tacrolimus and Hearing-Loss--Sensorineural

Early trials of tacrolimus in renal transplant recipients have not revealed hearing loss as an adverse effect. Here, we present a case report and a review of the literature of deafness after tacrolimus use. The review of the literature and our experience suggested that the possible reason for hearing loss could be due to an initiation of a sudden spike in the tacrolimus serum level, which was later worsened by its cumulative toxic effect.

Topics: Calcineurin Inhibitors; Hearing; Hearing Loss, Sensorineural; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Ototoxicity; Tacrolimus; Treatment Outcome

Type 4 Bartter syndrome (BS) is caused by genetic mutations in barttin, which is coded for by BSND. Barttin serves as the β-subunit of the ClC-K chloride (Cl

Topics: Animals; Bartter Syndrome; Calcineurin Inhibitors; Disease Models, Animal; Hearing Loss, Sensorineural; Hypokalemia; Mice; Mice, Inbred C57BL; Phosphorylation; Sodium-Potassium-Chloride Symporters; Solute Carrier Family 12, Member 3; Tacrolimus

Most degenerative diseases begin with a gradual loss of specific cell types before reaching a threshold for symptomatic onset. However, the endogenous regenerative capacities of different tissues are difficult to study, because of the limitations of models for early stages of cell loss. Therefore, we generated a transgenic mouse line (Mos-iCsp3) in which a lox-mismatched Cre/lox cassette can be activated to produce a drug-regulated dimerizable caspase-3. Tissue-restricted Cre expression yielded stochastic Casp3 expression, randomly ablating a subset of specific cell types in a defined domain. The limited and mosaic cell loss led to distinct responses in 3 different tissues targeted using respective Cre mice: reversible, impaired glucose tolerance with normoglycemia in pancreatic β cells; wound healing and irreversible hair loss in the skin; and permanent moderate deafness due to the loss of auditory hair cells in the inner ear. These mice will be important for assessing the repair capacities of tissues and the potential effectiveness of new regenerative therapies.

Topics: Alopecia; Animals; Apoptosis; Caspase 3; Cell Lineage; Dimerization; Disease Models, Animal; Epidermis; Gene Expression Regulation; Gene Knockdown Techniques; Genes, Transgenic, Suicide; Glucose Intolerance; Hair Cells, Auditory, Inner; Hearing Loss, Bilateral; Hearing Loss, Sensorineural; Homeodomain Proteins; Insulin; Islets of Langerhans; Keratin-14; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mosaicism; Organ Specificity; Phenotype; Tacrolimus; Transcription Factor Brn-3C; Transgenes; Wound Healing

Round window membrane application of immunosuppressives reduces cochlear inflammation and hearing loss in a guinea pig model of sterile labyrinthitis.. Systemic immunosuppressives are used to treat sensorineural hearing loss due to inflammation (autoimmune, bacterial, viral), which in animal models causes hearing loss. Transtympanic application of drugs is an attractive and possibly efficacious method of treatment that avoids systemic toxicities.. Sterile labyrinthitis was created using keyhole limpet hemocyanin (KLH). Dexamethasone (0.048 mg/day and 0.288 mg/day), cyclosporine (0.5%), prednisolone acetate (1%), fluorouracil, (5%), and FK506 (0.01%) were delivered to the round window membrane with one injection (filling middle ear space) or osmotic minipumps. Efficacy was evaluated by auditory brainstem response and histology.. No drug was effective at reducing hearing loss or inflammation.. Local application of immunosuppressives did not suppress inner ear inflammatory infiltrates and hearing loss in KLH-induced labyrinthitis in a guinea pig model.

Topics: Animals; Anti-Inflammatory Agents; Cyclosporine; Dexamethasone; Disease Models, Animal; Drug Evaluation, Preclinical; Fluorouracil; Guinea Pigs; Hearing Loss, Sensorineural; Hemocyanins; Immunosuppressive Agents; Injections; Labyrinthitis; Prednisolone; Round Window, Ear; Tacrolimus