Goreisan regulates cerebral blood flow according to barometric pressure fluctuations in female C57BL/6J mice.

Goreisan is a Kampo medicine used to treat headaches associated with climate change. Here, by using an implantable complementary metal-oxide-semiconductor (CMOS) device, we evaluated the effects of Goreisan and loxoprofen on cerebral blood flow (CBF) dynamics associated with barometric pressure fluctuations in freely moving mice. In the vehicle group, decreasing barometric pressure increased CBF that was prevented by Goreisan and loxoprofen. Notably, Goreisan, but not loxoprofen, reduced CBF after returning to atmospheric pressure. These results indicate that, unlike the mechanism of action of antipyretic analgesics, Goreisan normalizes CBF abnormalities associated with barometric pressure fluctuations by actively reducing CBF increase.

Different contra-sound effects between noise and music stimuli seen in N1m and psychophysical responses.

Auditory-evoked responses can be affected by the sound presented to the contralateral ear. The different contra-sound effects between noise and music stimuli on N1m responses of auditory-evoked fields and those on psychophysical response were examined in 12 and 15 subjects, respectively. In the magnetoencephalographic study, the stimulus to elicit the N1m response was a tone burst of 500 ms duration at a frequency of 250 Hz, presented at a level of 70 dB, and white noise filtered with high-pass filter at 2000 Hz and music stimuli filtered with high-pass filter at 2000 Hz were used as contralateral noise. The contralateral stimuli (noise or music) were presented in 10 dB steps from 80 dB to 30 dB. Subjects were instructed to focus their attention to the left ear and to press the response button each time they heard burst stimuli presented to the left ear. In the psychophysical study, the effects of contralateral sound presentation on the response time for detection of the probe sound of a 250 Hz tone burst presented at a level of 70 dB were examined for the same contra-noise and contra-music used in the magnetoencephalographic study. The amplitude reduction and latency delay of N1m caused by contra-music stimuli were significantly larger than those by contra-noise stimuli in bilateral hemisphere, even for low level of contra-music near the psychophysical threshold. Moreover, this larger suppressive effect induced by contra-music effects was also observed psychophysically; i.e., the change in response time for detection of the probe sound was significantly longer by adding contralateral music stimuli than by adding contra-noise stimuli. Regarding differences in effect between contra-music and contra-noise, differences in the degree of saliency may be responsible for their different abilities to disturb auditory attention to the probe sound, but further investigation is required to confirm this hypothesis.

Propranolol prevents cerebral blood flow changes and pain-related behaviors in migraine model mice.

Propranolol, a ß-adrenergic receptor blocker, is one of the most commonly used prophylactic drugs for migraines. Cortical spreading depression (CSD) is the propagation wave of neuronal excitation along with cerebral blood flow (CBF) changes over the cerebral cortex and has been implicated in the pathological process of migraine auras and its pain response. However, the effect of propranolol on CSD-related CBF changes and behavioral responses remains poorly understood. In this study, we measured CSD-related CBF responses using a micro-device with a green light emitting diode (LED) and micro-complementary-metal-oxide-semiconductor (CMOS) image sensor and evaluated pain-related reduced locomotor activity in mice. An injection of KCl into the visual cortex led to CSD-related CBF changes; however, propranolol prevented the increase in CBF as well as delayed the propagation velocity in KCl-induced CSD. Furthermore, an injection of KCl reduced locomotor activity and induced freezing behavior in awake and freely moving mice, which were prevented by propranolol treatment. These results suggest that the modulation of CSD-related CBF responses by the blockade of ß-adrenergic receptor contributes to its prophylactic effects on migraines.

Reducing of salivary α-amylase inhibition by using bovine serum albumin and calcium chloride for forensic saliva screening.

Inhibiting salivary α-amylase is a critical issue of forensic saliva identification using the catalytic method. This study aims to identify human α-amylase inhibitors in forensic saliva screening by using a blue starch amylase test and to measure the extent of enzyme inhibition. Thus, in order to demonstrate the presence of inhibitors, we prepared positively charged metal ion sources or chelators that were mixed into the saliva stains. The results of this study show that ferric chloride (FeCl3), magnesium chloride, ethylenediaminetetraacetic acid, and citric acid significantly decrease the α-amylase activity of saliva stains. We also verified this approach using blood, a magnesium-containing liquid supplement, and two citric acid-containing soft drinks that were contaminated with saliva stains as forensic mock samples; these samples also showed a significant reduction in salivary α-amylase activity. To establish an inhibitor-resistant blue starch amylase test, we applied bovine serum albumin (BSA) and calcium chloride (CaCl2) to the reaction system. The results show that salivary α-amylase inhibition of the forensic mock samples occurred under normal test conditions (i.e., 300ng/µL BSA, 0mM CaCl2), and that inhibition was significantly relieved under the BSA+CaCl2 conditions (i.e., 1000ng/µL BSA, 5mM CaCl2). Therefore, the results of this study demonstrate that both BSA and CaCl2 can be utilized as reaction stabilizers in forensic saliva screening.

Predictors of poor response to secondary alternative antiandrogen therapy with flutamide in metastatic castration-resistant prostate cancer.

OBJECTIVE: In Japan, flutamide had been commonly used as second-line alternative antiandrogen hormonal therapy for metastatic castration-resistant prostate cancer that relapses after initial hormone therapy before new androgen pathway inhibitors became available. In this study, we attempted to identify predictive factors for efficacy of alternative antiandrogen as second-line hormone therapy. METHODS: We identified consecutive 65 patients with metastatic castration-resistant prostate cancer who were treated with alternative antiandrogen as second-line hormonal therapy (bicalutamide to flutamide). All patients were treated with combined androgen blockade initially. We analyzed correlations between progression-free survival of alternative antiandrogen and clinicopathological characteristics, including patients' ages, initial prostate-specific antigen levels, prostate-specific antigen levels at flutamide induction, Gleason scores, T stage, N stage, extent of disease grades on bone scan and previous duration of prostate cancer response to combined androgen blockade. RESULTS: In univariate analysis, T stage, N stage and previous duration of response to combined androgen blockade were correlated with shorter progression-free survival. We found four significant risk factors for shorter progression-free survival in multivariate analysis: initial prostate-specific antigen level, clinical N stage, extent of disease grades and previous duration of response to combined androgen blockade. CONCLUSIONS: Initial prostate-specific antigen, N stage, extent of disease grades on bone scan and previous duration of response to combined androgen blockade were the significant predictors for efficacy of alternative antiandrogen as second-line hormone therapy in patients with metastatic castration-resistant prostate cancer. These findings might support that decision-making of when to start the new androgen receptor pathway inhibitors.

Functional verification of pulse frequency modulation-based image sensor for retinal prosthesis by in vitro electrophysiological experiments using frog retina.

The functioning of a 16 x 16 pixel pulse frequency modulation (PFM) image sensor for retinal prosthesis is verified through in vitro electrophysiological experiments using detached frog retinas. This image sensor is a prototype for demonstrating the application to in vitro electrophysiological experiments. Each pixel of the image sensor consists of a pulse generator (PFM photosensor), a stimulus circuit, and a stimulus electrode (Al bonding pad). The image sensor is fabricated using standard 0.6 microm CMOS technology. For in vitro electrophysiological experiments, a Pt/Au stacked electrode is formed on the Al bonding pad of each pixel and the entire sensor is fixed in epoxy resin. The PFM image sensor is confirmed experimentally to provide electrical stimulus to the retinal cells in a detached frog retina.