The basic action mechanism of sodium-glucose cotransporter 2 (SGLT2) inhibitor is to lower the glucose burden by excreting the glucose filtered by the kidney into the urine. Although SGLT2 inhibitors are primarily indicated as glucose-lowering agents, they have a broad range of effects on renal function and plasma volume homeostasis, as well as on adiposity and energy metabolism across the entire body. That might be why SGLT2 inhibition causes spill-over of sodium and glucose beyond the proximal tubule, triggering dynamic and reversible realignment of energy metabolism, renal filtration, and plasma volume. A better understanding of SGLT2 inhibition in the kidney and the entire body will lead to more benefits in people with and without diabetes.
Adiposity ; Diabetes Mellitus ; Energy Metabolism ; Filtration ; Glucose ; Homeostasis ; Kidney ; Molecular Mechanisms of Pharmacological Action ; Plasma Volume ; Sodium

BACKGROUND/AIMS: Several studies have identified a role for nuclear factor erythroid 2-related factor 2 (Nrf2) in the development of chronic obstructive pulmonary disease (COPD). However, the relationship between the plasma Nrf2 level and the extent of systemic inflammation associated with COPD status remains unclear. METHODS: Patients diagnosed with COPD were recruited from St. Paul’s Hospital, The Catholic University of Korea, between July 2009 and May 2012. Patients were classified into two groups according to the severity of their symptoms on initial presentation, a COPD-stable group (n = 25) and a COPD-exacerbation group (n = 30). Seventeen patients were enrolled as a control group (n = 17). The plasma levels of Nrf2 and other systemic inf lammatory biomarkers, including interleukin 6 (IL-6), surfactant protein D (SP-D), and C-reactive protein (CRP), were measured. We collected clinical data including pulmonary function test results, and analyzed the relationships between the biomarker levels and the clinical parameters. RESULTS: Plasma Nrf2 and CRP levels significantly increased in a stepwise manner with an increase in inflammatory status (control vs. COPD-stable vs. COPD-exacerbation) (p = 0.002, p < 0.001). Other biomarkers of systemic inflammation (IL-6, SP-D) exhibited similar tendencies, but significant differences were not apparent. Furthermore, we observed negative correlations between the plasma level of Nrf2 and both the forced expiratory volume in 1 second (FEV1) (r = –0.339, p = 0.015) and the forced expiratory ratio (FEV1/forced vital capacity [FVC]) (r = –0.342, p = 0.014). However, CRP level was not correlated with any measured parameter. CONCLUSIONS: Plasma Nrf2 levels gradually increased in line with disease severity and the extent of systemic inflammation in patients with COPD.
Biomarkers ; C-Reactive Protein ; Forced Expiratory Volume ; Humans ; Inflammation ; Interleukin-6 ; Korea ; Lung Diseases ; NF-E2-Related Factor 2 ; Plasma ; Pulmonary Disease, Chronic Obstructive* ; Pulmonary Surfactant-Associated Protein D ; Respiratory Function Tests ; Vital Capacity

PURPOSE: The tight junction protein claudin-5 (CLDN5) is critical to the control of endothelial cellular polarity and pericellular permeability. The role of CLDN5 in chronic obstructive pulmonary disease (COPD) remains unclear. The aim of this study was to investigate the association between CLDN5 levels and clinical variables in patients with COPD. METHODS: In total, 30 patients with COPD and 30 healthy controls were enrolled in the study. The plasma CLDN5 level was checked in patients with stable or exacerbated COPD and in healthy controls. RESULTS: The mean plasma CLDN5 level of patients with COPD was 0.63 ± 0.05 ng/mL and that of healthy controls was 6.9 ± 0.78 ng/mL (P = 0.001). The mean plasma CLDN5 level was 0.71 ± 0.05 ng/mL in exacerbated COPD patients and 0.63 ± 0.04 ng/mL in patients with stable COPD (P < 0.05). The plasma CLDN5 level among COPD subjects was correlated with the smoking amount (r = −0.530, P = 0.001). The plasma CLDN5 level in stable COPD patients was correlated with forced expiratory volume in one second (FEV1, %pred.) (r = −0.481, P = 0.037). CONCLUSIONS: The plasma CLDN5 level was not correlated with age. CLDN5 may be involved in the pathogenesis of COPD. Further studies having a larger sample size will be needed to clarify CLDN5 in COPD.
Claudin-5* ; Forced Expiratory Volume ; Humans ; Permeability ; Plasma ; Pulmonary Disease, Chronic Obstructive* ; Sample Size ; Smoke ; Smoking ; Tight Junctions*

The electrogenic sodium/bicarbonate cotransporter 1 (NBCe1) on the basolateral side of the renal proximal tubule plays a pivotal role in systemic acid-base homeostasis. Mutations in the gene encoding NBCe1 cause severe proximal renal tubular acidosis accompanied by other extrarenal symptoms. The proximal tubule reabsorbs most of the sodium filtered in the glomerulus, contributing to the regulation of plasma volume and blood pressure. NBCe1 and other sodium transporters in the proximal tubule are regulated by hormones, such as angiotensin II and insulin. Angiotensin II is probably the most important stimulator of sodium reabsorption. Proximal tubule AT(1A) receptor is crucial for the systemic pressor effect of angiotensin II. In rodents and rabbits, the effect on proximal tubule NBCe1 is biphasic; at low concentration, angiotensin II stimulates NBCe1 via PKC/cAMP/ERK, whereas at high concentration, it inhibits NBCe1 via NO/cGMP/cGKII. In contrast, in human proximal tubule, angiotensin II has a dose-dependent monophasic stimulatory effect via NO/cGMP/ERK. Insulin stimulates the proximal tubule sodium transport, which is IRS2-dependent. We found that in insulin resistance and overt diabetic nephropathy, stimulatory effect of insulin on proximal tubule transport was preserved. Our results suggest that the preserved stimulation of the proximal tubule enhances sodium reabsorption, contributing to the pathogenesis of hypertension with metabolic syndrome. We describe recent findings regarding the role of proximal tubule transport in the regulation of blood pressure, focusing on the effects of angiotensin II and insulin.
Acidosis, Renal Tubular ; Angiotensin II ; Blood Pressure* ; Diabetic Nephropathies ; Homeostasis ; Humans ; Hypertension ; Insulin ; Insulin Resistance ; Kidney Tubules, Proximal ; Plasma Volume ; Rabbits ; Rodentia ; Sodium ; Sodium-Bicarbonate Symporters

This study explored the relationship between the fractional exhaled nitric oxide (FeNO) level and the efficacy of inhaled corticosteroid (ICS) in asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) patients with different disease severity. A total of 127 ACOS patients with ACOS (case group) and 131 healthy people (control group) were enrolled in this study. Based on the severity of COPD, the ACOS patients were divided into: mild ACOS; moderate ACOS; severe ACOS; and extremely severe ACOS groups. We compared FeNO levels, pulmonary function parameters including percentage of forced expiratory volume in 1 second (FEV1) to predicted value (FEV1%pred), ratio of FEV1 to forced vital capacity (FEV1/FVC), inspiratory capacity to total lung capacity (IC/TLC) and residual volume to total lung capacity (RV/TLC), arterial blood gas parameters, including PH, arterial partial pressure of oxygen (PaO₂) and arterial partial pressure of carbon dioxide (PaCO₂), total serum immunoglobulin E (IgE), induced sputum eosinophil (EOS), plasma surfactant protein A (SP-A), plasma soluble receptor for advanced glycation end products (sRAGE), sputum myeloperoxidase (MPO), sputum neutrophil gelatinase-associated lipocalin (NGAL) and Asthma Control Test (ACT) scores, and COPD Assessment Test (CAT) scores. Compared with pre-treatment parameters, the FeNO levels, RV/TLC, PaCO₂, total serum IgE, induced sputum EOS, plasma SP-A, sputum MPO, sputum NGAL, and CAT scores were significantly decreased after 6 months of ICS treatment, while FEV1%pred, FEV1/FVC, IC/TLC, PH, PaO₂, plasma sRAGE, and ACT scores were significantly increased in ACOS patients with different disease severity after 6 months of ICS treatment. This finding suggests that the FeNO level may accurately predict the efficacy of ICS in the treatment of ACOS patients.
Animals ; Asthma ; Carbon Dioxide ; Cats ; Eosinophils ; Forced Expiratory Volume ; Glycosylation End Products, Advanced ; Humans ; Hydrogen-Ion Concentration ; Immunoglobulin E ; Immunoglobulins ; Inspiratory Capacity ; Lipocalins ; Lung Diseases, Obstructive ; Neutrophils ; Nitric Oxide* ; Oxygen ; Partial Pressure ; Peroxidase ; Plasma ; Pulmonary Disease, Chronic Obstructive ; Pulmonary Surfactant-Associated Protein A ; Residual Volume ; Sputum ; Total Lung Capacity ; Vital Capacity

In the field of orofacial surgery, a red blood cell transfusion (RBCT) is occasionally required during double jaw and oral cancer surgery. However, the question remains whether the effect of RBCT during the perioperative period is beneficial or harmful. The answer to this question remains challenging. In the field of orofacial surgery, transfusion is performed for the purpose of oxygen transfer to hypoxic tissues and plasma volume expansion when there is bleeding. However, there are various risks, such as infectious complications (viral and bacterial), transfusion-related acute lung injury, ABO and non-ABO associated hemolytic transfusion reactions, febrile non-hemolytic transfusion reactions, transfusion associated graft-versus-host disease, transfusion associated circulatory overload, and hypersensitivity transfusion reaction including anaphylaxis and transfusion-related immune-modulation. Many studies and guidelines have suggested RBCT is considered when hemoglobin levels recorded are 7 g/dL for general patients and 8-9 g/dL for patients with cardiovascular disease or hemodynamically unstable patients. However, RBCT is occasionally an essential treatment during surgeries and it is often required in emergency cases. We need to comprehensively consider postoperative bleeding, different clinical situations, the level of intra- and postoperative patient monitoring, and various problems that may arise from a transfusion, in the perspective of patient safety. Since orofacial surgery has an especially high risk of bleeding due to the complex structures involved and the extensive vascular distribution, measures to prevent bleeding should be taken and the conditions for a transfusion should be optimized and appropriate in order to promote patient safety.
Acute Lung Injury ; Anaphylaxis ; Cardiovascular Diseases ; Emergencies ; Erythrocyte Transfusion* ; Erythrocytes* ; Graft vs Host Disease ; Hemorrhage ; Humans ; Hypersensitivity ; Jaw ; Monitoring, Physiologic ; Mouth Neoplasms ; Oxygen ; Patient Safety ; Perioperative Period ; Plasma Volume ; Transfusion Reaction

BACKGROUND AND OBJECTIVES: Myocardial wall stretch is the main trigger for pro-brain natriuretic peptide (pro-BNP) secretion. The reduced heart rate associated with bradyarrhythmia increases stroke volume, resulting in increased wall tension. Therefore, we propose that bradyarrhythmia could increase plasma N-terminal pro-BNP (NT-pro-BNP) levels. SUBJECTS AND METHODS: We enrolled 125 patients who received a temporary pacemaker because they had sinus node dysfunction (SND) or atrioventricular blocks (AVBs). Patients with renal dysfunction, hyperkalemia, reduced left ventricular systolic function (left ventricular ejection fraction [LVEF], <40%), and atrial fibrillation were excluded. Heart failure (HF) was defined as an NT-pro-BNP level of >300 pg/mL. We evaluated history of hypertension, diabetes mellitus, and ischemic heart disease, plasma NT-pro-BNP levels, body mass index (BMI), LVEF, left atrial diameter (LAD), and escape rhythm rate. RESULTS: The log plasma NT-pro-BNP level of the patients with AVBs was significantly increased compared to that of the patients with SND (3.17±0.55 vs. 2.93±0.64 pg/mL, respectively; p=0.03). The incidence of HF was 72.5% (106 patients; 44 male patients). Further, the incidence of HF was significantly higher among patients with AVBs than among patients with SND. The type of bradyarrhythmia was found to be the only predictor of HF after adjusting for age, history of hypertension, LAD, and LVEF. The LVEF, LAD, and ventricular rate were similar between the 2 groups. CONCLUSION: As in the case of patients with tachyarrhythmia, bradyarrhythmia may increase plasma NT-pro-BNP levels, leading to HF. Therefore, the possibility of HF should be considered in patients with bradyarrhythmia.
Arrhythmias, Cardiac ; Atrial Fibrillation ; Atrioventricular Block ; Body Mass Index ; Bradycardia* ; Diabetes Mellitus ; Heart Failure ; Heart Rate ; Humans ; Hyperkalemia ; Hypertension ; Incidence ; Male ; Myocardial Ischemia ; Plasma* ; Sick Sinus Syndrome ; Stroke Volume ; Tachycardia ; United Nations

Picosulfate sodium/Magnesium citrate (PS/MC) is a common bowel cleansing agent for colonoscopy. It is equally effective and better tolerated by patients with regard to taste and volume than polyethylene glycol. However, because of its osmotically active characteristics, PS/MC can cause plasma volume depletion and electrolyte disturbances, such as hyponatremia. Here, we report a case of severe hyponatremia combined with loss of consciousness in a 59-year-old woman following ingestion of PS/MC as bowel preparation for a screening colonoscopy. Upon arrival, serum sodium level was 109 mEq/L and urine osmolality and sodium levels were 393 mOms/Kg and 99 mmol/L, respectively. She was euvolemic and showed normal kidney, thyroid, and adrenal function. Based on these findings, inappropriate anti-diuretic hormone syndrome (SIADH) was diagnosed. She was treated with 3% hypertonic saline and completely recovered without any neurologic sequelae. This case shows that SIADH can be caused by PS/MC (not accompanied by dehydration), even in patients without any underlying renal, heart, or liver diseases.
Citric Acid* ; Colonoscopy ; Detergents ; Eating* ; Female ; Heart ; Humans ; Hyponatremia* ; Inappropriate ADH Syndrome ; Kidney ; Liver Diseases ; Mass Screening ; Middle Aged ; Osmolar Concentration ; Plasma Volume ; Polyethylene Glycols ; Sodium ; Thyroid Gland ; Unconsciousness

OBJECTIVES: Argon plasma coagulation (APC) is a noncontact form of electrocautery that utilizes ionized argon as the electrical current. A rigid bronchoscopic use of APC for the management of central airway obstruction could be safe and rapidly effective. This study evaluated the usefulness of rigid bronchoscopy with APC for the management of central airway obstructions due to benign or malignant tumors. METHODS: Twenty patients with obstructing central airway tumors were retrospectively reviewed from February 2008 to February 2013 at Chonnam National University Hospital. All patients received rigid bronchoscopic tumor removal under general anesthesia. APC was applied before and after tumor removal. RESULTS: The median age of patients was 59 years (interquartile range [IQR], 51 to 67 years) and 70% were female. The causes of airway obstruction included malignancy (n=8) and benign tumor (n=12). Airway tumors comprised intraluminal lesions (n=11, 55%) and mixed intraluminal/extraluminal lesions (n=9, 45%). The median tumor size was 15 mm (IQR, 10 to 18 mm). The median degree of airway obstruction was significantly reduced after intervention (90% [IQR, 88% to 96%] vs. 10% [IQR, 0% to 20%], P<0.001). The median American Thoracic Society dyspnea grade (3 [IQR, 1 to 4] vs. 1 [IQR, 0 to 1], P<0.001) and forced expiratory volume in one second (1.03 L [IQR, 0.52 to 1.36 L] vs. 1.98 L [IQR, 1.57 to 2.64 L], P=0.004) were significantly improved after intervention. There were no procedure-related acute complications and deaths. CONCLUSION: Rigid bronchoscopy with APC is an effective and safe procedure to alleviate central airway obstruction caused by tumors.
Airway Obstruction ; Anesthesia, General ; Argon Plasma Coagulation* ; Argon* ; Bronchoscopy ; Dyspnea ; Electrocoagulation ; Female ; Forced Expiratory Volume ; Humans ; Jeollanam-do ; Retrospective Studies

PURPOSE: Dysregulated cysteinyl leukotriene (CysLT) synthesis is prominent in exercise-induced bronchoconstriction (EIB). Secreted phospholipase A2 (sPLA2) plays a key regulatory role in the biosynthesis of CysLTs. We previously found that serum leptin levels correlate with (EIB) in children with asthma. The aim of this study was to address the relationship between plasma sPLA2/leptin levels and EIB. METHODS: Sixty-seven prepubertal children between the ages of 6 and 10 years were included in the study. They were asthmatics with EIB (n=25), asthmatics without EIB (n=21), and healthy subjects (n=21). We measured the plasma sPLA2 and leptin levels. We also performed pulmonary function tests at baseline, after bronchodilator inhalation, and after exercise. RESULTS: The sPLA2 and leptin levels were significantly higher in asthmatics with EIB than in those without and control subjects. In addition, sPLA2 levels were significantly correlated with body mass index (Speraman correlation coefficient r=0.343, P=0.023) and leptin levels (partial correlation coefficient r=318, P=0.033). The maximum decrease in % forced expiratory volume in 1 second after exercise was significantly correlated with both PLA2 levels (r=0.301, P=0.041) and leptin levels (r=0.346, P=0.018). CONCLUSION: The sPLA2 and leptin levels were significantly higher in asthmatics with EIB than in asthmatics without EIB and control subjects. In addition, sPLA2 levels were significantly correlated with leptin levels and EIB in asthmatic children.
Asthma ; Body Mass Index ; Bronchoconstriction* ; Child* ; Forced Expiratory Volume ; Humans ; Inhalation ; Leptin* ; Phospholipases A2* ; Plasma* ; Respiratory Function Tests