Seo Young Lee

Surgical Outcome and Prognostic Factors of Cryptogenic Neocortical Epilepsy

Surgical treatment of cryptogenic neocortical epilepsy is challenging. The aim of this study was to evaluate surgical outcomes and to identify possible prognostic factors including the results of various diagnostic tools. Eighty‐nine patients with neocortical epilepsy with normal magnetic resonance imaging (35 patients with frontal lobe epilepsy, 31 with neocortical temporal lobe epilepsy, 11 with occipital lobe epilepsy, 11 with parietal lobe epilepsy, and 1 with multifocal epilepsy) underwent invasive study and focal surgical resection. Patients were observed for at least 2 years after surgery. The localizing values of interictal electroencephalogram (EEG), ictal scalp EEG, interictal 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET), and subtraction ictal single‐photon emission computed tomography were evaluated. Seventy‐one patients (80.0%) had a good surgical outcome (Engel class 1–3); 42 patients were seizure free. Diagnostic sensitivities of interictal EEG, ictal scalp EEG, FDG‐PET, and subtraction ictal single‐photon emission computed tomography were 37.1%, 70.8%, 44.3%, and 41.1%, respectively. Localization by FDG‐PET and interictal EEG was correlated with a seizure‐free outcome. The localizing value of FDG‐PET was greatest in neocortical temporal lobe epilepsy. The focalization of ictal onset and also ictal onset frequency in invasive studies were not related to surgical outcome. Concordance with two or more presurgical evaluations was significantly related to a seizure‐free outcome. Ann Neurol 2005

Prognostic factors in neocortical epilepsy surgery : Multivariate analysis

Summary:  Purpose: Defining prognostic factors for neocortical epilepsy surgery is important for the identification of ideal candidates and for predicting the prognosis of individual patients. We use multivariate analysis to identify favorable prognostic factors for neocortical epilepsy surgery.

Proteomic Analysis of the Anti-Cancer Effect of 20S-Ginsenoside Rg3 in Human Colon Cancer Cell Lines

Ginseng is a well known herbal medicine in Asia, and ginsenoside Rg3 has anti-cancer and various pharmacological effects. In particular, 20S-ginsenoside Rg3 may increase the anti-proliferative effects of chemotherapy. The authors investigated the mechanism of the anti-proliferative effect of 20S-Rg3 at the protein level in HT29 colon cancer cells. MTT, caspase-3 assays, and flow cytometry analysis were performed to determine cytotoxicity and apoptosis, and proteomic analysis was performed by two-dimensional gel electrophoresis and MALDI-TOF/TOF MS, and a database was used to identify protein changes in 20S-Rg3 treated HT29 cells. The proteins identified included down-regulated Rho GDP dissociation inhibitor, up-regulated tropomyosin1, and annexin5 and glutathione s-transferase p1, which are apoptosis associated proteins. The anti-proliferative mechanism of 20S-Rg3 was found to be involved in mitotic inhibition, DNA replication, and repair and growth factor signaling. The findings of this study suggest that the cytotoxicity of 20S-Rg3 in colon cancer is dependent on several mechanisms, including apoptosis.

Processed Vietnamese ginseng: Preliminary results in chemistry and biological activity

Background This study was carried out to investigate the effect of the steaming process on chemical constituents, free radical scavenging activity, and antiproliferative effect of Vietnamese ginseng. Methods Samples of powdered Vietnamese ginseng were steamed at 120°C for various times and their extracts were subjected to chemical and biological studies. Results Upon steaming, contents of polar ginsenosides, such as Rb1, Rc, Rd, Re, and Rg1, were rapidly decreased, whereas less polar ginsenosides such as Rg3, Rg5, Rk1, Rk3, and Rh4 were increased as reported previously. However, ocotillol type saponins, which have no glycosyl moiety at the C-20 position, were relatively stable on steaming. The radical scavenging activity was increased continuously up to 20 h of steaming. Similarly, the antiproliferative activity against A549 lung cancer cells was also increased. Conclusion It seems that the antiproliferative activity is closely related to the contents of ginsenoside Rg3, Rg5, and Rk1.

Processed Panax ginseng, Sun Ginseng, Decreases Oxidative Damage Induced by tert-butyl Hydroperoxide via Regulation of Antioxidant Enzyme and Anti-apoptotic Molecules in HepG2 Cells

Potential antioxidant effect of processed ginseng (sun ginseng, SG) on oxidative stress generated by tert-butyl hydroperoxide (t-BHP) was investigated in HepG2 cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and lactate dehydrogenase (LDH) leakage test demonstrated that SG dose-dependently prevents a loss of cell viability against t-BHP-induced oxidative stress. Also, SG treatment dose-dependently relieved the increment of activities of hepatic enzymes, such as aspartate aminotrasferase and alanine aminotransferase, and lipid peroxidation mediated by t-BHP treatment in HepG2 cells. SG increased the gene expression of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. However, high dose of SG treatment caused decrease in mRNA level of glutathione peroxidase as compared to low dosage of SG-treated cells. The gene expression of glutathione reductase was found to be slightly increased by SG treatment. In addition, SG extract attributed its hepaprotective effect by inducing the mRNA level of bcl-2 and bcl-xL but reducing that of bax. But, the gene expression of bad showed no significant change in SG-treated HepG2 cells. These findings suggest that SG has hepatoprotective effect by showing reduction of LDH release, activities of hepatic enzymes and lipid peroxidation and regulating the gene expression of antioxidant enzymes and apoptosis-related molecules against oxdative stress caused by t-BHP in HepG2 cells.

Effects of steaming on saponin compositions and antiproliferative activity of Vietnamese ginseng

Background Steaming of ginseng is known to change its chemical composition and biological activity. This study was carried out to investigate the effect of different steaming time-scales on chemical constituents and antiproliferative activity of Vietnamese ginseng (VG). Methods VG was steamed at 105°C for 2–20 h. Its saponin constituents and antiproliferative activity were studied. The similarity of chemical compositions between steamed samples at 105°C and 120°C were compared. Results Most protopanaxadiol and protopanaxatriol ginsenosides lost the sugar moiety at the C-20 position with 10–14 h steaming at 105°C and changed to their less polar analogues. However, ocotillol (OCT) ginsenosides were reasonably stable to steaming process. Antiproliferative activity against A549 lung cancer cells was increased on steaming and reached its plateau after 12 h steaming. Conclusion Steaming VG at 105°C showed a similar tendency of chemical degradation to the steaming VG at 120°C except the slower rate of reaction. Its rate was about one-third of the steaming at 120°C.

Optimal follow-up strategies for adrenal incidentalomas: reappraisal of the 2016 ESE-ENSAT guidelines in real clinical practice

OBJECTIVE Recently, the European Society of Endocrinology (ESE), in collaboration with the European Network for the Study of Adrenal Tumors (ENSAT), asserted that adrenal incidentalomas (AIs) <4 cm and ≤10 Hounsfield units (HU) do not require further follow-up imaging. To validate the clinical application of the follow-up strategies suggested by the 2016 ESE-ENSAT guidelines, we explored the clinical characteristics and natural course of AIs in a single center over 13 years. DESIGN AND METHODS This retrospective cohort study included a total of 1149 patients diagnosed with AIs between 2000 and 2013 in a single tertiary center. Hormonal examination and radiological evaluations were performed at the initial diagnosis of AI and during the follow-up according to the appropriate guidelines. RESULTS The mean age at diagnosis was 54.2 years, and the majority of AIs (68.0%) were nonfunctional lesions. Receiver operating curve analysis was used to discriminate malignant from benign lesions; the optimal cut-off value for mass size was 3.4 cm (sensitivity: 100%; specificity: 95.0%), and that for the pre-contrast HU was 19.9 (sensitivity: 100%; specificity: 67.4%). The majority of nonfunctional lesions did not change in size during the 4-year follow-up period. Applying a cut-off value of 1.8 μg/dL after a 1-mg overnight dexamethasone suppression test, 28.0% of all nonfunctional AIs progressed to autonomous cortisol secretion during the follow-up period. However, we observed no development of overt Cushings syndrome in the study. CONCLUSIONS We advocate that no follow-up imaging is required if the detected adrenal mass is <4 cm and has clear benign features. However, prospective studies with longer follow-up are needed to confirm the appropriate follow-up strategies.

Anti-programmed cell death 1 therapy triggering diabetic ketoacidosis and fulminant type 1 diabetes.

Programmed cell death 1 (PD-1) is a co-inhibitory molecule expressed on effector T cells and is involved in regulation of immune checkpoints. One of the known ligands of PD-1 protein is programmed cell death ligand 1 (PDL1), which is expressed in many tumor cells. Activation of PD-1/PDL-1 axis results in suppression of anti-tumor immune checkpoints. Pembrolizumab is an immunoglobulin G4 monoclonal antibody targeting PD-1 molecule that increases immune response and induces anti-tumor activity. It has been approved for treating metastatic melanoma and is currently on clinical investigation for several other tumors including non-small cell lung cancer. On the other hand, PD-1 or PDL-1 blockade induced type 1 diabetes mellitus (T1DM) in non-obese prediabetic mice regardless of age [1]. In humans, few case reports of anti-PD-1 therapy induced T1DM have been reported including one case of fulminant T1DM [2, 3]. Here, we described a case of new-onset fulminant T1DM after anti-PD-1 therapy along with measures of glucose and C-peptide levels before and after the therapy. Case report

The efficacy of medical treatment in patients with acromegaly in clinical practice

Although somatostatin analogues (SSAs) are recommended as the first-line medical therapy for acromegaly, dopamine agonists (DAs) are also a therapeutic option for treatment. We aimed to assess and compare the efficacies of DAs and SSAs in treating acromegaly in clinical practice. We included 89 patients with acromegaly who took DAs (bromocriptine [BCT], n = 63; cabergoline [CAB], n = 11) or SSAs (n = 15) as a primary medical therapy for more than 3 months in the Seoul National University Hospital. The CAB (45.5%) and SSA (33.3%) groups achieved random GH levels of <2.5 ng/mL and the normal IGF-1 levels were significantly higher than in the BCT group (11.1%) (p = 0.009). We further included all the patients with acromegaly (n = 132) who had taken CAB, BCT, and SSAs as first- or second-line medical therapy. The CAB group showed similar efficacy as the SSA group in terms of the GH and insulin-like growth factor-1 (IGF-1) levels (57.6% for random GH level <2.5 ng/mL, 42.4% for normal IGF-1 levels, 36.4% for both). Logistic regression analysis revealed that medications, age, GH level, or IGF-1 level before medication, hyperprolactinemia, and prior gamma-knife surgery or radiation therapy, did not affect the therapeutic response. High pretreatment GH levels predicted poor treatment outcomes (odds ratio [95% confidence interval] = 0.95 [0.90-0.99]). CAB was effective in treating acromegaly at a relatively lower cost in patients with low pretreatment GH levels.

Depression and Mortality in Type 2 Diabetes Mellitus

Corresponding author: Sung Hee Choi https://orcid.org/0000-0003-0740-8116 Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro 173beon-gil, Bundang-gu, Seongnam 13620, Korea E-mail: shchoimd@gmail.com There has been increasing evidence about the linkage between depression and type 2 diabetes mellitus (T2DM). One of the risk factors for major depressive disorder (MDD) includes chronic or disabling medical conditions such as diabetes [1]. However from previous studies, the relationship and influence between diabetes and depression seems to be bidirectional. Previous study in a prospective design showed that MDD predicted the onset of diabetes after controlling for age, sex, race, socioeconomic status, and body weight [2]. On the contrary, a meta-analysis revealed that patients with T2DM had 24% increased risk of depression compared to non-diabetic controls [3]. The linking mechanism between diabetes and depression seems to be originated from its shared etiology. Patterson et al. [4] reported that a mouse which was exposed to a social defeat paradigm had increased ghrelin and insulin secretion, which increases appetite and fat accumulations, consequently leads to dysregulation of glucose metabolism and weight gain. Additionally, both depression and diabetes seemed to be related with hypothalamic-pituitary-adrenal (HPA) axis, which also controls the cortisol excretion [5]. Along with changes in endocrine system, some researchers revealed that both diseases are associated with the change of neurological system. The hippocampus of the limbic system in brain which has anatomically linked with HPA axis, has main role in controlling memory and emotion. The hippocampus has shown to be deficient in rodent models with depressive symptoms of anhedonia, food avoidance, and immobility [6]. Similarly, T2DM rodents exhibited decreased neurogenesis in the hippocampus [7]. In addition, some researchers suggested that the comorbid diabetes and depression seemed to have additive effect on the rate of mortality. Since patients with MDD had general characteristics that poor self-care, lack of medication compliance, not caring about their diet and exercise [8], the patients with depressed T2DM resulted in increased diabetic complications and higher mortality. Jeong et al. [9] retrospectively showed that the annual prevalence of depression was higher in T2DM and higher morality was shown in the depressed subjects from the nationwide health insurance service database in Korea. It was the first longitudinal data from Koreans, and the findings are consistent with the previous results that patients with depressed symptoms showed increased mortality in patients with diabetes mellitus. Especially they revealed that the younger age groups and male had higher mortality compared to other subgroups. These findings could be related with more distressing state of younger age patients with diabetic complications. However, accurate statistical analysis considering the presence of diabetic complications or the cause of death was not performed; thus, we could not assume the direct causality only based on the result of this study. Additionally, they could not adjust wellknown confounding factors relating to mortality in patients with diabetes due to the limitation of national insurance database itself. Further study should be needed in prospective, large number cohorts is needed to confirm this results and the clear association to increasing mortality in patients with diabetes and depression. Especially, obesity and metabolic syndrome had Editorial Epidemiology