bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanism of action of β2-glycoprotein I-dependent lupus anticoagulants
Authors: Amout J , Vermylen J
Published: March 2009

There is accumulating evidence showing that lupus anticoagulants (LA) are more strongly associated with thrombosis than anticardiolipin antibodies. In addition, indirect evidence has been presented indicating that β2GPI-dependent LA are more strongly associated with thrombosis than prothrombin-dependent LA. From this, one may assume that anti-β2GPl antibodies with LA activity are more pathogenic than anti-β2GPI antibodies without LA activity. Therefore, it is of the utmost importance to understand the molecular basis on which some anti-β2GPI antibodies behave as LA. In this presentation, the current knowledge on the interaction of β2GPI with phospholipids and with anti-β2GPI antibodies is reviewed and an integrated model for the anti-β2GPI - dependent LA activity is proposed with implications for a pathogenic role of these particular antibodies.
Prothrombin as cofactor for antiphospholipids
Authors: Galli M , Barbui T
Published: March 2009

Prothrombin is a common antigenic target of antiphospholipid antibodies, since anti-prothrombin antibodies are detected in about 50-90% of the patients. To allow proper immune recognition, prothrombin must be adsorbed on suitable anionic surfaces. The epitope(s) have not yet been identified: the majority of anti-prothrombin antibodies appear to be of poly- or oligoclonal nature. Anti-prothrombin antibodies, either alone or in combination with anti-β2-glycoprotein I antibodies, are responsible for the lupus anticoagulant activity of about 75% of the cases of phospholipid-dependent inhibitors of coagulation. The two antibodies may be discriminated by means of specific coagulation profiles generated by the comparison of the ratio of the Kaolin Clotting Time (KCT) and the dilute Russell's Viper Venom Time (dRVVT): the KCT profile, which mainly reflects the presence of anti-prothrombin antibodies and the dRVVT profile, which is mostly associated with anti-β2-glycoprotein I antibodies. This distinction, although somewhat artificial, may be clinically useful, since the KCT profile identifies patients at low risk to develop thrombosis. Similarly, most of the studies that measured anti-prothrombin antibodies by ELISA failed to find a significant association with thrombosis. In conclusion, the clinical relevance of these antibodies has not yet been established.
Platelet activation markers and the primary antiphospholipid syndrome (PAPS)
Authors: Joseph JE , Harrison P , Mackie IJ , Machin SJ
Published: March 2009

Platelets play an important part in normal haemostasis, and are likely to be involved in the thromboembolism seen in the primary antiphospholipid syndrome (PAPS). Evidence exists for platelet activation in this disorder, and new flow cytometric techniques have made it possible to detect low levels of activation. We have previously studied the expression of the platelet activation markers CD62p and CD63, percentage of reticulated platelets, and levels of soluble P-selectin in a group of PAPS patients. Median platelet CD63 expression and plasma soluble P-selectin levels were significantly increased in PAPS patients compared to a group of controls; there was no difference in reticulated platelet percentages between the two groups. Additional assays of platelet activation (PAC-1 expression, Annexin V binding, platelet microparticles and complexes) are being developed and assessed with respect to disease activity, thrombosis risk and effects of antithrombotic therapy.
The catastrophic antiphospholipid syndrome, 1998. A review of the clinical features, possible pathogenesis and treatment
Authors: Asherson RA
Published: March 2009

A review of 50 patients who manifest features of the catastrophic antiphospholipid syndrome (CAPS) is presented. The clinical features comprise mainly organ involvement as opposed to large-vessel venous or arterial occlusions as is seen in patients with ‘simple’ antiphospholipid syndrome (APS), which makes the pathogenesis of this unusually rare complication perhaps somewhat different from that of patients with the APS. The mortality of the condition is 50%, most patients dying as a result of a combination of cardiac and respiratory failure. Fifteen patients (28%) suffered from disseminated intravascular coagulation (DIC) as well, which may have contributed to the multiorgan thrombotic microangiopathy characteristic of the CAPS. Although most patients were treated with high-dose i.v. steroids, heparin, cyclophosphamide and other modalities of therapy (such as i.v. globulin), plasmapheresis (advocated for TTP, a similar microangiopathic condition) seemed to offer some benefit (68% recovery). The systemic inflammatory response syndrome (SIRS) was responsible for some of the clinical manifestations such as adult respiratory distress syndrome (ARDS) seen in 15 patients. Pathogenesis of the CAPS seems dependent on a ‘two-hit’ or even ‘three-hit’ hypothesis in patients already suffering from a hypercoagulable state. Precipitating factors include infections, trauma (surgical), drug administration and warfarin withdrawal. A recent view that the multiple thrombotic lesions themselves may contribute to further thrombosis (‘thrombotic storm’) is also discussed.
Neurological manifestations of antiphospholipid antibody syndrome
Authors: Brey R.L. , Escalante A
Published: March 2009

Thrombosis, thrombocytopenia, recurrent fetal loss and a variety of non-thrombotic neurological disorders have all been associated with antiphospholipid antibodies (aPL). Cerebral ischemia associated with aPL is the most common arterial thrombotic manifestation. Depression, cognitive dysfunction, depression and psychosis have all been associated with aPL. The presumed pathophysiologic mechanism underlying these manifestations is thought to be a result of cerebral ischemia in some, but not all cases. Seizures, chorea and transverse myelitis all appear to be associated with aPL. An interaction between aPL and central nervous system cellular elements rather than aPL-associated thrombosis seems to be a more plausible mechanism for these clinical manifestations. Migraine on the other hand, does not appear to be associated with aPL in either lupus or non-lupus populations. Neuroimaging studies show an increased frequency of brain abnormalities in patients with aPL, but none appear to be specific. The best treatment strategy for preventing neurological manifestations of aPL is not fully defined. For thrombotic manifestations, both antiplatelet and anticoagulant therapies have been suggested. In some patients, immunosuppressant therapy has been used. For non-thrombotic manifestations, some combination of immunosuppressant therapy and symptomatic treatment may be warranted.
Antiphospholipid antibodies and infertility: Fact or fallacy
Authors: Branch D Ware , Hatasaka HH
Published: March 2009

Some clinicians are convinced that antiphospholipid antibodies, including antibodies to any one of five-to-seven phospholipid antigens, are associated with infertility. Additionally, some clinicians recommend that infertile women who have antiphospholipid antibodies and are undergoing in-vitro fertilization should be treated with heparin to improve the rate of pregnancy. However, experts disagree regarding the relationship between antiphospholipid antibodies and infertility. There is also substantial evidence that treatment with heparin does not alter the rate of pregnancy following in-vitro fertilization. Why the confusion? Probable culprits include variation in study design and the selection of infertile patients. Another important problem is that assays for antiphospholipid antibodies other than anticardiolipin are not standardized. Before the real relationship between antiphospholipid antibodies and infertility is discovered, assays for antiphospholipid antibodies other than anticardiolipin must be standardized and properly designed studies conducted. Randomized, controlled trials must be done to determine if heparin should be recommended as an adjunctive treatment for in-vitro fertilization in women with antiphospholipid antibodies.
Anti-β2-glycoprotein I antibodies
Authors: Tsutsumi A , Ichikawa K , Matsuura E , Koike T
Published: March 2009

The relationship between presence of anti-β2-glycoprotein I autoantibodies (aβ2-GPI) and history of thrombosis is now widely known. However, differences in the methodology of aβ2-GPI detection have made the comparison of data from different laboratories extremely difficult. We discuss the significance of aβ2-GPI of the IgG, IgM and IgA isotypes, and our approach to developing an easier and more reproducible method for the detection of this autoantibody. In addition, we present data that shows that commercially available enzyme immunoassay plates differ regarding detectability of aβ2-GPI. Since the clinical significance of this heterogeneity is presently unclear, the set-up of the detection systems and interpretation of data need great care.
Anti β2-glycoprotein I antibodies: Clinical significance
Authors: Tincani A , Spatola L , Cinquini M , Cattaneo R , Meroni P , Balestrieri G
Published: March 2009

The introduction of anticardiolipin antibody (aCL) assay, described in 1983, was able to focus much attention on the study of patients suffering from thrombosis, repeated fetal loss and thrombocytopenia, and allowing the identification of the so called antiphospholipid syndrome (APS). The identification of β2 glycoprotein I (β22GPI) as an essential component of the antigenic complex recognized by aCL suggested that this molecule could be a direct target of the antibody response. Since then, different groups have described ELISAs for the detection of anti β2GPI antibodies, applied to the clinical evaluation of patients with APS, and showing an overall better specificity. Recently, anti β2GPI were also shown to bind apoptotic bodies resulting in an alteration of their physiological clearance with the triggering of TNFα release. This observation suggests that anti β2GPI may also modify the immunogenicity of apoptotic bodies and of the autoantigens that they contain.
Significance of IgA antiphospholipid antibodies
Authors: Wilson WA , Faghiri Z , Taheri F , Gharavi AE
Published: March 2009

IgA anticardiolipin (IgA aCL) and IgA anti β2-glycoprotein-I(IgA anti β2GP1) antibodies are common in SLE and have been associated in some studies with thromboses and thrombocytopenia. Experimental work suggests that IgA aCL are as prothrombotic as the IgG-IgM isotypes. However, in SLE there appears to be less concordance between IgA aCl and IgA anti β2GP1 as compared with the concordance between IgG and IgM isotypes, suggesting significant differences in their origins and specificities. For example, there may be a greater mucosal contribution to production of IgA antiβ2GPl than IgA aCL. Infections may have a greater role in the presence of IgA aCL than IgA antiβ2GP1 antibodies.
Mechanisms of autoantibody-mediated thrombosis
Authors: Roubey R.A.S.
Published: March 2009

It is widely hypothesized that autoantibodies directly contribute to the prothrombotic state in the antiphospholipid syndrome (APS). The discovery that antiphospholipid autoantibodies are specific for phospholipid-binding plasma proteins (β2-glycoprotein I, prothrombin, etc.) has allowed a much more precise investigation of the interactions of autoantibodies and antigens, and the effects of these interaction on hemostastis. Recent studies suggest that two types of interactions may be important in the pathophysiology of APS: (1) antibody cross-linking of membrane bound antigens may alter the kinetics of phospholipid-dependent reactions; and (2) antibody cross-linking of antigens bound to cell surface receptors may trigger signal transduction and cellular activation. In light of these findings, previous reports implicating various mechanisms of autoantibody-mediated thrombosis are being re-evaluated.
Management of thrombosis and pregnancy loss in the antiphospholipid syndrome
Authors: Khamashta MA
Published: March 2009

More than a decade has gone by since the detailed clinical description of the Antiphospholipid (Hughes) Syndrome. Because of the wide spectrum of manifestations, virtually any physician may encounter patients with this potentially treatable condition. Because of limited controlled, prospective data, current therapy remains empirical and directed at coagulation mechanisms, immune mechanisms, or both. There is now good evidence that patients with antiphospholipid-associated thrombosis will be subject to recurrences and require prophylactic therapy. Although most authorities agree about the efficacy of warfarin alone or warfarin plus low-dose aspirin in preventing recurrences of venous and arterial thrombosis, there is still doubt regarding the intensity and duration of warfarin therapy. Steroids and immunosuppressive drugs have not provided long-term benefit. Controlled clinical trials of the treatment of pregnant women with antiphospholipid antibody demonstrated that prednisolone is ineffective, and possibly detrimental, in treatment of recurrent pregnancy loss and that heparin plus low-dose aspirin is beneficial.
Support for Alzheimer’s Caregivers
Authors: Wilks Scott E.
Published: March 2009

Objective: Information on the shortened, 20-item version of the Perceived Social Support Scale (S-PSSS) is scarce. The purpose of this study is to evaluate the psychometric properties of the S-PSSS Family (SSfa) and Friends (SSfr) subscales. Method: Because of their common coping method of social support, a cross-sectional sample of Alzheimer’s caregivers was relevant for this evaluation. Self-reported data were collected from 229 participants at two caregiver conferences. Results: Factor analysis on each measure indicated a three-factor solution with all items loaded. Reliability was satisfactory. Correlational analyses and odds ratios indicated preliminary construct validity for SSfa and SSfr. Conclusion: The S-PSSS subscales appear to be psychometrically appropriate for potential use in appraising family and friend support among Alzheimer’s caregivers.
Overview: PPO Performance Measurement: Agenda for the Future
Authors: Greenberg Liza
Published: March 2009

This special issue of Medical Care Research and Review features articles developed for a national conference on performance measurement in preferred provider organizations (PPOs). The conference, “PPO Performance Measurement: Agenda for the Future,” was held March 15-16, 2001, in Washington, D.C. It brought together various stake-holders—industry representatives, consumers, purchasers, and regulators—to discuss the state of PPO performance reporting and develop a strategy for future directions. These articles provided the background for an informed dialogue. The American Accreditation HealthCare Commission (URAC), the Consumer Coalition for Quality HealthCare, the Joint Commission on Accreditation of Healthcare Organizations, and the National Committee for Quality Assurance cosponsored the conference with a grant from the Agency for Healthcare Research and Quality to URAC.
Covered Lives in PPOs
Authors: Smith Dean G. , Scanlon Dennis P.
Published: March 2009

Many measures of health plan performance require a count of covered lives to make the results meaningful. For both organizational and economic reasons, many preferred provider organizations (PPOs) do not collect enrollment data. Enrollment can be estimated, but current techniques for estimating enrollment are quite imprecise. Imprecision introduces considerable uncertainty into measures of PPO performance. Furthermore, uncertainty may exist even when enrollment data are available and complete because of challenges that PPOs face in linking enrollment data to claims and administrative data. Efforts to increase accountability through performance reporting may require PPOs to devote additional resources for the collection and management of enrollment data. The authors describe practices in tracking enrollment in PPOs and provide data to illustrate variations at both the regional and company levels. Variations in tracking dependents and lack of information on the demographic characteristics of PPO subscribers affect a PPO’s ability to produce standardized performance measures comparable to health maintenance organization performance measures.
Use of interferon beta in multiple sclerosis: rationale for early treatment and evidence for dose- and frequency-dependent effects on clinical response
Authors: Coyle PK , Hartung H-P.
Published: March 2009

The current approach to the use of interferon (IFN) beta in the treatment of multiple sclerosis (MS) is, in general, conservative. However, recent findings about early events in MS and data on dose-response relationships with IFN beta indicate that such an approach may be suboptimal. Four lines of evidence suggest that delays in the initiation of therapy with IFN beta may be detrimental: I) axonal damage secondary to inflammation starts very early in the course of MS; 2) pathological events occurring early in MS are predictive of the future course of the disease; 3) inflammatory activity in relapsing MS is not confined to episodes of clinical impairment, but often starts before the first such episode and generally continues during remissions; and 4) the immune-mediated activity that underlies MS may become more difficult to control as the disease progresses. An early treatment strategy is also supported by data from two recently published clinical studies. In addition, preclinical and clinical results suggest that the beneficial effects of IFN may be dose- and frequency-dependent Taken together, these findings indicate that treatment with IFN beta should be started as early as possible in the course of MS, and suggest that, in order to maximize patient benefit, the highest possible dose of IFN beta should be chosen. Multiple Sclerosis (2002) 8, 2-9
Contribution of cervical cord MRI and brain magnetization transfer imaging to the assessment of individual patients with multiple sclerosis: a preliminary study
Authors: Rovaris M. , Holtmannspötter M. , Rocca MA , Iannucci G. , Codella M. , Viti B. , Campi A. , Comi G. , Yousry TA , Filippi M.
Published: March 2009

This study was performed to assess how established diagnostic criteria for brain magnetic resonance imaging (MRI) interpretation in cases of suspected multiple sclerosis (MS) (Barkhofs criteria) would perform in the distinction of MS from other diseases and whether other MR techniques (cervical cord imaging and brain magnetization transfer imaging [MTI]), might help in the diagnostic work-up of these patients. We retrospectively identified 64 MS and 59 non-MS patients. The latter group included patients with systemic immune-mediated disorders (SID; n=44) and migraine (n=15). All patients had undergone MRI scans of the brain (dual echo and MTI) and of the cervical cord (fast short-tau inversion recovery). The number and location of brain T2-hyperintense lesions and the number and size of cervical cord lesions were assessed. Brain images were also postprocessed to quantify the total lesion volumes (TLV) and to create histograms of magnetization transfer ratio (MTR) values from the whole of the brain tissue. Barkhofs criteria correctly classified 108/123 patients, thus showing an accuracy of 87.8%. "False negative" MS patients were 13, while 2 patients with systemic lupus erythematosus (SLE) were considered as "false positives". Using brain T2 TLV, nine of the"false negative" patients were correctly classified. Correct classification of 10 MS patients and both the SLE patients was possible based upon the presence or absence of one cervical cord lesion. Two MS patients with negative Barkhofs criteria and no cervical cord lesions were correctly classified based on their brain MTR values. Overall, only one MS patient could not be correctly classified by any of the assessed MR quantities. These preliminary data support a more extensive use of cervical cord MRI and brain MTI to differentiate between MS and other disorders in case of inconclusive findings on T2-weighted MRI scans of the brain. Multiple Sclerosis (2002) 8, 52-58
Incidence of enhancement of the trigeminal nerve on MRI in patients with multiple sclerosis
Authors: van der Meijs Ahc , Tan IL , Barkhof F.
Published: March 2009

The purpose of this study is to review the incidence of contrast enhancement of the trigeminal nerve on magnetic resonance imaging (MRI) in a large cohort of patients with multiple sclerosis (MS). MRI scans of 851 MS patients participating in a phase III clinical trial were reviewed for the presence of gadolinium enhancement on postcontrast TI-weighted images. If enhancement was present, it was documented whether this involved only the proximal or also the distal part of the fifth nerve, and whether the abnormality was unilateral or bilateral. In 24 (2.8%) patients, enhancement of the trigeminal nerve was observed, and was bilateral in 16 (66.7%) of those. In 19 (79.2%) patients with abnormal nerves, enhancement extended to the distal part of the trigeminal nerve (into Meckel's cave). The results of this study indicate a high, probably clinically silent, incidence of trigeminal nerve demyelination in MS and frequent involvement of the peripheral type of myelin in MS. Multiple Sclerosis (2002) 8, 64-67
ADMA: its role in vascular disease
Authors: Cooke John P
Published: March 2009

Endothelium-derived nitric oxide (NO) is the most potent endogenous vasodilator and, by virtue of its anti-inflammatory and anti-thrombotic effects, it is an endogenous anti-atherogenic agent. Accordingly, impairment of NO synthesis or bioactivity may increase the risk of vascular disease. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of the NO synthase pathway. Plasma levels of ADMA are increased in patients with vascular disease, or with risk factors for vascu lar disease. Preclinical and clinical studies indicate that ADMA may mediate the adverse effects of traditional risk factors on endothelial vasodilator function. By impairing endothelial function, ADMA may contribute to pulmonary or systemic hypertension, as well as to vascular disease. Several drugs known to treat cardiovas cular disease also reduce plasma ADMA levels, such as angiotensin receptor antag onists, converting enzyme inhibitors, and insulin sensitizing agents. Plasma ADMA may be a common mediator of endothelial dysfunction induced by vascular risk factors. Insights into the mechanisms by which plasma ADMA is regulated may lead to new therapeutic knowledge.
ADMA and hyperhomocysteinemia
Authors: Dayal Sanjana , Lentz Steven R
Published: March 2009

Hyperhomocysteinemia is a risk factor for cardiovascular disease and stroke. Like many other cardiovascular risk factors, hyperhomocysteinemia produces endothelial dysfunction due to impaired bioavailability of endothelium-derived nitric oxide (NO). The molecular mechanisms responsible for decreased NO bioavailabil ity in hyperhomocysteinemia are incompletely understood, but emerging evidence suggests that asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, may be a key mediator. Homocysteine is produced during the synthesis of ADMA and can alter ADMA metabolism by inhibiting dimethylarginine dimethy laminohydrolase (DDAH). Several animal and clinical studies have demonstrated a strong association between plasma total homocysteine, plasma ADMA, and endothelial dysfunction. These observations suggest a model in which elevation of ADMA may be a unifying mechanism for endothelial dysfunction during hyper homocysteinemia. The recent development of transgenic mice with altered ADMA metabolism should provide further mechanistic insights into the role of ADMA in hyperhomocysteinemia.
Insulin resistance: potential role of the endogenous nitric oxide synthase inhibitor ADMA
Authors: Sydow Karsten , Mondon Carl E , Cooke John P
Published: March 2009

The insulin resistance syndrome (IRS) is considered to be a new target of risk-reduction therapy. The IRS is a cluster of closely associated and interdependent abnormalities and clinical outcomes that occur more commonly in insulin resistant/hyperinsulinemic individuals. This syndrome predisposes individuals to type 2 diabetes, cardiovascular diseases, essential hypertension, certain forms of cancer, polycystic ovary syndrome, nonalcoholic fatty liver disease, and sleep apnea. In patients at high risk for cardiovascular diseases, endothelial dysfunction is observed in morphologically intact vessels even before the onset of clinically mani fest vascular disease. Indeed, there are several lines of evidence that indicate that endothelial function is compromised in situations where there is reduced sensitivity to endogenous insulin. It is well established that a decreased bioavailability of nitric oxide (NO) contributes to endothelial dysfunction. Furthermore, NO may modulate insulin sensitivity. Activation of NO synthase (NOS) augments blood flow to insulin- sensitive tissues (i.e. skeletal muscle, liver, adipose tissue), and its activity is impaired in insulin resistance. Inhibition of NOS reduces the microvascular delivery of nutrients and blunts insulin-stimulated glucose uptake in skeletal muscle. Furthermore, induction of hypertension by administration of the NOS inhibitor NG-monomethyl-L-arginine is also associated with insulin resistance in rats. Increased levels of asymmetric dimethylarginine (ADMA) are associated with endothelial vasodilator dysfunction and increased risk of cardiovascular diseases. An intriguing relationship exists between insulin resistance and ADMA. Plasma levels of ADMA are positively correlated with insulin resistance in nondiabetic, normotensive people. New basic research insights that provide possible mechanisms underlying the development of insulin resistance in the setting of impaired NO bioavailability will be discussed.
Pharmacotherapies and their influence on asymmetric dimethylargine (ADMA)
Authors: Maas Renke
Published: March 2009

Elevated plasma concentrations of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) are found in various clinical settings, including renal failure, coronary heart disease, hypertension, diabetes and pre eclampsia. In healthy people acute infusion of ADMA promotes vascular dysfunc tion, and in mice chronic infusion of ADMA promotes progression of atherosclerosis. Thus, ADMA may not only be a marker but also an active player in cardiovascular disease, which makes it a potential target for therapeutic interventions. This review provides a summary and critical discussion of the presently available data concern ing the effects on plasma ADMA levels of cardiovascular drugs, hypoglycemic agents, hormone replacement therapy, antioxidants, and vitamin supplementation. We assess the evidence that the beneficial effects of drug therapies on vascular func tion can be attributed to modification of ADMA levels. To develop more specific ADMA-lowering therapies, mechanisms leading to elevation of plasma ADMA con centrations in cardiovascular disease need to be better understood. ADMA is formed endogenously by degradation of proteins containing arginine residues that have been methylated by S-adenosylmethionine-dependent methyltransferases (PRMTs). There are two major routes of elimination: renal excretion and enzymatic degrada tion by the dimethylarginine dimethylaminohydrolases (DDAH-1 and -2). Oxidative stress causing upregulation of PRMT expression and/or attenuation of DDAH activity has been suggested as a mechanism and possible drug target in clinical conditions associated with elevation of ADMA. As impairment of DDAH activity or capacity is associated with substantial increases in plasma ADMA concentrations, DDAH is likely to emerge as a prime target for specific therapeutic interventions.
Spotlight on endothelial progenitor cell inhibitors: short review
Authors: Thum Thomas , Bauersachs Johann
Published: March 2009

Endothelial progenitor cells (EPCs) are bone-marrow-derived cells that enter the systemic circulation to replace defective or injured mature endothelial cells. EPCs also contribute to neovascularization and limit the progression of atherosclero sis. Patients with reduced EPC levels or dysfunctional EPCs are at increased risk for coronary artery disease. Drug-mediated improvement of the mobilization, differenti ation, function and homing of EPCs to sites of ischemia or injured endothelium may therefore be a promising novel therapeutic approach for various cardiovascular dis eases. On the other hand, endogenous inhibitors of EPCs could also be valuable drug targets. The identification of EPC inhibitors and the development of novel drugs that can efficiently regulate production or elimination of these molecules may also be a promising approach for the future treatment of atherosclerosis. In the present review we summarize potential endogenous and exogenous inhibitors of EPCs, such as oxidized low-density lipoproteins, angiotensin II, glucose, cigarette smoke and others. Whenever possible, we also describe the underlying molecular events. Drug- induced mobilization and improvement of EPC function, as well as reduction of EPC inhibitors, is likely to enhance endothelial function and reduce atherosclerotic processes.
ADMA metabolism and clearance
Authors: Teerlink Tom
Published: March 2009

The plasma concentration of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is the resultant of many processes at cellular and organ levels. Post-translational methylation of arginine residues of pro teins plays a crucial role in the regulation of their functions, which include processes such as transcription, translation and RNA splicing. Because protein methylation is irreversible, the methylation signal can be turned off only by proteolysis of the entire protein. Consequently, most methylated proteins have high turnover rates. Free ADMA, which is formed during proteolysis, is actively degraded by the intracellular enzyme dimethylarginine dimethylaminohydrolase (DDAH). Some ADMA escapes degradation and leaves the cell via cationic amino acid transporters. These trans porters also mediate uptake of ADMA by neighboring cells or distant organs, thereby facilitating active interorgan transport. Clearance of ADMA from the plasma occurs in small part by urinary excretion, but the bulk of ADMA is degraded by intracellular DDAH, after uptake from the circulation. This review discusses the various processes involved in ADMA metabolism: protein methylation, proteolysis of methylated proteins, metabolism by DDAH, and interorgan transport. In addition, the role of the kidney and the liver in the clearance of ADMA is highlighted.
Biomechanical Analysis of Functional Electrical Stimulation on Trunk Musculature During Wheelchair Propulsion
Authors: Yang Yu-Sheng , Koontz Alicia M. , Triolo Ronald J. , Cooper Rory A. , Boninger Michael L.
Published: March 2009

Background. The objective of this study was to examine how surface electrical stimulation of trunk musculature influences the kinematic, kinetic, and metabolic characteristics, as well as shoulder muscle activity, during wheelchair propulsion. Methods. Eleven participants with spinal cord injury propelled their own wheelchairs on a dynamometer at a speed of 1.3 m/s for three 5-minute trials. During a propulsion trial, 1 of 3 stimulation levels (HIGH, LOW, and OFF) was randomly applied to the participant’s abdominal and back muscle groups with a surface functional electrical stimulation device. Propulsion kinetics, trunk kinematics, metabolic responses, and surface electromyographic (EMG) activity of 6 shoulder muscles were collected synchronously. Kinetic, kinematic, and EMG variables were recorded during 3 time intervals (30 seconds each) within a 5-minute trial. Metabolic variables were recorded through the entire 5-minute trial. Results. Participants with HIGH stimulation increased their gross mechanical efficiency ( P = .05) during wheelchair propulsion. No differences were found in shoulder EMG activity, energy expenditure, and trunk motion between stimulation levels. Conclusion. Functional electrical stimulation on the trunk musculature has potential advantages in helping manual wheelchair users with spinal cord injury improve propulsion efficiency without placing additional demands on shoulder musculature.
DrosophilaNeurexin IV stabilizes neuron-glia interactions at the CNS midline by binding to Wrapper
Authors: Stork Tobias , Thomas Silke , Rodrigues Floriano , Silies Marion , Naffin Elke , Wenderdel Stephanie , Klämbt Christian
Published: March 2009

Ensheathment of axons by glial membranes is a key feature of complex nervous systems ensuring the separation of single axons or axonal fascicles. Nevertheless, the molecules that mediate the recognition and specific adhesion of glial and axonal membranes are largely unknown. We use the Drosophila midline of the embryonic central nervous system as a model to investigate these neuron glia interactions. During development, the midline glial cells acquire close contact to commissural axons and eventually extend processes into the commissures to wrap individual axon fascicles. Here, we show that this wrapping of axons depends on the interaction of the neuronal transmembrane protein Neurexin IV with the glial Ig-domain protein Wrapper. Although Neurexin IV has been previously described to be an essential component of epithelial septate junctions (SJ), we show that its function in mediating glial wrapping at the CNS midline is independent of SJ formation. Moreover, differential splicing generates two different Neurexin IV isoforms. One mRNA is enriched in septate junction-forming tissues, whereas the other mRNA is expressed by neurons and recruited to the midline by Wrapper. Although both Neurexin IV isoforms are able to bind Wrapper, the neuronal isoform has a higher affinity for Wrapper. We conclude that Neurexin IV can mediate different adhesive cell-cell contacts depending on the isoforms expressed and the context of its interaction partners.
Helping Men Decide About Scheduling a Prostate Cancer Screening Exam
Authors: Liberatore Matthew , Nydick Robert , Daskalakis Constantine , Kunkel Elisabeth , Cocroft James , Myers Ronald
Published: March 2009

This paper reports on the application of decision counseling based on the analytic hierarchy process (AHP) to assist men in deciding whether or not to schedule a prostate cancer screening exam. The study is based on data that we collected from 129 men enrolled in the intervention arm of two randomized, controlled trials. First, we administered a baseline survey to gather data on participant sociodemographic characteristics and perceptions about prostate cancer and screening. Subsequently, a health educator conducted a session with each man to review an informational booklet on prostate cancer screening. Then, the health educator used an AHP-based decision process that identified the most important factors (both pro or con) that might influence prostate cancer screening preferences, clarified preferences related to scheduling a prostate screening exam, and elicited a scheduling decision. We performed univariable and multivariable logistic regression analyses to identify variables associated with the decision. Of the 129 men enrolled, 85 men (66 percent) decided to schedule a prostate cancer screening exam. Multivariable analyses showed that preference strengths and favorable perceptions of prostate cancer screening predicted the decision to screen.
Structural Integrity of Fasteners
Authors: Toor PM
Published: March 2009

Description

The first publication of its kind offering the latest information on fatigue and fracture behavior, as well as evaluation standards and design criteria for safe, sturdy industrial fasteners. Features current data from leading designers, researchers and analysts active in the field.

Thirteen peer-reviewed papers cover a comprehensive range of topics including fatigue, fracture mechanics, stress analysis testing, stress intensity factors, failure evaluation and design criteria for fasteners.

The papers are divided into four major categories: Fatigue in Fasteners; • Failure Evaluation and Criteria; • Fracture Mechanics in Fasteners; • and Structural Integrity Criteria for Fasteners.
Effects of Mechanical Stiffness and Vibration on Wear
Authors: Bayer RG
Published: March 2009

Description

The most current data available on the impact of vibrations and stiffness on test apparatus and machine wear. This comprehensive volume includes wide-ranging examples of machine wear, current experimental and analysis techniques to investigate these effects, as well as an extensive bibliography on the subject. Specific areas addressed:

• How vibrations can reduce or increase wear and friction

• Methods to study vibration effects

• Self-induced vs.machine-induced vibrations

• Evaluating different design parameters on bearing load dynamics

• Increasing spindle life in grinding machines

• Orthopedic biomaterial wear tests

•The effects of ultra sonic vibration on tool life.
Probing the Routes, Rates, and Mechanisms of Xenobiotic Elimination by Rainbow Trout (ONCORHYNCHUS MYKISS) with a Physiological Chamber.
Authors: Black MC , Björkroth K , Oikari A
Published: March 2009

The ability of aquatic organisms to efficiently biotransform and eliminate xenobiotics is an important strategy for reducing body burdens and thereby avoiding toxic effects of xenobiotic exposure. We have developed a plexiglass chamber that isolates the different xenobiotic elimination routes in fish, enabling the collection of biotransformation products over time from the gills, skin, urine, and feces of rainbow trout (Oncorhynchus mykiss). Trout were exposed to [14C]-labeled pentachlorophenol (PCP) in the physiological chamber using two experimental treatments: (1) intraperitoneal (i.p.) injection of PCP into fish having no chemical or effluent preexposure (controls) and (2) i.p. injection of PCP into fish following preexposure to a complex pulp mill effluent for 2 weeks. Elimination of PCP residues was monitored from all routes for 24 to 48 h. Specific PCP biotransformation products were identified and quantified in urine, feces, and bile using high performance liquid chromatography (HPLC) to determine the effects of pulp mill effluent preexposure on the routes and rates of PCP elimination in exposed trout. This study demonstrates the utility of using the physiological chamber for studying the mechanisms of xenobiotic biotransformation and elimination.
The Production of Calibration Specimens for Impact Testing of Subsize Charpy Specimens
Authors: Alexander DJ , Corwin WR , Owings TD
Published: March 2009

Calibration specimens have been manufactured for checking the performance of a pendulum impact testing machine that has been configured for testing subsize specimens, both half-size (5.0 × 5.0 × 25.4 mm) and third-size (3.33 × 3.33 × 25.4 mm). Specimens were fabricated from quenched-and-tempered 4340 steel heat treated to produce different microstructures that would result in either high or low absorbed energy levels on testing. A large group of both half- and third-size specimens were tested at -40°C. The results of the tests were analyzed for average value and standard deviation, and these values were used to establish calibration limits for the Charpy impact machine when testing subsize specimens. These average values plus or minus two standard deviations were set as the acceptable limits for the average of five tests for calibration of the impact testing machine.
Results of ISO CORRAG Program: Processing of One-Year Data in Respect to Corrosivity Classification
Authors: Knotkova D , Boschek P , Kreislova K
Published: March 2009

Elaboration and publishing of four International Standards Organization (ISO) standards, 9223 to 9226, covering the classification system and criteria, the prognostic guiding corrosion values, and the methods to be used for atmospheric corrosivity derivation, were a result of an extensive international cooperation. During this standardization procedure, the international testing program, ISOCORRAG, started with the aim to work out a database for statistical verification of the classification methods.

The outcome of this broad common testing, evaluation, and statistical analysis of the data is presented in the ISO technical report elaborated in ISO/TC 156/WG 4, and in this paper.

Broad acceptance of ISO standards, 9223 to 9226, was supported by new agreements between ISO/TC 156/WG 4, ISO/TC 35/SC 14, and CEN/TC 262/WG 3.
Atmospheric Corrosion in Ibero-America: The MICAT Project
Authors: Morcillo M
Published: March 2009

The Ibero-American Map of Atmospheric Corrosiveness (MICAT) project was set up in 1988 sponsored by the International Ibero-American Programme “Science and Technology for Development (CYTED)”. Fourteen countries are currently involved in the project: Argentina, Brazil, Chile, Colombia, Costa Rica, Cuba, Ecuador, Mexico, Panama, Peru, Portugal, Spain, Uruguay and Venezuela. Research is conducted both at laboratories and in a network of 72 atmospheric exposure test sites throughout the Ibero-American region, thus considering a broad spectrum of climatological and pollution conditions. Although with its own peculiarities, the project basically follows the outline of the ISOCORRAG and ICP/UNECE projects, with the aim of a desirable link between the three projects. In the paper the update annual corrosion results are reported. An attempt is also made to correlate corrosion data with meteorological and pollution parameters.
Weathering of Various Sealants in the Field — A Comparison
Authors: Gorman PD
Published: March 2009

Many controlled environment tests have been performed trying to predict weathering of sealants in the field. This paper will look at over 220 samples of sealants cut from field sites. The sealants range in age from one to 33 years. The samples are compared for weathering characteristics of sealants on different building elevations, painted versus unpainted sealants, polysulfides versus polyurethanes or silicones, and a variety of joint sizes. Field adhesion tests were done on each sample. Durometer (Shore A) hardness data shows relative hardness of the samples.

Most samples were taken from the desert climate of El Paso, Texas. High ultra violet radiation and heat in this area give insight to compare against earlier laboratory studies. Lack of ambient or surface moisture on samples that exhibited “reversion” suggests that this phenomenon can occur without moisture.

The information collected here will provide field data for future studies on the subject of sealant weathering. It also offers a valuable data base for evaluating other publications on the subject.
Effects of Natural and Artificial Weathering on Building Sealants
Authors: Beech J , Beasley J
Published: March 2009

A variety of commercial sealant products have been studied at BRE over the past 20 years, during which changes in key properties have been measured in samples exposed to artificial laboratory ageing and weathering, and to natural weather in England and in more severe climates abroad. Most recently the results of a detailed study of cure and durability of sealant products have been reported at ASTM Symposia in 1992 and 1993.

The results of this laboratory study have been compared with data obtained from samples exposed to natural weather in a temperate climate in Southern England and a middle eastern climate for 6½ years and in a tropical climate for 4 years. Highly significant correlations have been found between modulus changes after exposure for 40 and 52 weeks in an accelerated weathering apparatus, and the effects of weather in all three climates. The implications for the prediction of the durability of sealants from laboratory test data are discussed, and recommendations made for suitable test regimes in relation to the climates to which the sealants were exposed.
Property Database on Shape Memory Alloys for Engineering Design
Authors: Tang W , Sandström R
Published: March 2009

Shape memory alloys (SMAs) as functional materials have many unique characteristics that are quite different from traditional engineering materials. They require an entirely new philosophy of engineering and design. The most fundamental descriptors of property are transformation temperatures, recovery stress, and stress rate rather than yield strength, modulus, and ductility for engineering materials. A particular feature of SMAs is that their properties are very sensitive not only to the intrinsic parameters, such as alloy system, composition, and lattice structure, but to the external conditions, namely, thermomechanical treatments, training history, working environmental temperature, etc. Any minor change of these parameters may largely influence the behavior of an SMA. This has been taken into account when representing and evaluating SMA properties.

Published data for SMAs have been collected and evaluated with the emphasis on transformation temperatures, stress rate, recovery stress, recovery strain, and superelastic behavior as well as their changes with thermal and stress cycling. Some engineering design principles are discussed for different application categories that are defined by their SMA functions. Furthermore, a user interface that allows easy access to the properties and related metadata is described.
Temperature Dependent Tensile Strength of Asphalt Mixtures in Relation to Field Cracking Data
Authors: Chapuis RP , Gatien A
Published: March 2009

The relative performance of conventional and polymer modified asphalt mixtures was evaluated in the laboratory and in the field. Homogeneous beams of several mixtures were tested in four-point-flexion tests at controlled temperature. The test results enabled a fast and accurate determination of how the tensile strength and apparent modulus decrease when the temperature increases. The three polymer modified mixtures had significantly higher tensile strength and modulus than the conventional mixture at any temperature. A method was developed for quantitative evaluation of the field cracking degree and its evolution with time (position, length, orientation, evolution of damage condition). Surveys were performed on several rigid base and flexible pavements of various ages. Usually, new overlays with polymer bitumen were less fissured (by a factor of 2 after three years) than overlays with conventional bitumen. It was also observed that flexible pavements with polymer bitumen show practically no cracks after three years of service. These results are encouraging for the polymer bitumen, but three years is too short for a rigourous comparison of performance.
Wide Range CTOD Estimation Formulae for SE(B) Specimens
Authors: Kirk MT , Wang Y-Y
Published: March 2009

Fracture testing of single edge notch bend, SE(B), specimens containing shallow cracks is often undertaken to match constraint conditions between specimen and structure, thereby obtaining a more accurate assessment of structural integrity. However, standardized methods for measuring fracture toughness in terms of the crack-tip opening displacement (CTOD) do not currently provide formulae which relate experimentally measurable quantities to CTOD for shallow cracks. A CTOD estimation equation, based on results from plane-strain finite element analyses, is proposed to fill this gap. This equation applies to specimens having a wide range of crack depths (0.05 ≤ a/W ≤ 0.70) and Ramberg-Osgood work hardening exponents (4 ≤ n ≤ 50). The proposed equation provides CTOD estimates which are up to five times more accurate than those obtained using the procedures recommended by ASTM E1290. This improved accuracy is achieved by estimating the plastic part of CTOD from a work-like quantity rather than as a scalar multiple of CMODpl (as is done in E1290). Accuracy improvements of the new equation over the E1290 equation are especially notable for materials having a moderate to high work hardening capacity because the linear proportionality that E1290 assumes between CTODpl and CMODpl breaks down in the presence of work hardening. A procedure for estimating the value of the work hardening exponent (n) from the results of a simple tension test is presented and validated. Use of this procedure permits routine application of the proposed CTOD estimation equation in the characterization of fracture toughness. The only material property data that is needed to apply this equation in addition to that currently required by E1290 is the ultimate tensile strength.