Can a white nurse get it? 'Reflexive practice' and the non-Indigenous clinician/researcher working with Aboriginal people.

CONTEXT: Reflexivity is crucial for non-Aboriginal researchers working with Aboriginal people. This article describes a process of 'reflexive practice' undertaken by a white clinician/researcher while working with Aboriginal people. The clinician/researcher elicited Aboriginal people's experience of being haemodialysis recipients in rural Australia and their perceptions of their disease and treatment. The aim of this article is to report the methods used during this qualitative project to guide the researcher in conducting culturally appropriate health research with Aboriginal people. The goal of this work was to improve health services, informed and guided by the Aboriginal recipients themselves. The article describes the theory and methods used to develop reflexive skills. It also reports how the clinician/researcher managed her closeness to the topic and participants (some being patients under her care) and the processes used to ensure her subjectivity did not interfere with the quality of research. ISSUES: Three layers of reflexive practice are described: examining self within the research, examining interpersonal relationships with participants, and examining health systems. The alignment of the three 'lenses' used to describe the study is exposed. Complex insider/outsider roles are explored through multiple layers of reflexive practice. Regular journal writing was the primary tool used to undertake this reflexive practice. An Aboriginal advisory group and co-investigators collaborated and assisted the clinician/researcher to scrutinise and understand her positioning within the study. Researcher positioning, power and unequal relationships are discussed. Issues such as victim blaming and the disconnect between clinicians' views about treatment compliance and Aboriginal peoples' prioritisation of family obligations for before treatment are presented. LESSONS LEARNED: Aboriginal patients must negotiate a health services system where racism and victim blaming are institutionalised, but the effect of these on the research relationship can be mitigated through reflexive practice. Using a framework for relational accountability that incorporates respect, responsibility and reciprocity can enable non-Aboriginal clinicians and/or researchers to work effectively with Aboriginal patients. These results may assist clinicians and policy makers develop strategies for improving quality of care.

Pyridinones are not antioxidants as shown by kinetics of free radical autoxidation, but they prevent radical oxidations catalyzed by toxic heavy metals.

Three 2-methyl-3-hydroxypyridinones, 1-methyl-, 1; 1-(4-methoxy)phenyl-, 2; and 1-(4-dimethylamino)phenyl-, 3, were discovered not to possess strong antioxidant properties contrary to literature reports. These pyridinones were not active chain-breaking antioxidants toward peroxyl radicals generated from styrene or methyl oleate initiated by azobis-2-methylpropylnitrile (AIBN) in solution compared to known phenolic antioxidants, 2,2,5,7,8-pentamethyl-6-hydroxychroman (PMHC) or 2,6-di-tert-butyl-4-methoxyphenyl (DBHA). Pyridinone 2 exhibited weak antioxidant activity in cumene, kinh = 1.3 × 10(3) M(-1) s(-1), compared to 2,6-di-tert-butyl-4-methylphenol (BHT), kinh = 4.3 × 10(3) M(-1) s(-1). The pyridinones were not active antioxidants during lipid peroxidation initiated by azobis-2-amidinopropane·2HCl (ABAP) in aqueous-lipid dispersions of 0.50 M sodium dodecyl sulfate (SDS) micelles where 2 did not inhibit peroxidation of methyl oleate at pH 7.0 or 4.0, while BHT exhibited effective suppression of oxygen uptake. In addition, 2 did not exhibit any cooperative antioxidant effect in combination with Trolox during inhibited peroxidation of linoleic acid in micelles. Pyridinones were effective preventative antioxidants in aqueous-lipid dispersions against reactions initiated by heavy metal ions, notably copper; for example, 2 blocked peroxidation of linoleic acid initiated by Cu ions in SDS micelles. In particular, both 2 and 3 were active in preventing the rapid pro-oxidation effects, "spikes", of very rapid oxygen uptake when phenolic antioxidants PMHC or Trolox were added to peroxidations initiated by Cu(2+). A proposal is given to account for such pro-oxidant effects.

PRIME: impact of previous mental health problems on health-related quality of life in women with childbirth trauma.

We investigated the impact of pre-existing mental ill health on postpartum maternal outcomes. Women reporting childbirth trauma received counselling (Promoting Resilience in Mothers' Emotions; n = 137) or parenting support (n = 125) at birth and 6 weeks. The EuroQol Five dimensional (EQ-5D)-measured health-related quality of life at 6 weeks, 6 and 12 months. At 12 months, EQ-5D was better for women without mental health problems receiving PRIME (mean difference (MD) 0.06; 95 % confidence interval (CI) 0.02 to 0.10) or parenting support (MD 0.08; 95 % CI 0.01 to 0.14). Pre-existing mental health conditions influence quality of life in women with childbirth trauma.

Can the fetal fibronectin test be used by remote dwelling pregnant women to predict the onset of labour at term and delay transfer for birth in regional settings?

INTRODUCTION: The closure of rural maternity units in Australia means an increasing number of women are transferred into major centres to await birth. Accurately excluding the onset of labour could delay relocation. The fetal fibronectin (fFN) test is used to predict preterm birth; however, the accuracy of this test for determining impending term birth is unclear. METHODS: 75 women were recruited to this study from two remote maternity units. Eligibility criteria were: aged ≥18 years, singleton pregnancy, 37+0-40+3 weeks (37 weeks to 40 weeks and 3 days gestation) and no indication for induction of labour or caesarean section in next 7 days. The Quikcheck fFN® test was performed at 37 weeks and then repeated at 7 day intervals. Time-to-birth from test date was modelled using linear regression. Logistic regression models estimated odds of birth within 7 days. Separate models considered first and last test results and those at 38 weeks; adjusted for use of lubricant and gestational age. RESULTS: A shorter time-to-birth was found in women with positive compared with negative fFN tests; significant at first fFN test (adjusted mean difference [AMD] 5.4 days, 95% CI 2.0-8.8) and 38 weeks (AMD 5.7 days, 95% CI 2.2-9.2 days). A positive test was also associated with a significant increase in the odds of birthing within 7 days: first fFN test adjusted odds ratio (AOR) 11.0 (95% CI 2.5-48.7), 38 weeks test AOR 14.4 (95% CI 3.4-60.2), last fFN test AOR 8.1 (95% CI 1.6-39.8). However, of women who gave birth within 7 days of testing a significant proportion had a negative fFN result; first fFN test 8/17(47.1%), 38 weeks test 4/14(28.6%) and last fFN test 29/58(50.0%). CONCLUSION: The presence of fFN in cervical secretions was associated with impending term birth but its absence did not reliably exclude the onset of birth. Delaying transfer based on these findings would result in some women birthing in their home communities.

New understanding of the complex structure of knee menisci: implications for injury risk and repair potential for athletes.

Menisci help maintain the structural integrity of the knee. However, the poor healing potential of the meniscus following a knee injury can not only end a career in sports but lead to osteoarthritis later in life. Complete understanding of meniscal structure is essential for evaluating its risk for injury and subsequent successful repair. This study used novel approaches to elucidate meniscal architecture. The radial and circumferential collagen fibrils in the meniscus were investigated using novel tissue-preparative techniques for light and electron microscopic studies. The results demonstrate a unique architecture based on differences in the packaging of the fundamental collagen fibrils. For radial arrays, the collagen fibrils are arranged in parallel into ∼10 µm bundles, which associate laterally to form flat sheets of varying dimensions that bifurcate and come together to form a honeycomb network within the body of the meniscus. In contrast, the circumferential arrays display a complex network of collagen fibrils arranged into ∼5 µm bundles. Interestingly, both types of architectural organization of collagen fibrils in meniscus are conserved across mammalian species and are age and sex independent. These findings imply that disruptions in meniscal architecture following an injury contribute to poor prognosis for functional repair.

Problems measuring community health status at a local level: Papua New Guinea's health information system.

INTRODUCTION: The Papua New Guinea Department of Health monitors the performance of the health system using a computerised national health information system. This article draws on the recent evaluation of a national-wide donor-project community development initiative to highlight the problems of the lack of and disaggregated village health data. This data could be used to monitor health status, health worker performance and intervention impact. METHODS: An extensive outcome evaluation conducted in 2006 used qualitative and quantitative data. The in-depth study covered 10 provinces (50%) and 19 districts (21%), obtaining data from 175 health personnel informal interviews and 77 community focus group discussions. Quantitative data from the health information system were examined for validation of the qualitative findings over a 7 year period (1998-2004). RESULTS: Healthier lifestyle and enhanced social and economic wellbeing were claimed by the community to be the result of the project intervention. The evaluation found village claims of post-project improved physical health, increased use of health services and reduced maternal and child mortality could not be substantiated statistically. Health-centre data failed to provide a complete and accurate assessment of community health status within the national health information system. CONCLUSION: This article highlights problems in evaluating community interventions or local service performance if reliable village-level data is absent. The health information system does not allow reporting of villages separately or the tracking of changes in health status over time according to identifiable villages. Assessing changes in physical health status is not possible without village-level baseline data to measure illness trends and improvements in health in identifiable villages. There is a need for policy changes to occur at national level to prevent loss of aid-post data from the system. Future planning for community health intervention strategies need to include disaggregated village-level baseline data against which to measure changes in community health status over time.

'Closing the Gap': how maternity services can contribute to reducing poor maternal infant health outcomes for Aboriginal and Torres Strait Islander women.

CONTEXT: The reproductive health outcomes for Aboriginal and Torres Strait Islander mothers and infants are significantly poorer than they are for other Australians; they worsen with increasing remoteness where the provision of services becomes more challenging. Australia has committed to 'Overcoming Indigenous Disadvantage' and 'Closing the Gap' in health outcomes. ISSUES: Fifty-five per cent of Aboriginal and Torres Strait Islander birthing women live in outer regional and remote areas and suffer some of the worst health outcomes in the country. Not all of these women are receiving care from a skilled provider, antenatally, in birth or postnatally while the role of midwives in reducing maternal and newborn mortality and morbidity is under-utilised. The practice of relocating women for birth does not address their cultural needs or self-identified risks and is contributing to these outcomes. An evidence based approach for the provision of maternity services in these areas is required. Australian maternal mortality data collection, analysis and reporting is currently insufficient to measure progress yet it should be used as an indicator for 'Closing the Gap' in Australia. LESSONS LEARNED: A more intensive, coordinated strategy to improve maternal infant health in rural and remote Australia must be adopted. Care needs to address social, emotional and cultural health needs, and be as close to home as possible. The role of midwives can be enabled to provide comprehensive, quality care within a collaborative team that includes women, community and medical colleagues. Service provision should be reorganised to match activity to need through the provision of caseload midwives and midwifery group practices across the country. Funding to embed student midwives and support Aboriginal and Torres Strait Islander women in this role must be realised. An evidence base must be developed to inform the provision of services in these areas; this could be through the testing of the Rural Birth Index in Australia. The provision of primary birthing services in remote areas, as has occurred in some Inuit and New Zealand settings, should be established. 'Birthing on Country' that incorporates local knowledge, on-site midwifery training and a research and evaluation framework, must be supported.

A unified call to action from Australian nursing and midwifery leaders: ensuring that Black lives matter.

Nurses and midwives of Australia now is the time for change! As powerfully placed, Indigenous and non-Indigenous nursing and midwifery professionals, together we can ensure an effective and robust Indigenous curriculum in our nursing and midwifery schools of education. Today, Australia finds itself in a shifting tide of social change, where the voices for better and safer health care ring out loud. Voices for justice, equity and equality reverberate across our cities, our streets, homes, and institutions of learning. It is a call for new songlines of reform. The need to embed meaningful Indigenous health curricula is stronger now than it ever was for Australian nursing and midwifery. It is essential that nursing and midwifery leadership continue to build an authentic collaborative environment for Indigenous curriculum development. Bipartisan alliance is imperative for all academic staff to be confident in their teaching and learning experiences with Indigenous health syllabus. This paper is a call out. Now is the time for Indigenous and non-Indigenous nurses and midwives to make a stand together, for justice and equity in our teaching, learning, and practice. Together we will dismantle systems, policy, and practices in health that oppress. The Black Lives Matter movement provides us with a 'now window' of accepted dialogue to build a better, culturally safe Australian nursing and midwifery workforce, ensuring that Black Lives Matter in all aspects of health care.

Reduced mismatch repair of heteroduplexes reveals "non"-interfering crossing over in wild-type Saccharomyces cerevisiae.

Using small palindromes to monitor meiotic double-strand-break-repair (DSBr) events, we demonstrate that two distinct classes of crossovers occur during meiosis in wild-type yeast. We found that crossovers accompanying 5:3 segregation of a palindrome show no conventional (i.e., positive) interference, while crossovers with 6:2 or normal 4:4 segregation for the same palindrome, in the same cross, do manifest interference. Our observations support the concept of a "non"-interference class and an interference class of meiotic double-strand-break-repair events, each with its own rules for mismatch repair of heteroduplexes. We further show that deletion of MSH4 reduces crossover tetrads with 6:2 or normal 4:4 segregation more than it does those with 5:3 segregation, consistent with Msh4p specifically promoting formation of crossovers in the interference class. Additionally, we present evidence that an ndj1 mutation causes a shift of noncrossovers to crossovers specifically within the "non"-interference class of DSBr events. We use these and other data in support of a model in which meiotic recombination occurs in two phases-one specializing in homolog pairing, the other in disjunction-and each producing both noncrossovers and crossovers.

Outcome evaluation of community health promotion intervention within a donor funded project climate in Papua New Guinea.

INTRODUCTION: The Australian Agency for International Development (AusAID) funded Women and Children's Health Project sought to improve the health of women and children throughout Papua New Guinea between 1998 and 2004. The project utilised education, community development and health promotion interventions aimed to increase community support for the health of women and children. METHODS: An outcome evaluation in 2006 investigated the long-term impact of the project using a multi-methods approach and covering 10 selectively sampled provinces, 19 districts and 93 communities. Qualitative data were collected from 175 interviews (national to village level) and 77 community discussions. Quantitative data from national, provincial and district levels were examined to attempt to validate findings. RESULTS: The evaluation found new-health-knowledge initiated changes to lifestyle practices and improved physical health and social and economic well-being in villages where volunteers and staff had been trained. Factors influencing success were a health-motivated person acting as a catalyst for change, empowered leadership through new community governance structures, effective visual tools and village health volunteers linking community and rural health workers. Failure was attributed to poor understanding of community development, limited information sharing, a 'top down' approach to community development and weak community leadership. CONCLUSION: The project's community health interventions improved the interaction between the community and health system, and influenced improved use of maternal and child health services. Evaluation suggests sustainable improvements in health can be achieved through community led and maintained activity.

Pre-existent depression in the 2 weeks before an acute coronary syndrome can be associated with delayed presentation of the heart attack.

BACKGROUND: Depression is common among patients with acute coronary syndrome (ACS). AIM: To examine how depression may alter outcome of ACS. DESIGN: Observational study on how ongoing depression influences the time delay to seeking help and its effects on subsequent treatment compliance after discharge. METHODS: Depression was measured by Beck Depression Inventory (BDI) 2 weeks prior to presentation on consecutive patients with ACS. RESULTS: Of the 276 patients, 81 had BDI > or =10 and 195 had BDI score <10. The time from onset of the predominant symptom to seeking help tended to be longer in those with BDI > or =10 than in those with BDI <10 [180 (IQR 37.5-1042.5) min vs. 120 (IQR 30-735) min, P = 0.099]. Results were similar for the 68 with ST elevation myocardial infarction (MI) [238 (IQR 49-709) min vs. 60 (IQR 20-352) min, P = 0.071]. Each point increase of BDI predicted an approximately 4.2% [95% confidence interval (CI) 0.4-8.0%] increase in the time duration, P = 0.029. On multivariable analysis, the effect of BDI persisted (6.0% increase in duration per each point increase in BDI, 95% CI 2.4-9.7%, P = 0.001). Among the 68 patients who had ST elevation MI, results were similar with an 8.0% (95%CI 1.7-14.7%, P = 0.013) increase in time duration for each unit increase in BDI. Results were also similar when BDI was evaluated as a dichotomous variable. Small differences were observed for subsequent treatment compliance. CONCLUSION: Ongoing depression delays the presentation of ACS.

Pyrroles as antioxidants: solvent effects and the nature of the attacking radical on antioxidant activities and mechanisms of pyrroles, dipyrrinones, and bile pigments.

The absolute rate constants, k(inh), and stoichiometric factors, n, of pyrroles, 2-methyl-3-ethylcarboxy-4,5-di-p-methoxyphenylpyrrole, 6, 2,3,4,5-tetraphenylpyrrole, 7, and 2,3,4,5-tetra-p-methoxyphenylpyrrole, 8, compared to the phenolic antioxidant, di-tert-butylhydroxyanisole, DBHA, during inhibited oxidation of cumene initiated by AIBN at 30 degrees C gave the relative antioxidant activities (k(inh)) DBHA > 8 > 7 > 6 and n = 2, whereas in styrene, 8 > DBHA. These results are explained by hydrogen atom transfer, HAT, from the N-H of pyrroles to ROO(*) radicals. The k(inh) values in styrene of dimethyl esters of the bile pigments of bilirubin ester (BRDE), of biliverdin ester (BVDE), and of a model compound (dipyrrinone, 1) gave k(inh) in the order pentamethylhydroxychroman (PMHC) >> BRDE > 1 > BVDE. These antioxidant activities for BVDE and the model compound, 1, and PMHC dropped dramatically in the presence of methanol due to hydrogen bonding at the pyrrolic N-H group. In contrast the k(inh) of BRDE increased in methanol. We now show that pyrrolic compounds may react by HAT, proton-coupled electron transfer, PCET, or single electron transfer, SET, depending on their structure, the nature of the solvent, and the attacking radical. Compounds BVDE and 1 react by the HAT or PCET pathway (HAT/PCET) in styrene/chlorobenzene with ROO(*) and with the DPPH(*) radical in chlorobenzene according to N-H/N-D kH/kD of 1.6, whereas the DKIE with BRDE was only 1.2 with ROO(*). The antioxidant properties of polypyrroles of the BVDE class and model compounds (e.g., 1) are controlled by intramolecular H bonding which stabilizes an intermediate pyrrolic radical in HAT/PCET. According to kinetic polar solvent effects on the monopyrrole, 8, and BRDE, which gave increased rates in methanol, some pyrrolic structures are also susceptible to SET reactions. This conclusion is supported by some calculated ionization potentials. The antioxidant mechanism for BRDE with peroxyl radicals is described by the PCET reaction. Experiments using the 2,6-di-tert-butyl-4-(4'-methoxyphenyl)phenoxyl radical (DBMP(*)) showed this to be a better radical to monitor HAT activities in stopped-flow kinetics compared to the use of the more popular DPPH(*) radical.

Evaluation of RIDA®GENE norovirus GI/GII real time RT-PCR using stool specimens collected from children and adults with acute gastroenteritis.

BACKGROUND: Norovirus is the leading cause of epidemic and sporadic acute gastroenteritis (AGE) in the United States. Widespread prevalence necessitates implementation of accurate norovirus detection assays in clinical diagnostic laboratories. OBJECTIVE: To evaluate RIDA®GENE norovirus GI/GII real-time RT-PCR assay (RGN RT-PCR) using stool samples from patients with sporadic AGE. STUDY DESIGN: Patients between 14 days to 101 years of age with symptoms of AGE were enrolled prospectively at four sites across the United States during 2014-2015. Stool specimens were screened for the presence of norovirus RNA by the RGN RT-PCR assay. Results were compared with a reference method that included conventional RT-PCR and sequencing of a partial region of the 5'end of the norovirus ORF2 gene. RESULTS: A total of 259 (36.0%) of 719 specimens tested positive for norovirus by the reference method. The RGN RT-PCR assay detected norovirus in 244 (94%) of these 259 norovirus positive specimens. The sensitivity and specificity (95% confidence interval) of the RGN RT-PCR assay for detecting norovirus genogroup (G) I was 82.8% (63.5-93.5) and 99.1% (98.0-99.6) and for GII was 94.8% (90.8-97.2) and 98.6% (96.9-99.4), respectively. Seven specimens tested positive by the RGN-RT PCR that were negative by the reference method. The fifteen false negative samples were typed as GII.4 Sydney, GII.13, GI.3, GI.5, GI.2, GII.1, and GII.3 in the reference method. CONCLUSIONS: The RGN RT-PCR assay had a high sensitivity and specificity for the detection of norovirus in stool specimens from patients with sporadic AGE.

What are the effects of distance management on the retention of remote area nurses in Australia?

INTRODUCTION: Australian remote area nurses (RANs) are specialist advanced practice nurses. They work in unique, challenging and sometimes dangerous environments to provide a diverse range of healthcare services to remote and predominantly Aboriginal communities. There is an emerging skills gap in the remote nursing workforce as experienced and qualified RANs leave this demanding practice. There is a shortage of new nurses interested in working in these areas, and many of those who enter remote practice leave after a short time. Distance management was examined in order to gain a better understanding of its effects on the retention of RANs in the Australian states of Northern Territory (NT), Western Australia (WA) and South Australia (SA). Distance management in this context occurs when the health service's line management team is located geographically distant from the workplace they are managing. METHODS: The study used a mixed method design, with a combination of anonymous surveys and interviews conducted by telephone and face to face. Qualitative and quantitative data were collected. The data were thematically analysed and basic descriptive statistics were also used. All RANs who worked in government and other non-Aboriginal controlled remote health services in NT, SA and WA were included in the sample. Sixty-one RANs (anonymous survey, 55% response rate) and 26 ex-RANs (telephone interview) participated in the research. The ex-RANs were sampled using a snowball technique where interviewees recommended former colleagues for interview. Nine nursing executives with expertise in distance management of remote health services also contributed (face-to-face interview), and they are referred to as 'the experts'. RESULTS: Respondents expressed a dichotomy in their reactions to remote area nursing. On one hand, they expressed a strong sense of pleasure and satisfaction in the nature of their work; while, on the other, they expressed dissatisfaction with aspects of infrastructure, support and management practices. Positive aspects included autonomy of practice, working in a small team, cross-cultural practice, and the beauty and isolation of the setting. Negative aspects included poor orientation, high stress, inadequate resources, poor systems, unrealistic expectations from communities and managers leading to excessive workload, and perceived lack of support from management. The greatest negative issue raised was poor handling of leave replacement, where RANs on leave were not replaced with appropriately qualified and skilled nurses. Respondents noted a frequent change in managers, and reported that the lack of stability in management contributed to lack of support for both RANs and their managers. Lack of support from managers was frequently cited as a main cause for ex-RANs leaving their employment. Despite this, almost all respondents indicated a willingness to remain in the remote workforce if possible. Experts noted that where management was dysfunctional, RAN retention rates fell. They also acknowledged the need for good communication, interpersonal skills, availability of staff development, leave, relief staff, feedback, debriefing, professional support and working conditions. Experts believed managers should make use of available and emerging technology to communicate with RANs, and work to improve RANs' understanding of the role of the management team. CONCLUSIONS: Remote Australian Aboriginal communities are mainly served by RANs in a health system that is sometimes ill-equipped and at times poorly managed. The theme of a second-class health system being serviced by RANs who felt they were treated as second-class health practitioners appeared throughout the data. Poor distance management practices may contribute to the high turnover of staff in remote Australia. Retention of RANs may increase with better managerial practices, such as effective communication and leadership, staffing replacement and leave, prompt attention to infrastructure issues, and staff development and appraisal. These are the keys to ensuring that RANs feel supported and valued. Remote area nursing is a rewarding career and, with systemic support, RANs may stay longer in remote practice.

Partitioning and antioxidant action of the water-soluble antioxidant, Trolox, between the aqueous and lipid phases of phosphatidylcholine membranes: 14C tracer and product studies.

The water-soluble antioxidant, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic (Trolox), (4-14C)-labelled, was used to trace its location in the aqueous and lipid phases of liposomes. Trolox was found to partition 20 to 25% into the lipid phase of multilamellar (MLV) and 38-46% into the lipid phase of unilamellar (ULV) egg lecithin liposomes. Trolox and its oxidation products partition readily (40%) into the lipid phase of dilinoleoylphosphatidylcholine (DLPC) MLV liposomes during inhibited peroxidation, thermally initiated by azo-bis(2,4-dimethylvaleronitrile) (ADVN). The time-course of the consumption of Trolox during peroxidation of DLPC liposomes, initiated by ADVN, was followed by separation and analyses of [4-14C]Trolox and its oxidation products. Such studies showed that the consumption of Trolox followed the profile of the inhibition of oxygen uptake. This indicates that Trolox can be used in quantitative studies of membrane peroxidation; for example, to measure the rate of chain initiation (Ri). The product distribution of hydroperoxides, the 9- and 13-cis,trans (c,t) and trans,trans (t,t) isomers, formed during inhibited peroxidation of linoleate, in DLPC and methyl linoleate in dimyristoyl PC (DMPC) liposomes was determined by HPLC of the derived hydroxy methyl esters. The c,t/t,t (kinetic/thermodynamic) ratios were related to the antioxidant activity of the inhibitors. Both Trolox and alpha-tocopherol (vitamin E) gave relatively high initial c,t/t,t ratios (6.6 and 7.1) during inhibited peroxidation of DLPC, initiated by water-soluble azo-bis(2-amidinopropane.HCl) (ABAP). High initial c,t/t,t ratios (6.2) were also observed for alpha-tocopherol-inhibited peroxidation of DLPC liposomes, initiated by lipid-soluble ADVN. On the other hand, the combination of Trolox with ADVN-initiated peroxidation of DLPC or of methyl linoleate in DMPC gave relatively low initial c,t/t,t ratios of 3.5 and 1.3. These results are interpreted in terms of the relative hydrogen atom donating ability of the antioxidants and the homogeneity of the system used. The 9/13 ratios of hydroperoxides were constant (0.9 to 1.0) in all experiments and did not give evidence for preferential trapping by Trolox of peroxyls at the 9-position.

The relative contributions of vitamin E, urate, ascorbate and proteins to the total peroxyl radical-trapping antioxidant activity of human blood plasma.

The Total (Peroxyl) Radical-trapping Antioxidant Parameter (TRAP) of six freshly prepared human plasma samples and 45 frozen plasma samples has been determined. It is shown that contributions from urate (35-65%), plasma proteins (10-50%), ascorbate (0-24%) and vitamin E (5-10%) to TRAP account for all of the peroxyl radical-trapping antioxidant activity in the majority of the samples. The changes in concentrations of the plasma antioxidants during peroxyl radical attack show that the first line of defense is provided by the plasma sulfhydryl groups, even urate being spared during the initial stages of the reaction. The modes of action of all of these plasma antioxidants and possible interactions between them are discussed, with particular emphasis on the abilities of the water-soluble antioxidants to regenerate or spare the only lipid-soluble antioxidant, vitamin E.

The efficiency of antioxidants delivered by liposomal transfer.

Phenolic antioxidants of the hydroxychroman class, alpha-tocopherol (alpha-TOC) and 2,2,5,6,7-pentamethyl-6-hydroxychroman (PMHC), and the hindered phenols 2,3-dihydro-5-hydroxy-2,2,4-trimethylnaphtho[1,2-b]furan (NFUR), 2,6-di-tert-butyl-4-methoxyphenol (DBHA), and 2,6-di-tert-butyl-4-methyl phenol (BHT), were delivered into oxidizable (ACCEPTOR) liposomes of dilinoleoylphosphatidylcholine (DLPC) or 1-palmitoyl-2-linoleoyl-phosphatidylcholine (PLPC) from saturated DONOR liposomes of dimyristoylphosphatidylcholine (DMPC) by liposomal transfer. The antioxidant activities, k(inh), by the inhibited oxygen uptake method were compared with the k(inh)s determined when the antioxidants were introduced into the liposomes by coevaporation from organic solvents. The peroxidations were initiated using either thermal initiators, water-soluble azo-bis-amidinopropane hydrochloride (ABAP), lipid-soluble azo-bis-2,4-dimethylvaleronitrile (ADVN) and di-tert-butylhyponitrite (DBHN), or the photoinitiator benzophenone. The antioxidants PMHC, NFUR, DBHA, and BHT transferred rapidly between liposomes, but several hours of incubation were needed to transfer alpha-TOC. The average k(inh)s in liposomes, in the relative order NFUR approximately DBHA > PMHC > BHT approximately alpha-TOC, were markedly lower than known values in organic solvent. k(inh) values in liposomes appear to be controlled by effects of hydrogen bonding with water and by restricted diffusion of antioxidants, especially in the case of alpha-TOC. Product studies of the hydroperoxides formed during inhibited oxygen consumption were carried out. The cis,trans/trans,trans (c,t/t,t) product ratios of the 9- and 13-hydroperoxides formed from PLPC during inhibited peroxidation by PMHC were similar for both the coevaporated and liposomal transfer procedures. The c,t/t,t ratio for the same concentration of alpha-TOC, 1.52, compares to a value of 1.69 for PMHC at the start of the inhibition period. The higher c,t/t,t ratio observed for NFUR in DLPC, which varied between values of 7.0 at the start of the inhibition to about 1.8 after the break in the induction period, is a reflection of the increased hydrogen atom donating ability of the antioxidant plus the increased concentration of oxidizable lipid provided by DLPC.

Cholesterol: free radical peroxidation and transfer into phospholipid membranes.

Cholesterol, when sequestered in saturated liposomes of dimyristoylphosphatidylcholine (DMPC) or dipalmitoylphosphatidylcholine (DPPC), undergoes peroxidation thermally initiated either by a lipid-soluble or a water-soluble azo initiator and in both cases the reaction is inhibited effectively by the water-soluble antioxidant, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylate (Trolox). Quantitative kinetic methods of autoxidation show that the oxidizability, kp/(2kt)1/2 (where kp and 2kt are the rate constants of radical chain propagation and termination, respectively) of cholesterol in DMPC or DPPC multilamellar liposomes, where kp/(2kt)1/2 is 3.0.10(-3) to 4.3.10(-3) M-1/2 s-1/2 at 37-45 degrees C, is similar to that measured in homogeneous solution in chlorobenzene, where kp/(2kt)1/2 is 3.32.10(-3). However, its oxidizability in smaller unilamellar vesicles of DMPC or DPPC increases by at least 3-times that measured in multilamellar systems. Autoxidation/antioxidant methods show that cholesterol partitions directly from the solid state into DMPC or DPPC liposomes by shaking and this is confirmed by 31P and 2H quadrupole NMR spectra of deuterated cholesterol when membrane bound. Analytical studies indicate that up to 21 mol% cholesterol will partition into the membranes by shaking.

Cytotoxicity and cytoprotective activity in naphthalenediols depends on their tendency to form naphthoquinones.

We consider the cytotoxicity and the protection against oxidative stress for members of the naphthalenediol family and the known antioxidant epigallocatechin gallate (EGCG). Compounds include the 1,2-naphthalenediol (1,2-ND), 1,4-ND, 2,3-ND, 1,8-ND, and 1,4-dipropyl-2,3-naphthalenediol (DPND). The cell line is an adherent clone of rat pheochromocytoma (PC12-AC). Oxidative stress was induced by the peroxyl radical generator AAPH. The relative order of cytotoxicity was 1,4-ND > 1,2-ND > DPND > 2,3-ND > 1,8-ND > EGCG, with EC(50)'s of 15, 40, 160, >250, >250, >>250 muM, respectively. Despite their high toxicity, both 1,4-ND and 1,2-ND showed narrow zones of protective behavior whereas DPND, 2,3-ND and 1,8-ND and especially EGCG showed an extended protective range. The total protection obtained for the combination of cells/oxidative stressor/protective compounds (PC12-AC/AAPH/naphthalenediols) was defined by an integrated measure, the cytoprotective area (CPA). We relate the observed cytotoxicity and CPA to the different electronic structures of the naphthalenediols, characterized by the first and second bond dissociation enthalpies and the pK(a)'s for parent (diol) and semiquinone. Since the 2,3- and 1,8-naphthalenediols do not form quinones, their cytotoxicity is much lower than for the compounds which do. Thus selected members of the naphthalenediol family show promise as antioxidants.

Factors associated with duration of survival in Alzheimer's disease.

With a computerized data base, a data retrieval system, and a computer program using the actuarial method of life-table analysis, we compared survival rates in different subgroups of patients with dementia of the Alzheimer type (DAT; n = 199). Men (n = 71) had a shorter duration of survival than women (n = 128), with 500-day survival (mean +/- SEM) 84 +/- 5% vs. 99 +/- 3%, p less than 0.01; 1000-day survival 49 +/- 10% vs. 96 +/- 8%, p less than 0.001; 50% survival 1000 days vs. 1550 days. Patients younger than 65 years at onset had a decreased relative duration of survival compared with patients over 65 at onset, suggesting a more malignant course. Patients with a longer duration of illness tended to die sooner, but this effect was not statistically significant. The Kahn-Goldfarb mental-status quotient was not a predictor of survival. Patients with high Haycox behavioral score (greater than 20; n = 50), indicating more severe behavioral impairment, had lower survival rates at 500 days than patients with low scores (less than 12; n = 65) (80 +/- 6% vs. 95 +/- 3%, p less than 0.05). Hachinski ischemic score, measuring signs and symptoms of vascular disease, had no correlation with survival. Factors associated with decreased duration of survival in DAT include male sex, presenile onset, and increased severity of behavioral impairment.