Purpose: Neuroinflammation is considered an important pathway associated with several diseases that result in cognitive decline. 18F-THK5351 positron emission tomography (PET) signals might indicate the presence of neuroinflammation, as well as Alzheimer’s disease-type tau aggregates. β-amyloid (Aβ)-negative (Aβ–) amnestic mild cognitive impairment (aMCI) may be associated with non-Alzheimer’s disease pathophysiology. Accordingly, we investigated associations between 18F-THK5351 PET positivity and cognitive decline among Aβ– aMCI patients. Materials and Methods: The present study included 25 amyloid PET negative aMCI patients who underwent a minimum of two follow-up neuropsychological evaluations, including clinical dementia rating-sum of boxes (CDR-SOB). The patients were classified into two groups: 18F-THK5351-positive and -negative groups. The present study used a linear mixed effects model to estimate the effects of 18F-THK5351 PET positivity on cognitive prognosis among Aβ– aMCI patients. Results: Among the 25 Aβ– aMCI patients, 10 (40.0%) were 18F-THK5351 positive. The patients in the 18F-THK5351-positive group were older than those in the 18F-THK5351-negative group (77.4±2.2 years vs. 70.0±5.5 years; p<0.001). There was no difference between the two groups with regard to the proportion of apolipoprotein E ε4 carriers. Interestingly, however, the CDR-SOB scores of the 18F-THK5351-positive group deteriorated at a faster rate than those of the 18F-THK5351-negative group (B=0.003, p=0.033). Conclusion The results of the present study suggest that increased 18F-THK5351 uptake might be a useful predictor of poor prognosis among Aβ– aMCI patients, which might be associated with increased neuroinflammation (ClinicalTrials.gov NCT02656498).

The KOrean College of Rheumatology BIOlogics and targeted therapy (KOBIO) registry is a nationwide observational cohort that captures detailed data on exposure of patients to biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs). This registry was launched in December 2012 with an aim to prospectively investigate clinical manifestations and outcomes of patients with rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis who initiated a biologic or targeted synthetic DMARD or switched to another. Demographic data, disease activity, current treatment, adverse events, terms based on Medical Dictionary for Regulatory Activities, and so on are registered for patients who are then followed up annually in a web-based unified platform. The KOBIO registry also recruits and collects data of patients with RA on conventional DMARDs for comparison. As of today, more than 5,500 patients were enrolled from 47 academic and community Rheumatology centers across Korea. The KOBIO registry has evolved to become a powerful database for clinical research to improve clinical outcomes and quality of treatment.

The KOrean College of Rheumatology BIOlogics and targeted therapy (KOBIO) registry is a nationwide observational cohort that captures detailed data on exposure of patients to biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs). This registry was launched in December 2012 with an aim to prospectively investigate clinical manifestations and outcomes of patients with rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis who initiated a biologic or targeted synthetic DMARD or switched to another. Demographic data, disease activity, current treatment, adverse events, terms based on Medical Dictionary for Regulatory Activities, and so on are registered for patients who are then followed up annually in a web-based unified platform. The KOBIO registry also recruits and collects data of patients with RA on conventional DMARDs for comparison. As of today, more than 5,500 patients were enrolled from 47 academic and community Rheumatology centers across Korea. The KOBIO registry has evolved to become a powerful database for clinical research to improve clinical outcomes and quality of treatment.

BACKGROUND/OBJECTIVES: Premenstrual syndrome (PMS) is a disorder characterized by repeated emotional, behavioral, and physical symptoms before menstruation, and the exact cause and mechanism are uncertain. Hyperprolactinemia interferes with the normal production of estrogen and progesterone, leading to PMS symptoms. Thus, we judged that the inhibition of prolactin hypersecretion could mitigate PMS symptoms.MATERIALS/METHODS: Hordeum vulgare L. extract (HVE), Chrysanthemum zawadskii var. latilobum extract (CZE), and Lomens-P0 the mixture of these extracts were tested in subsequent experiments. The effect of extracts on prolactin secretion at the in vitro level was measured in GH3 cells. Nitric oxide and pro-inflammatory mediator expression were measured in RAW 264.7 cells to confirm the anti-inflammatory effect. Also, the hyperprolactinemic Institute for Cancer Research (ICR) mice model was used to measure extract effects on prolactin and hormone secretion and uterine inflammation. RESULTS: Anti-inflammatory effects of and prolactin secretion suppress by HVE and CZE were confirmed through in vitro experiments (P < 0.05). Treatment with Lomens-P0 inhibited prolactin secretion (P < 0.05) and restored normal sex hormone secretion in the hyperprolactinemia mice model. In addition, extracts significantly inhibited the expression of pro-inflammatory biomarkers, including interleukin-1β, and -6, tumor necrosis factor-α, inducible nitric oxide synthase, and cyclooxygenase-2 (P < 0.01). We used high-performance liquid chromatography analyses to identify tricin and chlorogenic acid as the respective components of HVE and CZE that inhibit prolactin secretion. The Lomens-P0, which includes tricin and chlorogenic acid, is expected to be effective in improving PMS symptoms in the human body. CONCLUSIONS The Lomens-P0 suppressed the prolactin secretion in hyperprolactinemia mice, normalized the sex hormone imbalance, and significantly suppressed the expression of inflammatory markers in uterine tissue. This study suggests that Lomens-P0 may have the potential to prevent or remedy materials to PMS symptoms.

The short release half-life of carbon monoxide (CO) is a major obstacle to the effective therapeutic use of carbon monoxide-releasing molecule-2 (CORM-2). The potential of CORM-2-entrapped ultradeformable liposomes (CORM-2-UDLs) to enhance the release half-life of CO and alleviate skin inflammation was investigated in the present study. CORM-2-UDLs were prepared by using soy phosphatidylcholine to form lipid bilayers and Tween 80 as an edge activator. The deformability of CORM-2-UDLs was measured and compared with that of conventional liposomes by passing formulations through a filter device at a constant pressure. The release profile of CO from CORM-2-UDLs was evaluated by myoglobin assay.

BACKGROUND: To evaluate the therapeutic benefits of the treat-to-target (T2T) strategy for Asian patients with early rheumatoid arthritis (RA) in Korea. METHODS: In a 1-year, multicenter, open-label strategy trial, 346 patients with early RA were recruited from 20 institutions across Korea and stratified into 2 groups, depending on whether they were recruited by rheumatologists who have adopted the T2T strategy (T2T group) or by rheumatologists who provided usual care (non-T2T group). Data regarding demographics, rheumatoid factor titer, anti-cyclic citrullinated peptide antibody titer, disease activity score of 28 joints (DAS28), and Korean Health Assessment Questionnaire (KHAQ) score were obtained at baseline and after 1 year of treatment. In the T2T group, the prescription for disease-modifying antirheumatic drugs was tailored to the predefined treatment target in each patient, namely remission (DAS28 < 2.6) or low disease activity (LDA) (2.6 ≤ DAS28 < 3.2). RESULTS: Data were available for 163 T2T patients and 162 non-T2T patients. At the end of the study period, clinical outcomes were better in the T2T group than in the non-T2T group (LDA or remission, 59.5% vs. 35.8%; P < 0.001; remission, 43.6% vs. 19.8%; P < 0.001). Compared with non-T2T, T2T was also associated with higher rate of good European League Against Rheumatism response (63.0% vs. 39.8%; P < 0.001), improved KHAQ scores (−0.38 vs. −0.13; P = 0.008), and higher frequency of follow-up visits (5.0 vs. 2.0 visits/year; P < 0.001). CONCLUSION: In Asian patients with early RA, T2T improves disease activity and physical function. Setting a pre-defined treatment target in terms of DAS28 is recommended.
Antirheumatic Agents ; Arthritis, Rheumatoid* ; Asian Continental Ancestry Group* ; Demography ; Follow-Up Studies ; Humans ; Joints ; Korea* ; Multicenter Studies as Topic* ; Prescriptions ; Rheumatic Diseases ; Rheumatoid Factor ; Treatment Outcome

PURPOSE: This study was conducted to establish the production conditions through optimization of the production process of beverages using Aspergillus oryzae CF1001, and to analyze volatile compounds and antidiabetic activity. METHODS: The optimum condition was selected using the response surface methodology (RSM), through a regression analysis with the following independent variables gelatinization temperature (GT, X1), saccharogenic time (ST, X2), and dependent variable; DeltaE value (y). The condition with the lowest DeltaE value occurred with combined 45 min ST and 50degrees C GT. The volatile compounds were analyzed quantitatively by GC-MS. RESULTS: Assessment of antidiabetic activity of saccharogenic mixed grain beverage (SMGB) was determined by measurement of alpha-glucosidase inhibition activity, and glucose uptake activity and glucose metabolic protein expression by reverse transcriptase polymerase chain reaction (RT-PCR) and western blot analysis. Results of volatile compounds analysis, 62 kinds of volatile compounds were detected in SMGB. Palmitic acid (9.534% ratio), benzaldehyde (8.948% ratio), benzyl ethyl ether (8.792% ratio), ethyl alcohol (8.35% ratio), and 2-amyl furan (4.826% ratio) were abundant in SMGB. We confirmed that alpha-glucosidase inhibition activity, glucose uptake activity, and glucose-metabolic proteins were upregulated by SMGB treatment with concentration dependent manner. CONCLUSION: Saccharogenic mixed grain beverage (SMGB) showed potential antidiabetic activity. Further studies will be needed in order to improve the taste and functionality of SMGB.
alpha-Glucosidases ; Aspergillus oryzae ; Beverages* ; Blotting, Western ; Edible Grain* ; Ethanol ; Ether ; Gelatin ; Glucose ; Palmitic Acid ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVE: The safety and efficacy of intravenous (IV) abatacept in patients with active RA unresponsive to methotrexate have been demonstrated in short-term (ST) studies in global populations and a ST, Phase III study in a Korean patient population. Abatacept's long-term safety and efficacy profile has been established in open-label global studies with treatment up to 5 years. The objective of this study was to determine the long-term safety and efficacy of abatacept in patients with RA from the ST Korean study. METHODS: This was an open-label long-term extension (LTE) of a Phase III, multicenter, randomized, double-blind, placebo-controlled study in which Korean patients who had received IV abatacept or placebo in the ST trial (169 days) were given the option to receive open-label abatacept to Day 1485 with 84 days' follow-up (total 1,569 days, ~4 years). RESULTS: A total of 105 patients were enrolled in the LTE (86.7% female, median age 49.0 years). Abatacept was generally well tolerated. Adverse events were mostly mild or moderate and no new safety signals were identified. Improvement in disease activity (assessed by ACR response and DAS28 [CRP]), physical function (assessed by KHAQ-DI), and quality of life (assessed by SF-36 score) were maintained in patients initially treated with abatacept or observed in patients who had switched to abatacept after placebo in the ST study. CONCLUSION: Long-term treatment with IV abatacept over 1485 days was generally well tolerated in Korean patients with RA. Additionally, the efficacy profile from the ST study was maintained over the LTE.
Arthritis, Rheumatoid ; Female ; Follow-Up Studies ; Humans ; Immunoconjugates ; Korea ; Methotrexate ; Quality of Life ; Abatacept

OBJECTIVE: The safety and efficacy of intravenous (IV) abatacept in patients with active RA unresponsive to methotrexate have been demonstrated in short-term (ST) studies in global populations and a ST, Phase III study in a Korean patient population. Abatacept's long-term safety and efficacy profile has been established in open-label global studies with treatment up to 5 years. The objective of this study was to determine the long-term safety and efficacy of abatacept in patients with RA from the ST Korean study. METHODS: This was an open-label long-term extension (LTE) of a Phase III, multicenter, randomized, double-blind, placebo-controlled study in which Korean patients who had received IV abatacept or placebo in the ST trial (169 days) were given the option to receive open-label abatacept to Day 1485 with 84 days' follow-up (total 1,569 days, ~4 years). RESULTS: A total of 105 patients were enrolled in the LTE (86.7% female, median age 49.0 years). Abatacept was generally well tolerated. Adverse events were mostly mild or moderate and no new safety signals were identified. Improvement in disease activity (assessed by ACR response and DAS28 [CRP]), physical function (assessed by KHAQ-DI), and quality of life (assessed by SF-36 score) were maintained in patients initially treated with abatacept or observed in patients who had switched to abatacept after placebo in the ST study. CONCLUSION: Long-term treatment with IV abatacept over 1485 days was generally well tolerated in Korean patients with RA. Additionally, the efficacy profile from the ST study was maintained over the LTE.
Arthritis, Rheumatoid ; Female ; Follow-Up Studies ; Humans ; Immunoconjugates ; Korea ; Methotrexate ; Quality of Life ; Abatacept

Pheochromocytoma is a rare neuroendocrine tumor that is usually derived from adrenal medulla or chromaffin cells along with sympathetic ganglia. In Western countries, the prevalence of pheochromocytoma is estimated to be between 1:6,500 and 1:2,500, compared with an incidence in the United States of 500 to 1,100 cases per year. Despite this low incidence, pheochromocytoma should always be considered for differential diagnoses because previous studies have shown that this condition can be cured in approximately 90% of cases. However, an untreated tumor is likely to be fatal due to catecholamine-induced malignant hypertension, heart failure, myocardial infarction, stroke, ventricular arrhythmias or metastatic disease. Symptoms that result primarily from excess circulating catecholamines and hypertension include severe headaches, generalized inappropriate sweating and palpitations (with tachycardia or occasionally bradycardia). Pheochromocytoma, however, has highly variable and heterogeneous clinical manifestations, including fever, general weakness and dyspepsia, and can be observed in patients who are suffering from infectious diseases. Several of such case reports have been presented, but most of these included infectious patients with high blood pressure and severe fluctuations. In this study, we presented the case of a 53-year-old male who showed normal blood pressure, but had a sustained fever. He was diagnosed with diabetic ketoacidosis, infective endocarditis and asymptomatic adrenal incidentaloma. Despite treatment with antibiotics and valve replacement, the fever persisted. After the patient underwent evaluation for the fever, adrenal incidentaloma was identified as pheochromocytoma. After removal of the abdominal mass, his fever improved.
Adrenal Gland Neoplasms ; Adrenal Medulla ; Anti-Bacterial Agents ; Arrhythmias, Cardiac ; Blood Pressure ; Catecholamines ; Chromaffin Cells ; Communicable Diseases ; Diabetic Ketoacidosis ; Diagnosis, Differential ; Dyspepsia ; Endocarditis ; Fever ; Ganglia, Sympathetic ; Headache ; Heart Failure ; Humans ; Hypertension ; Hypertension, Malignant ; Incidence ; Male ; Middle Aged ; Myocardial Infarction ; Neuroendocrine Tumors ; Pheochromocytoma ; Prevalence ; Stress, Psychological ; Stroke ; Sweat ; Sweating ; Tachycardia ; United States