Bilateral subthalamic stimulation for advanced Parkinson disease: early experience at an Eastern center.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) can improve the life quality of patients with advanced Parkinson disease (PD). However, previous studies have stemmed mainly from Western centers. Present study analyzed the 6-month outcomes of bilateral STN-DBS therapy that were observed during a 9-year period at a Taiwanese institute. We retrospectively reviewed 72 consecutive patients, whose mean disease history was 8 years when they underwent surgery. The median "drug-off" Hoehn and Yahr stage was 3. The STN was targeted using T2-weighted magnetic resonance imaging and electrophysiological guidance. The over-time mean differences in the Unified PD Rating Scale (UPDRS) scores and daily levodopa-equivalent dose (LED) were assessed using the repeated measurements ANOVA at 3 and 6 months relative to those of presurgical drug-off baseline. At 6 months postsurgery, the mean UPDRS total, Part II and Part III subscores significantly decreased by 27, 30 and 25 %, respectively, with clinically high effect size. Tremors were markedly (66 %) ameliorated. Moreover, problems of akinesia, rigidity, and locomotion were significantly improved by 20 %. The mean daily LED needs decreased by 25 %; thus, drug-induced dyskinesia was markedly (80 %) diminished. STN-DBS therapy could provide similarly effective impacts to Eastern and Western PD patients. Preoperative optimal selection of patients and postoperative delicate programming ensure a better surgical improvement.

1.5T versus 3T MRI for targeting subthalamic nucleus for deep brain stimulation.

BACKGROUND: Accurate stereotactic placement of the electrode into the subthalamic nucleus (STN) is imperative to the therapeutic efficacy of deep brain stimulation (DBS). However, it is not always possible to directly visualize the very small STN using 1.5T MR imaging. OBJECTIVE: To evaluate whether 3T MR imaging can provide better identification of the STN and clinical outcome than 1.5T MR imaging. METHODS: Thirty-nine patients with advanced Parkinson's disease underwent 1.5T (n = 16) or 3T (n = 23) fast spin echo T2-weighted (FSE-T2WI) MR imaging for targeting the STN. A semi-quantitative 3-point scoring system was proposed to rank the clearness of STN contour: Score "0" if non-visible; Score "1" if visible but with blurred margin; and "2" if visible with clear margin. The unified Parkinson's disease rating scale (UPDRS) was also compared before operation and post-operation. RESULTS: The STN score was 2 in all the patients of the 3T group, whereas it was relatively blurred (mean score, 1.19) in the 1.5T group (P < 0.001). The number of microelectrode trajectories (1.2 versus 1.5; P < 0.05) was lower in the 3T group; consequently, the operative time was also less (P < 0.05) as compared with that in the 1.5T group. The outcome of UPDRS motor examination showed no significant difference in two groups. CONCLUSION: 3T MR imaging is a reliable and more accurate method for direct targeting of the STN for DBS surgery. However, the technique of high-sequence MR imaging may not influence the clinical outcome significantly.

Danthron triggers ROS and mitochondria-mediated apoptotic death in C6 rat glioma cells through caspase cascades, apoptosis-inducing factor and endonuclease G multiple signaling.

This research focused on the induction of cytotoxic effects by danthron, a natural anthraquinone derivative on C6 rat glioma cells through exploring the means of cell death and the effects on mitochondrial function. We found that danthron decreased the percentage of viable C6 cells and induced cell morphological changes in a dose-and time-dependent manner. The morphological and nuclei changes (DAPI staining) in C6 cells were observed using a contrast-microscope and fluorescence microscopy, respectively. The results suggest that cell death of C6 cells which are induced by danthron is closely related to apoptotic death. Danthron decreased the level of mitochondrial membrane potential (ΔΨ( m )), stimulated the release of cytochrome c from mitochondria to cytosol and promoted the levels of caspase-9 and caspase-3, or induced the release of AIF and Endo G from mitochondria. Based on both observations, we suggest that the danthron-provoked apoptotic death of C6 cells is mediated through the mitochondria-dependent pathway. Furthermore, our results also indicated that danthron triggered apoptosis through reactive oxygen species (ROS) production which were increased after 1 h exposure of danthron, which was reversed by the ROS scavenger N-acetyl-L: -cysteine (NAC). As a consequence, danthron-mediated cell death of C6 cells via ROS production, mitochondrial transmembrane potential collapse and releases of cytochrome c, AIF and Endo G. Taken together, danthron was demonstrated to be effective in killing C6 rat glioma cells via the ROS-promoted and mitochondria-dependent apoptotic pathways.

Capability of identifying red nuclei in different pulse sequences of regular 1.5-tesla magnetic resonance images.

OBJECTIVE: To investigate the optimal pulse sequences of commonly used 1.5-tesla MRI for identifying the red nucleus (RN) to aid targeting of the subthalamic nucleus (STN). METHODS: Forty-six healthy adults were enrolled for this prospective study. All subjects underwent MR studies of 5 sequences: diffusion-weighted imaging (DWI), T(1)-weighted fluid-attenuated inversion recovery (T1IR), fast spin echo T(2)-weighted imaging (FSE-T2WI), T(2)-weighted fluid-attenuated inversion recovery (T2FLAIR) and T(2)*-weighted gradient-echo (T2*-GRE) sequences. The clearness of the RN contour was analyzed. RESULTS: Overall, the RN was identified in 98% subjects without gender and age differences. The RN was demarcated on a 5-mm slice relatively better in T2FLAIR (93.5%), followed by FSE-T2WI (78.3%), T2*-GRE (65.2%) and DWI (43.5%) sequences, but was completely invisible on the T1IR image. Generally, the signal intensity in all MR sequences decreased mildly on 2-mm slices with a similar identifying power. The detecting power on 5-mm slices was in favor of T2FLAIR with 94% sensitivity, 10% specificity, and 1.89 odds ratio compared to FSE-T2WI. In addition, the scanning time of T2FLAIR was longer in comparison to the FSE-T2WI study. CONCLUSION: T2FLAIR is an alternative to FSE-T2WI that can readily demarcate the RN to help target the STN.

Cucurbitacin E Induces G(2)/M Phase Arrest through STAT3/p53/p21 Signaling and Provokes Apoptosis via Fas/CD95 and Mitochondria-Dependent Pathways in Human Bladder Cancer T24 Cells.

Cucurbitacin E, a tetracyclic triterpenes compound extracted from cucurbitaceous plants, has been shown to exhibit anticancer and anti-inflammatory activities. The purpose of this study was to elucidate whether cucurbitacin E promotes cell cycle arrest and induces apoptosis in T24 cells and further to explore the underlying molecular mechanisms. The effects of cucurbitacin E on T24 cell's growth and accompanied morphological changes were examined by MTT assay and a phase-contrast microscope. DNA content, mitochondrial membrane potential (ΔΨ(m)) and annexin V/PI staining were determined by flow cytometry. The protein levels were measured by Western blotting. Our results demonstrated that cucurbitacin E-induced G(2)/M arrest was associated with a marked increase in the levels of p53, p21 and a decrease in phospho-signal transducer and activator of transcription 3 (STAT3), cyclin-dependent kinase 1 (CDK1) and cyclin B. Cucurbitacin E-triggered apoptosis was accompanied with up-regulation of Fas/CD95, truncated BID (t-BID) and a loss of ΔΨ(m), resulting in the releases of cytochrome c, apoptotic protease activating factor 1 (Apaf-1) and apoptosis-inducing factor (AIF), and sequential activation of caspase-8, caspase-9, and caspase-3. Our findings provided the first evidence that STAT3/p53/p21 signaling, Fas/CD95 and mitochondria-dependent pathways play critical roles in cucurbitacin E-induced G(2)/M phase arrest and apoptosis of T24 cells.

Zolpidem improves neuropsychiatric symptoms and motor dysfunction in a patient with Parkinson's disease after deep brain stimulation.

PURPOSE: To illustrate the beneficial effect of zolpidem on the neuropsychiatric and motor symptoms in a patient with Parkinson disease (PD) after bilateral subthalamic nucleus deep brain stimulation. CASE REPORT: The 61-year-old housewife was diagnosed to have PD for 12 years with initial presentation of clumsiness and rest tremor of right limbs. She was referred to our hospital in March 2009 due to shortening of drug beneficial period since 3 years ago and on-phase dyskinesia in recent 2 years. Bilateral STN DBS was conducted on 18 June, 2009. Fluctuating spells of mental confusion were developed on the next day after surgery. Electric stimuli via DBS electrodes were delivered with parameters of 2 volts, 60 µs, 130 Hz on bilateral STN 32 days after DBS. The incoherent behaviors and motor fluctuation remained to occur. The beneficial effect of zolpidem on her neuropsychiatric and motor symptoms was detected incidentally in early July 2009. She could chat normally with her caregiver and walk with assistance after taking zolpidem. The beneficial period may last for 2 hours. Zolpidem was then given in dosage of 10 mg three times per day. The neuropsychiatric inventory was scored 56 during zolpidem 'off' and 30 during zolpidem 'on'. To understand the intriguing feature, we conducted FDG-PET during 'off' and 'on' zolpidem conditions. The results revealed that the metabolism was decreased in the right frontal, parietal cortex and caudate nucleus during zolpidem 'off'. These cool spots can be partially restored by zolpidem. CONCLUSION: Zolpidem ameliorated the neuropsychiatric and parkinsonian motor symptom in the PD patient. Since GABAA benzodiazepine receptors are widely distributed throughout the central nervous system, zolpidem probably acts via modulating structures lying within the cortico-subcortical loop or by direct effect on these cortical regions.

Induction of apoptotic death by curcumin in human tongue squamous cell carcinoma SCC-4 cells is mediated through endoplasmic reticulum stress and mitochondria-dependent pathways.

Curcumin from the rhizome of the Curcuma longa plant has been noted for its chemo-preventative and chemo-therapy activities, and it inhibits the growth of many types of human cancer cell lines. In this study, the mechanisms of cell death involved in curcumin-induced growth inhibition, including cell cycle arrest and induction of apoptosis in human tongue cancer SCC-4 cells, were investigated. Herein, we observed that curcumin inhibited cell growth of SCC-4 cells and induced cell death in a dose-dependent manner. Treatment of SCC-4 cells with curcumin caused a moderate and promoted the G(2) /M phase arrest, which was accompanied with decreases in cyclin B/CDK1 and CDC25C protein levels. Moreover, curcumin significantly induced apoptosis of SCC-4 cells with a decrease of the Bcl-2 level, reduction of mitochondrial membrane potential (ΔΨ(m) ), and promoted the active forms of caspase-3. Curcumin also promoted the releases of AIF and Endo G from the mitochondria in SCC-4 cells by using confocal laser microscope. Therefore, we suggest that curcumin induced apoptosis through a mitochondria-dependent pathway in SCC-4 cells. In addition, we also found that curcumin-induced apoptosis of SCC-4 cells was partly through endoplasmic reticulum stress. In conclusion, curcumin increased G(2) /M phase arrest and induced apoptosis through ER stress and mitochondria-dependent pathways in SCC-4 cells.

Three-dimensional reconstructed CT scanning for targeting hypertensive putaminal hemorrhage.

We developed an accurate frontal targeting method for hypertensive putaminal hemorrhage (HPH) using three-dimensional (3D) reconstructed CT scanning. Five consecutive unconscious patients with a significant volume of HPH were treated neuroendoscopically via frontal trephination. CT images were examined and reconstructed by an independent neuroradiologist for measuring the selected frontal entry point, depth of penetrating path, and surgical trajectory on the basis of the plane formed by the bilateral orbitomental lines delineated on the reconstructed 3D CT images. All patients regained consciousness post-operatively without complications. All had an accurate trajectory of penetrating path and the average percentage hematoma evacuation was 84%. Use of the 3D reconstructed CT imaging technique combined with neuroendoscopy may prove valuable as a minimally invasive and time-saving method of targeting HPH. Using this method, no further CT scanning is needed for subsequent surgical planning.

Burr hole drainage for complicated spontaneous intracranial hypotension syndrome.

Spontaneous intracranial hypotension is a potentially severe condition that is caused by continuous cerebrospinal fluid leakage. Clinically, most patients have a benign course and the condition remits after conservative management. We report two consecutive patients who presented with acute expansion of subdural collection and disturbed consciousness. Both patients recovered completely after undergoing burr hole drainage.

Benefits of subthalamic stimulation for elderly parkinsonian patients aged 70 years or older.

OBJECTIVES: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an accepted treatment for advanced Parkinson disease (PD). However, there is general reluctance in considering this therapy for PD patients over age 70 years with limited supporting evidence. Present study investigates age impacts in STN-DBS outcomes, focusing particularly on the elderly patients. PATIENTS AND METHODS: Seventy-two consecutive patients were divided into younger and elderly (n=16, cutoff age=70years) groups. Both groups were comparable in preoperative clinical severity, except the elderly exhibited a levodopa (LD) response (P<0.05) inferior to that of the younger. Improvements in drug-off/DBS-on Unified PD Rating Scale (UPDRS) scores and reduction in daily LD-equivalent dose (LED) after 6 months were evaluated relative to the presurgical drug-off baseline. Preoperative factors predictive of favorable surgical outcomes were analyzed using a multivariate linear regression model. RESULTS: After DBS therapy, elderly patients exhibited clinical improvements particularly in the tremor (56%) and LD-induced dyskinesia (78%). Improvement of axial dysfunction (24%) and reduction of daily LED (24%) showed no intergroup difference. Adverse events, particularly dysarthria, occurred frequently in elderly group. The overall improvements in UPDRS scores were suboptimal in elderly group, correlating with their preoperative inferior LD responses. Elderly patients who presented predominantly with akinesia before surgery achieved superior surgical outcomes (adjusted R(2)=0.657, P<0.001). CONCLUSION: STN-DBS therapy is beneficial to some elderly PD patients aged 70 years or older. Tremor, axial dysfunctions and drug-induced dyskinesia are the main indications for the elderly; however, their clinical benefits are inferior to those of younger patients.

Investigation of Motor Cortical Plasticity and Corticospinal Tract Diffusion Tensor Imaging in Patients with Parkinsons Disease and Essential Tremor.

Parkinson's disease (PD) and essential tremor (ET) are characterized with motor dysfunctions. Motor circuit dysfunctions can be complementarily investigated by paired associative stimulation (PAS)-induced long-term potentiation (LTP)-like plasticity and diffusion tensor imaging (DTI) of the corticospinal tract (CST). Three groups of twelve subjects with moderate severity PD, ET with intention tremor and healthy controls (HC) were studied. The primary motor cortex (M1) excitability, measured by motor evoked potential (MEP) amplitude and by short-interval and long-interval intracortical inhibition (SICI and LICI) was compared between the three groups before and after PAS. The DTI measures of fractional anisotropy (FA) and mean diffusivity (MD) were acquired. PAS effects and DTI data were simultaneously examined between groups. PAS increased MEP amplitude in HC but not in PD and ET. SICI and LICI were significantly reduced after PAS irrespective of groups. No significant differences of the mean FA and MD were found between groups. There was no significant correlation between the PAS effects and the DTI measures. Findings suggest that both PD and ET with intention tremor have impairment of the associative LTP-like corticospinal excitability change in M1. The microstructure of the CST is not relevant to the deficiency of M1 associative plasticity in PD and ET.

Sex-Related Prognostic Predictors for Parkinson Disease Undergoing Subthalamic Stimulation.

BACKGROUND: A few reports have addressed the sex-related efficacy of deep brain stimulation (DBS) in the subthalamic nucleus (STN) to treat advanced Parkinson disease (PD). The present study evaluates the sex-related prognostic factors for STN-DBS outcomes. METHODS: Seventy-two consecutive patients (48 men and 24 women) were reviewed retrospectively. Changes in the Unified PD Rating Scale scores were compared between men and women in the 6-month drug-off/DBS-on state relative to the preoperative drug-off baseline. A multivariate linear regression model was used to identify the preoperative factors predictive of motor improvements after surgery. RESULTS: Before surgery, the male and female patient groups were comparable in clinical severity, except the women were associated with slightly inferior cognition (P < 0.05) and a relatively better response to levodopa (LD) (P < 0.05) than the men. Both sexes showed similar clinical improvements after STN-DBS therapy. In men, preoperative lower LD requirement and higher motor dysfunction, particularly tremor (adjusted R(2) = 0.613, P < 0.001), as well as greater improvement in tremor and rigidity after LD therapy (adjusted R(2) = 0.232, P = 0.001) were favorable predictors of surgical outcomes. Women achieved a significant improvement if they performed well in activities of daily living even with higher baseline motor scores (adjusted R(2) = 0.620, P < 0.001), or exhibited improvements in akinesia disability after preoperative LD therapy (adjusted R(2) = 0.305, P = 0.003). CONCLUSIONS: STN-DBS therapy is equally beneficial for both sexes. Sex-related differences exist with regard to favorable prognostic predictors for early surgical outcomes.

One-year Outcome of Bilateral Subthalamic Stimulation in Parkinson Disease: An Eastern Experience.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is widely accepted as a treatment for advanced Parkinson disease (PD). However, published studies were conducted mainly in Western centers and recruited small numbers of patients. This study presents 1-year outcomes in Taiwanese patients with PD. METHODS: Sixty-two consecutive patients underwent STN-DBS surgery during a 7-year period. Their median drug-off Hoehn and Yahr stage was 3 and mean illness history was 8 years. Clinical outcomes were evaluated by the change in drug-off/DBS-on Unified Parkinson Disease Rating Scale (UPDRS) scores relative to presurgical drug-off baseline and change in daily levodopa-equivalent dose (LED). RESULTS: After 1 year of DBS therapy, patients showed significant improvements with a clinically high effect size in cardinal signs, particularly in tremor (63%). Posture instability was also improved, whereas speech dysfunction was hardly corrected. The LED need was significantly reduced, therefore preoperative drug-induced complications were prominently (51%) ameliorated after surgery and drug-induced dyskinesia was remarkably (63%) diminished. No serious adverse effects were encountered after surgery. Overall, motor functions declined by 15% within 1 year in drug-off state. CONCLUSIONS: Bilateral STN-DBS therapy provided effective and sustained benefits to Eastern patients with PD over a 1-year period.

Resetting tremor by single and paired transcranial magnetic stimulation in Parkinson's disease and essential tremor.

OBJECTIVE: The pathogenesis of tremor in Parkinson's disease (PD) and essential tremor (ET) is not fully understood. This study tested the role of primary motor cortex (M1), supplementary motor area (SMA) and cerebellar cortex on PD and ET tremor by single- and paired-pulse transcranial magnetic stimulation (TMS). METHODS: Ten PD patients with resting tremor, six of them also with postural tremor, and ten ET patients with postural tremor were studied. Randomized single- and paired-pulse TMS with an interstimulus interval of 100 ms were delivered over M1, SMA and cerebellum. TMS effects were evaluated by calculating a tremor-resetting index (RI). RESULTS: Single- vs. paired-pulse TMS showed no difference. M1-TMS and SMA-TMS but not by cerebellar TMS induced a significant RI in PD and ET. M1-TMS resulted in a significantly higher RI in PD than ET. Furthermore, M1-TMS in PD but not in ET resulted in a significantly higher RI than SMA-TMS. CONCLUSIONS: Findings suggest a stronger involvement of M1 in resting and postural tremor in PD than postural tremor in ET. SIGNIFICANCE: RI provides a useful marker to explore the differential functional role of M1, SMA and cerebellum in PD vs. ET tremor.

Survival of brain metastatic patients treated with gamma knife radiosurgery alone.

PURPOSE: To evaluate the impact of gamma knife radiosurgery (GKRS) alone on the survival of brain metastasis patients. METHODS: Fifty patients, 17 men and 33 women, with 169 metastatic tumors were retrospectively reviewed. Before therapy, their mean Karnofsky Performance Score was 78. The majority of their primary cancers stemmed from the lung (56%). Thirty-five patients harbored multiple tumors. The mean tumor volume was 3.7 ml. The mean margin dose was 16 Gy. The mean/median clinical follow-up period was 37/25 weeks. RESULTS: The overall image-proven tumor control rate was 76%, and the median tumor progression-free period was 26 weeks after radiosurgery. The survival rate of the patients was 58% and 30% at 6 and 12 months, respectively, and the overall median post-radiosurgery survival time was 38 weeks. Both uni- and multi-variate Cox analyses demonstrated that patients with KPS ≧80 or who were in Recursive Partitioning Analysis Class I survived significantly longer (p<0.05). CONCLUSIONS: Patients treated with GKRS alone can prolong their median lifespan by a range of 6-10 months if they are in a good pre-GKRS functional state.

Suppression of cell invasion and migration by propofol are involved in down-regulating matrix metalloproteinase-2 and p38 MAPK signaling in A549 human lung adenocarcinoma epithelial cells.

Metastasis is a major cause of death of patients with malignant tumors. Matrix metalloproteinases (MMPs) are important for the migration and invasion of various types of cancer cell. Propofol is a known anesthetic agent, widely used for short-term anesthesia and for longer-term sedation. Propofol inhibits the proliferation of a variety of tumor cells, but there is no available information regarding propofol-inhibited migration and invasion of tumor cells in vitro. In this study, we investigated the effects of propofol on the migration and invasion of human lung carcinoma A549 cells. Wound healing assay and Boyden chamber assays indicated that propofol inhibited the migration and invasion of A549 cells in vitro. Gelatin zymographic analysis showed the inhibitory effect of propofol on the activation of expression MMP-2. Western blot analysis also indicated that propofol suppressed the protein expiration of growth factor receptor-bound protein 2 (GRB2), Jun N-terminal kinases 1/2 (p-JNK1/2), p-p38, MMP-2 and MMP-9 in A549 cells. Results from real-time PCR assay also showed that propofol inhibited the mRNA gene expression of MMP-2, -7 and -9, and enhanced that of tissue inhibitor of metalloproteinase 1 (TIMP1) and TIMP2 in A549 cells. Taken together, these data show that propofol inhibits MMP-2 and -9 mRNA and protein expressions, resulting in suppression of lung cancer cell invasion and migration in vitro.

Bufalin induces G0/G1 phase arrest through inhibiting the levels of cyclin D, cyclin E, CDK2 and CDK4, and triggers apoptosis via mitochondrial signaling pathway in T24 human bladder cancer cells.

Most of the chemotherapy treatments for bladder cancer aim to kill the cancer cells, but a high recurrence rate after medical treatments is still occurred. Bufalin from the skin and parotid venom glands of toad has been shown to induce apoptotic cell death in many types of cancer cell lines. However, there is no report addressing that bufalin induced cell death in human bladder cancer cells. The purpose of this study was investigated the mechanisms of bufalin-induced apoptosis in a human bladder cancer cell line (T24). We demonstrated the effects of bufalin on the cell growth and apoptosis in T24 cells by using DAPI/TUNEL double staining, a PI exclusion and flow cytometric analysis. The effects of bufalin on the production of reactive oxygen species (ROS), the level of mitochondrial membrane potential (ΔΨ(m)), and DNA content including sub-G1 (apoptosis) in T24 cells were also determined by flow cytometry. Western blot analysis was used to examine the expression of G(0)/G(1) phase-regulated and apoptosis-associated protein levels in bufalin-treated T24 cells. The results indicated that bufalin significantly decreased the percentage of viability, induced the G(0)/G(1) phase arrest and triggered apoptosis in T24 cells. The down-regulation of the protein levels for cyclin D, CDK4, cyclin E, CDK2, phospho-Rb, phospho-AKT and Bcl-2 with the simultaneous up-regulation of the cytochrome c, Apaf-1, AIF, caspase-3, -7 and -9 and Bax protein expressions and caspase activities were observed in T24 cells after bufalin treatment. Based on our results, bufalin induces apoptotic cell death in T24 cells through suppressing AKT activity and anti-apoptotic Bcl-2 protein as well as inducing pro-apoptotic Bax protein. The levels of caspase-3, -7 and -9 are also mediated apoptosis in bufalin-treated T24 cells. Therefore, bufalin might be used as a therapeutic agent for the treatment of human bladder cancer in the future.

The role of the sub-thalamic nucleus in the preparation of volitional movement termination in Parkinson's disease.

The sub-thalamic nucleus (STN) is relevant to the preparation of movement ignition but its role in movement termination is uncertain. Fourteen patients with Parkinson's disease (PD) received local field potentials (LFPs) recording at the left STN on the fourth day after deep brain stimulation surgery. They performed phasic and tonic movements of the right wrist extensor. Movement onset (Mon) and movement offset (Moff) of the electromyographic activities were used as triggers to determine an eight-second LFPs epoch for time-frequency analysis. Movement-related power changes were assessed by repeated measures analysis of variance with within-subject factors of Event (Mon and Moff), Period (ten time periods for phasic movement and six time periods for tonic movement), and Frequency (alpha, low-beta, and high-beta). There was significant triple interaction in both the phasic and tonic movements. By post-hoc analysis, high-beta event-related de-synchronization (ERD) appeared earlier (3s prior to Mon) than those of low-beta and alpha for the Mon phasic movement. There was no alpha ERD for the Mon tonic movement. Alpha, low-beta, and high-beta ERD all appeared about 1s prior to the Moff tonic movement. The current findings suggest that STN participates in the preparation of volitional movement termination but via a different mechanism from that in movement initiation. Unlike asynchronous ERD frequency bands present in movement initiation, a simultaneous ERD across wide frequency bands in STN may play a pivotal role in terminating volitional movement.

Etomidate induces cytotoxic effects and gene expression in a murine leukemia macrophage cell line (RAW264.7).

Etomidate is an important tool in the arsenal of the emergency physician, and it has been used in a variety of scenarios for both intubation and procedural sedation. In the present study, we investigated the cytotoxicity of etomidate including induction of apoptosis, and levels of protein and gene expressions associated with apoptotic cell death in murine leukemia RAW264.7 cells in vitro. Cytotoxic and apoptotic responses to etomidate of RAW264.7 cells, including cell morphological changes and cell viability were examined and measured by phase-contrast microscopy and flow cytometric assay, respectively. Results indicated that etomidate increased apoptotic cell morphological changes and reduced cell viability in RAW264.7 cells. 4',6-Diamidino-2-phenylindole (DAPI) staining also showed that etomidate induced the formation of apoptotic bodies, a characteristic of apoptosis. Results from Western blotting indicated that etomidate enhanced the levels of cytochrome c, apoptosis-inducing factor (AIF), endonuclease G (Endo G), caspase-9, caspase-3 active form and Bax proteins, but it inhibited the expression of Bcl-xl, leading to apoptosis. DNA microarray assay indicated that etomidate increased the expression of 17 genes (LOC676175; Gm14636; 2810021G02Rik; Iltifb; Olfr1167; Ttc30b; Olfr766; Gas5; Rgs1; LOC280487; V1rd4; Hist1h2bc; V1rj3; Gm10366; Olfr192; Gm10002 and Cspp1) and reduced the expression of 15 genes: (Gm10152; Gm5334; Olfr216; Lcn9; Gm10683; Gm5100; Tdgf1; Cypt2; Gm5595; 1700018F24Rik; Gm10417; Maml2; Olfr591; Trdn and Apol7c). In conclusion, etomidate induced cytotoxic and apoptotic effects the in murine leukemia RAW264.7 cells in vitro.

Stimulation of the subthalamic region at 20 Hz slows the development of grip force in Parkinson's disease.

Excessive synchronization of basal ganglia neuronal activity at ~20 Hz is characteristic of patients with untreated Parkinson's disease (PD). Correlative evidence suggests that this activity may contribute to bradykinesia. Attempts to demonstrate causality through stimulation imposed synchronization at 20 Hz in the region of the subthalamic nucleus (STN) have had limited success. Finger-tapping is slowed by about 8% and only in those PD patients that have a relatively normal baseline performance in this task. Here we investigate whether greater performance decrements might be seen in a reaction time grip task. We studied 32 sides in 16 patients with PD after overnight withdrawal of medication. Patients were asked to grip as hard and as fast as possible without STN stimulation and during bilateral stimulation at 5 Hz, 10 Hz, 20 Hz, 50 Hz and 130 Hz. Stimulation at 20 Hz slowed the development of force by 14.7±8.3% (P=0.044) across all patients. Slowing increased by 22±7% (P=0.005) in those patients with the best performance in the task without stimulation. The effect was frequency specific. These data provide direct interventional evidence of a mechanistic link between excessive neuronal synchronization in the beta range and motor impairment in PD.