Search

Eeffects of perfluorooctane sulfonate (PFOS) on maleic dialdehyde (MDA) content, superoxide dismutase (SOD) activity and total antioxidation capability (T-AOC) were compared in mice at different postnatal developmental stages, and concentrations and distributions of PFOS in different tissues were measured simultaneously. The male and female mice at postnatal day (PD) 7, PD 14, PD 21, PD 28 and PD 35 were distributed randomly to dosage group (50 mg/kg body weight) and control group (0 mg/kg body weight). Mice were administered with PFOS by once subcutaneous injection. Subsequently, after 24 hr, MDA content, SOD activity and T-AOC in brain and liver were analyzed. The PFOS concentrations in blood, brain and liver were determined by high-performance liquid chromatography nega- tive electrospray tandem mass spectrometry (LC-MS). PFOS induced degression of the body weights of mice evidently and increase of relative weights of liver. Meanwhile, it depressed the SOD activity and T- AOC in brain and liver. The concentrations and distribution percentages of PFOS in blood, brain and liver of mice were significantly different at various postnatal developmental stages. Achieved results in this study indicate that younger mice pups were more sensitive to PFOS exposure. In addition, significant distinctions in concentrations and distribution percentages of PFOS in various tissues were demonstrated in this study. The gender difference observed was greater in the older mice. Thus it is worth giving attention especially to adverse effects of PFOS on foetus and children. [ABSTRACT FROM AUTHOR]

Objectives: This study explored collaboration models between primary care physicians (PCPs) and care managers (CMs) and assessed each model's potential in meeting the support needs of individuals with early-stage dementia., Methods: In 2022, a cross-sectional survey was conducted among the PCPs in Tokyo. The data regarding the participant and clinic characteristics and daily practices for individuals with early-stage dementia were collected. The clinical collaborative practice was classified using a latent class analysis; comparisons were made between the identified classes based on 14 items in seven domains of support., Results: Two collaborative and one stand-alone models were identified. The former varied in the professionals' roles, with one led by PCPs and the other by CMs. We named them PCP-led, CM-led, and stand-alone models, accounting for 46.4%, 32.8%, and 20.6% of the clinics, respectively. The PCP-led clinics were significantly more likely to provide support than the stand-alone ones across five domains: cognitive function, care planning, carers' support, information, and social health. The CM-led model clinics generally fell between those of the other two models., Conclusion: Different leadership styles exist in the PCP-CM collaborations in care delivery for people with early-stage dementia. This collaboration offers distinct advantages for clinics in addressing their needs., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Background: Post-war Japanese tend to avoid discussion of death, resulting in a lack of death communication within clinical settings. However, with the aging of society, the significance of conversations and decisions related to end-of-life issues has grown. In 2007, the government established guidelines for decision-making in end-of-life care. Nonetheless, death communication remains a challenge for healthcare professionals in clinical settings. In contrast, death cafés have spontaneously emerged within communities as informal gatherings to openly discuss and explore death. Learning from death café organizers may help healthcare professionals encourage death communication in a death-avoidant society. Therefore, a qualitative study was conducted to describe death cafés by examining the underlying motivation and practices through interviews with death café organizers., Methods: Individual in-depth interviews were conducted with death café organizers. Two key aspects were explored: 1) the underlying motivations of organizers; and 2) the practices and challenges encountered in running death cafés. The interviews were transcribed verbatim and analyzed using a qualitative descriptive approach. Thematic analysis was used., Results: The study identified two themes representing the underlying motivation of death café organizers: individually-oriented and community-oriented. These themes exhibited contrasting orientations and were collectively termed "individual-community orientation". Regarding the practice of death cafés, the focus was on the "attitude towards having attendees with and without grief in the same session." Participants' attitudes towards this aspect fell into two categories with opposing orientations: "purification" and "inclusion." The "purification-inclusion orientation" was more prevalent among organizers who initiated death cafés due to their personal experiences. A matrix was created to categorize death cafés based on their underlying motivations (individual vs. community-oriented) and practices (purification vs. inclusion). This classification resulted in quadrant 1 (community-oriented, inclusive) and quadrant 3 (individually-oriented, purification). Notably, death cafés in quadrant 1 were often held in temples., Conclusions: Japanese death cafés can be classified into two categories: individually and purification-oriented and community and inclusive-oriented categories. Healthcare professionals can learn valuable insights from death café organizers, particularly in promoting death communication. Specifically, temple death cafés, with their inclusive practices and orientation towards community, can be particularly beneficial in fostering inclusivity and community engagement., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Although people with cognitive impairment highly value social participation in out-of-home activities, their families typically perceive concerns and experience anxiety over such activities. This study aimed to elucidate the underlying concerns and factors associated with family caregivers' anxiety over the individual's unaccompanied out-of-home activities., Methods: In December 2021, we conducted a cross-sectional e-survey of family caregivers of individuals with early-stage cognitive impairment. Caregivers' concerns about ten common risks related to out-of-home activities were cross-tabulated by specific anxiety levels to examine trend associations. With the variables of caregivers and their individuals across the five domains, we ran logistic regression analyses to determine explanatory models for anxiety., Results: The study participants were 1,322 family caregivers of people whose cognitive function varied from intact to possible mild dementia according to the Dementia Assessment Sheet for Community-based Integrated Care System 8-item. Significant associations were found between the prevalence of concerns and the degree of anxiety, even without actual experience with the issues of concern. Among the five domains, individual dementia characteristics and social behaviors were the predominant factors attributed to caregiver anxiety. Caregivers' no anxiety state was significantly associated with: younger age (OR 4.43, 95% CI 1.81-10.81), no detectable cognitive decline (OR 3.34, 95% CI 1.97-5.64), free from long-term care (LTC) (OR 3.52, 95% CI 1.72-7.21), no manifestation of behavioral and psychological symptoms of dementia (BPSD) (OR 13.22, 95% CI 3.06-57.01), and not engaging in unaccompanied out-of-home activities (OR 3.15, 95% CI 1.87-5.31). Their severe anxiety was positively associated with being on LTC (OR 3.39, 95% CI 2.43-4.72) and minor BPSD (OR 1.43, 95% CI 1.05-1.95), and negatively associated with engagement in unaccompanied out-of-home activities (OR 0.31, 95% CI 0.23-0.43)., Conclusions: The study found that family caregivers' anxiety was associated with concerns about behavioral issues, regardless of actual experiences. There were two significant associations in opposite directions between caregivers' anxiety and the individual's engagement in out-of-home activities. In the early phase of cognitive impairment, caregivers may intuitively interpret the individual's behavior and feel anxious. Educational support may provide reassurance and enable caregivers to facilitate out-of-home activities., (© 2023. The Author(s).)

Aim: The present studyinvestigated the roles expected of Dementia Support Doctors (DSDs) in dealing with complex cases., Methods: The participants were attendees of the education programs organised by the Center for Promoting Dementia Support and the Medical Center for Dementia at the Tokyo Metropolitan Geriatric Hospital from April 2021 to March 2022. A self-administered postal questionnaire survey was conducted. The questionnaire included items on the basic attributes of the participants, their experiences with the issues associated with complex cases, and role expectations of consulting/collaboration partners when dealing with complex cases., Results: The valid response rate was 49.3%. DSDs were expected by primary physicians, Community General Support Center staff and administrative staff to diagnose dementia and give advice on support strategies for complex cases. Primary physicians further expected them to initiate pharmacotherapy with anti-dementia drugs and address the pharmacotherapy needs for managing Behavioral and Psychological Symptoms of Dementia. It was also found that DSDs' experience with complex cases was comparable to that of the staff at the Medical Centers for Dementia. Of note, DSDs were mentioned less frequently as consulting/collaboration partners than Medical Centers for Dementia and primary physicians., Conclusions: The study showed that DSDs play an important role in dealing with complex cases. The roles of DSDs and ways to collaborate with them need to be communicated through interprofessional education.

Aim: Older people with severe and complex needs are a major challenge in the realm of community health. However, despite the importance of the issue there is a lack of knowledge regarding complex cases of community-dwelling older people with cognitive impairment (hereafter referred to as "complex cases"). The first aim of this study was to develop a framework for the comprehensive assessment and analysis of the issues faced by complex cases. The second aim was to identify the relationships between these issues and the clinical stages of dementia using the Clinical Dementia Rating (CDR)., Methods: A consecutive case series study was conducted using the records of 293 cases in municipal psychogeriatric services. Descriptions regarding the issues faced by complex cases were extracted from the case records and categorized. Next, trends according to CDR were analyzed. The association between each category and the CDR was then examined by multivariate analysis., Results: The issues faced by complex cases were categorized into five categories: A, Mental Health Issues; B, Physical Health Issues; C, Family Issues; D, Issues of Neighborhood Communication; and E, Financial Issue. The higher the CDR score, the higher the frequency of categories C and E, the lower the frequency of category A, and the more categories each case faced. After adjusting for possible confounders, CDRs were associated with the categories of issues faced by complex cases., Conclusions: The analytical framework developed in the present study will help in the categorization of the complexity of complex cases and the development of intervention strategies. In addition, by incorporating the perspective of the clinical stage of dementia, more effective support can be provided. Geriatr Gerontol Int 2022; 22: 997-1004., (© 2022 Japan Geriatrics Society.)

Background: People living with dementia face a constant struggle in re-establishing their means of living a meaningful life. Journal writing exhibits the potential to help them regain a sense of control over their lives. This study explores the experience, meaning, and value of journal writing for people living with dementia who autonomously engage in the activity., Methods: We conducted individual, semi-structured interviews with eight people living with dementia who each kept a personal, paper-based daily journal. The interviews were thematically analyzed., Results: We identified four main themes. Theme 1. Recognition of the harsh reality of life under dementia. Theme 2. Observation of and compensation for weaknesses. Theme 3. Reacknowledgement and reaffirmation of one's identity, and Theme 4. Resignation and regret over comparisons to one's 'former' self. Themes 2 and 3 suggest that journal writing enabled self-reflection on daily activity functions and sense of self. However, Theme 4 represents the downside where an individual more acutely realises their deteriorating condition and regrets over their perceived loss of self., Conclusion: While acknowledging the possible adverse effect of amplifying pessimistic perceptions toward life, journal writing is a powerful 'self-help' strategy for people living with dementia and provides an avenue to recover and thrive., (© 2022 Japanese Psychogeriatric Society.)

Background: The aim of the present study was to explore factors associated with (i) the inability to attend a follow-up assessment in the community-based participatory research (CBPR) framework; (ii) mortality; and (iii) institutionalization, across a 5-year period among older people with cognitive impairment identified via an epidemiological survey., Methods: The participants were 198 older people whose score on the Mini-Mental State Examination was below 24, and who were living in our CBPR region in the Tokyo metropolitan area. Baseline data included sociodemographic factors, health-related factors, social factors, and assessments by healthcare professionals. Over the following 5 years we observed what happened to the subjects within the CBPR framework. Bivariate and stepwise multiple logistic regression analyses were performed to explore the factors associated with the inability to attend a follow-up assessment, 5-year mortality, and institutionalization., Results: Participants who did not attend a follow-up assessment tended to live alone. Being older (>80), living with others, frailty, and the need for rights protection and daily living support were associated with increased mortality. Long-term care insurance certification was strongly associated with institutionalization as a natural consequence of the health-care system. Having dementia and low access to doctors were also positively associated with institutionalization., Conclusions: Older people with cognitive impairment who are living alone are at higher risk of being overlooked by society. To move toward more inclusive communities, the following are recommended: (i) more interventions focusing on older people living alone; (ii) social interventions to detect daily life collapse or rights violations; and (iii) more support to help people with dementia continue living in the community., (© 2022 Japanese Psychogeriatric Society.)

Background: Effective strategies to develop dementia-friendly communities (DFCs) are needed in aging societies. We aimed to propose a strategy to develop DFCs from a Japanese perspective and to evaluate an intervention program that adopted the strategy., Methods: This study implemented a multi-level intervention that emphasized nurturing community social capital in a large apartment complex in the Tokyo metropolitan area in 2017. We offered an inclusive café that was open for extended hours as a place to socialize and a center for activities that included monthly public lectures. Individual consultation on daily life issues was also available for free at the café. Postal surveys were sent out to all older residents aged 70 years and older in 2016 and 2019. With a one-group pre-test and post-test design, we assessed changes in the proportion of older residents who had social interaction with friends and those who were confident about living in the community, even if they were living with dementia., Results: Totals of 2633 and 2696 residents completed the pre and post-intervention surveys, respectively. The mean age of the pre-intervention respondents was 77.4 years; 45.7% lived alone and 7.7% reported living with impaired cognitive function. The proportion of men who had regular social interaction and were confident about living in their community with dementia increased significantly from 38.8 to 44.5% (p = 0.0080) and from 34.1 to 38.3% (p = 0.045), respectively. Similar significant increases were observed in the subgroup of men living with impaired cognitive function, but not in the same subgroup for women., Conclusions: The intervention benefitted male residents who were less likely to be involved in the community's web of social networks at baseline. A strategy to create DFCs that emphasizes nurturing community social capital can form a foundation for DFCs., Trial Registration: This study was retrospectively registered in the University hospital Medical Information Network (UMIN) Clinical Trial Registry (registry number: UMIN000038193 , date of registration: Oct 3, 2019)., (© 2022. The Author(s).)

Objectives: Supporting people suffering from Diogenes Syndrome (DS) is a challenge for geriatric psychiatry. However, there is a lack of knowledge about DS in Japan. Therefore, a systematic longitudinal study to clarify the factors associated with DS and its prognosis was conducted., Methods/design: A retrospective study using data from case records of a municipal psychogeriatric service was conducted. The study population was socially isolated older adults with complex mental health and social care needs who had been referred to the service over 10 years. The participants were stratified into DS and non-DS groups, multivariate analysis was performed to identify factors associated with DS, and survival analysis was performed., Results: Of the 270 participants, 61 with Environmental Cleanliness and Clutter Scale (ECCS) scores >12 were assigned to the DS group, and 209 with ECCS scores ≤12 were assigned to the non-DS group. On multiple logistic regression analysis, significantly more people in the DS group were living alone, had advanced dementia, and had reduced basic activities of daily living (BADL) compared to the non-DS group. Furthermore, survival analysis showed that the DS group had a higher risk of early death than the non-DS group., Conclusions: In the present study, social isolation, living alone, advanced dementia, and reduced BADL were found to be associated with DS. In addition, DS had a high risk of early death. Support for DS must take into account not only mental and social health, but also physical health from an early stage., (© 2021 John Wiley & Sons Ltd.)

Background: The study aim was to identify depressed mood and frailty and its related factors in older people during the coronavirus disease 19 pandemic., Methods: Since 2010, we have conducted questionnaire surveys on all older residents, who are not certified in the long-term care insurance, living in one district of Tokyo municipality. These residents are divided into two groups by birth month, that is those born between April and September and those born between October and March, and each group completes the survey every 2 years (in April and May). Study participants were older residents who were born between April and September and who completed the survey in spring 2018 and in spring 2020, the pandemic period. Depressed mood and frailty were assessed using the Kihon Checklist, which is widely used by local governments in Japan. We had no control group in this study., Results: A total of 1736 residents responded to both surveys. From 2018 to 2020, the depressed mood rate increased from 29% to 38%, and frailty increased from 10% to 16%. The incidence of depressed mood and frailty was 25% and 11%, respectively. Incidence of depressed mood was related to subjective memory impairment and difficulty in device usage, and incidence of frailty was related to being older, subjective memory impairment, lack of emotional social support, poor subjective health, and social participation difficulties., Conclusions: Older people with subjective memory impairment may be a high-risk group during the coronavirus pandemic. Telephone outreach for frail older people could be an effective solution. We recommend extending the scope of the 'reasonable accommodation' concept beyond disability and including older people to build an age-friendly and crisis-resistant community., (© 2021 Japanese Psychogeriatric Society.)

Objective: To identify factors related to decisional conflict among surrogate decision makers for home medical care (HMC) patients. Design: Prospective Cohort Study. Setting/Subjects: For older patients receiving HMC from four different primary care clinics in Japan from January 2016 to June 2017, we studied the family member with the main potential for surrogate decision making. Measurements: At the baseline, surrogates filled out a baseline questionnaire on their characteristics and decision readiness, while the attending doctors provided information about the patients' characteristics. Patient-and-surrogate pairs were tracked for up to six months after the baseline or for three months in the case of death, hospitalization, or admittance to a nursing home. After this tracking, surrogates filled out a follow-up questionnaire on their decision-making experiences, including decisional conflict. Results: Of the original 159 patient-and-surrogate pairs, 121 (76.1%) responded to the follow-up questionnaire. During the follow-up period, 32 patients (26.4% of the patients followed up) died and 69 (57.0%) experienced decision making. Among surrogates who made decisions, the mean score of decisional conflict was 36.2 (standard deviation 14.7), and 43.5% were above the threshold relating to decision delay. Anticipatory guidance and discussion on the patient's care goals at the beginning of HMC were the two variables significantly associated with less decisional conflict of surrogates. Conclusions: Families felt less conflict with surrogate decision making if they had participated in previous discussions with doctors regarding the patients' care goals. Early-stage anticipatory guidance and discussion are a good opportunity for families to prepare for surrogate decision making.

Background: Home medical care (HMC) patients and their families are expected to prepare for end-of-life decision making., Objective: We investigated the decision readiness of HMC patients and their family surrogates., Design: Cross-sectional survey., Setting/subjects: We collected data from dyads, consisting of a HMC patient aged 65 years or older and a family member of the patient, recruited at four Japanese primary care clinics from January 2016 to November 2016., Measurements: Surrogates completed a questionnaire on their sociodemographic and health status and their decision readiness. Primary HMC physicians provided information on their patients., Results: A total of 337 dyads were screened, and 159 were included. The mean age of patients and surrogates was 86 and 64 years, respectively, and 29% of patients were cognitively impaired. Only 1.9% of the patients left written advance directives, and 32% were entrusting all decision making to the doctor or their families. Regarding the surrogate's preferred decision-making role, 21.9% of the surrogates preferred doctors to assume decision-making responsibility. A multivariate analysis revealed that no discussion of care goals (odds ratio [OR] 2.88, 95% confidence interval [CI] 1.02-8.17) and patients having expressed their wishes verbally, including entrusting decision making to others (OR 2.51, 95% CI 1.07-5.89), were associated with surrogates' preference for doctors to have decision-making responsibility., Conclusions: Many patients preferred to entrust the end-of-life decisions to others rather than utilizing advance directives, which made surrogates more dependent on doctors for decision making. Qualified advance care planning is required to promote familial discussion and surrogates' decision readiness.

To examine the kinetics of low doses of perfluoro compounds (PFCs), we administered perfluorohexanoic acid (C6A), perfluorooctanoic acid (C8A), perfluorononanoic acid (C9A) and perfluorooctane sulfonate (C8S) with a single oral dose (50-100 μg/kg BW), and in drinking water at 1, 5, and 25 μg/L for one and three months to male rats; and examined the distribution in the brain, heart, liver, spleen, kidney, whole blood and serum. C6A was very rapidly absorbed, distributed and eliminated from the tissues with nearly the same tissue t 1/2 of 2-3 hr. Considering serum Vd, and the tissue delivery, C6A was mainly in the serum with the lowest delivery to the brain; and no tissue accumulation was observed in the chronic studies as estimated from the single dose study. For the other PFCs, the body seemed to be an assortment of independent one-compartments with a longer elimination t 1/2 for the liver than the serum. The concentration ratio of liver/serum increased gradually from C 0 to a steady state. The high binding capacity of plasma protein may be the reason for the unusual kinetics, with only a very small fraction of free PFCs moving gradually to the liver. Although the tissue specific distribution was time dependent and different among the PFCs, the Vd and k e of each tissue were constant throughout the study. The possibility of extremely high C6A accumulation in the human brain and liver was suggested, by comparing the steady state tissue concentration of this study with the human data reported by Pérez et al. (2013).

Cadmium and lead were measured in liver and kidney samples of 242 Japanese black bears (Ursus thibetanus japonicus) captured from 1999 to 2014 from two local populations in Japan. The median concentration of cadmium was 0.54 (mean: 0.80) mg/kg-w.w. in liver and 7.7 (mean: 11.8) mg/kg-w.w. in kidney. The median concentration of lead was 0.24 (mean: 0.40) and 0.21 (mean: 0.32) mg/kg-w.w. in liver and kidney, respectively. Bears in the Kita-ou local population had higher concentrations of cadmium and lead than those in the Kitakami Highlands local population. No chronological change was observed in cadmium levels in tissues, but the percentage of bears whose lead levels exceeded 0.5 mg/kg-w.w. has been decreasing in recent years. Countermeasures against lead poisoning in wildlife, which were instituted in 2002, may have contributed to the decrease in lead contamination of the Japanese black bear.

8-Hydroxy-2'-deoxyguanosine (8-OHdG) is the most common biomarker of oxidative DNA damage, it is formed by chemical carcinogens and can be measured in any species. Perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA) are suspected genotoxic carcinogens through induction of reactive oxygen species that are responsible for oxidative DNA damage. This study was conducted to investigate the in vitro genotoxicity of PFOA and PFNA in human lymphoblastoid (TK6) cell line. TK6 cells were exposed to PFOA at 0, 125, 250, and 500 ppm and PFNA at 125 and 250 ppm for 2 h. Single cell gel electrophoresis (comet assay) was used to measure DNA damage; at least 50 cells per sample were analyzed using comet Assay Software Project (CASP). 8-OHdG was measured in DNA of exposed cells using high-performance liquid chromatography (HPLC)-mass spectrometry (MS)/MS. Results showed that both PFOA and PFNA induced DNA damage indicated by increased tail length (DNA migration). The level of 8-OHdG was increased in a dose-dependent manner in both PFOA and PFNA exposure. We concluded that PFOA and PFNA induced DNA damage and the biomarker of oxidative DNA damage (8-OHdG) could be measured by HPLC-MS/MS. In addition, PFNA produced high level of 8-OHdG at concentrations lower than PFOA, this may indicate that PFNA is more potent genotoxicant for TK6 cells than PFOA., (© 2014 Wiley Periodicals, Inc.)

With the limited but ongoing usage of perfluorooctane sulfonate (PFOS), the health effects of both PFOS and its alternatives are far from being understood. Long-term potentiation (LTP) was evaluated in rats after exposure to PFOS and its alternatives, aiming to provide some evidence about their potential to affect cognitive ability. Different dosages of PFOS and alternative chemicals, including perfluorohexane sulfonate (PFHxS), perfluorobutane sulfonate (PFBS) and chlorinated polyfluorinated ether sulfonate (Cl-PFAES), were given to rats via acute intracerebroventricular injection. The field excitatory postsynaptic potential (fEPSP) amplitude of the input/output functions, paired-pulse facilitations, and LTP in vivo were recorded. PFOS and its alternatives inhibited LTP in varying degrees, without significant effects on the normal synaptic transmission. In addition, PFHxS and Cl-PFAES exhibited comparable potential to PFOS in disturbing LTP. The results suggested that acute exposure to PFOS and its alternatives impaired the synaptic plasticity by a postsynaptic rather than a presynaptic mechanism. Besides, the fEPSP amplitude of the baseline was reduced by Cl-PFAES but not by other compounds, indicating that Cl-PFAES might act in a different mode. Providing some electrophysiological evidence and the potential mechanism of the neurotoxicity induced by PFOS and its alternatives, the present study addresses further evaluation of their safety and health risks.

Perfluoroalkyl substances (PFASs) are persistent environmental contaminants. Perfluorooctane sulfonate (PFOS) and Perfluorooctanoic acid (PFOA) are representatives of PFASs. Recently, the U.S. Environmental Protection Agency (US EPA) set the health advisory level as 70 parts per trillion for lifetime exposure to PFOS and PFOA from drinking water, based on the EPA's 2016 Health Effects Support Documents. Then, a monograph on PFOA was made available online by the International Agency for Research on Cancer, where the agency classified PFOA as "possibly carcinogenic to humans" (Group 2B). The distinction between PFOS and PFOA, however, may not be easily understood from the above documents. This paper discussed differential toxicity between PFOS and PFOA focusing on neurotoxicity, developmental toxicity and carcinogenicity, mainly based on these documents. The conclusions are as follows: Further mechanistic studies may be necessary for ultrasonic-induced PFOS-specific neurotoxicity. To support the hypothesis for PFOS-specific neonatal death that PFOS interacts directly with components of natural lung surfactant, in vivo studies to relate the physicochemical effects to lung collapse may be required. PFOA-induced DNA damage secondary to oxidative stress may develop to mutagenicity under the condition where PFOA-induced apoptosis is not sufficient to remove the damaged cells. A study to find whether PFOA induces apoptosis in normal human cells may contribute to assessment of human carcinogenicity. Studies for new targets such as hepatocyte nuclear factor 4α (HNF4α) may help clarify the underlying mechanism for PFOA-induced carcinogenicity.

Hair analysis is potentially advantageous in exposure assessment of perfluoroalkyl acids (PFAAs) as a non-invasive method, combined with the ability to reflect long-term exposure. The present study aims to assess the feasibility of using hair as an indicator of PFAA exposure. Adult male and female rats were subchronically exposed to selected PFAAs, including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorooctanesulfonate (PFOS), for 90 days. Hair, serum, and other tissues, including liver, kidney, spleen, lung, brain and heart, as well as the urine and feces excretions, were analyzed for PFAA levels. PFOA/PFNA/PFOS were detected in rat hair in a dose-dependent manner, in the order of PFOS>PFNA>PFOA. Hair PFAA concentrations were higher in male rats than the female rats, except for PFOS at low dose. Moreover, significant positive correlations as well as similar PFAA profiles were observed between hair, serum, and other tissues. Besides, hair PFAAs were negatively correlated with the urinary excretion rate. Although the influencing factors in humans still need further investigation, the results suggested that hair is capable of reflecting PFAA exposure, and could be employed as an alternative exposure bioindicator of PFAAs.

Introduction: According to published information, it has not been determined whether the inhalation of cigarette smoke can induce chromosome aberrations and/or point mutations in mice, though cigarette smoke is clearly carcinogenic to mice. We tested clastogenicity of inhaled cigarette smoke in mouse by a micronucleus test using peripheral erythrocytes. Since it is important to determine the in vivo anti-genotoxic effect against inhaled cigarette smoke to reduce the risk of tobacco carcinogenesis, we also tested in vivo anti-gnotoxic effect against inhaled cigarette smoke of a Connarus extract whose in vitro anti-genotoxic effect was shown., Results: Male ICR mice were exposed for 1 min to a 6-fold dilution of the smoke once a day for up to 14 consecutive days. Although the frequencies of reticulocytes with micronucleus (MNRETs) and erythrocytes with micronuclei (MN erythrocytes) did not increase within 72 h after a single inhalation of cigarette smoke, the frequency of MN erythrocytes increased significantly upon inhalation for 7 and 14 days. When the Connarus extract was fed to mice at >23.7 ppm during the inhalation period of 14 days, frequency of MN erythrocytes was significantly lower than that at 0 ppm. In vitro antioxidant activity of Connarus extract was almost same to that of vitamin C. The antioxidant activity of the Connarus extract might play an important role in its anti-genotoxic effect against cigarette smoke in vivo, like vitamins C., Conclusions: Consecutive inhalation of cigarette smoke is clastogenic to mouse bone marrow as shown by the increased frequency of MN erythrocytes. Also, it was shown the possibility that the Connarus extract reduces the risk of tobacco carcinogenesis.

Extensive human exposure to perfluoroalkyl compounds (PFAA) together with their persistence and various toxicities have arisen increasing concern. A noninvasive method would improve exposure assessment for large population, especially the children susceptible to contaminants. The aim of the study was to assess the use of PFAA measurements in human nails as a biomarker of exposure to PFAAs. Fingernail, toenail, and blood samples were collected from 28 volunteers. The PFAA concentrations were determined by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Six PFAA were detected in nails, with perfluorooctane sulfonate (PFOS) being the compound with the highest median concentration (33.5 and 26.1 ng/g in fingernail and toenail, respectively). Followed was perfluorononanoate (PFNA), with the median concentrations of 20.4 and 16.8 ng/g, respectively, in fingernail and toenail. Other PFAA detected were perfluorooctanoate (PFOA), perfluorodecanoate (PFDA), perfluorododecanoate (PFDoA), and perfluorotetradecanoate (PFTA), with median levels ranging between 0.19 and 8.94 ng/g. PFOS and PFNA concentrations in fingernail significantly correlated with those in serum. Fingernail PFOS and PFNA levels were 2.8 and 24.4 times, respectively, higher than the serum levels. The accumulation of PFAA in nails, together with its advantages in noninvasive sampling and ability of reflecting long-term exposure, made nails PFAA an attractive biomarker of exposure.

A fluorochemical industrial park was built in 2004 in Fuxin, China, for the production of polytetrafluoroethylene (PTFE) and perfluorobutane sulfonate (PFBS). Yet little is known about the distribution of fluorochemicals in the environment and in people living in and around the park. In this study, environmental samples were collected from 22 sites in Fuxin to investigate the extent of perfluorinated compound (PFC) contamination in the environment around the park, and in drinking water from the public water supply system and groundwater in shallow aquifers from private wells near the park. Serum samples were also collected from nonoccupationally exposed residents living in Fuxin to determine the PFC load of local residents. As the dominant contaminant of eight target PFCs, the maximum concentrations of perfluorooctanoic acid (PFOA) in sediment and river water of the River Xi along the industrial park were 48 ng/g dry weight and 668 ng/L, respectively; the highest PFOA concentration in groundwater beneath the park was 524 ng/L; and the PFOA levels in drinking water from the public water supply system ranged between 1.3 and 2.7 ng/L. In human serum, PFOA had the geometric mean at 4.3 ng/mL, ranging from 0.02 to 93 ng/mL. This study serves to document what should be the beginning of a long-term surveillance effort to minimize potential exposure of residents living in Fuxin.

Perfluorooctane sulfonate (PFOS) is one of the persistent organic pollutants distributed widely in the global environment. We have found that a single oral administration of PFOS induced tonic convulsion in mice and rats when a brief ultrasonic stimulus was applied to the animals. The aim of this study is to examine whether the neurotoxicity is caused by subchronic dietary exposure to PFOS. Rats were treated with dietary PFOS at 0, 2, 8, 32 and 128 ppm for 13 weeks. Animals were carefully observed for pharmacotoxic signs and responses to the ultrasonic stimulus applied biweekly. PFOS increased liver weight and decreased food consumption and body weight. PFOS concentrations in the serum, brain, liver and kidney were increased almost proportional to its total dose, although the ratios of PFOS concentrations in tissues to total doses in the group treated with the highest concentration were a little lower. The ranges of relative concentrations in the brain, liver and kidney to serum concentration were 0.13 to 0.24, 2.7 to 6.3 and 0.82 to 1.6, respectively. PFOS alone did not cause any neurotoxic symptoms; however, 5 rats out of 6 showed tonic convulsion in the 6th week when ultrasonic stimulus was applied to the 128 ppm rats with the total PFOS dose of 338 mg/kg. The ultrasonic stimulus did not cause convulsion in the other groups. Histopathological examination including electron microscopic examination could not detect any abnormality in the brain. Because the acute oral dose of PFOS causing the convulsion was 250 mg/kg (Sato et al., 2009), the convulsion induced by PFOS seemed to depend on its total dose regardless of treatment schedule.

To determine the optimum timing of partial hepatectomy (PH) in a previously developed mouse liver micronucleus test (Igarashi and Shimada, 1997), the relation between DNA damage and micronucleus was examined using the in vivo alkaline comet assay and the micronucleus test on the liver of the same individual mouse. Five genotoxic carcinogens, 1-nitropyrene (1-NP) (125 mg/kg), cyclophosphamide (CP) (50 mg/kg), methylmethan sulfonate (MMS) (80 mg/kg), mitomycin C (MMC) (2 mg/kg) and diethylnitrosamine (DEN) (50 mg/kg) were intraperitoneally dosed to each group consisting of 4 male ddY mice. The mice were subjected to PH 3, 8 or 24 hr after dosing of each carcinogen, and comet assay was performed using the removed liver. The regenerated hepatocyte was sampled five days after PH, and the incidence of micronucleus was measured. CP, MMS, MMC and DEN induced DNA damage at 8 and 24 hr after dosing, while 1-NP induced DNA damage only 8 hr after dosing. All five carcinogens induced micronuclei whenever PH was performed. In the case of CP, the peak of DNA damage was 24 hr after dosing and the timing of PH did not remarkably affect the incidence of micronuclei. The other 4 carcinogens showed peak DNA damage at 8 hr and the highest incidence of micronuclei when PH was operated 24 hr after dosing. In conclusion, we are the first to show the relation of induction between DNA damage and micronucleus in the liver from the same mouse, and tentatively showed the optimal timing of PH as 24 hr after dosing.