Determination of microviscosity and location of 1,3-Di(1-pyrenyl)propane in brain membranes

We determined the microviscosity of synaptosomal plasma membrane vesicles (SPMV) isolated from bovine cerebral cortex and liposomes of total lipids (SPMTL) and phospholipids (SPMPL) extracted from SPMV. Changes in the microviscosity induced by the range and rate of lateral diffusion were measured by the intramolecular excimerization of 1,3-di(1-pyrenyl)-propane (Py-3-Py). The microviscosity values of the direct probe environment in SPMV, SPMTL and SPMPL were 38.17, 31.11 and 27.64 cP, respectively, at 37°C and the activation energies (E_a) of the excimer formation of Py-3-Py in SPMV, SPMTL and SPMPL were 8.236, 7.448 amd 7.025 kcal/mol, respectively. Probe location was measured by polarity and polarizability parameters of the probe Py-3-Py and probe analogues, pyrene, 1-pyrenenonanol and 1-pyrenemethyl-3β-hydroxy-22,23-bisnor-5-cholenate (PMC), incorporated into membranes or solubilized in reference solvents. There existed a good linear relationship between the first absorption peak of the¹L_a band and the polarizability parameter (n ²−1)/(2n ²+1). The calculated refractive index values for SPMV, SPMTL and SPMPL were close to 1.50, which is higher than that of liquid paraffin (n=1.475). The probe location was also determined by using a polarity parameter (f−1/2f¹). Here f=(ε−1)/(2ε+1) is the dielectric constant function and f'=(n ²−1)/(2n ²+1) is the refractive index function. A correlation existed between the monomer fluorescence intensity ratio and the solvent polarity parameter. The probes incorporated in SPMV, SPMTL, and SPMPL report a polarity value close to that of 1-hexanol (ε=13.29). In conclusion, Py-3-Py is located completely inside the membrane, not in the very hydrophobic core, but displaced toward the polar head groups of phospholipid molecules, e.g., central methylene region of aliphatic chains of phospholipid molecules.     

Psammaplin A, a natural bromotyrosine derivative from a sponge, possesses the antibacterial activity against methicillin-resistantStaphylococcus aureus and the DNA gyrase-inhibitory activity

Psammaplin A, a natural bromotyrosine derivative from an associated form of two sponges (Poecillastra sp. and Jaspis sp.) was found to possess the antimicrobial effect on the Gram-positive bacteria, especially on methicillin-resistant Staphylococcus aureus (MRSA). The minimal inhibitory concentration of psammaplin A against twenty one MRSAs ranged from 0.781 to 6.25 microg/ml, while that of ciprofloxacin was 0.391-3.125 microg/ml. Psammaplin A could not bind to penicillin binding protein, but inhibited the DNA synthesis and the DNA gyrase activity with the respective 50% (DNA synthesis) and 100% (DNA gyrase) inhibitory concentration 2.83 and 100 microg/ml. These results indicate that psammaplin A has a considerable antibacterial activity, although restricted to a somewhat narrow range of bacteria, probably by inhibiting DNA gyrase.     

Studies on corneal penetration ofp-hydroxybenzoic acid esters

Corneal permeability of variousn-alkylp-hydroxybenzoates (parabens) was studiedin vitro using excised rabbit corneas, and the effect of lipophilicity of parabens on the corneal permeability was also investigated. Permeability coefficients were obtained from the least-square linear regression after the steady state had been reached. Lipophilicity of parabens was calculated by distribution coefficients determined in octanol-S \(12_\phi [\kern-0.15em[ \) rensen’s buffer solution (pH 5.0). The relationship between lipophilicity and corneal permeability of parabens was not linear, but the optimum lipophilicity for the maximum permeation was found. The influence of tween 80 on corneal permeability of methyl and butylparaben was not significant.     

Value of lying-down nystagmus in the lateralization of horizontal semicircular canal benign paroxysmal positional vertigo.

BACKGROUND: Horizontal canal benign paroxysmal positional vertigo is characterized by horizontal direction-changing nystagmus induced by lateral head turning in supine position. According to Ewald's second law, the direction of head turning that creates a stronger response represents the affected side in geotropic nystagmus and the healthy side in apogeotropic nystagmus. However, it may not always be possible to lateralize the involved ear only by comparing the intensity of the nystagmus. We studied the values of nystagmus induced by position change from sitting to supine in the lateralization of horizontal canal benign paroxysmal positional vertigo. METHODS: A retrospective study of 54 patients who had been diagnosed as having horizontal canal benign paroxysmal positional vertigo at the Dizziness Clinic of Seoul National University Bundang Hospital from May 2003 to February 2004 was performed. The directions of the nystagmus induced by lying down were compared with those determined by Ewald's second law. RESULTS: Of the 54 patients, 32 (20 apogeotropic and 12 geotropic) showed horizontal nystagmus induced by lying down. The nystagmus tended to be ipsilesional in apogeotropic patients (80%) and contralesional in their geotropic counterparts (75%). CONCLUSION: In horizontal canal benign paroxysmal positional vertigo, lying-down nystagmus mostly beats toward the involved ear in the apogeotropic type and directs to the healthy ear in the geotropic type. The direction of lying-down nystagmus may help lateralizing the involved ear in horizontal canal benign paroxysmal positional vertigo.     

A GoldenBraid-Compatible Virus-Based Vector System for Transient Expression of Heterologous Proteins in Plants

We have developed a Potato virus X (PVX)-based vector system compatible with the GoldenBraid 2.0 (GB) cloning strategy to transiently express heterologous proteins or peptides in plants for biotechnological purposes. This vector system consists of three domestication vectors carrying three GB parts—the cauliflower mosaic virus (CaMV) 35S promoter with PVX upstream of the second subgenomic promoter of the PVX coat protein (PVX CP SGP), nopaline synthase (NOS) terminator with PVX downstream of the first PVX CP SGP and the gene of interest (GOI). The full-length PVX clone carrying the sequence encoding a green fluorescent protein (GFP) as GOI was incorporated into the binary GB vector in a one-step reaction of three GB parts using the four-nucleotide GB standard syntax. We investigated whether the obtained vector named GFP/pGBX enables systemic PVX infection and expression of GFP in Nicotiana benthamiana plants. We show that this GB-compatible vector system can be used for simple and efficient assembly of PVX-based expression constructs and that it meets the current need for interchange of standard biological parts used in different expression systems.     

Triple Therapy-Based on Tegoprazan,a New Potassium-Competitive Acid Blocker,for First-Line Treatment of Helicobacter pylori Infection: A Randomized,Double-Blind,Phase III,Clinical Trial

Background/AimsWe examined the efficacy and safety of tegoprazan as a part of first-line triple therapy for Helicobacter pylori eradication.MethodsA randomized, double-blind, controlled, multicenter study was performed to evaluate whether tegoprazan (50 mg)-based triple therapy (TPZ) was noninferior to lansoprazole (30 mg)-based triple therapy (LPZ) (with amoxicillin 1 g and clarithromycin 500 mg; all administered twice daily for 7 days) for treating H. pylori. The primary endpoint was the H. pylori eradication rate. Subgroup analyses were performed according to the cytochrome P450 (CYP) 2C19 genotype, the minimum inhibitory concentration (MIC) of amoxicillin and clarithromycin, and underlying gastric diseases.ResultsIn total, 350 H. pylori-positive patients were randomly allocated to the TPZ or LPZ group. The H. pylori eradication rates in the TPZ and LPZ groups were 62.86% (110/175) and 60.57% (106/175) in an intention-to-treat analysis and 69.33% (104/150) and 67.33% (101/150) in a per-protocol analysis (non-inferiority test, p=0.009 and p=0.013), respectively. Subgroup analyses according to MICs or CYP2C19 did not show remarkable differences in eradication rate. Both first-line triple therapies were well-tolerated with no notable differences.ConclusionsTPZ is as effective as proton pump inhibitor-based triple therapy and is as safe as first-line H. pylori eradication therapy but does not overcome the clarithromycin resistance of H. pylori in Korea (ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT03317223","term_id":"NCT03317223"}}NCT03317223).     

Utility of Direct Peroral Cholangioscopy Using a Multibending Ultraslim Endoscope for Difficult Common Bile Duct Stones

Background/AimsTreatment options for difficult bile duct stones are limited. Direct peroral cholangioscopy (POC)-guided lithotripsy may be an option. A newly developed multibending (MB) ultraslim endoscope has several structural features optimized for direct POC. We evaluated the utility of direct POC using an MB ultraslim endoscope for lithotripsy in patients with difficult bile duct stones.MethodsTwenty patients with difficult bile duct stones, in whom stone removal using conventional endoscopic methods, including mechanical lithotripsy, had failed were enrolled from March 2018 to August 2019. Direct POC-guided lithotripsy was performed by electrohydraulic lithotripsy or laser lithotripsy. The primary outcome was complete ductal clearance, defined as the retrieval of all bile duct stones after lithotripsy confirmed by balloon-occluded cholangiography and/or direct POC.ResultsThe technical success rate of direct POC was 100% (20/20), and the free-hand insertion rate was 95% (19/20). Direct POC-guided lithotripsy, attempted by electrohydraulic lithotripsy in nine patients (45%) and laser lithotripsy in 11 patients (55%), was successful in 95% (19/20) of the patients. Complete ductal clearance after direct POC-guided lithotripsy was achieved in 95% (19/20) of patients. Patients required a median of 2 (range, 1–3) endoscopic retrograde cholangiopancreatography sessions for complete stone removal. Adverse event was observed in one patient (5%) with hemobilia and was treated conservatively.ConclusionsDirect POC using an MB ultraslim endoscope was safe and effective for lithotripsy in patients with difficult bile duct stones.     

Changes in antioxidant,inflammatory and metabolic markers during 1 week cultivation of human skin explants

Human skin explant (HSE) seems to be a useful model for dermatological/cosmetic testing. HSE prepared from donor superfluous skin from plastic surgery operations is cheap and easily obtainable compared to reconstructed models. The HSE use, however, may be limited by the degeneration processes during cultivation. The aim was to monitor changes in metabolic activity and selected apoptotic, inflammatory and antioxidant parameters during 7 day cultivation. The significant changes were found in the superoxide dismutase‐2 level from day 5, glutathione S‐reductase level from day 6, metabolic activity and fibulin‐5 level from day 4, cyclooxygenase‐2, interleukin‐6 and interleukin‐10 from day 1 to 2. Other selected markers (lipid peroxidation products and glutathione level, glutathione S‐transferase, catalase, superoxide dismutase and glutathione S‐reductase activity, glutathione peroxidase and glutathione S‐reductase levels) were not modified significantly due to high inter‐individual variability of skin donors. The HSE microstructure as well as cytokeratin‐10 and proliferation marker Ki67 expression was also only minimally affected during cultivation. Collectively, the results demonstrate that HSE represents a good model for short‐term studies focused on the physical and chemical agent toxicity, protective potential of compounds or metabolic biotransformation. However, reduced metabolic activity, increased inflammation and the high inter‐individual variability and sensitivity of donors have to be taken into consideration.     

Three-vessel view of the fetal heart: in utero development of the great vessels

OBJECTIVES: The purpose of our study is to provide reference values for the great vessels obtained from images of the three-vessel view of the fetal heart, with an emphasis on the size discrepancy of the great vessels. METHODS: From February 2003 to May 2003, the main pulmonary artery (MPA), ascending aorta (AA), and SVC were measured in well-dated, nonanomalous fetuses scanned at 14-38 weeks of gestation. RESULTS: The size of each great vessel had a significant positive relationship with advance in gestation (P < 0.001); MPA (mm) = -2.76 + 0.34 x GA, ascending aorta (AA) (mm) = -1.73 + 0.26 x GA - 1.18E - 05 x GA(3), and SVC (mm) = 0.33 + 0.01 x GA(2) - 4.12E - 05 x GA(3). The AA/MPA ratio was significantly decreased with advance in gestation, while the SVC/AA ratio was significantly increased; AA/MPA ratio = -1.24 - 0.03 x GA + 3.88E - 04 x GA(2); P < 0.001, SVC/AA ratio = 0.63 - 5.43E - 03 x GA + 1.96E - 04 x GA(2); P < 0.001. CONCLUSION: On the three-vessel view of the fetal heart, the interpretation of the size discrepancy of the great vessels needs to be adjusted according to fetal growth.