ABSTRACT
OBJECTIVES/HYPOTHESIS: Autoimmune inner ear disorder is one of a few types of sensorineural hearing loss that is treatable and potentially reversible. Treatment involves oral steroids and methotrexate. Other treatment modalities have been tried with variable success. All such treatments are systemic, with inherent side effects limiting their effectiveness. Recently, tumor necrosis factor (TNF)-α blockers have been suggested as a modality of treatment. The objective of this study was to assess the round window membrane permeability to golimumab, a TNF-α blocker. This study is the first to look at the feasibility of local golimumab delivery into the inner ear, which may allow for targeted immune modulation of autoimmune inner ear disorders without the consequences of systemic treatment. STUDY DESIGN: This is a single-blinded, placebo-controlled, pilot study using guinea pigs to assess round window membrane permeability to golimumab. METHODS: Golimumab was instilled into the guinea pigs' middle ear. Inner ear fluid was sampled through the round window membrane after approximately 30 minutes of drug exposure. Golimumab presence in the inner ear was assessed by enzyme-linked immunosorbent assay in both drug-treated and control ears. RESULTS: Higher concentrations of golimumab were detected in the inner ear fluid samples of golimumab-exposed ears than in the control ears. The difference was statistically significant (P < .001). CONCLUSIONS: Golimumab crosses the round window membrane and is detected in measurable concentrations in the inner ear fluid after 30 minutes of exposure to the membrane. Further studies are needed to learn its pharmacokinetics and the time needed to reach optimal concentration in the inner ear. LEVEL OF EVIDENCE: NA. Laryngoscope, 123:2840-2844, 2013.
Subject(s)
Antibodies, Monoclonal/pharmacokinetics , Round Window, Ear/metabolism , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Animals , Antibodies, Monoclonal/analysis , Body Fluids/chemistry , Ear, Inner , Feasibility Studies , Female , Guinea Pigs , Permeability , Pilot ProjectsABSTRACT
BACKGROUND: The effects of soy isoflavones on prostate cancer may be concentration-dependent. The impact of soy supplementation on isoflavone concentrations in prostate tissues and serum remain unclear. OBJECTIVE: To assess and compare concentrations of soy isoflavones in prostate tissue and serum among 19 men with prostate cancer who had elected to undergo radical prostatectomy. METHODS: Participants were randomized to receive either daily soy supplements (82 mg/day aglycone equivalents) or placebos for 2 weeks (14 days) prior to surgery. Serum samples were obtained at the time of the surgery. Isoflavone concentrations were measured by HPLC/ESI-MS-MS. RESULTS: The median (25th, 75th percentile) total isoflavone concentration in the isoflavone-supplemented group was 2.3 micromol/L (1.2, 6.9) in the prostate tissue and 0.7 micromol/L (0.2, 1.2) in the serum. Total isoflavone concentrations in this group were an average of approximately 6-fold higher in prostate tissue compared to serum; the tissue versus serum ratio was significantly lower for genistein than daidzein, 4-fold versus 10-fold, P = 0.003. Tissue and serum levels of isoflavones among the placebo group were negligible with a few exceptions. CONCLUSIONS: The findings from the present study suggest that prostate tissue may have the ability to concentrate dietary soy isoflavones to potentially anti-carcinogenic levels.
