Optimization and Evaluation of Novel Antifungal Agents for the Treatment of Fungal Infection.

Due to the increased morbidity and mortality by fungal infections and the emergence of severe antifungal resistance, there is an urgent need for new antifungal agents. Here, we screened for antifungal activity in our in-house library through the minimum inhibitory concentration test and derived two hit compounds with moderate antifungal activities. The hit compounds' antifungal activities and drug-like properties were optimized by substituting various aryl ring, alkyl chain, and methyl groups. Among the optimized compounds, 22h was the most promising candidate with good drug-like properties and exhibited potent fast-acting fungicidal antifungal effects against various fungal pathogens and synergistic antifungal activities with some known antifungal drugs. Additionally, 22h was further confirmed to disturb fungal cell wall integrity by activating multiple cell wall integrity pathways. Furthermore, 22h exerted significant antifungal efficacy in both the subcutaneous infection mouse model and ex vivo human nail infection model.

Day Temperature Difference and Aggravation of Low Urinary Tract Symptom in Benign Prostate Hypertrophy Patients in Korea: A National Health Insurance Service-National Cohort-based Study.

OBJECTIVE: To investigate the symptom deterioration of patients with benign prostatic hyperplasia (BPH) according to the difference in daily temperature. PATIENTS AND METHODS: From the National Health Insurance Service database, we collected and analyzed data on patients with BPH in 6 major metropolitan areas in Korea between January 2008 and December 2017. We investigated the rate of emergency room visits as well as the rate of urethral catheter insertion. RESULTS: In total, 1,446,465 patients were enrolled in this study. When the daily temperature difference was below 4°C, 28.5 patients visited the emergency room daily, while 42.2 patients visited the emergency room daily when the daily temperature difference exceeded 14°C. When the daily temperature difference was more than 14°C, about 48.0% more patients visited the emergency room than when the daily temperature difference was below 4°C. After visiting the emergency room, there were 11.9 patients who had a catheter inserted daily at the daily temperature difference below 4°C. When the daily temperature difference was more than 14°C, the number of catheter insertion cases was 17.8 patients daily, which was 49.2% higher than that of below 4°C. By time, surgery was performed most frequently within 3 months after visiting the emergency room. CONCLUSION: Day temperature difference appear to be related to the Lower urinary tract symptom of BPH patients.

Risk Factor Analysis of Ciprofloxacin-Resistant and Extended Spectrum Beta-Lactamases Pathogen-Induced Acute Bacterial Prostatitis in Korea.

The objectives of this study were to investigate risk factors and the incidence of ciprofloxacin resistance and extended-spectrum beta-lactamases (ESBL) in patients with acute bacterial prostatitis (ABP). We reviewed the medical records of 307 patients who were diagnosed with ABP between January 2006 and December 2015. The etiologic pathogens and risk factors for ciprofloxacin-resistant E. coli and ESBL-producing microbes, susceptibility to ciprofloxacin, and the incidence of ESBL in patients with ABP were described. History of prior urologic manipulation was an independent risk factor for ciprofloxacin-resistant (P = 0.005) and ESBL-producing microbes (P = 0.005). Advanced age (over 60 years) was an independent risk factor for ciprofloxacin-resistant microbes (P = 0.022). The ciprofloxacin susceptibility for Escherichia coli in groups without prior manipulation was documented 85.7%. For groups with prior manipulation, the susceptibility was 10.0%. Incidence of ESBL-producing microbes by pathogen was 3.8% for E. coli and 1.0% for Klebsiella pneumonia in the absence of manipulation group, and 20% and 33.3% in the presence of manipulation group, respectively. Initial treatment of ABP must consider patient's age and the possibility of prior manipulation to optimize patient treatment. With the high rate of resistance to fluoroquinolone, cephalosporins with amikacin, or carbapenems, or extended-spectrum penicillin with beta lactamase inhibitor should be considered as the preferred empirical ABP treatment in the patients with history of prior urologic manipulation.

Effect of rutin from tartary buckwheat sprout on serum glucose-lowering in animal model of type 2 diabetes.

This study investigates the anti-diabetic effects of rutin from tartary buckwheat sprout in type 2 diabetes mouse model. The rutin content in tartary buckwheat sprout (TBS) is five times higher than that found in common buckwheat sprout (CBS) as evident from high-performance liquid chromatography analysis. Administration of either rutin or TBS ethanolic extract to diabetes mice decreased the serum glucose level significantly. Rutin down-regulated the expression levels of protein-tyrosine phosphatase 1B; it is negative regulator of insulin pathway, both transcriptionally and translationally in myocyte C2C12 in a dose-dependent manner. In conclusion, rutin can play a critical role in down-regulation of serum glucose level in type 2 diabetes.

An enzymatically fortified ginseng extract inhibits proliferation and induces apoptosis of KATO3 human gastric cancer cells via modulation of Bax, mTOR, PKB and IκBα.

Accumulative evidence suggests ginseng extract and/or its major components, ginsenosides and compound K, a metabolized ginseng saponin, have anti-cancer effects. In the present study, the effects of a ginseng butanolic extract (GBX) and an enzymatically fortified ginseng extract (FGX), with enriched ginsenosides and compound K, on the growth of KATO3 human gastric cancer cells were investigated using a cell viability assay. While treatment with GBX at 31.25-125 mg/ml for 24 h did not affect the proliferation of KATO3 cells, FGX under the same conditions inhibited cell proliferation in a concentration-dependent manner. Furthermore, Annexin V/PI-staining and flow cytometric analysis demonstrated that the population of apoptotic KATO3 cells was increased following treatment with FGX, which was greater than in the GBX-treated cells, suggesting that FGX had a stronger apoptotic effect than GBX. To investigate the underlying mechanism of the cytostatic and cytotoxic effects of the ginseng extracts, apoptosis-associated proteins were assessed using western blot analysis. The data revealed higher expression levels of B-cell lymphoma 2-associated X protein (Bax), lower expression of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor α (IκBα) and reduced phosphorylation of mammalian target of rapamycin (mTOR) and protein kinase B (PKB) in the FGX-treated KATO3 cells than in the GBX-treated cells. Collectively, these results demonstrated for the first time, to the best of our knowledge, that FGX had stronger anti-proliferative and pro-apoptotic effects on KATO3 cells than GBX. The anti-proliferative and/or pro-apoptotic effects of FGX appeared to be mediated via the upregulation of Bax, IκBα proteolysis (activation of nuclear factor-κB) and the blocking of mTOR and PKB signals.

Acute pyelonephritis: clinical characteristics and the role of the surgical treatment.

The epidemiology of acute pyelonephritis (APN) has changed with time. Therefore we investigated the current clinical characteristics of APN and the significance of proper surgical management for treatment of 1,026 APN patients in South Korea for the past 5 yr. The male-to-female ratio was about 1:8. The peak ages of female patients were 20s (21.3%) and over 60s (23.7%), while that of male was over 60s (38.1%). The occurrence of sepsis was 10.1%. Complicated APN patients were 35.4%. Ninety-four patients (9.2%) needed urological procedures. The duration of the flank pain and of the costovertebral angle tenderness in complicated APN patients was statistically significantly longer than that with simple APN patients (4.3 vs. 3.4 days, 4.4 vs. 4.0 days). If flank pain and costovertebral angle tenderness sustain over 4 days, proper radiologic studies should be performed immediately with the consideration of surgical procedure. Also the resistance to antibiotics was increasing. As the sensitivities to ampicillin (27.2%) and trimethoprim/sulfamethoxazole (44.7%) of Escherichia coli and Klebsiella pneumoniae were very low, it is necessary to take the careful choice of antibiotics into consideration.

The effects of epidural magnesium on postoperative pain management in patients with patient-controlled epidural analgesia after a thoracotomy.

BACKGROUND: Magnesium presents analgesic effects by blocking the non-competitive N-methyl-D-aspartate receptor in the spinal cord. The purpose of this study was to evaluate the effects of epidural magnesium on cumulative dose of ropivacaine in patients with patient-controlled epidural analgesia (PCEA) after a thoracotomy. METHODS: In a randomized, prospective, double-blind trial, we enrolled 40 patients undergoing PCEA after a thoracotomy. Control group (n = 20) received an initial dose of 0.375% ropivacaine 0.1 ml/kg, and following demand doses of 0.2% ropivacaine 2 ml with 15 min lockout interval on the patient demand. Magnesium group (n = 20) additionally received MgSO4 100 mg in the initial dose and 4 mg in the demand doses. Cumulative dose of ropivacaine, the resting and coughing visual analog scale (VAS) score were measured at 3, 6, 12, 24, and 48 hours after surgery. RESULTS: Magnesium group showed lower cumulative dose of ropivacaine than control group at 12, 24, and 48 hours after the surgery (P<0.05), but not at 3 and 6 hours (P < 0.05). The VAS score was not different between 2 groups (P < 0.05). CONCLUSIONS: Epidural magnesium may be useful as an adjuvant to ropivacaine after a thoracotomy. However, because magnesium showed no beneficial effect at the early period after the surgery, more investigation about proper initial dose is required.