Fourier transform microwave spectroscopy of the 13C- and 18O-substituted tropolone. Proton tunneling effect for the isotopic species with the asymmetric potential wells.

Fourier-transform microwave spectroscopy has been applied for the 13C/18O-substituted tropolone to observe tunneling-rotation transitions as well as pure rotational transitions. The tunneling-rotation transitions were observed between the 13C-4 and -6 forms as well as between 13C-3 and -7, between 13C-1 and -2, and between 18O-8 and -9 (we denote these tunneling pairs as 13C-46, etc., below) although they have an asymmetric tunneling potential due to the difference in the zero point energy (ZPE). From the observed tunneling splittings ΔEij (0.9800-1.6824 cm-1), the differences in ZPE Δij for the 13C-46, -37, -12, and 18O-89 species are derived to be -0.1104, 0.5652, -1.3682, and 1.3897 cm-1 to agree well with the DFT calculation. The state mixing ratio of the tunneling states decreases drastically from (44%:56%) to (8.7%:91.3%) for 13C-46 and 18O-89 with an increase in the asymmetry Δij of the tunneling potential function. The observed tunneling-rotation interaction constants Fij decrease from 16.001 to 9.224 cm-1 as the differences in ZPE Δij increase, while the diagonal tunneling-rotation interaction constants Fu increase from 1.767 to 13.70 cm-1, explained well by the mixing ratio of the tunneling states.

Methyl-11C-L-methionine positron emission tomography for radiotherapy planning for recurrent malignant glioma.

OBJECTIVE: To investigate differences in uptake regions between methyl-11C-L-methionine positron emission tomography (11C-MET PET) and gadolinium (Gd)-enhanced magnetic resonance imaging (MRI), and their impact on dose distribution, including changing of the threshold for tumor boundaries. METHODS: Twenty consecutive patients with grade 3 or 4 glioma who had recurrence after postoperative radiotherapy (RT) between April 2016 and October 2017 were examined. The study was performed using simulation with the assumption that all patients received RT. The clinical target volume (CTV) was contoured using the Gd-enhanced region (CTV(Gd)), the tumor/normal tissue (T/N) ratios of 11C-MET PET of 1.3 and 2.0 (CTV (T/N 1.3), CTV (T/N 2.0)), and the PET-edge method (CTV(P-E)) for stereotactic RT planning. Differences among CTVs were evaluated. The brain dose at each CTV and the dose at each CTV defined by 11C-MET PET using MRI as the reference were evaluated. RESULTS: The Jaccard index (JI) for concordance of CTV (Gd) with CTVs using 11C-MET PET was highest for CTV (T/N 2.0), with a value of 0.7. In a comparison of pixel values of MRI and PET, the correlation coefficient for cases with higher JI was significantly greater than that for lower JI cases (0.37 vs. 0.20, P = 0.007). D50% of the brain in RT planning using each CTV differed significantly (P = 0.03) and that using CTV (T/N 1.3) were higher than with use of CTV (Gd). V90% and V95% for each CTV differed in a simulation study for actual treatment using CTV (Gd) (P = 1.0 × 10-7 and 3.0 × 10-9, respectively) and those using CTV (T/N 1.3) and CTV (P-E) were lower than with CTV (Gd). CONCLUSIONS: The region of 11C-MET accumulation is not necessarily consistent with and larger than the Gd-enhanced region. A change of the tumor boundary using 11C-MET PET can cause significant changes in doses to the brain and the CTV.

Acute toxicity and patient-reported symptom score after conventional versus moderately hypofractionated proton therapy for prostate cancer.

INTRODUCTION: To confirm the feasibility of hypofractionated proton beam therapy (PBT), we compared the acute adverse event rates and International Prostate Symptom Score (IPSS) in prostate cancer patients treated with hypofractionated versus conventionally fractionated (2.0 Gy relative biological effectiveness (RBE)/fraction) PBT. METHODS: We reviewed 289 patients with prostate cancer, of whom 73, 100, and 116 patients were treated with 2.0, 2.5, and 3.0 Gy (RBE)/fraction, respectively. The endpoints were acute genitourinary and gastrointestinal toxicities and the IPSS, evaluated up to 6 months after PBT initiation. RESULTS: No significant differences were found in acute toxicity rates or the IPSS among the fractionation schedules. Diabetes mellitus, age, and androgen deprivation therapy were not identified as factors associated with the IPSS. CONCLUSION: There were no significant differences in adverse events or quality of life among the three fractionation schedules early after PBT.

Peritumoral edema status of glioblastoma identifies patients reaching long-term disease control with specific progression patterns after tumor resection and high-dose proton boost.

BACKGROUND: Glioblastoma peritumoral edema (PE) extent is associated with survival and progression pattern after tumor resection and radiotherapy (RT). To increase tumor control, proton beam was adopted to give high-dose boost (> 90 Gy). However, the correlation between PE extent and prognosis of glioblastoma after postoperative high-dose proton boost (HDPB) therapy stays unknown. We intend to utilize the PE status to classify the survival and progression patterns. METHODS: Patients receiving HDPB (96.6 GyE) were retrospectively evaluated. Limited peritumoral edema (LPE) was defined as PE extent < 3 cm with a ratio of PE extent to tumor maximum diameter of < 0.75. Extended progressive disease (EPD) was defined as progression of tumors extending > 1 cm from the tumor bed edge. RESULTS: After long-term follow-up (median 88.7, range 63.6-113.8 months) for surviving patients with (n = 13) and without (n = 32) LPE, the median overall survival (OS) and progression-free survival (PFS) were 77.2 vs. 16.7 months (p = 0.004) and 13.6 vs. 8.6 months (p = 0.02), respectively. In multivariate analyses combined with factors of performance, age, tumor maximum diameter, and tumor resection extent, LPE remained a significant factor for favorable OS and PFS. The rates of 5-year complete response, EPD, and distant metastasis with and without LPE were 38.5% vs. 3.2% (p = 0.005), 7.7% vs. 40.6% (p = 0.04), and 0% vs. 34.4% (p = 0.02), respectively. CONCLUSIONS: The LPE status effectively identified patients with relative long-term control and specific progression patterns after postoperative HDPB for glioblastoma.

Alginate-coated activated charcoal enhances fecal excretion of 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice, with fewer side effects than uncoated one.

Activated charcoal (AC) is a potential candidate antidote against dioxins. However, it is difficult to take AC as a supplement on a daily basis, because its long-term ingestion causes side effects such as constipation and deficiency of fat-soluble essential nutrients and hypocholesterolemia. Alginate-coated AC, termed Health Carbon (HC), was developed to decrease the side effects of AC, but its pharmacological effects, including side effects, remains unclear. Here, we show that HC enhanced fecal excretion of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and decreased some side effects of unmodified AC, such as hypocholesterolemia, in male mice. Basal diet mixed with HC or unmodified AC at various concentrations was fed to mice for 16 days following a single intraperitoneal administration of [3H]TCDD. Both HC and unmodified AC at 3% or more significantly increased fecal excretion of [3H]TCDD in comparison with the control basal diet. Consistent with this, [3H]TCDD radioactivity in the liver-a major TCDD storage organ-was markedly decreased by HC at concentrations of 3% and 10%. In an examination of potential side effects, unmodified AC at 10% or more caused significant body weight reduction and at 20% caused significant hypocholesterolemia. In contrast, HC caused weight gain reduction only at a concentration of 20%, and there was no evidence of hypocholesterolemia at any dietary HC concentration. HC not only retains the ability of AC to enhance fecal excretion of TCDD but also reduces some of the side effects of AC.

High sensitivity X-ray analysis for a low accelerating voltage scanning electron microscope using a transition edge sensor.

A scanning electron microscope transition edge sensor has been developed to analyze the minor or trace constituents contained in a bulk sample and small particles on the sample under a low accelerating voltage (typically <3 keV). The low accelerating voltage enables to improve the spatial analysis resolution because the primary electron diffusion length is limited around the sample surface. The characteristic points of our transition edge sensor are 1) high-energy resolution at 7.2 eV@Al-Kα, 2) continuous operation by using a cryogen-free dilution refrigerator and 3) improvement of transmission efficiency at B-Kα by using thin X-ray film windows between the sample and detector (about 30 times better than our previous system). Our system could achieve a stabilization of the peak shift at Nd-Mα (978 eV) within 1 eV during an operation time of 27 000 s. The detection limits with B-Kα for detection times 600 and 27 000 s were 0.27 and 0.038 wt%, respectively. We investigated the peak separation ability by measuring the peak intensity ratio between the major constitute (silicon) and the minor constitute (tungsten) because the Si-Kα line differs from the W-Mα line by only 35 eV and a small W-Mα peak superimposed on the tail of the large Si-Kα peak. The peak intensity ratio (I(W-Mα)/I(Si-Kα)) was adjusted by the W particle area ratio compared with the Si substrate area. The transition edge sensor could clearly separate the Si-Kα and W-Mα lines even under a peak intensity ratio of 0.01.

Impact of RhoA overexpression on clinical outcomes in cervical squamous cell carcinoma treated with concurrent chemoradiotherapy.

The Rho-associated coiled-coil-containing protein kinase (ROCK) pathway is known to influence metastasis in several cancers; however, the impact of the pathway on clinical outcomes in patients undergoing radiotherapy remains unknown. In the present study, the expression of RhoA, RhoC, ROCK-1, ROCK-2 and p53 was immunohistochemically evaluated using biopsy specimens obtained from 49 patients with stage II-III cervical squamous cell carcinoma treated with concurrent chemoradiotherapy (CCRT). The relationship between the expression of these proteins and patient outcomes was investigated. RhoA overexpression was associated with significantly impaired disease-free survival and distant metastasis-free survival (P = 0.045 and P = 0.041, respectively) in stage III cancer patients. No differences in survival were observed based on the expression of the other proteins among stage III cancer patients. In stage II cancer patients, no differences in survival were noted based on the expression of any of the proteins. The expression of RhoA was able to successfully differentiate cervical cancer patients with distant metastasis after CCRT. This information may help stratify patients according to the risk of metastasis, thereby leading to the potential to provide individualized treatment.

Patient Transfer to Receive Proton Beam Therapy During Intensive Multimodal Therapy is Safe and Feasible for Patients With Newly Diagnosed High-risk Neuroblastoma.

Neuroblastoma (NB) predominantly presents as high-risk disease, requiring intensive multimodal therapy. Proton beam therpy (PBT) is a promising option for many childhood cancers, but is not widely available. Patients with NB hoping to receive PBT may therefore need to be transferred between institutions during intensive multimodal therapy, risking undesirable effects. We evaluated patients with high-risk NB who received PBT at our institute as part of first-line therapy, mainly focusing on the safety and feasibility of mid-treatment patient transfer. Eighteen patients with newly diagnosed high-risk NB who received PBT between April 2010 and June 2016 were retrospectively analyzed for local control, outcomes, and toxicity. Survival (3-y overall survival 71%±11%; 3-y event-free survival 44%±12%) and local control rate (100%) were comparable with previous studies. Few acute adverse events were recorded, and all patients completed PBT without treatment delay. PBT for high-risk NB was safe and feasible for patients requiring mid-treatment interinstitutional transfer.

Millimeter-wave spectroscopy of HDC=CH.

Rotational transitions of the mono(ß)-deuterated vinyl radical, HDC=CH, produced in a supersonic jet expansion by the ArF excimer laser photolysis, were observed by millimeter-wave spectroscopy. The b-type rotational transitions together with the weak a-type transitions were observed only for the lower component of the tunneling doublet, and no tunneling-rotation transitions connecting the lower and upper components were observed, suggesting that state mixing between the two components is negligibly small. The derived molecular constants such as the A rotational constant, Fermi contact interaction constants, and magnetic dipolar interaction constants indicate that the carrier of the observed spectrum is the trans-form of HDC=CH isomers, where the α-proton is located on the opposite side of the ß-deuteron. The present conclusion of the trans-form of HDC=CH was also supported by the ab initio calculation in the CCSD(T)/cc-pVTZ level since the trans-form is calculated to be located by 30.04 cm-1 lower than the cis-form due to the difference in the zero point energy. As a result, the tunneling components in the ground state of HDC=CH behave as two different isomers localized at the trans- and cis-wells of the asymmetric double minimum potential. Observed hyperfine constants for HDC=CH were compared with those for H2C=CH to be consistent with each other.

A retrospective study of late adverse events in proton beam therapy for prostate cancer.

The efficacy and safety of proton beam therapy (PBT) were retrospectively evaluated in 111 consecutive patients with prostate cancer who underwent definitive PBT between 2008 and 2012. Following exclusion of 18 patients due to treatment suspension, loss to follow-up, and histology, the analysis included 93 patients with a median age of 68 years (range, 49-81 years). A total of 7, 32 and 54 prostate cancer patients were classified as low-, intermediate- and high-risk, respectively, as follows: High-risk, T≥3a or prostate-specific antigen (PSA) ≥20 ng/ml or Gleason Score ≥8; low-risk, T ≤2b and PSA≤10 ng/ml and Gleason Score=6; intermediate-risk, all other combinations. The median initial prostate-specific antigen (PSA) level was 9.75 ng/ml (range, 1.4-100 ng/ml) and the median Gleason score was 7 (range, 6-10). Patients with low-risk disease received 74 GyE (relative biological effectiveness=1.1) in 37 fractions, and those at intermediate or higher risk received 78 GyE in 39 fractions. Complete androgen blockade (CAB) therapy was performed from 6 months prior to PBT for patients with intermediate- or high-risk disease. CAB was continued during PBT and then terminated at the end of PBT for intermediate-risk patients. Patients at high risk continued CAB for 3 years. No combination therapy was used for low-risk patients. All the patients were followed up for >2 years after PBT, and all but one were PSA failure-free. The Common Terminology Criteria for Adverse Events v.4.0 was used to evaluate late adverse events. One patient developed grade 3 non-infectious cystitis and hematuria. Grade 2 urinary frequency was observed in 1 patient, and grade 2 rectal bleeding occurred in 4 patients. Of the 4 patients with grade 2 rectal bleeding, 2 received anticoagulant therapy, but none had diabetes mellitus or another high-risk comorbidity. The median time to occurrence of an adverse event of grade ≥2 was 14 months (range, 3-41 months). Therefore, the present retrospective study revealed that PBT at 78 GyE/39 Fr was well-tolerated and achieved good tumor control in patients with prostate cancer.

Anti-allodynic action of the disease-modifying anti-rheumatic drug iguratimod in a rat model of neuropathic pain.

OBJECTIVE: Patients with rheumatoid arthritis experience nociceptive as well as neuropathic pain. The effect of iguratimod (IGU), a disease-modifying anti-rheumatic drug, on neuropathic pain in a rat model of chronic constriction injury (CCI) was examined in this study. METHODS: CCI was induced by making four ligations on the left sciatic nerve. Rats with stable signs of static allodynia were selected 2 weeks after the surgery and drug treatments were started (day 0). The test drugs were orally administered once daily for 15 days. The threshold of mechanical pain response in the hind paw was evaluated by the von Frey hair test in a blinded manner. To observe histological changes in the spinal cord, the L4 region was subjected to immunohistochemical analysis for the detection of microglial cells. RESULTS: IGU showed an anti-allodynic effect on CCI-induced neuropathic pain at days 6 and 14, but not at 90 min after the first administration of IGU. This effect of IGU was observed until day 21. Furthermore, IGU decreased the number of Iba-1-positive cells, which had been increased at the ipsilateral side of the dorsal horn by CCI. CONCLUSIONS: These results suggest that IGU suppresses neuropathic pain via a different mechanism from that of current therapeutics.

High-resolution Fourier transform emission spectroscopy of the A∼2Πi-X∼2Πi band of the OCS+ ion.

High resolution Fourier transform emission spectroscopy of the A∼2Πi-X∼2Πi band of the OCS+ ion was performed in the UV region to observe the ν1 (CO stretch) progression bands (υ1 = 0 → 2-5) for both the Ω=3/2 and 1/2 spin components. Accurate molecular constants including the rotational constants, B0 = 0.194 765(13) and 0.187 106(13) cm-1, and the spin-orbit interaction constants, A0 = -381.0(56) and -126.5(56) cm-1, were determined for the X∼2Π and A∼2Π states, respectively, by the simultaneous analysis of the observed progression bands. The CO bond length (rCO = 1.2810 Å) for the A∼2Π state, derived from the rotational constant B0 and Franck-Condon factors, is longer by 0.1756 Å than that (1.1054 Å) for the X∼2Π state, while the CS bond length for the A∼2Π state is shorter by 0.0905 Å than that for the X∼2Π state. Pure rotational transition frequencies in the ground X∼2Π state are predicted, as well as transition frequencies of the ν1 fundamental band, with the present molecular constants.

Pharmacokinetic and Pharmacodynamic Analyses of Drug-Drug Interactions between Iguratimod and Warfarin.

Iguratimod (IGU), a disease-modifying antirheumatic drug launched in September 2012, has been reported to carry a risk of severe hemorrhages through a suspected interaction with warfarin (WF) in the all-case surveillance and early postmarketing-phase vigilance. To elucidate possible mechanisms of adverse interaction between IGU and WF, we analyzed the effects of IGU on the pharmacodynamics and pharmacokinetics of WF in rats. IGU was orally administered to male Wistar rats once daily for 5 d at 10 or 30 mg/kg in combination with WF at an oral dose of 0.25 mg/kg. Coadministration of IGU 30 mg/kg enhanced the anticoagulant activity of WF; prolonged blood coagulation time (prothrombin time and activated partial thromboplastin time) and decreased levels of vitamin K (VK)-dependent blood coagulation factors (II, VII, IX, and X) were observed. On the other hand, the pharmacokinetic parameters of WF including maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from 0 to 24 h (AUC0-24 h) were not affected by the combination with IGU. IGU alone did not change blood coagulation time at doses up to 100 mg/kg, while VK-dependent blood coagulation factors decreased slightly at 30 and 100 mg/kg. These results suggest that the pharmacodynamic effect of IGU on VK-dependent blood coagulation factors is involved in the mechanism of drug-drug interaction of IGU with WF.

Dietary Deficiency of Calcium and/or Iron, an Age-Related Risk Factor for Renal Accumulation of Cadmium in Mice.

The major route of cadmium (Cd) intake by non-smokers is through food ingestion. Cd is a non-essential metal absorbed through one or more transporters of essential metal ions. Expression of these transporters is affected by nutritional status. To investigate the risk factors for Cd toxicity, the effects of deficiency of essential metals on hepatic and renal accumulation of Cd were studied in mice of different ages. Mice were administered a control diet or one of the essential metal-deficient diets, administered Cd by gavage for 6 weeks, and killed; then, Cd accumulation was evaluated. Iron deficiency (FeDF) or calcium deficiency (CaDF) resulted in remarkable increases in hepatic and renal Cd accumulation compared with control-diet mice and other essential metal-deficient mice. Cd accumulation in hepatic and renal tissue was increased significantly at all ages tested in FeDF and CaDF mice. Renal Cd concentrations were higher in 4-week-old mice than in 8- and 25-week-old mice. Increase in intestinal mRNA expression of calcium transporter (CaT)1, divalent metal ion transporter-1, and metallothionein (MT)1 was also higher in 4-week-old mice than in other mice. Renal accumulation of Cd showed strong correlation with intestinal mRNA expression of CaT1 and MT1. These data suggest that CaDF and FeDF at younger ages can be a risk factor for Cd toxicity.

Millimeter-wave spectroscopy of the FeCO radical in the ν2 and ν3 vibrationally excited states.

The pure rotational spectra of the FeCO radical in the ν2 (bending) and ν3 (Fe-C stretching) vibrational states of the ground X̃(3)Σ(-) electronic state were observed in the millimeter-wave region. The equilibrium rotational and centrifugal distortion constants were determined to be Be = 4374.631 (58) MHz and De = 1.1666 (20) kHz together with the spin-spin coupling constant λe = 691.89 (37) GHz and spin-rotation coupling constant γe = - 1079.4 (55) MHz with use of the millimeter-wave results and the ν1 IR data. The equilibrium bond length for Fe-C was derived to be 1.725 Å assuming that for C-O to be 1.159 Å. Since the vibronic symmetry of the excited state of bending vibration is (3)Π, the analysis of spectrum in the ν2 state required an effective spin-orbit interaction constant of A2 = 6.0219 (61) GHz together with three parity doubling constants of o2 = 36.168 (10) GHz, p2 = 85.18 (34) MHz, and q2 = 4.7024 (17) MHz. The effective spin-orbit interaction constant A2 is attributed to the vibronic mixing of the (3)Π excited electronic states. The vibronic mixing also cause the parity doubling constants o2 and p2, but the main contribution to q2 is given by the vibrational l-type doubling.

Iguratimod for the treatment of rheumatoid arthritis in Japan.

Iguratimod (IGU), a small-molecule compound, was developed as a disease-modifying antirheumatic drug in Japan. The pharmacological studies showed that inhibition of the production of cytokines and immunoglobulins mainly contributes to its improvement effect on animal arthritis models. The first clinical study of IGU in Japanese patients with rheumatoid arthritis was started in 1992 and Phase III studies were started in 1998. From the results of Phase II studies, a dose-escalating regimen was recommended to relieve the side effects. In a double-blind study comparing the efficacy and safety of the drug with those of placebo and salazosulfapyridine, it was confirmed that IGU was superior to placebo and was not inferior to salazosulfapyridine. Furthermore, a double-blind controlled trial of IGU in combination with methotrexate revealed an efficacious and manageable safety profile. IGU would be widely used as a new option for rheumatoid arthritis treatment and combination drug with methotrexate.

Effects of zinc deficiency and supplementation on leptin and leptin receptor expression in pregnant mice.

Leptin is an adipose-derived hormone that primarily regulates energy balance in response to nutrition. Human placental cells produce leptin, whereas murine placental cells produce soluble leptin receptors (Ob-R). However, the roles of these proteins during pregnancy have not been elucidated completely. As an essential metal, zinc (Zn) is central to insulin biosynthesis and energy metabolism. In the present study, the effects of Zn deficiency and supplementation on maternal plasma leptin and soluble Ob-R regulation in pregnant mice placentas were examined using enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction, and Western blotting. Nutritional Zn deficiency significantly reduced plasma insulin concentrations and fetal and placental weights in pregnant mice. Plasma leptin concentrations in pregnant mice also increased 20- to 40-fold compared with those in non-pregnant mice. Although dietary Zn deficiency and supplementation did not affect plasma leptin concentrations in non-pregnant mice, Zn-deficient pregnant mice had significantly reduced plasma leptin concentrations and adipose leptin mRNA expression. In contrast, Zn-supplemented pregnant mice had increased plasma leptin concentrations without increased adipose leptin mRNA expression. Placental soluble Ob-R mRNA expression also decreased in Zn-deficient mice and tended to increase in Zn-supplemented mice. These results indicate that Zn influences plasma leptin concentrations by modulating mRNA expression of soluble Ob-R in the placenta, and leptin in visceral fat during pregnancy. These data suggest that both adipose and placenta-derived leptin system are involved in the regulation of energy metabolism during fetal growth.

Nitric oxide promotes survival of cerebral cortex neurons with simultaneous addition of [Fe(II)(ß-citryl-L-glutamate)] complex in primary culture.

It has been reported that the activity of mitochondrial aconitase (m-aconitase) is rapidly inhibited in a variety of cells when exposed to nitric oxide (NO). In present study, we found that NO significantly increased the number of surviving neurons via enhanced mitochondrial functions with simultaneous addition of the [Fe(II)(ß-citryl-L-glutamate; ß-CG)] complex. In vitro, a variety of aconitase-inhibitors, such as fluorocitrate, cyanide ion, ferricyanide ([Fe(CN)6]), and various oxidants including superoxide anion, inhibited the activity of m-aconitase even in the presence of Fe(II), whereas a NO-donor, nitroprusside (SNP) ([Fe(CN)5NO]), was the only agent that significantly increased activity of that enzyme. Therefore, it is reasonable to assume that NO released from SNP promotes Fe-dependent activation of aconitase. All other tested NO-donors, including 3-morpholino-sydnonimine (SIN), Deta NONOate (NOC18), and NaNO2, also promoted activation of m-aconitase in time- and dose-dependent manners in the presence of Fe(II). The promoting effects of the NO-donors on activation disappeared with the addition of NO-scavengers. In intact mitochondria, all tested NO-donors promoted reactivation of aconitase in a dose-dependent manner in the presence of Fe(II), whereas that was not seen in its absence. These findings suggest that NO released from NO-donors promotes Fe-dependent activation of aconitase. In mixed neuronal and glial cultures, NO-donors except for SNP enhanced mitochondrial activity at low concentrations. Furthermore, simultaneous addition of the [Fe(II)(ß-CG)] complex significantly enhanced those activities and greatly increased the number of surviving neurons. Thus, NO can carry Fe ions into m-aconitase via the guide of the tag of ß-CG addressed to the enzyme.

A patient who showed a pathologically complete response after undergoing treatment with XELOX plus bevacizumab for synchronous liver metastasis of grade H2 from sigmoid colon cancer.

We herein report the case of a patient who showed a pathological complete response after undergoing chemotherapy with capecitabine, oxaliplatin and bevacizumab. The patient presented with synchronous solitary liver metastasis from sigmoid colon cancer. The maximum diameter of the liver deposit was 5.7 cm and the grade of the liver metastasis was H2 according to the Japanese classification. Deferred hepatectomy after sigmoidectomy was performed, followed by the administration of neoadjuvant chemotherapy. After undergoing sigmoidectomy, the patient received 1,000 mg/m(2) of capecitabine and 130 mg/m(2) of oxaliplatin without bevacizumab as the first cycle of chemotherapy followed by eight cycles of chemotherapy with bevacizumab (7.5 mg/kg) every three weeks. The liver deposit was reduced to 2.2 cm in diameter and the patient showed a partial response to chemotherapy. The patient then underwent metastasectomy of segment 8 of the liver instead of the central hepatectomy that was possibly needed before chemotherapy. Histopathologically, the tumor consisted of fibrous tissue, and no cancer cells were detected in the resected specimen. A pathological complete response in a patient with H2 liver metastasis is considered rare and suggests that capecitabine, oxaliplatin and bevacizumab are efficacious as neoadjuvant chemotherapy.

Ortho-para mixing hyperfine interaction in the H2O+ ion and nuclear spin equilibration.

The ortho to para conversion of water ion, H2O(+), due to the interaction between the magnetic moments of the unpaired electron and protons has been theoretically studied to calculate the spontaneous emission lifetime between the ortho- and para-levels. The electron spin-nuclear spin interaction term, Tab(SaΔIb + SbΔIa) mixes ortho (I = 1) and para (I = 0) levels to cause the "forbidden" ortho to para |ΔI| = 1 transition. The mixing term with Tab = 72.0 MHz is 4 orders of magnitude higher for H2O(+) than for its neutral counterpart H2O where the magnetic field interacting with proton spins is by molecular rotation rather than the free electron. The resultant 10(8) increase of ortho to para conversion rate possibly makes the effect of conversion in H2O(+) measurable in laboratories and possibly explains the anomalous ortho to para ratio recently reported by Herschel heterodyne instrument for the far-infrared (HIFI) observation. Results of our calculations show that the ortho ↔ para mixings involving near-degenerate ortho and para levels are high (∼10(-3)), but they tend to occur at high energy levels, ∼300 K. Because of the rapid spontaneous emission, such high levels are not populated in diffuse clouds unless the radiative temperature of the environment is very high. The low-lying 101 (para) and 111 (ortho) levels of H2O(+) are mixed by ∼10(-4) making the spontaneous emission lifetime for the para 101 → ortho 000 transition 520 years and 5200 years depending on the F value of the hyperfine structure. Thus the ortho ↔ para conversion due to the unpaired electron is not likely to seriously affect thermalization of interstellar H2O(+) unless either the radiative temperature is very high or number density of the cloud is very low.