Evidence for the Inhibition by Temozolomide, an Imidazotetrazine Family Alkylator, of Intermediate-Conductance Ca2+-Activated K+ Channels in Glioma Cells.

BACKGROUND: Temozolomide (TMZ), an oral alkylator of the imidazotetrazine family, is used to treat glioma. Whether this drug has any ionic effects in glioma cells remains largely unclear. METHODS: With the aid of patch-clamp technology, we investigated the effects of TMZ on the ionic currents in U373 glioma cells. The mRNA expression of KCNN4 (KCa3.1) in U373 glioma cells and TMZ's effect on K+ currents in these KCNN4 siRNA-transfected U373 cells were investigated. RESULTS: In whole-cell recordings, TMZ decreased the amplitude of voltage-dependent K+ currents (IK) in U373 cells. TMZ-induced IK inhibition was reversed by ionomycin or 1-ethyl-2-benzimidazolinone (1-EBIO). In cell-attached configuration, TMZ concentration-dependently reduced the activity of intermediate-conductance Ca2+-activated K+ (IKCa) channels with an IC50 value of 9.2 µM. Chlorzoxazone or 1-EBIO counteracted the TMZ-induced inhibition of IKCa channels. Although TMZ was unable to modify single-channel conductance, its inhibition of IKCa channels was weakly voltage-dependent and accompanied by a significant prolongation in the slow component of mean closed time. However, neitherlarge-conductance Ca2+-activated (BKCa) nor inwardly rectifying K+ (Kir) channels were affected by TMZ. In current-clamp mode, TMZ depolarized the cell membrane and 1-EBIO reversed TMZ-induced depolarization. TMZ had no effect on IK in KCNN4 siRNA-transfected U373 cells. CONCLUSION: In addition to the DNA damage it does, its inhibitory effect on IKCa channels accompanied by membrane depolarization could be an important mechanism underlying TMZ-induced antineoplastic actions.

Speech Recognition Performance under Noisy Conditions of Children with Hearing Loss.

OBJECTIVES: In order to understand the communicative abilities of hearing impaired children in noisy situations and their communication problems, this study was undertaken to examine speech recognition at different background noise levels, and to compare how context cues in noisy situations affect speech recognition. METHODS: Thirty-four children with severe/profound hearing impairment were enrolled. Fifteen children had cochlear implants (CIs) and 19 used hearing aids (HAs). The Mandarin Speech Perception in Noise (SPIN) test was performed under two levels of background noise, signal-to-noise ratio (SNR) 10 dB and SNR 0 dB (high and low levels, respectively). High predictive (HP) and low predictive (LP) sentences SPIN test scores were recorded to test the effect of context cues on speech recognition. RESULTS: Performance was significantly better in children with CIs (SNR 10: mean, 49.44, standard deviation [SD], 13.90; SNR 0: mean, 31.95, SD, 15.72) than in children with HAs (SNR 10: mean, 33.33, SD, 9.72; SNR 0: mean, 19.52, SD, 6.67; P<0.05) in both noise backgrounds, but no significant interaction was found between devices and background noise level. Hearing-impaired children performed better at SNR 10 dB (mean, 40.44; SD, 14.12) than at SNR 0 dB (mean, 25.0; SD, 12.98), significantly (P<0.001). Performance for HP sentences (mean, 38.6; SD, 12.66) was significantly (P<0.001) better than that for LP sentences (mean, 25.25; SD, 12.93). An interaction was found to between background noise level and contextual cues in sentences (F=8.47, P<0.01). CONCLUSION: The study shows that SNR conditions significantly influence speech recognition performance in children with severe/profound hearing impairment. Under better SNR listening situations, children have better speech recognition when listening to sentences with contextual cues. Children with CIs perform better than children with HAs at both noise levels.

Work-related musculoskeletal disorders in athletic trainer.

INTRODUCTION Athletic trainers often work for elongated and irregular hours or days, and need to react in emergency situations. These professionals are at risk for work-related musculoskeletal disorders (WMSDs). This study investigated the WMSDs experienced by athletic trainers (ATs), plus related personal and occupational factors. METHODS A customized questionnaire with subject's demographic and WMSDs information was constructed and administered in all accessible ATs in Taiwan. In addition to descriptive analysis of demographics and WMSDs, the relationship between personal/occupational-related factors and WMSD symptoms were also evaluated. Results A total of 146 effective questionnaires were returned. The results indicated that a 48.5% prevalence rate of athletic trainers in Taiwan, and these disorders are mainly located in low back (42%), finger (38%) and shoulder (26%) regions. Logistic regression revealed that average work hour (odds ratio (OR) = 1.834, 95% confidence interval (CI): 1.066-3.156) and continue education participation (OR = 0.346, 95% CI: 0.140-0.854) were the most significant predictors for WMSDs occurrence. Performing taping was the most significant predictor for the low back (OR = 28.274, 95% CI: 2.568-311.423) and finger (OR = 19.535, 95% CI:2.273-167.912) symptoms; while performing providing first aid (OR = 12.128, 95% CI:3.881-37.899) was the most significant predictor for the shoulder's. Conclusion This study revealed that athletic trainers in Taiwan area suffered from high rate of WMSDs, and the relationship between WMSDs and specific job features were reported. Preventive and therapeutic modifications of the work environment to decrease the occurrence of WMSDs are in need for athletic trainers and other similar professions. Further research examining safe patient handling ergonomics, proper equipment in the context of athletic training and professional development strategies must be pursued.

Effects of lamotrigine on field potentials, propagation, and long-term potentiation in rat prefrontal cortex in multi-electrode recording.

Lamotrigine (LTG) is an anti-epileptic drug that is widely used clinically in various neuropsychiatric disorders. Although consensus is found on the general mode of action by LTG on voltage-gated sodium current, its effect on field potential, neuropropagation, and long-term potentiation, especially in prefrontal cortex (PFC), is still not understood completely. We investigated LTG effects on synaptic response in rat prefrontal cortical slice with the aid of a novel multi-electrode dish (MED64) system. The amplitude and propagation of field excitatory postsynaptic potentials (fEPSP), presynaptic fiber volleys (PrV) were expressed dimensionally in the MED64 system. Lamotrigine (3-100 microM) inhibited the amplitude and propagation of fEPSP and PrV in a concentration dependent manner. It exerted a predominant presynaptic action, as indicated by the increment in paired-pulse facilitation. Stimulating dependency with reduction fEPSP was seen in the presence of LTG at clinically relevant concentrations as well as with PrV, both in amplitude and propagation. In addition, the depression of PrV amplitudes in the presence of LTG showed a use-dependent fashion. As to LTP in PFC, it was not fEPSP amplitude but propagation reduced by LTG. In PFC, LTG exerts its use- and concentration-dependent inhibitory effect on presynaptic action and depresses fEPSP amplitude and propagation in a clinically relevant concentration. LTP was preserved in its fEPSP amplitude but not propagation in PFC in the presence of LTG.

Sodium cyanate-induced opening of calcium-activated potassium currents in hippocampal neuron-derived H19-7 cells.

We investigated the chemical toxic agent sodium cyanate (NaOCN) on the large conductance calcium-activated potassium channels (BK(Ca)) on hippocampal neuron-derived H19-7 cells. The whole-cell and cell-attach configuration of patch-clamp technique were applied to investigate the BK(Ca) currents in H19-7 cells in the presence of NaOCN (0.3 mM). NaOCN activated BK(Ca) channels on H19-7 cells. The single-channel conductance of BK(Ca) channels was 138+/-7pS. The presence of NaOCN (0.3 mM) caused an obvious increase in open probability of BK(Ca) channels. NaOCN did not exert effect on the slope of the activation curve and stimulated the activity of BK(Ca) channels in a voltage-dependent fashion in H19-7 cells. The presence of paxilline or EGTA significantly reduced the BK(Ca) amplitude, in comparison with the presence of NaOCN. These findings suggest that during NaOCN exposure, the activation of BK(Ca) channels in neurons could be one of the ionic mechanisms underlying the decreased neuronal excitability and neurological disorders.

Inflammatory pseudotumor of the bladder: a rare cause of hematuria with impending shock in a child.

Hematuria is one of the most common disorders in children. Bladder tumors are rare in children, and inflammatory pseudotumor (IP) is especially rare. We report a case of inflammatory pseudotumor of the bladder in a 13-year-old girl manifested as acute onset of non-traumatic and painless gross hematuria with impending hypovolemic shock. A huge intravesicular mass (6.5 x 3.8 cm) was noted on renal-bladder ultrasound, cystoscopy, and computed tomography. Partial cystectomy was performed to remove the mass. Pathology led to a diagnosis of leiomyoma and subsequent confirmation as an IP. To our knowledge, our case is the first presentation of bladder IP in Taiwan among the reported pediatric cases.