Role of nuclear receptor-independent pathways in the mechanism of action of peroxisome proliferators

Peroxisome proliferators are a structurally diverse group of chemicals that are non-genotoxic hepatocarcinogens in rodents. For decades there has been controversy surrounding these compounds because of the uncertainty of human risk, high potential for exposure and insufficient understanding of their mechanism of action in rodents. Two key molecular pathways are thought to be important in the mode of action: activation of the nuclear receptor PPARα in liver parenchymal cells, and activation of Kupffer cells, which do not express PPARα. In hepatocytes, PPARα mediates peroxisome induction, increased fatty acid metabolism and alterations in gene expression. Furthermore, activation of the PPARα is required for peroxisome proliferator-induced carcinogenesis. In Kupffer cells, acute administration of peroxisome proliferators stimulates oxidant production and mitogenic cytokine release, as well as activation of NFκB, a transcription factor implicated in cell proliferation and apoptosis. The role that Kupffer cells play in chronic effects of peroxisome proliferators is not yet known. We hypothesized that peroxisome proliferators activate Kupffer cells to produce oxidants that may be involved in oxidative cellular damage, and that mediate cytokine production. The cytokines stimulate proliferative and anti-apoptotic effects of these chemical agents. To test this hypothesis, we first evaluated whether peroxisome proliferators cause a sustained increase in reactive oxygen species (ROS) in rodent liver. In vivo measurements of ROS in PPARα -null or NADPH oxidase-deficient (p47phox-null) mice following sub-acute treatment with di-(2-ethylhexyl) phthalate (DEHP) or 4-chloro-6-(2,3- xylidino)-2-pyrimidinylthio acetic acid (WY-14,643), both model peroxisome proliferators revealed a persistent elevation in oxidant production with parenchymal cells, not Kupffer cells as the primary molecular source. Next, the role of Kupffer cell oxidants and PPARα in mediating proliferative, apoptotic and oxidative stress responses was assessed. Findings from a five month WY-14,643 feeding study suggest that NADPH oxidase is not required for increased hepatocellularl proliferation or DNA damage, but may be important to antiapoptotic effects. Finally, gene expression profiling revealed a temporal shift from Kupffer cell to PPARα-dependence of peroxisome proliferator-induced changes. Collectively, our findings demonstrate that Kupffer cell-mediated events play an important role in early responses, but are short-lived and likely not required for chronic effects of peroxisome proliferators, including hepatocarcinogenesis

Health-Related Quality of Life among Artisanal Fisherwomen/Shellfish Gatherers: Lower than the General Population

Quality of life is an indicator of how well one perceives that he/she is functioning physically and mentally. The aim of this paper is to determine the health-related quality of life (HRQOL) of artisanal fisherwomen/shellfish gatherers from the Saubara municipality in Bahia, Brazil in comparison to the general population. A structured questionnaire was administered to a sample of 209 artisanal fisherwomen selected at random. The HRQOL questionnaire, known as the 36-Item Short-Form Health Survey version 1 (SF-36v01), was also used, having been translated and verified cross-culturally for the Brazilian population. Sociodemographic, lifestyle and comorbidity information was also collected. Chronic diseases and indicators of musculoskeletal disorders (MSDs) were self-reported. The study population consisted primarily of individuals between 30 and 45 years of age (78%), of self-classified races black or brown (96.2%), with no more than an elementary school education (77%) and married (64.6%). In all the SF-36v01 dimensions, the values in the sample were lower than in the general population of Brazil, which was used as the reference population. In the “Physical Health” domain (Physical Functioning; Physical Role Limitations; Bodily Pain; General Health Perception) a tendency toward a lower health-related quality of life was observed among those who were older, had a lower education level, and had a prevalence of MSDs, hypertension or arthritis. The interference of health conditions linked to the fisherwomen’s work activities may contribute to lower HRQOL in all analyzed aspects, in comparison to the general population. In light of these findings, public health policies must consider these informal workers who contribute greatly to Brazil’s economy and food system

Artisanal fisherwomen/shellfish gatherers: analyzing the impact of upper limb functioning and disability on health-related quality of life

Abstract The aim is to analyze upper limb functioning and disability, and its association with health-related quality of life among artisanal fisherwomen from Bahia, Brazil. Cross-sectional epidemiological study was conducted with a sample of 209 fisherwomen. Structured questionnaires were used for socio-demographic and comorbidity information, as well as the instruments Disabilities of the Arm, Shoulder and Hand (DASH) and Short-Form Healthy Survey (SF-36) respectively, to evaluate the upper limbs and health-related quality of life. The results demonstrated that the presence of musculoskeletal disorders in the upper limbs directly affects the values of the DASH instrument and the SF-36v01 questionnaire scores, while also generating a negative correlation between the DASH and SF-36v01. The varying functioning abilities, pain and social aspects negatively affect upper limb function, and the daily activities and work of fisherwomen. The presence of chronic disease and the absence of intervention and rehabilitation for these professionals, that could produces, in a long-term, cases of disability

Health-Related Quality of Life among Artisanal Fisherwomen/Shellfish Gatherers: Lower than the General Population

Quality of life is an indicator of how well one perceives that he/she is functioning physically and mentally. The aim of this paper is to determine the health-related quality of life (HRQOL) of artisanal fisherwomen/shellfish gatherers from the Saubara municipality in Bahia, Brazil in comparison to the general population. A structured questionnaire was administered to a sample of 209 artisanal fisherwomen selected at random. The HRQOL questionnaire, known as the 36-Item Short-Form Health Survey version 1 (SF-36v01), was also used, having been translated and verified cross-culturally for the Brazilian population. Sociodemographic, lifestyle and comorbidity information was also collected. Chronic diseases and indicators of musculoskeletal disorders (MSDs) were self-reported. The study population consisted primarily of individuals between 30 and 45 years of age (78%), of self-classified races black or brown (96.2%), with no more than an elementary school education (77%) and married (64.6%). In all the SF-36v01 dimensions, the values in the sample were lower than in the general population of Brazil, which was used as the reference population. In the “Physical Health” domain (Physical Functioning; Physical Role Limitations; Bodily Pain; General Health Perception) a tendency toward a lower health-related quality of life was observed among those who were older, had a lower education level, and had a prevalence of MSDs, hypertension or arthritis. The interference of health conditions linked to the fisherwomen’s work activities may contribute to lower HRQOL in all analyzed aspects, in comparison to the general population. In light of these findings, public health policies must consider these informal workers who contribute greatly to Brazil’s economy and food system

Prevalence and Work-Related Factors Associated with Lower Back Musculoskeletal Disorders in Female Shellfish Gatherers in Saubara, Bahia-Brazil

Lower back musculoskeletal disorders (MSDs) are an important public health problem and the leading cause of disability worldwide, but with yet unknown prevalence among shellfish gatherers. To investigate the prevalence and work-related factors associated with lower back MSD in a population of female shellfish gatherers, an epidemiological cross-sectional study was carried out in Saubara, Bahia-Brazil, in 2013. The Brazilian version of the Job Content Questionnaire (JCQ) and the Nordic Musculoskeletal Questionnaire (NMQ), in addition to a questionnaire containing the physical demands adapted to the artisanal work, were applied to a random sample of 209 female shellfish gatherers. The prevalence of lower back MSD was 72.7%. Using multivariate logistic regression, the shellfish gatherers who had worked for more than 26 years in the activity showed a prevalence of 1.22 (95% CI: 1.04–1.44) times higher compared to those unexposed. Lower back MSD was 1.24 (95% CI: 1.08–1.42) times higher among those more exposed to work sitting with trunk flexion. Those performed manual handling and muscle force with the arms had a prevalence ratio of 1.18 (95% CI: 1.01–1.39). These results show the need for greater awareness of health and social welfare factors impacting workers in small-scale fisheries and will promote the elaboration of health care policies for this occupational class

Artisanal fisherwomen/shellfish gatherers: analyzing the impact of upper limb functioning and disability on health-related quality of life

<div><p>Abstract The aim is to analyze upper limb functioning and disability, and its association with health-related quality of life among artisanal fisherwomen from Bahia, Brazil. Cross-sectional epidemiological study was conducted with a sample of 209 fisherwomen. Structured questionnaires were used for socio-demographic and comorbidity information, as well as the instruments Disabilities of the Arm, Shoulder and Hand (DASH) and Short-Form Healthy Survey (SF-36) respectively, to evaluate the upper limbs and health-related quality of life. The results demonstrated that the presence of musculoskeletal disorders in the upper limbs directly affects the values of the DASH instrument and the SF-36v01 questionnaire scores, while also generating a negative correlation between the DASH and SF-36v01. The varying functioning abilities, pain and social aspects negatively affect upper limb function, and the daily activities and work of fisherwomen. The presence of chronic disease and the absence of intervention and rehabilitation for these professionals, that could produces, in a long-term, cases of disability.</p></div