Validation of the Absorption-Enhancing Ability of Oligoarginines Grafted onto a Backbone of Hyaluronic Acid through Animal Studies from Rodents to Primates.

The purpose of our research is to develop functional additives that enhance mucosal absorption of biologics, such as peptide/protein and antibody drugs, to provide their non-to-poor invasive dosage forms self-managed by patients. Our previous in vivo and in vitro studies demonstrated that the intranasal absorption of biologics in mice was significantly improved when coadministered with oligoarginines anchored chemically to hyaluronic acid via a glycine spacer, presumably through syndecan-4-mediated macropinocytosis under activation by oligoarginines. The present mouse experiments first revealed that diglycine-L-tetraarginine-linked hyaluronic acid significantly enhanced the intranasal absorption of sulpiride, which is a poor-absorptive organic compound with a low molecular weight.

Adverse effect of the Epley maneuver: Anterior canal crisis.

Objective: In the Epley maneuver performed on patients with posterior semicircular canal-benign paroxysmal positional vertigo-canalolithiasis (P-BPPV-Can), an intense downbeat nystagmus and retropulsion rarely appear as soon as they reach the last upright sitting position. It is considered an anterior canal crisis that appears when the otoliths move to the ampullofugal direction in the anterior semicircular canal by changing head and body positions from the healthy-ear-down 135° head position (the third head position) to the upright sitting position (the fourth head position). This study aimed to determine the prevention of this anterior canal crisis.

Subjective visual vertical deviation in patients with early-onset direction-changing horizontal positional nystagmus.

Objective: Otolithic dysfunction is investigated in cases of direction-changing horizontal positional nystagmus (DCHPN) due to peripheral vestibular disorders.

Methods: The static-subjective visual vertical (S-SVV) was conducted in DCHPN cases within 48 h after onset.

Results: The absolute values of S-SVV deviations of patients with Light cupula and lateral canal-benign paroxysmal positional vertigo-cupulolithiasis (L-BPPV-Cup) were significantly different from those of healthy subjects (p < 0.

Solid-State-Activated Sintering of ZnAlO Ceramics Containing CuNbO with Superior Dielectric and Thermal Properties.

Low-temperature co-fired ceramics (LTCCs) are dielectric materials that can be co-fired with Ag or Cu; however, conventional LTCC materials are mostly poorly thermally conductive, which is problematic and requires improvement. We focused on ZnAlO (gahnite) as a base material. With its high thermal conductivity (~59 W·m·K reported for 0.

Acquisition of absorption-enhancing abilities of cationic oligopeptides with short chain arginine residues through conjugation to hyaluronic acid.

Cell-penetrating peptides such as oligoarginines are one of promising tools that improve mucosal absorption of poorly membrane-permeable biologics. We have already demonstrated that conjugation of L-octaarginine to hyaluronic acid via a tetraglycine spacer resulted in a 3-fold enhancement of nasal absorption of somatropin (Mw: ca. 22.

Mechanism on antigen delivery under mucosal vaccination using cell-penetrating peptides immobilized at multiple points on polymeric platforms.

We have developed an aggregate of D-octaarginine immobilized at multiple points on a co-polymer of N-vinylacetamide and acrylic acid. Previous studies revealed that immunoglobulin G and A were induced when mice were inoculated with influenza virus antigens under coadministration with the D-octaarginine-immobilized polymers as a mucosal vaccine adjuvant. Infection experiments demonstrated that mice vaccinated with a mixture of inactivated influenza viruses and the polymers were protected from infection with mouse-adapted infectious viruses.

Variants of benign paroxysmal positional vertigo in relation to head position during sleep.

Background: Patients with posterior- and lateral-(canal)-benign paroxysmal positional vertigo (BPPV)-canalolithiasis sleep in the affected-ear-down head position. Posterior-BPPV-canalolithiasis typically affects the right than left ear; sleeping in the right-ear-down head position may be causal.

Objective: To investigate the relationship between habitual head position during sleep and the onset of BPPV variants.

Verbascoside from Verbena incompta is a plant root growth inhibitor.

The use of biopesticides has expanded rapidly in recent years; however, their use in weed control is less advanced. Herein, we describe the development of a weed control agent by screening 208 plant extracts (104 species) for their plant growth-inhibition activities, which resulted in 142 active samples (from 89 plant species). Verbascoside, isolated from the shoots of Verbena incompta, was identified as a growth inhibitor against rice root (EC50, 1.

A new variant of posterior canal-benign paroxysmal positional vertigo-canalolithiasis.

Objective: The characteristics of typical posterior canal-benign paroxysmal positional vertigo-canalolithiasis (P-BPPV-Can) are well known. We found 10 patients with a new variant of P-BPPV-Can: Reverse (Rev)-P-BPPV-Can. The characteristics and pathophysiology of Rev-P-BPPV-Can are discussed.

Bone regeneration utilizing a newly developed octacalcium phosphate/weakly denatured collagen scaffold.

Introduction: Autologous bone grafting or various bone-regenerating materials are used to treat bone defects caused by tumor resection and accident trauma. Octacalcium phosphate, a reasonable bone regenerative material, activates osteoblasts. We fabricated a composite material, octacalcium phosphate/weakly denatured collagen, as a new scaffold.

Biodegradable Hyaluronic Acid Modified with Tetraglycine-l-octaarginine as a Safe Adjuvant for Mucosal Vaccination.

We have been investigating the potential use of polymers modified with cell-penetrating peptides as an adjuvant for mucosal vaccination and have already developed nondegradable poly( N-vinylacetamide- co-acrylic acid) (PNVA- co-AA) with which d-octaarginine, a typical cell-penetrating peptide, was grafted. Our previous murine infection experiments demonstrated that immunoglobulin G (IgG) and immunoglobulin A (IgA) were induced in systemic circulation and secreted on nasal mucosa, respectively, through 4-time nasal inoculations with a mixture of influenza viral antigens and d-octaarginine-linked PNVA- co-AA at 7-day intervals, and that immunized mice were perfectly protected from homologous virus infection. In the present study, we designed novel biodegradable polymers bearing cell-penetrating peptides from a perspective of clinical application.

Ethanol-Induced Cervical Sympathetic Ganglion Block Applications for Promoting Canine Inferior Alveolar Nerve Regeneration Using an Artificial Nerve.

Polyglycolic acid collagen (PGA-C) tubes are bio-absorbable nerve tubes filled with collagen of multi-chamber structure, which consist of thin collagen films. Favorable clinical outcomes have been achieved when using these tubes for the treatment of damaged inferior alveolar nerve (IAN). A critical factor for the successful nerve regeneration using PGA-C tubes is blood supply to the surrounding tissue.

Discovery of 3-Ethyl-4-(3-isopropyl-4-(4-(1-methyl-1 H-pyrazol-4-yl)-1 H-imidazol-1-yl)-1 H-pyrazolo[3,4- b]pyridin-1-yl)benzamide (TAS-116) as a Potent, Selective, and Orally Available HSP90 Inhibitor.

The molecular chaperone heat shock protein 90 (HSP90) is a promising target for cancer therapy, as it assists in the stabilization of cancer-related proteins, promoting cancer cell growth, and survival. A novel series of HSP90 inhibitors were discovered by structure-activity relationship (SAR)-based optimization of an initial hit compound 11a having a 4-(4-(quinolin-3-yl)-1 H-indol-1-yl)benzamide structure. The pyrazolo[3,4- b]pyridine derivative, 16e (TAS-116), is a selective inhibitor of HSP90α and HSP90β among the HSP90 family proteins and exhibits oral availability in mice.

Evaluating the mandibular condyles of patients with osteoarthritis for bone marrow abnormalities using magnetic resonance T2 mapping.

Objectives: This study investigated whether erosion and osteophyte correlates with condyle bone marrow abnormalities (BMA), as detected with quantitative T2 mapping.

Methods: Fifty-six joints (in 44 patients) that demonstrated evidence of bony erosion (ER) or osteophytes (OS) related to disc displacement without reduction were studied with MR images. A control group of 50 joints (in 50 patients) was included.

Infectious complications in adults undergoing intensive chemotherapy for acute myeloid leukemia in 2001-2005 using the Japan Adult Leukemia Study Group AML201 protocols.

Purpose: The Japan Adult Leukemia Study Group (JALSG) AML201 protocols are regimens for remission induction and consolidation chemotherapy of acute myeloid leukemia (AML) and have been widely accepted in Japan since 2001. Management of infectious complications during chemotherapy has a key role in the supportive care of AML patients.

Methods: By using case report forms collected in December 2001 and December 2005, we retrospectively analyzed the infectious complications in adult patients treated by using the JALSG AML201 protocols against AML (excluding promyelocytic leukemia).

Influence of technique used to attach the infusion set to peristaltic finger smart-pumps on dispensing time: an experimental study.

Background: Infusion sets designed for peristaltic finger smart pumps (PFSPs) are necessary for the pumps' accurate handling. We previously found that medication dispensing is occasionally incomplete following the calculated infusion time when using certain combinations of PFSPs and infusion sets at a Japanese hospital. Thus, in this study, we investigated the cause of this observed delay by determining the effect of infusion set attachment technique on dispensing time using a combination of three kinds of PFSPs and five kinds of polyvinyl chloride (PVC) and polybutadiene (PB) infusion sets.

Biocompatible Polymers Modified with d-Octaarginine as an Absorption Enhancer for Nasal Peptide Delivery.

Peptide and protein drugs, which are categorized as biologics, exhibit poor membrane permeability. This pharmacokinetic disadvantage has largely restricted the development of noninvasive dosage forms of biologics that deliver into systemic circulation. We have been investigating the potential use of cell-penetrating peptide-linked polymers as a novel absorption enhancer to overcome this challenge.

Effects of the Chemical Structures of Oligoarginines Conjugated to Biocompatible Polymers as a Mucosal Adjuvant on Antibody Induction in Nasal Cavities.

We have been investigating the potential of oligoarginine-linked polymers as an adjuvant for mucosal vaccination that induces immunoglobulin G (IgG) in systemic circulation and immunoglobulin A (IgA) secreted on the mucosa. Our latest infection experiments demonstrated that mice immunized nasally with a mixture of inactivated influenza viruses and poly(N-vinylacetamide-co-acrylic acid) (PNVA-co-AA) modified with D-octaarginine were perfectly protected from homologous virus infection. On the contrary, virus infection was observed in mice immunized with the antigen alone.

Can nerve regeneration on an artificial nerve conduit be enhanced by ethanol-induced cervical sympathetic ganglion block?

This study aimed to determine whether nerve regeneration by means of an artificial nerve conduit is promoted by ethanol-induced cervical sympathetic ganglion block (CSGB) in a canine model. This study involved two experiments-in part I, the authors examined the effect of CSGB by ethanol injection on long-term blood flow to the orofacial region; part II involved evaluation of the effect of CSGB by ethanol injection on inferior alveolar nerve (IAN) repair using polyglycolic acid-collagen tubes. In part I, seven Beagles were administered left CSGB by injection of 99.

Artificial sensory organs: latest progress.

This study introduces the latest progress on the study of artificial sensory organs, with a special emphasis on the clinical results of artificial nerves and the concept of in situ tissue engineering. Peripheral nerves have a strong potential for regeneration. An artificial nerve uses this potential to recover a damaged peripheral nerve.

Management of infection during chemotherapy for acute leukemia in Japan: a nationwide questionnaire-based survey by the Japan Adult Leukemia Study Group.

Purpose: We performed a nationwide questionnaire-based survey to evaluate the current clinical practices of infectious complications during chemotherapy for acute leukemia in Japan.

Methods: We e-mailed a questionnaire to member institutions of the Japan Adult Leukemia Study Group in September, 2013. The questionnaire consisted of 50 multiple-choice questions covering therapeutic environment, antimicrobial prophylaxis, screening test during neutropenia, empirical therapy for febrile neutropenia, and the use of granulocyte-colony stimulating factor.