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2.  Effects of dextromethorphan on MDMA-induced serotonergic aberration in the brains of non-human primates using [123I]-ADAM/SPECT 
Scientific Reports  2016;6:38695.
3,4-Methylenedioxymethamphetamine (MDMA), a common recreational drug, is known to cause serotonergic neurotoxicity in the brain. Dextromethorphan (DM) is a widely used antitussive reported to exert anti-inflammatory effect in vivo. In this study, we examined the long-term effect of MDMA on the primate serotonergic system and the protective property of DM against MDMA-induced serotonergic abnormality using single photon emission computed tomography (SPECT). Nine monkeys (Macaca cyclopis) were divided into three groups, namely control, MDMA and co-treatment (MDMA/DM). [123I]-ADAM was used as the radioligand for serotonin transporters (SERT) in SPECT scans. SERT levels of the brain were evaluated and presented as the uptake ratios (URs) of [123I]-ADAM in several regions of interest of the brain including midbrain, thalamus and striatum. We found that the URs of [123I]-ADAM were significantly lower in the brains of MDMA than control group, indicating lower brain SERT levels in the MDMA-treated monkeys. This MDMA-induced decrease in brain SERT levels could persist for over four years. However, the loss of brain SERT levels was not observed in co-treatment group. These results suggest that DM may exert a protective effect against MDMA-induced serotonergic toxicity in the brains of the non-human primate.
doi:10.1038/srep38695
PMCID: PMC5150522  PMID: 27941910
3.  Effect of MDMA-Induced Axotomy on the Dorsal Raphe Forebrain Tract in Rats: An In Vivo Manganese-Enhanced Magnetic Resonance Imaging Study 
PLoS ONE  2015;10(9):e0138431.
3,4-Methylenedioxymethamphetamine (MDMA), also known as “Ecstasy”, is a common recreational drug of abuse. Several previous studies have attributed the central serotonergic neurotoxicity of MDMA to distal axotomy, since only fine serotonergic axons ascending from the raphe nucleus are lost without apparent damage to their cell bodies. However, this axotomy has never been visualized directly in vivo. The present study examined the axonal integrity of the efferent projections from the midbrain raphe nucleus after MDMA exposure using in vivo manganese-enhanced magnetic resonance imaging (MEMRI). Rats were injected subcutaneously six times with MDMA (5 mg/kg) or saline once daily. Eight days after the last injection, manganese ions (Mn2+) were injected stereotactically into the raphe nucleus, and a series of MEMRI images was acquired over a period of 38 h to monitor the evolution of Mn2+-induced signal enhancement across the ventral tegmental area, the medial forebrain bundle (MFB), and the striatum. The MDMA-induced loss of serotonin transporters was clearly evidenced by immunohistological staining consistent with the Mn2+-induced signal enhancement observed across the MFB and striatum. MEMRI successfully revealed the disruption of the serotonergic raphe-striatal projections and the variable effect of MDMA on the kinetics of Mn2+ accumulation in the MFB and striatum.
doi:10.1371/journal.pone.0138431
PMCID: PMC4574734  PMID: 26378923
4.  Added Value of Dual-Time-Point 18F-FDG PET/CT With Delayed Imaging for Detecting Aortic Graft Infection 
Medicine  2015;94(27):e1124.
Abstract
18F-FDG PET/CT is a promising tool in detecting aortic graft infection. Present study investigated the value of dual-time-point 18F-FDG PET/CT imaging (DTPI) with delayed imaging in assessing aortic graft infection.
Twenty-nine patients with suspected aortic graft infection were prospectively enrolled in this DTPI study. Two nuclear medicine physicians read all the images and achieved consensus about the measurement of maximal standardized uptake value (SUVmax) and grading of image quality. The percentages of SUVmax change between initial and delayed images were recorded as retention index (RI); sensitivity, specificity, and accuracy were calculated based on reference standard.
All the 5 infected aortic grafts had positive RIs, which were generally higher than that of noninfected grafts. Those noninfected grafts had variable RIs. Seven patients had improved image quality in delayed imaging. DTPI with delayed image detected all the infected grafts with improved specificity (88%) and accuracy (90%), providing conspicuous delineation of the infected graft extent.
In conclusion, noninfected aortic grafts had more variable RIs than infected ones. DTPI might be useful for detecting aortic graft infection, improving image quality, and enhancing delineation of the infected aortic grafts.
doi:10.1097/MD.0000000000001124
PMCID: PMC4504531  PMID: 26166113
5.  Added Value of Dual-Time-Point 18F-FDG PET/CT With Delayed Imaging for Detecting Aortic Graft Infection 
Medicine  2015;94(27):e1124.
Abstract
18F-FDG PET/CT is a promising tool in detecting aortic graft infection. Present study investigated the value of dual-time-point 18F-FDG PET/CT imaging (DTPI) with delayed imaging in assessing aortic graft infection.
Twenty-nine patients with suspected aortic graft infection were prospectively enrolled in this DTPI study. Two nuclear medicine physicians read all the images and achieved consensus about the measurement of maximal standardized uptake value (SUVmax) and grading of image quality. The percentages of SUVmax change between initial and delayed images were recorded as retention index (RI); sensitivity, specificity, and accuracy were calculated based on reference standard.
All the 5 infected aortic grafts had positive RIs, which were generally higher than that of noninfected grafts. Those noninfected grafts had variable RIs. Seven patients had improved image quality in delayed imaging. DTPI with delayed image detected all the infected grafts with improved specificity (88%) and accuracy (90%), providing conspicuous delineation of the infected graft extent.
In conclusion, noninfected aortic grafts had more variable RIs than infected ones. DTPI might be useful for detecting aortic graft infection, improving image quality, and enhancing delineation of the infected aortic grafts.
doi:10.1097/MD.0000000000001124
PMCID: PMC4504531  PMID: 26166113
6.  Incongruent Reduction of Serotonin Transporter Associated with Suicide Attempts in Patients with Major Depressive Disorder: A Positron Emission Tomography Study with 4-[18F]-ADAM 
Background:
Much evidence supports the role of the serotonin transporter (SERT) in the pathophysiology and pharmacotherapy of major depressive disorder (MDD) and suicidal behaviors.
Methods:
In this study, we recruited 17 antidepressant-naïve patients with MDD and 17 age- and gender-matched healthy controls. SERT availability was measured in vivo with N,N-dimethyl-2-(2-amino-4-[18F]fluorophenylthio)benzylamine (4-[18F]-ADAM) positron emission tomography (PET) imaging. The 21-item Hamilton Depression Rating Scale (HDRS) and Beck Scale for Suicide Ideation were used to assess the severity of depression and the intent of suicide ideation prior to PET imaging. All subjects with MDD were in a current state of depression with HDRS scores ≧18. Subjects who attempted suicide within two weeks of the study onset were recruited in the depressed suicidal group (n = 8). Subjects with MDD who denied any prior suicide attempt were recruited into the depressed non-suicidal group (n = 9).
Results:
A significant reduction of SERT availability in the midbrain, thalamus, and striatum was noted in the MDD group relative to the control group (Bonferroni-adjusted p-value < 0.05). Moreover, this effect was more pronounced in the depressed suicidal group compared to the control group (Bonferroni-adjusted p-value < 0.01). Relative to both the depressed non-suicidal and control groups, the depressed suicidal group showed an increased prefrontal cortex (PFC)/midbrain SERT binding ratio (Bonferroni-adjusted p-value < 0.01).
Conclusions:
This study suggests an incongruent reduction of PFC SERT binding relative to the midbrain might discriminate between depressed suicide attempters and non-attempters in patients with MDD and may be involved in the pathophysiology of suicide behaviors.
doi:10.1093/ijnp/pyu065
PMCID: PMC4360239  PMID: 25522405
4-[18F]-ADAM; major depressive disorder; positron emission tomography; serotonin transporter; suicide
7.  Predictive Value of 18F-FDG PET and CT Morphologic Features for Recurrence in Pathological Stage IA Non-Small Cell Lung Cancer 
Medicine  2015;94(3):e434.
Abstract
Patients with pathological stage IA non-small cell lung cancer (NSCLC) may relapse despite complete surgical resection without lymphovascular invasion. A method of selecting a high-risk group for adjuvant therapy is necessary. The aim of this study was to assess the predictive value of 18F-fluorodeoxyglucose (FDG) uptake and the morphologic features of computed tomography (CT) for recurrence in pathological stage IA NSCLC.
One hundred forty-five patients with pathological stage IA NSCLC who underwent pretreatment with FDG positron emission tomography and CT evaluations were retrospectively enrolled. The associations among tumor recurrence and patient characteristics, maximal standard uptake value (SUVmax) of primary tumors, and CT imaging features were investigated using univariate and multivariate analyses. A receiver operating characteristic (ROC) curve analysis was performed to quantify the predictive value of these factors.
Tumor recurrence developed in 21 (14.5%) of the 145 patients, and the 5-year recurrence-free survival rate was 77%. The univariate analysis demonstrated that SUVmax, the grade of histological differentiation, tumor size, and the presence of bronchovascular bundle thickening were significant predictive factors (P < 0.05). A higher SUVmax (≥2.5) (P = 0.021), a lower ground-glass opacity ratio (≤17%) (P = 0.014), and the presence of bronchovascular bundle thickening (P = 0.003) were independent predictive factors of tumor recurrence in the multivariate analysis. The use of this predictive model yielded a greater area under the ROC curve (0.877), which suggests good discrimination.
The combined evaluation of FDG uptake and CT morphologic features may be helpful in the prediction of recurrence in patients with pathological stage IA NSCLC and in the stratification of a high-risk group for postoperative adjuvant therapy or prospective clinical trials.
doi:10.1097/MD.0000000000000434
PMCID: PMC4602644  PMID: 25621697
8.  Time Sensitivity Factor of Single Pulmonary Nodule: A New Cancer Characteristic Metabolic Parameter by 18F-FDG PET 
BioMed Research International  2014;2014:830135.
Objective. To calculate the time sensitivity factor (S) for discriminating the solitary pulmonary nodule (SPN) by FDG PET at different time points. Methods. The multiple time-point FDG PET images from 41 patients for evaluating SPN seen on chest X-ray or CT were prospectively analyzed to calculate and evaluate S against the gold standard of tissue histology (n = 38) or long term clinicoradiographic follow-up (n = 3). The maximal standardized uptake values (SUV) at the 3 hourly time points were measured. The S was calculated using S = d{ln⁡(SUV)}/d{ln⁡(t)} at 3 different time intervals. ROC analysis of the S parameters was performed to evaluate the optimal cut-off value and their accuracy in classifying the SPN. Results. The SUV in malignant SPN was higher than the corresponding value in benign lesions at all 3 hourly time points (P < 0.003). The S parameters using 3 different time intervals all significantly separated the two groups (P < 0.0005) with an optimal cut-off point near the theoretical value of zero with a high sensitivity of 100% and specificity of 86%. Conclusion. The S can be calculated for SPNs using multiple time-point FDG PET, providing a tumor characteristic metabolic parameter with high discrimination power using a simple positive value representing malignancy.
doi:10.1155/2014/830135
PMCID: PMC4052123  PMID: 24982908
9.  Modulation of formation of the 3’-end of the human argininosuccinate synthetase mRNA by GT-repeat polymorphism 
Microsatellites are abundant in the human genome and may acquire context-dependent functions. A highly polymorphic GT microsatellite is located downstream of the poly(A) signal of the human argininosuccinate synthetase (ASS1) gene. The ASS1 participates in urea and nitric oxide production and is a rate-limiting enzyme in arginine biosynthesis. To examine possible involvement of the GT microsatellite in ASS1 mRNA 3’-end formation, ASS1 minigene constructs were used in transient transfection for assessment of poly(A) site usage by S1 nuclease mapping. Synthesis of the major human ASS1 mRNA is found to be controlled by two consecutive non-canonical poly(A) signals, UAUAAA and AUUAAA, located 7 nucleotides apart where a U-rich sequence and the GU microsatellite serve as their respective downstream GU/U-rich elements. Moreover, AUUAAA utilization is affected by the GU-repeat number possibly leading to differential regulation of ASS1 polyadenylation in individuals with different repeat numbers. Interestingly, the less efficient UAUAAA motif is noted to be the major ASS1 poly(A) signal possibly as a result of an indispensable downstream U-rich element and restricted utilization of the AUUAAA motif by the presence of extended GU-repeats. The UAUAAA motif and the GT microsatellite are conserved only in primates whereas AUUAAA motif is present in all mammals analyzed. The suboptimal UAUAAA motif and the utilization of the polymorphic GT microsatellite as polyadenylation signal of the ASS1 gene may be used as a strategy in primates to modulate ASS1 level in response to interactions of genetic and environmental factors.
PMCID: PMC3867704  PMID: 24380022
Argininosuccinate synthetase 1 (ASS1); GT-repeat polymorphism; microsatellite; polyadenylation signal; poly(A) downstream element; gene regulation
10.  A Comparison of Epithelial Cells, Fibroblasts, and Osteoblasts in Dental Implant Titanium Topographies 
The major challenge for dental implants is achieving optimal esthetic appearance and a concept to fulfill this criterion is evaluated. The key to an esthetically pleasing appearance lies in the properly manage the soft tissue profile around dental implants. A novel implant restoration technique on the surface was proposed as a way to augment both soft- and hard-tissue profiles at potential implant sites. Different levels of roughness can be attained by sandblasting and acid etching, and a tetracalcium phosphate was used to supply the ions. In particular, the early stage attaching and repopulating abilities of bone cell osteoblasts (MC3T3-E1), fibroblasts (NIH 3T3), and epithelial cells (XB-2) were evaluated. The results showed that XB-2 cell adhesive qualities of a smooth surface were better than those of the roughened surfaces, the proliferative properties were reversed. The effects of roughness on the characteristics of 3T3 cells were opposite to the result for XB-2 cells. E1 proliferative ability did not differ with any statistical significance. These results suggest that a rougher surface which provided calcium and phosphate ions have the ability to enhance the proliferation of osteoblast and the inhibition of fibroblast growth that enhance implant success ratios.
doi:10.1155/2012/687291
PMCID: PMC3263600  PMID: 22287942

Results 1-10 (10)