Questionnaire-Based Development of an Educational Program of Traditional Japanese Kampo Medicine.

Traditional Japanese Kampo medicine has been widely used in clinical practice in Japan. Though it is a compulsory subject in Japanese medical schools, a standard educational program in Kampo medicine does not exist. Tohoku University has incorporated Kampo medicine into clinical education via didactic lectures since 2003; however, student evaluations have been lower for Kampo than for all other clinical specialties. We administered a questionnaire about a Kampo medicine course for fifth-year students from 2009 to 2012 and developed an educational program based on feedback obtained. The questionnaire consisted of nine questions (a clear training plan; opportunities for learning, practice, and patient contact; acquisition of medical knowledge and physical examination; learning professionalism; understanding the specialty; overall assessment) that were rated on a 5-point Likert scale along with open-ended questions about the course's strengths and weaknesses. The students responded to the questionnaire after clinical practice in Kampo medicine and other clinical specialty courses. Scores for Kampo medicine and the average of other clinical specialties were compared. All 389 students who participated in Kampo clinical practice answered the questionnaire. In 2009, scores for Kampo medicine for nine questions were lower than for the average of the other clinical specialties. After curriculum reformation involving hands-on training in 2012, all scores except "opportunities to learn about clinical cases" and "opportunities to practice involvement" were higher than the average of all other clinical specialties. In conclusion, we have successfully developed a Kampo medicine educational program for our university through this survey study.

Physicians' attitude toward recurrent hypercalcemia in terminally ill cancer patients.

BACKGROUND: There is no consensus regarding whether cancer-induced hypercalcemia should be treated up until the patient's death. The primary aim of this study was to clarify physicians' attitude toward treating recurrent hypercalcemia in terminally ill cancer patients and associated factors. METHODS: A nationwide, cross-sectional survey was performed involving 757 physicians of the Japanese Society for Palliative Medicine. Physicians' attitude toward treating hypercalcemia in terminally ill patients was assessed based on the response to the question: do you agree that you provide medical treatment for recurrent hypercalcemia up until a patient's death? As the potential determinants of physicians' attitudes, we examined their characteristics, beliefs about hypercalcemia, and beliefs about a good death. RESULTS: We obtained a total of 380 (50.2%) analyzable responses. A total of 163 physicians (43%) agreed that hypercalcemia should be treated up until the patient's death, while the remaining 217 physicians (57%) disagreed. The independent determinants of the attitude included the following: physicians' specialty, belief that hypercalcemia treatment improves pain, belief that hypercalcemia treatment improves nausea, belief that hypercalcemia treatment improves quality of life, belief that hypercalcemia treatment prolongs life, belief that the effect of hypercalcemia treatment reduces gradually, belief that death with hypercalcemia is less distressing, and the perception that being mentally clear is important for a good death. CONCLUSION: Japanese physicians had different attitudes toward treating hypercalcemia in terminally ill patients. Physicians' beliefs about the efficacy of medical treatment for hypercalcemia markedly influenced their attitudes. Clarifying evidence on the effect of hypercalcemia treatment on patients' symptoms and prognoses is strongly encouraged.

Total Synthesis of Mycalolides A and B through Olefin Metathesis.

An asymmetric total synthesis of the trisoxazole marine macrolides mycalolides A and B is described. This synthesis involves the convergent assembly of highly functionalized C1-C19 trisoxazole and C20-C35 side-chain segments through the use of olefin metathesis and esterification as well as Julia-Kocienski olefination and enamide formation as key steps.

Coherent nuclear dynamics in ultrafast photoinduced structural change of bis(diimine)copper(I) complex.

The photoinduced structural change of a prototype metal complex, [Cu(dmphen)(2)](+) (dmphen = 2,9-dimethyl-1,10-phenanthroline), was studied by ultrafast spectroscopy with time resolution as high as 30 fs. Time-resolved absorption measured with direct S(1) excitation clearly showed spectral changes attributable to the D(2d) (perpendicular) → D(2) (flattened) structural change occurring in the metal-to-ligand charge transfer singlet excited state ((1)MLCT) and the subsequent S(1) → T(1) intersystem crossing. It was confirmed that the two processes occur with time constants of ~0.8 ps (structural change) and ~10 ps (intersystem crossing), and their time scales are clearly well-separated. A distinct oscillation of the transient absorption signal was observed in the femtosecond region, which arises from the coherent nuclear motion of the perpendicular S(1) state that was directly generated by photoexcitation. This demonstrated that the perpendicular S(1) state has a well-defined vibrational structure and can vibrate within its subpicosecond lifetime. In other words, the S(1) state stays undistorted in a short period, and the coherent nuclear motion is maintained in this state. Time-dependent density functional theory (TDDFT) calculations gave consistent results, indicating a very flat feature and even a local minimum at the perpendicular structure on the S(1) potential energy surface. The vibrational assignments of the S(1) nuclear wavepacket motion were made on the basis of the TDDFT calculation. It was concluded that photoexcitation induces a(1) vibrations containing the Cu-ligand bond length change and a b(1) vibration attributed to the ligand-twisting motion that has the same symmetry as the flattening distortion. Ultrafast spectroscopy and complementary quantum chemical calculation provided an overall picture and new understanding of the photoinduced structural change of the prototypical metal complex.

"Up" versus "down" alignment and hydration structures of solutes at the air/water interface revealed by heterodyne-detected electronic sum frequency generation with classical molecular dynamics simulation.

We unambiguously demonstrate the "up" versus "down" alignment of a pair of prototypical solute molecules adsorbed at the air/water interface for the first time using heterodyne-detected electronic sum frequency generation spectroscopy. This molecular alignment is also reproduced by classical molecular dynamics (MD) simulation theoretically. Furthermore, the MD simulation indicates distinctly different interface-specific hydration structures around the two solute molecules, which dictate the molecular alignment at the interface. It is concluded that the hydrophilicity difference between the terminal functional groups of the solute governs the molecular orientation and surrounding hydration structures at the interface.

"Half-hydration" at the air/water interface revealed by heterodyne-detected electronic sum frequency generation spectroscopy, polarization second harmonic generation, and molecular dynamics simulation.

A solute-solvent interaction at the air/water interface was investigated both experimentally and theoretically, by studying a prototypical surface-active polarity indicator molecule, coumarin 110 (C110), adsorbed at the air/water interface with heterodyne-detected electronic sum frequency generation (HD-ESFG) spectroscopy, polarization second harmonic generation (SHG), and a molecular dynamics (MD) simulation. The second-order nonlinear optical susceptibility (chi((2))) tensor elements of C110 at the air/water interface were determined experimentally by HD-ESFG and polarization SHG, and information on "intermediate" polarity sensed by C110 at the interface was obtained by HD-ESFG. An MD simulation and a time-dependent density functional theory calculation were used to theoretically evaluate the chi((2)) tensor elements, which were in good agreement with the experimental results of HD-ESFG and polarization SHG. The microscopic "half-hydration" structure around C110 at the water surface was visualized on the basis of the MD simulation data, with which we can intuitively understand the microscopic origin of the surface activity of C110 and the intermediate polarity sensed by C110 at the air/water interface.

Methamphetamine-induced hyperthermia and lethal toxicity: role of the dopamine and serotonin transporters.

We examined the hyperthermic and lethal toxic effects of methamphetamine in dopamine transporter (DAT) and/or serotonin transporter (SERT) knockout (KO) mice. Methamphetamine (45 mg/kg) caused significant hyperthermia even in the mice with a single DAT gene copy and no SERT copies (DAT+/- SERT-/- mice). Mice with no DAT copies and a single SERT gene copy (DAT-/- SERT+/- mice) showed significant but reduced hyperthermia when compared to wild-type mice after methamphetamine. Surprisingly, DAT/SERT double KO mice exhibited a paradoxical hypothermia after methamphetamine. These results demonstrate that methamphetamine exerts a hyperthermic effect via DAT, or via SERT, in the absence of DAT. The selective norepinephrine transporter blocker (20 mg/kg nisoxetine) caused hyperthermia in DAT/SERT double KO mice, suggesting that the norepinephrine system is not responsible for methamphetamine-induced paradoxical hypothermia in the double KO mice. DAT gene deletion in mice strikingly increased LD50 of methamphetamine by 1.7-1.8 times that of wild-type mice, suggesting that the lethal toxic effect of methamphetamine is mainly dependent on DAT. Moreover, dissociation between hyperthermic and lethal toxic effects of methamphetamine in DAT single KO mice and DAT/SERT double KO mice suggest that hyperthermia is not a prerequisite for methamphetamine-induced lethality. Methamphetamine (45 mg/kg) significantly increased mRNA of interleukin-1beta, which is the major endogenous pyrogen, in the hypothalamus of wild-type mice but not in DAT/SERT double KO mice, which provides a partial mechanism of methamphetamine-induced paradoxical hypothermia. These results suggest that DAT and SERT are key molecules for hyperthermic and lethal toxic effects of methamphetamine.

Synthesis and biological activities of vitamin D3 derivatives with cyanoalkyl side chain at C-2 position.

We synthesized and evaluated novel vitamin D3 derivatives with cyanoalkyl side chain at C-2 position on the basis of our previous research for 2α side chain which bears nitrogen atom-containing functional group. Through a study of X-ray co-crystal structures of human VDR and compound 3, we demonstrated that the 2α alkyl side chain in compound 3 shows a novel interaction in the complex of hVDR-LBD and ligand. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.

[The attempt to standardize treatment protocols for cancer-related hypercalcemia: developing a data-based flowchart].

We developed a flowchart for the treatment of cancer-related hypercalcemia based on the review of previous reports. The treatment protocols were standardized in each group of four different ranges of serum calcium concentration (< 12, 12-14, 14-16, < 16 mg/dl). In each Ca range, specific treatment was adjusted according to the clinical evaluation of symptoms and progression of illness of the patients.

Inhibitory effects of excess sympathetic activity on parasympathetic vasodilation in the rat masseter muscle.

The present study was designed to examine the effect of sympathetic tonic activity on parasympathetic vasodilation evoked by the trigeminal-mediated reflex in the masseter muscle in urethane-anesthetized rats. Sectioning of the superior cervical sympathetic trunk (CST) ipsilaterally increased the basal level of blood flow in the masseter muscle (MBF). Electrical stimulation of the peripheral cut end of the CST for 2 min using 2-ms pulses ipsilaterally decreased in a dependent manner the intensity (0.5-10 V) and frequency (0.1-5 Hz) of the MBF. The CST stimulation for 2 min at <0.5 Hz with 5 V using 2-ms pulses seems to be comparable with the spontaneous activity in the CST fibers innervating the masseter vasculature, because this stimulation restored the basal level of the MBF to the presectioned values. Parasympathetic vasodilation evoked by electrical stimulation of the central cut end of the lingual nerve in the masseter muscle was markedly reduced by CST stimulation for 2 min with 5 V using 2-ms pulses in a frequency-dependent manner (0.5-5 Hz). Intravenous administration of phentolamine significantly reduced the vasoconstriction induced by CST stimulation in a dose-dependent manner (0.1-1 mg/kg), but pretreatment with either phentolamine or propranolol failed to affect the sympathetic inhibition of the parasympathetic vasodilation. Our results suggest that 1) excess sympathetic activity inhibits parasympathetic vasodilation in the masseter muscle, and 2) alpha- and beta-adrenoceptors do not contribute to sympathetic inhibition of parasympathetic vasodilation, and thus some other types of receptors must be involved in this response.

Supported phospholipid bilayer formation on hydrophilicity-controlled silicon dioxide surfaces.

We investigated the influence of surface hydroxyl groups (-OHs) on the supported planar phospholipid bilayer (SPB) formation and characteristics. We prepared SiO2 surfaces with different hydrophilicity degree by annealing the SiO2 layer on Si(100) formed by wet chemical treatments. The hydrophilicity reduced with irreversible thermal desorption of -OHs. We formed SPB of dimyristoylphosphatidylcholine on the SiO2 surfaces by incubation at a 100-nm-filtered vesicle suspension. The formation rate was faster on less hydrophilic surfaces. We proposed that a stable hydrogen-bonded water layer on the SiO2 surface worked as a barrier to prevent vesicle adhesion on the surface. Theoretical calculation indicates that water molecules on vicinal surface -OHs take a stable surface-unique geometry, which disappears on an isolated -OH. The surface -OH density, however, affected little the fluidity of once formed SPBs, which was measured by the fluorescence recovery after the photobleaching method. We also describe the area-selective SPB deposition using surface patterning by the focused ion beam.

Theoretical studies on the structure of hydration in perfluorinated lithium salt membranes.

Using an ab initio molecular orbital (MO) method, the normal frequencies are calculated for perfluorinated lithium sulfonate and carboxylate membranes by construction of a cluster model, which severs the ion core from the polymer chain, and then analysis of the experimentally observed infrared (IR) spectra is carried out. During the process of dehydration, small sharp peaks at about 3650 and 3700 cm(-1) appeared on the shoulder of the broad band at about 3500 cm(-1). These sharp peaks are identified as the symmetric and asymmetric stretching modes of the free water molecule. Furthermore, by estimation of the evaporation ratio based on thermochemical analysis, it can be assumed that the first hydration shells are naked in some part of the ion core, thereby allowing evaporation to take place within the external hydration shell during the dehydration process.