Mitochondrial membrane potential in a small subset of artemisinin-induced dormant plasmodium falciparum parasites in vitro

Artemisinin induced dormancy is a proposed mechanism for failures of mono-therapy and is linked with artemisinin resistance in Plasmodium falciparum. The biological characterization and dynamics of dormant parasites are not well understood. Here we report that following dihydroartemisinin (DHA) treatment in vitro, a small subset of morphologically dormant parasites was stained with rhodamine 123 (RH), a mitochondrial membrane potential (MMP) marker, and persisted to recovery. FACS sorted RH-positive parasites resumed growth at 10,000/well while RH-negative parasites failed to recover at 5 million/well. Furthermore, transcriptional activity for mitochondrial enzymes was only detected in RH-positive dormant parasites. Importantly, after treating dormant parasites with different concentrations of atovaquone, a mitochondrial inhibitor, the recovery of dormant parasites was delayed or stopped. This demonstrates that mitochondrial activity is critical for survival and regrowth of dormant parasites and that RH staining provides a means of identifying these parasites. These findings provide novel paths for studying and eradicating this dormant stage.

Blood in our hearts or blood on our hands? The viscosity, vitality and validity of Aboriginal 'blood talk'

Blood metaphors abound in everyday social discourse among both Aboriginal and non-Aboriginal people. However, ‘Aboriginal blood talk’, more specifically, is located within a contradictory and contested space in terms of the meanings and values that can be attributed to it by Aboriginal and non-Aboriginal people. In the colonial context, blood talk operated as a tool of oppression for Aboriginal people via blood quantum discourses, yet today, Aboriginal people draw upon notions of blood, namely bloodlines, in articulating their identities. This paper juxtaposes contemporary Aboriginal blood talk as expressed by Aboriginal people against colonial blood talk and critically examines the ongoing political and intellectual governance regarding the validity of this talk in articulating Aboriginalities.

Polybrominated diphenyl ethers and age: analysis of pooled human blood serum from birth to over 60 years

Polybrominated diphenyl ethers (PBDEs) are considered to be a cost effective and efficient way to reduce flammability therefore reducing harm caused by fires. PBDEs are incorporated into a variety of manufactured products and are found worldwide in biological and environmental samples (e.g. Hites et al. 2004). Unlike other persistent organic pollutants there is limited data on PBDE concentrations by age and/or other population specific factors. Some studies have shown no variation in adult serum PBDE concentrations with age (e.g. Mazdai et al., 2003, Meironyte Guvenius et al., 2003) while Petreas et al. (2003) and Schecter et al. (2005) found results to be suggestive of an age trend in adult data but no statistically significant correlation was found. In addition to the data on adult concentrations there is limited data which investigates the levels of PBDEs in infants and young children. Fangström et al. (2005) showed that in seven year olds there was no difference in PBDE concentration when compared to adult concentrations. While Thomsen et al. (2002, 2005) found the concentration of PBDEs in pooled samples of blood serum from a 0-4 years age group to be higher than other age groups (4 to > 60 years). In addition, a family of four was studied in the U.S. and the concentrations were found to be greatest in the 18-month-old infant followed by the 5 year old child, then the mother and father (Fischer et al., 2006). The objectives of this study were to assess age, gender and regional trends of PBDE concentrations in a representative sample of the Australian population.

Determination of the levels of Polybrominated Diphenylethers (PBDEs) in pooled blood sera obtained from Australians aged 31-45 years

Polybrominated diphenylethers (PBDEs) are widely used as flame retardants in polymer materials, textiles, electronic boards and various other materials. Technical PBDE preparations are produced as mixtures of mainly penta-, octa- or decabrombiphenyl ethers1,2. PBDEs are structurally similar to other environmental pollutants like dioxins and PCBs, they are lipophilic and persistent compounds and are widespread in the environment. To date, no information is available on the levels of PBDEs in human serum in Australia. In 2003, more than 9000 blood samples were collected in Australia as part of the National Dioxins Program. The aim of this study was to evaluate PBDE concentrations in these samples, focusing on one age group.

Assessment of the concentrations of polybrominated diphenyl ether flame retardants in the Australian population : levels in blood

Polybrominated diphenyl ethers (PBDEs), a common class of brominated flame retardants, are a ubiquitous part of our built environment, and for many years have contributed to improved public safety by reducing the flammability of everyday goods. Recently, PBDEs have come under increased international attention because of their potential to impact upon the environment and human health. Some PBDE compounds have been nominated for possible inclusion on the Stockholm Convention on Persistent Organic Pollutants, to which Australia is a Party. Work under the Stockholm Convention has demonstrated the capacity of some PBDEs to persist and accumulate in the environment and to be carried long distances. Much is unknown about the impact of PBDEs on living organisms, however recent studies show that some PBDEs can inhibit growth in colonies of plankton and algae and depress the reproduction of zooplankton. Laboratory mice and rats have also shown liver disturbances and damage to developing nervous systems as a result of exposure to PBDEs. In 2004, the Australian Government Department of the Environment and Water Resources began three studies to examine levels of PBDEs in aquatic sediments, indoor environments and human blood, as knowledge about PBDEs in Australia was very limited. The aim of these studies was to improve this knowledge base so that governments were in a better position to consider appropriate management actions. Due to the high costs for laboratory analysis of PBDEs, the number of samples collected for each study was limited and so caution is required when interpreting the findings. Nevertheless, these studies will provide governments with an indication of how prevalent PBDEs are in the Australian population and the environment and will also contribute to international knowledge about these chemicals. The Department of the Environment and Water Resources will be working closely with othergovernment agencies, industry and the community to investigate any further action that may be required to address PBDEs in Australia.

Cord blood vitamin D and neurocognitive development are nonlinearly related in toddlers

Background Little is known about the relation between vitamin D status in early life and neurodevelopment outcomes. Objective This study was designed to examine the association of cord blood 25-hydroxyvitamin D [25(OH)D] at birth with neurocognitive development in toddlers. Methods As part of the China-Anhui Birth Cohort Study, 363 mother-infant pairs with completed data were selected. Concentrations of 25(OH)D in cord blood were measured by radioimmunoassay. Mental development index (MDI) and psychomotor development index (PDI) in toddlers were assessed at age 16–18 mo by using the Bayley Scales of Infant Development. The data on maternal sociodemographic characteristics and other confounding factors were also prospectively collected. Results Toddlers in the lowest quintile of cord blood 25(OH)D exhibited a deficit of 7.60 (95% CI: −12.4, −2.82; P = 0.002) and 8.04 (95% CI: −12.9, −3.11; P = 0.001) points in the MDI and PDI scores, respectively, compared with the reference category. Unexpectedly, toddlers in the highest quintile of cord blood 25(OH)D also had a significant deficit of 12.3 (95% CI: −17.9, −6.67; P < 0.001) points in PDI scores compared with the reference category. Conclusions This prospective study suggested that there was an inverted-U–shaped relation between neonatal vitamin D status and neurocognitive development in toddlers. Additional studies on the optimal 25(OH)D concentrations in early life are needed.

Numerical investigation of motion and deformation of a single red blood cell in a stenosed capillary

It is generally assumed that influence of the red blood cells (RBCs) is predominant in blood rheology. The healthy RBCs are highly deformable and can thus easily squeeze through the smallest capillaries having internal diameter less than their characteristic size. On the other hand, RBCs infected by malaria or other diseases are stiffer and so less deformable. Thus it is harder for them to flow through the smallest capillaries. Therefore, it is very important to critically and realistically investigate the mechanical behavior of both healthy and infected RBCs which is a current gap in knowledge. The motion and the steady state deformed shape of the RBCs depend on many factors, such as the geometrical parameters of the capillary through which blood flows, the membrane bending stiffness and the mean velocity of the blood flow. In this study, motion and deformation of a single two-dimensional RBC in a stenosed capillary is explored by using smoothed particle hydrodynamics (SPH) method. An elastic spring network is used to model the RBC membrane, while the RBC's inside fluid and outside fluid are treated as SPH particles. The effect of RBC's membrane stiffness (kb), inlet pressure (P) and geometrical parameters of the capillary on the motion and deformation of the RBC is studied. The deformation index, RBC's mean velocity and the cell membrane energy are analyzed when the cell passes through the stenosed capillary. The simulation results demonstrate that the kb, P and the geometrical parameters of the capillary have a significant impact on the RBCs' motion and deformation in the stenosed section.

Antidepressants, but not antipsychotics, modulate GR function in human whole blood: An insight into molecular mechanisms

Clinical studies have demonstrated an impairment of glucocorticoid receptor (GR)-mediated negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis in patients with major depression (GR resistance), and its resolution by antidepressant treatment. Recently, we showed that this impairment is indeed due to a dysfunction of GR in depressed patients (Carvalho et al., 2009), and that the ability of the antidepressant clomipramine to decrease GR function in peripheral blood cells is impaired in patients with major depression who are clinically resistant to treatment (Carvalho et al. 2008). To further investigate the effect of antidepressants on GR function in humans, we have compared the effect of the antidepressants clomipramine, amytriptiline, sertraline, paroxetine and venlafaxine, and of the antipsychotics, haloperidol and risperidone, on GR function in peripheral blood cells from healthy volunteers (n=33). GR function was measured by glucocorticoid inhibition of lypopolysaccharide (LPS)-stimulated interleukin-6 (IL-6) levels. Compared to vehicle-treated cells, all antidepressants inhibited dexamethasone (DEX, 10-100nM) inhibition of LPS-stimulated IL-6 levels (p values ranging from 0.007 to 0.1). This effect was specific to antidepressants, as antipsychotics had no effect on DEX-inhibition of LPS-stimulated IL-6 levels. The phosphodiesterase (PDE) type 4 inhibitor, rolipram, potentiated the effect of antidepressants on GR function, while the GR antagonist, RU-486, inhibited the effect of antidepressants on GR function. These findings indicate that the effect of antidepressants on GR function are specific for this class of psychotropic drugs, and involve second messenger pathways relevant to GR function and inflammation. Furthermore, it also points towards a possible mechanism by which one maybe able to overcome treatment-resistant depression. Research in this field will lead to new insights into the pathophysiology and treatment of affective disorders.

Effectiveness of in-office blood pressure measurement by eye care practitioners in early detection and management of hypertension

AIM To investigate the number of hypertensive patients, the optometrist is able to identify by routinely taking blood pressure (BP) measurements for patients in "at -risk" groups, and to sample patients' opinions regarding in -office BP measurement. Many of the optometrists in Saudi Arabia practice in optical stores. These stores are wide spread, easily accessible and seldom need appointments. The expanding role of the optometrist as a primary health care provider (PHCP) and the increasing global prevalence of hypertension, highlight the need for an integrated approach towards detecting and monitoring hypertension. METHODS Automated BP measurements were made twice (during the same session) at five selected optometry practices using a validated BP monitor (Omron M6) to assess the number of patients with high BP (HBP) - in at -risk groups -visiting the eye clinic routinely. Prior to data collection, practitioners underwent a two-day training workshop by a cardiologist on hypertension and how to obtain accurate BP readings. A protocol for BP measurement was distributed and retained in all participating clinics. The general attitude towards cardiovascular health of 480 patients aged 37.2 (依12.4)y and their opinion towards in-office BP measurement was assessed using a self -administered questionnaire. RESULTS A response rate of 83.6% was obtained for the survey. Ninety -three of the 443 patients (21.0% ) tested for BP in this study had HBP. Of these, (62 subjects) 67.7% were unaware of their HBP status. Thirty of the 105 subjects (28.6%) who had previously been diagnosed with HBP, still had HBP at the time of this study, and only 22 (73.3%) of these patients were on medication. Also, only 25% of the diagnosed hypertensive patients owned a BP monitor. CONCLUSION Taking BP measurements in optometry practices, we were able to identify one previously undiagnosed patient with HBP for every 8 adults tested. We also identified 30 of 105 previously diagnosed patients whose BP was poorly controlled, twenty-two of whom were on medication. The patients who participated in this study were positively disposed toward the routine measurement of BP by optometrists.

A novel approach to increasing inventory with the current panel: Increasing donation frequency by asking for a different blood product

BACKGROUND Ongoing shortages of blood products may be addressed through additional donations. However, donation frequency rates are typically lower than medically possible. This preliminary study aims to determine voluntary nonremunerated whole blood (WB) and plasmapheresis donors' willingness, and subsequent facilitators and barriers, to make additional donations of a different type. STUDY DESIGN AND METHODS Forty individual telephone interviews were conducted posing two additional donation pattern scenarios: first, making a single and, second, making multiple plasmapheresis donations between WB donations. Stratified purposive sampling was conducted for four samples varying in donation experience: no-plasma, new-to-both-WB-and-plasma, new-to-plasma, and plasma donors. Interviews were analyzed yielding excellent (κ values > 0.81) inter-rater reliability. RESULTS Facilitators were more endorsed than barriers for a single but not multiple plasmapheresis donation. More new-to-both donors (n = 5) were willing to make multiple plasma donations between WB donations than others (n = 1 each) and identified fewer barriers (n = 3) than those more experienced in donation (n = 8 no plasma, n = 10 new to both, n = 11 plasma). Donors in the plasma sample were concerned about the subsequent reduced time between plasma donations by adding WB donations (n = 3). The no-plasma and new-to-plasma donors were concerned about the time commitment required (n = 3). CONCLUSION Current donors are willing to add different product donations but donation history influences their willingness to change. Early introduction of multiple donation types, variation in inventory levels, and addressing barriers will provide blood collection agencies with a novel and cost-effective inventory management strategy.

Using an extended theory of planned behavior to predict a change in the type of blood product donated

Background Demand for essential plasma-derived products is increasing. Purpose This prospective study aims to identify predictors of voluntary non-remunerated whole blood (WB) donors becoming plasmapheresis donors. Methods Surveys were sent to WB donors who had recently (recent n = 1,957) and not recently donated (distant n = 1,012). Theory of Planned Behavior (TPB) constructs (attitude, subjective norm, self-efficacy) were extended with moral norm, anticipatory regret, and donor identity. Intentions and objective plasmapheresis donation for 527 recent and 166 distant participants were assessed. Results Multi-group analysis revealed that the model was a good fit. Moral norm and self-efficacy were positively associated while role identity (suppressed by moral norm) was negatively associated with plasmapheresis intentions. Conclusions The extended TPB was useful in identifying factors that facilitate conversion from WB to plasmapheresis donation. A superordinate donor identity may be synonymous with WB donation and, for donors with a strong moral norm for plasmapheresis, may inhibit conversion.

Assessment of dynamic susceptibility contrast cerebral blood flow response to amphetamine challenge: A human pharmacological magnetic resonance imaging study at 1.5 and 4 T

Pharmacological MRI (phMRI) techniques can be used to monitor the neurophysiological effects of central nervous system (CNS) active drugs. In this study, we investigated whether dynamic susceptibility contrast (DSC) perfusion imaging employing the use of superparamagnetic iron oxide nanoparticles (Resovist) could be used to measure hemodynamic response to d-amphetamine challenge in human subjects at both 1.5 and 4 T. Significant changes in cerebral blood flow (CBF) were found in focal regions associated with the nigrostriatal circuit and mesolimbic and mesocortical dopaminergic pathways. More significant CBF responses were found at higher field strength, mainly within striatal structures. The results from this study indicate that DSC perfusion imaging using Resovist can be used to assess the efficacy of CNS-active drugs and may play a role in the development of novel psychiatric therapies at the preclinical level. © 2005 Wiley-Liss, Inc.