A novel small molecule, CU05-1189, targeting the pleckstrin homology domain of PDK1 suppresses VEGF-mediated angiogenesis and tumor growth by blocking the Akt signaling pathway.

Inhibition of angiogenesis is considered a promising therapeutic approach for cancer treatment. Our previous genetic research showed that the use of a cell-penetrating peptide to inhibit the pleckstrin homology (PH) domain of 3-phosphoinositide-dependent kinase 1 (PDK1) was a viable approach to suppress pathological angiogenesis. Herein, we synthesized and characterized a novel small molecule, CU05-1189, based on our prior study and present evidence for the first time that this compound possesses antiangiogenic properties both and .

Prevalence and Risk Factors of Respiratory Viral Infections in Exacerbations of Chronic Obstructive Pulmonary Disease.

Exacerbations of chronic obstructive pulmonary disease (COPD) lead to high morbidity and mortality. Respiratory virus infection is considered as one of the important causes of COPD exacerbations. The aim of this study was to assess the prevalence of respiratory virus infection in COPD exacerbations and to find the factors associated with susceptibility to viral infections.

Anti-inflammatory effect of a selective 11β-hydroxysteroid dehydrogenase type 1 inhibitor via the stimulation of heme oxygenase-1 in LPS-activated mice and J774.1 murine macrophages.

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts inactive cortisone to the active cortisol. 11β-HSD1 may be involved in the resolution of inflammation. In the present study, we investigate the anti-inflammatory effects of 2-(3-benzoyl)-4-hydroxy-1,1-dioxo-2H-1,2-benzothiazine-2-yl-1-phenylethanone (KR-66344), a selective 11β-HSD1 inhibitor, in lipopolysaccharide (LPS)-activated C57BL/6J mice and macrophages.

Pharmacokinetic characterization of 2-(3-benzoyl)-4-hydroxy-1,1-dioxo-2H-1,2-benzothiazine-2-yl-1-phenylethanone, a novel 11β-hydroxysteroid dehydrogenase type 1 inhibitor in rats.

11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is associated with metabolic syndromes such as type 2 diabetes mellitus and obesity. A new 11β-HSD1 inhibitor known as 2-(3-benzoyl)-4-hydroxy-1, 1-dioxo-2H-1, 2-benzothiazine-2-yl-1-phenylethanone (KR-66344) is being developed as a therapeutic agent for these metabolic diseases. The purpose of this study was to characterize the pharmacokinetics of KR-66344 to support further preclinical development.

The Wnt/β-catenin signaling pathway regulates the development of airway remodeling in patients with asthma.

Airway remodeling is a key characteristic of chronic asthma, particularly in patients with a fixed airflow limitation. The mechanisms underlying airway remodeling are poorly understood, and no therapeutic option is available. The Wnt/β-catenin signaling pathway is involved in various physiological and pathological processes, including fibrosis and smooth muscle hypertrophy.

Pulmonary Foreign Body Granulomatosis in Dental Technician.

Occupational lung diseases are caused by several toxic substances including heavy metals; however, the exact pathologic mechanisms remain unknown. In the workplace, dental technicians are often exposed to heavy metals such as cobalt, nickel, or beryllium and occasionally develop occupational lung diseases. We described a case of occupational lung disease in a patient who was employed as a dental technician for over a decade.

A Case of Significant Endobronchial Injury due to Recurrent Iron Pill Aspiration.

Gastric mucosal damage by iron pills is often reported. However, iron pill aspiration is uncommon. Oxidation of the impacted iron pill causes bronchial mucosal damage that progresses to chronic bronchial inflammation, necrosis, endobronchial stenosis and rarely, perforation.

Discovery and optimization of adamantane carboxylic acid derivatives as potent diacylglycerol acyltransferase 1 inhibitors for the potential treatment of obesity and diabetes.

We have developed a series of adamantane carboxylic acid derivatives exhibiting potent diacylglycerol acyltransferase 1 (DGAT1) inhibitory activities. Optimization of the series led to the discovery of E-adamantane carboxylic acid compound 43c, which showed excellent in vitro activity with an IC50 value of 5 nM against human and mouse DGAT1, also good druggability as well as microsomal stability and safety profiles such as hERG, CYP and cytotoxicity. Compound 43c significantly reduced plasma triglyceride levels in vivo (in rodents and zebrafish) and also showed bodyweight gain reduction and glucose area under curve (AUC) lowering efficacy in diet-induced obesity (DIO) mice.

Fatal clinical course of probable invasive pulmonary aspergillosis with influenza B infection in an immunocompetent patient.

Invasive pulmonary aspergillosis (IPA) is rarely reported in patients who have normal immune function. Recently, IPA risk was reported in nonimmunocompromised hosts, such as patients with chronic obstructive pulmonary disease and critically ill patients in intensive care units. Moreover, influenza infection is also believed to be associated with IPA among immunocompetent patients.

The effects of secondhand smoke on chronic obstructive pulmonary disease in nonsmoking Korean adults.

Background/aims: Smoking is widely acknowledged as the single most important risk factor for chronic obstructive pulmonary disease (COPD). However, the risk of COPD in nonsmokers exposed to secondhand smoke remains controversial. In this study, we investigated the association of secondhand smoke exposure with COPD prevalence in nonsmokers who reported never smoking.

The extended rapid response system: 1-year experience in a university hospital.

The rapid response system (RRS) is an innovative system designed for in-hospital, at-risk patients but underutilization of the RRS generally results in unexpected cardiopulmonary arrests. We implemented an extended RRS (E-RRS) that was triggered by actively screening at-risk patients prior to calls from primary medical attendants. These patients were identified from laboratory data, emergency consults, and step-down units.

Preclinical pharmacokinetic characterization of 2-(4-(4-(5-(2-phenyl-5-(trifluoromethyl)oxazole-4-carboxamido)-1H-benzo[d]imidazol-2-yl)phenyl)cyclohexyl) acetic acid, a novel DGAT-1 inhibitor.

1. A novel diacylglyceride acyltransferase-1 (DGAT-1) inhibitor, 2-(4-(4-(5-(2-phenyl-5-(trifluoromethyl) oxazole-4-carboxamido)-1H-benzo[d]imidazol-2-yl)phenyl)cyclohexyl) acetic acid (KR-69232), was synthesized for a potential therapeutic use against several metabolic disorders, such as obesity, insulin resistance, and type II diabetes, characterized by excessive triglycerides (TGs) in the blood. 2.

Determination of a novel diacylglycerol acyltransferase 1 inhibitor, 2-[4-(4-{5-[2-phenyl-5-(trifluoromethyl) oxazole-4-carboxamido]-1H-benzo[d]imidazol-2-yl} phenyl) cyclohexyl] acetic acid (KR-69232) in rat plasma using liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study.

A liquid chromatography-tandem mass spectrometry method was developed and validated for the quantification of KR-69232, a diacyltransferase 1 inhibitor, in rat plasma. KR-69232 in the concentration range of 0.004-4 µg/mL was linear.

Cerebral air embolism following pigtail catheter insertion for pleural fluid drainage.

Pigtail catheter drainage is a common procedure for the treatment of pleural effusion and pneumothorax. The most common complications of pigtail catheter insertion are pneumothorax, hemorrhage and chest pains. Cerebral air embolism is rare, but often fatal.

Synthesis and biological evaluation of aminobenzimidazole derivatives with a phenylcyclohexyl acetic acid group as anti-obesity and anti-diabetic agents.

A series of benzimidazole derivatives with a phenylcyclohexyl acetic acid group as DGAT-1 inhibitors was developed. Among the benzimidazole series, compound 5k showed submicromolar in vitro activity toward human and mouse DGAT-1, good selectivity toward DGAT-2, human liver metabolic stability, and pharmacokinetic (PK) and safety profiles such as hERG, CYP and acute toxicity. Additionally, 5k showed good in vivo efficacy in 4weeks study with DIO mouse model.

Incidence and risk factors of contrast-induced nephropathy after bronchial arteriography or bronchial artery embolization.

Background: In uncontrolled hemoptysis patient, bronchial arteriography and bronchial artery embolization (BAE) is a important procedure in diagnosis and treatment. The aim of this study is to assess the incidence of contrast-induced nephropathy and the risk factors of contrast-induced nephropathy (CIN) after bronchial arteriography and BAE.

Methods: We retrospectively reviewed the medical records of the patients who underwent bronchial arteriography and BAE in two university hospitals from January 2003 to December 2011.

Regioselective synthesis of 2-amino-substituted 1,3,4-oxadiazole and 1,3,4-thiadiazole derivatives via reagent-based cyclization of thiosemicarbazide intermediate.

A regioselective, reagent-based method for the cyclization reaction of 2-amino-1,3,4-oxadiazole and 2-amino-1,3,4-thiadiazole core skeletons is described. The thiosemicarbazide intermediate 3 was reacted with EDC·HCl in DMSO or p-TsCl, triethylamine in N-methyl-2-pyrrolidone to give the corresponding 2-amino-1,3,4-oxadiazoles 4 and 2-amino-1,3,4-thiadiazoles 5 through regioselcective cyclization processes. The regioselectivity was affected by both R(1) and R(2) in p-TsCl mediated cyclization.

Congenital cystic adenomatoid malformation with bronchial atresia in elderly patients.

Unlabelled: Congenital cystic adenomatoid malformation (CCAM) is an uncommon, nonhereditary anomaly caused by arrest of lung. Patients with CCAM may present with respiratory distress as newborns, or may remain asymptomatic until later in life. CCAM type I is rarely found in association with bronchial atresia (BA) in adults; we present such a case.

Comparison of two exhaled nitric oxide analyzers: the NIOX MINO hand-held electrochemical analyzer and the NOA280i stationary chemiluminescence analyzer.

Background And Objective: Measurement of the fraction of nitric oxide (FeNO) in exhaled air is useful in the management of asthma. A new hand-held nitric oxide (NO) analyzer, the NIOX MINO, is simple and easy to use in clinical practice. In this study, FeNO values measured using the NIOX MINO were compared with those obtained using a stationary chemiluminescence analyzer, the Sievers NOA280i.

Measurement of nasal nitric oxide is useful for the diagnosis of sinusitis-induced prolonged cough.

Upper airway cough syndrome (UACS), the most common cause of prolonged cough, is diagnosed based on clinical findings without specific diagnostic test. The concentration of nitric oxide in nasal cavity air (nNO) is influenced by allergic rhinitis and/or sinusitis, both of which are common causes of UACS. We measured nNO levels in patients with UACS and those with other causes.

Blockade of the Wnt/β-catenin pathway attenuates bleomycin-induced pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease and characterized by abnormal growth of fibroblasts and lung scarring. While the pathogenesis of IPF is not clearly understood, activation of transforming growth factor-β (TGF-β) and disruption of alveolar basement membrane seem to play important roles in leading to excess disruption of the matrix, which is associated with activated matrix metalloproteinase (MMP) and aberrant proliferation of myofibroblasts. The Wnt/β-catenin pathway is an important regulator of cellular proliferation and differentiation and abnormal activation of Wnt/β-catenin signal was observed in IPF.

High prevalence of bronchiectasis in adults: analysis of CT findings in a health screening program.

Bronchiectasis is one of the common chronic respiratory diseases and associated with respiratory morbidity and mortality. However, neither its prevalence nor its etiology is well-defined. We aimed to estimate the prevalence and risk factors of bronchiectasis in adults.

Inappropriate techniques used by internal medicine residents with three kinds of inhalers (a metered dose inhaler, Diskus, and Turbuhaler): changes after a single teaching session.

Background: While initial education and regular evaluation of inhaler technique in patients are emphasized in the management of asthma and chronic obstructive pulmonary disease, health care professionals are not experienced in using inhalers. This study assessed whether internal medicine residents used common inhalers correctly and whether a single teaching session successfully improved their performance.

Methods: We evaluated 142 internal medicine residents from six university hospitals in Korea for their techniques with three different inhaler devices: a metered dose inhaler (MDI), Diskus, and Turbuhaler.

Genetic and epigenetic analysis of the EPHB2 gene in gastric cancers.

EPHB2 is a member of the Eph receptor tyrosine kinase family and a direct transcriptional target of beta-catenin/TCF. EPHB2 plays an important role in maintaining the correct positioning of the proliferative compartment in the crypt-villous axis. A loss of EPHB2 expression has been observed in human tumors, particularly in colonic adenomas and carcinomas.