Platelet collagen receptors

Collagens are important platelet activators in the vascular subendothelium and vessel wall. Since the regulation of platelet activation is a key step in distinguishing normal haemostasis from pathological thrombosis, collagen interactions with platelets are important targets for pharmacological control. Platelets have two major receptors for collagens, the integrin alpha2beta1, with a major role in adhesion and platelet anchoring and the Ig superfamily member, GPVI, principally responsible for signalling and platelet activation. In addition, GPIb-V-IX, can be considered as an indirect collagen receptor acting via von Willebrand factor as bridging molecule and is essential for platelet interactions with collagen at high shear rates. There is some evidence for additional receptors, which may regulate the response to individual collagen types. This review discusses how these receptors work separately with specific agonists and proposes possible mechanisms for how they work together to regulate platelet activation by collagen, which remains controversial and poorly understood.

Cement distribution, volume, and compliance in vertebroplasty: some answers from an anatomy-based nonlinear finite element study

STUDY DESIGN: The biomechanics of vertebral bodies augmented with real distributions of cement were investigated using nonlinear finite element (FE) analysis. OBJECTIVES: To compare stiffness, strength, and stress transfer of augmented versus nonaugmented osteoporotic vertebral bodies under compressive loading. Specifically, to examine how cement distribution, volume, and compliance affect these biomechanical variables. SUMMARY OF BACKGROUND DATA: Previous FE studies suggested that vertebroplasty might alter vertebral stress transfer, leading to adjacent vertebral failure. However, no FE study so far accounted for real cement distributions and bone damage accumulation. METHODS: Twelve vertebral bodies scanned with high-resolution pQCT and tested in compression were augmented with various volumes of cements and scanned again. Nonaugmented and augmented pQCT datasets were converted to FE models, with bone properties modeled with an elastic, plastic and damage constitutive law that was previously calibrated for the nonaugmented models. The cement-bone composite was modeled with a rule of mixture. The nonaugmented and augmented FE models were subjected to compression and their stiffness, strength, and stress map calculated for different cement compliances. RESULTS: Cement distribution dominated the stiffening and strengthening effects of augmentation. Models with cement connecting either the superior or inferior endplate (S/I fillings) were only up to 2 times stiffer than the nonaugmented models with minimal strengthening, whereas those with cement connecting both endplates (S + I fillings) were 1 to 8 times stiffer and 1 to 12 times stronger. Stress increases above and below the cement, which was higher for the S + I cases and was significantly reduced by increasing cement compliance. CONCLUSION: The developed FE approach, which accounts for real cement distributions and bone damage accumulation, provides a refined insight into the mechanics of augmented vertebral bodies. In particular, augmentation with compliant cement bridging both endplates would reduce stress transfer while providing sufficient strengthening.

Adapting health-risk communication to the specific cultural contexts of diverse populations : an assessment of malaria-treatment programs in Liberia

Drawing on theories of technical communication, rhetoric, literacy, language and culture, and medical anthropology, this dissertation explores how local culture and traditions can be incorporated into health-risk-communication-program design and implementation, including the design and dissemination of health-risk messages. In a modern world with increasing global economic partnerships, mounting health and environmental risks, and cross-cultural collaborations, those who interact with people of different cultures have “a moral obligation to take those cultures seriously, including their social organization and values” (Hahn and Inhorn 10). Paradoxically, at the same time as we must carefully adapt health, safety, and environmental-risk messages to diverse cultures and populations, we must also recognize the increasing extent to which we are all becoming part of one, vast, interrelated global village. This, too, has a significant impact on the ways in which healthcare plans should be designed, communicated, and implemented. Because communicating across diverse cultures requires a system for “bridging the gap between individual differences and negotiating individual realities” (Kim and Gudykunst 50), both administrators and beneficiaries of malaria-treatment-and-control programs (MTCPs) in Liberia were targeted to participate in this study. A total of 105 people participated in this study: 21 MTCP administrators (including designers and implementers) completed survey questionnaires on program design, implementation, and outcomes; and 84 MTCP beneficiaries (e.g., traditional leaders and young adults) were interviewed about their knowledge of malaria and methods for communicating health risks in their tribe or culture. All participants showed a tremendous sense of courage, commitment, resilience, and pragmatism, especially in light of the fact that many of them live and work under dire socioeconomic conditions (e.g., no electricity and poor communication networks). Although many MTCP beneficiaries interviewed for this study had bed nets in their homes, a majority (46.34 percent) used a combination of traditional herbal medicine and Western medicine to treat malaria. MTCP administrators who participated in this study rated the impacts of their programs on reducing malaria in Liberia as moderately successful (61.90 percent) or greatly successful (38.10 percent), and they offered a variety of insights on what they might do differently in the future to incorporate local culture and traditions into program design and implementation. Participating MTCP administrators and beneficiaries differed in their understanding of what “cultural incorporation” meant, but they agreed that using local indigenous languages to communicate health-risk messages was essential for effective health-risk communication. They also suggested that understanding the literacy practices and linguistic cultures of the local people is essential to communicating health risks across diverse cultures and populations.

Extracellular matrix of the charophycean green algae

A comprehensive knowledge of cell wallstructure and function throughout the plant kingdom is essential to understanding cell wall evolution. The fundamental understanding of the charophycean green algal cell wall is broadening. The similarities and differences that exist between land plant and algal cell walls provide opportunities to understand plant evolution. A variety of polymers previously associated with higher plants were discovered in the charophycean green algae (CGA), including homogalacturonans, cross-linking glycans, arabinogalactan protein, β-glucans, and cellulose. The cellulose content of CGA cell walls ranged from 6% to 43%, with the higher valuescomparable to that found in the primary cell wall of land plants (20-30%). (1,3)β-glucans were found in the unicellular Chlorokybus atmophyticus, Penium margaritaceum, and Cosmarium turpini, the unbranched filamentous Klebsormidium flaccidum, and the multicellular Chara corallina. The discovery of homogalacturonan in Penium margaritaceum representsthe first confirmation of land plant-type pectinsin desmids and the second rigorous characterization of a pectin polymer from the charophycean algae. Homogalacturonan was also indicated from the basal species Chlorokybus atmophyticus and Klebsormidium flaccidum. There is evidence of branched pectins in Cosmarium turpini and linkage analysis suggests the presence of type I rhamnogalacturonan (RGI). Cross-linking β-glucans are associated with cellulose microfibrils during land plant cell growth, and were found in the cell wall of CGA. The evidence of mixed-linkage glucan (MLG) in the 11 charophytesis both suprising and significant given that MLG was once thought to be specific to some grasses. The organization and structure of Cosmarium turpini and Chara corallina MLG was found to be similar to that of Equisetumspp., whereas the basal species of the CGA, Chlorokybus atmophyticus and Klebsormidium flaccidum, have unique organization of alternating of 3- and 4-linkages. The significance of this result on the evolution of the MLG synthetic pathway has yet to be determined. The extracellular matrix (ECM) of Chlorokybus atmophyticus, Klebsormidium flaccidum, and Spirogyra spp. exhibits significant biochemical diversity, ranging from distinct “land plant” polymers to polysaccharides unique to these algae. The neutral sugar composition of Chlorokybus atmophyticus hot water extract and Spirogyra extracellular polymeric substance (EPS), combined with antibody labeling results, revealed the distinct possibility of an arabinogalactan protein in these organisms. Polysaccharide analysis of Zygnematales (desmid) EPS, indicated a probable range of different EPS backbones and substitution patterns upon the core portions of the molecules. Desmid EPS is predominately composed of a complex matrix of branched, uronic acid containing polysaccharides with ester sulfate substitutions and, as such, has an almost infinite capacity for various hydrogen bonding, hydrophobic interaction and ionic cross-bridging motifs, which characterize their unique function in biofilms. My observations support the hypothesis that members of the CGA represent the phylogenetic line that gave rise to vascular plants and that the primary cell wall of vascular plants many have evolved directly from structures typical of the cell wall of filamentous green algae found in the charophycean green algae.

Syntheses and characterization of monomeric Mo(VI) complexes with bidentate phosphine oxide ligands and dimeric and tetrameric Mo(V) clusters with benzoic acid and phosphinic acid derivatives, containing MoO2, Mo2O2(μ-O)2 and Mo4O4(μ3-O)4

Mo(VI) oxo complexes have been persistently sought after as epoxidation catalysts. Further, Mo(V) oxo clusters of the form M4(µ3-X)4 (M = transition metal, X = O, S) have been rigorously studied due to their remarkable structures and also their usefulness as models for electronic studies. The syntheses and characterizations of new Mo(VI) and Mo(V) oxo complexes have been described in this dissertation. Two new complexes MoO2Cl2Ph2P(O)CH2COOH and MoO2Cl2Ph2P(O)C6H4tBuS(O) were synthesized from reactions of “MoO2Cl2” with ligands Ph2P(O)CH2COOH and Ph2P(O)C6H4tBuS(O). Tetrameric packing arrangements comprised of hydrogen bonds were obtained for the complex MoO2Cl2Ph2P(O)CH2COOH and the ligand Ph2P(O)CH2COOH. Further the stability of an Mo-O bond was preferred over the Mo-S bond even though this resulted in the formation of a more strained seven membered ring. Tetranuclear Mo(V) complexes of the form [Mo4(µ3-O)4(µ-O2PR2)4O4], (PR2 = PPh2, PMe2) were synthesized using reactions of MoO2(acac)2 with diphenyl and dimethyl phosphinic acids, in ethanol. In the crystal structure of these complexes four Mo=O units are interconnected by four triply bridging oxygen atoms and bridging phosphinate ligands. The complex exhibited fourfold symmetry as evidenced by a single 31P NMR peak for the P atoms in the coordinated ligands. Reaction of WO2(acac)2 with Ph2POOH in methanol resulted in a dimeric W(VI) complex [(CH3O)2(O)W(µ-O)( µ-O2PPh2)2W(O)(CH3O)2] which contained a packing disorder in its crystal structure. Similar reactions of MoO2(acac)2 with benzoic acid derivatives resulted in dimeric complexes of the form [Mo2O2(acac)2(µ-O)(µ-OC2H5)(µ-O2CR)] (R = C6H5, (o-OH)C6H4, (p-Cl)C6H4, (2,4-(OH)2)C6H3, (o-I)C6H4) and one tetrameric complex [Mo2O2(acac)2(µ-O)(µ-OC2H5)(µ-O2C)C6H4(p-µ-O2C)Mo2O2(acac)2(µ-O)(µ-OC2H5)] with terephthalic acid. 1H NMR proved very useful in the prediction of the formation of dimers with the substituted benzoic acids, which were also confirmed by elemental analyses. The reductive capability of ethanol proved instrumental in the syntheses of Mo(V) tetrameric and dimeric clusters. Synthetic details, IR, 1H and 31P NMR spectroscopy and elemental analyses are reported for all new complexes. Further, single crystal X-ray structures of MoO2Cl2Ph2P(O)CH2COOH, MoO2Cl2Ph2P(O)C6H4tBuS(O), [Mo4(µ3-O)4(µ-O2PR2)4O4], (PR2 = PPh2, PMe2), [(CH3O)2(O)W(µ-O)( µ-O2PPh2)2W(O)(CH3O)2] and [Mo2O2(acac)2(µ-O)(µ-OC2H5)(µ-O2CR)] (R = C6H5, (o-OH)C6H4) are also presented.

Emergency lung transplantation after extracorporeal membrane oxygenation

In some patients with acute respiratory failure, the native lungs do not recover during extracorporeal membrane oxygenation (ECMO), or complications occur that preclude the meaningful continuation of ECMO therapy. In such cases, emergency lung transplantation (LTx) represents the only therapeutic alternative. Between May 1988 and April 1993, the authors have performed LTx after ECMO support in five of 111 lung or heart-lung transplantations (4.5%). Two patients presented with early graft failure after unilateral LTx. In these patients, ECMO was used as a bridging device to unilateral re-LTx for 1, resp. 11 days. One patient died 6 months post-operatively from chronic rejection; the other underwent a third LTx and is doing well after 42 months. In three further patients already treated with ECMO for 5 to 12 days for ARDS (n = 2) or acute respiratory failure after liver and kidney transplantation, the native lungs did not recover (n = 2) or pulmonary hemorrhage developed. The last patient (unilateral LTx) and one of the former (bilateral LTx for ARDS) are long-term survivors (12, 30 months). The remaining patient (unilateral LTx for ARDS) had severe multiorgan failure at the time of his operation and died intraoperatively. The authors conclude that ECMO no longer represents a contraindication to subsequent LTx. Their results also support the continued investigation of this combined therapeutic approach.

Structural characterization and reliable biomechanical assessment of integrative cartilage repair

Structural and functional characterization of integrative cartilage repair in controlled model systems can play a key role in the development of innovative strategies to improve the long-term outcome of many cartilage repair procedures. In this work, we first developed a method to reproducibly generate geometrically defined disk/ring cartilage composites and to remove outgrown fibrous layers which can encapsulate cartilaginous tissues during culture. We then used the model system to test the hypothesis that such fibrous layers lead to an overestimation of biomechanical parameters of integration at the disk/ring interface. Transmission electron microscopy images of the composites after 6 weeks of culture indicated that collagen fibrils in the fibrous tissue layer were well integrated into the collagen network of the cartilage disk and ring, whereas molecular bridging between opposing disk/ring cartilage surfaces was less pronounced and restricted to regions with narrow interfacial regions (< 2 microm). Stress-strain profiles generated from mechanical push-out tests for composites with the layers removed displayed a single and distinct peak, whereas profiles for composites with the layers left intact consisted of multiple superimposed peaks. As compared to composites with removed layers, composites with intact layers had significantly higher adhesive strengths (161+/-9 vs. 71+/-11 kPa) and adhesion energies (15.0+/-0.7 vs. 2.7+/-0.4 mJ/mm2). By combining structural and functional analyses, we demonstrated that the outgrowing tissue formed during in vitro culture of cartilaginous specimens should be eliminated in order to reliably quantify biomechanical parameters related to integrative cartilage repair.

Hemostasis management in pediatric mechanical circulatory support

In a 9-year-old boy, bridging to transplantation was successful with an external biventricular device, the Berlin Heart Excor (Berlin Heart, Berlin, Germany), during a 7-month period. Main long-term complications consisted of infection and hypercoagulability with clotting inside the chambers necessitating six pump exchanges, but without thromboembolic events. This report reviews hemostasis monitoring and management of long-term mechanical circulatory support.