Absorption, Metabolism, and Excretion by Freely Moving Rats of 3,4-DHPEA-EDA and Related Polyphenols from Olive Fruits (Olea europaea).

Absorption, metabolism, and excretion of 3,4-DHPEA-EDA, oleuropein, and hydroxytyrosol isolated from olive fruits were newly evaluated after oral and intravenous administration in freely moving rats cannulated in the portal vein, jugular vein, and bile duct. Orally administered 3,4-DHPEA-EDA, an important bioactive compound in olive pomace, was readily absorbed and metabolized to hydroxytyrosol, homovanillic acid, and homovanillyl alcohol, as shown by dose-normalized 4 h area under the curve (AUC0→4 h/Dose) values of 27.7, 4.

Strategic balance of drug lifecycle management options differs between domestic and foreign companies in Japan.

Introduction: Drug approvals and patent protections are critical in drug lifecycle management (LCM) in order to maximize drug discovery investment returns.

Area Covered: We analyzed drug LCM activities implemented by 10 top companies in Japan, focusing on drug approvals and patent term extensions.

Expert Opinion: Foreign companies acquired numerous drug approvals primarily for new molecular entities (NMEs), while Japanese companies mainly obtained approvals for improved drugs including new indications, and intensively extended patent terms.

Effectiveness of superselective intra-arterial chemoradiotherapy targeting retropharyngeal lymph node metastasis.

We sought to evaluate the efficacy and feasibility of superselective intra-arterial infusion of high-dose cisplatin with concomitant radiotherapy (hereafter RADPLAT) for head and neck squamous cell cancer (hereafter HNSCC) patients with retropharyngeal lymph node (hereafter RPLN) metastasis. A retrospective case series review was conducted at University medical center in Japan. Ten HNSCC patients with RPLN metastasis treated by RADPLAT were analyzed.

Clinical Outcomes and Prognostic Factors for Salivary Duct Carcinoma: A Multi-Institutional Analysis of 141 Patients.

Background: Among salivary gland malignancies, the prognosis of salivary duct carcinoma (SDC) is assumed to be the poorest. However, because of its low incidence, reliable survival estimates and prognostic factors based on a large number of patients remain to be elucidated, thereby making it impossible to standardize the optimal treatment for SDC.

Methods: We performed this multi-institutional, retrospective analysis by collecting the clinical information of 141 patients with SDC without distant metastasis who underwent curative surgery as the initial treatment to elucidate overall survival (OS) and disease-free survival (DFS) along with their prognostic factors.

Mapping lifecycle management activities for blockbuster drugs in Japan based on drug approvals and patent term extensions.

Drug lifecycle management (LCM), which entails acquiring drug approvals and patent protections, contributes to maximizing drug discovery investment returns. In a previous survey, a comparative analysis between Japan and the USA indicated that a unique patent term extension system has an important role in Japanese drug LCM. Therefore, in this survey, we focused on drug approvals and patent term extensions, and found that the LCM for blockbuster drugs in Japan can be categorized into three types (drug approval-oriented LCM, patent term extension-oriented LCM, and inactive-type LCM), of which the first two have been implemented recently.

Usefulness of routine aortic valve calcium score measurement for risk stratification of aortic stenosis and coronary artery disease in patients scheduled cardiac multislice computed tomography.

Objectives: This study sought to investigate the clinical utility of aortic valve calcium score (AVCS) determined by using cardiac multislice computed tomography (MSCT).

Methods: Data of 1315 consecutive patients who underwent both conventional echocardiography and MSCT were reviewed. Degree of aortic stenosis (AS) was assessed according to mean pressure gradient (mPG) measured by echocardiography.

Extreme late-phase observation using coronary angioscopy until 7 years after sirolimus-eluting stent implantation.

Background: Little is known about the very late-phase morphological vessel characteristics within the sirolimus-eluting stent (SES).

Methods And Results: We assessed a total of 12 patients with 15 SES implantations who underwent repeat angiographic and angioscopic procedures after 5 and 7 years. The degree of neointimal stent coverage (NSC) was classified as follows: grade 0, uncovered struts; grade 1, visible struts through a thin neointima; or grade 2, invisible struts with complete neointimal coverage.

Infection and characterization of Toxoplasma gondii in human induced neurons from patients with brain disorders and healthy controls.

Toxoplasma gondii is a protozoan parasite capable of establishing persistent infection within the brain. Serological studies in humans have linked exposure to Toxoplasma to neuropsychiatric disorders. However, serological studies have not elucidated the related molecular mechanisms within neuronal cells.

Patent term extension systems differentiate Japanese and US drug lifecycle management.

Drug lifecycle management (LCM) contributes to maximizing drug discovery investment returns. After initial drug approval, additional approvals can be sought for novel indications and formulations to extend product marketability. Patents provide additional barriers to entry and patent term extension systems facilitate extension of these.

Enhanced conversion of induced neuronal cells (iN cells) from human fibroblasts: Utility in uncovering cellular deficits in mental illness-associated chromosomal abnormalities.

The novel technology of induced neuronal cells (iN cells) is promising for translational neuroscience, as it allows the conversion of human fibroblasts into cells with postmitotic neuronal traits. However, a major technical barrier is the low conversion rate. To overcome this problem, we optimized the conversion media.

Detection of anaerobic carbon monoxide-oxidizing thermophiles in hydrothermal environments.

Carboxydotrophic anaerobic thermophiles have been isolated from various hydrothermal environments and are considered to be important carbon monoxide (CO) scavengers or primary producers. However, the ecological factors that influence the distribution, abundance and CO-oxidizing activities of these bacteria are poorly understood. A previous study detected the carboxydotrophic bacteria Carboxydothermus spp.

Patient Knowledge on Malaria Symptoms Is a Key to Promoting Universal Access of Patients to Effective Malaria Treatment in Palawan, the Philippines.

Introduction: Palawan, where health care facilities are still limited, is one of the most malaria endemic provinces in the Philippines. Since 1999, microscopists (community health workers) have been trained in malaria diagnosis and feasibility of early diagnosis and treatments have been enhanced throughout the province. To accelerate the universal access of malaria patients to diagnostic testing in Palawan, positive health seeking behavior should be encouraged when malaria infection is suspected.

Radio-frequency capacitance spectroscopy of metallic nanoparticles.

Recent years have seen great progress in our understanding of the electronic properties of nanomaterials in which at least one dimension measures less than 100 nm. However, contacting true nanometer scale materials such as individual molecules or nanoparticles remains a challenge as even state-of-the-art nanofabrication techniques such as electron-beam lithography have a resolution of a few nm at best. Here we present a fabrication and measurement technique that allows high sensitivity and high bandwidth readout of discrete quantum states of metallic nanoparticles which does not require nm resolution or precision.

Viral protein R of HIV type-1 induces retrotransposition and upregulates glutamate synthesis by the signal transducer and activator of transcription 1 signaling pathway.

Viral protein R (Vpr) of HIV-1 plays an important role in viral replication in macrophages. Various lines of evidence suggest that expression of Vpr in macrophages causes immunopathogenesis; however, the underlying mechanism is not yet fully understood. In this study, it was shown that recombinant Vpr (rVpr) induces retrotransposition of long interspersed element-1 in RAW264.

[A clinical study of cases diagnosed as being oropharyngeal carcinoma after cervical mass extirpation/biopsy].

In the case of oropharyngeal carcinoma, patients may present with symptoms similar to cervical lymphadenopathy, and the primary lesion may only be diagnosed after cervical mass extirpation/biopsy. We retrospectively analyzed the clinical course in 11 oropharyngeal carcinoma patients that were diagnosed after cervical mass extirpation/biopsy between 1998 and 2013. Before the diagnosis was made of oropharyngeal carcinoma, a cervical lymph node biopsy was performed in six patients; the lymph node was extirpated due to an initial diagnosis of lateral cervical cyst in four patients; and neck dissection was performed due to an initial diagnosis of primary unknown carcinoma in one patient.

Indications for superselective intra-arterial cisplatin infusion and concomitant radiotherapy in cases of hypopharyngeal cancer.

Objective: We retrospectively assessed the indications for superselective intra-arterial infusion of cisplatin with concomitant radiotherapy (RADPLAT) in patients with hypopharyngeal cancer (HPC).

Methods: Between April 2000 and March 2013, 41 previously untreated patients received superselective intra-arterial infusion of cisplatin (100-120mg/m(2) per week) with simultaneous intravenous infusions of thiosulfate to neutralize cisplatin toxicity and conventional radiotherapy (65-70Gy).

Results: During the median follow-up period of 5.

The efficacy of superselective intra-arterial infusion with concomitant radiotherapy for adenoid cystic carcinoma of the head and neck.

Conclusions: Superselective intra-arterial cisplatin infusion with concomitant radiotherapy (RADPLAT) is considered to be one of the treatments of choice for patients with adenoid cystic carcinoma (ACC) who prefer not to undergo radical surgery.

Objective: To evaluate the efficacy of RADPLAT for patients with ACC of the head and neck.

Patients And Methods: Between 2001-2010, nine patients with untreated ACC were given superselective intra-arterial infusion of cisplatin (100-120 mg/m(2)/week) with simultaneous intravenous infusion of thiosulfate to neutralize cisplatin toxicity and radiotherapy (65-70 Gy).

Comparison of acute toxicities associated with cetuximab-based bioradiotherapy and platinum-based chemoradiotherapy for head and neck squamous cell carcinomas: A single-institution retrospective study in Japan.

Conclusion: Grade ≥ 3 mucositis/stomatitis and inability to feed orally were problematic for patients undergoing cetuximab-based bioradiotherapy (BRT) as well as platinum-based chemoradiotherapy (CRT). Severe mucositis/stomatitis and radiation dermatitis should be addressed carefully in patients undergoing cetuximab-based BRT as well.

Objectives: The efficacy of cetuximab-based BRT in locally advanced head and neck squamous cell carcinomas has been established.

Clinical outcomes of weekly cisplatin chemoradiotherapy for patients with pyriform sinus cancer.

Background: Pyriform sinus squamous cell carcinoma (SCC) has one of the worst prognoses of all upper aerodigestive tract cancers. Improving clinical outcomes for patients with hypopharyngeal SCC has been particularly challenging for head and neck surgeons and oncologists.

Methods: We investigated 30 patients with pyriform sinus SCC to verify the effectiveness of weekly cisplatin chemotherapy with concurrent radiotherapy.

[Malaria cases treated with artemether/lumefantrine in Japanese travelers].

Artemisinin-based combination therapy (ACT) has been the standard treatment for uncomplicated malaria. Although not licensed in Japan, artemether/lumefantrine (AL), one type of ACT, has been administered to patients with malaria since 2002 by the Research Group on Chemotherapy of Tropical Diseases. Herein, we reviewed malaria cases treated with AL in Japanese travelers.

Management for squamous cell carcinoma of the nasal cavity and ethmoid sinus: A single institution experience.

Objective: Here we report our experience of patients with squamous cell carcinoma (SCC) of the nasal cavity and ethmoid sinus (NC&ES) together with an analysis of treatment outcomes.

Methods: A retrospective analysis was performed using data from 25 consecutive patients treated between 2000 and 2012. Four patients were diagnosed with T1, 3 with T2, 4 with T3, 7 with T4a, and 7 with T4b disease.

Clinical utility of neuronal cells directly converted from fibroblasts of patients for neuropsychiatric disorders: studies of lysosomal storage diseases and channelopathy.

Methodologies for generating functional neuronal cells directly from human fibroblasts [induced neuronal (iN) cells] have been recently developed, but the research so far has only focused on technical refinements or recapitulation of known pathological phenotypes. A critical question is whether this novel technology will contribute to elucidation of novel disease mechanisms or evaluation of therapeutic strategies. Here we have addressed this question by studying Tay-Sachs disease, a representative lysosomal storage disease, and Dravet syndrome, a form of severe myoclonic epilepsy in infancy, using human iN cells with feature of immature postmitotic glutamatergic neuronal cells.

Patients' perceptions of vocal problems: results from a survey in the Tokyo area.

Laryngoscopy in cases of sulcus vocalis reveals bowed vocal folds, resulting in a spindle-shaped chink with glottal incompetence. The anatomic and functional problems and resulting incomplete glottal closure during phonation lead to the presenting symptoms of breathy hoarseness, decrease in maximum phonation time (MPT), and vocal fatigue. These symptoms, however, have been reported from the physician's viewpoint, not the patient's.

Control of charging energy in chemically assembled nanoparticle single-electron transistors.

We show the control of a charging energy in chemically assembled nanoparticle single-electron transistors (SETs) by altering the core diameter of Au nanoparticles. The charging energy is a fundamental parameter that decides the operating temperature of SETs. Practical application of SETs requires us to regulate the value of the charging energy by tuning the diameter of quantum dots.

Granulomatous cheilitis with intralymphatic histiocytosis possibly associated with calcium deposition caused by chronic inflammation owing to dental metals and periodontitis.

Granulomatous cheilitis (GC) is an uncommon disease and the pathogenesis of GC has not been clear. Here, we present two cases of GC associated with calcium deposition caused by chronic inflammation owing to dental metal allergy and periodontitis. Histopathologically, intralymphatic histiocytosis (IH) in addition to non-caseating granulomas was seen in both cases.