Utility of Blood Culture in Patients with Community-Acquired Pneumonia: A Propensity Score-Matched Analysis Based on a Japanese National Health Insurance Database.

Community-acquired pneumonia (CAP) is an acute pulmonary parenchymal infection acquired outside the hospital. The utility of blood cultures in inpatients with CAP to reduce mortality and length of hospital stay is controversial. This study aimed to determine the utility of blood cultures on the first day of hospitalization for CAP inpatients and its influence on mortality, length of hospital stay, and antibiotics use.

Development of a DNA Vaccine for Melanoma Metastasis by Inhalation Based on an Analysis of Transgene Expression Characteristics of Naked pDNA and a Ternary Complex in Mouse Lung Tissues.

The present study investigated a pulmonary delivery system of plasmid DNA (pDNA) and its application to melanoma DNA vaccines. pCMV-Luc, pEGFP-C1, and pZsGreen were used as a model pDNA to evaluate transfection efficacy after inhalation in mice. Naked pDNA and a ternary complex, consisting of pDNA, dendrigraft poly-l-lysine (DGL), and γ-polyglutamic acid (γ-PGA), both showed strong gene expression in the lungs after inhalation.

[Influence of Storage Conditions after One-dose Packaging on Stability of Magnesium Oxide Tablets].

The intestinal motor function declines in the elderly. Many patients have constipation and ingest magnesium oxide for a prolonged period. One-dose packaging of drugs is adopted for many elderly patients to help them to avoid forgetting to take an increase in the number of oral drugs to be taken and improve convenience.

Methotrexate-Coated Complexes of Plasmid DNA and Polyethylenimine for Gene Delivery.

Folate receptors are overexpressed on the surface cancer cells. We successfully constructed a new gene delivery vector of methotrexate (MTX)-coated plasmid DNA-polyethylenimine (pDNA-PEI) complexes (PEI complexes) by electrostatic binding. The stable anionic nanoparticle was optimized at MTX charge ratios of 120 or more.

Splenic Delivery System of pDNA through Complexes Electrostatically Constructed with Protamine and Chondroitin Sulfate.

We developed and optimized a novel gene delivery vector constructed electrostatically with an anionic biological component and a cationic biological component. Cationic binary complexes of plasmid DNA (pDNA) with novo-protamine sulfate as a medical product (PRT complexes) demonstrated high gene expression with minimal cytotoxicity, likely related with its total cationic charge. Subsequently, anionic compounds were added to the PRT complexes to form ternary complexes with neutral or anionic charges.

Gene delivery system of pDNA using the blood glycoprotein fetuin.

Fetuin is a biocompatible plasma protein and strongly enhances phagocytosis of bacteria, DNA and apoptotic cells by peripheral blood cells such as monocytes, macrophages and dendritic cells. We developed a novel gene delivery system: ternary complexes constructed with pDNA, polyethylenimine (PEI) and fetuin. Without covalent binding, fetuin was able to coat pDNA-PEI complexes, and stable anionic nanoparticles formed at a weight ratio greater than 30.

DNA Microcapsule for Photo-Triggered Drug Release Systems.

In this study we constructed spherical photo-responsive microcapsules composed of three photo-switchable DNA strands. These strands first formed a three-way junction (TWJ) motif that further self-assembled to form microspheres through hybridization of the sticky-end regions of each branch. To serve as the photo-switch, multiple unmodified azobenzene (Azo) or 2,6-dimethyl-4-(methylthio)azobenzene (SDM-Azo) were introduced into the sticky-end regions via a d-threoninol linker.

Biocompatible complex coated with glycosaminoglycan for gene delivery.

The purpose of this study was to develop a ternary complex of plasmid DNA (pDNA) electrostatically assembled with dendrigraft poly-l-lysine (DGL) and biodegradable glycosaminoglycan for effective and secure gene delivery. High gene expression of pDNA/DGL complex was confirmed with slight cytotoxicity and erythrocyte agglutination. Anionic ternary complexes of 55.

Application of biodegradable dendrigraft poly-l-lysine to a small interfering RNA delivery system.

Dendrigraft poly-l-lysine (DGL), including its central core, consists entirely of lysine, hence it is completely biodegradable. We applied DGL in a small interfering RNA (siRNA) delivery system. Binary complexes with siRNA and DGL had particle sizes of 23-73 nm and ζ-potentials of 34-42 mV.

Splenic gene delivery system using self-assembling nano-complex with phosphatidylserine analog.

The recognition of phosphatidylserine on the erythrocyte membrane mediates erythrophagocytosis by resident spleen macrophages. The application of phosphatidylserine to a gene vector may be a novel approach for splenic drug delivery. Therefore, we chose 1,2-dioleoyl-sn-glycero-3-phospho-L-serin (DOPS) as an analogue of phosphatidylserine for splenic gene delivery of plasmid DNA (pDNA).

Quaternary complexes modified from pDNA and poly-l-lysine complexes to enhance pH-buffering effect and suppress cytotoxicity.

We developed a modified complex of pDNA and poly-l-lysine (PLL) by the addition of poly-l-histidine (PLH) and γ-polyglutamic acid (γ-PGA) to enhance its pH-buffering effect and suppress cytotoxicity. The binary and ternary complexes of pDNA with PLL or/and PLH showed particle sizes of approximately 52-76 nm with cationic surface charge. The ternary complexes showed much higher gene expression than the binary complexes with PLL.

Novel siRNA delivery system using a ternary polymer complex with strong silencing effect and no cytotoxicity.

We developed a novel small interfering RNA (siRNA) delivery system using a ternary complex with polyethyleneimine (PEI) and γ-polyglutamic acid (γ-PGA), which showed silencing effect and no cytotoxicity. The binary complexes of siRNA with PEI were approximately 73-102 nm in particle size and 45-52 mV in ζ-potential. The silencing effect of siRNA/PEI complexes increased with an increase of PEI, and siRNA/PEI complexes with a charge ratio greater than 16 showed significant luciferase knockdown in a mouse colon carcinoma cell line regularly expressing luciferase (Colon26/Luc cells).

Biodegradable nanoparticles composed of dendrigraft poly-L-lysine for gene delivery.

We developed novel gene vectors composed of dendrigraft poly-L-lysine (DGL). The transgene expression efficiency of the pDNA/DGL complexes (DGL complexes) was markedly higher than that of the control pDNA/poly-L-lysine complex. However, the DGL complexes caused cytotoxicity and erythrocyte agglutination at high doses.

Ternary complex of plasmid DNA electrostatically assembled with polyamidoamine dendrimer and chondroitin sulfate for effective and secure gene delivery.

The purpose of this study was to develop a ternary complex of plasmid DNA (pDNA) electrostatically assembled with polyamidoamine (PAMAM) dendrimer and chondroitin sulfate (CS) for effective and secure gene delivery. PAMAM dendrimers are new cationic polymers that are expected to be used as gene delivery vectors. However, cationic non-viral gene vectors showed cytotoxicity by binding to negative cellular membranes.

Secure splenic delivery of plasmid DNA and its application to DNA vaccine.

In this experiment, we developed a novel safe and effective gene delivery vector coated with γ-polyglutamic acid (γ-PGA-coated complexes). The γ-PGA-coated complex was composed of chiseled spherical nano-particles with anionic charges. The plasmid DNA/polyethyleneimine complex (non-coated complex) showed high transgene efficiency in the spleen and lung after intravenous administration in mice, with high liver toxicity and lethality.

Ternary complex of plasmid DNA with protamine and γ-polyglutamic acid for biocompatible gene delivery system.

The purpose of the present study was to investigate the usefulness of the ternary complex with protamine and γ-polyglutamic acid (γ-PGA), which are biodegradable materials for foods and medical products, as a safe gene delivery vector. We formed cationic binary complexes (plasmid DNA (pDNA)/protamine complexes) with high transfection efficiency. The binary complex showed slight toxicity probably related to its total cationic charge.

Safe and effective delivery of small interfering RNA with polymer- and liposomes-based complexes.

We developed binary and ternary complexes based on polymers and liposomes for safe and effective delivery of small interfering RNA (siRNA). Anti-luciferase siRNA was used as a model of nucleic acid medicine. The binary complexes of siRNA were prepared with cationic polymers and cationic liposomes such as polyethylenimine (PEI), polyamidoamine (PAMAM) dendrimer, poly-L-arginine (PLA), trimethyl[2,3-(dioleoxy)-propyl]ammonium chloride (DOTMA), and cholesteryl 3β-N-(dimetylaminnoethyl)carbamate hydrochloride (DC-Chol).