Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multipotent protein that plays essential roles in cellular responses to oxidative stress. Methods: To examine the role of APE1/Ref-1 in ischemia-reperfusion (I/R) injuries and hydrogen peroxide (H2O2)-induced renal tubular apoptosis, we studied male C57BL6 mice and human proximal tubular epithelial (HK-2) cells treated with H2O2 at different concentrations. The colocalization of APE1/Ref-1 in the proximal tubule, distal tubule, thick ascending limb, and collecting duct was observed with confocal microscopy. The overexpression of APE1/Ref-1 with knockdown cell lines using an APE1/Ref-1–specific DNA or small interfering RNA (siRNA) was used for the apoptosis assay. The promotor activity of nuclear factor kappa B (NF-κB) was assessed and electrophoretic mobility shift assay was conducted. Results: APE1/Ref-1 was predominantly localized to the renal tubule nucleus. In renal I/R injuries, the levels of APE1/Ref-1 protein were increased compared with those in kidneys subjected to sham operations. The overexpression of APE1/Ref-1 in HK-2 cells enhanced the Bax/Bcl-2 ratio as a marker of apoptosis. Conversely, the suppression of APE1/Ref-1 expression by siRNA in 1-mM H2O2-treated HK-2 cells decreased the Bax/Bcl-2 ratio, the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, p38, c-Jun N-terminal kinase (JNK) 1/2, and NF-κB. In HK-2 cells, the promoter activity of NF-κB increased following H2O2 exposure, and this effect was further enhanced by APE1/Ref-1 transfection. Conclusion: The inhibition of APE1/Ref-1 with siRNA attenuated H2O2-induced apoptosis through the modulation of mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 and the nuclear activation of NF-κB and proapoptotic factors.

There have been controversies on the prophylactic effect of hydroxychloroquine against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We describe a patient, 60-year old Korean woman, with coronavirus disease 2019 (COVID-19) who had been taking hydroxychloroquine for 6 months. Her serum and saliva concentrations of hydroxychloroquine were 280 μg/L and 4,890 μg/L, respectively. The present case raises concerns on hydroxychloroquine's role as a prophylactic agent for COVID-19.

Tracheomalacia is characterized by weakness of the tracheal walls and supporting cartilage. It results in dynamic compression of the airway, where the cross-sectional area of the trachea is reduced by expiratory compression. Acquired tracheomalacia results from complications associated with the use of endotracheal or tracheostomy tubes. In this report, we present three cases of patients with amyotrophic lateral sclerosis (ALS) successfully treated for tracheomalacia, including one case where the patient underwent surgery for combined tracheoesophageal fistula. We discuss the appropriate management strategies for tracheomalacia in patients with ALS. Through these case reports, we note the results of ALS patients who will have tracheostomy, and who are therefore at risk of sustaining a long term high cuff pressure, this study provides an evaluation for tracheomalacia and therapeutic management which should be considered for improving patient care outcomes.
Amyotrophic Lateral Sclerosis* ; Cartilage ; Humans ; Patient Care ; Trachea ; Tracheoesophageal Fistula ; Tracheomalacia* ; Tracheostomy

OBJECTIVE: To analyze the amount of weight-bearing during tilt table increments, with a review of neutral and unilateral knee flexion postures. METHODS: There were 17 healthy participants enrolled in this study. The subjects were tilted from 10° to 90°, and their body weight was measured at each 10° increment. In the first test, both plantar pressures, with the subjects in neutral posture, were recorded. During the second and third tests, the angle of inclination was thus recorded and increased, with the subjects in unilateral knee flexion posture; flexion was maintained at 25° by attaching a cylindrical support to the tilt table at the level of the popliteal fossa. RESULTS: The study was divided into two types of postures: neutral and unilateral knee flexion. The percentage of body weight (%BW) between each leg during neutral posture was noted as not being statistically significant. The %BW of one side during tilt table inclination was significantly different between the two postures at 10° to 80° (p < 0.05). The weight during unilateral knee flexion posture was lower as analyzed, regardless of tilt table inclination compared with that in neutral posture. We note that fifty percent of the ratio of %BW was noted at 33.12° and 38.76° in neutral and flexion postures, respectively. CONCLUSION: The unilateral knee flexion could induce the effect of decreased body weight compared with non-flexion side. The results of this study will help in setting a safe and quantitative percentage of weight-bearing on the lower extremity during tilt training.
Body Weight ; Healthy Volunteers ; Knee* ; Leg ; Lower Extremity ; Orthopedics ; Posture* ; Rehabilitation ; Weight-Bearing*

PURPOSE: There are few reports from Asian countries about the long-term results of aromatase inhibitor adjuvant treatment for breast cancer. This observational study aimed to evaluate the long-term effects of letrozole in postmenopausal Korean women with operable breast cancer. METHODS: Self-reported quality of life (QoL) scores were serially assessed for 3 years during adjuvant letrozole treatment using the Korean version of the Functional Assessment of Cancer Therapy-Breast questionnaires (version 3). Changes in bone mineral density (BMD) and serum cholesterol levels were also examined. RESULTS: All 897 patients received the documented informed consent form and completed a baseline questionnaire before treatment. Adjuvant chemotherapy was administered to 684 (76.3%) subjects, and 410 (45.7%) and 396 (44.1%) patients had stage I and II breast cancer, respectively. Each patient completed questionnaires at 3, 6, 12, 18, 24, 30, and 36 months after enrollment. Of 897 patients, 749 (83.5%) completed the study. The dropout rate was 16.5%. The serial trial outcome index, the sum of the physical and functional well-being subscales, increased gradually and significantly from baseline during letrozole treatment (p<0.001). The mean serum cholesterol level increased significantly from 199 to 205 after 36 months (p=0.042). The mean BMD significantly decreased from −0.39 at baseline to −0.87 after 36 months (p<0.001). CONCLUSION: QoL gradually improved during letrozole treatment. BMD and serum cholesterol level changes were similar to those in Western countries, indicating that adjuvant letrozole treatment is well tolerated in Korean women, with minimal ethnic variation.
Aromatase ; Asian Continental Ancestry Group ; Bone Density ; Breast Neoplasms* ; Breast* ; Chemotherapy, Adjuvant ; Cholesterol ; Consent Forms ; Female ; Humans ; Observational Study ; Quality of Life*

Pylephlebitis, or suppurative thrombophlebitis of the portal venous system, is a rare condition occurring secondary to abdominal infections such as diverticulitis. Pylephlebitis can be diagnosed via ultrasonography or CT scan, and is characterized by the presence of a thrombus in the portal vein and bacteremia. However, the diagnosis may be delayed due to the vague nature of the clinical symptoms, causing morbidity and mortality due to pylephlebitis to remain high. Early diagnosis and immediate antibiotic therapy are important for favorable prognosis. Therefore, pylephlebitis should be considered in the differential diagnosis for cases of nonspecific abdominal pain and fever. We report a case of pylephlebitis secondary to diverticulitis, associated with Pseudomonas aeruginosa sepsis. Such cases have not been widely reported.
Abdominal Pain ; Bacteremia ; Diagnosis ; Diagnosis, Differential ; Diverticulitis* ; Early Diagnosis ; Fever ; Liver Abscess* ; Liver* ; Mortality ; Portal Vein ; Prognosis ; Pseudomonas aeruginosa* ; Pseudomonas* ; Sepsis* ; Thrombophlebitis ; Thrombosis ; Tomography, X-Ray Computed ; Ultrasonography

Nafamostat mesilate (NM), a synthetic serine protease inhibitor, has anticoagulant and anti-inflammatory properties. The intracellular mediator and external anti-inflammatory external signal in the vascular wall have been reported to protect endothelial cells, in part due to nitric oxide (NO) production. This study was designed to examine whether NM exhibit endothelium dependent vascular relaxation through Akt/endothelial nitric oxide synthase (eNOS) activation and generation of NO. NM enhanced Akt/eNOS phosphorylation and NO production in a dose- and time-dependent manner in human umbilical vein endothelial cells (HUVECs) and aorta tissues obtained from rats treated with various concentrations of NM. NM concomitantly decreased arginase activity, which could increase the available arginine substrate for NO production. Moreover, we investigated whether NM increased NO bioavailability and decreased aortic relaxation response to an eNOS inhibitor in the aorta. These results suggest that NM increases NO generation via the Akt/eNOS signaling pathway, leading to endothelium-dependent vascular relaxation. Therefore, the vasorelaxing action of NM may contribute to the regulation of cardiovascular function.
Animals ; Aorta ; Arginase ; Arginine ; Biological Availability ; Endothelial Cells ; Endothelium ; Human Umbilical Vein Endothelial Cells ; Mesylates* ; Nitric Oxide ; Nitric Oxide Synthase ; Nitric Oxide Synthase Type III ; Phosphorylation ; Rats ; Relaxation ; Serine Proteases ; Vasodilation*

BACKGROUND AND OBJECTIVES: Apurinic/apyrimidinic endonuclease 1/redox effector factor-1 (APE1/Ref-1) is a multifunctional protein involved in the DNA base excision repair pathway, inflammation, angiogenesis, and survival pathways. We investigated serum APE1/Ref-1 in patients with coronary artery disease (CAD). SUBJECTS AND METHODS: Serum APE1/Ref-1 was measured with a sandwich enzyme-linked immunosorbent assay from 360 patients who received coronary angiograms. They were divided into two groups; a control (n=57) and a CAD group (n=303), the latter included angina (n=128) and myocardial infarction (MI, n=175). RESULTS: The levels of APE1/Ref-1 were higher in the CAD than the control (0.63+/-0.07 vs. 0.12+/-0.07 ng/100 microL, respectively; p<0.01). They were also higher in MI than angina (0.81+/-0.10 vs. 0.38+/-0.11 ng/100 microL, respectively; p<0.01) and different according to the thrombolysis in myocardial infarction (TIMI) flow (0.88+/-0.09 for TIMI flow 0, 1, 2 vs. 0.45+/-0.13 ng/100 microL for TIMI flow 3, p<0.01) in acute coronary syndrome. In correlation analysis, the levels of APE1/Ref-1 were positively correlated with Troponin I (r=0.222; p<0.0001) and N-terminal pro-B type natriuretic peptide (NT-proBNP, r=0.217; p<0.0001) but not high sensitivity to C-reactive protein. Also, they revealed a negative correlation with ejection fraction (EF, r=-0.221; p=0.002). However, there were no significant differences among the three groups, were divided by their levels of APE1/Ref-1, for major adverse cardiovascular events (death, recurrent MI, stroke, revascularization) (8.2 vs. 14.0 vs. 12.5%, p=ns). CONCLUSION: The levels of serum APE1/Ref-1 are elevated in CAD, and are higher in MI than in angina. They are correlated with Troponin I, NT-proBNP, and EF.
Acute Coronary Syndrome ; Biomarkers ; C-Reactive Protein ; Coronary Artery Disease* ; Coronary Vessels* ; DNA ; DNA Repair ; Enzyme-Linked Immunosorbent Assay ; Humans ; Inflammation ; Myocardial Infarction ; Stroke ; Troponin I

We report a case of duodenal metastasis from squamous cell carcinoma of the cervix confirmed by histopathological diagnosis. A 48-year-old woman was diagnosed with uterine cervix cancer stage IVB and underwent chemotherapy. During follow-up after chemotherapy, a mass suspicious of malignancy was found at the 3rd portion of the duodenum on the magnetic resonance imaging of the abdomen. Esophagogastroduodenoscopy with biopsy was done for an ulcerofungating mass at the 3rd portion of the duodenum. Squamous cell carcinoma was confirmed on the biopsy which was same as the histopathological diagnosis confirmed by cervix biopsy and right supraclavicular lymph node biopsy resulting from metastasis of cervix. Since 1981, only ten cases of small bowel metastasis from squamous cell carcinoma of cervix have been reported. It is exceedingly rare to find metastasis to the duodenum from uterine cervix cancer.
Abdomen ; Biopsy ; Carcinoma, Squamous Cell* ; Cervix Uteri* ; Diagnosis ; Drug Therapy ; Duodenum ; Endoscopy, Digestive System ; Female ; Follow-Up Studies ; Humans ; Lymph Nodes ; Magnetic Resonance Imaging ; Middle Aged ; Neoplasm Metastasis* ; Uterine Cervical Neoplasms

Pseudoxanthoma elasticum (PXE)-like disorder with multiple coagulation factor deficiency is a genetic disease characterized by dystrophic mineralization of the connective tissue in multiple organs such as the skin, arteries, and retina. Patients with this disorder have excessive folding and sagging of the skin with loss of recoil, as well as coagulopathy. Crohn's disease is a chronic inflammatory condition of the gastrointestinal tract, which primary affects the small intestine, often leading to malnutrition. Here, we describe the case of a 25-year-old woman who presented with these diseases. We found that nutrient deficiency due to long-term Crohn's disease aggravated the coagulopathy associated with PXE-like disorder.
Adult ; Arteries ; Blood Coagulation Factors* ; Connective Tissue ; Crohn Disease* ; Female ; Gastrointestinal Tract ; Humans ; Intestine, Small ; Malnutrition ; Pseudoxanthoma Elasticum ; Retina ; Skin