High Dietary Phosphorus Is Associated with Increased Breast Cancer Risk in a U.S. Cohort of Middle-Aged Women.

Research has shown that high amounts of dietary phosphorus that are twice the amount of the U.S. dietary reference intake of 700 mg for adults are associated with all-cause mortality, phosphate toxicity, and tumorigenesis. The present nested case-control study measured the relative risk of self-reported breast cancer associated with dietary phosphate intake over 10 annual visits in a cohort of middle-aged U.S. women from the Study of Women's Health Across the Nation. Analyzing data from food frequency questionnaires, the highest level of daily dietary phosphorus intake, >1800 mg of phosphorus, was approximately equivalent to the dietary phosphorus levels in menus promoted by the United States Department of Agriculture. After adjusting for participants' energy intake, this level of dietary phosphorus was associated with a 2.3-fold increased risk of breast cancer incidence compared to the reference dietary phosphorus level of 800 to 1000 mg, which is based on recommendations from the U.S. National Kidney Foundation, (RR: 2.30, 95% CI: 0.94-5.61, p = 0.07). Despite the lack of statistical significance, likely due to the small sample size of the cohort, the present nested case-control study's clinically significant effect size, dose-response, temporality, specificity, biological plausibility, consistency, coherence, and analogy with other research findings meet the criteria for inferred causality in observational studies, warranting further investigations. Furthermore, these findings suggest that a low-phosphate diet should be tested on patients with breast cancer.

The allostatic load model: a framework to understand the cumulative multi-system impact of work-related psychosocial stress exposure among firefighters.

Firefighting is recognised as a profession where health and well-being can be affected by a variety of occupational factors, such as physical, thermal, and chemical stressors. Along with the risks intuitively associated with the fire service, however, psychosocial stress has begun to attract attention as another variable deserving of consideration. Indeed, long-term exposure to work-related psychosocial stress has been linked with poor health outcomes in many workers; however, despite this association, very little has been done to examine how such stressors become biologically embedded in firefighters. To help facilitate research into how psychosocial stress can affect health-related outcomes in the fire service, we propose a framework centered on the notion of allostatic load. First, we reviewed the occupational characteristics that may generate psychosocial stress within firefighters before introducing allostatic load (that is, dysregulation across various physiological systems caused by the need to manage ongoing stressors). Next, we provided a summary of how allostatic load can be measured and touched on the framework's utility for studying the cumulative effects of work-related stress on firefighter health. After this, factors that may influence the steps leading from stress exposure to health outcomes were discussed; in particular, we commented upon how research in this area should consider specific non-modifiable (age, sex, and ethnicity) and modifiable (psychosocial resources and behavioural habits) factors. Finally, we presented methodological barriers and opportunities that may arise when using the allostatic load framework with this professional group. By introducing the framework, we hope to provide a tool that may be used by those interested in stress-health research in firefighters to build the evidence needed to inform primary prevention measures.

Chronic early-life social isolation enhances spatial memory in male and female rats.

Social adversity during childhood and adolescence can alter brain development in ways that may increase the likelihood of many prominent mental illnesses. To determine the underlying mechanisms, several animal models have been developed, such as Chronic Early-Life Social Isolation (CELSI), which sees rats isolated for several weeks after weaning. Although such a paradigm does cause many consistent changes in adult behaviour, one area where uncertainty exists concerns its effect upon hippocampal-dependent learning and memory. To help sort out how CELSI affects spatial learning and memory, male and female siblings from 15 Sprague-Dawley rat litters were stratified by sex and then randomly assigned to either group-housing (3 animals/cage), or social isolation (1 animal/cage) for 7 weeks. Spatial learning and memory were then tested over 5 days using the Morris water maze. Next, the animals were euthanised, and stress-sensitive biometrics, including serum corticosterone levels, were collected. Lastly, to determine whether CELSI affected neural cell density, the expression of key neuronal and glial proteins (such as PSD-95 and GFAP, respectively) was assessed in isolated hippocampal tissue using immunoblotting. Notably, both male and female rats that had experienced post-weaning social isolation displayed stronger spatial learning and memory abilities than their group-housed counterparts. As well, socially isolated male rats exhibited a clear increase in expression of PSD-95. However, housing condition did not seem to affect either stress-sensitive biometrics, or hippocampal GFAP expression. Our results support the possibility that CELSI may enhance some aspects of hippocampal-dependent behaviour in a fashion similar among male and female rats.

Sex differences in hippocampal-dependent memory and the hippocampal lipidome in adolescent rats raised on diets with or without DHA.

Recent studies suggest the effects of DHA supplementation on human memory may differ between females and males during infancy, adolescence, and early adulthood, but the underlying mechanisms are not clear. As a result, this study sought to examine the spatial memory and brain lipidomic profiles in female and male adolescent rats with or without a DHA-enriched diet that began perinatally with the supplementation of dams. Spatial learning and memory were examined in adolescent rats using the Morris Water Maze beginning at 6 weeks of age and animals were sacrificed at 7 weeks of age to permit isolation of brain tissue and blood samples. Behavioral testing showed that there was a significant diet x sex interaction for two key measures of spatial memory (distance to zone and time spent in the correct quadrant during the probe test), with female rats benefiting the most from DHA supplementation. Lipidomic analyses suggest levels of arachidonic acid (ARA) and n-6 docosapentaenoic acid (DPA) containing phospholipid species were lower in the hippocampus of DHA supplemented compared with control animals, and principal component analyses revealed a potential dietary treatment effect for hippocampal PUFA. Females fed DHA had slightly more PE P-18:0_22:6 and maintained levels of PE 18:0_20:4 in the hippocampus in contrast with males fed DHA. Understanding how DHA supplementation during the perinatal and adolescent periods changes cognitive function in a sex-specific manner has important implications for determining the dietary requirements of DHA. This study adds to previous work highlighting the importance of DHA for spatial memory and provides evidence that further research needs to consider how DHA supplementation can cause sex-specific changes.

The effects of synthetic glucocorticoid treatment for inflammatory disease on brain structure, function, and dementia outcomes: A systematic review.

Many regions of the brain have a high density of glucocorticoid receptors, and the prolonged elevation of endogenous glucocorticoids may cause neurotoxicity and increase risk for cognitive decline and dementia. However, despite synthetic glucocorticoids being the first line of treatment for many inflammatory diseases, few studies have addressed whether therapeutic glucocorticoids may have similar undesirable effects on the brain. Thus, our systematic review investigated the impact of long-term glucocorticoid usage on adult brain structure, cognitive function, and dementia risk. We identified 13 studies that met our eligibility criteria and found conflicting results dependent on the outcome studied. In particular, all but one study on hippocampal and amygdalar volumes found significant atrophy of both structures occurred in those who took glucocorticoids. Additionally, executive function, particularly working memory, and global cognitive function were significantly poorer in those taking long-term glucocorticoids. Notably, declines in episodic memory were not associated with long-term usage. Furthermore, most studies of dementia (all-cause) and Alzheimer's disease, excluding vascular dementia, showed null to negative associations with glucocorticoids, suggesting a potential protective effect. Therefore, glucocorticoid therapy in those with inflammatory disease may impair certain brain structures and specific cognitive functions, but could lead to a significantly reduced risk of dementia.

The combined effects of corticosterone and brain-derived neurotrophic factor on plasticity-related receptor phosphorylation and expression at the synaptic surface in male Sprague-Dawley rats.

Following acute exercise, a temporal window exists wherein neuroplasticity is thought to be heightened. Although a number of studies have established that pairing this post-exercise period with motor training enhances learning, the mechanisms through which exercise-induced priming occurs are not well understood. Previously, we characterized a rodent model of acute exercise that generates significant enhancement in glutamatergic receptor phosphorylation as a possible mechanism to explain how exercise-induced priming might occur. However, whether these changes are stimulated by peripheral factors (e.g., glucocorticoids), central effects (e.g., brain-derived neurotrophic factor (BDNF), or a combination of the two remains unclear. Herein, we explored the possible individual and/or cumulative contribution corticosterone (CORT) and BDNF may have on glutamate receptor phosphorylation and synaptic surface expression. Tissue slices from the sensorimotor cortex were prepared and acutely (30 min) incubated with either CORT (200 nM), BDNF (20 ng/mL), or the simultaneous application of CORT and BDNF (CORT+BDNF). Immunoblotting with biotinylated synaptoneurosomes (which provide an enrichment of proteins from the synaptic surface) suggested divergent effects between CORT and BDNF. Acute CORT application enhanced NMDA- (GluN2A, B) and AMPA- (GluA1) receptor phosphorylation, whereas BDNF preferentially increased synaptic surface expression of both NMDA- and AMPA-receptor subunits. The combined effects of CORT+BDNF resulted in a unique subset of signaling patterns that favored phosphorylation in the absence of surface expression. Taken together, these data provide a mechanistic framework for how CORT and BDNF may alter glutamatergic synapses during exercise-induced priming.

Do subjective and objective measures of stress agree in a clinical sample of youth and their parents?

This study explored agreement and potential relationships among perceived stress (self-reported using the Perceived Stress Scale), hair cortisol concentration (HCC), and mental disorders in a clinical sample of youth and their parents. Data were collected from a cross-sectional sample of 48 youth (38 females; mean age = 15.6 years) with a mental disorder and 72 parents (65 females; mean age = 45.49 years). Agreement was assessed using Bland-Altman plots and intraclass correlation coefficients. Multiple regression was used to model the association between covariates and HCC and perceived stress for youth and parents. Agreement between perceived stress and HCC was low for both youth and parents (ICC = 0.15 to 0.31). Among youth, lower income (ß = 0.24) and parent psychopathology (ß = 0.42) were associated with higher HCC. Female sex (ß = 0.42) and higher parent psychopathology (ß = 0.28) were associated with higher perceived stress, whereas chronic physical illness was associated with lower perceived stress (ß = -0.24). Among parents, female sex (ß = -0.21) was associated with lower HCC and family functioning (ß = 0.46) was associated with higher perceived stress. In youth, higher HCC was associated with generalized anxiety (OR = 1.14) and higher perceived stress was associated with major depressive episode (OR = 1.33), generalized anxiety (OR = 1.10), and separation anxiety (OR = 1.14). Among parents, higher HCC was associated with depression (ß = 0.27) and perceived stress was associated with depression (ß = 0.53) and anxiety (ß = 0.45). This exploratory study shows that agreement between psychological and physiological stress is low in a clinical sample of youth and their parents. Sociodemographic and psychosocial factors, and mental health, are differentially associated with psychological and physiological stress.

Biological Embedding of Psychosocial Stressors Within a Sample of Canadian Firefighters: An Exploratory Analysis.

OBJECTIVE: We wanted to determine whether the biological embedding of perceived psychosocial stress could be observed within a sample of Canadian firefighters. METHODS: We collected sociodemographic and general health-related information from 58 firefighters. In addition, measures of work-related and general life psychosocial stress, perceived social support, and physiological parameters thought to reflect the embedding of stress were gathered and analyzed using analysis of variance and linear regression models. RESULTS: Despite observing a positive relationship between psychosocial stress and allostatic load, the association was not significant; however, age did significantly predict allostatic load ( B = 0.09, P = 0.04). Notably, our participants reported abundant social support that was inversely associated with perceived stress. CONCLUSIONS: Although perceived stress did not significantly affect allostatic load in our sample, high levels of social support may have provided an important countervailing force.

Building Families Through Healthcare: Experiences of Lesbians Using Reproductive Services.

The use of assisted human reproduction (AHR) represents a meaningful and important life event for lesbians wishing to create biologically related families. Despite increasing numbers of lesbians utilizing AHR services, barriers to access persist. This qualitative study investigated the experiences of lesbians and their interactions with reproductive services in Ontario, Canada, where limited public funding is available for all AHR patients and where the lesbian, gay, bisexual, transgender, and queer (LGBTQ) community makes up to 30% of clientele. Eleven semi-structured interviews were conducted, and findings revealed a wide range of experiences. Lesbian patients expressed a desire for more support from their care providers in navigating a complex and costly medical journey through a system largely designed for the needs of heterosexual patients. Additionally, private fertility clinics, as the environment for accessing publicly funded services, were felt to contribute pressure to pay out-of-pocket for add-on medical procedures. To improve the quality of care, participants recommended providing more high-level information on the medical journey and taking an individual approach with lesbian patients, in particular, assuming a patient has sufficient fertility until proven otherwise.

Global executive dysfunction, not core executive skills, mediate the relationship between adversity exposure and later health in undergraduate students.

Executive function (EF) represents a set of higher-order cognitive skills that permit engagement in goal-oriented behavior. EF deficits are associated with wide-ranging negative health-related consequences, including psychopathology and engagement in risky health-related behaviors. Because neural substrates supporting EF develop over a protracted period of time, an extended window of vulnerability exists whereby environmental stressors can interrupt development, culminating in lifelong EF deficits. We capitalized on this understanding of the vulnerability of EF-relevant neural structures to elucidate the link between adverse childhood experiences (ACEs) and early mortality. ACEs are highly prevalent in the general population and exert negative downstream implications for many health-related behaviors, ultimately hastening mortality. However, underlying mechanisms linking ACEs with poor health remain less understood. To address this gap in the literature, we assessed ACE history and health factors, including psychopathology and risky alcohol use behaviors in undergraduates. We further assessed EF using performance-based and rating scale measures. Results revealed that some measures of EF mediated the relationship between ACEs and current mental health, but EF did not mediate the association between ACEs and engagement in risky health-related behaviors. These results partially support a neurodevelopmental model of ACE exposure vis-à-vis future health, focusing on the role of EF.

Hair Cortisol and Health-Related Quality of Life in Children with Mental Disorder.

INTRODUCTION: Children living with mental disorder are at risk for lower health-related quality of life (HRQoL) compared to their peers. While evidence suggests that cortisol dysregulation is implicated in the onset of mental disorder, the extent to which cortisol is associated with HRQoL is largely unknown. Further, it remains unknown how comorbid physical illness may alter this relationship. This study examined whether the presence of a comorbid physical illness moderated the association between hair cortisol concentration (HCC) and HRQoL among children with mental disorder. METHODS: One-hundred children (4-17 years) receiving care from a pediatric hospital were recruited. The Mini International Neuropsychiatric Interview was used to measure mental disorder and the KIDSCREEN-27 to assess HRQoL. Cortisol extracted from children's hair was assayed using high-sensitivity ELISA. Multiple regression analyses tested the association between HCC and HRQoL. RESULTS: Presence of a physical illness was found to moderate the relationship between HCC and HRQoL in the domain of peers and social support [comorbidity: ß = -0.57 (-0.97, -0.17); no comorbidity: ß = 0.22 (-0.11, 0.55)]. CONCLUSION: The association between HCC and HRQoL in children with mental disorder is moderated by the presence of a physical illness, such that in children with comorbid physical and mental disorder, elevated HCC is associated with lower HRQoL. Approaches that reduce stress in these children may help promote optimal well-being. More research investigating physiological stress and psychosocial outcomes in children with mental disorder, particularly those with comorbid physical illness, is needed.

Chronic early-life social isolation affects NMDA and TrkB receptor expression in a sex-specific manner.

Exposing mammals to adverse social environments early in life can affect brain development in ways that alter adult behaviour. For example, chronic, early-life social isolation (CELSI) has been found to cause novelty-induced hyperactivity, impaired pre-pulse inhibition, and enhanced anxiety-related behaviour. Although the molecular mechanism(s) underlying the embedding of CELSI have not been fully elucidated, evidence suggests changes in the level of excitatory neurotransmission and neurotrophic factor signalling may be quite important. Since much of the work in this area has focused upon mRNA-level analyses, and has shown variable responses across both brain region and animal sex, our study aimed to explore the impact of CELSI on the expression of two important plasticity-related proteins (Tropomyosin receptor kinase B and the GluN2B subunit of the NMDA receptor) in the pre-frontal cortex and hippocampus of both male and female rats. We observed that the expression of both proteins was clearly changed by CELSI, but that the effect occurred in a sex (but not region) specific manner. Our results support the growing view that early-life adversity can cause structural changes reasonably associated with adult behaviour, and emphasise that the study of such changes benefits from a sex-based analysis.

Resilience of network activity in preconditioned neurons exposed to 'stroke-in-a-dish' insults.

Exposing cultured cortical neurons to stimulatory agents - the K+ channel blocker 4-aminopyridine (4-ap), and the GABAA receptor antagonist bicuculline (bic) - for 48 h induces down-regulated synaptic scaling, and preconditions neurons to withstand subsequent otherwise lethal 'stroke-in-a-dish' insults; however, the degree to which usual neuronal function remains is unknown. As a result, multi-electrode array and patch-clamp electrophysiological techniques were employed to characterize hallmarks of spontaneous synaptic activity over a 12-day preconditioning/insult experiment. Spiking frequency increased 8-fold immediately upon 4-ap/bic treatment but declined within the 48 h treatment window to sub-baseline levels that persisted long after washout. Preconditioning resulted in key markers of network activity - spiking frequency, bursting and avalanches - being impervious to an insult. Surprisingly, preconditioning resulted in higher peak NMDA mEPSC amplitudes, resulting in a decrease in the ratio of AMPA:NMDA mEPSC currents, suggesting a relative increase in synaptic NMDA receptors. An investigation of a broad mRNA panel of excitatory and inhibitory signaling mediators indicated preconditioning rapidly up-regulated GABA synthesis (GAD67) and BDNF, followed by up-regulation of neuronal activity-regulated pentraxin and down-regulation of presynaptic glutamate release (VGLUT1). Preconditioning also enhanced surface expression of GLT-1, which persisted following an insult. Overall, preconditioning resulted in a reduced spiking frequency which was impervious to subsequent exposure to 'stroke-in-a-dish' insults, a phenotype initiated predominantly by up-regulation of inhibitory neurotransmission, a lower neuronal postsynaptic AMPA: NMDA receptor ratio, and trafficking of GLT-1 to astrocyte plasma membranes.

Health outcomes of psychosocial stress within firefighters: A systematic review of the research landscape.

BACKGROUND AND OBJECTIVES: Much of the research surrounding firefighter health has concerned the hazards intuitively associated with the occupation, such as physical, thermal, and chemical risks. However, an additional aspect of their work environment, psychosocial stressors, has begun to attract a growing level of attention. Work-related psychosocial stress may best be described as mental and emotional strain caused by a combination of workplace events and characteristics, and the objective of our review was to identify the health outcomes associated with these stressors in firefighters. METHODS: A systematic review was performed of studies reporting on the psychosocial stressors and the associated health outcomes experienced by firefighters. Data sources included the MEDLINE, PsychInfo, and CINAHL databases. RESULTS: Twenty-nine studies met the inclusion criteria. Upon analysis, we found that firefighters experienced a range of psychosocial stressors (including interpersonal conflict and concerns over organizational fairness) and observed that these stressors were associated with a number of health-related outcomes that could be arranged into six areas: depression-suicidality, non-depressive mental health problems, burnout, alcohol use disorders, sleep quality, and physiological parameters and somatic disorders. CONCLUSION: Our findings strongly suggest that work-related psychosocial stressors can affect the health and well-being of those in the fire service, and highlight that interventions meant to address these psychosocial risk factors should focus upon promoting self-esteem, enhancing self-efficacy, and strengthening social support.

How do adverse childhood experiences impact health? Exploring the mediating role of executive functions.

Objective: Adverse childhood experiences (ACEs) are stressful life events that occur during development. It is well-established that ACE exposure has negative downstream implications for a broad range of health-related behaviors, ultimately hastening mortality. Underlying mechanisms linking the experience of early life adversity with poor health remain less understood, however, and thus potential targets for intervention remain elusive. This work seeks to fill an important theoretical gap in the ACE literature by evaluating whether executive functions (EFs) constitute a biologically plausible mediating mechanism in this causal pathway. Methods: Two separate studies were conducted. In Study 1, undergraduate students completed measures of ACE exposure, EF, health-risk behaviors (e.g., drug and alcohol use, unsafe sexual practices), and psychopathology (e.g., anxiety, depression). Study 2 sought to replicate this work in a community sample. Results: Multivariate modeling determined that executive dysfunction in daily life mediated the relationship between childhood adversity exposure and mental health concerns but not the effect between ACEs and health-risk behaviors in an undergraduate sample. In a community sample, EF difficulties in daily life mediated the relationship between ACEs and both psychopathology symptoms and health-risk behavior, but not physical health status. Conclusions: These results partially support a neurodevelopmental model of ACE exposure vis-à-vis future health, focusing on the role of EF. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Maternal risk factors for birth asphyxia in low-resource communities. A systematic review of the literature.

Birth asphyxia (BA) affects millions of newborns annually, especially in low-resource communities. Given that much of the attention to this point has focussed upon secondary prevention, we sought to inform the development of primary prevention strategies for BA in resource-limited settings by identifying maternal risk factors. To this end, we systematically reviewed the MEDLINE, PsychInfo, and EMBASE databases, and identified 38 relevant studies. Upon analysis, we found 12 maternal variables associated with BA, and thematically arranged them into 3 categories: sociodemographic factors (age, literacy, gravidity, parity), health care factors (antenatal care, delivery location), and health status (hypertension, pre-eclampsia, eclampsia, anaemia, antepartum haemorrhage, pyrexia). The factors with the greatest, and/or most consistent influence upon likelihood for BA were: young maternal age (<20 years), limited maternal literacy, insufficient antenatal care, non-hospital delivery, maternal hypertension, and anaemia. We hope our review will assist stakeholders guiding the development of BA-related policies and programmes.

A Single Session of Aerobic Exercise Mediates Plasticity-Related Phosphorylation in both the Rat Motor Cortex and Hippocampus.

A single session of aerobic exercise may offer one means to "prime" motor regions to be more receptive to the acquisition of a motor skill; however, the mechanisms whereby this priming may occur are not clear. One possible explanation may be related to the post-translational modification of plasticity-related receptors and their associated intracellular signaling molecules, given that these proteins are integral to the development of synaptic plasticity. In particular, phosphorylation governs the biophysical properties (e.g., Ca2+ conductance) and the migratory patterns (i.e., trafficking) of plasticity-related receptors by altering the relative density of specific receptor subunits at synapses. We hypothesized that a single session of exercise would alter the subunit phosphorylation of plasticity-related receptors (AMPA receptors, NMDA receptors) and signaling molecules (PKA, CaMKII) in a manner that would serve to prime motor cortex. Young, male Sprague-Dawley rats (n = 24) were assigned to either exercise (Moderate, Exhaustion), or non-exercising (Sedentary) groups. Immediately following a single session of treadmill exercise, whole tissue homogenates were prepared from both the motor cortex and hippocampus. We observed a robust (1.2-2.0× greater than sedentary) increase in tyrosine phosphorylation of AMPA (GluA1,2) and NMDA (GluN2A,B) receptor subunits, and a clear indication that exercise preferentially affects pPKA over pCaMKII. The changes were found, specifically, following moderate, but not maximal, acute aerobic exercise in both motor cortex and hippocampus. Given the requirement for these proteins during the early phases of plasticity induction, the possibility exists that exercise-induced priming may occur by altering the phosphorylation of plasticity-related proteins.

Single session, high-intensity aerobic exercise fails to affect plasticity-related protein expression in the rat sensorimotor cortex.

Typical responses in muscle following acute aerobic exercise have been well documented, but the responses in brain have remained relatively unexplored. Recent reports suggest that a single bout of aerobic exercise can prime motor regions of the human brain to experience use-dependent plasticity, however, the mechanisms underlying this priming phenomenon are unclear. As a result, we asked whether a graded test to exhaustion (GXT), the most widely employed test to examine relationships between exercise and integrated responses within the musculoskeletal, cardiopulmonary, and neuropsychological systems, would be able to upregulate the expression of plasticity-related proteins in sensorimotor cortex in rats. We examined immediate responses in animals following either a GXT, or two resting conditions: non-exercising treadmill controls (TC), and acclimatization controls (AC). Young, male Sprague-Dawley rats (n = 20) on a reverse light cycle (12 h/12 h) were exposed to a treadmill acclimatization procedure consisting of 8 days of increasing exercise intensity (10 m/min up to 25 m/min) for 10 min at the same time each day. The acclimatization was followed by 2 days of rest to reduce any carryover effects. On testing day, rats performed either a GXT, or rested (TC and AC), were then sacrificed and sensorimotor cortex dissected. Homogenates were probed for a physiological marker of stress (HSP 70), and plasticity-related proteins (CaMKII, GluN2A, GluN1, GluA1, GluA2) by Western blotting analysis. Both our acclimatization protocol and single event GXT yielded no observable differences in protein expression, suggesting that single session exercise does not prime brain via altered plasticity-related protein expression.

Amyloid-ß Inhibits PDGFß Receptor Activation and Prevents PDGF-BBInduced Neuroprotection.

BACKGROUND: PDGFß receptors and their ligand, PDGF-BB, are upregulated in vivo after neuronal insults such as ischemia. When applied exogenously, PDGF-BB is neuroprotective against excitotoxicity and HIV proteins. OBJECTIVE: Given this growth factor's neuroprotective ability, we sought to determine if PDGF-BB would be neuroprotective against amyloid-ß (1-42), one of the pathological agents associated with Alzheimer's disease (AD). METHODS AND RESULTS: In both primary hippocampal neurons and the human-derived neuroblastoma cell line, SH-SY5Y, amyloid-ß treatment for 24 h decreased surviving cell number in a concentrationdependent manner. Pretreatment with PDGF-BB failed to provide any neuroprotection against amyloid-ß in primary neurons and only very limited protective effects in SH-SY5Y cells. In addition to its neuroprotective action, PDGF promotes cell growth and division in several systems, and the application of PDGFBB alone to serum-starved SH-SY5Y cells resulted in an increase in cell number. Amyloid-ß attenuated the mitogenic effects of PDGF-BB, inhibited PDGF-BB-induced PDGFß receptor phosphorylation, and attenuated the ability of PDGF-BB to protect neurons against NMDA-induced excitotoxicity. Despite the ability of amyloid-ß to inhibit PDGFß receptor activation, immunoprecipitation experiments failed to detect a physical interaction between amyloid-ß and PDGF-BB or the PDGFß receptor. However, G protein-coupled receptor transactivation of the PDGFß receptor (an exclusively intracellular signaling pathway) remained unaffected by the presence of amyloid-ß. CONCLUSIONS: As the PDGF system is upregulated upon neuronal damage, the ability of amyloid-ß to inhibit this endogenous neuroprotective system should be further investigated in the context of AD pathophysiology.

Capillary isoelectric focusing with whole column imaging detection (iCIEF): A new approach to the characterization and quantification of salivary α-amylase.

Saliva is an easily collected biological fluid with potentially important diagnostic value. While gel electrophoresis is generally used for salivary analysis, we employed the capillary isoelectric focusing technique to allow for a rapid, automated mode of electrophoresis. Capillary isoelectric focusing coupled with UV whole column imaging detection (iCIEF) was used to develop a robust protocol to characterize salivary α-amylase collected from various glands. Notably, three sample preparation methods were examined: ultrafiltration, gel-filtration, and starch affinity interaction with salivary amylase. Salivary α-amylase separated into two major peaks before sample treatment; while both filtration methods and starch affinity interaction of salivary amylase enhanced the resolution of isozymes, desalting with gel-filtration displayed the best recovery and the highest resolution of isozymes. Good agreement existed between the observed isoelectric points and the values reported in the literature. In addition, a high level of precision was apparent, and the relative standard deviation for replicates was less than 0.5% for pIs (peak positions) and below 10% for peak area. Furthermore, saliva secreted from the parotid gland proved to have a higher amylase content compared to either secretions from the submandibular/sublingual complex, or whole saliva, as well as amylase enhancement under stimulation. The results suggest that the iCIEF technique can be used to accurately resolve and quantitate amylase isozymes in a rapid and automated fashion, and that gel-filtration should be applied to saliva samples beforehand to allow for optimal purification and characterization.