Bcl-2 protects tumor cells from the apoptotic effects of various anti-neoplastic agents. Increased expression of Bcl-2 has been associated with a poor response to chemotherapy in various malignancies, including leukemia. Hence, bypassing the resistance conferred by anti-apoptotic factors such as Bcl-2 represents an attractive therapeutic strategy against cancer cells, including leukemic cells. This study was undertaken to examine whether the anticancer drug, cisplatin and the synthetic chenodeoxycholic acid (CDCA) derivative, HS-1200 show anti-tumor activity in U937 and U937/Bcl-2 cells. Viability assays revealed that HS-1200 overcomes the resistance conferred by Bcl-2 in human leukemic U937 cells. Various apoptosis assessment assays further demonstrated that HS-1200 overcomes the resistance conferred by Bcl-2 in human leukemic U937 cells by inducing apoptosis. In addition HS-1200, but not cisplatin, overcomes the anti-apoptotic effects of Bcl-2 in Bcl-2 over-expressing human leukemic cells (U937/Bcl-2 cells). Notably, we observed that the HS-1200-induced formation of mature promyelocytic leukemia (PML) nuclear bodies (NBs) correlates with a suppression of the anti-apoptotic effects of Bcl-2 in human leukemic cells over-expressing this protein (U937/Bcl-2 cells). Furthermore, HS-1200 was found to induce the association between PML and SUMO-1, Daxx, Sp100, p53 or CBP in the aggregated PML-NBs of U937/Bcl-2 cells. Thus, PML protein and the formation of mature PML-NBs could be considered as therapeutic targets that may help to bypass the resistance to apoptosis conferred by Bcl-2. Elucidating the exact mechanism by which PML regulates Bcl-2 will require further work.
Apoptosis ; Chenodeoxycholic Acid ; Cisplatin ; Humans ; Leukemia ; U937 Cells

Hyponatremia is a frequent condition of body fluid and electrolyte imbalance encountered in clinical practice. However, rhabdomyolysis has rarely been reported in association with hyponatremia. We experienced a 56-year-old woman who had developed symptomatic hyponatremia after prolonged nausea and subsequent rhabdomyolysis. Hyponatremia was probably mediated by hypersecretion of antidiuretic hormones.The woman had developed severe hypotonic hyponatremia with an alternation in mental status after suffering from severe nausea and vomiting for x months/years. She recovered with intensive supportive therapy, including hypertonic saline administration. One day after hospitalization, she complained of thigh pains; furthermore her serum creatine phosphokinase level had increased. She was treated with alkaline diuresis. Renal failure or compartment syndrome did not complicate the clinical course. The patient was discharged and returned to her normal daily activities. The possibility of rhabdomyolysis should be considered in patients with acute hyponatremia who have developed muscle pain.
Body Fluids ; Compartment Syndromes ; Creatine Kinase ; Diuresis ; Female ; Hospitalization ; Humans ; Hyponatremia* ; Middle Aged ; Myalgia ; Nausea ; Renal Insufficiency ; Rhabdomyolysis* ; Thigh ; Vomiting

Photodynamic therapy has been widely used in the treatment of various cancerous diseases. However, photodynamic therapy with a photosensitizer can cause a photosensitivity reaction on the skin. We report a case of a 64-year-old woman diagnosed with photosensitivity reaction after photodynamic therapy using the photosensitizer, porfimer. She presented to the emergency room with a skin rash on her face, neck, and both upper and lower extremities nine days after the photodynamic therapy. She denied any outdoor activity during that period. After administration of systemic corticosteroid and anti-histamine, her skin lesions resolved completely within seven days.
Dihematoporphyrin Ether ; Emergencies ; Exanthema ; Female ; Humans ; Lower Extremity ; Middle Aged ; Neck ; Papilloma ; Photochemotherapy ; Skin

BACKGROUND: This is a subgroup analysis of Korean patients from a phase 3 clinical trial investigating the efficacy and safety of ipragliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin. METHODS: This multicenter, placebo-controlled, double-blind, parallel-group study was carried out between November 2011 and January 2013. Patients entered a 2-week placebo pretreatment period, followed by a 24-week treatment period with either ipragliflozin (50 mg/day) or placebo, while continuing metformin. Efficacy outcomes (glycosylated hemoglobin [HbA1c], fasting plasma glucose [FPG], and body weight) and safety outcomes (treatment-emergent adverse events [TEAEs]) were measured and compared between the two treatment groups for patients enrolled in all 18 study sites in Korea. RESULTS: Eighty-two Korean patients received ipragliflozin (n=43) or placebo (n=39) during the study period. Mean changes in HbA1c levels from baseline to the end of treatment were –0.97% in the ipragliflozin group and –0.31% in the placebo group, with an adjusted between-group difference of –0.60% (P<0.001). Compared to placebo, FPG and body weight also decreased significantly (both P<0.001) from baseline after treatment in the ipragliflozin group, with between-group differences of –21.4 mg/dL and –1.53 kg, respectively. Decreased weight was the most common TEAE in the ipragliflozin group (7.0%); there were no reports of genital and urinary tract infection. CONCLUSION: Ipragliflozin treatment in addition to metformin led to significant improvement in glycemic outcomes and reduction in body weight in Korean patients with type 2 diabetes mellitus, compared with metformin treatment alone; the safety profile was comparable in both groups.
Asia ; Blood Glucose ; Body Weight ; Diabetes Mellitus, Type 2* ; Fasting ; Humans ; Korea ; Metformin* ; Urinary Tract Infections

BACKGROUND: The effects of dipeptidyl peptidase-4 inhibitors on adipokines remain obscure. The aim of this study was to evaluate the effect of the addition of vildagliptin on visfatin, an adipokine that represents inflammatory biomarkers of adipose tissue, in patients with type 2 diabetes inadequately controlled with prior metformin monotherapy. METHODS: In this 16-week, double-blind, randomized, parallel-group, placebo-controlled study, 71 patients were randomly assigned to vildagliptin 50 mg twice a day (n = 35) or placebo (n = 36) added to ongoing metformin therapy. Fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), plasma lipids, and visfatin levels were measured at baseline and 16 weeks after treatment. RESULTS: After 16 weeks, significant reduction in HbA1c and FPG was observed with vildagliptin addon treatment compared to placebo (-0.54 +/- 0.52%, P = 0.001 and -14.80 +/- 19.21 mg/dL, P = 0.004, respectively). However, no other clinically meaningful changes in lipid parameters or visfatin were observed. CONCLUSION: Vildagliptin add-on to metformin significantly improved fasting blood glucose and HbA1c. However, in this study, no significant differences in lipid parameters or visfatin level were observed between the two groups.
Adipokines ; Adipose Tissue ; Biomarkers ; Blood Glucose ; Diabetes Mellitus ; Fasting ; Hemoglobin A, Glycosylated ; Humans ; Metformin ; Nicotinamide Phosphoribosyltransferase* ; Plasma ; Prospective Studies*

OBJECTIVES: The aim of this study is to develop guideline for evaluation of depression. METHODS: Development of this guideline was processed according to the ADAPTE manual, which was developed for adaptation of good clinical practice guidelines. Important key questions were determined, and a systematic review of clinical practice guidelines was performed. The contents of guidelines selected by comparison of the methodological quality and currency were evaluated with regard to the applicability and acceptability. Answers to key questions and clinical recommendations were established by peer review. RESULTS: Careful evaluations on the characteristics of depression, including subtype, severity, suicidality, and psychiatric and physical comorbidities were recommended because these factors can have an influence on course and prognosis in treatment of depression. CONCLUSION: The results of this study may contribute to the systematic evaluation of depression, based on clinical importance. However, this guideline did not include systematic reviews regarding useful scales for evaluation of depression. In the future, amendment of this guideline might be needed in order to supplement limitations.
Comorbidity ; Depression* ; Depressive Disorder ; Diagnosis* ; Methods ; Peer Review ; Prognosis ; Weights and Measures

OBJECTIVES: The aim of this study is to develop guideline for use in diagnosis of depression. METHODS: Development of this guideline was processed according to the ADAPTE manual, which was developed for adaptation of good clinical practice guidelines. Important key questions were determined, and a systematic review of clinical practice guidelines was performed. The contents of guidelines selected by comparison of the methodological quality and currency were evaluated with regard to the applicability and acceptability. Answers to key questions and clinical recommendations were established by peer review. RESULTS: There has been no evidence on strategies to improve the accuracy and rate of diagnosis of depression. The screening tools for depression were useful in diagnosis of depression in clinical practice. CONCLUSION: The results of this study may suggest the necessity of strategies to improve the validity and reliability of diagnosis of depression. In contrast, scales for screening depression can be useful in diagnosis of depression. This guideline did not include systematic reviews regarding useful scales for diagnosis of depression. In the future, amendment of this guideline might be needed in order to supplement limitations.
Depression* ; Depressive Disorder ; Diagnosis* ; Mass Screening ; Methods ; Peer Review ; Reproducibility of Results ; Weights and Measures

BACKGROUND AND PURPOSE: The one-day rivastigmine patch is reportedly well tolerated and has minimal side effects. However, Asian patients show more side effects than those in Western countries. We evaluated tolerability of the rivastigmine patch in South Korean patients with Alzheimer's disease (AD) and the specific factors affecting adverse events of the skin. METHODS: A 6-month, open labeled, multi-centered, observational study was carried out in 440 patients with probable AD from July 2009 to September 2010 (NCT01312363). RESULTS: A total of 25.9% of the patients experienced adverse skin events at the rivastigmine patch application site and 17.0% discontinued treatment due to adverse events at the skin application site. The most common adverse events were itching and erythema. Patients with an allergic history and users of electric heating appliances reported skin discomfort. Older age was associated with discontinuing treatment. CONCLUSION: These results suggest that the rivastigmine patch induced some adverse skin events and may contribute to understanding and improving skin tolerability to the rivastigmine patch.
Alzheimer Disease* ; Asian Continental Ancestry Group ; Erythema ; Heating ; Hot Temperature ; Humans ; Observational Study ; Pruritus ; Skin* ; Rivastigmine

BACKGROUND: Considering the functional role of red blood cells (RBC) in maintaining oxygen supply to tissues, RBC transfusion can be a life-saving intervention in situations of severe bleeding or anemia. RBC transfusion is often inevitable to address intraoperative massive bleeding; it is a key component in safe perioperative patient management. Unlike general medical resources, packed RBCs (pRBCs) have limited availability because their supply relies entirely on voluntary donations. Additionally, excessive utilization of pRBCs may aggravate prognosis or increase the risk of developing infectious diseases. Appropriate perioperative RBC transfusion is, therefore, crucial for the management of patient safety and medical resource conservation. These concerns motivated us to develop the present clinical practice guideline for evidence-based efficient and safe perioperative RBC transfusion management considering the current clinical landscape. METHODS: This guideline was obtained after the revision and refinement of exemplary clinical practice guidelines developed in advanced countries. This was followed by rigorous evidence-based reassessment considering the healthcare environment of the country. RESULTS: This guideline covers all important aspects of perioperative RBC transfusion, such as preoperative anemia management, appropriate RBC storage period, and leukoreduction (removal of white blood cells using filters), reversal of perioperative bleeding tendency, strategies for perioperative RBC transfusion, appropriate blood management protocols, efforts to reduce blood transfusion requirements, and patient monitoring during a perioperative transfusion. CONCLUSIONS: This guideline will aid decisions related to RBC transfusion in healthcare settings and minimize patient risk associated with unnecessary pRBC transfusion.
Anemia ; Blood Transfusion ; Communicable Diseases ; Delivery of Health Care ; Erythrocyte Transfusion ; Erythrocytes ; Hemorrhage ; Humans ; Leukocytes ; Monitoring, Physiologic ; Oxygen ; Patient Safety ; Prognosis

BACKGROUND: Considering the functional role of red blood cells (RBC) in maintaining oxygen supply to tissues, RBC transfusion can be a life-saving intervention in situations of severe bleeding or anemia. RBC transfusion is often inevitable to address intraoperative massive bleeding; it is a key component in safe perioperative patient management. Unlike general medical resources, packed RBCs (pRBCs) have limited availability because their supply relies entirely on voluntary donations. Additionally, excessive utilization of pRBCs may aggravate prognosis or increase the risk of developing infectious diseases. Appropriate perioperative RBC transfusion is, therefore, crucial for the management of patient safety and medical resource conservation. These concerns motivated us to develop the present clinical practice guideline for evidence-based efficient and safe perioperative RBC transfusion management considering the current clinical landscape. METHODS: This guideline was obtained after the revision and refinement of exemplary clinical practice guidelines developed in advanced countries. This was followed by rigorous evidence-based reassessment considering the healthcare environment of the country. RESULTS: This guideline covers all important aspects of perioperative RBC transfusion, such as preoperative anemia management, appropriate RBC storage period, and leukoreduction (removal of white blood cells using filters), reversal of perioperative bleeding tendency, strategies for perioperative RBC transfusion, appropriate blood management protocols, efforts to reduce blood transfusion requirements, and patient monitoring during a perioperative transfusion. CONCLUSIONS This guideline will aid decisions related to RBC transfusion in healthcare settings and minimize patient risk associated with unnecessary pRBC transfusion.