The effects of citric acid on the hydration of calcium phosphate cement

INTRODUCTION　　 Calcium phosphate cements (CPC) overcome the practical disadvantages ofblocks or granules1 can be handled as a paste and sit in situ.Their structure andcomposition close to that of HAP make them biocompatible materials.2 Theconventional calcium phosphate cementhad some problems such as long setting time(3 0～ 60 min) and low compressive strength,etc.In our system,anα-TCP/TTCPpowder mixture was mixed with water containing citric acid to control the settingtime and co…     

The effects of anxiety on the interpretation of emotion in the face�Cvoice pairs

Anxious individuals have been shown to interpret others' emotional states negatively. Since most studies have used facial expressions as emotional cues, we examined whether trait anxiety affects the recognition of emotion in a dynamic face and voice that were presented in synchrony. The face and voice cues conveyed either matched (e.g., happy face and voice) or mismatched emotions (e.g., happy face and angry voice). Participants with high or low trait anxiety were to indicate the perceived emotion using one of the cues while ignoring the other. The results showed that individuals with high trait anxiety were more likely to interpret others' emotions in a negative manner, putting more weight on the to-be-ignored angry cues. This interpretation bias was found regardless of the cue modality (i.e., face or voice). Since trait anxiety did not affect recognition of the face or voice cues presented in isolation, this interpretation bias appears to reflect an altered integration of the face and voice cues among anxious individuals.     

The effects of β-2-microglobulin on the infectivity of murine cytomegalovirus

Summary The role of -2-microglobulin (2m) in murine cytomegalovirus (MCMV) infection of susceptible (H-2^d) and resistant (H-2^k) murine embryo fibroblasts (MEF) and peritoneal macrophages was evaluated using serum-free virus (SF-MCMV). The infectivity of SF-MCMV was significantly lower than virus propagated in serum, although the concentrations of virions were similar. Infection of cells with SF-MCMV was assessed by measuring the proportion of cells expressing viral antigens, the sizes of plaques formed in fibroblast monolayers and TCID₅₀ titers. Infection of susceptible fibroblasts was significantly increased 1.6–4.7 fold by the addition of whole FCS, a<20 kDa FCS fraction, or purified human 2m. These supplements also significantly enhanced infection of susceptible macrophages and increased TCID₅₀ titers by 3.5–10 fold in susceptible MEF. In relatively resistant H-2^k cells, the TCID₅₀ titer and the proportion of cells expressing viral antigens after infection with SF-MCMV were not affected by 2m or FCS, but plaque sizes were increased 2.5–3 fold in resistant BALB.K MEF.When human or murine 2m was added to infected cultures, immunogold electron microscopy revealed these proteins to be always associated extracellularly with the tegument material of disrupted multicapsid virions, but rarely with the envelope of intact virions. However, no murine 2m was found in association with the envelope or tegument of SF-MCMV. These relatively modest effects of 2m which were restricted to genetically susceptible cells, may be due to tegument-bound 2m facilitating infection by capsids, or the stabilisation of the conformation of Class 1 molecules by exogenous 2m, promoting MCMV binding to the target cell.     

The effects of progressive dehydration on strength and power: is there a dose response?

This study examined the effect of exercise- and heat-induced dehydration on strength, jump capacity and neuromuscular function. Twelve recreationally active males completed six resistance exercise bouts (baseline and after each 5 exposure sessions) in an increasing state of hypohydration obtained by repeated heat exposure and exercise sessions (5 periods of 20 min jogging at up to ~80% age predicted heart rate maximum at 48.5 ± 0.48°C, relative humidity 50 ± 4%). Relative to starting values, body mass decreased 1.0 ± 0.5, 1.9 ± 0.7, 2.6 ± 0.8, 3.3 ± 0.9 and 3.9 ± 1.0% after exposure 1, 2, 3, 4 and 5, respectively. However, plasma volume remained constant. No significant differences existed amongst trials in vertical jump height, electromyography data or isokinetic leg extension at a rate of 120° s⁻¹. Isometric leg extensions were significantly reduced (P < 0.05) after the first (1% body mass loss) and subsequent exposures in comparison to baseline. Isokinetic leg extensions at a rate of 30° s⁻¹ were significantly reduced after the third (2.6% body mass loss) and subsequent exposures compared with baseline. No dose response was identified in any of the tested variables yet a threshold was observed in isometric and isokinetic strength at 30° s⁻¹. In conclusion, dehydration caused by jogging in the heat had no effect on vertical jumping or isokinetic leg extensions at a rate of 120° s⁻¹. Alternatively, exercise-induced dehydration was detrimental to isometric and isokinetic leg extensions at a rate of 30° s⁻¹, suggesting the force–velocity relationship in hypohydration merits further research.     

The effects of fatty deposits on the accuracy of the Fibroscan® liver transient elastography ultrasound system

A new generation of ultrasound transient elastography (TE) systems have emerged which exploit the well-known correlation between the liver's pathological and mechanical properties through measurements of the Young's elastic modulus; however, little work has been carried out to examine the effect that fatty deposits may have on the TE measurement accuracy. An investigation was carried out on the effects on the measurement accuracy of a TE ultrasound system, the Fibroscan?, caused by overlaying fat layers of varying thickness on healthy liver-mimicking phantoms, simulating in vivo conditions for obese patients. Furthermore, a steatosis effect similar to that in non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) was simulated to investigate its effect on the TE system. A range of novel elastography fat-mimicking materials were developed using 6-10 wt% poly(vinyl alcohol) cryogel capable of achieving a range of acoustic velocities (1482-1530 m s(-1)) and attenuation coefficients (0.4-1 dB MHz(-1)?cm(-1)) for simulating different liver states. Laboratory-based acoustic velocities and attenuation coefficients were measured while the Young's modulus was established through a gold standard compression testing method. A significant variation of the Young's elastic modulus was measured in healthy phantoms with overlaying fat layers of thicknesses exceeding 45 mm, impinging on the scanners region of interest, overestimating the compression tested values by up to 11 kPa in some cases. Furthermore, Fibroscan??measurements of the steatosis phantoms showed a consistent overestimation (～54%), which strongly suggests that the speed of sound mismatch between that of liver tissue and that assumed by the scanner is responsible for the high clinical cut-offs established in the case of ALD and NAFLD.     

The effect of matrix stiffness on the differentiation of mesenchymal stem cells in response to TGF-β

Bone marrow mesenchymal stem cells (MSCs) are a valuable cell source for tissue engineering and regenerative medicine. Transforming growth factor β (TGF-β) can promote MSC differentiation into either smooth muscle cells (SMCs) or chondrogenic cells. Here we showed that the stiffness of cell adhesion substrates modulated these differential effects. MSCs on soft substrates had less spreading, fewer stress fibers and lower proliferation rate than MSCs on stiff substrates. MSCs on stiff substrates had higher expression of SMC markers α-actin and calponin-1; in contrast, MSCs on soft substrates had a higher expression of chondrogenic marker collagen-II and adipogenic marker lipoprotein lipase (LPL). TGF-β increased SMC marker expression on stiff substrates. However, TGF-β increased chondrogenic marker expression and suppressed adipogenic marker expression on soft substrates, while adipogenic medium and soft substrates induced adipogenic differentiation effectively. Rho GTPase was involved in the expression of all aforementioned lineage markers, but did not account for the differential effects of substrate stiffness. In addition, soft substrates did not significantly affect Rho activity, but inhibited Rho-induced stress fiber formation and α-actin assembly. Further analysis showed that MSCs on soft substrates had weaker cell adhesion, and that the suppression of cell adhesion strength mimicked the effects of soft substrates on the lineage marker expression. These results provide insights of how substrate stiffness differentially regulates stem cell differentiation, and have significant implications for the design of biomaterials with appropriate mechanical property for tissue regeneration.     

Preaching to the choir? The influence of personal relevance on the effects of gain- and loss-framed health-promoting messages

This article examines the moderating influence of personal relevance on the persuasive effects of gain- and loss-framed messages. We assessed current behaviour as a proxy for personal relevance, provided 169 participants with gain- and loss-framed messages advocating skin self-examination (SSE) and assessed intention to engage in SSE as the outcome measure. The results showed that loss-framed information was more persuasive than gain-framed information, but only for low-relevance participants. This suggests that loss-framed information might be mainly effective for recipients who need little persuading and, in fact, runs the risk of 'preaching to the choir'.     

Further studies on the antinociceptive effects ofΔ acid

The antinociceptive effects of (THC-7-oic) acid have been investigated further with particular regard to the influence of certain experimental parameters in the hot plate test. These included the degree of the thermal stimulus, the nature of the vehicle and a possible role for copper in the response. A temperature effect similar to that seen with nonsteroidalantiinflammatory drugs (NSAIDs) was observed, 55° produced observable antinociception, however, at a surface temperature of 58°C no drug effect was seen. Non-aqeous vehicles such as peanut oil increased the potency of THC-7-oic acid. Finally, the substitution of purified water for tap water reduced,the drug response which could be partially restored by adding copper to the purified drinking water. An increase in the inhibitory effect when copper was added was also seenin vitro in a cell culture model where the acid reduced prostaglandin synthesis induced by THC. Our findings suggest that THC-7-oic acid probably acts by mechanisms similar to the NSAIDs and that the above mentioned experimental conditions can greatly influence the outcome of studies with this agent.     

Molecular mechanisms of the biphasic effects of interferon-γ on osteoclastogenesis

Although interferon-γ (IFN-γ) potently inhibits osteoclastogenesis, the suppressive effect is significantly reduced when osteoclast precursors are pre-exposed to the receptor activator of NF-κB (RANK) ligand (RANKL). However, the molecular mechanism underlying the biphasic effects of IFN-γ on osteoclastogenesis remains elusive. Here, we recapitulate the biphasic functions of IFN-γ in osteoclastogenesis in both tissue culture dishes and on bone slices. We further demonstrate that IFN-γ markedly suppresses the RANKL-induced expression of nuclear factor of activated T-cells c1 (NFATc1) in normal, but not RANKL-pretreated bone marrow macrophages (BMMs). Similarly, IFN-γ impairs the activation of the nuclear factor-κB (NF-κB) and c-Jun N-terminal kinase (JNK) pathways in normal, but not RANKL-pretreated, BMMs. These findings indicate that IFN-γ inhibits osteoclastogenesis partially by suppressing the expression of NFATc1 and the activation of the NF-κB and JNK pathways. Moreover, IFN-γ inhibits the RANKL-induced expression of osteoclast genes, but RANKL pretreatment reprograms osteoclast genes into a state in which they can no longer be suppressed by IFN-γ, indicating that IFN-γ inhibits osteoclastogenesis by blocking the expression of osteoclast genes. Finally, the IVVY(535-538) motif in the cytoplasmic domain of RANK is responsible for rendering BMMs refractory to the inhibitory effect of IFN-γ. Taken together, these findings provide important mechanistic insights into the biphasic effects of IFN-γ on osteoclastogenesis.     

Quantitative BOLD response of the renal medulla to hyperoxic challenge at 1.5 T and 3.0 T

The aim of this study was to gage the magnitude of changes of the apparent renal medullary transverse relaxation time (ΔT₂*) induced by inhalation of pure oxygen (O₂) or carbogen (95% O₂, 5% CO₂) versus baseline breathing of room air. Eight healthy volunteers underwent 2D multi‐gradient echo MR imaging at 1.5 T and 3.0 T. Parametrical T₂* relaxation time maps were computed and average T₂* was measured in regions of interest placed in the renal medulla and cortex. The largest T₂* changes were measured in the renal medulla, with a relative ?T₂* of 33.8 ± 22.0% (right medulla) and 34.7 ± 17.6% (left medulla) as compared to room air for oxygen breathing (p > 0.01), and 53.8 ± 23.9% and 53.5 ± 33.9% (p < 0.01) for carbogen breathing, respectively at 3 T. At 1.5 T, the corresponding values were 13.7 ± 18.5% and 24.1 ± 17.1% (p < 0.01) for oxygen breathing and 23.9 ± 17.2% and 38.9 ± 37.6% (p < 0.01) for carbogen breathing. As a result, we showed that renal medullary T₂* times responded strongly to inhalation of hyperoxic gases, which may be attributed to the hypoxic condition of the medulla and subsequent reduction in deoxyhemoglobin. Copyright © 2012 John Wiley & Sons, Ltd.     

The influence of acute and 23 days of intermittent hypoxic exposures on the exercise-induced forehead sweating response

The effect of acute and 23 days of intermittent exposures to normobaric hypoxia on the forehead sweating response during steady-state exercise was investigated. Eight endurance athletes slept in a normobaric hypoxic room for a minimum of 8 h per day at a simulated altitude equivalent to 2,700 m for 23 days (sleep high–train low regimen). Peak oxygen uptake and peak work rate (WR_peak) were determined under normoxic (20.9%O₂) and hypoxic (13.5%O₂) conditions prior to (pre-IHE), and immediately after (post-IHE) the intermittent hypoxic exposures (IHE). Also, each subject performed three 30-min cycle-ergometry bouts: (1) normoxic exercise at 50% WR_peak attained in normoxia (control trial; CT); (2) hypoxic exercise at 50% WR_peak attained in hypoxia (hypoxic relative trial; HRT) and (3) hypoxic exercise at the same absolute work rate as in CT (hypoxic absolute trial; HAT). Exposure to hypoxia induced a 33 and 37% decrease (P < 0.001) in pre-IHE and post-IHE, respectively. Despite similar relative oxygen uptake during HAT pre-IHE and post-IHE, the ratings of perceived whole-body exertion decreased substantially (P < 0.05) post-IHE. Pre-IHE the sweat secretion on the forehead was greater (P < 0.01) in the HAT (2.60 (0.80) mg cm⁻² min⁻¹) compared to the other two trials (CT = 1.87 (1.09) mg cm⁻² min⁻¹; HRT = 1.57 (0.82) mg cm⁻² min⁻¹) despite a similar exercise-induced elevation in body temperatures, resulting in an augmented (P < 0.01) gain of the sweating response The augmented and during the HAT were no longer evident post-IHE. Thus, it appears that exercise sweating on the forehead is potentiated by acute exposure to hypoxia, an effect which can be abolished by 23 days of intermittent hypoxic exposures.     

The amplitude and phase precision of 40 Hz auditory steady-state response depend on the level of arousal

The aim of this study was to investigate, in healthy subjects, the modulation of amplitude and phase precision of the auditory steady-state response (ASSR) to 40 Hz stimulation in two resting conditions varying in the level of arousal. Previously, ASSR measures have shown to be affected by the level of arousal, but the findings are somewhat controversial. Generally, ASSR is diminished in sleep but it may be increased in drowsiness. Besides, ASSR reduction has been observed in schizophrenia. However, schizophrenic patients are known to have a disturbance of arousal level, what makes it pertinent to know the effects of fluctuations in arousal on passive response to gamma-range stimulation. In nine healthy volunteers trains of 40 Hz click stimuli were applied during two conditions: in the “high arousal” condition subjects were sitting upright silently reading a book of interest; in the “low arousal” condition subjects were sitting in a reclined position with eyes closed and the lights turned off. The 64-channel EEG data was wavelet transformed and the amplitude and phase precision of the wavelet transformed evoked potential were decomposed by the recently proposed multi-subject non-negative multi-way factorization (NMWF) (Morup et al. in J Neurosci Methods 161:361–368, 2007). The estimates of these measures were subjected to statistical analysis. The amplitude and phase precision of the ASSR were significantly larger during the low arousal state compared to the high arousal condition. The modulation of ASSR amplitude and phase precision by differences in the arousal level during recording warrants caution when investigating oscillatory brain activity and interpreting the findings of reduced ASSR in schizophrenia. It also emphasizes the necessity of standardized recording procedures and monitoring the level of arousal during ASSR testing.     

The effects of high fat diets on the blood-brain barrier transport of leptin: failure or adaptation?

Leptin is a pluripotent regulatory protein secreted by fat and exerts many effects through the CNS. Interpretation of the characteristics by which it crosses the blood-brain barrier (BBB) supports the view that leptin most potently signals the brain at serum levels well below those associated with the current definition of ideal body weight. This fits with the perspective that low serum levels of leptin are a signal to brain that a sufficient store of calories are available for the organism to expend energy for efforts unrelated to acquisition of calories. This would explain why low serum levels of leptin are permissive in many of the non-feeding actions of leptin, such as enhancing CNS-mediated immune function, memory, bone growth, reproduction, breathing, and neurogenesis. Triglycerides inhibit the transport of leptin across the BBB and so could be key in the onset of the peripheral leptin resistance, which is a hallmark of obesity. These results explain the paradox of why obesity should induce resistance to an anorectic: hypertriglyceridemia also occurs with starvation and we postulate that triglyceride-induced resistance to leptin transport across the BBB initially evolved to limit the signal of an anorectic to the brain during starvation.     

The effects of inverting prisms on the horizontal–vertical illusion: a systematic effect of downward gaze

The purpose of this work is to compare the relative contributions from the extraocular and sensory systems on the magnitude of the horizontal–vertical illusion (HVI). The visual HVI refers to the general tendency to overestimate vertical extensions of small-scale lines on a picture plane relative to the horizontal by 4–16% depending on the method of measurement. The HVI line stimuli consisted of luminous vertical and horizontal lines forming “L-profiles” located in the frontoparallel plane at a 45 cm viewing distance, collinearly with a binocular gaze. The home position of gaze was aligned to the center of the screen with the ear–eye angle concordant with the environmental horizontal. Illusion strength was quantified when subjects fixated the HVI line stimuli in four quadrants of the visual field. The HVI was also viewed through prism lenses that inverted the retinal images by 180°, thereby dissociating the sensory “up-down” direction from the oculomotor up-down frame of reference. The results revealed a systematically lower magnitude of the HVI in the bottom visual field regardless of whether subjects fixated the HVI with the distorting prisms or without. Taken together, these results suggest that the HVI is sensitive to small-angle gaze shifts. In agreement with several recent findings, these results are interpreted as implying that the brain imposes an enhanced analytic structure on the ascending sensory information during downward gaze. Hans O. Richter and Jaanus Raudsepp contributed equally to this work.     

Functionalization of poly-L-lactic-co-ε-caprolactone: effects of surface modification on endothelial cell proliferation and hemocompatibility

A copolymer of L-lactic acid and ε-caprolactone (PLLACL) was synthesized with the aim of preparing a bioartificial, small-diameter and partially resorbable vascular graft. The material was submitted to surface functionalizations (i.e. chemical modification by means of hydrolytic 'etching' and plasma discharge) to promote endothelial cell (EC) adhesion and growth avoiding platelet adhesion or coagulation factor absorption. Furthermore, the behaviour of human microvascular endothelial cells (HMVEC) seeded on the untreated and treated copolymer is described, as well as the platelet adhesion and the modifications of coagulation factors determined by the copolymer itself. PLLACL in its native state provided little support for EC adhesion. Improved EC adherence was obtained when functional groups were provided on the polymer surface by surface chemical hydrolysis. HMVEC seeded and cultured on the polymer surface did not show any ultrastructural alteration, thus demonstrating the absence of the polymer cytotoxicity. Moreover, SEM analysis performed on cold plasma modified specimens showed the presence of a subconfluent monolayer of EC, with an elongated spread morphology. Both the untreated and treated copolymers induced only slight variations of platelet number, but determined the activated partial thromboplastin time (APTT) increase, due to factor XI reduction. Finally,a prototype of partially biodegradable vascular prosthesis was prepared with NaOH/HCl-treated copolymer. Pre-cultured HMVEC seeding of the prosthesis by means of a rotation device resulted in an almost completely coverage of the graft inner surface.     

The duplicitous effects of interleukin 4 on tumour immunity: how can the same cytokine improve or impair control of tumour growth?

Successful tumour immunity relies on innate and adaptive immune responses, with cytokines like interleukin 4 (IL-4) known to influence tumour clearance in both positive and negative ways. Here, we summarise some of the murine tumour models used over the past two decades to assess the impact of IL-4 on tumour immunity, with emphasis on the effects of IL-4 on the tumour-induced CD8 T-cell response. These data are compared with our own recent studies showing that IL-4 impairs CD8+ T-cell-mediated immunity against the mastocytoma cell line P815 expressing the immunogenic HLA-CW3 gene; moreover, we hypothesise that quantitative and qualitative differences in the HLA-CW3-induced CD8+ T-cell response impair control of tumour growth and aid the development of secondary tumours. We conclude that the duplicitous effects of IL-4 on tumour immunity depend on the type of effector cell (adaptive/innate) mediating tumour clearance and whether tumour growth depends on stromal infrastructure. Thus, the search for factors that improve or weaken the effectiveness of tumour-specific T cells has to be continued to improve modern approaches of immunotherapy against cancer.     

Immunostimulatory activities of Haberlea rhodopensis leaf extract on the specific antibody response: protective effects against γ-radiation-induced immunosuppression

Immunomodulatory and radioprotective properties of Haberlea rhodopensis extract (HRE) in relation to the primary and secondary specific antibody production were evaluated in New Zealand white rabbits. Rabbits were immunised with keyhole limpet hemocyanin (KLH) and were treated with HRE before irradiation with single dose of 2Gy. Control group without irradiation were also treated with HRE. Rabbits were reimmunised and treated again with HRE on Day 36. KLH-specific total IgM, G, A and KLH-specific IgG antibody production were determined during primary and secondary antibody response by enzyme-linked immunosorbent assay (ELISA). We observed a well-defined γ-radiation-induced immunosuppression on the total primary antibody production. Application of HRE restored primary total KLH-specific antibody as well as significantly increased primary KLH-specific IgG antibody response. We also established that HRE strongly enhanced KLH-specific antibody production after reimmunisation. We concluded that HRE exhibits immunostimulatory properties and could play protective role against γ-irradiation damage of immune response.