• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 제4회 추계심포지움
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• pp.171-172
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• 1996

Cocaine is a powerful reinforcer that has become a popular drug of abuse in man. CNS effects that are related to the abuse of cocaine include feeling of well-being and euphoria. Brain dopamine systems are thought to mediate reinforcement and it is often assumed that cocaine's inhibition of dopamine uptake is the mechanism underlying its reinforcing effects. With increase in cocaine use among general population in recent years, adverse effects of the drug have occurred in all social strata and age groups. Therefore, it has been recognized that the epidemic of cocaine abuse is a growing major concerning public health. One of the most troubling aspects of cocaine abuse is its use by pregnant women. Drug abuse during pregnancy puts two lives at risk. Cocaine produces toxic effects on the fetus at concerntrations that are apparently nontoxic to the mother. Not only does cocaine cross the placenta via diffusion and via rapid penetration to mucous membranes, due to its high lipid solubility, but cocaine can also be found in breast milk, the effects of the cocaine can persist long after the child is born. Although it is known that prenatal cocaine exposure is associated with developmental risk to the fetus ana newborn, few studies have been conducted to assess the mechanisms whereby either short-term or long-term administration of cocaine can exert its harmful effects on the mother or the child. Therefore, it was our great interest to investigate the pharmacological and neurobehavioral changes in offspring that are prenatally exposed to cocaine.

• 대한핵의학회지
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• 제32권1호
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• pp.10-19
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• 1998

The SPECT radiopharmaceuticals labeled with I-123 for dopamine transporter imaging have been used to measure dopamine transporters in patients with movement disorders. However, a cyclotron produced I-123 limits its availiability and ease of use as a radioisotope to be labeled with pharmaceuticals in routine clinical diagnostic procedures. Recently, new radiophannaceuticals for Tc-99m which has optimal characteristic for SPECT imaging have been developed to overcome the limits of using I-123. The purpose of this study was to compare the quality of [Tc-99m]TRODAT-1 with [I-123]IPT SPECT data and then to evaluate the usefulness of [Tc-99m]TRODAT-1 SPECT by using three noninvasive simplified quantitative methods. TRODAT-1 labeled with Tc-99m($15.93{\pm}0.82mCi$) and IPT labeled with I-123($6.60{\pm}0.11mCi$) were injected into five normal controls. Dynamic [Tc-99m]TRODAT-1 SPECT scans of brain were performed for 10 minutes each over 180 minnutes, and for 20 minutes at 4 hrs and 5 hrs. [I-123]IPT SPECT scans were performed for 5 minutes each over 120 minutes. Time activity curves were generated for the left basal ganglia(LBG), right basal ganglia(RBG), and occipital cortex(OCC). Dopamine transporter parameters were ohtained using (BG-OCC)/OCC, graphical method($R_V$), and area ratio method($R_A$). TRODAT-1 and IPT SPECT imaging showed high uptake at the level of the basal ganglia. (BG-OCC)/OCC ratios for TRODAT-1 and IPT were $0.80{\pm}0.14$, and $3.22{\pm}0.81$, $R_Vs$ were $0.62{\pm}0.12$, and $2.30{\pm}0.35$, and $R_As$ were $0.37{\pm}0.08$ and $1.73{\pm}0.31$, respectively. In conclusion, further improvement of [Tc-99m]TRODAT-1 imaging characteristics may be required to estimate the dopamine transporter concentrations in human brains although it shows clear BG localization.

• Journal of Korean Neurosurgical Society
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• 제30권3호
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• pp.342-348
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• 2001

Objective : Dopamine transporter concentrations have been known to decrease in Parkinson's disease(PD). The aim of the present study was to evaluate the correlation between SPECT measurements of [I-123]N-(3-iodopropene-2-yl)-$2{\beta}$-carbomethoxy-$3{\beta}$-(4-chlorophenyl) tropane(IPT) as an imaging agent for measuring changes in transporter concentrations with PD. Patients and Methods : IPT labelled with $4.87{\pm}1.29mCi$($180.19{\pm}47.73MBq$) of [I-123] was intravenously injected into 23 patients(age : $58{\pm}12$) with PD and three normal controls(NC)(age : $37{\pm}7$) as bolus. Brain SPECT were then performed at 1 hour and 2 hours after injection on a double headed camera. The statistical parameters were the contrast ratio of left basal ganglia(BG) and right basal ganglia to occipital cortex(OCC) per milli curies of injected radiotracer at 1 hour and 2 hours. The correlations were evaluated between these parameters and Hoehn-Yahr classification of the patients. Results : The(BG - OCC)/OCC/mCi ratios at 1 hour and 2 hours for PD and NC were $0.14{\pm}0.07$ and $0.27{\pm}0.07$(1 hour) and $0.12{\pm}0.07$ and $0.34{\pm}0.04$(2 hour), respectively. The(BG - OCC)/OCC/mCi ratios of Parkinson's disease were decreased with higher grade of Hoehn-Yahr classification of the patients. The ratio between BG and OCC for PD were clearly separated from NC and may be useful outcome measures for clinical diagnosis. Conclusion : The findings suggest that IPT may be a very useful tracer for early diagnosis and treatment of PD and study of dopamine re-uptake site.

• 대한핵의학회지
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• 제30권1호
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• pp.35-46
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• 1996

Dopamine transporter concentrations have been known to decrease in Parkinson's disease (PD) or increase in Tourette's disorder. The purpose of this study was to evaluate the effectiveness of [I-123]N-(3-iodopropene-2-yl)-$2{\beta}$-carbomethoxy-$3{\beta}$-(4-chlorophenyl) tropane (IPT) as an imaging agent for measuring changes in transporter concentrations with PD. IPT labelled with 6.69+/-0.64 mCi(247.53+/-23.68 MBq) of I-123 was intravenously injected into ten patients(age: 55+/-11) with PD, and six normal controls(NC)(age: 46+/-14) as a bolus. Dynamic SPECT scans of the brain were then performed for 5 minutes each over 120 minutes on a triple headed camera. Time activity curves were generated for the left basal ganglia(LBG), right basal ganglia(RBC), and occipital cortex(OCC). The statistical parameters included the time to peak activity, the contrast ratio of LBG and RBG to OCC at several time points, and the accumulated specific binding counts/mCi/pixel(ASBC) from 0 to 115 minutes. The uptake of IPT in the brains of PD and NC peaked within 10 minutes of injection in all subjects. The maximum target to background ratio in the basal ganglia of PD and NC occurred at 85+/-20 min and 110+/-6 min of injection, respectively. The BG/OCC ratios at 115 minutes for PD and NC were 2.15+/-0.54 and 4.26+/-0.73, respectively. The ASBC at 115 minutes for PD and NC were 152.91+/-50.09 and 289.51+/-49.00, respectively. The ratio of BG/OCC for the NC was significantly higher than the ratio for PD. SPECT data matched with clinical diagnosis for PDs. The ratio between BG and OCC and the ASBC for PD were clearly separated from NC and may be useful outcome measures for clinical diagnosis. The findings suggest that IPT may be a very useful tracer for early diagnosis of PD and study of dopamine reuptake site.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.88-93
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• 1994

The mechanisms controlling the intensity and duration of synaptic transmission are numerous. Once an action potential reaches a nerve terminal, the stored neurotransmitters are released in a quantum fashion into the synaptic cleft. At that point neurotransmitters can act on post-synaptic receptors to elicit an action on the post-synaptic cell or net at so-called auto-receptors that are located on the presynaptic side and which often regulate the further release of the neutotransmitter. Whereas the action of the neurotransmitter receptors is regulated by desensitization phenomenon, the major mechanism by which the intensity and duration of neurotransmitter action is presumably regulated by either its degradation or its removal from the synaptic cleft. In the central nervous system, specialized proteins located in fe plasma membrane of presynaptic terminals function to rapidly remove neurotransmitters from the synaptic cleft in a sodium chloride-dependent fashion. These proteins have been referred to as uptake sites or neurotransmitter transporters. Once taken up by the plasma membrane transporters, neurotransmitters are repackaged into secretory vesicles by distinct transporters which depend on a proton gradient.

• Nuclear Medicine and Molecular Imaging
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• 제42권sup1호
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• pp.177-180
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• 2008

Parkinson's disease is the second most common neurodegenerative disorder. It is slowly progressive disease that affects a small area of cells in the mid brain known as the substantia nigra. Gradual degeneration of these cells causes a reduction in a vital chemical known as dopamine. In the diagnosis of Parkinson's disease, it has difficulty in biopsy and limits in radiologic modalities. $^{18}F-FDG$ PET shows various findings from normal to diffuse decrement of FDG uptake. $^{18}F-FDG$ PET is expected to be a evaluation tool in the treatment of Parkinson's disease.

• 생명과학회지
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• 제19권9호
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• pp.1232-1238
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• 2009

신경전달물질의 분비는 시냅스전 신경말단의 active zone에 있는 다양한 단백질들에 의해 조절된다. 도파민은 정신분열병, 약물중독과 같은 여러 가지 행동, 정신질환의 병태생리와 연관된 필수적인 신경전달물질이다. 저자들은 본 연구에서 신경 전달물질 분비와 관련된 주요 유전자가 결여 된 knockout (KO) 생쥐의 시냅토좀(synaptosome) 도파민 분비를 측정하였다. 시냅토좀 도파민 흡수와 분비는 [$^3H$]-도파민과 관류실험을 이용하여 시행, 측정하였다. 17 KO 생쥐 가운데 3 종류의 생쥐에서 그들의 littermate 대조군과 비교하였을 때 변화된 도파민 분비를 보였다. $Rim1{\alpha}$ KO에서 세포막 탈분극에 의한 [$^3H$]-도파민은 유의하게 감소되었으며, 또한 $Rim1{\alpha}$의 도파민 신경에서의 조건 KO에서는 생리적 완충용액에 의한 기본적인 도파민 분비 및 세포막 탈분극에 의한 도파민 분비 모두가 유의하게 감소되어 있었다. neurexin3의 도파민 신경에서의 조건 KO에서는 세포막 탈분극에 의한 도파민 분비의 증가를 보였다. 이 데이터들은 도파민 분비와 글루타메이트, GABA와 같은 전통적 신경전달물질 분비의 유사성과 차별성을 설명한다. 결론적으로, $Rim1{\alpha}$와 neurexin3는 시냅스전 도파민 분비의 중요한 조절자이며 신경계 질환과 연관될 가능성이 있다.

• BMB Reports
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• 제50권1호
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• pp.31-36
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• 2017

High-dose caffeine uptake is a developmental stressor and causes food-avoidance behavior (aversion phenotype) in C. elegans, but its mode of action is largely unknown. In this study, we investigated the molecular basis of the caffeine-induced aversion behavior in C. elegans. We found that aversion phenotype induced by 30 mM caffeine was mediated by JNK/MAPK pathway, serotonergic and dopaminergic neuroendocrine signals. In this process, the dopaminergic signaling appears to be the major pathway because the reduced aversion behavior in cat-2 mutants and mutants of JNK/MAPK pathway genes was significantly recovered by pretreatment with dopamine. RNAi depletion of hsp-16.2, a cytosolic chaperone, and cyp-35A family reduced the aversion phenotype, which was further reduced in cat-2 mutants, suggesting that dopaminergic signal is indeed dominantly required for the caffeine-induced food aversion. Our findings suggest that aversion behavior is a defense mechanism for worms to survive under the high-dose caffeine conditions.

• 대한불안의학회지
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• 제19권2호
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• pp.56-60
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• 2023

Progressive supranuclear palsy (PSP) is rare atypical Parkinsonism accompanied by various psycho-behavioural problems. In this case report, we describe the diagnostic and treatment progress of a 65-year-old PSP patient who visited the psychiatric clinic with a depressed mood and lumbar pain resulting in a suicide attempt. Over the course of 30 months of treatment, typical characteristics of PSP, such as postural instability, dyskinesia, cognitive dysfunction and supranuclear gaze palsy, became prominent, and magnetic resonance imaging and the F-18 FP-CIT positron emission tomography revealed midbrain atrophy and reduced dopamine uptake in the basal ganglia. When treating elderly patients with depression, parkinsonism symptoms such as gait disturbances, frequent falls, tremors, and rigidity should be closely examined.

• Journal of Yeungnam Medical Science
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• 제40권4호
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• pp.435-441
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• 2023

Pheochromocytomas and paragangliomas (PPGLs) may secrete hormones or bioactive neuropeptides such as interleukin-6 (IL-6), which can mask the clinical manifestations of catecholamine hypersecretion. We report the case of a patient with delayed diagnosis of paraganglioma due to the development of IL-6-mediated systemic inflammatory response syndrome (SIRS). A 58-year-old woman presented with dyspnea and flank pain accompanied by SIRS and acute cardiac, kidney, and liver injuries. A left paravertebral mass was incidentally observed on abdominal computed tomography (CT). Biochemical tests revealed increased 24-hour urinary metanephrine (2.12 mg/day), plasma norepinephrine (1,588 pg/mL), plasma normetanephrine (2.27 nmol/L), and IL-6 (16.5 pg/mL) levels. ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/CT showed increased uptake of FDG in the left paravertebral mass without metastases. The patient was finally diagnosed with functional paraganglioma crisis. The precipitating factor was unclear, but phendimetrazine tartrate, a norepinephrine-dopamine release drug that the patient regularly took, might have stimulated the paraganglioma. The patient's body temperature and blood pressure were well controlled after alpha-blocker administration, and the retroperitoneal mass was surgically resected successfully. After surgery, the patient's inflammatory, cardiac, renal, and hepatic biomarkers and catecholamine levels improved. In conclusion, our report emphasizes the importance of IL-6-producing PPGLs in the differential diagnosis of SIRS.