Anti-staphylococcal activity of a cyclic lipopeptide, C15 -bacillomycin D, produced by Bacillus velezensis NST6.

AIM: The aim of this study was to assess antibacterial activity of a novel Bacillus velezensis strain NST6, and further identify its active compound against pathogenic Staphylococcus strains for clinical therapeutic applications. METHODS AND RESULTS: In this study, a novel B. velezensis strain NST6 harbouring strong antimicrobial activity against human pathogenic bacteria was isolated from a soil sample. The solvent extract of the strain exhibited strong antibacterial activity against Gram-positive and Gram-negative bacteria in disc diffusion assay and measurement of minimal inhibitory concentration and bactericidal concentration, of which it showed notable efficacy to Staphylococcus species including Staphylococcus epidermidis, Staphylococcus aureus and methicillin-resistant S. aureus. Strong antibacterial effect against pathogenic S. aureus and low toxicity of the bacterial extract were further validated in Caenorhabditis elegans model. Moreover, by antibacterial activity-guided fractionation using RP-HPLC and LC-MS, we defined C15 -bacillomycin D as the anti-staphylococcal compound produced by the strain. CONCLUSION: The primary anti-staphylococcal compound from B. velezensis NST6 was identified as a cyclic lipopeptide, C15 -bacillomycin D, which proved its potential to treat Staphylococcus strains in vitro and in vivo experiments with insignificant level of toxicity. SIGNIFICANCE AND IMPACT OF THE STUDY: We provide an alternative treatment option to Staphylococcus infections by investigating the specific anti-staphylococcal activity of C15 -bacillomycin D produced by a B. velezensis strain.

An effective diagnostic strategy for accurate detection of RhD variants including Asian DEL type in apparently RhD-negative blood donors in Korea.

BACKGROUND AND OBJECTIVES: The purpose of this study was to provide an effective RHD genotyping strategy for the East Asian blood donors. MATERIAL AND METHODS: RhD phenotyping, weak D testing and RhCE phenotyping were performed on 110 samples from members of the RhD-negative club, private organization composed of RhD-negative blood donors, in the GwangJu-Chonnam region of Korea. The RHD promoter, intron 4, and exons 7 and 10 were analysed by real-time PCR. Two nucleotide changes (c.1227 G>A, and c.1222 T>C) in exon 9 were analysed by sequencing. RESULTS: Of 110 RhD-negative club members, 79 (71·8%) showed complete deletion of the RHD gene, 10 (9·1%) showed results consistent with RHD-CE-D hybrid, and 21 (19·1%) showed amplification of RHD promoter, intron 4, and exons 7 and 10. Of the latter group, 16 (14·5%) were in the DEL blood group including c.1227 G>A (N = 14) and c.1222 T>C (N = 2), 2 (1·8%) were weak D, 1(0·9%) was partial D, and 2 (1·8%) were undetermined. The RhD-negative phenotype samples consisted of 58 C-E-c+e+, 19 C-E+c+e+, 3 C-E+c+e-, 21 C+E-c+e-, 6 C+E-c+e+ and 3 C+E-c-e + . Notably, all 58 samples with the C-E-c+e+ phenotype were revealed to have complete deletion of the RHD gene. The C-E-c+e+ phenotype showed 100% positive predictive value for detecting D-negative cases. CONCLUSIONS: RHD genotyping is not required in half of D-negative cases. We suggest here an effective RHD genotyping strategy for accurate detection of RhD variants in apparently RhD-negative blood donors in East Asia.

Highly Efficient Phosphorescent Light-Emitting Diodes by Using New Host Material.

An electron-transporting triazole (Tz) and hole transporting carbazole (Cz) moieties were introduced into the fluorene structure via a Suzuki coupling reaction. The resulting material, 9-(4'-(9-(4'-(4,5-diphenyl-4H-1,2,4-triazol-3-y)-[1,1'-biphenyl]-4-yl)-9H-fluoren-9-yl)-[1,1'-biphenyl]-4-yl)-9H-carbazole (Tz-FL-Cz), was synthesized and can be used as the host layer in phosphorescent OLEDs. The synthesized material exhibits wide energy gap (3.46 eV). The absorption and emission maximum of the Tz-FL-Cz was observed at 300 nm and 389 nm, respectively. Blue phosphorescent devices using Tz-FL-Cz as host material exhibited maximum current efficiency of 3.2 cd/A and power efficiency of 1.3 lm/W, respectively.

Cervicofacial Subcutaneous Emphysema and Pneumomediastinum Following Class V Resin Restoration: A Case Report.

Air can become trapped within the subcutaneous layer of the cervicofacial area, a condition known as subcutaneous emphysema (SE), unexpectedly after routine dental procedures. SE can worsen by extending superiorly to the peri-orbital region and inferiorly to the thorax and abdomen along the fascial planes. Upward progression can result in cavernous sinus thrombosis. Conversely, downward progression can cause a variety of complications such as pneumothorax, mediastinitis, and compression of the venous trunks. The presence of these conditions highlights the significance of prompt identification, precise diagnosis to ascertain the need for immediate intervention, and suitable management to prevent additional unfavorable consequences.

Physicochemical, microbial, and sensory properties of yogurt supplemented with nanopowdered chitosan during storage.

This study was carried out to determine the possibility of adding nanopowdered chitosan (NPC) into cholesterol-reduced yogurt to improve the functionality of yogurt and the effects of adding NPC on the physicochemical, microbial, and sensory properties of the products during storage. The pH values and mean lactic acid bacteria counts of NPC-added (0.3 to approximately 0.7%, wt/vol) and cholesterol-reduced yogurt ranged from 4.19 to 4.41 and from 4.75 x 10(8) to 9.70 x 10(8) cfu/mL, respectively, when stored at 4 degrees C for 20 d, thereby indicating a possibility of prolonging the shelf life of yogurt. In color, the a* and b* values for cholesterol-reduced yogurt were not significantly influenced by the addition of NPC (0.1 to approximately 0.7%, wt/vol); however, the L* values significantly decreased with the addition of the greatest concentration (0.7%, wt/vol) of NPC at 0-d storage. The sensory test revealed that the astringency scores significantly increased at 0-d storage when the greatest concentration (0.7%, wt/vol) of NPC was added into cholesterol-reduced yogurt. Based on the data obtained from the current study, it is concluded that concentrations (0.3 to ~0.5%, vol/vol) of NPC could be used to produce an NPC-added and cholesterol-reduced yogurt without significantly adverse effects on the physicochemical, microbial, and sensory properties.

In vivo evaluation of polymeric micellar paclitaxel formulation: toxicity and efficacy.

Although the current clinical formulation of paclitaxel (Taxol) has a promising clinical activity against a wide variety of tumors, it has significant toxic side effects, some of which are associated with its formulation in a 1:1 (v/v) mixture of Cremophor EL and dehydrated alcohol. One of the problems associated with the intravenous administration of paclitaxel is its low solubility in water. Our study was designed to evaluate the pharmacokinetics, tissue distribution, toxicity and efficacy of a paclitaxel (Genexol)-containing biodegradable polymeric micellar system (Genexol-PM) in comparison to Taxol. Genexol-PM was newly developed by using a low molecular weight, nontoxic and biodegradable amphiphilic diblock copolymer, monomethoxy poly(ethylene glycol)-block-poly(D,L-lactide) (mPEG-PDLLA) and paclitaxel (Genexol, Samyang Genex Co., Seoul, Korea). In a human cancer cell line model, Genexol-PM and Taxol showed comparable in vitro cytotoxicity against human ovarian cancer cell line OVCAR-3 and human breast cancer cell line MCF7. The maximum tolerated dose (MTD) of Genexol-PM and Taxol in nude mice was determined to be 60 and 20 mg/kg, respectively. The median lethal dose (LD(50)) in Sprague--Dawley rats was 205.4 mg/kg (male) and 221.6 mg/kg (female) for Genexol-PM, while 8.3 mg/kg (male) and 8.8 mg/kg (female) for Taxol. After intravenous administration of Genexol-PM in murine B16 melanoma-induced female SPF C57BL/6 mice at a dose of 50 mg/kg, the area under the plasma concentration-time curve (AUC) was similar to Taxol((R)) at a dose of 20 mg/kg, but biodistribution of paclitaxel after administration of Genexol-PM showed 2 to 3-fold higher levels in tissues including liver, spleen, kidneys, lungs, heart and tumor as compared to Taxol. The in vivo antitumor efficacy of Genexol-PM as measured by reduction in tumor volume of SKOV-3 human ovarian cancer implanted in nude (nu/nu) athymic mice and MX-1 human breast cancer implanted in Tac:Cr:(NCr)-nu athymic mice was significantly greater than that of Taxol. The results of cytotoxicity, MTD, LD(50) and antitumor efficacy suggest that Genexol-PM may have a great advantage over present-day chemotherapy with Taxol.

Biodegradable block copolymers for delivery of proteins and water-insoluble drugs.

Release of several drugs from new ABA-type biodegradable thermal gels, ReGel, including proteins and conventional molecules, are presented. These are biodegradable, biocompatible polymers that demonstrate reverse thermal gelation properties. Organic solvents are not used in the synthesis, purification, or formulation of these polymers. The unique characteristics of ReGel hinge on the following two key properties: (1) ReGel is a water soluble, biodegradable polymer at temperatures below the gel transition temperature; (2) ReGel forms a water-insoluble gel once injected. This is consistent with a hydrophobically bonded gel state where all interactions are physical, with no covalent crosslinking. An increase in viscosity of approximately 4 orders of magnitude accompanies the sol--gel transition. The gel forms a controlled release drug depot with delivery times ranging from 1 to 6 weeks. ReGel's inherent ability to solubilize (400 to >2000-fold) and stabilize poorly soluble and sensitive drugs, including proteins is a substantial benefit. The gel provided excellent control of the release of paclitaxel for approximately 50 days. Direct intratumoral injection of ReGel/paclitaxel (OncoGel) results in a slow clearance of paclitaxel from the injection site with minimal distribution into any organ. Efficacies equivalent to maximum tolerated systemic dosing were observed at OncoGel doses that were 10-fold lower. Data on protein release (pGH, G-CSF, insulin, rHbsAg) and polymer biocompatibility are discussed.

ATP-induced histamine release is in part related to phospholipase A2-mediated arachidonic acid metabolism in rat peritoneal mast cells.

Histamine and arachidonic acid (AA) release was measured using the P2-purinoceptor antagonists, phospholipase A2 (PLA2) and cyclooxygenase (COX)/lipoxygenase (LOX) inhibitors to determine whether or not ATP-induced histamine release is associated with arachidonic acid (AA) release in rat peritoneal mast cells. ATP increased histamine release in a dose dependent manner, whereas adenosine did not. PPADS (a selective P2X-purinoceptor antagonist) and suramin (a nonselective P2X,2Y-purinoceptor antagonist) inhibited ATP-induced histamine release in a dose dependent manner. However, RB-2 (a P2Y-purinoceptor antagonist) did not block ATP-induced histamine release. Manoalide and oleyloxyethyl phosphorylcholine (OPC), secretory PLA2 inhibitors, also inhibited ATP-induced histamine release dose-dependently. Both COX inhibitors (ibuprofen and indomethacin) and LOX inhibitors (baicalein and caffeic acid) inhibited ATP-induced histamine in a dose dependent manner. ATP significantly increased [3H]AA release by 54%. PPADS and suramin significantly inhibited ATP-induced [3H]AA release by 81% and 39%, respectively. ATP-induced histamine release was significantly inhibited by a variety of protein kinase inhibitors, such as bisindolmaleimide, genistein, methyl 2,5-dihydroxycinnamate, W-7 and trifluoperazine. Overall, the results suggest that ATP-induced histamine release is in part related to the PLA2-mediated AA metabolism and P2X-purinoceptors.

[A study on family pattern and psychological aspects of parent and child].

PIP: This study reviews the relationship between family patterns and psychological aspects of the mother-child relationship. As the population increase in Korea will reach 50 million in 2020, population policy must deal with population quality. The data come from 118 5th and 6th grade students and their mothers. Survey results shows that the number of children and the family type are related to mothers' child rearing attitudes. Mothers in nuclear families tended to be warmer and freer towards their children than others. Family type was not related to the self-esteem of children, and the number of siblings showed a weak relationship. Children with siblings have stronger self-esteem. Birth order and younger sibling spacing had a stronger relationship with self-esteem. First borns and those who had younger siblings within a 2-year interval had the weakest self-esteem. Since families are becoming smaller, child quality is becoming more important. Not only family size but also family type, birth order, and spacing need to be considered for the psychological well-being of the population.^ieng

Current status and future directions of the population control policies in Korea.

PIP: Recent changes in demographic and socioeconomic conditions in Korea are reviewed, as are population control policies so that future policy directions can be established. Major data sources include the 1988 National Fertility and Family Health Survey and the 1985 Population and Housing Census of NBOS, EPB. The Korean population increased from 25.0 million in 1960 to 42.4 million in 1989. Population growth rate declined from 3.0% per annum to l.0% at the same time. The total fertility rate went down from 6.0/women to 1.6, from 1960 to 1987. This was due to a family planning program and socioeconomic development. In the Sixth Five-Year Plan (1987-1991), the government changed the demographic goals to further reduce the population growth rate to 0.96% by 1991. The estimated 1987 population of 41.6 million should reach 43.2 million by 1991. Korea will face 3 major population problems: an increase of the elderly population, rapid urbanization and shortage of resources. Emigration programs have been carried out to relieve the pressure of population. For the last 29 years, rural to urban migration has existed. A national family planning program exists. 16.4 million acceptors have received contraception under this program. There are, however, a number of problems. Reduction in population growth will help the world food supply problem and the housing shortage. Energy use has grown. Population and environmental planning should work together. Goals should change from reduction of fertility to eliminating problems with contraceptive acceptance and use effectiveness. There should be a greater choice of methods of contraception. The government functions of the family planning program should be given over to private organizations. The family planning program should be integrated with public health programs. Acceptors should pay for their contraceptives. The family planning program should enlarge its realm of activities. The information, education, communication part of the program should be revised. Individual program activities should be evaluated. Appendix 1 presents new population projections for 1987-2020. Changes in composition of the population are given in table form in Appendix 2.^ieng

Analysis of factors contributing to fertility decline in Korea.

With the successful Korean national family planning program and rapid socioeconomic advancement since 1962, the contraceptive prevalence rate has risen from 9% in 1964 to 79% in 1991, with the corresponding total fertility rate (TFR) going from 6.0 in 1960 to 1.6 in 1988, which is considerably below the replacement fertility rate. The main purpose of this study is, therefore, to identify the structural and causal factors that contributed to the fall in fertility over the last 3 decades, in an effort to formulate future population policy directions and strategies. The 2 methods used for the study were: the standardization approach to examine the structural factors on fertility decline, and the bongaarts model to measure the effects of the proximate variables in the fertility decline. The study indicated that the fall in the crude birth rate and the general fertility rate for the periods of 1960-70 and 1980-90 were largely influenced by the decline in marital fertility which was triggered by the national family planning program initiated in 1962. The analysis based on the bongaarts model revealed that the 3 principal factors which exercised a strong influence on the fertility decline were the rise in age at marriage, the increase in induced abortion, and the increase in contraceptive use, but the influence of induced abortion has been decreasing in recent years. In general, the study results suggest that the main concerns of the national family planning program should be shifted from the past quantitative approach with emphasis on fertility reduction to a qualitative approach which stresses maternal and child health and other public health programs.

Recent changes in the population control policy and its future directions in Korea.

PIP: The total fertility rate (TFR) in Korea decreased from 6.0 to 1.6 over the period 1960-87. A national family planning program and socioeconomic development have played roles in this decline. Should this most recent TFR prevail, the nation's population will increase to 50.2 million by 2020, shifting to negative growth thereafter. Demographic aging and labor shortages will ensue. Future population policy should consider Korea's socioeconomic conditions and its burgeoning population in relation to the available land area, and aim to maintain a minimum positive population growth rate. In this context, this paper considers future population policy directions for Korea, acknowledging that its strategies and objectives must change. Postponing reaching the goal of zero population growth rate is suggested to allow a moderate population infusion of economically active individuals. These people will help facilitate greater economic development and work to improve the quality of life in Korea. Strengthened family planning/maternal-child health programs which encourage and support temporary contraceptive methods instead of sterilization will help to achieve this goal. Improving qualitative program aspects should be the center of attention in these programs. The paper also calls upon the Korea Institute for Health and Social Affairs to strengthen its research and evaluation capabilities.^ieng