorbidities and long-term management.

Muenke syndrome (MIM #602849), the most common syndromic craniosynostosis, results from the recurrent pathogenic p.P250R variant in FGFR3. Affected patients exhibit wide phenotypic variability. Common features include coronal craniosynostosis, hearing loss, carpal and tarsal anomalies, and developmental/behavioral issues. Our study examined the phenotypic findings, medical management, and surgical outcomes in a cohort of 26 probands with Muenke syndrome identified at the Children's Hospital of Philadelphia. All probands had craniosynostosis; 69.7% had bicoronal synostosis only, or bicoronal and additional suture synostosis. Three male patients had autism spectrum disorder. Recurrent ear infections were the most common comorbidity, and myringotomy tube placement the most common extracranial surgical procedure. Most patients (76%) required only one fronto-orbital advancement. de novo mutations were confirmed in 33% of the families in which proband and both parents were genetically tested, while in the remaining 66% one of the parents was a mutation carrier. In affected parents, 40% had craniosynostosis, including 71% of mothers and 13% of fathers. We additionally analyzed the medical resource utilization of probands with Muenke syndrome. To our knowledge, these data represent the first comprehensive examination of long-term management in a large cohort of patients with Muenke syndrome. Our study adds valuable information regarding neuropsychiatric and medical comorbidities, and highlights findings in affected relatives.

The Protease-Dependent Mesenchymal Migration of Tumor-Associated Macrophages as a Target in Cancer Immunotherapy.

Macrophage recruitment is essential for tissue homeostasis but detrimental in most cancers. Tumor-associated macrophages (TAMs) play a key role in cancer progression. Controlling their migration is, thus, potentially therapeutic. It is assumed that macrophages use amoeboid motility in vivo like other leukocytes. However, it has not yet been explored. We examined TAM migration using intravital microscopy in mouse tumors and by monitoring ex vivo tissue infiltration in human surgical samples. We demonstrated that TAMs perform protease-dependent and ROCK-independent mesenchymal migration inside mouse fibrosarcoma and breast cancer explants using their own matrix metalloproteases (MMP). In contrast, macrophages use ROCK-dependent and protease-independent amoeboid migration inside inflamed ear derma and in connective tissue at the tumor periphery. We also showed that inhibition of mesenchymal migration correlates with decreased TAM recruitment and tumor growth. In conclusion, this study elucidates how macrophages migrate in vivo, and it reveals that the MMP-dependent migration mode of TAMs provides a rationale for a new strategy in cancer immunotherapy: to target TAMs specifically through their motility. Cancer Immunol Res; 6(11); 1337-51. ©2018 AACR.

Idiopathic, Infectious and Reactive Lesions of the Ear and Temporal Bone.

A number of infectious, inflammatory and idiopathic lesions develop within otologic tissues that may share similar clinical and/or microscopic features. This review first provides a working classification for otitis externa, and then otitis media and includes two recently described entities, eosinophilic otitis media and otitis media with ANCA-associated vasculitis. Next, the microscopic findings of a spectrum of otopathologic conditions are described, including post-inflammatory conditions such as tympanosclerosis and aural polyps, an overview of animate aural foreign body as well as iatrogenic aural foreign body reactions. Finally, a review of fungal disease affecting the ear with a brief synopsis of Candida auris, a recently described and virulent organism, is presented.

Mimic Cochlear Implant Surgery-Induced Cochlear Infection Fails to Further Damage Auditory Pathway in Deafened Guinea Pigs.

BACKGROUND Kanamycin and subsequent furosemide administration was applied to the healthy guinea pigs to induce deafness. MATERIAL AND METHODS Of the deafened guinea pigs, 10 were further infused with anti-infection procedures (Group B) and the other 10 animals did not undergo anti-infection procedures (Group C). In Group B, the deafened animals were able to restore cochlear and middle ear functions following the anti-infection procedure. In Group C, all animals developed cochlear and middle ear infections. RESULTS Compared to the healthy guinea pigs, hair cells and spiral ganglion neurons (SGN) of deafened animals (in Group B and Group C) were severely damaged. SGN density of deafened animals was significantly lower than that of healthy control animals in all ear turns except the basal turn. There was no significant difference between Group B and Group C in SGN density. The average optical density value of neurofilaments of deafened animals was also significantly decreased after the ototoxic drug administration. Notably, the density of the neurons in the cochlear nucleus region (CNR) of the brainstem were not significantly different between the healthy control guinea pigs and deafened animals. CONCLUSIONS Mimic cochlear implant surgery-induced cochlear infection caused no significant damage to the auditory pathway in ototoxic drug-induced deafened guinea pigs.

Rare case of otomastoiditis due to Coxiella burnetii chronic infection.

Q fever is a zoonotic disease caused by Coxiella burnetii that usually presents with non-specific or benign constitutional symptoms. Diagnosis is often challenging and, after acute Q fever, 1%-5% of patients can develop chronic disease. We present an 80-year-old male patient who was admitted due to a 3 months history of fever, productive cough, myalgia, weight loss, headache and hearing loss. Chronic Q fever was confirmed by positive antiphase I immunoglobulin G. Frequent locations of chronic infection was discarded, and ear CT revealed a right mastoid infection. He was treated with doxycycline and hydroxychloroquine for 18 months with significant improvement. This is a rare case of chronic Q fever presenting with otomastoiditis that has never been described.

Multisystem Langerhans Cell Histiocytosis in Adults Revealed by Skin Lesions.

A 37-year-old woman with no remarkable medical or family history presented with papules and vesicles on an erythematous background involving the neck, sacrum, and folds (postauricular, axillary, inguinal, and under the breasts) (Figure 1). During the previous year, she was treated with local and systemic antifungals without improvement. Her history included a secondary amenorrhea, polydipsia, and polyuria (6 L/d) that started 2 years prior. Physical examination revealed chronic bilateral purulent otorrhea with thick eardrums. Histologic examination of skin biopsy revealed a highly suggestive appearance of multisystem Langerhans cell histiocytosis (LCH) with immunohistochemistry (anti-PS100 and anti-CD1a), which were positive (Figure 2A and 2B). Pituitary magnetic resonance imaging showed a thickening of the pituitary stalk in relation to a location histiocytic (Figure 3). Bone gaps were objectified on two radiographic tibial diaphyseal. Results from computed tomography (CT) scan showed a magma coelio mesenteric, axillary, and inguinal lymph nodes.

Self-Assembly of Multi-nanozymes to Mimic an Intracellular Antioxidant Defense System.

In this work, for the first time, we constructed a novel multi-nanozymes cooperative platform to mimic intracellular antioxidant enzyme-based defense system. V2 O5 nanowire served as a glutathione peroxidase (GPx) mimic while MnO2 nanoparticle was used to mimic superoxide dismutase (SOD) and catalase (CAT). Dopamine was used as a linker to achieve the assembling of the nanomaterials. The obtained V2 O5 @pDA@MnO2 nanocomposite could serve as one multi-nanozyme model to mimic intracellular antioxidant enzyme-based defense procedure in which, for example SOD, CAT, and GPx co-participate. In addition, through assembling with dopamine, the hybrid nanocomposites provided synergistic antioxidative effect. Importantly, both in vitro and in vivo experiments demonstrated that our biocompatible system exhibited excellent intracellular reactive oxygen species (ROS) removal ability to protect cell components against oxidative stress, showing its potential application in inflammation therapy.

Discharging mastoid cavity caused by necrosis of the modiolus / Supuración de cavidad mastoidea por necrosis del modiolo

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Anti CD163+, Iba1+, and CD68+ Cells in the Adult Human Inner Ear: Normal Distribution of an Unappreciated Class of Macrophages/Microglia and Implications for Inflammatory Otopathology in Humans.

HYPOTHESIS: Identification, characterization, and location of cells involved in the innate immune defense system of the human inner ear may lead to a better understanding of many otologic diseases and new treatments for hearing and balance-related disorders. BACKGROUND: Many otologic disorders are thought to have, as part of their disease process, an immune component. Although resident macrophages are known to exist in the mouse inner ear, the innate immune cells in the human inner ear are, to date, unknown. METHODS: Primary antibodies against CD163, Iba1, and CD68 (markers known to be specific for macrophages/microglia) were used to immunohistochemically stain celloidin embedded archival temporal bone tissue of normal individuals with no known otologic disorders other than changes associated with age. RESULTS: Cells were positively stained throughout the temporal bone within the connective tissue and supporting cells with all three markers. They were often associated with neurons and on occasion entered the sensory cell areas of the auditory and vestibular epithelium. CONCLUSIONS: We have immunohistochemically identified an unappreciated class of cells in the normal adult inner ear consistent in staining characteristics and morphology with macrophages/microglia. As in other organ systems, it is likely these cells play an essential role in organ homeostasis that has not yet been elucidated within the ear.

IMQ Induced K14-VEGF Mouse: A Stable and Long-Term Mouse Model of Psoriasis-Like Inflammation.

An imiquimod (IMQ) induced wild type (WT) mouse can mimic some features of psoriasis, such as thickened skin, abnormal keratinocyte-related proteins, infiltration of inflammatory cells and pro-inflammatory cytokines. This model is a prevalent model that is widely used in the study of psoriasis. However, skin inflammation decreases during the eighth day when IMQ is given to WT mice, which may result in false results when evaluating the pharmacodynamics effects of a drug. To extend the timeliness and inherit the advantages of this model, we applied IMQ to the skin of 8-week-old homozygous K14-VEGF mice to investigate whether IMQ can prolong mice ear inflammation. In our experiments, we found that, compared to the IMQ induced WT mice model, the IMQ induced K14-VEGF mice have serious skin inflammation, even on the fourteenth day. We also evaluated the stability of skin inflammation at days 8, 10, and 13, and the inflammatory situation remained stable in the skin. This research intends to improve the existing model, and we hypothesize that the IMQ induced K14-VEGF mouse will become a practical mouse model in psoriasis research.

Microanatomy of the tympanic membrane in chronic myringitis obtained with optical coherence tomography.

A microscope-based optical coherence tomography (OCT) device was used to assess the microanatomy of the tympanic membrane in patients with chronic myringitis. A prospective study was designed for this purpose. OCT measurements of the tympanic membrane were done on 11 patients with myringitis with a microscope-based spectral domain OCT system. The in vivo findings were compared with those findings of a control group consisting of 36 patients with retraction pockets or atrophic tympanic membranes (n = 13), myringosclerosis (n = 12) and perforations (n = 11). In active chronic myringitis, the thickness of the tympanic membrane is increased compared to healthy membranes and to other pathological conditions of the tympanic membrane. Consistent changes of the microanatomy of the tympanic membrane were found in chronic myringitis with OCT. Serial OCT measurements revealed no biofilm suspicious findings in all patients with active chronic myringitis. Intraoperative and in vivo OCT measurements may help to detect microanatomical changes of the tympanic membrane in chronic myringitis and in other conditions of the tympanic membrane.

Suppurative otitis and ascending meningoencephalitis associated with Bacteroides tectus and Porphyromonas gulae in a captive Parma wallaby (Macropus parma) with toxoplasmosis.

A 6-year-old female Parma wallaby (Macropus parma) at a zoo in California developed acute ataxia and left-sided circling. Despite intensive care, clinical signs progressed to incoordination and prostration, and the animal was euthanized. At necropsy, the left tympanic cavity was filled with homogeneous suppurative exudate that extended into the cranium expanding the meninges and neuroparenchyma in the lateral and ventral aspect of the caudal ipsilateral brainstem and medulla oblongata. Microscopically, the brainstem showed regional severe suppurative meningoencephalitis with large numbers of neutrophils, fewer macrophages, and lymphocytes admixed with fibrin, necrotic cellular debris, hemorrhage, and mineralization, with numerous intralesional Gram-negative bacilli. Bacteroides spp. and Porphyromonas spp. were isolated on anaerobic culture from the meninges, and the bacteria were further characterized by partial 16S ribosomal RNA gene sequencing as Bacteroides tectus and Porphyromonas gulae. Bacterial aerobic culture from the meninges yielded very low numbers of mixed flora and Proteus spp., which were considered contaminants. Culture of Mycoplasma spp. from middle ear and meninges was negative. Additionally, Toxoplasma gondii cysts were detected by immunohistochemistry in the heart and brain, and anti-Toxoplasma antibodies were detected in serum. The genera Bacteroides and Porphyromonas have been associated with oral disease in marsupials; but not with otitis and meningoencephalitis. The results of the present work highlight the importance of performing anaerobic cultures in the diagnostic investigation of cases of suppurative otitis and meningoencephalitis in macropods.