Magnetic resonance monitoring of superparamagnetic iron oxide (SPIO)-labeled stem cells transplanted into the inner ear.

In the field of regenerative medicine, cell transplantation or cell-based therapies for inner ear defects are considered to be promising candidates for a therapeutic strategy. In this paper, we report on a study that examined the use of magnetic resonance imaging (MRI) to monitor stem cells transplanted into the cochlea labeled with superparamagnetic iron oxide (SPIO), a contrast agent commonly used with MRI. First, we demonstrated in vitro that stem cells efficiently took up SPIO particles. This was confirmed by Prussian blue staining and TEM. In MRI studies, T2 relaxation times of SPIO-labeled cells decreased in a dose-dependent manner. Next, we transplanted SPIO-labeled cells directly into the cochlea in vivo and then performed MRI 1h, 2 weeks, and 4 weeks after transplantation. The images were evaluated objectively by measuring signal intensity (SI). SI within the ears receiving transplants was significantly lower (P<0.05) than that of control sides at the 1-h assessment. This novel method will be helpful for evaluating stem cell therapies, which represents a new strategy for inner ear regeneration. To the best of our knowledge, this study is the first to demonstrate that local transplantation of labeled stem cells into the inner ear can be visualized in vivo via MRI.

The assessment of the optimal duration of early intervention with montelukast in the treatment of Japanese cedar pollinosis symptoms induced in an artificial exposure chamber.

OBJECTIVE: The study objective was to investigate the prophylactic efficacy of montelukast (MLK) 10 mg in suppressing seasonal allergic rhinitis (SAR) symptoms induced by Japanese cedar (JC) pollen and to determine how many days before exposure to JC in the artificial exposure chamber (OHIO chamber) would be optimal to start administration. METHODS: This was a single-institution, double-blind, randomized placebo-controlled four-group parallel inter-group comparison study. Adult volunteers with JC pollinosis were divided into four groups: an MLK 7-day administration group (n = 27), an MLK 3-day administration group (n = 27), an MLK 1-day administration group (n = 26), and a placebo group (n = 26). The mean change in total nasal symptom scores (nasal obstruction, nasal discharge and sneezing) (TNSS) and each of the nasal symptom scores during exposure of JC pollen in the OHIO chamber were investigated. RESULTS: The mean change in TNSS was significantly lower in the MLK treatment group, regardless of the number of days of administration, than in the placebo group (p = 0.0192). The results for the individual nasal symptoms showed that nasal obstruction was significantly suppressed in the 1-day administration group as compared with placebo (p = 0.0076), but no differences were found in sneezing score between any of the groups. For nasal discharge, we found a trend towards the effect clearing up after 3 days of administration. No serious adverse events were observed during the study. CONCLUSION: Although this study was acute and this artificial exposure model was conducted out of the pollen season, nasal symptoms that developed in the pollen exposure chamber, especially nasal obstruction, were significantly suppressed by starting oral administration of MLK 10 mg at least 1 day before exposure. These results suggest that prophylactic administration of MLK is effective and safe in the treatment of SAR.

Repetitive transcranial magnetic stimulation (rTMS) for treatment of chronic tinnitus.

OBJECTIVE: There is compelling evidence that tinnitus is associated with functional alterations in the central nervous system. Repetitive transcranial magnetic stimulation (rTMS) is a potent tool for modifying neural activity at the stimulated area and at a distance along the functional anatomical connections. Depending on the stimulation parameters, cortical networks can be functionally disturbed or modulated in their activities. Low-frequency rTMS has been shown to result in a decrease in cortical excitability. The technique can alleviate tinnitus by modulating the excitability of neurons in the auditory cortex. We aimed to investigate the effects of low-frequency rTMS in patients and determine the factors that predict a beneficial outcome with rTMS treatment. METHODS: Sixteen patients (male 10, female 6) with chronic tinnitus underwent low-frequency (1Hz) rTMS (intensity: 110% motor threshold; number of stimuli: 1200) to the left auditory cortex. The treatment outcome was assessed with a visual analog scale (VAS) of loudness, annoyance and duration, loudness balance test, and tinnitus handicap inventory (THI). Therapeutic success was studied according to the patients' clinical characteristics. RESULTS: A significant reduction in the VAS (loudness and annoyance) occurred immediately after rTMS, with a gradual return to pretreatment levels after 7 days. The tinnitus patients with sudden deafness were significant resistant to rTMS treatment compared with those diagnosed with age-related hearing loss. CONCLUSION: These results support the potential of rTMS as a new therapeutic tool for the treatment of chronic tinnitus. Because this study was performed with a small sample size and showed high interindividual variability in treatment effects, further development of the technique is needed before it can be recommended for clinical applications.