The glycoprotein IIb/IIIa antagonist c7E3 inhibits platelet aggregation in the presence of heparin-associated antibodies

AbstractPurpose: Heparin-associated antibodies (HAAb), in the presence of heparin, can cause platelet activation and aggregation. The purpose of this study was to assess whether a platelet glycoprotein (GP) IIb/IIIa receptor antagonist, c7E3, would inhibit platelet aggregation in the presence of HAAb. If aggregation is inhibited by c7E3, enzyme-linked immunosorbent assays (ELISA) would be done to determine whether c7E3 interfered with the binding of heparin and the HAAb.Methods: HAAb-positive plasmas from 21 patients (determined by platelet aggregation assays) were studied. Normal donor platelet-rich plasmas (PRP) were incubated (1 minute) with either saline solution or 3 μg/ml of c7E3. Platelet-poor plasma from patients with HAAb and one of three sources of heparin (25 μl, 10 U/ml; porcine heparin, bovine heparin, and low molecular weight heparin [enoxaparin]) were added to the PRP mixture. Aggregation was determined using a platelet aggregometer by measuring time to aggregation, the slope of the aggregation curve, and the percent change in optical density.Results: Platelet aggregation occured in 100%, 100%, and 95% of the saline solution incubations exposed to porcine heparin, bovine heparin, and enoxaparin, respectively. Incubation with c7E3 caused 100% inhibition of platelet aggregation in plasma exposed to porcine heparin, bovine heparin, and enoxaparin. The optical density curves obtained from the ELISA, which were dependent on the binding of HAAb to heparin, were not significantly different when c7E3 was compared to buffer alone.Conclusions: The GP IIb/IIIa receptor antagonist, c7E3, inhibits HAAb-induced platelet aggregation via a mechanism that does not appear to interfere with the binding between heparin and HAAb. Clinical trials are warranted to assess whether GP IIb/IIIa antagonists may allow patients with HAAb to safely receive heparin. (J Vasc Surg 1997;25:124-30.

VARIATIONS IN THE RESPONSES OF C57BL/10J AND A/J MICE TO SHEEP RED BLOOD CELLS : I. SEROLOGICAL CHARACTERIZATION AND GENETIC ANALYSIS

In response to repeated injections of sheep red blood cells, C57BL/10J mice produce predominantly 19S antibody in increasingly higher amounts, while A/J mice initially produce 19S antibody and then switch to produce increasing 7S antibody titers. In an F1 generation all mice responded like the C57BL/10J mice. Backcross data implied genetic control involving at least three loci

Water solubility in aluminosilicate melts of haplogranite composition at 2 kbar

The compositional dependence of H2O solubility was investigated at 2 kbar and 800°C in haplogranite melts (system SiO2---1bNaAlSi3O8---1bKAlSi3O8 or Qz---1bAb---1bOr). The sixteen investigated compositions contained 25, 35 or 45 wt.% normative Qz and various Ab/(Ab+Or) ratios (0.15–0.92). Starting solid materials were anhydrous bubble-free glasses to which 10 wt.% H2O was added. The H2O contents of the isobarically quenched melts (glasses) were measured by Karl-Fischer titration. The results show that H2O solubility in aluminosilicate melts depends significantly upon anhydrous composition. The highest solubility values are obtained for the most Ab-rich melts. At a constant normative quartz content, the solubility of water decreases from 6.49 ± 0.20 wt.% H2O for a composition Qz35Ab60Or05 (normative composition expressed in wt.%) to 5.50 ± 0.15 wt.% H2O for a composition Qz35Ab10Or55. Along this join, the most significant changes are observed for Ab-rich melts whereas H2O solubility in Or-rich melts remains almost constant. The H2O solubility data imply that H2O is preferentially associated with the Ab component in aluminosilicate melts. Application of the results to natural granitic melts suggests that Na-rich, H2O-saturated melts may be significantly less viscous than H2O-saturated, K-rich melts. The temperature dependence of H2O solubility, investigated for composition Qz28Ab38Or34 at 2 kbar, is low. Increasing temperature from 750° to 1150°C only causes a decrease in H2O solubility from 6.00 to 5.41 wt.% H2O. These data are in agreement with previous data obtained for albite melts

Exploring the Perspectives of South African Parents and Primary Caregivers Living in Low-Income Communities on What Children Need to Thrive within the First 1000 Days of Life

The first 1000 days is recognised as a critical period for the development of children. What children need to thrive in this particular phase of development may be different from any other phase. In South Africa, parents’ perception of children’s needs within the first 1000 days of life could be considered as emerging. Therefore, this study aims to explore the perspectives of South African parents and primary caregivers on what children need to thrive within the first 1000 days. An exploratory qualitative study design was used to explore the parents’ understanding of what children need to thrive in the first 1000 days. A purposive sampling approach was employed to select parents and primary caregivers in low-income communities. In all, thirty respondents participated in the study. The data were analysed using thematic analysis. During the analysis, four themes emerged. The themes included (1) the importance of parenting, care and support; (2) children’s need for holistic development; (3) parental roles; and (4) sharing responsibilities. Parents and primary caregivers living in low-income communities understand what children need to thrive within the first thousand days of life. The study could assist policymakers and service providers to design appropriate interventions for parents within these communities

Experimental strategies for the investigation of low temperature properties in granitic and pegmatitic melts

The physical behavior of silicate melts during the final stages of intrusion in the earth's crust are poorly understood. In particular, the low temperature limit of igneous petrogenesis is poorly constrained. The extreme differentiates of granitic magmatism that lead to pegmatite genesis span a very large range of composition not normally considered to be within the domain of igneous melt compositions. This combination of very low petrogenetic temperatures and extreme chemistries requires a concentrated effort for the determination of melt properties under conditions of pressure, temperature and composition appropriate to these systems. An experimental strategy for the determination of melt properties under appropriate conditions is presented. The determination of individual melt properties at very low temperatures is described with the aid of three examples, heat capacity, volume and viscosity. In this way the physical behavior of an important component of the earth's crust will become accessible

Fate of Biological Control Introductions: Monitoring an Australian Fungal Pathogen of Grasshoppers in North America

In North America there are two generally recognized pathotypes (pathotypes 1 and 2) of the fungus Entomophaga grylli which show host-preferential infection of grasshopper subfamilies. Pathotype 3, discovered in Austra- lia,hasabroadergrasshopperhostrangeandwasconsidered to be a good biocontrol agent. Between 1989 and 1991 patho- type3wasintroducedattwofieldsitesinNorthDakota.Since resting spores are morphologically indistinguishable among pathotypes, we used pathotype-specific DNA probes to con- firm pathotype identification in E. grylli-infected grasshop- pers collected at the release sites in 1992, 1993, and 1994. In 1992, up to 23% of E. grylli-infected grasshoppers of the subfamilies Melanoplinae, Oedipodinae, and Gomphocerinae were infected by pathotype 3,with no infections \u3e1 km from the release sites. In 1993, pathotype 3 infections declined to 1.7%. In 1994 grasshopper populations were low and no pathotype3infectionswerefound.Thefrequencyofpathotype 3 infection has declined to levels where its long-term survival in North America is questionable. Analyses of biocontrol releases are critical to evaluating the environmental risks associatedwiththeseecologicalmanipulations,andmolecular probesarepowerfultoolsformonitoringbiocontrolreleases

Sex Differences in Clinical Outcomes and Biological Profiles in Systemic Sclerosis-Associated Interstitial Lung Disease: A Post-Hoc Analysis of Two Randomised Controlled Trials

BACKGROUND: Observational studies have shown that men with systemic sclerosis have an increased risk of interstitial lung disease (ILD) and mortality compared with women. However, previous studies have not controlled for treatment effect or evaluated the biological mechanism or mechanisms underlying this sex difference. We aimed to compare ILD progression and long-term morbidity and mortality outcomes in male and female participants of two randomised controlled trials for systemic sclerosis-associated ILD. METHODS: For this post-hoc analysis, data from all participants in the Scleroderma Lung Study (SLS) I and SLS II were analysed. The primary objective was to explore the effect of sex on the course of the percentage predicted forced vital capacity (FVC) during and after active treatment over the 24-month study periods. In SLS I, 158 participants (111 women, 47 men) were randomly assigned to receive oral cyclophosphamide (cyclophosphamide; ≤2 mg/kg daily) or placebo; in SLS II, 142 participants (105 women, 37 men) were randomly assigned to receive oral mycophenolate mofetil (1500 mg twice daily) or oral cyclophosphamide (≤2 mg/kg daily). Sex (ie, male or female) was self-reported in both studies by the participants. Changes in radiographic fibrosis and time to death and respiratory failure were secondary outcomes of the present analysis. Baseline levels of biomarkers implicated in the pathobiology of systemic sclerosis-associated ILD were measured in bronchoalveolar lavage fluid in SLS I. FINDINGS: In the SLS I placebo group, the rate of decline in percentage predicted FVC from 3 months to 12 months was greater in men than in women, but the difference was not significant (estimated effect -0·29 [95% CI -0·67 to 0·10]; p=0·14). In SLS II, the rate of decline in percentage predicted FVC from 3 months to 12 months was significantly worse in men treated with either cyclophosphamide (estimated effect -0·72; [95% CI -1·14 to -0·31]; p=0·00060) or mycophenolate mofetil (estimated effect -0·34 [-0·58 to -0·10]; p=0·0051) than in women. A greater proportion of men had a decline in percentage predicted FVC of 10% or greater compared with women for the pooled active treatment groups from SLS I and SLS II and the placebo group of SLS I. Men had worse radiographic outcomes at 2 years than women in SLS II, even after adjusting for baseline disease severity and treatment arm assignment. Long-term survival was worse in men in SLS I (log-rank test p=0·080) and SLS II (log-rank test p=0·030). In SLS II, male sex was independently associated with increased mortality (hazard ratio 2·42 [95% CI 1·16 to 5·04]; p=0·018). In bronchoalveolar lavage fluid, men had increased concentrations of pro-fibrotic mediators (eg, matrix metalloproteinase-13 and tissue inhibitor of metallopeptidase 1), whereas women had increased pro-inflammatory mediators (eg, interleukin [IL]-12, IL-7, and granulocyte-colony stimulating factor). INTERPRETATION: In two randomised controlled trials, men with systemic sclerosis-associated ILD had a less favourable course of ILD both with and without active treatment, as well as worse long-term survival. Sex differences in pro-fibrotic or inflammatory mediators of disease might account for these differences and warrant future study. FUNDING: US National Institutes of Health; US National Heart, Lung, and Blood Institute; US National Institute of Arthritis and Musculoskeletal and Skin Diseases; Bristol Myers Squibb; and Hoffmann-LaRoche

Relations between mud volcanoes, thrust deformation, slope sedimentation, and gas hydrate, offshore north Panama

SeaMARC II swath-mapping and migrated seismic reflection data show a high concentration of mud volcanoes in the primary sediment depocentre along the lower slope of a thrust belt, offshore north Panama. The mud volcanoes are 0.4-2.0 km wide, Sonar reflectivity (backscattering), sediment cores, and seismic stratigraphic relations indicate that the depocentre contains thick sequences of basinal turbidites which are ponded between the anticlinal ridges. The ridges are composed of the deformed turbidites of the Colombian basin and exhibit a strong bottom-simulating reflector (BSR), apparently associated with a gas hydrate layer. Based on the concentration of mud volcanoes along the crests of the anticlinal ridges in the depocentre and the structural position of the BSR, we suggest that folding along the deformation front, sediment ponding leading to differential loading, methane migration and accumulation in the anticlines, and gas hydrate formation are important factors in the development of mud volcanoes in this region.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28727/1/0000553.pd