Development of a Sustainable Release System for a Ranibizumab Biosimilar Using Poly(lactic-co-glycolic acid) Biodegradable Polymer-Based Microparticles as a Platform.

Ranibizumab is a humanized monoclonal antibody fragment against vascular endothelial growth factor (VEGF)-A and is widely used to treat age-related macular degeneration (AMD) caused by angiogenesis. Ranibizumab has a short half-life in the eye due to its low molecular weight and susceptibility to proteolysis. Monthly intravitreal injection of a large amount of ranibizumab formulation is a burden for both patients and medical staff.

Efficient synthesis of α-galactosyl oligosaccharides using a mutant Bacteroides thetaiotaomicron retaining α-galactosidase (BtGH97b).

Unlabelled: The preparation of a glycosynthase, a catalytic nucleophile mutant of a glycosidase, is a well-established strategy for the effective synthesis of glycosidic linkages. However, glycosynthases derived from α-glycosidases can give poor yields of desired products because they require generally unstable β-glycosyl fluoride donors. Here, we investigate a transglycosylation catalyzed by a catalytic nucleophile mutant derived from a glycoside hydrolase family (GH) 97 α-galactosidase, using more stable β-galactosyl azide and α-galactosyl fluoride donors.

Development of Intra-knee Joint Sustained-Release Gel Formulation and Evaluation of Its Pharmacological Efficiency in Rats.

In the development of a drug for intra-articular administration, a sustained-release formulation is desirable since it is difficult to sustain the effects of conventional injections due to fast drug leakage from the joint cavity. In this study, we prepared sustained release gel formulations for intra-articular administration containing indocyanine green (ICG) as a model drug to follow its fate after intra-articular administration in rats with in-vivo imaging system (IVIS). ICG administered as an aqueous solution leaked from the joint cavity in a short time and was excreted out of the body within a day.

Controlled release of clarithromycin from PLGA microspheres enhances bone regeneration in rabbit calvaria defects.

This study evaluated the sustained release effect of clarithromycin-loaded in PLGA microspheres in a rabbit calvaria defect model. Four bone defects (ø5.0) were created in the calvaria of New Zealand White rabbits (n = 21, n = 7/time point).

A case of reverse takotsubo cardiomyopathy caused by an eating disorder.

Takotsubo cardiomyopathy is an acquired transient cardiomyopathy that causes severe systolic dysfunction in the absence of coronary disease. Here we present a case of reverse takotsubo cardiomyopathy. A 67-year-old female was admitted for weakness and falls due to severe malnutrition.

Fabrication of liposomal doxorubicin exhibiting ultrasensitivity against phospholipase A for efficient pulmonary drug delivery to lung cancers.

Phospholipase A (PLA) is expressed in inflammation-related tissue, including cancer tumors. We report that a hybrid liposome composed of phospholipid (DPPC) and PEGylated block-copolymer (Poloxamer 188) can rapidly release an encapsulated hydrophilic drug in the presence of PLA. DPPC/P188 liposomes released approximately 80% of the encapsulated calcein (a fluorescence marker) within 10min in the presence of 120 mU of PLA at 37°C in vitro, whereas several other liposomal compositions used for inhalation therapy did not.

Enantioseparation of the carboxamide-type synthetic cannabinoids N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-1H-indazole-3-carboxamide and methyl [1-(5-fluoropentyl)-1H-indazole-3-carbonyl]-valinate in illicit herbal products.

Synthetic cannabinoids, recently used as alternatives to Cannabis sativa, are among the most frequently abused drugs. Identified in 2014, the synthetic cannabinoids N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-1H-indazole-3-carboxamide (5F-AB-PINACA) and methyl [1-(5-fluoropentyl)-1H-indazole-3-carbonyl]-valinate (5F-AMB) are carboxamides composed of 1-(5-fluoropentyl)-1H-indazole-3-carboxylic acid and valine amide/methyl ester. Because of their composition, these molecules have pairs of enantiomers derived from the chiral center of their amino acid structures.

Isomeric discrimination of synthetic cannabinoids by GC-EI-MS: 1-adamantyl and 2-adamantyl isomers of N-adamantyl carboxamides.

N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (APINACA) and N-(1-adamantyl)-1-pentyl-1H-indole-3-carboxamide (APICA) are carboxamide-type synthetic cannabinoids comprising indazole/indole-3-carboxylic acid and adamantan-1-amine moieties. However, in the case of compounds like APINACA or APICA, adamantyl positional isomers exist, wherein either adamantan-1-amine or adamantan-2-amine is present. These adamantyl positional isomers have not been reported in previous studies, and no analytical data are available.

Early antibiotics administration during targeted temperature management after out-of-hospital cardiac arrest: a nationwide database study.

Background: Patients resuscitated after cardiac arrest are reportedly at high risk for infection and sepsis, especially those treated with targeted temperature management (TTM). There is, however, limited evidence suggesting that early antibiotic use improves patient outcomes. We examined the hypothesis that early treatment with antibiotics reduces mortality in patients with cardiac arrest receiving TTM.

Functional characterization of UDP-rhamnose-dependent rhamnosyltransferase involved in anthocyanin modification, a key enzyme determining blue coloration in Lobelia erinus.

Because structural modifications of flavonoids are closely related to their properties, such as stability, solubility, flavor and coloration, characterizing the enzymes that catalyze the modification reactions can be useful for engineering agriculturally beneficial traits of flavonoids. In this work, we examined the enzymes involved in the modification pathway of highly glycosylated and acylated anthocyanins that accumulate in Lobelia erinus. Cultivar Aqua Blue (AB) of L.

Amiodarone Compared with Lidocaine for Out-Of-Hospital Cardiac Arrest with Refractory Ventricular Fibrillation on Hospital Arrival: a Nationwide Database Study.

Purpose: The latest resuscitation guidelines recommend the use of amiodarone in adult patients with out-of-hospital cardiac arrest (OHCA) and refractory ventricular fibrillation (VF) to improve the rates of return of spontaneous circulation. However, there is limited evidence to suggest that amiodarone is superior to lidocaine with respect to survival at discharge. The purpose of the present study was to evaluate the hypothesis that amiodarone is superior to lidocaine with regard to the rate of survival to hospital discharge for OHCA patients with VF/pulseless VT (pVT) on hospital arrival.

Amiodarone or nifekalant upon hospital arrival for refractory ventricular fibrillation after out-of-hospital cardiac arrest.

Background: We evaluated the association between nifekalant or amiodarone on hospital admission and in-hospital mortality for cardiac arrest patients with persistent ventricular fibrillation on hospital arrival.

Methods: This was a retrospective cohort study using the Japanese Diagnosis Procedure Combination inpatient database. We identified 2961 patients who suffered cardiogenic out-of-hospital cardiac arrest and who had ventricular fibrillation on hospital arrival between July 2007 and March 2013.

Solid dispersions of efonidipine hydrochloride ethanolate with improved physicochemical and pharmacokinetic properties prepared with microwave treatment.

Drug absorption into the body is known to be greatly affected by the solubility of the drug itself. The active pharmaceutical ingredient efonidipine hydrochloride ethanolate (NZ-105) is a novel 1,4-dihydropyridine calcium antagonist that has a very low solubility in water. It is classified as a poorly soluble drug, and improvements in its solubility and higher bioavailability with oral administration are needed.

Paraneoplastic Dermatosis in a Patient with Anaplastic Large-Cell Lymphoma: Case Report and Literature Review.

Background/aims: Paraneoplastic dermatoses are skin disorders that are associated with malignancy. Anaplastic large T-cell lymphoma (ALTCL) has rarely been associated with paraneoplastic skin manifestations such as gangrenous foot ulcers and erythroderma.

Methods: We describe a case of ALTCL presenting as a large annular skin rash.

Vitamin D3/VDR resists diet-induced obesity by modulating UCP3 expression in muscles.

Background: The impact of vitamin D3 (VD3) on obesity has been reported in the past. Our study was aimed at investigating the possible mechanisms by which VD3 affects obesity induced by a high fat diet.

Methods: Eight-week-old C57BL/6 J male mice were fed a normal- or high-fat diet for 9 weeks and were treated with a gavage of vehicle (corn oil) or cholecalciferol (50 μg/kg, daily).

Preparation of polymer-blended quinine nanocomposite particles by spray drying and assessment of their instrumental bitterness-masking effect using a taste sensor.

Context: The development of taste-masking technologies for foods and drugs is essential because it would enable people to consume and receive healthy and therapeutic effect without distress.

Objective: In the current study, in order to develop a novel method to prepare nanocomposite particles (microparticles containing bitter nanoparticles) in only one step, by using spray drying, a two-solution mixing nozzle-equipped spray dryer that we previously reported was used. The nanocomposite particles with or without poorly water-soluble polymers prepared using our spray-drying technique were characterized.

De-escalation versus continuation of empirical antimicrobial therapy in community-acquired pneumonia.

Objectives: To compare mortality between de-escalation and continued empirical treatment in patients with community-acquired pneumonia.

Methods: Using a nationwide administrative database, we identified adult patients with community-acquired pneumonia caused by Streptococcus pneumoniae, other streptococci, Haemophilus influenzae, Klebsiella pneumoniae, or Escherichia coli (n = 10,231) or of unknown etiology (n = 8247), discharged between July 2010 and March 2013. De-escalation was determined by the spectrum and number of antimicrobials at day 4.

Fabrication of nanocomposite particles using a two-solution mixing-type spray nozzle for use in an inhaled curcumin formulation.

A unique two-solution mixing-type spray nozzle is useful for producing nanocomposite particles (microparticles containing drug nanoparticles) in one step. The nanocomposite particles can prevent nanoparticle aggregation. Curcumin has many reported pharmacological effects.

Two Novel Glycoside Hydrolases Responsible for the Catabolism of Cyclobis-(1→6)-α-nigerosyl.

The actinobacterium Kribbella flavida NBRC 14399(T) produces cyclobis-(1→6)-α-nigerosyl (CNN), a cyclic glucotetraose with alternate α-(1→6)- and α-(1→3)-glucosidic linkages, from starch in the culture medium. We identified gene clusters associated with the production and intracellular catabolism of CNN in the K. flavida genome.

Nighttime is associated with decreased survival and resuscitation efforts for out-of-hospital cardiac arrests: a prospective observational study.

Background: Whether temporal differences alter the clinical outcomes of patients with out-of-hospital cardiac arrest (OHCA) remains inconclusive. Furthermore, the relationship between time of day and resuscitation efforts is unknown.

Methods: We studied adult OHCA patients in the Survey of Survivors after Out-of-Hospital Cardiac Arrest in the Kanto Region (SOS-KANTO) 2012 study from January 2012 to March 2013 in Japan.

Transcriptional activation of the wild-type and mutant vitamin D receptors by vitamin D3 analogs.

The active form of vitamin D3 (1α,25(OH)2D3, also known as calcitriol) controls the expression of target genes via the vitamin D receptor (VDR). Vitamin D-dependent rickets type II (VDDRII) is a congenital disease caused by inactivating mutations in the VDR The condition is treated with high doses of calcitriol, but the therapeutic effects of other synthetic VD3 analogs have not yet been investigated. In the present study, we analyzed the transcriptional activity of seven different VD3 analogs with VDRs carrying ligand-binding domain mutations identified in VDDRII patients.

Growth hormone regulates the expression of UCP2 in myocytes.

Objective: To determine if and how growth hormone (GH) signaling is involved in energy metabolism.

Design: We used human embryonic kidney TSA201 cells, human H-EMC-SS chondrosarcoma cells, rat L6 skeletal muscle cells, and murine C2C12 skeletal muscle myoblasts to investigate GH-induced expression of uncoupling protein2 (UCP2) to the GHR/JAK/STAT5 pathway by a combination of a reporter assay, electrophoretic mobility shift assay (EMSA), real-time quantitative PCR, Western blotting.

Results: We demonstrated that the regulation energy metabolism, which was hypothesized to be directly acted on by GH, involves UCP2 via activated STAT5B, a signal transducer downstream of GH.

Targeted mutagenesis in chicken using CRISPR/Cas9 system.

The CRISPR/Cas9 system is a simple and powerful tool for genome editing in various organisms including livestock animals. However, the system has not been applied to poultry because of the difficulty in accessing their zygotes. Here we report the implementation of CRISPR/Cas9-mediated gene targeting in chickens.