Clinical outcomes of pneumococcal pneumonia caused by antibiotic-resistant strains in Asian countries: a study by the Asian network for surveillance of resistant pathogens

To evaluate the clinical outcomes of pneumococcal pneumonia caused by antibiotic-resistant strains in Asian countries, we performed a prospective observational study of 233 cases of adult pneumococcal pneumonia in 9 Asian countries from January 2000 to June 2001. Among 233 isolates, 128 (55%) were not susceptible to penicillin (25.3% were intermediately susceptible, and 29.6% were resistant). Clinical severity of pneumococcal pneumonia was not significantly different between antibiotic-resistant and antibiotic-susceptible groups. Mortality rates among patients with pneumococcal pneumonia caused by penicillin-, cephalosporin-, or macrolide-resistant strains were not higher than those with antibiotic-susceptible pneumococcal pneumonia. Bacteremia and mechanical ventilation were significant risk factors for death, but any kind of antibiotic resistance was not associated with increased mortality due to pneumococcal pneumonia. Outcome of pneumococcal pneumonia was not significantly affected by drug resistance, and current antimicrobial regimens are mostly effective in the treatment of pneumococcal pneumonia, despite the widespread emergence of in vitro resistance

Discovery of Novel Biased Opioid Receptor Ligands through Structure-Based Pharmacophore Virtual Screening and Experiment

G_i‐protein biased agonists with minimal β‐arrestin recruitment have shown opportunities for alternative safe pain treatment to overcome the serious adverse effects of human mu opioid receptor (μ‐OR) agonists. In order to discover novel non‐morphine OR agonists, we applied hierarchical virtual screening of our in‐house database against a pharmacophore based on modeling the active conformation of ORs.We discovered Initial hit compound (4), a novel μ‐OR agonist with pyrazoloisoquinoline scaffold. We applied computational R‐group screening to compound 4 and synthesized 14 derivatives predicted to be best. Of these, the new Gi‐protein biased compound (19) shows EC50 = 179 nM at μ‐OR. This resulting in significant pain‐relief effects for mice at the phase II period in formalin tests. This study provides a new strategy to identify diverse sets of promising compounds that might prove useful for drug developments targeting other G protein‐coupled receptors (GPCRs)

Discovery of Novel Biased Opioid Receptor Ligands through Structure-Based Pharmacophore Virtual Screening and Experiment

G_i‐protein biased agonists with minimal β‐arrestin recruitment have shown opportunities for alternative safe pain treatment to overcome the serious adverse effects of human mu opioid receptor (μ‐OR) agonists. In order to discover novel non‐morphine OR agonists, we applied hierarchical virtual screening of our in‐house database against a pharmacophore based on modeling the active conformation of ORs.We discovered Initial hit compound (4), a novel μ‐OR agonist with pyrazoloisoquinoline scaffold. We applied computational R‐group screening to compound 4 and synthesized 14 derivatives predicted to be best. Of these, the new Gi‐protein biased compound (19) shows EC50 = 179 nM at μ‐OR. This resulting in significant pain‐relief effects for mice at the phase II period in formalin tests. This study provides a new strategy to identify diverse sets of promising compounds that might prove useful for drug developments targeting other G protein‐coupled receptors (GPCRs)

High-temperature tensile and creep deformation of cross-weld specimens of weld joint between T92 martensitic and Super304H austenitic steels

International audienceThe high-temperature mechanical behavior of cross-weld specimens prepared from a dissimilar weld joint between T92 martensitic and Super304H austenitic heat-resistant steels incorporating Ni-based weld metal was evaluated at temperatures up to 650 degrees C. For both high temperature tensile and creep tests, failure took place in T92 due to its faster degradation with temperature increase. The heat-affected zone of T92 played a critical role during creep deformation, resulting in type IV failure under the long-term creep condition. For the creep specimens, the location of failure shifted from the base metal region to the fine-grained heat-affected zone as the creep duration time increased from the short-term to the long-term condition. The massive precipitation of Laves phase on the grain boundaries of the fine-grained heat-affected zone during creep deformation was observed and found to be responsible for the accelerated void formation in the area leading to the premature failure

Height-Based Formula Predicting Renal Length in Korean Children derived from Technesium-99m Dimercaptosuccinic Acid Scan

Purpose: The aim of this study was to establish a simple formula to predict renal length in children using a Technesium-99m dimercaptosuccinic acid (DMSA) scan data, and to compare it with the formula derived from ultrasonography, which is widely accepted. Methods: Children who underwent a DMSA scan and ultrasonography were reviewed retrospectively, and those who had anatomical urinary tract abnormalities or urinary tract infections were excluded. Results: A total of 230 children (84 males and 146 females; age, 1 month to 16 years; mean age, 16.8 ± 27.4 months). Mean renal length measured by DMSA scan was longer than that by ultrasonography (6.38 ± 1.16 vs. 6.02 ± 1.14 cm; P < 0.001). Renal length was correlated with age, weight, height, and body surface area on the DMSA scan and ultrasonography, and showed the strongest positive correlation with height. The following formulae were established to predict renal length: mean renal length (cm) = 5.433 × height (m) + 2.330 (R2, 0.833) using the DMSA scan data, and mean renal length (cm) = 5.367 × height (m) + 2.027 (R2, 0.853) using ultrasonography data. Conclusion: We propose a simple height-based formula to predict renal length in children using a DMSA scan data, and validate it by comparing with ultrasonography formula

Spatiotemporal variations in migratory bird diversity and abundance along the coast of Gochang getbol.

Tidal flats provide critical habitat for migratory waterbird species; however, populations of migratory waterbirds have significantly declined due to tidal flat loss and degradation caused by human activities, particularly in Asia. Gochang getbol is one of tidal flats located on the southwest coast of South Korea and a center of clam production. Using bird monitoring data collected at five zones (zone1 to zone5) established across Gochang getbol and near coastal area, we examined distribution patterns of migratory bird diversity and conservation-related species along the coast of Gochang getbol. The intensity of human activity ‒ mudflat culture (mostly bivalve) and aquaculture was relatively high at zone2 and zone3, occupying > 30% of 2km circular area surrounding most sample points of these zones. Zone1 and particularly zone4 contained more natural/semi-natural habitats (less disturbed mudflats and wetlands) and zone5 had smallest mudflat than others. Shannon diversity, species richness, and abundance of migratory birds differed between zones (Anova test, P ≤ 0.02) except Shannon diversity in winter. In fall, all values were higher at zone4 than zone3 and zone5. In winter, zone1 showed greatest species richness and higher abundance than zone2, zone3, and zone5. In spring, while most differences were found between zone4 and zone5, abundance at zone4 was somewhat higher than zone2. The results from the fourth corner analysis indicated that abundance of species foraging at mudflat level was positively associated with zone1 (winter) but negatively with zone3 (fall). Sandpipers were positively associated with zone4. Abundance distribution maps of conservation-related species, created by inverse distance-weighted interpolation modeling, also showed high abundance of most conservation-related species at zone4 and 1. The findings of our study suggest the importance of natural/semi-natural habitat, and the possible link between human activity and distribution patterns of migratory birds in Gochang getbol. While we need further investigation on direct response of migratory birds to human activity, areas with low human activity with more natural/semi-natural habitat, e.g., zone4 and zone1 may be crucial for the conservation of migratory birds

In vitro antibacterial and synergistic effect of phlorotannins isolated from edible brown seaweed Eisenia bicyclis against acne-related bacteria

To develop effective and safe acne vulgaris therapies with a continuing demand for new solutions, we investigated unique efficacy of an antibacterial agent from marine brown alga Eisenia bicyclis in treating acne vulgaris. The methanolic extract of E. bicyclis exhibited potential antibacterial activity against acne-related bacteria. The ethyl acetate fraction showed the strongest antibacterial activity against the bacteria among solvent fractions. Six compounds (1-6), previously isolated from the ethyl acetate fraction of E. bicyclis, were evaluated for antibacterial activity against acne-related bacteria. Among them, compound 2 (fucofuroeckol-A [FF]) exhibited the highest antibacterial activity against acne-related bacteria with a minimum inhibitory concentration (MIC) ranging from 32 to 128 μg mL -1 . Furthermore, FF clearly reversed the high-level erythromycin and lincomycin resistance of Propionibacterium acnes. The MIC values of erythromycin against P. acnes were dramatically reduced from 2,048 to 1.0 μg mL -1 in combination with MIC of FF (64 μg mL -1 ). The fractional inhibitory concentration indices of erythromycin and lincomycin were measured from 0.500 to 0.751 in combination with 32 or 64 μg mL -1 of FF against all tested P. acnes strains, suggesting that FF-erythromycin and FF-lincomycin combinations exert a weak synergistic effect against P. acnes. The results of this study suggest that the compounds derived from E. bicyclis can be a potential source of natural antibacterial agents and a pharmaceutical component against acnerelated bacteria. Key Words: acne-related bacteria; antimicrobial activity; Eisenia bicyclis; phlorotannins; synergistic effect INTRODUCTION Acne vulgaris is a common skin disease affecting children and adolescents. The pathogenesis of acne is multifactorial and complex. There are four important factors that cause acne in humans, such as an increase in sebum secretion, keratinization of the follicle, bacteria, and inflammation 48 MATERIALS AND METHODS Raw materials and extraction In late September 2010, E. bicyclis was purchased from Ulleung Trading Co. (Ulleung-gun, Korea). A voucher specimen has been deposited in the author&apos;s laboratory. Dried E. bicyclis was finely ground and powdered with a food mixer (HMF-1000A; Hanil Electronics, Seoul, Korea). The dried powder was vacuum-packed and kept at -20°C until use. The dried E. bicyclis powder (1.0 kg) was extracted with methanol (MeOH; 10 L × 3) at 70°C for 3 h (3 times) and the solvent was evaporated in vacuo with a rotary evaporator (N-1001S-W; Eyela, Tokyo, Japan). The crude MeOH extract of E. bicyclis was suspended in 10% MeOH (1.0 L) and then partitioned in turn with nhexane (Hexane), dichloromethane (DCM), ethyl acetate (EtOAc), and n-butanol (BuOH) in sequence. The concentration of each extract was adjusted to 200 mg mL -1 by dissolving in dimethyl sulfoxide under sterile conditions and stored at -70°C until used. Microorganism and culture The following bacterial strains obtained from the Korean Collection for Type Cultures (KCTC; Daejeon, Korea) were used as indicator microorganisms in the study: P. acnes (KCTC 3314), S. aureus (KCTC 1927), S. epidermidis (KCTC 1370), P. aeruginosa (KCTC 1637), which were used for evaluation of anti-acne-related bacterial effect. Two strains of P. acnes clinical isolates were provided by the Gyeongsang National University Hospital (Jinju, Korea), a member of the National Biobank of Korea. P. acnes strains were anaerobically cultivated in brain heart infusion broth (BHI; Difco Inc., Detroit, MI, USA) supplemented with 1.0% glucose, and incubated at 37°C for 24 h in a CO 2 incubator (NAPCO 5400; General Laboratory Supply, Pasadena, TX, USA), in a 10% CO 2 humidified atmosphere. As for determining the growth curves of bacterial cells under optimal growth conditions, cultures of P. acnes were diluted and plated on BHI-agar. The plates were incubated at 37°C for 24 h in a 10% CO 2 incubator and the number of colony-forming units (CFU) was determined. S. aureus, S. epidermidis, and P. aeruginosa were grown aerobically at 37°C in tryptic soy broth (TSB; Difco Inc.). The disk diffusion assay was prepared in Mueller-Hinton agar (MHA; Difco Inc.) and the broth dilution method was carried out in Mueller-Hinton broth (MHB; Difco Inc.) according to the Clinical and Laboratory Standards Institute (CLSI) guidelines (formerly been recognized as pus-forming organisms that trigger inflammation in acne. Especially, P. acnes, one of the commonly isolated skin organisms, induces an inflammation of the sebaceous glands in human face, neck, chest or back To overcome the problem of side effects, medicinal plants and marine organisms have been investigated for the treatment of acne. Therefore, we investigated the possibility that they may be effective acne treatments based on the previously known anti-methicillin-resistant S. aureus effects of phlorotannin isolated from brown alga Eisenia bicyclis. E. bicyclis is a common perennial phaeophyceae (brown alga) and generally inhabits the region of Ulleung Island in the East sea of Korea. This seaweed has been added to appetizers, casseroles, muffins, pilafs, and soups Lee et al. Antibacterial Activities of Eisenia bicyclis 49 http://e-algae.kr Synergistic effects of fucofuroeckol-A (FF) with tetracycline, erythromycin, and lincomycin against Propionibacterium acnes The interaction between FF and antibiotics including tetracycline, erythromycin, and lincomycin (Sigma Chemical Co., St. Louis, MO, USA) against P. acnes was tested by the checkerboard method Statistical analysis In all cases analyses were performed in triplicate and data were averaged over the three measurements. The standard deviation (SD) was also calculated. Significance of differences between average MICs for each individual microorganism were determined by Student&apos;s t test at the 95% significance level using SPSS version 12.0 (SPSS Inc., Chicago, IL, USA). RESULTS Anti-acne related bacteria activity of Eisenia bicyclis extracts The antibacterial activity of methanol extract and its solvent fractions are presented in National Committee for Clinical Laboratory Standards [NCCLS]). Disk diffusion assay The antibacterial efficacy was evaluated by disk diffusion assay described by the CLSI (2009). In brief, bacterial strains were cultured in TSB at 37°C until cells reached at an OD 600 nm of 0.5. One hundred microliter of bacterial culture containing approximately 10 4 -10 5 CFU mL -1 was spread on MHA agar plates. A paper disc (6 mm in diameter) containing 1 mg and 5 mg of each extract was placed in the above MHA plate. After incubating for 24 h at 37°C, the diameter of the inhibition zone was measured on bacterial culture plates. The experiment was carried out three times and the mean values were presented. Determination of minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) The concentration of MeOH extract and its solvent fractions of E. bicyclis was 200 mg mL -1 . Each extracts was diluted with MHB to obtain a stock solution of 2,048 μg mL -1 . To determine the MIC values of the MeOH extract and its solvent fractions of E. bicyclis, a stock solution of extracts was prepared in microbial culture medium for each microbial species. The MICs are the lowest concentration of MeOH extracts and its solvent fraction of E. bicyclis to inhibit the visible growth of microorganisms after overnight incubation using MHB, which was modified from the methods described for antimicrobial susceptibility testing by the CLSI (2006). MIC was defined as the lowest concentration of crude extract that inhibited the visual growth after incubating the aerobic bacteria for 18 h and the anaerobic bacteria for 48 h. MICs of the solvent-soluble extracts were determined by the two-fold serial dilution method in 96-well flat-bottomed microtitration plates at final concentration of 7 × 10 5 CFU mL -1 . The microtitration plates were read visually and the MIC of the extracts that exhibited no turbidity was recorded as the MIC. For MBC testing, an aliquot of inoculum was taken with a MIC test well that did not show turbidity, and was poured onto nutrient agar (Difco Inc.) plates for each bacterial species. The agar plates were incubated for 2 days for aerobic bacteria and 5 days for anaerobic bacteria. The MBC value was read as the lowest concentration of the solvent-soluble extracts at which 99.99% or more of the initial inoculum was killed. The MIC and MBC experiments were repeated in triplicate. 50 food-pathogen bacteria. The MBC values of EtOAc-soluble fraction against P. acnes strains were determined from 128 to 512 μg mL -1 MIC value of isolated phlorotannins from Eisenia bicyclis According to above results, the EtOAc-soluble fraction of E. bicyclis showed the strongest antibacterial activity against acne-related bacteria. In order to identify an anti-acne substance from the EtOAc-soluble fractions of E. bicyclis, we screened the antibacterial activity of previously isolated phlorotannins against acne-related bacteria. It is reported that marine-derived polyphenols (phlorotannins) are believed as the active components of E. bicycli