Effects of taurine and ginseng extracts on energy metabolism during exercise and their anti-fatigue properties in mice

BACKGROUND/OBJECTIVES@#Ginseng extract (GSE) and taurine (TR) are widely used antifatigue resources in functional foods. However, the mechanism underlying the antifatigue effects of GSE and TR are still unclear. Hence, we investigated whether GSE and TR have synergistic effects against fatigue in mice.MATERIALS/METHODS: L6 cells were treated with different concentrations of TR and GSE, and cell viability was determined using 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium. Oxidative stress was analyzed by immunocytochemistry using MitoTracker™ Red FM and an anti-8-oxoguanine antibody. Respiratory gas analysis was performed to investigate metabolism. Expression of an activated protein kinase was analyzed using immunohistochemistry. Gene expression of cluster of differentiation 36 and pyruvate dehydrogenase lipoamide kinase isozyme 4 was measured using reverse transcription– polymerase chain reaction. Mice were orally administered TR, GSE, or their combination for 30 days, and then fatigue-related parameters, including lactate, blood urea nitrogen, and glycogen, were measured after forced swimming. @*RESULTS@#TR and GSE reduced oxidative stress levels in hydrogen peroxide-stimulated L6 cells and enhanced the oxygen uptake and lipid metabolism in mice after acute exercise. After oral administration of TR or GSE for 30 days, the fatigue-related parameters did not change in mice. However, the mice administered GSE (400 mg/kg/day) alone for 30 days could swim longer than those from the other groups. Further, no synergistic effect was observed after the swimming exercise in mice treated with the TR and GSE combination for 30 days. @*CONCLUSIONS@#Taken together, our data suggest that TR and GSE may exert antifatigue effects in mice after acute exercise by enhancing oxygen uptake and lipid oxidation.

Heat shock protein 90 inhibitor AUY922 attenuates platelet-derived growth factor-BB-induced migration and proliferation of vascular smooth muscle cells

Luminespib (AUY922), a heat shock proteins 90 inhibitor, has anti-neoplastic and antitumor effects. However, it is not clear whether AUY922 affects events in vascular diseases. We investigated the effects of AUY922 on the platelet-derived growth factor (PDGF)-BB-stimulated proliferation and migration of vascular smooth muscle cells (VSMC). VSMC viability was detected using the XTT (2,3-bis-(2-methoxy- 4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) reagent. To detect the attenuating effects of AUY922 on PDGF-BB-induced VSMCs migration in vitro, we performed the Boyden chamber and scratch wound healing assays. To identify AUY922- mediated changes in the signaling pathway, the phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) 1/2 was analyzed by immunoblotting. The inhibitory effects of AUY922 on migration and proliferation ex vivo were tested using an aortic ring assay. AUY922 was not cytotoxic at concentrations up to 5 nM. PDGF-BB-induced VSMC proliferation, migration, and sprout outgrowth were significantly decreased by AUY922 in a dose-dependent manner. AUY922 significantly reduced the PDGF-BB-stimulated phosphorylation of Akt and ERK1/2. Furthermore, PD98059 (a selective ERK1/2 inhibitor) and LY294002 (a selective Akt inhibitor) decreased VSMC migration and proliferation by inhibiting phosphorylation of Akt and ERK1/2. Greater attenuation of PDGF-BB-induced cell viability and migration was observed upon treatment with PD98059 or LY294002 in combination with AUY922. AUY922 showed anti-proliferation and anti-migration effects towards PDGF-BBinduced VSMCs by regulating the phosphorylation of ERK1/2 and Akt. Thus, AUY922 is a candidate for the treatment of atherosclerosis and restenosis.

Heat shock protein 90 inhibitor AUY922 attenuates platelet-derived growth factor-BB-induced migration and proliferation of vascular smooth muscle cells

Luminespib (AUY922), a heat shock proteins 90 inhibitor, has anti-neoplastic and antitumor effects. However, it is not clear whether AUY922 affects events in vascular diseases. We investigated the effects of AUY922 on the platelet-derived growth factor (PDGF)-BB-stimulated proliferation and migration of vascular smooth muscle cells (VSMC). VSMC viability was detected using the XTT (2,3-bis-(2-methoxy- 4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) reagent. To detect the attenuating effects of AUY922 on PDGF-BB-induced VSMCs migration in vitro, we performed the Boyden chamber and scratch wound healing assays. To identify AUY922- mediated changes in the signaling pathway, the phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) 1/2 was analyzed by immunoblotting. The inhibitory effects of AUY922 on migration and proliferation ex vivo were tested using an aortic ring assay. AUY922 was not cytotoxic at concentrations up to 5 nM. PDGF-BB-induced VSMC proliferation, migration, and sprout outgrowth were significantly decreased by AUY922 in a dose-dependent manner. AUY922 significantly reduced the PDGF-BB-stimulated phosphorylation of Akt and ERK1/2. Furthermore, PD98059 (a selective ERK1/2 inhibitor) and LY294002 (a selective Akt inhibitor) decreased VSMC migration and proliferation by inhibiting phosphorylation of Akt and ERK1/2. Greater attenuation of PDGF-BB-induced cell viability and migration was observed upon treatment with PD98059 or LY294002 in combination with AUY922. AUY922 showed anti-proliferation and anti-migration effects towards PDGF-BBinduced VSMCs by regulating the phosphorylation of ERK1/2 and Akt. Thus, AUY922 is a candidate for the treatment of atherosclerosis and restenosis.

Invasive Lobular Carcinoma: Detection and Multiplicity with Multimodalities / 이화의대지

OBJECTIVES: We aimed to compare the diagnostic performances of digital mammography (DM), digital breast tomosynthesis (DBT), ultrasound (US), magnetic resonance imaging (MRI), breast specific gamma imaging (BSGI) and/or positron emission tomography/computed tomography (PET/CT) for the detection of invasive lobular carcinoma (ILC). METHODS: Index ILCs and multifocal/multicentric (multiple) ILCs were analyzed using various imaging modalities. The final surgical pathology was regarded as the reference standard. The detection rate for index cancers and the diagnostic performance for multiple ILCs per breast were evaluated. RESULTS: Seventy-eight ILCs in 76 women were enrolled. Twenty-six breasts had multiple ILCs. DM (n=72), DBT (n=15), US (n=77), MRI (n=76), BSGI (n=50), and /or PET/CT (n=74) were performed. For index cancer, the detection rate was 100% for DBT, US, and MRI. For multiple ILCs, the sensitivity was 100% for DBT and MRI (P<0.001). The diagnostic accuracy for multiple ILCs were 73.3% for DBT and 73.0% for PET/CT (P=0.460). CONCLUSION: DBT was the most accurate imaging modality for both index and multiple ILCs. PET/CT was also valuable for multiple ILCs, whereas DM and BSGI showed relatively low diagnostic performances. DBT and PET/CT have promising roles in the diagnosis of multiple ILCs.

Axillary Lymph Node-to-Primary Tumor Standard Uptake Value Ratio on Preoperative 18F-FDG PET/CT: A Prognostic Factor for Invasive Ductal Breast Cancer / 한국유방암학회지

PURPOSE: This study assessed the axillary lymph node (ALN)-to-primary tumor maximum standard uptake value (SUVmax) ratio (ALN/T SUV ratio) in invasive ductal breast cancer (IDC) on preoperative 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) to determine the effectiveness in predicting recurrence-free survival (RFS). METHODS: One hundred nineteen IDC patients (mean age, 50.5+/-10.5 years) with pathologically proven ALN involvement without distant metastasis and preoperative FDG PET/CT were enrolled in the study. SUVmax values of the ALN and primary tumor were obtained on FDG PET/CT, and ALN/T SUV ratio was calculated. Several factors were evaluated for their effectiveness in predicting RFS. These included several parameters on FDG PET/CT as well as several clinicopathological parameters: pathologic tumor/node stage; nuclear and histological grade; hormonal state; status with respect to human epidermal growth factor receptor 2, mindbomb E3 ubiquitin protein ligase 1 (MIB-1), and p53; primary tumor size; and ALN size. RESULTS: Among 119 patients with breast cancer, 17 patients (14.3%) experienced relapse during follow-up (mean follow-up, 28.4 months). The ALN/T SUV ratio of the group with disease recurrence was higher than that of the group without recurrence (0.97+/-1.60 and 0.45+/-0.40, respectively, p=0.005). Univariate analysis showed that the primary tumor SUVmax, ALN SUVmax, ALN/T SUV ratio, ALN status, nuclear and histological grade, estrogen receptor (ER) status, and MIB-1 status were predictors for RFS. Among these variables, ALN/T SUV ratio with hazard ratio of 4.20 (95% confidence interval [CI], 1.74-10.13) and ER status with hazard ratio of 4.33 (95% CI, 1.06-17.71) were predictors for RFS according to multivariate analysis (p=0.002 and p=0.042, respectively). CONCLUSION: Our study demonstrated that ALN/T SUV ratio together with ER status was an independent factor for predicting relapse in IDC with metastatic ALN. ALN/T SUV ratio on preoperative FDG PET/CT may be a useful marker for selecting IDC patients that need adjunct treatment to prevent recurrence.

Erratum: Cortico-Cortical Modulation Induced by 1-Hz rTMS of the Temporal Cortex

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Cortico-Cortical Modulation Induced by 1-Hz Repetitive Transcranial Magnetic Stimulation of the Temporal Cortex

BACKGROUND AND PURPOSE: Repetitive transcranial magnetic stimulation (rTMS) has potential as a noninvasive neuromodulation treatment method for various neuropsychiatric disorders, and repeated sessions of rTMS are more likely to enhance the therapeutic efficacy. This study investigated neurophysiologic and spatiodynamic changes induced by repeated 1-Hz rTMS of the temporal cortex using transcranial magnetic stimulation (TMS) indices and fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: Twenty-seven healthy subjects underwent daily 1-Hz active or sham rTMS of the right temporal cortex for 5 consecutive days. TMS indices of motor cortical excitability were measured in both hemispheres daily before and after each rTMS session, and 2 weeks after the last stimulation. FDG-PET was performed at baseline and after the 5 days of rTMS sessions. RESULTS: All subjects tolerated all of the sessions well, with only three of them (11.1%) reporting mild transient side effects (i.e., headache, tinnitus, or local irritation). One-Hz rTMS decreased motor evoked potential amplitudes and delayed cortical silent periods in the stimulated hemisphere. Statistical parametric mapping of FDG-PET data revealed a focal reduction of glucose metabolism in the stimulated temporal area and an increase in the bilateral precentral, ipsilateral superior and middle frontal, prefrontal and cingulate gyri. CONCLUSIONS: Repeated rTMS sessions for 5 consecutive days were tolerated in all subjects, with only occasional minor side effects. Focal 1-Hz rTMS of the temporal cortex induces cortico-cortical modulation with widespread functional changes in brain neural networks via long-range neural connections.

The Clinical Meaning of Benign Colon Uptake in 18F-FDG PET: Comparison with Colonoscopic Findings

BACKGROUND/AIMS: Benign colon 18F-fluorodeoxyglucose (FDG) uptake is frequently observed in asymptomatic individuals. Aims of this study were to investigate the benign colon uptake by whole body FDG-positron emission tomography (PET) in asymptomatic adults and to correlate those results with colonoscopic and histologic findings. METHODS: Among 3,540 subjects who had undergone FDG-PET, 43 subjects who were diagnosed to have benign colon uptake in FDG-PET and underwent colonoscopy were retrospectively reviewed. Subjects were classified as diffuse or focal groups based on their FDG uptake patterns. PET results were analyzed together with colonoscopic and histologic findings. RESULTS: Forty-three subjects showed benign colon uptake in FDG-PET; 28 of them were shown as the diffuse group, while other 15 subjects were classified as the focal group. Five subjects among those showed diffuse uptake were diagnosed as adenoma. Seven among 15 subjects who showed focal uptake were diagnosed as adenocarcinoma (n=2), adenoma (n=3), or non-neoplastic polyp (n=2). Positive predictive values were 25% in the diffuse group and 47% in the focal group. CONCLUSIONS: We recommend that patients showing benign FDG uptake in the colon should be further evaluated by colonoscopy, especially for patients with focal FDG uptake.

Evaluation of Multiple System Atrophy and Early Parkinson's Disease Using (123)I-FP-CIT SPECT / 핵의학분자영상

PURPOSE: We investigated quantification of dopaminergic transporter (DAT) and serotonergic transporter (SERT) on (123)I-FP-CIT SPECT for differentiating between multiple systemic atrophy (MSA) and idiopathic Parkinson's disease (IPD). MATERIALS AND METHODS: N-fluoropropyl-2beta-carbomethoxy-3beta-4-[(123)I]-iodophenylnortropane SPECT ((123)I-FP-CIT SPECT) was performed in 8 patients with MSA (mean age: 64.0+/-4.5yrs, m:f=6:2), 13 with early IPD (mean age: 65.5+/-5.3yrs, m:f=9:4), and 12 healthy controls (mean age: 63.3+/-5.7yrs, m:f=8:4). Standard regions of interests (ROIs) of striatum to evaluate DAT, and hypothalamus and midbrain for SERT were drawn on standard template images and applied to each image taken 4 hours after radiotracer injection. Striatal specific binding for DAT and hypothalamic and midbrain specific binding for SERT were calculated using region/reference ratio based on the transient equilibrium method. Group differences were tested using ANOVA with the postHoc analysis. RESULTS: DAT in the whole striatum and striatal subregions were significantly decreased in both patient groups with MSA and early IPD, compared with healthy control (p<0.05 in all). In early IPD, a significant increase in the uptake ratio in anterior and posterior putamen and a trend of increase in caudate to putamen ratio was observed. In MSA, the decrease of DAT was accompanied with no difference in the striatal uptake pattern compared with healthy controls. Regarding the brain regions where (123)I-FP-CIT binding was predominant by SERT, MSA patients showed a decrease in the binding of (123)I-FP-CIT in the pons compared with controls as well as early IPD patients (MSA: 0.22+/-0.1 healthy controls: 0.33+/-0.19, IPD: 0.29+/-0.19), however, it did not reach the statistical significance. CONCLUSION: In this study, the differential patterns in the reduction of DAT in the striatum and the reduction of pontine (123)I- FP-CIT binding predominant by SERT could be observed in MSA patients on (123)I- FP-CIT SPECT. We suggest that the quantification of SERT as well as DAT using (123)I- FP-CIT SPECT is helpful to differentiate parkinsonian disorders in early stage.

The Discriminating Nature of Dopamine Transporter Image in Parkinsonism: The Competency of Dopaminergic Transporter Imaging in Differential Diagnosis of Parkinsonism: 123I-FP-CIT SPECT Study / 핵의학분자영상

PURPOSE: The aim of this study was to evaluate the discriminating nature of 123I-FP-CIT SPECT in patients with parkinsonism. METHODS: 123I-FP-CIT SPECT images acquired from the 18 normal controls; NC (60.4+/-10.0 yr) and 237 patients with parkinsonism (65.9+/-9.2 yr) were analyzed. From spatially normalized images, regional counts of the caudate, putamen, and occipital lobe were obtained using region of interest method. Binding potential (BP) was calculated with the ratio of specific to nonspecific binding activity at equilibrium. Additionally, the BP ratio of putamen to caudate (PCR) and asymmetric index (ASI) were measured. RESULTS: BPs of NC (3.37+/-0.57, 3.10+/-0.41, 3.23+/-0.48 for caudate, putamen, whole striatum, respectively) had no significant difference with those of essential tremor; ET (3.31+/-0.64, 3.06+/-0.61, 3.14+/-0.63) and Alzheimer's disease; AD (3.33+/-0.60, 3.29+/-0.79, 3.31+/-0.70), but were higher than those of Parkinson's disease; PD (1.92+/-0.74,1.39+/-0.68, 1.64+/-0.68), multiple system atrophy; MSA (2.36+/-1.07, 2.16+/-0.91, 2.26+/-0.96), and dementia with Lewy body; DLB (1.95+/-0.72, 1.64+/-0.65, 1.79+/-0.66)(p<0.005). PD had statistically lower values of PCR and higher values of ASI than those of NC (p<0.005). And PD had significantly lower value of PCR, higher ASI and lower BP in the putamen and whole striatum than MSA (p<0.05). CONCLUSION: Dopamine transporter image of 123I-FP-CIT SPECT was a good value in differential diagnosis of parkinsonism.

The Discriminating Nature of Dopamine Transporter Image in Parkinsonism: The Competency of Dopaminergic Transporter Imaging in Differential Diagnosis of Parkinsonism: 123I-FP-CIT SPECT Study / 핵의학분자영상

PURPOSE: The aim of this study was to evaluate the discriminating nature of 123I-FP-CIT SPECT in patients with parkinsonism. METHODS: 123I-FP-CIT SPECT images acquired from the 18 normal controls; NC (60.4+/-10.0 yr) and 237 patients with parkinsonism (65.9+/-9.2 yr) were analyzed. From spatially normalized images, regional counts of the caudate, putamen, and occipital lobe were obtained using region of interest method. Binding potential (BP) was calculated with the ratio of specific to nonspecific binding activity at equilibrium. Additionally, the BP ratio of putamen to caudate (PCR) and asymmetric index (ASI) were measured. RESULTS: BPs of NC (3.37+/-0.57, 3.10+/-0.41, 3.23+/-0.48 for caudate, putamen, whole striatum, respectively) had no significant difference with those of essential tremor; ET (3.31+/-0.64, 3.06+/-0.61, 3.14+/-0.63) and Alzheimer's disease; AD (3.33+/-0.60, 3.29+/-0.79, 3.31+/-0.70), but were higher than those of Parkinson's disease; PD (1.92+/-0.74,1.39+/-0.68, 1.64+/-0.68), multiple system atrophy; MSA (2.36+/-1.07, 2.16+/-0.91, 2.26+/-0.96), and dementia with Lewy body; DLB (1.95+/-0.72, 1.64+/-0.65, 1.79+/-0.66)(p<0.005). PD had statistically lower values of PCR and higher values of ASI than those of NC (p<0.005). And PD had significantly lower value of PCR, higher ASI and lower BP in the putamen and whole striatum than MSA (p<0.05). CONCLUSION: Dopamine transporter image of 123I-FP-CIT SPECT was a good value in differential diagnosis of parkinsonism.

Comparison of the Results for Sentinel Lymph Node Mapping in the Breast Cancer Patients using 99mTc-Antimony Trisulfide Colloid, 99mTc-Tin Colloid, and 99mTc-Human Serum Albumin / 핵의학분자영상

PURPOSE: In the breast cancer patient, lymphatic mapping and sentinel lymph node biopsy are the most important procedure for axillary lymph node staging. We aimed to compare the three radiocolloids [99mTc-antimony trisulfide colloid (ASC), 99mTc-tin colloid (TC), and 99mTc-human serum albumin (HSA)] for sentinel lymph node mapping. SUBJECTS AND METHODS: Totally, 397 patients with clinically N0 stage were enrolled. 99mTc-ASC was injected in 202 out of 397 patients, 99mTc-TC was injected in 120 patients, and 99mTc-HSA was injected in the remaining 75 patients. The sentinel lymph nodes were localized by lymphoscintigraphy and selected using intraoperative gamma probe. All sentinel lymph nodes were investigated by intraoperative pathologic consultation. The axillary lymph nodes which were harvested by the lymph node dissection were also investigated. RESULTS: The patients of each group showed similar clinical characteristics. There were no significant differences (p>0.05) in the identification rate of sentinel lymph nodes (IR), false negative rate (FNR), and negative predictive value (NPV). The axillary lymphadenectomy revealed axillary lymph node metastases in those three groups (ASC-33.2%, TC-31.7%, HSA-22.7%). The IR, FNR, and NPV were not significantly different among those groups. CONCLUSION: Those three 99mTc-labeled radiocolloids showed equivalent results in sentinel lymph node mapping of breast cancer.

The Usefulness of F-18 FDG PET to Discriminate between Malignant and benign Nodule in Idiopathic Pulmonary Fibrosis / 핵의학분자영상

PURPOSE: Incidence of lung cancer in patients with idiopathic pulmonary fibrosis (IPF) is known to be higher than that in general population. However, it is difficult to discriminate pulmonary nodule in patients with IPF, because underlying IPF can be expressed as lung nodules. We evaluated the diagnostic performance of FDG PET in discriminating lung nodule in patients with IPF. METHODS: We retrospectively reviewed 28 lung nodules in 16 subjects (age; 67.53+/-9.83, M:F=14:2). Two patients had previous history of malignant cancer (small cell lung cancer and subglottic cancer). The diagnostic criteria on chest CT were size, morphology and serial changes of size. FDG PET was visually interpreted, and maximal SUV was calculated for quantitative analysis. RESULTS: From 28 nodules, 18 nodules were interpreted as benign nodules, 10 nodules as malignant nodules by histopahthology or follow-up chest CT. The sensitivity and specificity of FDG PET were 100% and 94.4%, while those of CT were 70.0% and 44.4%, respectively. Malignant nodule was higher maxSUV than that of benign lung nodules (7.68+/-3.96 vs. 1.22+/-0.65, p<0.001). Inflammatory lesion in underlying IPF was significantly lower maxSUV than that of malignant nodules (1.80+/-0.43, p<0.001). The size of malignant and benign nodule were 23.95+/-10.15 mm and 10.83+/-5.23 mm (p<0.01). CONCLUSION: FDG PET showed superior diagnostic performance to chest CT in differentiating lung nodules in patients with underlying IPF. FDG PET could be used to evaluate suspicious malignant lung nodule detected by chest in patients with IPF.