This study was aimed to determine the ultraviolet (UV: 235-310nm) action spectrum for killing normal human epidermal keratinocytes (NHEK) and to investigate the preventive effect of EPC-K1, a phosphate diester of vitamin C and vitamin E on UV radiation-induced NHEK injury. NHEK were cultured in EpiLife® medium supplemented with Human Keratinocyte Growth Supplement Kit. NHEK viability was determined by crystal violet (CV) staining 48 h after the UV irradiation. The mRNA expressions of the C/EBP homologous protein (Chop) transcription factor and endoplasmic reticulum-resident molecular chaperone, Bip, were determined by RT-PCR analyses. UV was especially effective in killing NHEK when applied in the wavelength region of 250-280nm. The minimum exposure dose required to kill 50% of cells (LD50) was 1.64mJ/cm² at 269nm. At 235 and 310nm, the LD50 for NHEK was 6.62 and 293mJ/cm², respectively. Irradiation of 660-mJ/cm² at 310nm significantly decreased the cell viability to 30% of control (without irradiation). The addition of 0.1mM EPC-K1 after irradiation returned the cell viability to 118%. Six hours after the 660-mJ/cm² irradiation at 310nm, Chop and Bip mRNA levels in NHEK were increased to 487% and 283%, respectively, and were not significantly affected by EPC-K1. Chop and Bip are responsive to ER stress. These results suggested that EPC-K1 exerts a protective effect against UV-induced NHEK injury, and further studies should investigate the molecular mechanism underlying this effect.

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The incidence of proximal extension in patients with ulcerative proctitis is reported to be 18%-46%, but recent data on the incidence in Japan is inadequate. The aim of this study was to investigate the incidence of proximal extension of ulcerative proctitis and factors associated with the extension in Japan. This is a retrospective observational study involving a cohort of 53 patients with an initial diagnosis of ulcerative proctitis. Following verification of the diagnoses, demographic and clinical data were compiled. The cumulative incidence of proximal extension was estimated as ‘person-years’ and cumulative probability was calculated by the Kaplan-Meyer method. Univariate and multivariate analyses were performed to identify association factors. During a mean follow-up of 6.8 years, proximal extension was observed in 14 patients (26.4%). The cumulative incidence of proximal extension was 4.22/100 person-years and the cumulative probability at 5 years was 20.1%, consistent with recent reports from Western countries and data obtained in Japan over 2 decades ago. Univariate analysis showed active smoking (P = 0.025) and corticosteroid therapy (P = 0.006) to be risk factors in proximal extension, however multivariate analysis revealed that corticosteroid therapy was the only significant factor (P = 0.005) separating patients with and without proximal extension. No patient underwent colectomy. The incidence of proximal extension in ulcerative proctitis in Japan is comparable to that in Western countries and has not changed significantly over the past two decades. Corticosteroid therapy was identified as the only significant factor in proximal extension.

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Alcoholic liver disease causes oxidative stress and induces apoptosis during alcohol metabolism. Ethanol causes endoplasmic reticulum (ER) stress in hepatocytes, stimulating the unfolded protein response (UPR) pathway and/or Ca²⁺-dependent calpain and caspase-4 activities. However, it is poorly understood whether ethanol-induced oxidative stress directly leads to apoptosis promoted by ER stress-associated pathways. This study investigated this question in human liver adenocarcinoma (SK-Hep1) cells, which were treated with 200 mM ethanol for 5 hours in the presence or absence of the antioxidant N-acetyl-cysteine (NAC). We found that treatment with ethanol significantly increased ROS production and cellular apoptosis in the SK-Hep1 cells, and that this response was significantly suppressed by pretreatment with NAC. Furthermore, pretreatment with NAC significantly reduced the observed increases in the mRNA expressions of Bip, Chop, and sXbp-1, and the activity of caspase-3 in ethanol-induced apoptotic cells. However, pretreatment with NAC did not attenuate the transient rise in cytosolic Ca²⁺ nor the activities of caspase-4 and calpain induced by ethanol. Together, these results revealed that ethanol-induced stress promotes apoptosis not only through mitochondria-mediated pathways, but also via ER stress. The findings further suggested that ethanol-induced oxidative stress and non-oxidative stress both stimulate the pathway regulating ER stress-mediated apoptosis.

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Nonalcoholic steatohepatitis (NASH) is regarded as a hepatic manifestation of the metabolic syndrome which can progress to hepatic cirrhosis and hepatocellular carcinoma. It is thought that matrix metalloproteinases (MMPs) play an important role in hepatic fibrosis and we previously reported a correlation between oxidative stress and MMP-9 expression. However, the expression of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in the progression of NASH is unclear. In this study we used spontaneously hypertensive and hyperlipidemic rats (SHHR) fed a high-fat diet and 30% sucrose solution (HFDS) as a model for NASH, in order to clarify the relationships between oxidative stress, liver weight (LW), MMPs and TIMPs at various time-points in the progression of NASH. Male SHHR and Sprague-Dawley (SD) rats were divided into four groups: SHHR-normal diet (ND), SHHR-HFDS, SD-ND and SD-HFDS. Hepatic fibrosis was clearly increased at 13 months in SHHR-HFDS, resembpling NASH. LW and oxidative stress markers in plasma were increased in SHHR-HFDS compared to the other groups. Oxidative stress was correlated with LW in all rats. Expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 mRNA, measured by real-time polymerase chain reaction, was increased in the liver of SHHR-HFDS at 13 months. This study suggests that oxidative stress, MMPs and TIMPs may play an important role in the progression of NASH.

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Current therapy for space-occupying fetal lung mass lesions (fetal pulmonary lobectomy) is invasive and technically demanding. Accordingly, new therapeutic procedures are required which are much less invasive and more efficient. The purpose of this study was to investigate the feasibility of high-intensity focused ultrasound (HIFU) as a new therapeutic modality for fetal lung mass lesions, using an experimental animal model. We created a solid fetal lung model by differential lung ventilation using anesthetized adult rabbits. In this model, experimental animals with a unilateral independent (fluid-filled) lung were maintained by single lung ventilation of the other dependent lung. Within the independent lung, target blood vessels depicted by color flow Doppler were repeatedly irradiated with HIFU energy beams (n=19). Occlusion of these blood vessels in vivo was confirmed by evaluation of the flow using color flow Doppler. After the procedure, the animals were sacrificed and their harvested lungs were assessed grossly and microscopically. Pulmonary blood vessels (artery and/or vein) were effectively occluded with 2 to 5 cycles of HIFU energy delivery (10.5 seconds each) with a success rate of 62.5% (arteries) and 72.7% (veins). No clear changes including tissue perforations were observed grossly on the surface of the lungs. Ultrasound-guided HIFU energy delivery seems promising for occlusion of the pulmonary blood vessels within a fluid-filled independent lung (fetal lung model). Thus in the future, HIFU irradiation could be used as a less invasive technique to occlude the feeding vessels of fetal lung mass lesions in utero.

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Flower arrangements are widely used for decoration, but also for emotional healing. Ikebana is the Japanese art of flower arrangement, dating back over 600 years. Although ikebana has been used for psychological rehabilitation, no research has examined its effect on physiological responses in individuals. We examined the effect of viewing photos of ikebana on anxiety and respiratory responses. For controls, we used photos of ikebana that were artificially changed from real, beautiful photos to non-beautiful altered photos. Participants' sense of beauty was measured by a visual analogue scale (VAS). Values were significantly higher while viewing the real photos compared to altered photos (P < 0.05). The VAS score differences between the real and altered photos were also significantly higher in subjects with low trait anxiety (P < 0.05). There was no significant change in respiratory rate (RR) between subjects viewing real and retouched photos. However, the mean difference in RR when viewing real photos compared to retouched photos was higher in subjects with low trait anxiety scores. There was no correlation between VAS score differences and trait anxiety scores. However, differences in RR when viewing real photos compared to viewing retouched photos had a significantly negative correlation (P < 0.05). Results indicated that RR was slower when viewing photos of ikebana in subjects with higher trait anxiety. Our findings suggest that viewing beautiful things may relax individuals who have high anxiety.

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In Japan, historically, doctors had refrained from disclosing a cancer diagnosis to patients, but attitudes regarding disclosure have recently been changing. We investigated the mental condition and treatment of patients after disclosure of cancer. Thirty-seven cancer patients (7 gastric cancer, 23 colorectal cancer, 5 breast cancer, 2 hepatocellular carcinoma) participated in this study. We divided the patients at Week 1 after disclosure of the diagnosis of cancer into two groups according to their score of Hospital Anxiety and Depression Scale (HADS): one group whose HADS was 8 points or more (Group A), and another group whose points were below 8 (Group B) at Week 1 after disclosure. There were 11 (29.7%) patients in Group A, and 26 (70.3%) in Group B. The average HADS differed between the two groups before disclosure, and at Weeks 1 to 5 after disclosure. Group A was treated with paroxetine hydrochloride hydrate (PAX) and about 70% of the patients showed an improvement of anxiety or depression by Week 5. While, there was 0% in HADS of 8 or more in breast cancer patients after disclosure. Some patients felt anxiety and depression unrelated to the stage of cancer. Furthermore, we noted that anxiety and depression were not detected after the cancer disclosure in any of the breast cancer patients, suggesting the possibility that anxiety and depression were alleviated by events such as surgery. It is necessary for medical treatment to advance to new steps in the treatment of cancer, providing enough support to the patients in the future.

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