Damage to sebaceous gland and the efficacy of moisturizer after whole breast radiotherapy: a randomized controlled trial.

BACKGROUND: We conducted a randomized trial to evaluate the efficacy of heparinoid moisturization for radiation dermatitis. We report the time-course of sebum content after whole breast radiotherapy (WBRT) and the efficacy of heparinoid moisturizer. METHODS: Patients receiving adjuvant breast RT were randomly assigned into three groups; prophylaxis, post-WBRT and control groups. Patients used moisturizer on the irradiated breast from the beginning of RT in the prophylaxis group, 2 weeks post-RT in the post-WBRT group, and no moisturizer in the control group. Sebum content of the irradiated and non-irradiated breast was measured to assess sebaceous gland damage. Sebum composition was also analyzed. RESULTS: A total of 76 patients were analyzed; 30 in the post-WBRT group, 32 in the control group, 14 in the prophylaxis group. The sebum content in the irradiated breast significantly decreased after WBRT in the post-WBRT and control groups. The decrease was sustained in the control group. In the non-irradiated breast, sebum content also decreased after WBRT in the post-WBRT and control groups. After moisturizer application, sebum content by sebumeter returned to pre-RT level in the post-WBRT group, while the decrease was sustained in the control group. Sebum content measured by evaporative light scattering detector and sebumeter was similar in the control group, but the dissociation was observed after moisturizer application in the post-WBRT group. The proportion of wax esters decreased in the irradiated breast after WBRT. CONCLUSIONS: Radiotherapy significantly reduced sebum content in both irradiated and non-irradiated breast, indicating that RT caused quantifiably persistent sebaceous gland damage in irradiated sites and the surrounding tissue. Combined with the results from our previous study, heparinoid moisturizer treatment effectively prevents water loss by retaining oil contents on the skin surface. TRIAL REGISTRATION: UMIN, UMIN000005532 . Registered 1 April 2011.

Efficacy of heparinoid moisturizer as a prophylactic agent for radiation dermatitis following radiotherapy after breast-conserving surgery: a randomized controlled trial.

BACKGROUND: The application of heparinoid moisturizer for 2 weeks following whole-breast radiotherapy (WBRT) was previously reported to significantly increase skin water content (WC) and help improve skin dryness and desquamation. The prospective open-label, randomized trial included an exploratory arm to investigate the preventive efficacy of heparinoid moisturizer for acute radiation dermatitis (ARD). METHODS: Between April 2011 and April 2013, patients receiving WBRT were assigned (1:2:2) to receive either: moisturizer for prophylaxis (group P), moisturizer starting 2 weeks after WBRT for treatment (group M), and no moisturizer (group C). This paper presents the results of comparison between the exploratory arm and no moisturizer group. Skin WC was measured prior to WBRT, on the last day of WBRT, and 2 weeks, 4 weeks and 3 months following WBRT. Signs and symptoms were also assessed. RESULTS: Comparing two groups, WC values were significantly higher in group P until 4 weeks following WBRT. At 2 weeks following WBRT, mean WC values in group P and C were 38.5 ± 6.1 arbitrary units (a.u.) and 30.2 ± 7.8 a.u., respectively (P < 0.001). In group C, dryness was more severe at 2 and 4 weeks following WBRT and desquamation more severe until 3 months following WBRT. However, the erythema score showed no difference between the two groups. Regarding symptoms, group C pain scores on the last day of WBRT were significantly higher than in group P (P < 0.030). CONCLUSIONS: The preventive application of heparinoid moisturizer has the potential of reducing skin desquamation and dryness in patients receiving WBRT.

Randomized, prospective assessment of moisturizer efficacy for the treatment of radiation dermatitis following radiotherapy after breast-conserving surgery.

OBJECTIVE: The effect of heparinoid moisturizer use after acute skin damage for patients receiving whole-breast radiotherapy after lumpectomy is understudied. METHODS: A total of 30 patients were randomly assigned to receive heparinoid moisturizer (Group M), and 32 patients comprised the control group (Group C). Patients in Group M were instructed to apply heparinoid moisturizer from 2 weeks following whole-breast radiotherapy, and to continue to use the moisturizer until 3 months after completion of whole-breast radiotherapy. Group C patients were instructed to not apply any topical moisturizer during the study period. The relative ratio of skin water content ratio (RWCR(t) = (It /Nt)/(I0/N0)) between irradiated and non-irradiated field was calculated. Signs and symptoms were also assessed. The primary endpoint was the difference in relative ratio of skin water content ratio between 2 and 4 weeks following whole-breast radiotherapy. RESULTS: In Group C, relative ratio of skin water content ratio dropped to 0.80 ± 0.15 at 2 weeks and maintained the low level at 4 weeks following whole-breast radiotherapy. Similarly, in Group M, relative ratio of skin water content ratio dropped to 0.81 ± 0.19 at 2 weeks (prior to application), however, it returned to baseline level (1.05 ± 0.23) at 4 weeks (2 weeks after application). The arithmetic difference of relative ratio of skin water content ratio in Group M was 0.24 ± 0.23 and was significantly larger than in Group C (0.06 ± 0.15; P < 0.01). Skin dryness and desquamation were less severe in Group M. CONCLUSIONS: The application of heparinoid moisturizer for 2 weeks following whole-breast radiotherapy significantly increased water content and helped improve skin dryness and desquamation compared with no use of moisturizer.

Psychological stress associated with skin marking during radiotherapy on breast cancer patients.

INTRODUCTION: This study aimed to further understand the psychological distress associated with skin marking during radiotherapy among patients with breast cancer. The potential benefits of skin mark-free radiotherapy were also explored. MATERIALS AND METHODS: The study population included female breast cancer patients scheduled for radiation therapy and skin marking. A 12-item survey was administered, encompassing demographics (age, treatment site and mode, and duration of hospital visits), awareness of skin marking, stress induced by skin marking in various life contexts, and perceived advantages of a skin mark-free alternative. Responses were recorded on a 5-point Likert scale. RESULTS: The survey was completed by 107 patients, of whom 90 (84%) underwent whole breast irradiation, 15 (14%) received breast/chest wall and supraclavicular lymph node irradiation, and 2 (2%) were unspecified. The common sources of stress were from the presence of skin markings (33%), bathing (41%), clothing selection (25%), and skincare (30%), whereas 17 patients (16%) were not stressed by any of those factors. Meanwhile, 73% of patients reported taking precautions to prevent the skin marks from fading. Most patients (63%, n = 76) expressed preference for a skin mark-free radiotherapy option, with many willing to spend extra finances and time for this. CONCLUSIONS: A significant proportion of female breast cancer patients experience stress from skin markings in various aspects of their daily lives. A preference for skin mark-free radiotherapy was noted among many patients, that next-generation technologies, such as surface-guided radiotherapy, could alleviate patient stress. IMPLICATIONS FOR PRACTICE: The need for permanent or temporary skin markings in the era of state-of-the-art imaging technology should be reconsidered.

Neonatal exposure to sevoflurane causes significant suppression of hippocampal long-term potentiation in postgrowth rats.

BACKGROUND: The inhaled anesthetic sevoflurane is commonly used for neonates in the clinical setting. Recent studies have indicated that exposure of neonatal rodents to sevoflurane causes acute widespread neurodegeneration and long-lasting neurocognitive dysfunction. Although acute toxic effects of sevoflurane on cellular viability in the hippocampus have been reported in some studies, little is known about the effects of neonatal sevoflurane exposure on long-term hippocampal synaptic plasticity, which has been implicated in the processes of learning and memory formation. Our study is the first to examine the long-term electrophysiological impact of neonatal exposure to a clinically relevant concentration of sevoflurane. METHODS: On postnatal day 7, rats were exposed to sevoflurane (1% or 2% for 2 hours) with oxygen. To eliminate the influence of blood gas abnormalities caused by sevoflurane-induced respiratory suppression, a group of rats were exposed to a high concentration of carbon dioxide (8% for 2 hours) to duplicate respiratory disturbances caused by 2% sevoflurane exposure. RESULTS: Exposure of neonatal rats to 2% sevoflurane for 2 hours caused significant suppression of long-term potentiation (LTP) induction in the postgrowth period. There was no significant difference between the control group and the CO2-exposed group in LTP induction, indicating that sevoflurane-induced LTP suppression was not caused by blood gas abnormalities. CONCLUSION: Our present findings indicate that neonatal exposure to sevoflurane at a higher concentration can cause alterations in the hippocampal synaptic plasticity that persists into adulthood.

Neonatal administration with dexmedetomidine does not impair the rat hippocampal synaptic plasticity later in adulthood.

BACKGROUND AND OBJECTIVE: The use of dexmedetomidine (DEX), a selective alpha-2 agonist, in pediatric practice is expanding as a result of its desirable properties. To clarify the long-term neurological consequences of neonatal administration of DEX, we investigated the long-term effects of neonatal administration of DEX on hippocampal synaptic activity. METHODS: The rat pups received a bolus intraperitoneal injection of either 5 or 10 µg·kg(-1) DEX, or an equivalent volume of vehicle on postnatal day 7 (P7). Nine weeks after administration, evoked potentials (population spike, PS) and long-term potentiation (LTP) in the hippocampal CA1 region of rats were studied in vivo. RESULTS: Dexmedetomidine had a considerable sedative effect at these doses with little respiratory depression on P7. Nine weeks after administration of DEX, the amplitude of PS in the two treated groups was similar to that in the control group. DEX-treated rats showed no impairment in the induction of LTP. Furthermore, the response in PS to the paired stimuli was not impaired by neonatal administration of DEX. CONCLUSION: These findings demonstrate that a single administration of DEX to rats on P7 preserves hippocampal synaptic plasticity as well as synaptic transmission later in life. In view of the some evidence that have demonstrated the permanent detrimental impact of commonly used anesthetics on neurological outcomes after neonatal exposure, our findings may suggest the relative safety of DEX administered as a sedative agent to neonatal animals with regard to the development of hippocampal synaptic functions.

Development of a Japanese Version of the Index of Sexual Satisfaction for Use in Couples with Young Children.

The occurrence of sexual dysfunction in couples after childbirth is well recognized, yet sexual satisfaction in couples with young children (CYC) has received little research attention. This study sought to enable this construct to be measured by developing and validating a Japanese version of the Index of Sexual Satisfaction (ISS) in CYC. Data were collected using a self-administered questionnaire. Scale construction and validation were conducted using two independent samples drawn from 316 mothers and 272 fathers in Japan who had at least one child aged 6 or younger. Two underlying factors were identified using exploratory factor analysis: sexual satisfaction, measured by eight items, and sexual dissatisfaction, measured by three. Polychoric ordinal alpha coefficients indicated the reliability of the resulting scale (overall: 0.89, factor 1: 0.89, factor 2: 0.78), and confirmatory factor analysis and testing supported its validity, showing good model fit (goodness of fit index: 0.984, root mean square residual: 0.062) and satisfactory composite reliability (scale: 0.93, factor 1: 0.90, factor 2: 0.81) and average variance extracted (all ≥0.5). The Japanese version of the ISS for Couples with Young Children will be useful for investigating sexual satisfaction, which is essential to marital stability.

Effect of Heparinoid Moisturizer on Quality of Life in Patients with Acute Radiation Skin Damage Following Hypofractionated Radiation Therapy After Breast-Conserving Surgery: A Randomized Controlled Study.

BACKGROUND: With few research reports on the effects of moisturizer use for dry skin associated with radiotherapy after breast-conserving surgery on patient quality of life (QOL), we conducted a randomized controlled trial to investigate this effect. METHODS: Patients with breast cancer were randomly assigned to receive either heparinoid moisturizer (Group M) or no treatment (Group C). Group M was instructed to apply heparinoid moisturizer during 3 weeks of hypofractionated whole-breast irradiation with or without boost until 4 weeks after completion of irradiation. Skin-related QOL was assessed using the Dermatology Life Quality Index (DLQI) for 7 weeks. The primary endpoint was total DLQI score at 4 weeks after the start date. RESULTS: In total, 35 patients in Group M and 37 patients in Group C were analyzed. The DLQI total score (2.06 ± 2.17: mean ± SD) at 4 weeks in Group M was slightly lower than in Group C (2.16 ± 2.13) but with no significant difference (p = 0.894). The "Symptoms and feelings" subscore indicated significant worsening at 3 weeks and maintained until 7 weeks in Group C. There was no significant change for this subscore during radiotherapy in Group M, and it significantly increased after radiotherapy (4-5 weeks) and returned to baseline in 7 weeks. The period of subscore worsening was shorter in Group M than in Group C. CONCLUSION: Concomitant and extended use of heparinoid moisturizer with radiation therapy may improve the QOL of breast cancer patients impaired by dry skin for patients with breast cancer.

Down-regulation of CD9 in human ovarian carcinoma cell might contribute to peritoneal dissemination: morphologic alteration and reduced expression of beta1 integrin subsets.

Peritoneal dissemination is one of the main causes of death in cancer patients. Pathophysiology of metastasis has been well investigated, but the mechanism of diffuse spread of tumor colonies in the peritoneal cavity is not fully understood. CD9 is a member of tetraspanin and its down-regulation is known to be involved in poor prognosis. To investigate the significance of the down-regulation of CD9, HTOA, an ovarian carcinoma cell line that highly expressed CD9, was transiently transfected with small interfering RNA (siRNA) against CD9, and CD9-negative cells (HTOA(CD9-)) were purified. HTOA(CD9-) showed altered adhesion patterns on Matrigel, collagen, fibronectin, and laminin compared with those of control siRNA-transfected HTOA (control-HTOA). Flow cytometry and fluorescence cytostainings revealed that the expression levels of integrins beta1, alpha2, alpha3beta1, alpha5, and alpha6 were lower in HTOA(CD9-) than those of control-HTOA. HTOA(CD9-) showed altered expression of junctional and cytoskeletal molecules. By time-lapse video microscopy, control-HTOA showed solid adhesion to extracellular matrix and formed cobblestone pattern, whereas HTOA(CD9-) showed weaker adhesion and were distributed as diffuse spots. To examine whether the expression level of CD9 change during tumor dissemination, HTOA-P, a highly disseminative subclone of HTOA, was established. HTOA-P showed distinctive down-regulation of CD9 at mRNA and protein levels, and showed similar morphologic alteration as HTOA(CD9-) did. These findings indicate that the down-regulation of CD9 may be an acquired event in the process of tumor dissemination. Down-regulated CD9 may attenuate the expression of several integrins and rearrange junctional and cytoskeletal molecules that might contribute to dissemination of ovarian carcinomas.

Identifying predictive clinical characteristics of the treatment efficacy of mirtazapine monotherapy for major depressive disorder.

BACKGROUND: Mirtazapine, which is classified as a noradrenergic and specific serotonergic antidepressant, is widely prescribed for the treatment of major depressive disorder. The potential predictive factors of the efficacy of mirtazapine and the tolerability based on the incidence of oversedation and jitteriness/anxiety syndrome were evaluated. PATIENTS AND METHODS: Patients with major depressive disorder were retrospectively investigated. Study subjects comprised 68 patients with depression who received mirtazapine as an initial antidepressant at the Department of Psychiatry of the Tokyo Women's Medical University Hospital from September 2009 to March 2013. The efficacy of mirtazapine monotherapy was evaluated based on the Clinical Global Impression Improvement score. Clinical characteristics were compared between remission and nonremission groups to determine the factors predicting the efficacy. Moreover, discontinuation rates due to adverse effects, including oversedation and jitteriness/anxiety syndrome, were examined, and the effects of confounding factors were evaluated. RESULTS: The remission rate of mirtazapine monotherapy was 36.8% among the 68 enrolled subjects. The mean final doses in the remission and nonremission groups were 27.6±13.5 mg and 26.0±14.1 mg, respectively, and there was no significant difference between them. Multiple logistic analyses revealed that the absence of guilt (odds ratio [OR] =0.15; 95% CI [1.66-37.24], P=0.006) and the presence of psychomotor retardation (OR =4.30; 95% CI [1.30-16.60], P=0.016) were significantly related to the efficacy of mirtazapine monotherapy. The discontinuation rates due to oversedation and jitteriness/anxiety syndrome were 13.2% and 11.8%, respectively. Age did not differ significantly between patients with or without oversedation or jitteriness/anxiety syndrome (P=0.078 and P=0.579, respectively). CONCLUSION: The absence of guilt and the presence of psychomotor retardation may predict the efficacy of mirtazapine, and mirtazapine may be tolerable for all ages.

[Effect of pranlukast on histamine release and leukotriene c4 (ltc4) generation from human peripheral basophils].

Human basophils may play a role in bronchial asthma. The effect of pranlukast on histamine release and LTC4 generation from human peripheral basophils was examined. Histamine release induced by FMLP and C5a was inhibited by pranlukast in concentration-dependent manner, whereas anti-IgE Ab-induced histamine release was not affected. Both anti-IgE Ab-and FMLP-induced LTC4 were inhibited by pranlukast. These results suggest that pranlukast may improve symptoms of bronchial asthma by inhibiting basophil function in addition to antagonizing Cys-LT receptor.

Neonatal exposure to high concentration of carbon dioxide produces persistent learning deficits with impaired hippocampal synaptic plasticity.

Although respiratory complications with blood gas abnormalities contribute significantly to neurodevelopment in the immature brain, little is known about the mechanisms via which blood gas abnormalities, such as hypoxic hypercapnia, impair neurocognitive outcomes. To investigate the possible long-term consequences of neonatal exposure to hypoxic hypercapnia regarding learning ability, we investigated the effect of neonatal hypoxic hypercapnia on later functions in the hippocampus, which is a structure that has been implicated in many learning and memory processes. Neonatal rat pups (postnatal day 7; P7) were exposed to a high concentration of carbon dioxide (CO2; 13%) for 2 or 4h. Exposure to CO2 in P7 rat pups caused blood gas abnormalities, including hypercapnia, hypoxia, and acidosis, and disrupted later learning acquisition, as assessed in 10-week-old adult rats subjected to a Morris water maze test. Induction of long-term potentiation (LTP) in the synapses of the hippocampal CA1 area was also impaired, whereas the paired-pulse responses of population spikes exhibited a significant increase, in CO2-exposed rats, suggesting decreased recurrent inhibition in the hippocampus. Such long-lasting modifications in hippocampal synaptic plasticity may contribute to the learning impairments associated with perinatal hypoxic hypercapnia and acidosis.

Thermodynamic quantities of surface formation of aqueous electrolyte solutions X. Aqueous solution of 2:1 valence-type salts.

The behaviors of a series of calcium halides and of alkali earth metal chlorides in the air/water surface region were studied in comparison with those of alkali metal halides by measuring the surface tension increments of solutions. The effect of salts with divalent cations on the surface tension increments is more pronounced than that of uni-univalent salts, but there are some similarities between these two types. It seems that the anions cause a marked effect on surface tension which is proportional to the magnitude of hydration in the bulk water. We also observed a decrease in the entropy change of surface formation with increasing concentration. The importance of an electrical double layer at the surface is discussed in relation to these surface tension increments.

Long-lasting effects of neonatal pentobarbital administration on spatial learning and hippocampal synaptic plasticity.

Exposure of newborn rats to antiepileptics such as barbiturates has long-lasting detrimental effects on the hippocampus and hippocampus-dependent behavior. However, the long-term consequences of neonatal administration with barbiturates on the hippocampal synaptic plasticity remain unresolved. In this study, we investigated the long-lasting effects of a neonatal administration of pentobarbital on spatial memory, paired-pulse plasticity in the population spikes, and long-term potentiation (LTP) in the hippocampal CA1 region of rats in vivo. Eight weeks after administration of pentobarbital (10 or 20mg/kg) on the seventh postnatal day (P7), rats showed impaired induction in LTP. During paired-pulse stimulation, pentobarbital-treated rats exhibited a greater facilitation of the test pulse population spike, suggesting a disruption in the inhibitory GABAergic synaptic transmission. Spatial learning in hidden platform task of the Morris water maze was impaired in pentobarbital-treated rats. Our present findings indicate that neonatal treatment with pentobarbital causes alterations in function of the hippocampal inhibitory synaptic transmission that persist into adulthood, likely contributing to the long-lasting abnormalities in the hippocampal LTP as well as learning ability. We also demonstrated significant respiratory disturbances, i.e., severe hypoxia, hypercapnia, and extracellular acidosis, in rats treated with pentobarbital on P7. Given that extracellular acidosis can also modulate synaptic transmission in the developing hippocampus, this finding led us to speculate regarding the influence of respiratory disturbances in pentobarbital-induced long-lasting hippocampal dysfunctions.