minocycline and Ear-Diseases

One of the most unfortunate side effects of aminoglycoside (AG) antibiotics such as neomycin is that they target sensory hair cells (HCs) and can cause permanent hearing impairment. We have observed HC loss and microglia-like cell (MLC) activation in the inner ear (cochlea) following neomycin administration. We focused on CX3CL1, a membrane-bound glycoprotein expressed on neurons and endothelial cells, as a way to understand how the MLCs are activated and the role these cells play in HC loss. CX3CL1 is the exclusive ligand for CX3CR1, which is a chemokine receptor expressed on the surface of macrophages and MLCs. In vitro experiments showed that the expression levels of CX3CL1 and CX3CR1 increased in the cochlea upon neomycin treatment, and CX3CL1 was expressed on HCs, while CX3CR1 was expressed on MLCs. When cultured with 1 μg/mL exogenous CX3CL1, MLCs were activated by CX3CL1, and the cytokine level was increased in the cochleae leading to apoptosis in the HCs. In CX3CR1 knockout mice, a significantly greater number of cochlear HCs survived than in wild-type mice when the cochlear explants were cultured with neomycin in vitro. Furthermore, inhibiting the activation of MLCs with minocycline reduced the neomycin-induced HC loss and improved the hearing function in neomycin-treated mice in vivo. Our results demonstrate that CX3CL1-induced MLC activation plays an important role in the induction of HC death and provide evidence for CX3CL1 and CX3CR1 as promising new therapeutic targets for the prevention of hearing loss.

Topics: Animals; Antibodies, Neutralizing; Cells, Cultured; Chemokine CX3CL1; Cochlea; CX3C Chemokine Receptor 1; Ear Diseases; Hair Cells, Auditory; Hearing Loss; Mice, Inbred C57BL; Mice, Knockout; Microglia; Minocycline; Myosin Light Chains; Neomycin; Protein Biosynthesis; Receptors, Chemokine; Up-Regulation

A 40-year-old woman was referred by her primary care physician for evaluation after a routine physical exam revealed bilateral brownish pigmentation of the tympanic membrane. Head and neck examination in the otolaryngology clinic revealed bluish hue of both sclera, teeth, and portions of her pinnae. A hearing test revealed bilateral mild sensorineural hearing loss. The patient had a history of taking minocycline for 14 years, and the hyperpigmentation that she had is known to be a rare complication of prolonged minocycline use. However, to our knowledge, this is the first case showing photographic evidence of minocycline-induced tympanic membrane hyperpigmentation. Minocycline-induced hyperpigmentation should be considered when a patient presents with brown or blue discoloration of the tympanic membrane.

Topics: Acne Vulgaris; Adult; Anti-Bacterial Agents; Ear Auricle; Ear Diseases; Female; Humans; Hyperpigmentation; Minocycline; Scleral Diseases; Tympanic Membrane

Minocycline is a broad-spectrum antibiotic belonging to the tetracycline family, often prescribed in infective skin conditions such as acne and rosacea. Minocycline-induced staining of the sclerae, ears, oral mucosa and teeth are rare but troublesome conditions. If patients already have concerns about their appearance due to an unsightly skin condition, careful consideration ought to be given to using minocycline as it could worsen the status quo, should potentially irreversible blue staining occur. This report describes one case and highlights some of the other dangers of long-term minocycline use which may present themselves to dentists.

Topics: Anti-Bacterial Agents; Ear Diseases; Ear, External; Female; Humans; Middle Aged; Minocycline; Mouth Diseases; Mouth Mucosa; Pigmentation Disorders; Scleral Diseases; Tooth Discoloration

Topics: Anti-Bacterial Agents; Ear Diseases; Female; Humans; Minocycline; Mouth Diseases; Pigmentation Disorders; Scleral Diseases; Tooth Discoloration

Some agents have been shown to prevent cisplatin-induced ototoxicity. The objective is to show that the agent minocycline protects the cochlea against cisplatin damage and enhances the cytotoxicity of anticancer therapies.. In vitro chemotherapeutic assessments of minocycline.. Research laboratory.. Hep-2 cells were cultured with and without 100 μM cisplatin, and cell growth inhibition was assessed. Autophagy in the samples was visually evaluated by electron microscopy and by beclin-1 expression using Western blotting. In another experiment, cochlear basilar membranes of 3-day-old rats were isolated and cultured. The cultures were treated with the same concentration of cisplatin or cisplatin combined with minocycline. Immunofluorescence staining was used to identify changes in spiral ganglions.. Cell growth was inhibited in a dose-dependent manner following minocycline treatment. Furthermore, the combination of cisplatin and minocycline effectively increased tumor cell death (P < .01). Autophagosomes were also evident in cells treated with minocycline. Beclin-l protein expression was increased after minocycline treatment in Hep-2 cells. In an experiment evaluating cochlear spiral ganglion neuron survival, it was found that the number of surviving cochlear neurons significantly increased in the minocycline pretreatment group compared with the group treated with cisplatin alone (P < .01).. This study shows that minocycline alone, or in combination with chemotherapeutic drugs, inhibits the growth of tumor cells and attenuates ototoxicity. It is also shown that minocycline activates cell autophagy via the beclin-1 signaling pathway, which may be an additional underlying cause of Hep- 2 cell death.

Topics: Animals; Anti-Bacterial Agents; Antineoplastic Agents; Basilar Membrane; Cell Proliferation; Cisplatin; Ear Diseases; Minocycline; Rats; Rats, Wistar; Tissue Culture Techniques; Tumor Cells, Cultured

Milia en plaque is an unusual eruption typically occurring in the retroauricular area. Two cases of this disorder occurring in a novel position and treated with oral minocycline are now reported.

Topics: Anti-Bacterial Agents; Ear Diseases; Ear, External; Humans; Male; Middle Aged; Minocycline; Skin Diseases