BACKGROUND: Current polymer-based drug-eluting stents (DESs) have fundamental issues about inflammation and delayed re-endothelializaton of the vessel wall. Substance-P (SP), which plays an important role in inflammation and endothelial cells, has not yet been applied to coronary stents. Therefore, this study compares poly lactic-co-glycolic acid (PLGA)-based everolimus-eluting stents (PLGA-EESs) versus 2-methacryloyloxyethyl phosphorylcholine (MPC)-based SP-eluting stents (MPC-SPs) in in-vitro and in-vivo models. METHODS: The morphology of the stent surface and peptide/drug release kinetics from stents were evaluated. The invitro proliferative effect of SP released from MPC-SP is evaluated using human umbilical vein endothelial cell. Finally, the safety and efficacy of the stent are evaluated after inserting it into a pig’s coronary artery. RESULTS: Similar to PLGA-EES, MPC-SP had a uniform surface morphology with very thin coating layer thickness (2.074 lm). MPC-SP showed sustained drug release of SP for over 2 weeks. Endothelial cell proliferation was significantly increased in groups treated with SP (n = 3) compared with the control (n = 3) and those with everolimus (n = 3) (SP:118.9 ± 7.61% vs. everolimus: 64.3 ± 12.37% vs. the control: 100 ± 6.64%, p < 0.05). In the animal study, the percent stenosis was higher in MPC-SP group (n = 7) compared to PLGA-EES group (n = 7) (MPC-SP: 28.6 ± 10.7% vs. PLGAEES: 16.7 ± 6.3%, p < 0.05). MPC-SP group showed, however, lower inflammation (MPC-SP: 0.3 ± 0.26 vs. PLGAEES: 1.2 ± 0.48, p < 0.05) and fibrin deposition (MPC-SP: 1.0 ± 0.73 vs. PLGA-EES: 1.5 ± 0.59, p < 0.05) around the stent strut. MPC-SP showed more increased expression of cluster of differentiation 31, suggesting enhanced reendothelialization. CONCLUSION Compared to PLGA-EES, MPC-SP demonstrated more decreased inflammation of the vascular wall and enhanced re-endothelialization and stent coverage. Hence, MPC-SP has the potential therapeutic benefits for the treatment of coronary artery disease by solving limitations of currently available DESs.

Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM).

Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM).

Background: Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM). Methods: From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated. Results: In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9± 14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, –1.1%±1.2%; P<0.001). The number of patients with HbA1c <7% increased significantly from 5 to 68 (P<0.005). In addition, lipid profiles and liver enzyme levels were also improved whereas no changes in body weight. There was no significant safety issue in patients treated with quadruple OHA therapy. Conclusion This study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

The molecular mechanism underlying the initiation of somatic cell reprogramming into induced pluripotent stem cells (iPSCs) has not been well described. Thus, we generated single-cell-derived clones by using a combination of drug-inducible vectors encoding transcription factors (Oct4, Sox2, Klf4 and Myc) and a single-cell expansion strategy. This system achieved a high reprogramming efficiency after metabolic and epigenetic remodeling. Functional analyses of the cloned cells revealed that extracellular signal-regulated kinase (ERK) signaling was downregulated at an early stage of reprogramming and that its inhibition was a driving force for iPSC formation. Among the reprogramming factors, Myc predominantly induced ERK suppression. ERK inhibition upregulated the conversion of somatic cells into iPSCs through concomitant suppression of serum response factor (SRF). Conversely, SRF activation suppressed the reprogramming induced by ERK inhibition and negatively regulated embryonic pluripotency by inducing differentiation via upregulation of immediate early genes, such as c-Jun, c-Fos and EGR1. These data reveal that suppression of the ERK-SRF axis is an initial molecular event that facilitates iPSC formation and may be a useful surrogate marker for cellular reprogramming.

OBJECTIVE: The purpose of this study is to evaluate the clinical and hematological effects of tocilizumab in active rheumatoid arthritis (RA) patients. METHODS: Fourteen patients with active RA were enrolled in this study. The patients received tocilizumab 8 mg/kg intravenously every four weeks for 6 months. Disease activity, anemia-related factors including serum hepcidin-25, and hematological parameters were monitored at baseline and at 1, 3, and 6 months after the initiation of treatment. RESULTS: Significant reductions in tender joint count, swollen joint count, visual analogue scale, erythrocyte sedimentation rate (ESR), and C-reactive (CRP) protein plus reductions in a 28-joint disease activity score were observed within one month after the first tocilizumab treatment. These effects lasted throughout the six-month study period. In addition, significant improvements in anemia-related factors such as hepcidin-25, ferritin, iron, hemoglobin, red blood cell counts and mean corpuscular volume were observed during the treatment period. Hematological parameters were improved with reductions in counts for leukocytes, monocytes, neutrophils, and platelets. The lymphocyte counts and their subset numbers were unchanged. Changes in hepcidin levels showed significant correlation with changes in CRP, ESR, ferritin, hemoglobin and counts for red blood cells, leukocytes, and neutrophils during the treatment period. CONCLUSION: This study demonstrates that tocilizumab significantly and meaningfully reduces disease burden in patients with active RA. In addition, tocilizumab diminishes the levels of inflammatory anemia by inhibiting hepcidin production. These clinical data provide evidence of a favorable outcome from tocilizumab in RA.
Anemia* ; Arthritis, Rheumatoid* ; Blood Sedimentation ; Erythrocyte Count ; Erythrocyte Indices ; Erythrocytes ; Ferritins ; Hepcidins* ; Humans ; Iron ; Joints ; Leukocytes ; Lymphocyte Count ; Monocytes ; Neutrophils

BACKGROUND: Diabetes is common among elderly, and low-income is associated with poor adherence to treatment and increased mortality. We evaluated whether comprehensive support using community networks improves glycemic control among low-income elderly patients with diabetes. METHODS: A total of 49 low-income elderly patients with type 2 diabetes, mean age 73 years, were enrolled. For 1 year, study subjects underwent various lifestyle modification programs provided by community networks. The biochemical data including glycemic markers and anthropometric data were obtained at the baseline and at the end of the study. Also, the patients were asked to complete a questionnaire about their quality of life, self-confidence and self-care behavior. RESULTS: After lifestyle modification program, overall changes of fasting plasma glucose, HbA1c, blood pressure, body weight, and other biochemical markers were not significantly different. In a subgroup analysis of 21 patients with poorly controlled diabetes (fasting glucose > 140 mg/dL or HbA1c > 7.5%), fasting plasma glucose was significantly reduced (P = 0.030). Among patients with baseline HbA1c level > or = 8%, HbA1c levels after intervention decreased from 9.33 +/- 1.07% to 8.27 +/- 1.15% (P = 0.092). The results of the questionnaires revealed significant increases in the scores of quality of life, self-confidence and self-care behavior (P < 0.05). CONCLUSION: Among low-income, elderly patients with type 2 diabetes, lifestyle modification through community networks showed no significant changes in glycemic control markers. More intensive and precise interventions using community networks are needed for the glycemic control of low-income, elderly patients with type 2 diabetes.
Aged ; Biomarkers ; Blood Pressure ; Body Weight ; Community Networks ; Fasting ; Glucose ; Humans ; Life Style ; Plasma ; Quality of Life ; Self Care ; Surveys and Questionnaires

Sheehan's syndrome occurs as a result of ischemic pituitary necrosis due to severe postpartum hemorrhage. The manifestations of this clinical syndrome are most often caused by a deficiency in the hormones produced by the anterior pituitary gland, whereas the neurohypophysis is usually preserved but can be involved in severe cases that manifest as diabetes insipidus. This is a report of Sheehan's syndrome that manifested with diabetes insipidus as presenting symptom 2 month's after delivery. The patient suffered massive bleeding, so received a blood transfusion. A combined pituitary stimulation and water deprivation test revealed deficiencies of not only anterior pituitary hormones, such as growth hormone and prolactin, but also of anti-diuretic hormone. We report this case, with a review of the literature.
Blood Transfusion ; Diabetes Insipidus ; Diabetes Insipidus, Neurogenic* ; Growth Hormone ; Hemorrhage ; Humans ; Hypopituitarism* ; Necrosis ; Pituitary Gland, Anterior ; Pituitary Gland, Posterior ; Pituitary Hormones, Anterior ; Postpartum Hemorrhage ; Prolactin ; Water Deprivation

Sheehan's syndrome occurs as a result of ischemic pituitary necrosis due to severe postpartum hemorrhage. The manifestations of this clinical syndrome are most often caused by a deficiency in the hormones produced by the anterior pituitary gland, whereas the neurohypophysis is usually preserved but can be involved in severe cases that manifest as diabetes insipidus. This is a report of Sheehan's syndrome that manifested with diabetes insipidus as presenting symptom 2 month's after delivery. The patient suffered massive bleeding, so received a blood transfusion. A combined pituitary stimulation and water deprivation test revealed deficiencies of not only anterior pituitary hormones, such as growth hormone and prolactin, but also of anti-diuretic hormone. We report this case, with a review of the literature.
Blood Transfusion ; Diabetes Insipidus ; Diabetes Insipidus, Neurogenic* ; Growth Hormone ; Hemorrhage ; Humans ; Hypopituitarism* ; Necrosis ; Pituitary Gland, Anterior ; Pituitary Gland, Posterior ; Pituitary Hormones, Anterior ; Postpartum Hemorrhage ; Prolactin ; Water Deprivation

BACKGROUND: As elderly people increasing, prevalence of diabetes will increase but there was paucity of data on the epidemiology of diabetes in Korean elderly population. In this study (Southwest Seoul, SWS study) we investigated the change of prevalence of diabetes mellitus for two points in time (the years 1999 and 2002) and 3-year incidence of diabetes in elderly Korean population of southwest area of Seoul. METHODS: A sampling of 1,652 subjects in 1999 and 1,214 subjects in 2002 who are over 60 years old in southwest area of Seoul were investigated. All subjects underwent a 75 g oral glucose tolerance test (OGTT), biochemical study and anthropometric measurements. Among the 1,652 subjects in 1999, 350 subjects were followed up for 3 years and 294 subjects without diabetes at baseline examination participated in retrospective cohort study. RESULTS: Prevalence of diabetes in 1999 was 20.5% [previous diagnosed people (11.9%), newly diagnosed people (8.6%)] and in 2002 was 22.1% [previous diagnosed people (15.2%), newly diagnosed people (6.9%)]. Prevalence of impaired fasting glucose (IFG) or impaired glucose intolerance (IGT) was 22.8% in 1999 and 27.8% in 2002. In 350 subjects were followed up for 3 years, prevalence of diabetes was 16.0% in 1999 and increased to 23.4% in 2002 (p=0.014). In retrospective cohort study, the annual incidence rate of diabetes was 2.9% (age and sex adjusted rate 2.5%). CONCLUSION: Prevalence of diabetes in elderly Korean population of southwest area of Seoul was 20.5% in 1999 and increased to 22.1% in 2002. Prevalence of IFG or IGT was 22.8% in 1999 and increased to 27.8% in 2002. This report supports that impaired glucose regulations and diabetes mellitus of elderly Korean population will increase in the future as aged Korean population increases.
Aged ; Asian Continental Ancestry Group ; Cohort Studies ; Diabetes Mellitus* ; Epidemiology ; Fasting ; Glucose ; Glucose Intolerance ; Glucose Tolerance Test ; Humans ; Incidence* ; Middle Aged* ; Prevalence* ; Retrospective Studies ; Seoul ; Social Control, Formal