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1.
Article in English | WPRIM | ID: wpr-924858

ABSTRACT

Bipolar disorder is a mental illness that causes extreme mood swings and has a chronic course. However, the mechanism by which mood episodes with completely opposite characteristics appear repeatedly, or a mixture of symptoms appears, in patients with bipolar disorder remains unknown. Therefore, mood stabilizers are indicated only for single mood episodes, such as manic episodes and depressive episodes, and no true mood-stabilizing drugs effective for treating both manic and depressive episodes currently exist. Therefore, in this review, therapeutic targets that facilitate the development of mood stabilizers were examined by reviewing the current understanding of the neuromolecular etiology of bipolar disorder.

2.
Article in English | WPRIM | ID: wpr-903452

ABSTRACT

Objectives@#The aim of this study was to examine the clinical presentation, treatment delivery, and cisplatin eligibility of Korean patients with urothelial carcinoma (UC) in a real-world setting. @*Methods@#We performed a retrospective cohort study of patients initially diagnosed with UC from March 2013 to June 2018. Creatinine clearance >60 mL/min and Eastern Cooperative Oncology Group performance status (0–1) were adopted as cisplatin eligibility criteria. @*Results@#This study included 557 eligible patients. Median age was 71.0 years (range, 33–94 years), and males were dominant (80%). Primary tumor sites were: upper genitourinary tract, 18%; bladder, 81%; and urethra, 0.4%. Initial disease status was non-muscle invasive bladder cancer (313, 56%), diffuse infiltrating non-muscle invasive bladder cancer (19, 3%), cTanyN0 upper tract UC (75, 13%), cT2-4N0 bladder UC (82, 15%), TanyN1-3 UC (36, 7%), or initially metastatic UC (32, 6%). At the time of analysis (June 2019), following treatments were delivered to 134 patients with localized UC: radical operation with or without perioperative treatment (89, 67%), definitive chemoradiation (7, 5%), and palliative surgery or supportive care only (36, 28%). In total, 89 patients had metastatic UC, including those with recurrent disease (n=57), and 34 (38%) of the 89 were eligible for cisplatin. @*Conclusion@#Clinical presentations in East Asian UC patients were consistent with those of previous studies in other countries, except for a relatively high incidence of upper genitourinary tract. Our results can serve as a benchmark for further advances and future research for treatments of UC in East Asian patients.

3.
Experimental Neurobiology ; : 232-243, 2021.
Article in English | WPRIM | ID: wpr-898363

ABSTRACT

Mutations in the Leucine-rich repeat kinase 2 (LRRK2 ) gene are the most prevalent cause of familial Parkinson’s disease (PD). The increase in LRRK2 kinase activity observed in the pathogenic G2019S mutation is important for PD development. Several studies have reported that increased LRRK2 kinase activity and treatment with LRRK2 kinase inhibitors decreased and increased ciliogenesis, respectively, in mouse embryonic fibroblasts (MEFs) and retinal pigment epithelium (RPE) cells. In contrast, treatment of SH-SY5Y dopaminergic neuronal cells with PD-causing chemicals increased ciliogenesis. Because these reports were somewhat contradictory, we tested the effect of LRRK2 kinase activity on ciliogenesis in neurons. In SH-SY5Y cells, LRRK2 inhibitor treatment slightly increased ciliogenesis, but serum starvation showed no increase. In rat primary neurons, LRRK2 inhibitor treatment repeatedly showed no significant change. Little difference was observed between primary cortical neurons prepared from wild-type (WT) and G2019S +/- mice. However, a significant increase in ciliogenesis was observed in G2019S +/- compared to WT human fibroblasts, and this pattern was maintained in neural stem cells (NSCs) differentiated from the induced pluripotent stem cells (iPSCs) prepared from the same WT/G2019S fibroblast pair. NSCs differentiated from G2019S and its gene-corrected WT counterpart iPSCs were also used to test ciliogenesis in an isogenic background. The results showed no significant difference between WT and G2019S regardless of kinase inhibitor treatment and B27-deprivation-mimicking serum starvation. These results suggest that LRRK2 kinase activity may be not a direct regulator of ciliogenesis and ciliogenesis varies depending upon the cell type or genetic background.

4.
Article in English | WPRIM | ID: wpr-895748

ABSTRACT

Objectives@#The aim of this study was to examine the clinical presentation, treatment delivery, and cisplatin eligibility of Korean patients with urothelial carcinoma (UC) in a real-world setting. @*Methods@#We performed a retrospective cohort study of patients initially diagnosed with UC from March 2013 to June 2018. Creatinine clearance >60 mL/min and Eastern Cooperative Oncology Group performance status (0–1) were adopted as cisplatin eligibility criteria. @*Results@#This study included 557 eligible patients. Median age was 71.0 years (range, 33–94 years), and males were dominant (80%). Primary tumor sites were: upper genitourinary tract, 18%; bladder, 81%; and urethra, 0.4%. Initial disease status was non-muscle invasive bladder cancer (313, 56%), diffuse infiltrating non-muscle invasive bladder cancer (19, 3%), cTanyN0 upper tract UC (75, 13%), cT2-4N0 bladder UC (82, 15%), TanyN1-3 UC (36, 7%), or initially metastatic UC (32, 6%). At the time of analysis (June 2019), following treatments were delivered to 134 patients with localized UC: radical operation with or without perioperative treatment (89, 67%), definitive chemoradiation (7, 5%), and palliative surgery or supportive care only (36, 28%). In total, 89 patients had metastatic UC, including those with recurrent disease (n=57), and 34 (38%) of the 89 were eligible for cisplatin. @*Conclusion@#Clinical presentations in East Asian UC patients were consistent with those of previous studies in other countries, except for a relatively high incidence of upper genitourinary tract. Our results can serve as a benchmark for further advances and future research for treatments of UC in East Asian patients.

5.
Experimental Neurobiology ; : 232-243, 2021.
Article in English | WPRIM | ID: wpr-890659

ABSTRACT

Mutations in the Leucine-rich repeat kinase 2 (LRRK2 ) gene are the most prevalent cause of familial Parkinson’s disease (PD). The increase in LRRK2 kinase activity observed in the pathogenic G2019S mutation is important for PD development. Several studies have reported that increased LRRK2 kinase activity and treatment with LRRK2 kinase inhibitors decreased and increased ciliogenesis, respectively, in mouse embryonic fibroblasts (MEFs) and retinal pigment epithelium (RPE) cells. In contrast, treatment of SH-SY5Y dopaminergic neuronal cells with PD-causing chemicals increased ciliogenesis. Because these reports were somewhat contradictory, we tested the effect of LRRK2 kinase activity on ciliogenesis in neurons. In SH-SY5Y cells, LRRK2 inhibitor treatment slightly increased ciliogenesis, but serum starvation showed no increase. In rat primary neurons, LRRK2 inhibitor treatment repeatedly showed no significant change. Little difference was observed between primary cortical neurons prepared from wild-type (WT) and G2019S +/- mice. However, a significant increase in ciliogenesis was observed in G2019S +/- compared to WT human fibroblasts, and this pattern was maintained in neural stem cells (NSCs) differentiated from the induced pluripotent stem cells (iPSCs) prepared from the same WT/G2019S fibroblast pair. NSCs differentiated from G2019S and its gene-corrected WT counterpart iPSCs were also used to test ciliogenesis in an isogenic background. The results showed no significant difference between WT and G2019S regardless of kinase inhibitor treatment and B27-deprivation-mimicking serum starvation. These results suggest that LRRK2 kinase activity may be not a direct regulator of ciliogenesis and ciliogenesis varies depending upon the cell type or genetic background.

6.
Mood and Emotion ; (2): 24-34, 2021.
Article in English | WPRIM | ID: wpr-918519

ABSTRACT

Background@#This study explores the correlation among obesity, suicide plans, and suicide attempts in adults over 19 years of age in South Korea. @*Methods@#The study used data from adults who had participated in the 2018 Korea National Health and Nutrition Examination Survey. Obesity was defined as having a body mass index of ≥25 kg/m 2 . To identify differences between the characteristics of those who had reported suicide plans and attempts, a complex sample chi-square test was conducted. To analyze the effect of obesity on suicide plans and attempts, a logistic regression analysis was performed. @*Results@#There was no significant difference in the rate of suicide plans in one year between obese and non-obese groups; however, the rate of actual suicide attempts was significantly high in the obese group (p<0.050). After correcting for variables that were significantly different between the groups, obesity was found to have no significant effect on suicide plans but was linked to a significant increase in suicide attempts (odds ratio=3.355, p=0.008). @*Conclusion@#Obesity was found to have no effect on the suicide planning rate; however, the probability of a suicide attempt was high in obese adults.

7.
Article | WPRIM | ID: wpr-836783

ABSTRACT

Purpose@#The Advanced Prostate Cancer Consensus Conference (APCCC) 2015 was based on topics withcontroversy in the field of advanced prostate cancer. To understand the Korean urologists perspective regardingthe issues, we have conducted a questionnaire named Prostate Cancer Summit (PCAS) 2016, with 9 importantsubtopics. @*Materials and Methods@#Total 9 subtopics have been decided and questions were developed regarding eachsubtopic. The questions were based on that of APCCC 2015 and translated into Korean for better understanding.Total 51 panelists have voted online on 85 different questions. @*Results@#The survey concluded that testosterone should be measured as a diagnostic criterion for castrationresistance prostate cancer (CRPC) and that consensus was reached on issues such as the use of androgenreceptor pathway inhibitors in the treatment of predocetaxel and postdocetaxel in CRPC patients. In addition,76% of the participants agreed that imaging tests were needed before new treatment in CRPC patients, anda majority of participants agreed that periodic imaging tests are necessary regardless of symptoms during treatmentfor CRPC. However, some issues, such as the use of prostate-specific antigen-based triggers for remediationin CRPC patients, the endocrine manipulation in nonmetastatic CRPC patients, and the onset of treatment inasymptomatic metastatic CRPC patients, were not agreed. @*Conclusions@#The results from PCAS 2016 has addressed some of the issues with controversy. Although thevoting results are subjective, it will help guide treatment decisions in topics with less evidence.

8.
Mood and Emotion ; (2): 83-89, 2020.
Article in English | WPRIM | ID: wpr-918507

ABSTRACT

Background@#This study aims to investigate the relationship between metabolic syndrome and depression in Korean adults using data from the 2016 and 2018 Korean National Health and Nutrition Examination Surveys (KNHANES). @*Methods@#The total number of participants in the 7th period 1st year (2016) and 3rd year (2018) surveys of KNHANES was 16142. This study was conducted with 10,722 subjects who met the diagnostic criteria for metabolic syndrome and responded to the Patient Health Questionnaire-9 (PHQ-9). Analysis of covariance was used to adjust the differences due to demographic factors, laboratory findings, and underlying diseases to understand the relationship between metabolic syndrome and PHQ-9 scores, if any. @*Results@#The prevalence of metabolic syndrome was determined to be 25.6% in this study. The PHQ-9 scores with and without metabolic syndrome were 2.56 and 2.48, respectively, and there was no significant difference when the confounding variable was corrected (p=0.406). According to the analysis of each PHQ-9 item and metabolic syndrome, the results were not significant. @*Conclusion@#In this cross-sectional study conducted in Korean adults, no significant correlation was found between metabolic syndrome and depression.

9.
Article in English | WPRIM | ID: wpr-831675

ABSTRACT

Background@#Calprotectin is the major cytosolic protein in neutrophil granulocytes.Although asthma is known to cause eosinophilic inflammation, some patients with asthma have non-eosinophilic inflammation, which is characterized by local neutrophilic inflammation. The aim of this study was to assess calprotectin expression levels in a mouse model of asthma, and to observe the relationship of serum calprotectin level and clinical variables in patients with asthma. @*Methods@#Mice were sensitized and challenged with 10 μg and 20 μg of Aspergillus fumigatus, respectively; mice treated with saline were used as a control. The levels of calprotectin were determined using enzyme-linked immunosorbent assay, immunoblotting, and immunohistochemical analysis. The serum levels of calprotectin were also assessed in patients with asthma. The relationship between calprotectin and clinicopathological characteristics was determined. @*Results@#Calprotectin, S100A8, and S100A9 expression was elevated in the mouse lungs, Calprotectin levels were higher in the serum of patients with asthma (n = 33) compared with those of healthy individuals (n = 28). Calprotectin levels correlated with forced expiratory volume in one second/forced vital capacity (r = −0.215, P = 0.043), smoke amount (r = 0.413, P = 0.017), body mass index (r = −0.445,P= 0.000), and blood neutrophil percentage (r = 0.300, P = 0.004) in patients with asthma. @*Conclusion@#Our data suggest that calprotectin could potentially be used as a biomarker for asthma.

10.
Article in English | WPRIM | ID: wpr-919461

ABSTRACT

Idiopathic interstitial pneumonia (IIP) is a histologically identifiable pulmonary disease without a known cause that usually infiltrates the lung interstitium. IIP is largely classified into idiopathic pulmonary fibrosis, idiopathic non-specific interstitial pneumonia, respiratory bronchiolitis-interstitial lung disease (ILD), cryptogenic organizing pneumonia, desquamative interstitial pneumonia, and acute interstitial pneumonia. Each of these diseases has a different prognosis and requires specific treatment, and a multidisciplinary approach that combines chest high-resolution computed tomography (HRCT), histological findings, and clinical findings is necessary for their diagnosis. Diagnosis of IIP is made based on clinical presentation, chest HRCT findings, results of pulmonary function tests, and histological findings. For histological diagnosis, video-assisted thoracoscopic biopsy and transbronchial lung biopsy are used. In order to identify ILD associated with connective tissue disease, autoimmune antibody tests may also be necessary. Many biomarkers associated with disease prognosis have been recently discovered, and future research on their clinical significance is necessary. The diagnosis of ILD is difficult because patterns of ILD are both complicated and variable. Therefore, as with other diseases, accurate history taking and meticulous physical examination are crucial.

11.
Article in English | WPRIM | ID: wpr-763651

ABSTRACT

BACKGROUND: Combination of metformin to reduce the fasting plasma glucose level and an α-glucosidase inhibitor to decrease the postprandial glucose level is expected to generate a complementary effect. We compared the efficacy and safety of a fixed-dose combination of voglibose plus metformin (vogmet) with metformin monotherapy in drug-naïve newly-diagnosed type 2 diabetes mellitus. METHODS: A total of 187 eligible patients aged 20 to 70 years, with a glycosylated hemoglobin (HbA1c) level of 7.0% to 11.0%, were randomized into either vogmet or metformin treatments for 24 weeks. A change in the HbA1c level from baseline was measured at week 24. RESULTS: The reduction in the levels of HbA1c was −1.62%±0.07% in the vogmet group and −1.31%±0.07% in the metformin group (P=0.003), and significantly more vogmet-treated patients achieved the target HbA1c levels of <6.5% (P=0.002) or <7% (P=0.039). Glycemic variability was also significantly improved with vogmet treatment, estimated by M-values (P=0.004). Gastrointestinal adverse events and hypoglycemia (%) were numerically lower in the vogmet-treated group. Moreover, a significant weight loss was observed with vogmet treatment compared with metformin (−1.63 kg vs. −0.86 kg, P=0.039). CONCLUSION: Vogmet is a safe antihyperglycemic agent that controls blood glucose level effectively, yields weight loss, and is superior to metformin in terms of various key glycemic parameters without increasing the risk of hypoglycemia.


Subject(s)
Blood Glucose , Diabetes Mellitus, Type 2 , Fasting , Glucose , Glycated Hemoglobin A , Humans , Hypoglycemia , Metformin , Weight Loss
12.
Article in English | WPRIM | ID: wpr-761966

ABSTRACT

Idiopathic interstitial pneumonia (IIP) is a histologically identifiable pulmonary disease without a known cause that usually infiltrates the lung interstitium. IIP is largely classified into idiopathic pulmonary fibrosis, idiopathic non-specific interstitial pneumonia, respiratory bronchiolitis-interstitial lung disease (ILD), cryptogenic organizing pneumonia, desquamative interstitial pneumonia, and acute interstitial pneumonia. Each of these diseases has a different prognosis and requires specific treatment, and a multidisciplinary approach that combines chest high-resolution computed tomography (HRCT), histological findings, and clinical findings is necessary for their diagnosis. Diagnosis of IIP is made based on clinical presentation, chest HRCT findings, results of pulmonary function tests, and histological findings. For histological diagnosis, video-assisted thoracoscopic biopsy and transbronchial lung biopsy are used. In order to identify ILD associated with connective tissue disease, autoimmune antibody tests may also be necessary. Many biomarkers associated with disease prognosis have been recently discovered, and future research on their clinical significance is necessary. The diagnosis of ILD is difficult because patterns of ILD are both complicated and variable. Therefore, as with other diseases, accurate history taking and meticulous physical examination are crucial.


Subject(s)
Biomarkers , Biopsy , Classification , Connective Tissue Diseases , Cryptogenic Organizing Pneumonia , Diagnosis , Idiopathic Interstitial Pneumonias , Idiopathic Pulmonary Fibrosis , Lung , Lung Diseases , Lung Diseases, Interstitial , Physical Examination , Prognosis , Respiratory Function Tests , Thorax
13.
Mood and Emotion ; (2): 21-27, 2019.
Article in English | WPRIM | ID: wpr-786412

ABSTRACT

BACKGROUND: The purpose of this study was to investigate the relationship between metabolic syndrome and depressive symptoms by administering the nine-item depression module from the Patient Health Questionnaire-9 (PHQ-9) to participants from the general population of Korea.METHODS: In total, 8,150 adults participated in the 1st year of the 7th Korea National Health and Nutrition Examination Survey, which was conducted in 2016. Of them, 5,556 participants underwent tests pertaining to the criteria for metabolic syndrome and responded to PHQ-9; 2,594 respondents were excluded. Analysis of covariance was performed to analyze the relationship between the presence of metabolic syndrome and the PHQ-9 score after adjusting for the effects of demographic and hematologic characteristics and underlying diseases.RESULTS: The total PHQ-9 score (mean=2.98) was significantly higher in participants with metabolic syndrome than in those without it (mean=2.59) (p=0.002). Among the individual PHQ-9 items, changes in sleep, thoughts of suicide or self-harm, and depressive mood showed the greatest differences.CONCLUSION: The PHQ-9 scores in Korea were higher in adults with metabolic syndrome, suggesting an association between metabolic syndrome and depressive symptoms.


Subject(s)
Adult , Depression , Humans , Korea , Nutrition Surveys , Suicide , Surveys and Questionnaires
14.
Article in English | WPRIM | ID: wpr-719629

ABSTRACT

PURPOSE: To evaluate changes in the expression of androgen receptor (AR) and its variants (ARVs) in human prostate cancer (PCa) tissues according to disease status, and its prognostic significance following radical prostatectomy (RP). MATERIALS AND METHODS: A total of 282 PCa cases were evaluated, which included 252 localized PCa, 8 metastatic castration resistant prostate cancer (CRPC), and 22 benign prostatic hyperplasia (BPH) cases. Samples were collected from patients who underwent RP or transurethral resection and were stored in ethically approved tissue banks. Quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry were performed for AR and ARVs. Each tissue was confirmed as cancerous (greater than 80%) using hematoxylin and eosin staining. AR and ARVs expression was compared according to disease status. The biochemical recurrence free survival (BCRFS) rates in men with localized PCa was analyzed according to AR and ARV7 expression using the Kaplan-Meier curve. RESULTS: Only 58 of the 252 localized PCa were included in the analysis because of insufficient cancer tissue. AR and ARV7 mRNA expression was higher in the CRPC tissue than in the localized PCa tissue (p=0.025, p=0.002, respectively). In localized PCa tissue, high AR mRNA and protein level was associated with a low BCRFS rate (log-ranked, p=0.019, p < 0.001, respectively). CONCLUSIONS: Overall AR and ARV7 mRNA expression levels were increased in CRPC tissues compared to localized PCa and BPH tissues. High AR protein and mRNA expression in the tumor tissue may be considered a predictive factor of BCRFS following RP.


Subject(s)
Blotting, Western , Castration , Eosine Yellowish-(YS) , Hematoxylin , Humans , Immunohistochemistry , Male , Passive Cutaneous Anaphylaxis , Prostate , Prostatectomy , Prostatic Hyperplasia , Prostatic Neoplasms , Real-Time Polymerase Chain Reaction , Receptors, Androgen , Recurrence , RNA, Messenger , Tissue Banks
15.
Article in English | WPRIM | ID: wpr-739390

ABSTRACT

PURPOSE: Claudin-4 has been reported to function as a paracellular sodium barrier and is one of the 3 major claudins expressed in lung alveolar epithelial cells. However, the possible role of claudin-4 in bronchial asthma has not yet been fully studied. In this study, we aimed to elucidate the role of claudin-4 in the pathogenesis of bronchial asthma. METHODS: We determined claudin-4 levels in blood from asthmatic patients. Moreover, using mice sensitized and challenged with OVA, as well as sensitized and challenged with saline, we investigated whether claudin-4 is involved in the pathogenesis of bronchial asthma. Der p1 induced the inflammatory cytokines in NHBE cells. RESULTS: We found that claudin-4 in blood from asthmatic patients was increased compared with that from healthy control subjects. Plasma claudin-4 levels were significantly higher in exacerbated patients than in control patients with bronchial asthma. The plasma claudin-4 level was correlated with eosinophils, total IgE, FEV1% pred, and FEV1/FVC. Moreover, lung tissues from the OVA-OVA mice showed significant increases in transcripts and proteins of claudin-4 as well as in TJ breaks and the densities of claudin-4 staining. When claudin-4 was knocked down by transfecting its siRNA, inflammatory cytokine expressions, which were induced by Der p1 treatment, were significantly increased. CONCLUSIONS: These findings thus raise the possibility that regulation of lung epithelial barrier proteins may constitute a therapeutic approach for asthma.


Subject(s)
Animals , Asthma , Claudin-4 , Claudins , Cytokines , Eosinophils , Epithelial Cells , Humans , Immunoglobulin E , Inflammation , Lung , Mice , Ovum , Plasma , RNA, Small Interfering , Sodium
16.
Article in English | WPRIM | ID: wpr-713174

ABSTRACT

BACKGROUND: Hypertriglyceridemia is known to have an association with increased risks of insulin resistance and diabetes. The aim of this study was to investigate the risk of diabetes mellitus, according to changes in the concentrations of triglycerides, over time. METHODS: A total of 15,932 non-diabetic participants (mean age 43.2 years, 68% men) who attended five consecutive annual health check-ups at Kangbuk Samsung Hospital, between January 2010 and December 2014, were recruited. Participants were classified according to their triglyceride concentrations; normal ( < 150 mg/dL) and abnormal (≥150 mg/dL). According to the triglyceride levels in 2010 and 2012, subjects were divided into four groups: normal-normal, normal-abnormal, abnormal-normal, and abnormal-abnormal. The risk for incident diabetes was assessed in 2014. RESULTS: Among the total subjects, 67.5% belonged to the normal-normal group, 8.6% to the normal-abnormal group, 9.4% to the abnormal-normal group, and 14.5% to the abnormal-abnormal group. A total of 234 subjects (1.5%) were newly diagnosed with diabetes, between 2010 and 2014. Over 4 years, 1%, 1.5%, 2.1%, and 3.0% of the subjects developed diabetes in the normal-normal, normal-abnormal, abnormal-normal, and abnormal-abnormal groups, respectively. When the risk for incident diabetes was analyzed in the groups, after adjusting the confounding variables, a 1.58-fold increase in the risk of diabetes (95% confidence interval [CI], 1.10 to 2.26) was observed in the participants with persistent hypertriglyceridemia (abnormal-abnormal group). This was attenuated by further adjustments for body mass index (BMI) (hazard ratio, 1.25; 95% CI, 0.86 to 1.80). CONCLUSION: In this large study population, persistent hypertriglyceridemia, over a period of 2 years, was significantly associated with the risk of incident diabetes, which was attenuated after adjustment for BMI.


Subject(s)
Body Mass Index , Diabetes Mellitus , Hypertriglyceridemia , Insulin Resistance , Triglycerides
17.
Article in English | WPRIM | ID: wpr-713168

ABSTRACT

BACKGROUND: The nuclear receptor peroxisome proliferator-activator gamma (PPARγ) is a useful therapeutic target for obesity and diabetes, but its role in protecting β-cell function and viability is unclear. METHODS: To identify the potential functions of PPARγ in β-cells, we treated mouse insulinoma 6 (MIN6) cells with the PPARγ agonist pioglitazone in conditions of lipotoxicity, endoplasmic reticulum (ER) stress, and inflammation. RESULTS: Palmitate-treated cells incubated with pioglitazone exhibited significant improvements in glucose-stimulated insulin secretion and the repression of apoptosis, as shown by decreased caspase-3 cleavage and poly (adenosine diphosphate [ADP]-ribose) polymerase activity. Pioglitazone also reversed the palmitate-induced expression of inflammatory cytokines (tumor necrosis factor α, interleukin 6 [IL-6], and IL-1β) and ER stress markers (phosphor-eukaryotic translation initiation factor 2α, glucose-regulated protein 78 [GRP78], cleaved-activating transcription factor 6 [ATF6], and C/EBP homologous protein [CHOP]), and pioglitazone significantly attenuated inflammation and ER stress in lipopolysaccharide- or tunicamycin-treated MIN6 cells. The protective effect of pioglitazone was also tested in pancreatic islets from high-fat-fed KK-Ay mice administered 0.02% (wt/wt) pioglitazone or vehicle for 6 weeks. Pioglitazone remarkably reduced the expression of ATF6α, GRP78, and monocyte chemoattractant protein-1, prevented α-cell infiltration into the pancreatic islets, and upregulated glucose transporter 2 (Glut2) expression in β-cells. Moreover, the preservation of β-cells by pioglitazone was accompanied by a significant reduction of blood glucose levels. CONCLUSION: Altogether, these results support the proposal that PPARγ agonists not only suppress insulin resistance, but also prevent β-cell impairment via protection against ER stress and inflammation. The activation of PPARγ might be a new therapeutic approach for improving β-cell survival and insulin secretion in patients with diabetes mellitus


Subject(s)
Animals , Apoptosis , Blood Glucose , Caspase 3 , Chemokine CCL2 , Cytokines , Diabetes Mellitus , Endoplasmic Reticulum Stress , Endoplasmic Reticulum , Glucose Transport Proteins, Facilitative , Humans , Inflammation , Insulin , Insulin Resistance , Insulin-Secreting Cells , Insulinoma , Interleukin-6 , Islets of Langerhans , Mice , Necrosis , Obesity , Peptide Initiation Factors , Peroxisomes , Repression, Psychology , Transcription Factors
18.
Article in English | WPRIM | ID: wpr-787091

ABSTRACT

BACKGROUND: Elderly patients with multiple myeloma (MM) are vulnerable to adverse events (AEs). This study evaluated adherence to chemotherapy and treatment outcomes in elderly patients treated with a frontline bortezomib (BTZ), melphalan, and prednisone (VMP) regimen and regimens without BTZ.METHODS: One-hundred and forty elderly patients who were diagnosed with MM from March 2007 to March 2015 were included in this retrospective study. To evaluate regimen adherence, patients who were treated with more than 4 cycles were assigned to the good adherence group.RESULTS: Among the 140 patients, 71 were treated with a frontline VMP and 69 with non-BTZ regimens. The median age was 71 years (range, 65-90 years). The VMP group showed a higher complete response rate than the non-BTZ group: 26.8% vs. 7.2%. More patients in the VMP group achieved ≥ very good partial response (VGPR) and ≥ PR. In the VMP group, 27 patients (38.0%) received less than 4 cycles. The VMP good adherence group showed a higher 3-year overall survival (OS) rate (70.9%) than the poor adherence group (60.2%, p=0.059). In the multivariate analysis, treatment with ≥ 4 cycles of VMP was a favorable factor for OS.CONCLUSION: A good adherence to a frontline VMP regimen resulted in favorable long-term survival. Adequate management of AEs will be needed to achieve favorable outcomes in elderly patients with MM.


Subject(s)
Aged , Bortezomib , Drug Therapy , Humans , Medication Adherence , Melphalan , Multiple Myeloma , Multivariate Analysis , Prednisone , Retrospective Studies
19.
Mood and Emotion ; (2): 38-43, 2018.
Article in Korean | WPRIM | ID: wpr-786873

ABSTRACT

OBJECTIVES: The purpose of this study is to inquire into the relationship between the association of suicidal ideation and the plasma C-reactive protein level in the general population.METHODS: This study selected a total of 5,090 subjects who have responded to the survey item on suicidal ideation status, and received the plasma C-reactive protein test, as a research subject using the 2015 data of the National Health and Nutrition Survey. This study conducted a covariance analysis by correcting a potential influence of demographic and hematological factors. Besides, this study intended to define the cut-off value of the optimum plasma C-reactive protein level, which once identified can distinguish between a subject with and without suicidal ideation using the model of the decision tree.RESULTS: The Plasma C-reactive protein level of a subject having suicidal ideation was noted as being significantly higher than the one having no suicidal ideation in the covariance analysis (p=0.046). In addition, the proper cut-off value of the plasma C-reactive protein level between the subjects with and without suicidal ideation was found to be 1.30 mg/L (p=0.003).CONCLUSION: It is noted that the high plasma C-reactive protein level showed a significant correlation with individuals with noted suicidal ideation. In addition, this study has significance in that it presented that the plasma C-reactive protein concentration has the possibility as an accurate and significant marker of suicidal ideation in the general population.


Subject(s)
C-Reactive Protein , Decision Trees , Humans , Nutrition Surveys , Plasma , Research Subjects , Suicidal Ideation
20.
Article in English | WPRIM | ID: wpr-715652

ABSTRACT

BACKGROUND/AIMS: The methacholine bronchial provocation test (MBPT) is used to detect and quantify airway hyper-responsiveness (AHR). Since improvements in the severity of asthma are associated with improvements in AHR, clinical studies of asthma therapies routinely use the change of airway responsiveness as an objective outcome. The aim of this study was to assess the relationship between serial MBPT and clinical profiles in patients with asthma. METHODS: A total of 323 asthma patients were included in this study. The MBPT was performed on all patients beginning at their initial diagnosis until asthma was considered controlled based on the Global Initiative for Asthma guidelines. A responder was defined by a decrease in AHR while all other patients were considered non-responders. RESULTS: A total of 213 patients (66%) were responders, while 110 patients (34%) were non-responders. The responder group had a lower initial PC20 (provocative concentration of methacholine required to decrease the forced expiratory volume in 1 second by 20%) and longer duration compared to the non-responder group. Members of the responder group also had superior qualities of life, compared to members of the non-responder group. Whole blood cell counts were not related to differences in PC20; however, eosinophil concentration was. No differences in sex, age, body mass index, smoking history, serum immunoglobulin E, or frequency of acute exacerbation were observed between responders and non-responders. CONCLUSIONS: The initial PC20, the duration of asthma, eosinophil concentrations, and quality-of-life may be useful variables to identify improvements in AHR in asthma patients.


Subject(s)
Asthma , Blood Cell Count , Body Mass Index , Bronchial Provocation Tests , Diagnosis , Eosinophils , Forced Expiratory Volume , Humans , Immunoglobulin E , Immunoglobulins , Methacholine Chloride , Respiratory Hypersensitivity , Smoke , Smoking
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