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Abstract Background The blood-brain tumor barrier (BTB) impedes the delivery of therapeutic agents to brain tumors. While adequate delivery of drugs occurs in systemic tumors, the BTB limits delivery of anti-tumor agents into brain metastases. Results In this study, we examined the function and regulation of calcium-activated potassium (KCa) channels in a rat metastatic brain tumor model. We showed that intravenous infusion of NS1619, a KCa channel agonist, and bradykinin selectively enhanced BTB permeability in brain tumors, but not in normal brain. Iberiotoxin, a KCa channel antagonist, significantly attenuated NS1619-induced BTB permeability increase. We found KCa channels and bradykinin type 2 receptors (B2R) expressed in cultured human metastatic brain tumor cells (CRL-5904, non-small cell lung cancer, metastasized to brain), human brain microvessel endothelial cells (HBMEC) and human lung cancer brain metastasis tissues. Potentiometric assays demonstrated the activity of KCa channels in metastatic brain tumor cells and HBMEC. Furthermore, we detected higher expression of KCa channels in the metastatic brain tumor tissue and tumor capillary endothelia as compared to normal brain tissue. Co-culture of metastatic brain tumor cells and brain microvessel endothelial cells showed an upregulation of KCa channels, which may contribute to the overexpression of KCa channels in tumor microvessels and selectivity of BTB opening. Conclusion These findings suggest that KCa channels in metastatic brain tumors may serve as an effective target for biochemical modulation of BTB permeability to enhance selective delivery of chemotherapeutic drugs to metastatic brain tumors.

Background: Many recipients of bilateral cochlear implants (CIs) may have differences in electrode insertion depth. Previous reports indicate that when a bilateral mismatch is imposed, performance on tests of speech understanding or sound localization becomes worse. If recipients of bilateral CIs cannot adjust to a difference in insertion depth, adjustments to the frequency table may be necessary to maximize bilateral performance., Purpose: The purpose of this study was to examine the feasibility of using real-time manipulations of the frequency table to offset any decrements in performance resulting from a bilateral mismatch., Research Design: A simulation of a CI was used because it allows for explicit control of the size of a bilateral mismatch. Such control is not available with users of CIs., Study Sample: A total of 31 normal-hearing young adults participated in this study., Data Collection and Analysis: Using a CI simulation, four bilateral mismatch conditions (0, 0.75, 1.5, and 3 mm) were created. In the left ear, the analysis filters and noise bands of the CI simulation were the same. In the right ear, the noise bands were shifted higher in frequency to simulate a bilateral mismatch. Then, listeners selected a frequency table in the right ear that was perceived as maximizing bilateral speech intelligibility. Word-recognition scores were then assessed for each bilateral mismatch condition. Listeners were tested with both a standard frequency table, which preserved a bilateral mismatch, or with their self-selected frequency table., Results: Consistent with previous reports, bilateral mismatches of 1.5 and 3 mm yielded decrements in word recognition when the standard table was used in both ears. However, when listeners used the self-selected frequency table, performance was the same regardless of the size of the bilateral mismatch., Conclusions: Self-selection of a frequency table appears to be a feasible method for ameliorating the negative effects of a bilateral mismatch. These data may have implications for recipients of bilateral CIs who cannot adapt to a bilateral mismatch, because they suggest that (1) such individuals may benefit from modification of the frequency table in one ear and (2) self-selection of a "most intelligible" frequency table may be a useful tool for determining how the frequency table should be altered to optimize speech recognition., (American Academy of Audiology)

The anti-Parkinsonian, monoamine oxidase-B inhibitor drug, rasagiline (Azilect®), is primarily metabolized by hepatic cytochrome P450 isoenzyme 1A2-mediated N-dealkylation to form its major metabolite, 1-(R)-aminoindan. The present study was undertaken to further investigate, for the first time, the possible neuroprotective effect of 1-(R)-aminoindan in two rat models of Parkinson's disease, the 6-hydroxydopamine- and lactacystin (a proteasomal inhibitor)-induced nigrostriatal degeneration. 1-(R)-aminoindan reversed behavioral asymmetry and restored striatal catecholamine levels in these two rat models and significantly protected neurons from hydrogen peroxide-induced oxidative stress. These observations indicate that 1-(R)-aminoindan may contribute to the overall neuroprotective activity of its parental compound, rasagiline.

Purpose. In recent years, endoscopic injection became the procedure of choice for the correction of vesicoureteral reflux in the majority of the centers. Unfortunately, endoscopic treatment is not always successful and sometimes requires more than one trial to achieve similar results to that of an open reimplantation surgery. Our aim of this study is to evaluate the feasibility and success rate of open ureteral reimplantation following failed endoscopic procedure. Patients and Methods. During 2004-2010, we evaluated 16 patients with persistent vesicoureteral reflux (grades II-IV) following failed endoscopic treatment. All patients underwent open ureteral reimplantation. All patients were followed with an ultrasound 6 weeks following surgery and every 6 months thereafter for an average of 22 months. Voiding cystography was performed at 3 months after surgery. Results. During unilateral open ureteral reimplantation, the implanted deposit from previous procedures was either excised, drained, or incorporated into the neotunnel with the ureter. Vesicoureteral reflux was resolved in all patients with 100% success rate. No new hydronephrosis or signs of obstruction developed in any of the patients. qDMSA renal scan was available in 8 patients showing improvement of function in 5 and stable function in 3, and no new scars were identified. Conclusions. Open ureteral reimplantation is an excellent choice for the correction of failed endoscopic treatment in children with vesicoureteral reflux.