[Measures to Ensure Safety of Docetaxel plus Ramucirumab for Advanced Non-Small-Cell Lung Cancer as the Second- or Later-Line].

With the standpoint ofref ining the chemotherapy regimen, we retrospectively reviewed adverse events encountered by the initial 10 cases during the first course of docetaxel plus ramucirumab for non-small-cell lung cancer that progressed after platinum-based chemotherapy. Febrile neutropenia(FN)was observed in 40% ofcases, and a halfofall patients experienced oral mucositis, including 2 Grade 3 cases. These results were concordant with a previous randomized phaseⅡstudy on Japanese patients. We amended the treatment regimen by adding the prophylactic use ofpegf ilgrastim. Post-amendment, FN was not observed in all 10 cases. However, the frequency and severity of chemotherapy-induced oral mucositis were not affected; Therefore, some patients discontinued treatment due to this toxicity as well as diarrhea. In conclusion, prophylactic granulocyte-colony stimulating factor is considered effective for reducing the risk of FN. Further intervention by an oral care team is required to validate our findings.

Intermolecular Dynamics of Positively and Negatively Charged Aromatics and Their Isoelectronic Neutral Analogs in Aqueous Solutions.

In this study, we investigated the temperature dependence of intermolecular vibrations and orientational dynamics in the aqueous solutions of imidazole hydrochloride, imidazole, sodium triazolide, and triazole using femtosecond Raman-induced Kerr effect spectroscopy (fs-RIKES) and steady-state Raman spectroscopy. The difference low-frequency Raman spectra under 250 cm-1 of the aqueous solutions relative to the neat water showed that the spectral shoulder in the high-frequency region at 60-100 cm-1, assigned to the libration of an aromatic ring, was higher in frequency for the imidazolium cation but lower for the triazolide anion than those of the respective neutral aromatics. The results of the ab initio quantum chemistry calculations of the clusters of the aromatics and water molecule(s) were consistent with the experimental spectra of the aqueous solutions. Further, the results of the temperature-dependent experiments showed that the signal intensity in the low-frequency region below 50 cm-1 increased for all solutions with an increase in temperature. In contrast, the spectral density in the high-frequency region above 80 cm-1 exhibited almost no shift for the 1.0 M solutions, while a significant red shift was observed for the 5.0 M solutions. In addition, the temperature-dependent densities, viscosities, and surface tensions were characterized for the aqueous aromatic solutions from 293 to 353 K.

Specific induction of PAG608 in cranial and spinal motor neurons of L-DOPA-treated parkinsonian rats.

We identified p53-activated gene 608 (PAG608) as a specifically induced gene in striatal tissue of L-DOPA (100mg/kg)-injected hemi-parkinsonian rats using differential display assay. In the present study, we further examined morphological distribution of PAG608 in the central nervous system of L-DOPA-treated hemi-parkinsonian rats. PAG608 expression was markedly induced in fibers and neuronal cells of the lateral globus pallidus and reticular thalamic nucleus adjacent to internal capsule, specifically in the parkinsonian side of L-DOPA-treated models. The protein was also constitutively expressed in motor neurons specifically in either side of the pontine nucleus and motor nuclei of trigeminal and facial nerves. Furthermore, L-DOPA-induced PAG608 expression on motor neurons in the contralateral side of the ventral horn of the spinal cord and the lateral corticospinal tract without cell loss. The specific induction of PAG608 6-48h after L-DOPA injection in the extrapyramidal tracts, pyramidal tracts and corresponding lower motor neurons of the spinal cords suggests its involvement in molecular events in stimulated motor neurons. Taken together with the constitutive expression of PAG608 in the motor nuclei of cranial nerves, PAG608 may be a useful marker of stressed or activated lower motor neurons.

Change of Tinnitus with Xenon Phototherapy of the Stellate Ganglion.

OBJECTIVE: To develop a treatment for tinnitus called xenon phototherapy of the stellate ganglion (XPSG) and analyze its effect on tinnitus. METHODS: Patients with chronic tinnitus received XPSG. Symptoms were assessed subjectively with tinnitus handicap inventory (THI) and numerical rating scale (NRS). THI and NRS scores were analyzed in XPSG (n = 43) and sham treatment (non-XPSG) (n = 18) groups. RESULTS: THI and NRS scores improved significantly after 3 months of XPSG. Severe cases with high THI or NRS score showed greater improvement. No significant difference was observed between before and after sham treatment in non-XPSG groups. CONCLUSIONS: XPSG significantly improved THI and NRS scores with high patient satisfaction.

Suppression of p53-activated gene, PAG608, attenuates methamphetamine-induced neurotoxicity.

The p53-activated gene 608 (PAG608) is a proapoptotic gene activated and regulated by p53 expression in oxidative stress-induced apoptosis of neuronal cells. In this study, we determined the role of PAG608 in methamphetamine-induced neurotoxicity. Treatment of mouse dopaminergic CATH.a cells with 2 mM methamphetamine increased PAG608 expression at 3h followed by increase in phosphorylated p53 expression. Transient transfection of PAG608 antisense cDNA or RNA interference using PAG608 small interfering RNA significantly attenuated the dose-dependent decrease in cell viability of CATH.a cells by methamphetamine (1-4 mM) exposure. In monoaminergic neuronal B65 cells, which contain serotonin rather than dopamine, methamphetamine-induced cell death was also significantly but partially protected by transient transfection of PAG608 antisense cDNA. Furthermore, cell death of PC12 cells produced by methamphetamine (1-5 mM) was almost completely prevented by stable expression of PAG608 antisense cDNA, compared with significant reduction of cell viability in control PC12 cells. Our results showed that suppression of PAG608 using transient and stable transfection with PAG608 antisense cDNA or small interfering RNA attenuates methamphetamine-induced death of various monoaminergic neuronal cells, suggesting that methamphetamine neurotoxicity in monoaminergic cells is related, at least in part, to induction of PAG608 expression.

Pramipexole has ameliorating effects on levodopa-induced abnormal dopamine turnover in parkinsonian striatum and quenching effects on dopamine-semiquinone generated in vitro.

OBJECTIVES AND METHODS: To clarify the effects of a non-ergot dopamine agonist pramipexole on levodopa-induced abnormal dopamine metabolism in the parkinsonian model, we examined striatal changes in dopamine and its metabolites after repeated administration of pramipexole and/or levodopa using 6-hydroxydopamine-lesioned hemi-parkinsonian mice. Moreover, the effects of pramipexole on dopamine-semiquinones were also accessed using an in vitro dopamine-semiquinone generating system to elucidate its neuroprotective property against dopamine quinone-induced neurotoxicity that appears as dopamine neuron-specific oxidative stress. RESULTS: Combined administration of pramipexole (0.5 or 1 mg/kg/day, 7 days) selectively suppressed the levodopa-induced (50 mg/kg/day) increase of striatal dopamine turnover in the parkinsonian side, but not in the non-lesioned side. In addition to the antioxidant properties previously reported, it was clarified that pramipexole scavenged dopamine-semiquinones generated in a dose-dependent manner either in simultaneous incubation or post-incubation. DISCUSSION: The neurotoxicity of dopamine quinones that appear as dopaminergic neuron-specific oxidative stress has recently been known to play a role in the pathogenesis of Parkinson's disease and neurotoxin-induced parkinsonism. Therefore, the present results revealed that pramipexole possesses neuroprotective effects against abnormal dopamine metabolism in excessively levodopa-administered parkinsonian brains and against cytotoxic dopamine quinones generated from excess dopamine, preventing consequently dopaminergic neuronal damage induced by excess dopamine or levodopa.

Asymmetric autocatalysis induced by meteoritic amino acids with hydrogen isotope chirality.

Achiral meteoritic amino acids, glycine and alpha-methylalanine, with hydrogen isotope (D/H) chirality, acted as the source of chirality in asymmetric autocatalysis with amplification of ee to afford highly enantioenriched 5-pyrimidyl alkanols.

Spontaneous absolute asymmetric synthesis in the presence of achiral silica gel in conjunction with asymmetric autocatalysis.

An enantiomerically enriched pyrimidyl alkanol with either S or R configurations was obtained stochastically from the reaction between pyrimidine-5-carbaldehyde and diisopropylzinc in the presence of achiral silica gel in conjunction with asymmetric autocatalysis with amplification of chirality.