[A study of 31 terminally ill cancer patients who received pure oxycodone injections at home].

Since the launch of pure oxycodone injections in May 2012, it has been possible to use oxycodone without opioid rotation. Although an extremely important step showing progress, very few studies regarding the use of pure oxycodone injections have been performed. In this study, we evaluated the safety and efficacy of pure oxycodone injections in 31 terminally ill cancer patients receiving home care. The difficulty in oral oxycodone intake was the main reason for changing to pure oxycodone injections. The mean administered period of subcutaneous pure oxycodone was 5.6 ± 6.7 days. One out of 5 patients receiving pure oxycodone injections complained of worsening sleepiness. However, other symptoms improved. In addition, in cases wherein pure oxycodone injection was the initiating opioid, 1 out of 6 patients showed no improvement of respiratory discomfort, while other symptoms improved. It was difficult to evaluate more patients because of the short period for administration. Although 5 patients experienced skin problems, they were successfully managed by changing the injection site. Of these 5 patients, 2 patients had sensitive skin, with a previous history of alcohol rash. In conclusion, our study suggests that pure oxycodone injections are beneficial over oral oxycodone treatment for terminally ill cancer patients. However, further evaluation of skin problems associated with pure oxycodone injections is required by performing larger studies.

Impact of variability of in silico and in vitro octanol/water partition coefficients of compounds on the input parameters and results of simplified human physiologically based pharmacokinetic models after virtual oral administrations.

The octanol/water partition coefficient, P (logP), is a hydrophobicity index and is one of the determining factors of the pharmacokinetics of chemical compounds. LogP values obtained from in silico software, open chemistry databases, and in vitro liquid chromatography retention factors may vary. Some chemicals (boscalid, etoxazole, and permethrin) have up to four-order-magnitude differences in in silico/in vitro P values. This study aimed to evaluate the effects of logP values of these three compounds, along with bisphenol A, 1,2-dibromobenzene, tetrabromobisphenol A, trazodone, and triazolam, on the input parameters and output plasma/hepatic concentration-time profiles of simple physiologically based pharmacokinetic (PBPK) models. Although the blood-to-plasma concentration ratios (~0.9-0.6) were slightly affected by variations in logP values, logarithmic plasma unbound fraction values and liver-to-plasma partition coefficients (Kp,h) were, respectively, inversely and linearly correlated with logP values (Kp,h was stable at ~6.7 for logP > 4). LogP was among the input parameters for previously established machine learning systems; consequently, the resulting logarithmic intrinsic clearance values were correlated with logP values in the range 2-8. However, the bioavailability, absorption rate constants, and volumes of distribution were not affected. PBPK-modeled plasma and hepatic maximum concentrations and areas under the concentration-time curves after virtual oral doses were mostly within ~0.5- to ~2-fold ranges, except for substances with low in vitro logP values, e.g., etoxazole and permethrin. These results suggest that in silico logP values are generally suitable for pharmacokinetic modeling; nevertheless, caution is needed for compounds with low in vitro logP values of ~2.

Unlocking the Full Potential of Electron-Acceptor Molecules for Efficient and Stable Hole Injection.

Understanding the hole-injection mechanism and improving the hole-injection property are of pivotal importance in the future development of organic optoelectronic devices. Electron-acceptor molecules with high electron affinity (EA) are widely used in electronic applications, such as hole injection and p-doping. Although p-doping has generally been studied in terms of matching the ionization energy (IE) of organic semiconductors with the EA of acceptor molecules, little is known about the effect of the EA of acceptor molecules on the hole-injection property. In this work, the hole-injection mechanism in devices is completely clarified, and a strategy to optimize the hole-injection property of the acceptor molecule is developed. Efficient and stable hole injection is found to be possible even into materials with IEs as high as 5.8 eV by controlling the charged state of an acceptor molecule with an EA of about 5.0 eV. This excellent hole-injection property enables direct hole injection into an emitting layer, realizing a pure blue organic light-emitting diode with an extraordinarily low turn-on voltage of 2.67 V, a power efficiency of 29 lm W-1 , an external quantum efficiency of 28% and a Commission Internationale de l'Eclairage y coordinate of less than 0.10.

Unravelling the electron injection/transport mechanism in organic light-emitting diodes.

Although significant progress has been made in the development of light-emitting materials for organic light-emitting diodes along with the elucidation of emission mechanisms, the electron injection/transport mechanism remains unclear, and the materials used for electron injection/transport have been basically unchanged for more than 20 years. Here, we unravelled the electron injection/transport mechanism by tuning the work function near the cathode to about 2.0 eV using a superbase. This extremely low-work function cathode allows direct electron injection into various materials, and it was found that organic materials can transport electrons independently of their molecular structure. On the basis of these findings, we have realised a simply structured blue organic light-emitting diode with an operational lifetime of more than 1,000,000 hours. Unravelling the electron injection/transport mechanism, as reported in this paper, not only greatly increases the choice of materials to be used for devices, but also allows simple device structures.

[Current status of palliative care in medical oncology].

A team approach is efficient in palliative care for cancer patients. People suffered from cancer have a right to receive high-quality palliative care earlier in cancer treatment. In Japan the National Act for Strategy against Cancer was enacted in 2007. Systematic educational programs supported by the Ministry of Health Labor and Welfare has been conducted for medical staffs, home care staffs, local pharmacists, care managers etc. at core institutes in each district. Pain control is still major target for cancer palliative medicine. Recently various types of opioids can be used routinely in daily clinical setting for Japanese cancer patients. Complementary and alternative medicine (CAM) may also effective in some patients but further study for proving scientific evidence in CAM should be warranted. Tailor-maid pain control will be established in the near future with molecular based pharmacogenomics.

Understanding coordination reaction for producing stable electrode with various low work functions.

The realisation of a cathode with various work functions (WFs) is required to maximise the potential of organic semiconductors that have various electron affinities. However, the barrier-free contact for electrons could only be achieved by using reactive materials, which significantly reduce the environmental stability of organic devices. We show that a stable electrode with various WFs can be produced by utilising the coordination reaction between several phenanthroline derivatives and the electrode. Although the low WF of the electrode realised by using reactive materials is specific to the material, the WF of the phenanthroline-modified electrode is tunable depending on the amount of electron transfer associated with the coordination reaction. A phenanthroline-modified electrode that has a higher electron injection efficiency than lithium fluoride has been demonstrated. The observation of various WFs induced by the coordination reaction affords strategic perspectives on the development of stable cathodes unique to organic electronics.

Effects of Energy-Level Alignment on Characteristics of Inverted Organic Light-Emitting Diodes.

Inverted organic light-emitting diodes (iOLEDs) without the use of alkali metals have attracted extensive attention owing to the demand for the realization of flexible OLEDs that do not require stringent encapsulation. In this paper, we discuss the correlation between the characteristics of iOLEDs and the energy-level alignment at cathode/organic layer interfaces examined by ultraviolet photoelectron spectroscopy. Two similar electron-transporting materials having different orbital energies, 2,8-bis(diphenylphosphoryl)dibenzo[ b, d]thiophene (PPT) and 2,8-bis(diphenylphosphoryl)dibenzo[ b, d]thiophene sulfone (PPT-S), are inserted between the cathode/polyethyleneimine and the emitting layer in the iOLED. The iOLED employing PPT-S exhibits a lower driving voltage and a higher efficiency than that employing PPT, which is consistent with the orbital energies of the two molecules. Although the stabilities of these two molecules are expected to be similar, the iOLED employing PPT-S exhibits an operational lifetime that is more than 100 times longer than that of the iOLED employing PPT. It was found that the difference in operational lifetime is caused by the difference in the energy-level alignment at the cathode/organic layer interfaces. Our results are expected to promote the development of promising materials and device configurations for fabricating efficient and operationally stable iOLEDs.

Universal Strategy for Efficient Electron Injection into Organic Semiconductors Utilizing Hydrogen Bonds.

Molecular n-dopants that can lower the electron injection barrier between organic semiconductors and electrodes are essential in present-day organic electronics. However, the development of stable molecular n-dopants remains difficult owing to their low ionization potential, which generally renders them unstable. It is shown that the stable bases widely used in organic synthesis as catalysts can lower the electron injection barrier similar to that in conventional n-doping in organic optoelectronic devices. In contrast to conventional n-doping, which is based on the electron transfer from dopants with low ionization potential, the reduction of the injection barrier caused by adding bases is determined by the formation of hydrogen bonds between the hosts and the bases, providing energy-level-independent electron injection. The observation of the efficient electron injection induced by hydrogen bonding affords new perspectives on the method for controlling the behavior of electrons unique to organic semiconductors.

N-terminal labeling of proteins by the Pictet-Spengler reaction.

The Pictet-Spengler reaction was applied to the N-terminal labeling of horse heart myoglobin. This was performed in the following two steps: (1) conversion of the N-terminal glycine residue to an alpha-keto aldehyde by a transamination reaction and (2) condensation of the resulting activated myoglobin with tryptamine analogues by the Pictet-Spengler reaction. Ultraviolet (UV)/visible (vis) absorption and circular dichroism (CD) spectral data revealed that the tertiary structure of myoglobin was not altered by the Pictet-Spengler reaction.

Long-Lived Flexible Displays Employing Efficient and Stable Inverted Organic Light-Emitting Diodes.

Although organic light-emitting diodes (OLEDs) are promising for use in applications such as in flexible displays, reports of long-lived flexible OLED-based devices are limited due to the poor environmental stability of OLEDs. Flexible substrates such as plastic allow ambient oxygen and moisture to permeate into devices, which degrades the alkali metals used for the electron-injection layer in conventional OLEDs (cOLEDs). Here, the fabrication of a long-lived flexible display is reported using efficient and stable inverted OLEDs (iOLEDs), in which electrons can be effectively injected without the use of alkali metals. The flexible display employing iOLEDs can emit light for over 1 year with simplified encapsulation, whereas a flexible display employing cOLEDs exhibits almost no luminescence after only 21 d with the same encapsulation. These results demonstrate the great potential of iOLEDs to replace cOLEDs employing alkali metals for use in a wide variety of flexible organic optoelectronic devices.

Electrochemical gating-induced reversible and drastic resistance switching in VO2 nanowires.

Reversible and drastic modulation of the transport properties in vanadium dioxide (VO2) nanowires by electric field-induced hydrogenation at room temperature was demonstrated using the nanogaps separated by humid air in field-effect transistors with planer-type gates (PG-FET). These PG-FETs allowed us to investigate behavior of revealed hydrogen intercalation and diffusion aspects with time and spatial evolutions in nanowires. These results show that air nanogaps can operate as an electrochemical reaction field, even in a gaseous atmosphere, and offer new directions to explore emerging functions for electronic and energy devices in oxides.