Orbital-resolved visualization of single-molecule photocurrent channels.

Given its central role in utilizing light energy, photoinduced electron transfer (PET) from an excited molecule has been widely studied1-6. However, even though microscopic photocurrent measurement methods7-11 have made it possible to correlate the efficiency of the process with local features, spatial resolution has been insufficient to resolve it at the molecular level. Recent work has, however, shown that single molecules can be efficiently excited and probed when combining a scanning tunnelling microscope (STM) with localized plasmon fields driven by a tunable laser12,13. Here we use that approach to directly visualize with atomic-scale resolution the photocurrent channels through the molecular orbitals of a single free-base phthalocyanine (FBPc) molecule, by detecting electrons from its first excited state tunnelling through the STM tip. We find that the direction and the spatial distribution of the photocurrent depend sensitively on the bias voltage, and detect counter-flowing photocurrent channels even at a voltage where the averaged photocurrent is near zero. Moreover, we see evidence of competition between PET and photoluminescence12, and find that we can control whether the excited molecule primarily relaxes through PET or photoluminescence by positioning the STM tip with three-dimensional, atomic precision. These observations suggest that specific photocurrent channels can be promoted or suppressed by tuning the coupling to excited-state molecular orbitals, and thus provide new perspectives for improving energy-conversion efficiencies by atomic-scale electronic and geometric engineering of molecular interfaces.

Seasonal variation in the incidence of aneurysmal subarachnoid hemorrhage associated with age and gender: 20-year results from the Yamaguchi cerebral aneurysm registry.

BACKGROUND: This study was a cerebral aneurysm registry study conducted in a region with few climatic differences. Based on data collected for over 20 years, seasonal variations and characteristics of subarachnoid hemorrhage (SAH) due to ruptured aneurysms were analyzed. METHODS: This study included 5,007 patients in the Yamaguchi Prefecture with aneurysmal SAH between 1986 and 2005. Incidence rates by month, sex, age, severity, and aneurysm site were analyzed. RESULTS: In women, seasonal variation was observed, in particular among those aged ≥50 years. Among those aged 50-69 years, the highest incidence was in October, and the nadir was in June (peak-to-trough ratio = 1.72). At age ≥70 years, this was slightly different, with the highest incidence in December and the nadir in July (peak-to-trough ratio = 1.48). However, there was no seasonal variation in men overall; it was limited to elderly men at age ≥70 years, with the highest incidence in January and the nadir in July (peak-to-trough ratio = 2.9). Aneurysm site and severity showed no relationship with seasonal variation. CONCLUSION: The present study shows seasonal variations in the onset of SAH. Seasonal variations in SAH differed depending on age and sex.

On-demand control system for deep brain stimulation for treatment of intention tremor.

OBJECTIVES: Intention tremor becomes evident only when patients intend to move their body and is characterized by dysmetria. We have developed an on-demand control system that triggers the switching on/off of deep brain stimulation (DBS) instantly for the control of intention tremor. MATERIAL AND METHODS: We used surface electrodes for the recording of electromyographic (EMG) activity, and the power of EMG activity was analyzed instantly employing the fast Fourier transform. The on-demand control system switched on DBS when only the power of tremor frequency exceeded the on-trigger threshold, and the system switched off DBS when the total power of EMG activity decreased below the off-trigger threshold. RESULTS: The on-demand control system triggered the switching on/off of DBS accurately, and controlled intention tremor completely. Our on-demand control system is small and portable, and suitable for clinical use. CONCLUSIONS: The on-demand control system for DBS is useful for controlling intention tremor and may decrease the incidence of tolerance to DBS and may be a powerful tool for various applications of neuromodulation therapy.

Heterogeneity of apex-to-base dispersion in diastolic lengthening is related to impaired global left ventricular relaxation in patients with hypertrophic cardiomyopathy.

BACKGROUND: The presence of apex-to-base disparity in diastolic left ventricle (LV) endocardial lengthening, based on an electromechanical activation sequence, has been recognized as an important determinant of LV diastolic properties. However, the behavior of LV apical and basal diastolic lengthening and its relationship to LV filling in hypertrophic cardiomyopathy (HCM) are unknown. METHODS: We obtained basal and apical LV short-axis views in 27 patients with non-obstructive HCM and 25 healthy volunteers. The patients with HCM were subdivided into two groups; those with apical hypertrophy [APH(+)] or those without apical hypertrophy [APH(-)]. Eight equiangular points on the endo-myocardium at end diastole were placed in each view, and the movements of these points were automatically tracked using a two-dimensional echocardiographic tissue tracking system. Time-LV internal diameter curves were obtained and averaged. The time intervals from the aortic valve closure to the point of the first 40% of peak diastolic lengthening (T 40) were measured in each view. The standard deviation of the time to peak systolic circumferential shortening at the base and apex were calculated to assess the heterogeneity of LV contraction. RESULTS: The time difference in the T 40 between the apex and base (dt-T 40) in the HCM-APH(+) and HCM-APH(-) groups was greater than that in the control group. The heterogeneities in LV apical systolic shortening in the HCM groups were greater than those in the control group. There were good linear correlations between the dt-T 40 and the LV early diastolic echo-parameters and the LV mass index. CONCLUSIONS: Delayed apical relaxation and filling in patients with HCM is related to LV diastolic dysfunction and systolic dyssynchronous contraction.

The impact of intermittent pneumatic compression devices on deep venous flow velocity in patients with congestive heart failure.

BACKGROUND: Intermittent pneumatic compression (IPC) has been used to prevent deep venous thrombosis (DVT), but the effects of IPC on the hemodynamics of popliteal and soleal veins, especially in patients with congestive heart failure (CHF) have not been evaluated. The aim of this study was to evaluate the effects of IPC on the flow velocity of deep veins in the lower extremities and to compare the efficacy of two different types of IPC in deep venous flow enhancement in patients with CHF. METHODS: Flow velocities of popliteal and soleal veins were recorded in 19 patients with CHF and in 19 control subjects using a high-resolution linear probe. Peak and mean flow velocities were measured (1) at rest, (2) with sequential foot and calf IPC (SFC-IPC) which consists of an electrically driven air compressor and four air chambers, and (3) with impulse foot IPC (IF-IPC) which consists of a pneumatic impulse generator operated at an applied pressure of 130 mmHg. RESULTS: In the resting condition, popliteal venous flow velocity in the CHF group was attenuated (12.8+/-4.7 cm/s vs. 21.1+/-13.5 cm/s; p<0.05). Both SFC-IPC and IF-IPC increased venous velocity, but the increase with IF-IPC in CHF patients was lower than that in control subjects. In the soleal veins, after applying SFC-IPC, the peak and mean velocity in CHF increased to the same extent as in the control group. IF-IPC increased soleal venous velocity in control subjects, but there was no increase in CHF patients. CONCLUSION: Two-dimensional Doppler scanning revealed a significant increase in the mean and peak velocities in the soleal and popliteal veins with SFC-IPC but not with IF-IPC in patients with CHF. These results indicate that SFC-IPC could have favorable effects in preventing DVT in patients with CHF.

Impact of intraoperative transesophageal echocardiography in cardiac and thoracic aortic surgery: experience in 1011 cases.

BACKGROUND: Although intraoperative transesophageal echocardiography (IOTEE) has been widely used in cardiovascular surgery, the exact incidence of abnormalities detected by IOTEE in each type of surgical procedure is still unclear. The aim of this study was to review our experiences of IOTEE, in patients who underwent different types of cardiovascular surgery and to evaluate the clinical usefulness of IOTEE. METHODS AND RESULTS: Our database of 1011 consecutive patients, who underwent cardiovascular surgery and IOTEE monitoring was reviewed. The incidence of abnormal findings was 115 of 1011 patients (11.4%), and the highest incidence was the appearance of new wall motion abnormalities after cardiopulmonary bypass. These findings influenced surgical decision-making in 59 of the evaluated 1011 patients (5.8%). CONCLUSIONS: IOTEE provides important intraoperative and postoperative information that may influence surgical decision-making in various cardiovascular surgeries.

No enhancing effects of diacylglycerol oil on tumor development in a medium-term multi-organ carcinogenesis bioassay using male F344 rats.

The modifying potential of diacylglycerol (DAG) oil on tumor development was investigated in a medium-term multi-organ carcinogenesis bioassay. DAG oil is a cooking oil that contains >80% diglycerides, <20% triglycerides and <5% monoglycerides. Male 6-week-old F344 rats (20 in each group) were sequentially treated with five carcinogens for initiation in different organ target sites for 4 weeks (DMBDD treatment), and then administered DAG oil at dietary levels of 0% (control), 1.375%, 2.75% or 5.5% [triacylglycerol (TGs), with the same fatty acid composition as DAG oil were also added at dietary levels of 5.5%, 4.125%, 2.75% and 0%, respectively, to maintain the same lipid level], or 5.5% high linoleic acid TG (HLTG), 5.5% high oleic acid TG (HOTG), or 5.5% medium-chain TG (MCTG) (as reference substances, mostly consisting of triacylglycerols) admixed into AIN-93G semi-synthetic diet, for an additional 24 weeks. Controls received standard diet without any supplementation as non-treated control. All animals were killed at the end of week 28, and the major organs were carefully examined for preneoplastic and neoplastic lesions. No DAG oil treatment-related changes were noted in survival, general conditions, body weights, food consumption and organ weights. Upon quantitative analysis of glutathione S-transferase placental form (GST-P) positive foci of the liver, DAG oil was not found to exert any effects. The incidence of colon adenomas was significantly increased in rats given 1.375% DAG oil, but not 2.75% and 5.5% DAG oil, when compared to the control (5.5% TG group) value. Furthermore, incidences and multiplicity of hyperplasias and adenomas and/or adenocarcinomas were comparable across all DAG oil-treated groups. In contrast, incidences of colon adenomas and/or adenocarcinomas were significantly increased in rats given 5.5% HOTG, and adenomas with MCTG, but not 5.5% HLTG, as compared to the 5.5% TG value. Preneoplastic and neoplastic lesions induced by DMBDD treatment in various organs other than the large intestine were comparable in all cases. Thus, the current results indicate that DAG oil may not exert modifying potential on tumor development, even in the colon because of the lack of dose-dependence. DAG oil was equivalent to HOTG (standard cocking oil composed of naturally occurring fatty acids), with regard to colon tumor development. Further dose-response study concerning HOTG may be needed to confirm whether the enhancing effect of large intestine carcinogenesis exert or not.

Ambient-pressure organic superconductors kappa-(DMEDO-TSeF)2[Au(CN)4](solv.): Tc tuning by modification of the solvent of crystallization.

The unsymmetrical pi donor dimethyl(ethylenedioxy)tetraselenafulvalene (DMEDO-TSeF) has provided six new organic superconductors with a monovalent square-planar [Au(CN)(4)](-) ion and cyclic ethers as solvent of crystallization. The six new organic superconductors kappa-(DMEDO-TSeF)(2)[Au(CN)(4)](solv.) [solv.=1,3-dioxolane (DOL), 2,5-dihydrofuran (DHF), tetrahydropyran (THP), 1,3-dioxane (1,3-DOX), 3,4-dihydro-2H-pyran (DHP), or 1,4-dioxane (1,4-DOX)] are classified into two subphases kappa(L) and kappa' according to the differences in their space group symmetry. kappa(L)-(DMEDO-TSeF)(2)[Au(CN)(4)](solv.) (solv.=DOL, DHF, THP, 1,3-DOX or DHP) crystallizes in the orthorhombic space group Pnma, and T(c) of the kappa(L) phase varies by 1.7-5.3 K according to the size and shape of the solvent of crystallization. On the other hand, kappa'-(DMEDO-TSeF)(2)[Au(CN)(4)](solv.) (solv.=DOL or 1,4-DOX) crystallizes in the noncentrosymmetric monoclinic space group Cc. The kappa'-phase containing 1,4-DOX shows superconductivity at 4.2 K, but the kappa'-phase containing DOL does not show superconductivity down to 1.4 K. Systematic investigation of the six new organic superconductors, together with the two previously reported superconductors kappa(H)- and kappa(L)-(DMEDO-TSeF)(2)[Au(CN)(4)](THF), revealed that the T(c) of the present system is finely tunable by utilizing the effect of the solvent of crystallization.

Modification of an in vivo lung metastasis model of hepatocellular carcinoma by low dose N-nitrosomorpholine and diethylnitrosamine.

Previously, we established the in vivo lung metastasis model of rat HCC induced by two hepatocarcinogens, diethylnitrosamine (DEN) and N-nitrosomorpholine (NMOR) at a dose of 120 ppm. This model allows us to investigate modifying factors leading to the inhibition of metastasis formation. However, low survival rates made the evaluation of metastasis formation difficult. The current experiments were conducted to modify the experimental protocol to improve survival and to establish a better animal metastasis model. Lower doses of NMOR (80 or 40 ppm in drinking water) were given to F344 rats for 14 weeks after DEN treatment. Survival rates in the 80 ppm group and in the 40 ppm group were 57% and 81%, respectively and these values were significantly higher than that in 120 ppm. Incidences of lung metastasis in the 40 ppm group steadily increased up to 67% by week 36 while that in the 80 ppm increased sharply up to 86% by week 24. Severity of lung metastases in the 40 ppm group at week 36 was mild compared with the 80 ppm group at week 24. In the second experiment, in order to characterize HCC development and lung metastasis in the 40 ppm group, rats given DEN and then followed with 40 ppm NMOR were killed sequentially. Development of HCC was observed at week 14 and reached 100% incidence at week 20. First lung metastatic lesions were evident at week 22, and incidence of lung metastasis reached 100%. Tumor cells were identified in the blood at week 20 by RT-PCR. The current study revealed that 40 ppm NMOR for 14 weeks after DEN treatment developed HCC without lung metastases at week 22, then HCC with a frequent lung metastasis at week 40. Thus, it can be said that this system is a more appropriate model for elucidation of mechanisms of metastasis and also for analysis of factors to inhibit natural metastasis.

Renal toxicity induced by folic acid is associated with the enhancement of male reproductive toxicity of di(n-butyl)phthalate in rats.

Reproductive effects have been observed in experimental animals treated with di(n-butyl)phthalate (DBP), one of phthalate esters used in soft plastics and a variety of consumer products. In this study, we investigated whether testicular toxicity of DBP is influenced by diminished renal function. To generate an experimental condition reflecting chronic renal disease in man, adult male F344 rats were given five consecutive weekly subcutaneous injections of folic acid at a dose of 300 mg/kg and then a diet containing 1200, 5000, and 20,000 ppm of DBP for 4 weeks. These concentrations roughly correspond to 60, 250, and 1000 mg/kg per day per rat, respectively. Folic acid clearly induced interstitial nephritis accompanied by impairment of renal function. Seminiferous degeneration, diminished spermatogenesis and increase in the number of morphologically abnormal sperm were more prominent in rats given folic acid and then 20,000 ppm DBP as compared to those exposed to DBP alone. These data suggest that DBP-induced male reproductive toxicity can be increased by folic acid-induced renal dysfunction.

Absence of liver tumor promoting effects of annatto extract (norbixin), a natural carotenoid food color, in a medium-term liver carcinogenesis bioassay using male F344 rats.

Modifying potential of annatto extract (norbixin) on liver carcinogenesis was investigated in male F344/DuCrj rats initially treated with N-nitrosodiethylamine (DEN). Two weeks after a single dose of DEN (200 mg/kg, intraperitoneally), rats were given annatto extract at dietary levels of 0, 0.03, 0.1 and 0.3%, or phenobarbital sodium at 0.05% as a positive control for 6 weeks. All animals were subjected to partial hepatectomy at week 3, and were killed at week 8. There were no deaths related to annatto extract ingestion, and the treatment had no effects on body weights, or food and water consumption. Statistically significant increases of absolute and relative liver weights were apparent in the 0.1 and 0.3% groups. However, annatto extract did not significantly increase the quantitative values for glutathione S-transferase placental form positive liver cell foci observed after DEN initiation, in clear contrast to the positive control case. The results thus demonstrate that annatto extract at a dietary level of 0.3% (200 mg/kg/day) lacks modifying potential for liver carcinogenesis in our medium-term bioassay system.

Lack of carcinogenic risk in the prostate with transplacental and lactational exposure to bisphenol A in rats.

The current study was designed to examine the modulating effects of bisphenol A (BPA) on prostate cancer risk in male offspring exposed transplacentally and lactationally. BPA was administered to F344 female rats by gavage at 0, 0.05, 7.5, 30, 120 mg/kg/day during pregnancy and lactation periods. When F1 males reached 5 weeks old, they were given 10 subcutaneous injections of 3,2'-dimethyl-4-aminobiphenyl (DMAB) or corn oil vehicle and rats were then sacrificed under ether anesthesia at week 60. There were no observable effects on the accessory sex organ weights of male offspring. Transplacental and lactational exposure to BPA did not affect the incidences of preneoplastic and neoplastic lesions in the accessory sex organs (prostate and seminal vesicle) of F1 rats and did not induce any proliferating lesions without DMAB. Our data suggest that maternal exposure to BPA during the period of pregnancy and lactation does not affect the risk of prostate carcinogenesis in male offspring.

Four-week oral toxicity study of 1-carboxy-5,7-dibromo-6-hydroxy-2,3,4-trichloroxanthone (HXCA), an impurity of Phloxine B, in F344 rats.

This study was designed to evaluate and characterize any subacute toxicity of 1-carboxy-5,7-dibromo-6-hydroxy-2,3,4-trichloroxanthone (HXCA), an impurity of Phloxine B (Food Red No. 104 in Japan, D&C Red No. 28 in the USA), when administered to both sexes of F344 rats at dietary levels of 0 (control), 0.005, 0.05 and 0.5%. During the study, the treatment had no effects on clinical signs, survival, urinalysis or ophthalmology. Hematology, blood biochemistry, gross pathology, organ weights, organ to body weight ratios and histopathology exhibited no differences of toxicological significance between control and treated rats. Reactions to treatment may be summarized as follows: there was a tendency for increased food and water consumption and decreased food efficiency in both sexes of the 0.5% group. Thus, these results indicated the no-observed-adverse-effect level (NOAEL) of HXCA to be 0.05% (39.3 mg/kg/day for males, and 41.0 mg/kg/day for females).

Effects of perinatal exposure to flutamide on sex hormones and androgen-dependent organs in F1 male rats.

Flutamide, which has antiandrogenic properties, was administered to pregnant rats, and effects on male offspring were examined. Crj: CD (SD) IGS (SPF) females were administered flutamide (0.15, 0.6, 2.5, 10.0, 100 mg/kg, p.o.) from gestation Day 14 to post parturition Day 3. The number of pups, body weights, clinical features, anogenital distance (AGD), nipple retention, testicular descent, and urogenital malformation in F1 males were examined. Hormone measurement, necropsy and histopathological examination were carried out at post-neonatal Day 4 (PND 4) and PND 60. Sperm analysis was also carried out at PND 60. Decrease in body weight was seen in the 100 mg/kg group and the AGD was decreased at 2.5 mg/kg and above. Retention of nipples, hypospadia, vaginal pouches, penis malformation, unilateral ectopic testis, and decrease of organ weights (prostate, seminal vesicles, levator ani muscle plus bulbocavernosus muscle, testis) were observed at 10 mg/kg and above. Testicular testosterone (T) was increased significantly with 100 mg/kg at PND 4 and tendencies for increase were observed in serum T, LH and FSH at 10 mg/kg and more at the same time point. In contrast, elevated levels of LH and FSH were seen with 100 mg/kg at PND 60. Histopathological examination revealed defects or hypoplastic changes of genital organs (> or = 10 mg/kg), squamous metaplasia (10 mg/kg) or mucification (100 mg/kg) of the urethral diverticulum epithelium and inflammation of genital organs (100 mg/kg). Though only undescended testes lacked spermatogenesis at 10 mg/kg, atrophic change of seminiferous tubules and azoospermia were observed in the 100 mg/kg group, despite testicular descent. Perinatal administration of flutamide affected F1 male rats at 2.5 mg/kg and above. In addition to urogenital malformation, 100 mg/kg flutamide caused high LH and FSH levels at PND 60. This study indicates that the most sensitive parameter is AGD, whereby reduction was observed at 2.5 mg/kg. A clear no-effect level (NOEL: 0.6 mg/kg) was obtained in this perinatal study of an antiandrogenic chemical.

Prevention by natural food anthocyanins, purple sweet potato color and red cabbage color, of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-associated colorectal carcinogenesis in rats initiated with 1,2-dimethylhydrazine.

The potential of purple sweet potato color (PSPC) and red cabbage color (RCC), natural anthocyanin food colors, to modify colorectal carcinogenesis was investigated in male F344/DuCrj rats, initially treated with 1,2-dimethylhydrazine (DMH) and receiving 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in the diet. After DMH initiation, PSPC and RCC were given at a dietary level of 5.0% in combination with 0.02% PhIP until week 36. No PSPC or RCC-treatment-related changes in clinical signs and body weight were found. Incidences and multiplicities of colorectal adenomas and carcinomas in rats initiated with DMH were clearly increased by PhIP. In contrast, lesion development was suppressed by RCC, or tended to be inhibited by PSPC administration. Furthermore, in the non-DMH initiation groups, induction of aberrant crypt foci (ACF) by PhIP was significantly decreased by RCC supplementation. The results thus demonstrate that while PhIP clearly exerts promoting effects on DMH-induced colorectal carcinogenesis, these can be reduced by 5.0% PSPC or 5.0% RCC in a diet under the present experimental conditions.

Lack of significant alteration in the prostate or testis of F344 rat offspring after transplacental and lactational exposure to bisphenol A.

Bisphenol A (BPA), a compound of great concern as an estrogenic xenobiotic, was assessed for its ability to cause alteration in the accessory sex organs and spermatogenesis in male offspring exposed preneonatally and neonatally. In a series of experiments focusing on rat sensitivity to gestational and lactational exposure to BPA, we investigated its effects on gestation period and reproductive organs in male offspring. In the first instance, BPA was administered to F344 female rats by gavage at 0, 7.5, 120 mg/kg/day during pregnancy and lactation period. There were no observable adverse effects in pregnant rats and the treatment did not induce any morphological abnormalities in the accessory sex organs of male offspring. However, lowered numbers of sperm in the testis were found with a dose of 120 mg/kg/day. In the second study, the same protocol with a higher number of male offspring was applied, but no reduction in the sperm count was apparent. We conclude that transplacental and lactational exposure to BPA dose not exert any adverse effects on morphogenesis of rat accessory sex organs or spermatogenesis.