Low blood glutathione levels in healthy aging adults.

The objective of this investigation was to test the hypothesis that blood glutathione levels are lower in aging human subjects as previously found in blood and tissues of standard rodent models of aging. Thus a study was conducted with 39 men and 130 women, 20 to 94 years old, who were selected by the criteria of being ambulatory, healthy, and free from diabetes mellitus, thyroid disease, anemias, and cancer. The reference group was comprised of the 20- to 39-year-old subjects, whose blood glutathione levels were 547 +/- 53.5 micrograms/10(10) erythrocytes (mean +/- SD) for 40 individuals and defined the reference range (95% confidence limits) of 440 to 654. Based on the 440 micrograms/10(10) erythrocyte cutoff, the incidence of low blood glutathione content in the older subjects increased significantly, particularly in the 60- to 79-year-old group. Their glutathione levels were 452 +/- 86.8 micrograms/10(10) erythrocytes, 17% lower than the reference group (p < 0.001). These findings demonstrate an increased incidence of low glutathione levels in apparently healthy elderly subjects, who thus may be at risk because of a decreased capacity to maintain many metabolic and detoxification reactions mediated by glutathione.     

Effects of per- and polyfluorinated compounds on adult rat testicular cells following in vitro exposure

Testicular toxicity is observed following exposure of rats to per- and polyfluorinated compounds (PFCs). Such compounds were also shown to induce oxidative stress and changes in ABC efflux transporters e.g. P-gp, implying two mechanisms which may contribute to testicular toxicity. We studied the toxicity of four PFCs (PFOA, PFNA, 8:2 FTOH and 6:2 FTOH) on primary rat testicular cells. DNA damage was studied by the comet assay including Fpg enzyme treatment to detect oxidative lesions. The levels of the ABC efflux transporters Bcrp1, Oat2 and P-gp were studied by real-time RT-PCR or flow cytometry. A PFNA associated increase in DNA SSBs was attributed to a subpopulation of moderately damaged cells possibly associated with cytotoxicity. No significant increase in oxidative DNA damage was measured for any of the PFCs. Expression levels of ABC efflux transporters suggest that PFCs may increase expression levels of the P-gp protein and the Oat2 gene.     

Gastrointestinal symptoms are associated with hypothalamic-pituitary-adrenal axis suppression in healthy individuals

OBJECTIVE: The brain-gut axis has been proposed to influence symptoms in irritable bowel syndrome (IBS). In animal studies corticotropin-releasing hormone (CRH) challenge has been associated with decreased upper gastrointestinal motility and increased colonic motility. The purpose of this study was to investigate the association between gastrointestinal symptoms and the effect of CRH on the hypothalamic-pituitary-adrenal (HPA) axis using a weight-adjusted low-dose dexamethasone test in a group of healthy individuals (n = 157). MATERIAL AND METHODS: Pre- and post-dexamethasone morning serum cortisol was analysed. All participants completed questionnaires regarding symptoms of IBS (GSRS-IBS (Gastrointestinal Symptom Rating Scale-IBS) and symptoms of anxiety and depression (HADS (Hospital Anxiety and Depression Scale)). After exclusions, 124 subjects were available for analysis (F/M: 60/64, mean age 55.8 years, SD 15.4, range 21-80 years). RESULTS: A positive correlation was found between the GSRS-IBS score and HADS score (rs =0.36; p <0.001). There was no linear correlation between either pre- (rs = 0.145; p = 0.11) or post-dexamethasone cortisol levels (rs =0.087; p =0.337) and GSRS-IBS scores. By subgrouping the subjects at the lower and higher 25th percentiles of their post-dexamethasone morning cortisol levels, we found a trend towards a higher GSRS-IBS score (median 7.0 versus 5.0; p =0.069) (multivariate adjusted OR 2.6; CI 0.80-8.3) and a significantly higher diarrhoea score (median 2 versus 0; p = 0.021) (multivariate adjusted OR 5.7; CI 1.5-22), and a higher early satiety score (p=0.008) (multivariate adjusted OR 6.7; CI: 1.9-23) in the subjects with high post-dexamethasone cortisol levels (low HPA suppression) compared with the subjects with intermediate post-dexamethasone cortisol levels. Furthermore, individuals with low post-dexamethasone cortisol levels (high HPA suppression) showed a significant, higher score for diarrhoea (median 2.0 versus 0; p =0.010) (multivariate adjusted OR 6.1; CI 1.8-20) and early satiety (p=0.076) (multivariate adjusted OR 3.2; CI 1.0-10) compared with those with intermediate cortisol levels. CONCLUSIONS: A trend toward a non-linear relationship between IBS-like symptoms and post-dexamethasone cortisol levels was observed in healthy individuals, with significantly more symptoms of diarrhoea and early satiety in individuals with high or low post-dexamethasone cortisol levels in comparison with those with intermediate post-dexamethasone cortisol levels.     

Aboriginal community-controlled art centres: Keeping Elders strong and connected. Articulating an ontologically situated,intergenerational model of care

Objective

To articulate how Aboriginal community-controlled art centres support the role of Elders and older people within an ontologically situated, intergenerational model of care.

Methods

In this paper, we draw on stories (data) generated through interviews involving 75 people associated with three Aboriginal community-controlled art centres and field notes taken during a Participatory Action Research (PAR) study. The study was undertaken in collaboration with three community-controlled art centres and two aged care providers over almost 4 years, in diverse Indigenous sovereignties, all located in geographically remote Australian locations.

Results

Engaging with decolonising and Indigenous theoretical frameworks, our analysis identified three interwoven meta-themes. These include connection to law and culture; purpose; and healing. Each theme had important subthemes, and all were central to upholding the well-being of older people and their families, as well as the art centre workforce, Country, and their broader communities.

Conclusions

Our analysis articulates an ontologically situated model of care within Aboriginal community-controlled art centres. The model sees that older people receive care from art centres and provide care to each other, to younger generations, to art centre staff, to Country, and to their broader communities. In this model, those in receipt of care, many of whom are older people, art centre directors, and important artists, govern how care is conceptualised and delivered.     

SOCS1 deficiency results in accelerated mammary gland development and rescues lactation in prolactin receptor–deficient mice

Prolactin is essential for proliferation and differentiation of the developing mammary gland. We have explored a role for Suppressor of Cytokine Signaling 1 (SOCS1) as a modulator of the prolactin response using mice deficient in SOCS1, which were rescued from neonatal death by deletion of the Interferon gamma (IFN gamma) gene. SOCS1(-/-)/IFN gamma(-/-) mice exhibited accelerated lobuloalveolar development in the mammary gland during late pregnancy and precocious lactation. Significantly, the lactogenic defect in prolactin receptor heterozygous females could be rescued by deletion of a single SOCS1 allele. These findings establish a role for SOCS1 as a negative regulator of prolactin signaling and suggest that SOCS1 is required for the prevention of lactation prior to parturition.