Drugs affecting blood

25. Drugs affecting blood 25.1 Introduction 25.2 Important dysfunctions of the blood system 25.3 Drugs used in to correct dysfunctions of the blood 25.3.1 Anti-thrombosis treatments 25.3.1.1 Platelet aggregation inhibitors 25.3.1.2 Anticoagulants 25.3.1.3 Thrombolytics 25.3.2 Treatments for anaemia 25.3.3 Treatments for bleeding disorders

Comparison of cervical and blood T-cell responses to human papillomavirus-16 in women with human papillomavirus-associated cervical intraepithelial neoplasia

Human papillomaviruses (HPVs) are obligate epithelial pathogens and typically cause localized mucosal infections. We therefore hypothesized that T-cell responses to HPV antigens would be greater at sites of pathology than in the blood. Focusing on HPV-16 because of its association with cervical cancer, the magnitude of HPV-specific T-cell responses at the cervix was compared with those in the peripheral blood by intracellular cytokine staining following direct ex vivo stimulation with both virus-like particles assembled from the major capsid protein L1, and the major HPV oncoprotein, E7. We show that both CD4 + and CD8 + T cells from the cervix responded to the HPV-16 antigens and that interferon-γ (IFN-γ) production was HPV type-specific. Comparing HPV-specific T-cell IFN-γ responses at the cervix with those in the blood, we found that while CD4 + and CD8 + T-cell responses to L1 were significantly correlated between compartments (P = 0.02 and P = 0.05, respectively), IFN-γ responses in both T-cell subsets were significantly greater in magnitude at the cervix than in peripheral blood (P = 0.02 and P = 0.003, respectively). In contrast, both CD4 + and CD8 + T-cell IFN-γ responses to E7 were of similar magnitude in both compartments and CD8 + responses were significantly correlated between these distinct immunological compartments (P = 0.04). We therefore show that inflammatory T-cell responses against L1 (but not E7) demonstrate clear compartmental bias and the magnitude of these responses do reflect local viral replication but that correlation of HPV-specific responses between compartments indicates their linkage.

Effects of acute multinutrient supplementation on rugby union game performance and recovery

Purpose: To investigate the effects of an acute multinutrient supplement on game-based running performance, peak power output, anaerobic by-products, hormonal profiles, markers of muscle damage, and perceived muscular soreness before, immediately after, and 24 h following competitive rugby union games. Methods: Twelve male rugby union players ingested either a comprehensive multinutrient supplement (SUPP), [RE-ACTIVATE:01], or a placebo (PL) for 5 d. Participants then performed a competitive rugby union game (with global positioning system tracking), with associated blood draws and vertical jump assessments pre, immediately post and 24 h following competition. Results: SUPP ingestion resulted in moderate to large effects for augmented 1st half very high intensity running (VHIR) mean speed (5.9 ± 0.4 vs 4.8 ± 2.3 m·min–1; d= 0.93). Further, moderate increases in 2nd half VHIR distance (137 ± 119 vs 83 ± 89 m; d= 0.73) and VHIR mean speed (5.9 ± 0.6 v 5.3 ± 1.7 m·min–1; d= 0.56) in SUPP condition were also apparent. Postgame aspartate aminotransferase (AST; 44.1 ± 11.8 vs 37.0 ± 3.2 UL; d= 1.16) and creatine kinase (CK; 882 ± 472 vs. 645 ± 123 UL; d= 0.97) measures demonstrated increased values in the SUPP condition, while AST and CK values correlated with 2nd half VHIR distance (r= –0.71 and r= –0.76 respectively). Elevated C-reactive protein (CRP) was observed postgame in both conditions; however, it was significantly blunted with SUPP (P= .05). Conclusions: These findings suggest SUPP may assist in the maintenance of VHIR during rugby union games, possibly via the buffering qualities of SUPP ingredients. However, correlations between increased work completed at very high intensities and muscular degradation in SUPP conditions, may mask any anticatabolic properties of the supplement.

Bioreactor for blood product production

The feasibility of ex vivo blood production is limited by both biological and engineering challenges. From an engineering perspective, these challenges include the significant volumes required to generate even a single unit of a blood product, as well as the correspondingly high protein consumption required for such large volume cultures. Membrane bioreactors, such as hollow fiber bioreactors (HFBRs), enable cell densities approximately 100-fold greater than traditional culture systems and therefore may enable a significant reduction in culture working volumes. As cultured cells, and larger molecules, are retained within a fraction of the system volume, via a semipermeable membrane it may be possible to reduce protein consumption by limiting supplementation to only this fraction. Typically, HFBRs are complex perfusion systems having total volumes incompatible with bench scale screening and optimization of stem cell-based cultures. In this article we describe the use of a simplified HFBR system to assess the feasibility of this technology to produce blood products from umbilical cord blood-derived CD34+ hematopoietic stem progenitor cells (HSPCs). Unlike conventional HFBR systems used for protein manufacture, where cells are cultured in the extracapillary space, we have cultured cells in the intracapillary space, which is likely more compatible with the large-scale production of blood cell suspension cultures. Using this platform we direct HSPCs down the myeloid lineage, while targeting a 100-fold increase in cell density and the use of protein-free bulk medium. Our results demonstrate the potential of this system to deliver high cell densities, even in the absence of protein supplementation of the bulk medium.

Brominated flame retardants in the Australian population : 1993-2009

Brominated flame retardants, including hexabromocyclododecane (HBCD) and polybrominated diphenyl ethers (PBDEs) are used to reduce the flammability of a multitude of electrical and electronic products, textiles and foams. The use of selected PBDEs has ceased, however, use of decaBDE and HBCD continues. While elevated concentrations of PBDEs in humans have been observed in Australia, no data is available on other BFRs such as HBCD. This study aimed to provide background HBCD concentrations from a representative sample of the Australian population and to assess temporal trends of HBCD and compare with PBDE concentrations over a 16 year period. Samples of human milk collected in Australia from 1993 to 2009, primarily from primiparae mothers were combined into 12 pools from 1993 (2 pools); 2001; 2002/2003 (4 pools); 2003/2004; 2006; 2007/2008 (2 pools); and 2009. Concentrations of ∑HBCD ranged from not quantified (nq) to 19 ng g−1 lipid while α-HBCD and γ-HBCD ranged from nq to 10 ng g−1 lipid and nq to 9.2 ng g−1 lipid. β-HBCD was detected in only one sample at 3.6 ng g−1 lipid while ∑4PBDE ranged from 2.5 to 15.8 ng g−1 lipid. No temporal trend was apparent in HBCD concentrations in human milk collected in Australia from 1993 to 2009. In comparison, PBDE concentrations in human milk show a peak around 2002/03 (mean ∑4PBDEs = 9.6 ng g−1 lipid) and 2003/04 (12.4 ng g−1 lipid) followed by a decrease in 2007/08 (2.7 ng g−1 lipid) and 2009 (2.6 ng g−1 lipid). In human blood serum samples collected from the Australian population, PBDE concentrations did not vary greatly (p = 0.441) from 2002/03 to 2008/09. Continued monitoring including both human milk and serum for HBCD and PBDEs is required to observe trends in human body burden of HBCD and PBDEs body burden following changes to usage.

Effects of acute multi-nutrient supplementation on rugby union match performance and recovery

Aim: To determine the effects of an acute multi-nutrient supplement on physiological, performance and recovery responses to intermittent-sprint running and muscular damage during rugby union matches. Methods: Using a randomised, double-blind, cross-over design, twelve male rugby union players ingested either 75 g of a comprehensive multi-nutrient supplement (SUPP), [Musashi] or 1 g of a taste and carbohydrate matched placebo (PL) for 5 days pre-competition. Competitive rugby union game running performance was then measured using 1 Hz GPS data (SPI10, SPI elite, GPSports), in addition to associated blood draws, vertical jump assessments and ratings of perceived muscular soreness (MS) pre, immediately post and 24 h post-competition. Baseline (BL) GPS data was collected during six competition rounds preceding data collection. Results: No significant differences were observed between supplement conditions for all game running, vertical jump, and ratings of perceived muscular soreness. However, effect size analysis indicated SUPP ingestion increased 1st half very high intensity running (VHIR) mean speed (d = 0.93) and 2nd half relative distance (m/min) (d = 0.97). Further, moderate increases in 2nd half VHIR distance (d = 0.73), VHIR m/min (d = 0.70) and VHIR mean speed (d = 0.56) in SUPP condition were also apparent. Moreover, SUPP demonstrated significant increases in 2nd half dist m/min, total game dist m/min and total game HIR m/min compared with BL data (P < 0.05). Further, large ES increases in VHIR time (d = 0.88) and moderate increases in 2nd half HIR m/min (d = 0.65) and 2nd half VHIR m/min (d = 0.74) were observed between SUPP and BL. Post-game aspartate aminotransferase (AST) (d = 1.16) and creatine kinase (CK) (d = 0.97) measures demonstrated increased ES values with SUPP, while AST and CK values correlated with 2nd half VHIR distance (r = −0.71 and r = −0.76 respectively). Elevated c-reactive protein (CRP) was observed post-game in both conditions, however was significantly blunted with SUPP (P = 0.05). Additionally, pre-game (d = 0.98) and post-game (d = 0.96) increases in cortisol (CORT) were apparent with SUPP. No differences were apparent between conditions for pH, lactate, glucose, HCO3, vertical jump assessments and MS (P > 0.05). Conclusion: These findings suggest SUPP may assist in the maintenance of VHIR speeds and distances covered during rugby union games, possibly via the buffering qualities of SUPP ingredients (i.e. caffeine, creatine, bicarbonate). While the mechanisms for these findings are unclear, the similar pH between conditions despite additional VHIR during SUPP may support this conclusion. Finally, correlations between increased work completed at very high intensities and muscular degradation in SUPP conditions, may mask any anti-catabolic properties of supplementation.

Behaviour and design of cold-formed steel beams subject to lateral-torsional buckling at elevated temperatures

Cold-formed steel beams are increasingly used as floor joists and bearers in buildings and often their behaviour and moment capacities are influenced by lateral-torsional buckling. With increasing usage of cold-formed steel beams their fire safety design has become an important issue. Fire design rules are commonly based on past research on hot-rolled steel beams. Hence a detailed parametric study was undertaken using validated finite element models to investigate the lateral-torsional buckling behaviour of simply supported cold-formed steel lipped channel beams subjected to uniform bending at uniform elevated temperatures. The moment capacity results were compared with the predictions from the available ambient temperature and fire design rules and suitable recommendations were made. European fire design rules were found to be over-conservative while the ambient temperature design rules could not be used based on single buckling curve. Hence a new design method was proposed that includes the important non-linear stress-strain characteristics observed for cold-formed steels at elevated temperatures. Comparison with numerical moment capacities demonstrated the accuracy of the new design method. This paper presents the details of the parametric study, comparisons with current design rules and the new design rules proposed in this research for lateral-torsional buckling of cold-formed steel lipped channel beams at elevated temperatures.

Flexural-torsional buckling tests of cold-formed steel compression members at elevated temperatures

Current design standards do not provide adequate guidelines for the fire design of cold-formed steel compression members subject to flexural-torsional buckling. Eurocode 3 Part 1.2 (2005) recommends the same fire design guidelines for both hot-rolled and cold-formed steel compression members subject to flexural-torsional buckling although considerable behavioural differences exist between cold-formed and hot-rolled steel members. Past research has recommended the use of ambient temperature cold-formed steel design rules for the fire design of cold-formed steel compression members provided appropriately reduced mechanical properties are used at elevated temperatures. To assess the accuracy of flexural-torsional buckling design rules in both ambient temperature cold-formed steel design and fire design standards, an experimental study of slender cold-formed steel compression members was undertaken at both ambient and elevated temperatures. This paper presents the details of this experimental study, its results, and their comparison with the predictions from the current design rules. It was found that the current ambient temperature design rules are conservative while the fire design rules are overly conservative. Suitable recommendations have been made in relation to the currently available design rules for flexural-torsional buckling including methods of improvement. Most importantly, this paper has addressed the lack of experimental results for slender cold-formed steel columns at elevated temperatures.

Elevated uric acid correlates with wound severity

Chronic venous leg ulcers are a major health issue and represent an often overlooked area of biomedical research. Nevertheless, it is becoming increasingly evident that new approaches to enhance healing outcomes may arise through better understanding the processes involved in the formation of chronic wounds. We have for the first time shown that the terminal purine catabolite uric acid (UA) is elevated in wound fluid (WF) from chronic venous leg ulcers with relative concentrations correlating with wound chronicity. We have also shown a corresponding depletion in UA precursors, including adenosine, with increased wound severity. Further, we have shown that xanthine oxidase, the only enzyme in humans that catalyses the production of UA in conjunction with a burst of free radicals, is active in chronic WF. Taken together, this provides compelling evidence that xanthine oxidase may play a critical role in the formation of chronic wounds by prolonging the inflammatory process.

Numerical simulation of red blood cells' deformation using SPH method

A numerical simulation method for the Red Blood Cells’ (RBC) deformation is presented in this study. The two-dimensional RBC membrane is modeled by the spring network, where the elastic stretch/compression energy and the bending energy are considered with the constraint of constant RBC surface area. Smoothed Particle Hydrodynamics (SPH) method is used to solve the Navier-Stokes equation coupled with the Plasma-RBC membrane and Cytoplasm- RBC membrane interaction. To verify the method, the motion of a single RBC is simulated in Poiseuille flow and compared with the results reported earlier. Typical motion and deformation mechanism of the RBC is observed.

Numerical simulation of red blood cells’ motion : a review

The micro-circulation of blood plays an important role in human body by providing oxygen and nutrients to the cells and removing carbon dioxide and wastes from the cells. This process is greatly affected by the rheological properties of the Red Blood Cells (RBCs). Changes in the rheological properties of the RBCs are caused by certain human diseases such as malaria and sickle cell diseases. Therefore it is important to understand the motion and deformation mechanism of RBCs in order to diagnose and treat this kind of diseases. Although, many methods have been developed to explore the behavior of the RBCs in micro-channels, they could not explain the deformation mechanism of the RBCs properly. Recently developed Particle Methods are employed to explain the RBCs’ behavior in micro-channels more comprehensively. The main objective of this study is to critically analyze the present methods, used to model the RBC behavior in micro-channels, in order to develop a computationally efficient particle based model to describe the complete behavior of the RBCs in micro-channels accurately and comprehensively

Molecular and structural requirements of the ß1L-adrenoceptor

Noradrenaline which occurs naturally in the body binds to beta-adrenoceptors on the heart, causing the heart to beat faster and with greater force in response to increased demand. This enables the heart to provide oxygenated blood to vital organs. Prolonged overstimulation by noradrenaline can be harmful to the heart and lead to the progression of heart disease. In these circumstances beta-adrenoceptors are blocked with drugs called beta-blockers. Beta-blockers block the effects of noradrenaline by binding to the same site on the beta-adrenoceptor. Some beta-blockers such as CGP12177 can also cause increases in heart rate. Therefore it was proposed that CGP12177 could bind in a different place to noradrenaline. The aim of this study was to determine where CGP12177 binds to on the beta-adrenoceptor. The results have revealed a separate binding site named beta-1-low. These results may lead to the development of improved -blockers for the management of heart conditions.

Does fundamental indexation lead to better risk-adjusted returns? New evidence from Australian Securities Exchange

We investigate the claims of superiority of fundamental indexation strategy over capitalisation-weighted indexation by using data for Australian Securities Exchange (ASX) listed stocks. Whilst our results are in line with the outperformance observed in other geographical markets, we find that the excess returns from fundamental indexation in Australian market are much higher. On a rolling 5-year basis, the fundamental index always outperforms the capitalisation-weighted index. Our results suggest that superior performance of fundamental indexation could not be entirely attributed to value, size, or momentum effects. The outperformance persists even after adjusting for slightly higher transaction costs related to turnover.

Abundance of Natural Riparian Forests and Tree Plantations in the Amudarya Delta of Uzbekistan and their impact on emissions of soil-borne greenhouse gases

Through a forest inventory in parts of the Amudarya river delta, Central Asia, we assessed the impact of ongoing forest degradation on the emissions of greenhouse gases (GHG) from soils. Interpretation of aerial photographs from 2001, combined with data on forest inventory in 1990 and field survey in 2003 provided comprehensive information about the extent and changes of the natural tugai riparian forests and tree plantations in the delta. The findings show an average annual deforestation rate of almost 1.3% and an even higher rate of land use change from tugai forests to land with only sparse tree cover. These annual rates of deforestation and forest degradation are higher than the global annual forest loss. By 2003, the tugai forest area had drastically decreased to about 60% compared to an inventory in 1990. Significant differences in soil GHG emissions between forest and agricultural land use underscore the impact of the ongoing land use change on the emission of soil-borne GHGs. The conversion of tugai forests into irrigated croplands will release 2.5 t CO2 equivalents per hectare per year due to elevated emissions of N2O and CH4. This demonstrates that the ongoing transformation of tugai forests into agricultural land-use systems did not only lead to a loss of biodiversity and of a unique ecosystem, but substantially impacts the biosphere-atmosphere exchange of GHG and soil C and N turnover processes.