Standards of care issues with anticoagulation in real-world populations.

Science.gov (United States)

2015-01-01

Current guidelines recommend anticoagulants for reducing the risk of stroke in appropriate patients with nonvalvular atrial fibrillation (NVAF) and for the acute treatment of venous thromboembolism (VTE) and the prevention of recurrent VTE. Warfarin is the standard of care for both NVAF and VTE, yet International Normalized Ratio (INR) control remains suboptimal, even in the clinical trial setting. Maintaining INR within the recommended therapeutic range is associated with better outcomes in these distinct populations. In VTE, high rates of recurrence have been reported during the first few weeks of treatment, emphasizing the importance of surveillance during this time and of early optimization of anticoagulation therapy. The NVAF population tends to have more comorbidities and requires longer-term therapy. It is important to keep in mind that real-world patient populations are more complex than those in controlled studies. Patients with multiple comorbidities are particularly challenging, and physicians may focus on clinically urgent issues rather than anticoagulation optimization. Despite the many complexities associated with the use of warfarin, it remains a mainstay of anticoagulation therapy. Aligning financial incentives and improving care coordination are important factors in moving toward better outcomes for patients who need anticoagulation therapy. The increased focus on value-based care and evolving approaches to patient treatment could lead more physicians and payers to consider alternatives to warfarin, including the use of novel oral anticoagulants.

Influence of some anticoagulants on dynamics of sugar concentration in the goats’ blood

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D. S. Zapryanova

2007-06-01

Full Text Available Dynamics of the content in the goats’ blood (at the instant the sample was taken, and then after 3, 6 and 24 hours under influence of 4 anticoagulants (sodium fluoride, sodium citrate, heparin and complexon III were studied. Long term storage of the blood samples resulted in the glucose level decrease. It was mostly pronounced under the sodium citrate treatment.

The influence of four different anticoagulants on dynamic light scattering of platelets.

Science.gov (United States)

Raczat, T; Kraemer, L; Gall, C; Weiss, D R; Eckstein, R; Ringwald, J

2014-08-01

For testing of dynamic light scattering of platelets with ThromboLUX (TLX) in platelet-rich plasma (PRP) derived from venous whole blood (vWB), anticoagulation is needed. We compared TLX score in PRPs containing citrate, ethylene-diamine-tetraacetic-acid (EDTA), citrate-phosphate-dextrose-adenine (CPDA) or citrate-theophylline-adenosine-dipyridamole. Initial and late TLX scores were measured after 30-120 min or four to six hours, respectively. Compared with citrate, mean differences in initial TLX score were only significant for CPDA. Also, mean differences between initial and late TLX scores were only significant for CPDA. TLX failed to detect EDTA-induced platelet alterations. The clinical relevance of TLX needs further studies. © 2014 International Society of Blood Transfusion.

Effects of sodium citrate and acid citrate dextrose solutions on cell counts and growth factor release from equine pure-platelet rich plasma and pure-platelet rich gel.

Science.gov (United States)

Giraldo, Carlos E; Álvarez, María E; Carmona, Jorge U

2015-03-14

There is a lack information on the effects of the most commonly used anticoagulants for equine platelet rich plasmas (PRPs) elaboration on cell counts and growth factor release from platelet rich gels (PRGs). The aims of this study were 1) to compare the effects of the anticoagulants sodium citrate (SC), acid citrate dextrose solution A (ACD-A) and ACD-B on platelet (PLT), leukocyte (WBC) and on some parameters associated to platelet activation including mean platelet volume (MPV) and platelet distribution width (PDW) between whole blood, pure PRP (P-PRP) and platelet-poor plasma (PPP); 2) to compare transforming growth factor beta 1 (TGF-β(1)) and platelet-derived growth factor isoform BB (PDGF-BB) concentrations in supernatants from pure PRG (P-PRG), platelet-poor gel (PPG), P-PRP lysate (positive control) and plasma (negative control); 3) to establish the possible correlations between all the studied cellular and molecular parameters. In all cases the three anticoagulants produced P-PRPs with significantly higher PLT counts compared with whole blood and PPP. The concentrations of WBCs were similar between P-PRP and whole blood, but significantly lower in PPP. The type of anticoagulant did not significantly affect the cell counts for each blood component. The anticoagulants also did not affect the MPV and PDW parameters. Independently of the anticoagulant used, all blood components presented significantly different concentrations of PDGF-BB and TGF-β(1). The highest growth factor (GF) concentrations were observed from P-PRP lysates, followed by PRG supernatants, PPP lysates, PPG supernatants and plasma. Significant correlations were observed between PLT and WBC counts (ρ = 0.80), PLT count and TGF-β(1) concentration (ρ = 0.85), PLT count and PDGF-BB concentration (ρ = 0.80) and PDGF-BB and TGF-β(1) concentrations (ρ = 0.75). The type of anticoagulant was not correlated with any of the variables evaluated. The anticoagulants did not

UPLC-ESI-QTOF/MS and multivariate data analysis for blood plasma and serum metabolomics: effect of experimental artefacts and anticoagulant

DEFF Research Database (Denmark)

Barri, Thaer; Dragsted, Lars Ove

2013-01-01

agents, e.g. heparin, EDTA and citrate. In the present study, we looked into metabolite and other differences in matched serum and plasma samples and different plasma preparations by using untargeted UPLC-ESI-QTOF/MS profiling and multivariate data analysis (PCA and OPLS-DA). Metabolite differences......Clotting and anticoagulation of blood samples may give rise to different metabolic profiles of serum and plasma samples, respectively. The anticoagulant used for blood plasma preparation may affect the resulting metabolic profile due to different mechanisms involved in anticoagulation by various...... between serum and plasma samples were mainly related to small peptides reflecting presence or absence of coagulation. Only subtle metabolite differences between the different plasma preparations were noticed, which were primarily related to ion suppression or enhancement caused by citrate and EDTA...

Comparison of equine platelet function and survival in whole blood collected in acid-citrate-dextrose solution or citrate-phosphate-dextrose-adenine solution.

Science.gov (United States)

Bozorgmanesh, Rana; Sutton-Burges, Julie W; Tablin, Fern

2017-06-01

Equine whole blood collection and storage methods have been evaluated to assess red blood cell viability; however, platelet (PLT) viability has not been comprehensively assessed. The purpose of the study was to compare viability of PLTs collected in whole blood into 2 different anticoagulants. Whole blood from 6 healthy adult Thoroughbred horses was collected into citrate-phosphate-dextrose-adenine (CPDA) or acid-citrate-dextrose (ACD). Platelet count, pH, and concentrations of glucose, lactate, carbon dioxide, oxygen, bicarbonate, sodium, potassium, and chloride were measured within 10 minutes of collection and then again one hour later at which time PLT aggregometry was performed to assess PLT function. Aggregometry mean amplitudes were significantly higher in CPDA compared to ACD. Blood glucose, pH, bicarbonate, sodium, and lactate concentrations were significantly higher in CPDA compared to ACD. Lactate concentration was higher following one hour in either anticoagulant. Potassium, oxygen, and carbon dioxide concentrations were significantly higher in ACD compared to CPDA at collection. Platelet aggregometry results suggest that CPDA is superior to ACD for maintaining PLT viability following whole blood collection. This may be associated with the higher, more neutral pH as well as an increase in glucose available for metabolism. Although lactate was increased in the CPDA samples it was not high enough to decrease pH and therefore may not have been high enough to cause morphologic lesions and loss of PLT viability. © 2017 American Society for Veterinary Clinical Pathology.

Collection and storage of red blood cells with anticoagulant and additive solution with a physiologic pH

NARCIS (Netherlands)

Burger, Patrick; Korsten, Herbert; Verhoeven, Arthur J.; de Korte, Dirk; van Bruggen, Robin

2012-01-01

BACKGROUND: A donation of whole blood is most commonly collected in acidic citrate-phosphate-dextrose (CPD) variants with pH 5.2 to 6.2 as anticoagulants. Previously, we have shown that the initial pH after red blood cell (RBC) preparation can have an effect on RBCs during storage. First, we

Anticoagulation period in idiopathic venous thromboembolism

International Nuclear Information System (INIS)

Farraj, Rami S.

2004-01-01

The period of anticoagulation of a first episode of idiopathic venous thromboembolism has been 6 months. It is unclear if such patients would benefit from longer treatment, as there appears to be an increased risk of recurrence after anticoagulation is stopped. In a randomized prospective study of 64 patients admitted to King Hussein Medical city, Amman, Jordan, who developed a first episode of venous thromboembolism, 32 patients were given warfarin for 24-months, while 32 patients stopped anticoagulation after completion of 6-months of therapy. Our goal was to determine the effects of extended anticoagulation on rates of recurrence of symptomatic venous thromboembolism and bleeding. The patients were followed for 12-months after stopping anticoagulation. After 24-months, 7 of the 32 patients (21%) who had standard anticoagulation for 6-months had a recurrent episode of thromboembolism compared to one of the 32 patients who received anticoagulation for 24 months (3%). Extended warfarin therapy for 24-months has resulted in an absolute risk reduction of 0.1% (p<0.05). This translates into 8 patients having to be treated for 24-months to avoid one recurrence without increasing the risk of major bleeding. Two patients in each group (6%) had major nonfatal bleeding, all 4 bleeding episodes occurring within the first 3-months of anticoagulation. After 36-months of follow up, the recurrence rate of extended warfarin therapy was only 3 patients (9%), which is a 43% relative reduction in recurrence of thromboembolism compared to standard therapy for 6-months. Patients with first episodes of idiopathic venous thromboembolism have an increased risk of recurrent venous thromboembolism and should be treated with oral anticoagulants for longer than 6-months, probably 24-months. (author)

A Retrospective Review of the Use of Regional Citrate Anticoagulation in Continuous Venovenous Hemofiltration for Critically Ill Patients

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Anne Kit-Hung Leung

2013-01-01

Full Text Available Background. The emergence of a commercially prepared citrate solution has revolutionized the use of RCA in the intensive care unit (ICU. The aim of this study was to evaluate the safety profile of a commercially prepared citrate solution. Method. Predilution continuous venovenous hemofiltration (CVVH was performed using Prismocitrate 10/2 at 2500 mL/h and a blood flow rate of 150 mL/min. Calcium chloride solution was infused to maintain ionized calcium within 1.0–1.2 mmol/L. An 8.4% sodium bicarbonate solution was infused separately. Treatment was stopped when the predefined clinical target was reached or the filter clotted. Result. 58 sessions of citrate RCA were analyzed. The median circuit lifetime was 26.0 h (interquartile range IQR 21.2–44.3. The percentage of circuits lasting more than 12 h, 24 h, and 48 h was 94.6%, 58.9%, and 16.1%, respectively. There was no incidence of hypernatremia and median pH was 2.5, only four patients had evidence of citrate accumulation. Conclusion. The commercially prepared citrate solution could be used safely in critically ill patients who required CVVH with no major adverse events.

The future of anticoagulation clinics.

Science.gov (United States)

Macik, B Gail

2003-01-01

Anticoagulation therapy is the foundation of treatment for thromboembolic disorders; and coumarin derivatives (warfarin in the United States) are the only orally administered anticoagulant medications currently available. Due to the expense and relative difficulties associated with this route of administration, parenteral drugs are not used routinely for long-term therapy, leaving warfarin as the anticoagulant of choice in the outpatient setting. The management of warfarin is problematic, however, due the nuances of its pharmacodynamic and pharmacokinetic profile and the requirement for frequent monitoring of blood levels. Although management by anticoagulation clinics is considered the gold standard for warfarin therapy, management by an anticoagulation clinic may not be the optimal option from a clinician's view and, in many cases, may not be an option at all. Anticoagulation clinics may impinge on the doctor-patient relationship. Difficulties of communication and reimbursement are not ameliorated by a specialty clinic. Innovations in warfarin management, including patient self-management and computerized dosing programs, are alternatives for improved care that are available with or without input by an anticoagulation service. New oral drugs on the horizon do not require the same intensity of monitoring and do not present the same pharmacodynamic problems associated with warfarin. Warfarin will become obsolete in the foreseeable future. If anticoagulation clinics continue, they must re-define their role as the major part of the workload, warfarin management, disappears. To adapt, clinics must strengthen and enhance their role as coordinators and educators, and less so, managers of anticoagulation therapy.

Heterofucans from Dictyota menstrualis have anticoagulant activity

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I.R.L. Albuquerque

2004-02-01

Full Text Available Fucan is a term used to denote a family of sulfated L-fucose-rich polysaccharides which are present in the extracellular matrix of brown seaweed and in the egg jelly coat of sea urchins. Plant fucans have several biological activities, including anticoagulant and antithrombotic, related to the structural and chemical composition of polysaccharides. We have extracted sulfated polysaccharides from the brown seaweed Dictyota menstrualis by proteolytic digestion, followed by separation into 5 fractions by sequential acetone precipitation. Gel electrophoresis using 0.05 M 1,3-diaminopropane-acetate buffer, pH 9.0, stained with 0.1% toluidine blue, showed the presence of sulfated polysaccharides in all fractions. The chemical analyses demonstrated that all fractions are composed mainly of fucose, xylose, galactose, uronic acid, and sulfate. The anticoagulant activity of these heterofucans was determined by activated partial thromboplastin time (APTT using citrate normal human plasma. Only the fucans F1.0v and F1.5v showed anticoagulant activity. To prolong the coagulation time to double the baseline value in the APTT, the required concentration of fucan F1.0v (20 µg/ml was only 4.88-fold higher than that of the low molecular weight heparin Clexane® (4.1 µg/ml, whereas 80 µg/ml fucan 1.5 was needed to obtain the same effect. For both fucans this effect was abolished by desulfation. These polymers are composed of fucose, xylose, uronic acid, galactose, and sulfate at molar ratios of 1.0:0.8:0.7:0.8:0.4 and 1.0:0.3:0.4:1.5:1.3, respectively. This is the fist report indicating the presence of a heterofucan with higher anticoagulant activity from brown seaweed.

Influence of novel oral anticoagulants on anticoagulation care management.

Science.gov (United States)

Janzic, Andrej; Kos, Mitja

2017-09-01

Anticoagulation treatment was recently improved by the introduction of novel oral anticoagulants (NOACs). Using a combination of qualitative and quantitative methods, this study explores the effects of the introduction of NOACs on anticoagulation care in Slovenia. Face-to-face interviews with key stakeholders revealed evolvement and challenges of anticoagulation care from different perspectives. Obtained information was further explored through the analysis of nationwide data of drug prescriptions and realization of health care services. Simplified management of anticoagulation treatment with NOACs and their high penetration expanded the capacity of anticoagulation clinics, and consequentially the treated population increased by more than 50 % in the last 5 years. The main challenge concerned the expenditures for medicines, which increased approximately 10 times in just a few years. At the same time, the anticoagulation clinics and their core organisation were not affected, which is not expected to change, since they are vital in delivering high-quality care.

Characterization and structural analysis of a potent anticoagulant phospholipase A2 from Pseudechis australis snake venom.

Science.gov (United States)

Du, Qianyun Sharon; Trabi, Manuela; Richards, Renée Stirling; Mirtschin, Peter; Madaras, Frank; Nouwens, Amanda; Zhao, Kong-Nan; de Jersey, John; Lavin, Martin F; Guddat, Luke W; Masci, Paul P

2016-03-01

Pseudechis australis is one of the most venomous and lethal snakes in Australia. Numerous phospholipase A2 (PLA2) isoforms constitute a major portion of its venom, some of which have previously been shown to exhibit not only enzymatic, but also haemolytic, neurotoxic and anticoagulant activities. Here, we have purified a potent anticoagulant PLA2 (identified as PA11) from P. australis venom to investigate its phospholipase, anticoagulant, haemolytic and cytotoxic activities and shown that addition of 11 nM PA11 resulted in a doubling of the clotting time of recalcified whole blood. We have also demonstrated that PA11 has high PLA2 enzymatic activity (10.9 × 10(4) Units/mg), but low haemolytic activity (0.6% of red blood cells hydrolysed in the presence of 1 nM PA11). PA11 at a concentration lower than 600 nM is not cytotoxic towards human cultured cells. Chemical modification experiments using p-bromophenacyl bromide have provided evidence that the catalytic histidine of PA11 is critical for the anticoagulant activity of this PLA2. PA11 that was subjected to trypsin digestion without previous reduction and alkylation of the disulfide bonds maintained enzymatic and anticoagulant activity, suggesting that proteolysis alone cannot abolish these properties. Consistent with these results, administration of PA11 by gavage in a rabbit stasis thrombosis model increased the clotting time of recalcified citrated whole blood by a factor of four. These data suggest that PA11 has potential to be developed as an anticoagulant in a clinical setting. Copyright © 2015. Published by Elsevier Ltd.

Laboratory Assessment of the Anticoagulant Activity of Direct Oral Anticoagulants: A Systematic Review.

Science.gov (United States)

Samuelson, Bethany T; Cuker, Adam; Siegal, Deborah M; Crowther, Mark; Garcia, David A

2017-01-01

Direct oral anticoagulants (DOACs) are the treatment of choice for most patients with atrial fibrillation and/or noncancer-associated venous thromboembolic disease. Although routine monitoring of these agents is not required, assessment of anticoagulant effect may be desirable in special situations. The objective of this review was to summarize systematically evidence regarding laboratory assessment of the anticoagulant effects of dabigatran, rivaroxaban, apixaban, and edoxaban. PubMed, Embase, and Web of Science were searched for studies reporting relationships between drug levels and coagulation assay results. We identified 109 eligible studies: 35 for dabigatran, 50 for rivaroxaban, 11 for apixaban, and 13 for edoxaban. The performance of standard anticoagulation tests varied across DOACs and reagents; most assays, showed insufficient correlation to provide a reliable assessment of DOAC effects. Dilute thrombin time (TT) assays demonstrated linear correlation (r 2  = 0.67-0.99) across a range of expected concentrations of dabigatran, as did ecarin-based assays. Calibrated anti-Xa assays demonstrated linear correlation (r 2  = 0.78-1.00) across a wide range of concentrations for rivaroxaban, apixaban, and edoxaban. An ideal test, offering both accuracy and precision for measurement of any DOAC is not widely available. We recommend a dilute TT or ecarin-based assay for assessment of the anticoagulant effect of dabigatran and anti-Xa assays with drug-specific calibrators for direct Xa inhibitors. In the absence of these tests, TT or APTT is recommended over PT/INR for assessment of dabigatran, and PT/INR is recommended over APTT for detection of factor Xa inhibitors. Time since last dose, the presence or absence of drug interactions, and renal and hepatic function should impact clinical estimates of anticoagulant effect in a patient for whom laboratory test results are not available. Copyright © 2016 American College of Chest Physicians. Published by Elsevier

Characterisation of citrate and iron citrate uptake by cultured rat hepatocytes

International Nuclear Information System (INIS)

Graham, R.M.; Morgan, E.H.; Baker, E.

1998-01-01

Background/Aims: the endogenous low molecular weight iron chelator, citrate, is considered to be an important contributor to iron transport and the liver the main site of uptake of iron citrate in subjects suffering from diseases of iron overload. Moreover, the citrate-metabolising enzyme, aconitase, is implicated in the regulation of cellular iron metabolism. This study was undertaken to determine the role of citrate and ferric citrate in the uptake of iron by rat hepatocytes. Methods: Cultured rat hepatocytes were incubated (37 deg. C, 15 min) with 100 μM [ 14 C]-citrate in the presence or absence of 1.0 μM 55 Fe. Membrane-bound and intracellular radiolabel were separated by incubation with the general protease, Pronase. Results: Our results suggest that ferric citrate uptake is mediated by a specific citrate binding site which exhibits a higher affinity for citrate in the presence of iron than in its absence. Citrate was internalised by hepatocytes, with at least 70% being oxidised to CO 2 within 15 min. Citrate uptake was pH-dependent, did not require the presence of sodium and increased with increasing iron concentration. Metabolic energy, anion channels, the Na + , K + -ATPase and vesicle acidification do not appear to play a role in uptake of ferric citrate, but functional sulphydryl groups may be involved. Conclusions: The data suggest either that ferric citrate complexes with higher molar ratios of iron to citrate relative to the incubation medium are bound preferentially to the membrane, or that once citrate has delivered its iron to the membrane, the complex dissociates and the components are internalised separately. (au)

Cost effectiveness of novel oral anticoagulants for stroke prevention in atrial fibrillation depending on the quality of warfarin anticoagulation control.

Science.gov (United States)

Janzic, Andrej; Kos, Mitja

2015-04-01

Vitamin K antagonists, such as warfarin, are standard treatments for stroke prophylaxis in patients with atrial fibrillation. Patient outcomes depend on quality of warfarin management, which includes regular monitoring and dose adjustments. Recently, novel oral anticoagulants (NOACs) that do not require regular monitoring offer an alternative to warfarin. The aim of this study was to evaluate whether cost effectiveness of NOACs for stroke prevention in atrial fibrillation depends on the quality of warfarin control. We developed a Markov decision model to simulate warfarin treatment outcomes in relation to the quality of anticoagulation control, expressed as percentage of time in the therapeutic range (TTR). Standard treatment with adjusted-dose warfarin and improved anticoagulation control by genotype-guided dosing were compared with dabigatran, rivaroxaban, apixaban and edoxaban. The analysis was performed from the Slovenian healthcare payer perspective using 2014 costs. In the base case, the incremental cost-effectiveness ratio for apixaban, dabigatran and edoxaban was below the threshold of €25,000 per quality-adjusted life-years compared with adjusted-dose warfarin with a TTR of 60%. The probability that warfarin was a cost-effective option was around 1%. This percentage rises as the quality of anticoagulation control improves. At a TTR of 70%, warfarin was the preferred treatment in half the iterations. The cost effectiveness of NOACs for stroke prevention in patients with nonvalvular atrial fibrillation who are at increased risk for stroke is highly sensitive to warfarin anticoagulation control. NOACs are more likely to be cost-effective options in settings with poor warfarin management than in settings with better anticoagulation control, where they may not represent good value for money.

in Critically Ill Patients: Success and Limits

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Filippo Mariano

2011-01-01

Full Text Available Citrate anticoagulation has risen in interest so it is now a real alternative to heparin in the ICUs practice. Citrate provides a regional anticoagulation virtually restricted to extracorporeal circuit, where it acts by chelating ionized calcium. This issue is particularly true in patients ongoing CRRT, when the “continuous” systemic anticoagulation treatment is per se a relevant risk of bleeding. When compared with heparin most of studies with citrate reported a longer circuit survival, a lower rate of bleeding complications, and transfused packed red cell requirements. As anticoagulant for CRRT, the infusion of citrate is prolonged and it could potentially have some adverse effects. When citrate is metabolized to bicarbonate, metabolic alkalosis may occur, or for impaired metabolism citrate accumulation leads to acidosis. However, large studies with dedicated machines have indeed demonstrated that citrate anticoagulation is well tolerated, safe, and an easy to handle even in septic shock critically ill patients.

Influence of centrifuge brake on residual platelet count and routine coagulation tests in citrated plasma.

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Daves, Massimo; Giacomuzzi, Katia; Tagnin, Enrico; Jani, Erika; Adcock Funk, Dorothy M; Favaloro, Emmanuel J; Lippi, Giuseppe

2014-04-01

Sample centrifugation is an essential step in the coagulation laboratory, as clotting tests are typically performed on citrated platelet (PLT) poor plasma (PPP). Nevertheless, no clear indication has been provided as to whether centrifugation of specimens should be performed with the centrifuge brake set to on or off. Fifty consecutive sodium citrate anticoagulated samples were collected and divided into two aliquots. The former was centrifuged as for Clinical Laboratory Standards Institute (CLSI) guidelines with the centrifuge brake set to on, whereas the latter was centrifuged again as for CLSI guidelines, but with the brake set to off. In the PPP of all samples, a PLT count was performed, followed by the analysis of activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrinogen (FBG). The PLT count after samples centrifugation was substantially reduced, either with centrifuge brake set to on or off (5 ± 1 versus 3 ± 1 × 10/l; P = 0.009). The frequency of samples exceeding a PLT count less than 10 × 10/l was nearly double in samples centrifuged with the brake on than in those with the brake off (14 versus 8%; P centrifuge brake set to on (mean bias 0.2 s; P centrifuge brake set to on (mean bias 0.29 g/l; P centrifugation for routine coagulation testing should be preferably performed with the centrifuge brake set to off for providing a better quality specimen.

Implementation of a more physiological plasma rich in growth factor (PRGF) protocol: Anticoagulant removal and reduction in activator concentration.

Science.gov (United States)

Anitua, Eduardo; Prado, Roberto; Troya, María; Zalduendo, Mar; de la Fuente, María; Pino, Ander; Muruzabal, Francisco; Orive, Gorka

2016-07-01

Plasma rich in growth factors (PRGF) is a biological therapy that uses patient's own growth factors for promoting tissue regeneration. Given the current European regulatory framework in which anticoagulant solution in blood extraction tubes could be considered as a medicinal product, a new PRGF protocol has been developed. The actual protocol (PRGF-A) and the new one (PRGF-B) have been performed and compared under Good Laboratory Practices. PRGF-A protocol uses extraction tubes with 0.9 mL of trisodium citrate as anticoagulant and 50 μL of calcium chloride/mL PRGF to activate it. The PRGF-B reduces the amount of sodium citrate and calcium chloride to 0.4 mL and to 20 μL, respectively. Basic hematological parameters, platelet function, the scaffold obtaining process, growth factors content, and the biological effect were compared between both PRGF obtaining protocols. PRGF-B protocol led to a statistically significant higher enrichment and recovery of platelets regarding to the PRGF-A. Hypotonic stress response by platelets was significantly better in the new protocol. A statistically significant decrease in the basal platelet activation status of PRGF-B compared to PRGF-A was also observed. The duration of the lag phase in the platelet aggregation assay was statistically lower for the PRGF-B protocol. Both the clotting and the clot retraction time were significantly reduced in the B protocol. A higher growth factor concentration was detected in the plasma obtained using the PRGF-B protocol. The new PRGF obtaining protocol, with a reduction in the amount of anticoagulant and activator, has even improved the actual one.

Survey of Botulinum Toxin Injections in Anticoagulated Patients: Korean Physiatrists' Preference in Controlling Anticoagulation Profile Prior to Intramuscular Injection.

Science.gov (United States)

Jang, Yongjun; Park, Geun-Young; Park, Jihye; Choi, Asayeon; Kim, Soo Yeon; Boulias, Chris; Phadke, Chetan P; Ismail, Farooq; Im, Sun

2016-04-01

To evaluate Korean physiatrists' practice of performing intramuscular botulinum toxin injection in anticoagulated patients and to assess their preference in controlling the bleeding risk before injection. As part of an international collaboration survey study, a questionnaire survey was administered to 100 Korean physiatrists. Physiatrists were asked about their level of experience with botulinum toxin injection, the safe international normalized ratio range in anticoagulated patients undergoing injection, their tendency for injecting into deep muscles, and their experience of bleeding complications. International normalized ratio injection by 41% of the respondents. Thirty-six respondents replied that the international normalized ratio should be lowered to sub-therapeutic levels before injection, and 18% of the respondents reported that anticoagulants should be intentionally withheld and discontinued prior to injection. In addition, 20%-30% of the respondents answered that they were uncertain whether they should perform the injection regardless of the international normalized ratio values. About 69% of the respondents replied that they did have any standardized protocols for performing botulinum toxin injection in patients using anticoagulants. Only 1 physiatrist replied that he had encountered a case of compartment syndrome. In accordance with the lack of consensus in performing intramuscular botulinum toxin injection in anticoagulated patients, our survey shows a wide range of practices among many Korean physiatrists; they tend to avoid botulinum toxin injection in anticoagulated patients and are uncertain about how to approach these patients. The results of this study emphasize the need for formulating a proper international consensus on botulinum toxin injection management in anticoagulated patients.

Lupus anticoagulants: first French interlaboratory Etalonorme survey.

Science.gov (United States)

Roussi, J; Roisin, J P; Goguel, A

1996-06-01

In 1994, the, French National Quality Control Group for Hematology, Etalonorme, conducted a large-scale interlaboratory survey concerning the detection of lupus anticoagulants (LA) involving all the 4,500 French laboratories. Each laboratory received the same batch of a lyophilized citrated plasma (94B3) prepared from a patient with LA that had been confirmed by all the techniques used in the intralaboratory study. In the interlaboratory survey, the screening test was activated partial thromboplastin time (APTT); mean APTT calculated from the results reported by 4,029 labs was prolonged (clotting ratio = 1.44) with a large dispersion (coefficients of variation = 18.8%). APTT of the mixture 94B3 + normal plasma were performed by 2,698 laboratories. No correction of APTT was obtained (R = 1.36, Rosner index = 24) with a wide variation between reagents (17 kaolin. This survey allowed Etalonorme to inform French biologists and draft an educational program for the biologic detection of LA and the identification of its mechanism of action.

Lupus anticoagulants and antiphospholipid antibodies

Science.gov (United States)

Blood clots - lupus anticoagulants; DVT - anticoagulants ... Most often, lupus anticoagulants and aPL are found in people with diseases such as systemic lupus erythematosus (SLE). Lupus anticoagulants and ...

Anticoagulant Resistance

DEFF Research Database (Denmark)

Heiberg, Ann-Charlotte

Although sewer rat control is carried out in more than 80 % of all Danish municipalities, with usage of large amounts of anticoagulant rodenticides, knowledge on anticoagulant resistance among rats living in the sewers is limited. As rat problems in urban areas are believed to be related to sewer...... problems (70-90 % in UK and DK) unawareness of resistance amongst these populations of Brown rats may constitute a future control problem and knowledge on this issue has become crucial. Rats were captured in sewers from seven different locations in the suburban area of Copenhagen. Locations was chosen...... to represent different sewer rat management strategies i) no anticoagulants for approx. 20 years ii) no anticoagulants for the last 5 years and iii) continuous control for many years. Animals were tested for resistance to bromadiolone by Blood-Clotting Response test, as bromadiolone is the most frequently used...

Association between Oral Anticoagulation Knowledge ...

African Journals Online (AJOL)

Association between Oral Anticoagulation Knowledge, Anticoagulation Control, and Demographic Characteristics of Patients Attending an Anticoagulation Clinic in Saudi Arabia: A Cross-Sectional Prospective Evaluation.

Anticoagulant Preferences and Concerns among Venous Thromboembolism Patients.

Science.gov (United States)

Lutsey, Pamela L; Horvath, Keith J; Fullam, Lisa; Moll, Stephan; Rooney, Mary R; Cushman, Mary; Zakai, Neil A

2018-03-01

 Warfarin and direct oral anticoagulants (DOACs) are used for the initial treatment and secondary prevention of venous thromboembolism (VTE), and have similar efficacy. Patient concerns and preferences are important considerations when selecting an anticoagulant, yet these are not well studied.  VTE patients ( n  = 519) were surveyed from online sources (clotconnect.org, stoptheclot.org and National Blood Clot Alliance Facebook followers [ n  = 495]) and a haematology clinic in Vermont ( n  = 24).  Patients were 83% females and on average (±standard deviation [SD]) 45.7 ± 13.1 years; 65% self-reported warfarin as their initial VTE treatment and 35% a DOAC. Proportions reporting being extremely concerned about the following outcomes were as follows: recurrent VTE 33%, major bleeding 21%, moderate bleeding 16% and all-cause death 29%. When asked about oral anticoagulant characteristics, patients strongly preferred anticoagulants that are reversible (53%), and for which blood drug levels can be monitored (30%). Lower proportions agreed with statements that regular blood testing is inconvenient (18%), that they are comfortable using the newest drug versus an established drug (15%) and that it is difficult to change their diet to accommodate their anticoagulant (17%). In multivariable-adjusted models, patients tended to have had as their initial treatment, and to currently be taking, the oral anticoagulant option they personally preferred.  Patients held the greatest concern for recurrent VTE and mortality, regardless of which treatment they were prescribed. Potential weaknesses of warfarin (e.g., dietary restrictions, regular monitoring) were generally not considered onerous, while warfarin's advantages (e.g., ability to monitor) were viewed favourably. Schattauer GmbH Stuttgart.

Optical sensing of anticoagulation status: Towards point-of-care coagulation testing.

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Diane M Tshikudi

Full Text Available Anticoagulant overdose is associated with major bleeding complications. Rapid coagulation sensing may ensure safe and accurate anticoagulant dosing and reduce bleeding risk. Here, we report the novel use of Laser Speckle Rheology (LSR for measuring anticoagulation and haemodilution status in whole blood. In the LSR approach, blood from 12 patients and 4 swine was placed in disposable cartridges and time-varying intensity fluctuations of laser speckle patterns were measured to quantify the viscoelastic modulus during clotting. Coagulation parameters, mainly clotting time, clot progression rate (α-angle and maximum clot stiffness (MA were derived from the clot viscoelasticity trace and compared with standard Thromboelastography (TEG. To demonstrate the capability for anticoagulation sensing in patients, blood samples from 12 patients treated with warfarin anticoagulant were analyzed. LSR clotting time correlated with prothrombin and activated partial thromboplastin time (r = 0.57-0.77, p<0.04 and all LSR parameters demonstrated good correlation with TEG (r = 0.61-0.87, p<0.04. To further evaluate the dose-dependent sensitivity of LSR parameters, swine blood was spiked with varying concentrations of heparin, argatroban and rivaroxaban or serially diluted with saline. We observed that anticoagulant treatments prolonged LSR clotting time in a dose-dependent manner that correlated closely with TEG (r = 0.99, p<0.01. LSR angle was unaltered by anticoagulation whereas TEG angle presented dose-dependent diminution likely linked to the mechanical manipulation of the clot. In both LSR and TEG, MA was largely unaffected by anticoagulation, and LSR presented a higher sensitivity to increased haemodilution in comparison to TEG (p<0.01. Our results establish that LSR rapidly and accurately measures the response of various anticoagulants, opening the opportunity for routine anticoagulation monitoring at the point-of-care or for patient self-testing.

Citrate and renal calculi: an update

Science.gov (United States)

Pak, C. Y.

1994-01-01

Citrate is an inhibitor of the crystallization of stone-forming calcium salts. Hypocitraturia, frequently encountered in patients with nephrolithiasis, is therefore an important risk factor for stone formation. Potassium citrate provides physiological and physicochemical correction and inhibits new stone formation, not only in hypocitraturic calcium nephrolithiasis but also in uric acid nephrolithiasis. Inhibition of stone recurrence has now been validated by a randomized trial. Ongoing research has disclosed additional causes of hypocitraturia (sodium excess, low intestinal alkali absorption, but not primary citrate malabsorption). Moreover, new insights on potassium citrate action have been shown, notably that some of absorbed citrate escapes oxidation and contributes to the citraturic response, that ingestion with a meal does not sacrifice physiological or physicochemical action, that orange juice mimics but does not completely duplicate its actions, that potassium citrate may have a beneficial bone-sparing effect, that it may reduce stone fragments following ESWL, and that danger of aluminum toxicity is not great in subjects with functioning kidneys. Finally, the research on potassium citrate has led to two promising products, calcium citrate as an optimum calcium supplement and potassium-magnesium citrate which may be superior to potassium citrate in the management of stone disease.

Citrat og nyresten

DEFF Research Database (Denmark)

Osther, P J

1993-01-01

Citrate is an important naturally occurring inhibitor of calcium stone formation in urine. Urinary citrate excretion was examined in 43 consecutive patients with recurrent idiopathic calcium nephrolithiasis and in 50 normal controls by a specific enzymatic technique. Hypocitraturia (<1.6 mmol/24h...

Human Protein C produces anticoagulation and increased fibrinolytic activity in the cat

International Nuclear Information System (INIS)

Burdick, M.D.; Schaub, R.G.

1986-01-01

The effect of activated human Protein C (PCa) infusion on the coagulation and fibrinolytic systems of the Nembutal anesthetized cat was assessed. Human Protein C was activated by incubation with thrombin or by passage over a column of thrombin immobilized on CNBr Sepharose 4B. Cats were given bolus i.v. injections of either vehicle or PCa in a dose range of 3-16 μg/mL of calculated whole body volume. Citrated blood samples (9:1) were taken from a femoral vein prior to and at 5, 10, 20, 30, 60, 120, and 180 min. after PCa. Activated partial thromboplastin time (APTT), thrombin time (TT) euglobulin clot lysis (ECLT) and I-125 fibrin release (FR) was measured. Vehicle treated cats had no change in any parameter. PCa produced a dose and time dependent prolongation of APTT while TT was unchanged. Anticoagulation was evident immediately after PCa infusion and began to normalize within 20 min. Fibrinolytic activity measured by ECLT and FR was also stimulated by PCa but was not evident until 40-60 minutes after PCa injection. The results show that human PCa induces anticoagulation effects in the cat similar to other species. However, stimulation of fibrinolysis requires a longer period of time before expression. This delay of fibrinolytic stimulation should be considered when assessing the effects of human Protein C in other species

Direct oral anticoagulants: An update.

Science.gov (United States)

Franco Moreno, Ana Isabel; Martín Díaz, Rosa María; García Navarro, María José

2017-12-30

Vitamin K antagonists were the only choice for chronic oral anticoagulation for more than half a century. Over the past few years, direct oral anticoagulants have emerged, including one direct thrombin inhibitor (dabigatran etexilate) and three factor Xa inhibitors (apixaban, edoxaban and rivaroxaban). In randomised controlled trials comparing direct oral anticoagulants with traditional vitamin K antagonists, the direct oral anticoagulants all showed a favourable benefit-risk balance in their safety and efficacy profile, in prevention of thromboembolic events in patients with atrial fibrillation and in the prevention and treatment of venous thromboembolism and acute coronary syndrome. In 2008, dabigatran was the first direct oral anticoagulant approved by the European Medicine Agency. Subsequently, rivaroxaban, apixaban and edoxaban were also authorised. This article reviews the evidence related to the use of these drugs. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Developing an Anti-Xa-Based Anticoagulation Protocol for Patients with Percutaneous Ventricular Assist Devices.

Science.gov (United States)

Sieg, Adam; Mardis, B Andrew; Mardis, Caitlin R; Huber, Michelle R; New, James P; Meadows, Holly B; Cook, Jennifer L; Toole, J Matthew; Uber, Walter E

2015-01-01

Because of the complexities associated with anticoagulation in temporary percutaneous ventricular assist device (pVAD) recipients, a lack of standardization exists in their management. This retrospective analysis evaluates current anticoagulation practices at a single center with the aim of identifying an optimal anticoagulation strategy and protocol. Patients were divided into two cohorts based on pVAD implanted (CentriMag (Thoratec; Pleasanton, CA) / TandemHeart (CardiacAssist; Pittsburgh, PA) or Impella (Abiomed, Danvers, MA)), with each group individually analyzed for bleeding and thrombotic complications. Patients in the CentriMag/TandemHeart cohort were subdivided based on the anticoagulation monitoring strategy (activated partial thromboplastin time (aPTT) or antifactor Xa unfractionated heparin (anti-Xa) values). In the CentriMag/TandemHeart cohort, there were five patients with anticoagulation titrated based on anti-Xa values; one patient developed a device thrombosis and a major bleed, whereas another patient experienced major bleeding. Eight patients received an Impella pVAD. Seven total major bleeds in three patients and no thrombotic events were detected. Based on distinct differences between the devices, anti-Xa values, and outcomes, two protocols were created to guide anticoagulation adjustments. However, anticoagulation in patients who require pVAD support is complex with constantly evolving anticoagulation goals. The ideal level of anticoagulation should be individually determined using several coagulation laboratory parameters in concert with hemodynamic changes in the patient's clinical status, the device, and the device cannulation.

STABILITY OF SYNTHESIZED SILVER NANOPARTICLES IN CITRATE AND MIXED GELATIN/CITRATE SOLUTION

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Jana Kavuličová

2018-04-01

Full Text Available The study focuses on an investigation of the influence of both citrate and mixed gelatin/citrate as a reductant and stabilizer on the colloidal stability of silver nanoparticles (AgNPssynthesized by a chemical reduction of Ag+ ions after a short - (7th day - and long - (118th day - term storage. Formed AgNPs were characterized by a UV–vis Spectroscopy, Transmission Electron Microscope (TEM, Dynamic light scattering (DLS and Zeta-potential (ZP. The obtained results revealed that a short-term stability of the synthesized AgNPs was greatly influenced by a citrate stabilizer with the absence of gelatin. Smaller-sized AgNPs (average particle diameter of 3 nm, roughly spherical in a shape, were obtained with a narrow size distribution. The very negative value of the Zeta-potential confirmed a strong stability of the citrate capped AgNPs. However, a surface coating of the AgNPs by a gelatin/citrate stabilizer was found to be a dominant contributor in improving a long-term stability of the AgNPs (average particle diameter of 26 nm. The use of gelatin in mixed stabilizer solution provided the AgNPs with higher monodispersity and a controllable size after both the short and long-term storage.

Old and new oral anticoagulants for secondary stroke prevention in atrial fibrillation

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Tommaso Sacquegna

2015-12-01

Full Text Available Vitamin K antagonists, such as warfarin, used in oral anticoagulation therapy currently represent the standard drugs for the primary and secondary prevention of stroke in non-valvular atrial fibrillation (AF, with a relative risk reduction close to 70%. Newer oral anticoagulants, such as direct thrombin inhibitors (i.e., dabigatran and direct factor Xa inhibitors (i.e., apixaban and rivaroxaban have been recently compared with warfarin in large randomized trials for stroke prevention in AF. The new oral anticoagulants showed, compared with warfarin, no statistically significant difference in the rate of stroke or systemic embolism in secondary prevention (patients with previous transient ischemic attack or stroke subgroups. With regard to safety, the risk of intracranial bleeding was reduced with new anticoagulants compared with warfarin. Indirect treatment comparisons of clinical trials on secondary prevention cohorts showed no significant difference in efficacy among apixaban, rivaroxaban, and dabigatran; but dabigatran 110 mg was associated with less intracranial bleedings than rivaroxaban.

[New oral anticoagulant drugs].

Science.gov (United States)

Berkovits, Alejandro; Aizman, Andrés; Zúñiga, Pamela; Pereira, Jaime; Mezzano, Diego

2011-10-01

Thromboembolic disease (TED) is the leading cause of morbidity and mortality worldwide. The hallmark of oral long-term anticoagulant therapy has been the use of vitamin K antagonists, whose anticoagulant effect is exerted inhibiting vitamin K epoxide reductase. Warfarin and acenocoumarol are the most commonly used. In the last five years several new drugs for long term anticoagulation have been developed, which can inhibit single clotting factors with the purpose of improving drug therapeutic range and, ideally, minimizing bleeding risks. This review addresses the state of the art on the clinical use of inhibitors of activated factor X and thrombin.

A survey of anticoagulation practice among German speaking microsurgeons – Perioperative management of anticoagulant therapy in free flap surgery [Erhebung über die antikoagulatorische Praxis unter deutschsprachigen Mikrochirurgen – Perioperatives Management der antikoagulatorischen Therapie bei freien Lappentransplantaten

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Jokuszies, Andreas

2012-02-01

Full Text Available [english] Background: Anticoagulation is a crucial element in microsurgery. Although various clinical studies and international surveys have revealed that anticoagulation strategies can vary and result in similar outcomes, anticoagulative regimen are far away from standardization. In Germany and german speaking countries standardized anticoagulation protocols concerning free flap surgery do not exist so far. Methods: To evaluate the current practice of clinics in Germany, Austria and Switzerland with specialization in microsurgery we performed a questionnaire surveying the perioperative regimen of anticoagulant and antiplatelet therapy in free flap surgery. The microsurgeons were interrogated on several anticoagulant, rheologic and antiplatelet medications, their dosage and perioperative frequency of application pre-, intra- and postoperative.Results: The questionnaire revealed that the used antithrombotic and perioperative regimens varied from department to department presumably based on the personal experience of the surgeon. Multiple approaches are used with a wide range of anticoagulants used either alone or in combination, with different intervals of application and different dosages. Conclusion: Therefore consensus meetings should be held in future leading to conduct prospective multicenter studies with formulation of standardized anticoagulative and perioperative protocols in microsurgery reducing flap failure to other than pharmacologic reasons.[german] Hintergrund: Die Antikoagulation stellt ein zentrales Element in der Mikrochirurgie dar. Zahlreiche klinische Studien und internationale Erhebungen zu antikoagulatorischen Strategien weisen eine grosse Varianz bei vergleichbaren Resultaten nach, entbehren jedoch einer Standardisierung. Auch in Deutschland und deutschsprachigen Ländern fehlen bislang standardisierte Regime zur Antikoagulation in der Mikrochirurgie.Methodik: Zur Erhebung der antikoagulatorischen Praxis unter

21 CFR 582.6195 - Calcium citrate.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium citrate. 582.6195 Section 582.6195 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Calcium citrate. (a) Product. Calcium citrate. (b) Conditions of use. This substance is generally...

Chronic kidney disease and anticoagulation

DEFF Research Database (Denmark)

Sciascia, Savino; Radin, Massimo; Schreiber, Karen

2017-01-01

Anticoagulation in patients with impaired kidney function can be challenging since drugs' pharmacokinetics and bioavailability are altered in this setting. Patients with chronic kidney disease (CKD) treated with conventional anticoagulant agents [vitamin K antagonist (VKA), low-molecular weight...... are eliminated via the kidneys pose additional challenges. More recently, two classes of direct oral anticoagulant agents (DOACs) have been investigated for the prevention and management of venous thromboembolic events: the direct factor Xa inhibitors rivaroxaban, apixaban and edoxaban, and the direct thrombin...

21 CFR 582.5195 - Calcium citrate.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium citrate. 582.5195 Section 582.5195 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Supplements 1 § 582.5195 Calcium citrate. (a) Product. Calcium citrate. (b) Conditions of use. This substance...

21 CFR 582.1195 - Calcium citrate.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Calcium citrate. 582.1195 Section 582.1195 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1195 Calcium citrate. (a) Product. Calcium citrate. (b) Conditions of use. This substance is...

Direct oral anticoagulants and venous thromboembolism

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Massimo Franchini

2016-09-01

Full Text Available Venous thromboembolism (VTE, consisting of deep vein thrombosis and pulmonary embolism, is a major clinical concern associated with significant morbidity and mortality. The cornerstone of management of VTE is anticoagulation, and traditional anticoagulants include parenteral heparins and oral vitamin K antagonists. Recently, new oral anticoagulant drugs have been developed and licensed, including direct factor Xa inhibitors (e.g. rivaroxaban, apixaban and edoxaban and thrombin inhibitors (e.g. dabigatran etexilate. This narrative review focusses on the characteristics of these direct anticoagulants and the main results of published clinical studies on their use in the prevention and treatment of VTE.

[Seronegative antiphospholipid syndrome, catastrophic syndrome, new anticoagulants: learning from a difficult case report].

Science.gov (United States)

Joalland, F; de Boysson, H; Darnige, L; Johnson, A; Jeanjean, C; Cheze, S; Augustin, A; Auzary, C; Geffray, L

2014-11-01

The diagnosis of the antiphospholipid syndrome (APS) is based on clinical and biological criteria including the persistent presence of antiphospholipid antibodies and thrombotic events or pregnancy morbidity. Heparins relayed by vitamin K antagonists (VKA) are the gold standard treatment for thrombosis. We report a 17-year-old man who presented with an initially seronegative antiphospholipid syndrome, in whom the diagnosis was late, only obtained after anticoagulation withdrawing, when a catastrophic antiphospholipid syndrome (CAPS) with cutaneous lesions and disseminated intravascular coagulation syndrome occurred. For personal convenience, this patient was initially treated with fondaparinux followed by a new oral anticoagulant (rivaroxaban) before to return to the conventional VKA treatment. The "seronegative" APS is a controversial concept reflecting the heterogeneity of antigenic targets for aPL. This diagnosis may be considered after a rigorous work-up, with the help of haemostasis laboratories testing new emerging aPL assays. In APS, the new anticoagulants represent an attractive option needing nevertheless prospective studies to evaluate their safety and efficacy. Lupus anticoagulant detection in patients treated by new oral anticoagulants is not easy by usually recommended coagulation tests. Copyright © 2014. Published by Elsevier SAS.

Anticoagulant Medicine: Potential for Drug-Food Interactions

Science.gov (United States)

... Medications Anticoagulants and Drug-Food Interactions Anticoagulants and Drug-Food Interactions Make an Appointment Ask a Question Refer Patient ... Jewish Health wants you to be aware these drug-food interactions when taking anticoagulant medicine. Ask your health care ...

Use of anticoagulants in elderly patients: practical recommendations

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Helia Robert-Ebadi

2009-04-01

Full Text Available Helia Robert-Ebadi, Grégoire Le Gal, Marc RighiniDivision of Angiology and Hemostasis (HRE, MR, Department of Internal Medicine, Geneva University Hospital and Faculty of Medicine, Geneva, Switzerland, and Department of Internal Medicine and Chest Diseases, EA 3878 (GETBO, Brest University Hospital, Brest, France (GLGAbstract: Elderly people represent a patient population at high thromboembolic risk, but also at high hemorrhagic risk. There is a general tendency among physicians to underuse anticoagulants in the elderly, probably both because of underestimation of thromboembolic risk and overestimation of bleeding risk. The main indications for anticoagulation are venous thromboembolism (VTE prophylaxis in medical and surgical settings, VTE treatment, atrial fibrillation (AF and valvular heart disease. Available anticoagulants for VTE prophylaxis and initial treatment of VTE are low molecular weight heparins (LMWH, unfractionated heparin (UFH or synthetic anti-factor Xa pentasaccharide fondaparinux. For long-term anticoagulation vitamin K antagonists (VKA are the first choice and only available oral anticoagulants nowadays. Assessing the benefit-risk ratio of anticoagulation is one of the most challenging issues in the individual elderly patient, patients at highest hemorrhagic risk often being those who would have the greatest benefit from anticoagulants. Some specific considerations are of utmost importance when using anticoagulants in the elderly to maximize safety of these treatments, including decreased renal function, co-morbidities and risk of falls, altered pharmacodynamics of anticoagulants especially VKAs, association with antiplatelet agents, patient education. Newer anticoagulants that are currently under study could simplify the management and increase the safety of anticoagulation in the future.Keywords: anticoagulation, elderly patients, venous thromboembolism, hemorrhagic risk, atrial fibrillation, thrombin inhibitors, factor Xa

21 CFR 184.1625 - Potassium citrate.

Science.gov (United States)

2010-04-01

... acid with potassium hydroxide or potassium carbonate. It occurs as transparent crystals or a white... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Potassium citrate. 184.1625 Section 184.1625 Food... Specific Substances Affirmed as GRAS § 184.1625 Potassium citrate. (a) Potassium citrate (C6H5K3O7·H2O, CAS...

Anticoagulation and high dose liver radiation. A preliminary report

International Nuclear Information System (INIS)

Lightdale, C.J.; Wasser, J.; Coleman, M.; Brower, M.; Tefft, M.; Pasmantier, M.

1979-01-01

Two groups of patients were observed for evidence of acute radiation hepatitis during high dose radiation to the liver. The first group of 18 patients with metastatic liver disease received an average of 4,050 rad to the whole liver. Half received anticoagulation with warfarin. One patient on anticoagulation developed evidence of acute radiation hepatitis while 2 patients did so without anticoagulation. Eleven patients with Hodgkin's disease received 4,000 rad to the left lobe of the liver during extended field radiation. Four of these 11 patients were anticoagulated to therapeutic range. Only one of the fully anticoagulated patients showed changes on liver scan consistent with radiation hepatitis whereas three did so without anticoagulation. No serious sequelae from anticoagulation occurred in either group. These preliminary data suggest that anticoagulation may be safely administered with high dose hepatic radiation and that further trials with anticoagulation are warranted

Managing reversal of direct oral anticoagulants in emergency situations Anticoagulation Education Task Force White Paper

NARCIS (Netherlands)

Ageno, Walter; Büller, Harry R.; Falanga, Anna; Hacke, Werner; Hendriks, Jeroen; Lobban, Trudie; Merino, Jose; Milojevic, Ivan S.; Moya, Francisco; van der Worp, H. Bart; Randall, Gary; Tsioufis, Konstantinos; Verhamme, Peter; Camm, A. John

2016-01-01

Anticoagulation is the cornerstone of prevention and treatment of venous thromboembolism (VTE) and stroke prevention in patients with atrial fibrillation (AF). However, the mechanisms by which anticoagulants confer therapeutic benefit also increase the risk of bleeding. As such, reversal strategies

Fatal consequences of synergistic anticoagulation

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Sen P

2018-05-01

Full Text Available Objective: Novel oral anticoagulants (NOACs are increasingly being preferred by clinicians (and patients because they have a wide therapeutic window and therefore do not require monitoring of anticoagulant effect. Herein, we describe the unfortunate case of a patient who had fatal consequences as a result of switching from warfarin to rivaroxaban. Case Summary: A 90-year-old Caucasian woman, with atrial fibrillation on chronic anticoagulation with warfarin, was admitted to the hospital for pneumonia. She was treated with levofloxacin. In the same admission, her warfarin was switched to rivaroxaban. On Day 3 after the switch, her INR was found to be 6, and she developed a cervical epidural hematoma from C2 to C7. She ultimately developed respiratory arrest, was put on comfort care and died. Discussion: Rivaroxaban and warfarin are known to have a synergistic anticoagulant effect, usually seen shortly after switching. Antibiotics also increase the effects of warfarin by the inhibition of metabolizing isoenzymes. It is hypothesized that these two effects led to the fatal cervical spinal hematoma. Conclusion: The convenience of a wide therapeutic window and no requirement of laboratory monitoring makes the NOACs a desirable option for anticoagulation. However, there is lack of data and recommendations on how to transition patients from Warfarin to NOACs or even how to transition from one NOAC to another. Care should be taken to ensure continuous monitoring of anticoagulation when stopping, interrupting or switching between NOACS to avoid the possibility of fatal bleeding and strokes.

Does plasmin have anticoagulant activity?

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Jane Hoover-Plow

2010-03-01

Full Text Available Jane Hoover-PlowJoseph J Jacobs Center for Thrombosis and Vascular Biology, Departments of Cardiovascular Medicine and Molecular Cardiology, Lerner Research Institute Cleveland Clinic, Ohio, USAAbstract: The coagulation and fibrinolytic pathways regulate hemostasis and thrombosis, and an imbalance in these pathways may result in pathologic hemophilia or thrombosis. The plasminogen system is the primary proteolytic pathway for fibrinolysis, but also has important proteolytic functions in cell migration, extracellular matrix degradation, metalloproteinase activation, and hormone processing. Several studies have demonstrated plasmin cleavage and inactivation of several coagulation factors, suggesting plasmin may be not only be the primary fibrinolytic enzyme, but may have anticoagulant properties as well. The objective of this review is to examine both in vitro and in vivo evidence for plasmin inactivation of coagulation, and to consider whether plasmin may act as a physiological regulator of coagulation. While several studies have demonstrated strong evidence for plasmin cleavage and inactivation of coagulation factors FV, FVIII, FIX, and FX in vitro, in vivo evidence is lacking for a physiologic role for plasmin as an anticoagulant. However, inactivation of coagulation factors by plasmin may be useful as a localized anticoagulant therapy or as a combined thrombolytic and anticoagulant therapy.Keywords: thrombosis, anticoagulant, cardiovascular disease, plasminogen’s protease, blood

Incompatibility of Contrast Medium and Trisodium Citrate

International Nuclear Information System (INIS)

Delcour, Christian; Bruninx, Guy

2013-01-01

To test the compatibility of trisodium citrate, a catheter lock solution, with iodinated contrast medium. Iohexol, iobitridol, iodixanol, ioxaglate, ioxithalamate, iomeprol, and iopromide were tested. In all tests, 2 ml of contrast medium were mixed with 2 ml of trisodium citrate solution. Iodixanol and ioxaglate provoked a highly viscous gluelike precipitation when mixed with trisodium citrate. A brief transient precipitate was observed with iohexol, iomeprol, and ioxithalamate. Permanent precipitation occurred with iobitridol and iopromide. One must be aware of the potential for precipitation when contrast medium is mixed with trisodium citrate solution. Before trisodium citrate solution is injected, the catheter should be thoroughly flushed with saline if a contrast medium has previously been injected through it.

The recent clinical trials on use of the novel direct oral anticoagulants in patients with venous thromboembolism: a review

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Gualtiero Palareti

2014-10-01

Full Text Available Venous thromboembolism (VTE, encompassing deep vein thrombosis and pulmonary embolism, requires an immediate anticoagulation, that has been carried out so far by administering a parenteral anticoagulant drug (heparin or derivatives overlapped with an oral vitamin K antagonist (VKA, more often warfarin. Several new direct oral anticoagulants (DOACs, with a mechanism of action completely different than VKA, have been developed in recent years. Recent clinical trials have investigated their use in VTE patients showing results at least equal for efficacy and safety, and sometime even better, as the standard anticoagulant treatment. There are differences in the design of the trials. In two cases the involved DOAC was administered immediately after VTE diagnosis as a single drug treatment (rivaroxaban and apixaban, whereas in the other trials (involving dabigatran and edoxaban the DOAC was administered after an initial course of approximately 7 days with heparin or derivatives. Some clinical trials have also investigated the use of DOACs for extended anticoagulant treatment after the acute phase. Aim of this article is to review the results of the currently available clinical trials that have compared the use of DOACs versus the standard of care in patients with VTE.

21 CFR 184.1195 - Calcium citrate.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Calcium citrate. 184.1195 Section 184.1195 Food and... Substances Affirmed as GRAS § 184.1195 Calcium citrate. (a) Calcium citrate (Ca3(C6H5O7)2·4H2O, CAS Reg. No. 813-0994-095) is the calcium salt of citric acid. It is prepared by neutralizing citric acid with...

Secondary poisoning of owls by anticoagulant rodenticides

Science.gov (United States)

Mendenhall, Vivian M.; Pank, L.F.

1980-01-01

Anticoagulants-compounds that prevent clotting of the blood-are extensively used for control of small mammal pests. The potential secondary hazards of 6 anticoagulant rodenticides to birds of prey were examined in this study. Whole rats or mice were killed with each anticoagulant and were fed to 1-3 species of owls. Owls died of hemorrhaging after feeding on rats killed with bromadiolone, brodifacoum, or diphacinone; sublethal hemorrhaging occurred in owls fed rats killed with difenacoum. These results demonstrate potential secondary hazards of 4 anticoagulants to avian predators. No abnormalities were observed in owls fed rats killed with fumarin and chlorophacinone

Effects of computer-assisted oral anticoagulant therapy

DEFF Research Database (Denmark)

Rasmussen, Rune Skovgaard; Corell, Pernille; Madsen, Poul

2012-01-01

: Patients randomized to computer-assisted anticoagulation and the CoaguChek® system reached the therapeutic target range after 8 days compared to 14 days by prescriptions from physicians (p = 0.04). Time spent in the therapeutic target range did not differ between groups. The median INR value measured...... prescribed by physicians, and the total time spent within the therapeutic target range was similar. Thus computer-assisted oral anticoagulant therapy may reduce the cost of anticoagulation therapy without lowering the quality. INR values measured by CoaguChek® were reliable compared to measurements......UNLABELLED: BACKGROUND: Computer-assistance and self-monitoring lower the cost and may improve the quality of anticoagulation therapy. The main purpose of this clinical investigation was to use computer-assisted oral anticoagulant therapy to improve the time to reach and the time spent within...

Monitoring of anticoagulant therapy in heart disease: considerations for the current assays.

Science.gov (United States)

Boroumand, Mohammadali; Goodarzynejad, Hamidreza

2010-01-01

Clinicians should be aware of new developments to familiarize themselves with pharmacokinetic and pharmacodynamic characteristics of new anticoagulant agents to appropriately and safely use them. For the moment, cardiologists and other clinicians also require to master currently available drugs, realizing the mechanism of action, side effects, and laboratory monitoring to measure their anticoagulant effects. Warfarin and heparin have narrow therapeutic window with high inter- and intra-patient variability, thereby the use of either drug needs careful laboratory monitoring and dose adjustment to ensure proper antithrombotic protection while minimizing the bleeding risk. The prothrombin time (PT) and the activated partial thromboplastin time (aPTT) are laboratory tests commonly used to monitor warfarin and heparin, respectively. These two tests depend highly on the combination of reagent and instrument utilized. Results for a single specimen tested in different laboratories are variable; this is mostly attributable to the specific reagents and to a much lesser degree to the instrument used. The PT stands alone as the single coagulation test that has undergone the most extensive attempt at assay standardization. The international normalized ratio (INR) was introduced to "normalize" all PT reagents to a World Health Organization (WHO) reference thromboplastin preparation standard, such that a PT measured anywhere in the world would result in an INR value similar to that which would have been achieved had the WHO reference thromboplastin been utilized. However, INRs are reproducible between laboratories for only those patients who are stably anticoagulated with vitamin K antagonists (VKAs) (i.e., at least 6 weeks of VKA therapy), and are not reliable or reproducible between laboratories for patients for whom VKA therapy has recently been started or any other clinical conditions associated with a prolonged PT such as liver disease, disseminated intravascular coagulation

Inducible transport of citrate in Lactobacillus rhamnosus ATCC 7469.

Science.gov (United States)

de Figueroa, R M; Benito de Cárdenas, I L; Sesma, F; Alvarez, F; de Ruiz Holgado, A P; Oliver, G

1996-10-01

Lactobacillus rhamnosus ATCC 7469 exhibited diauxie when grown in a medium containing both glucose and citrate as energy source. Glucose was used as the primary energy source during the glucose-citrate diauxie. Uptake of citrate was carried out by an inducible citrate transport system. The induction of citrate uptake system was repressed in the presence of glucose. This repression was reversible and mediated by cAMP.

Bridging Anticoagulation

Science.gov (United States)

... clinical centers in the United States, Canada, and Brazil. A more detailed description of the study is ... Your Personal Message Send Message Share on Social Media Bridging Anticoagulation The BRIDGE Study Investigators Circulation. 2012; ...

The mythology of anticoagulation therapy interruption for dental surgery.

Science.gov (United States)

Wahl, Michael J

2018-01-01

Continuous anticoagulation therapy is used to prevent heart attacks, strokes, and other embolic complications. When patients receiving anticoagulation therapy undergo dental surgery, a decision must be made about whether to continue anticoagulation therapy and risk bleeding complications or briefly interrupt anticoagulation therapy and increase the risk of developing embolic complications. Results from decades of studies of thousands of dental patients receiving anticoagulation therapy reveal that bleeding complications requiring more than local measures for hemostasis have been rare and never fatal. However, embolic complications (some of which were fatal and others possibly permanently debilitating) sometimes have occurred in patients whose anticoagulation therapy was interrupted for dental procedures. Although there is now virtually universal consensus among national medical and dental groups and other experts that anticoagulation therapy should not be interrupted for most dental surgery, there are still some arguments made supporting anticoagulation therapy interruption. An analysis of these arguments shows them to be based on a collection of myths and half-truths rather than on logical scientific conclusions. The time has come to stop anticoagulation therapy interruption for dental procedures. Copyright © 2018 American Dental Association. Published by Elsevier Inc. All rights reserved.

Aspergillus niger Secretes Citrate to Increase Iron Bioavailability

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Odoni, Dorett I.; van Gaal, Merlijn P.; Schonewille, Tom; Tamayo-Ramos, Juan A.; Martins dos Santos, Vitor A. P.; Suarez-Diez, Maria; Schaap, Peter J.

2017-01-01

Aspergillus niger has an innate ability to secrete various organic acids, including citrate. The conditions required for A. niger citrate overproduction are well described, but the physiological reasons underlying extracellular citrate accumulation are not yet fully understood. One of the less understood culture conditions is the requirement of growth-limiting iron concentrations. While this has been attributed to iron-dependent citrate metabolizing enzymes, this straightforward relationship does not always hold true. Here, we show that an increase in citrate secretion under iron limited conditions is a physiological response consistent with a role of citrate as A. niger iron siderophore. We found that A. niger citrate secretion increases with decreasing amounts of iron added to the culture medium and, in contrast to previous findings, this response is independent of the nitrogen source. Differential transcriptomics analyses of the two A. niger mutants NW305 (gluconate non-producer) and NW186 (gluconate and oxalate non-producer) revealed up-regulation of the citrate biosynthesis gene citA under iron limited conditions compared to iron replete conditions. In addition, we show that A. niger can utilize Fe(III) citrate as iron source. Finally, we discuss our findings in the general context of the pH-dependency of A. niger organic acid production, offering an explanation, besides competition, for why A. niger organic acid production is a sequential process influenced by the external pH of the culture medium. PMID:28824560

Iron(III) citrate speciation in aqueous solution.

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Silva, Andre M N; Kong, XiaoLe; Parkin, Mark C; Cammack, Richard; Hider, Robert C

2009-10-28

Citrate is an iron chelator and it has been shown to be the major iron ligand in the xylem sap of plants. Furthermore, citrate has been demonstrated to be an important ligand for the non-transferrin bound iron (NTBI) pool occurring in the plasma of individuals suffering from iron-overload. However, ferric citrate chemistry is complicated and a definitive description of its aqueous speciation at neutral pH remains elusive. X-Ray crystallography data indicates that the alcohol function of citrate (Cit4-) is involved in Fe(III) coordination and that deprotonation of this functional group occurs upon complex formation. The inability to include this deprotonation in the affinity constant calculations has been a major source of divergence between various reports of iron(III)-citrate affinity constants. However the recent determination of the alcoholic pKa of citric acid (H4Cit) renders the reassessment of the ferric citrate system possible. The aqueous speciation of ferric citrate has been investigated by mass spectrometry and EPR spectroscopy. It was observed that the most relevant species are a monoiron dicitrate species and dinuclear and trinuclear oligomeric complexes, the relative concentration of which depends on the solution pH value and the iron : citric acid molar ratio. Spectrophotometric titration was utilized for affinity constant determination and the formation constant for the biologically relevant [Fe(Cit)2]5- is reported for the first time.

Assessing Bleeding Risk in Patients Taking Anticoagulants

Science.gov (United States)

Shoeb, Marwa; Fang, Margaret C.

2013-01-01

Anticoagulant medications are commonly used for the prevention and treatment of thromboembolism. Although highly effective, they are also associated with significant bleeding risks. Numerous individual clinical factors have been linked to an increased risk of hemorrhage, including older age, anemia, and renal disease. To help quantify hemorrhage risk for individual patients, a number of clinical risk prediction tools have been developed. These risk prediction tools differ in how they were derived and how they identify and weight individual risk factors. At present, their ability to effective predict anticoagulant-associated hemorrhage remains modest. Use of risk prediction tools to estimate bleeding in clinical practice is most influential when applied to patients at the lower spectrum of thromboembolic risk, when the risk of hemorrhage will more strongly affect clinical decisions about anticoagulation. Using risk tools may also help counsel and inform patients about their potential risk for hemorrhage while on anticoagulants, and can identify patients who might benefit from more careful management of anticoagulation. PMID:23479259

21 CFR 522.800 - Droperidol and fentanyl citrate injection.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Droperidol and fentanyl citrate injection. 522.800... § 522.800 Droperidol and fentanyl citrate injection. (a) Specifications. Droperidol and fentanyl citrate injection is a sterile solution containing 20 milligrams of droperidol and 0.4 milligram of fentanyl citrate...

Reversing the Effect of Oral Anticoagulant Drugs: Established and Newer Options.

Science.gov (United States)

Ansell, Jack E

2016-06-01

The vitamin K antagonists (VKAs) have been the standard (and only) oral anticoagulants used for the long-term treatment or prevention of venous thromboembolism or stroke in patients with atrial fibrillation. The coagulopathy induced by VKAs can be reversed with vitamin K, and in urgent situations, the vitamin K-dependent coagulation factors can be replaced by transfusion. In the last decade, a new class of oral anticoagulants has been developed, direct oral anticoagulants that bind to a specific coagulation factor and neutralize it. These compounds were shown to be effective and safe compared with the VKAs and were licensed for specific indications, but without a specific reversal agent. The absence of a reversal agent is a barrier to more widespread use of these agents. Currently, for the management of major life-threatening bleeding with the direct oral anticoagulants, most authorities recommend the use of four factor prothrombin complex concentrates. There are now three reversal agents in development and poised to enter the market. Idarucizumab is a specific antidote targeted to reverse the direct thrombin inhibitor, dabigatran, which was recently approved for use in the USA. Andexanet alfa is an antidote targeted to reverse the oral direct factor Xa inhibitors as well as the indirect inhibitor enoxaparin. Ciraparantag is an antidote targeted to reverse the direct thrombin and factor Xa inhibitors as well as the indirect inhibitor enoxaparin.

MARINE LEECH ANTICOAGULANT DIVERSITY AND EVOLUTION.

Science.gov (United States)

Tessler, Michael; Marancik, David; Champagne, Donald; Dove, Alistair; Camus, Alvin; Siddall, Mark E; Kvist, Sebastian

2018-03-16

Leeches (Annelida: Hirudinea) possess powerful salivary anticoagulants and, accordingly, are frequently employed in modern, authoritative medicine. Members of the almost exclusively marine family Piscicolidae account for 20% of leech species diversity, and feed on host groups (e.g., sharks) not encountered by their freshwater and terrestrial counterparts. Moreover, some species of Ozobranchidae feed on endangered marine turtles and have been implicated as potential vectors for the tumor-associated turtle herpesvirus. In spite of their ecological importance and unique host associations, there is a distinct paucity of data regarding the salivary transcriptomes of either of these families. Using next generation sequencing, we profiled transcribed, putative anticoagulants and other salivary bioactive compounds that have previously been linked to bloodfeeding from 7 piscicolid species (3 elasmobranch-feeders; 4 non-cartilaginous fish-feeders) and 1 ozobranchid species (2 samples). In total, 149 putative anticoagulants and bioactive loci were discovered in varying constellations throughout the different samples. The putative anticoagulants showed a broad spectrum of described antagonistic pathways, such as inhibition of factor Xa and platelet aggregation, that likely have similar bioactive roles in marine fish and turtles. A transcript with homology to ohanin, originally isolated from king cobras, was found in Cystobranchus vividus but is otherwise unknown from leeches. Estimation of selection pressures for the putative anticoagulants recovered evidence for both positive and purifying selection along several isolated branches in the gene trees and positive selection was also estimated for a few select codons in a variety of marine species. Similarly, phylogenetic analyses of the amino acid sequences for several anticoagulants indicated divergent evolution.

Reversing anticoagulant effects of novel oral anticoagulants: role of ciraparantag, andexanet alfa, and idarucizumab

Directory of Open Access Journals (Sweden)

Hu TY

2016-02-01

Full Text Available Tiffany Y Hu,1 Vaibhav R Vaidya,2 Samuel J Asirvatham2,31Mayo Medical School, 2Division of Cardiovascular Diseases, Department of Internal Medicine, 3Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, MN, USAAbstract: Novel oral anticoagulants (NOACs are increasingly used in clinical practice, but lack of commercially available reversal agents is a major barrier for mainstream use of these therapies. Specific antidotes to NOACs are under development. Idarucizumab (aDabi-Fab, BI 655075 is a novel humanized mouse monoclonal antibody that binds dabigatran and reverses its anticoagulant effect. In a recent Phase III study (Reversal Effects of Idarucizumab on Active Dabigatran, a 5 g intravenous infusion of idarucizumab resulted in the normalization of dilute thrombin time in 98% and 93% of the two groups studied, with normalization of ecarin-clotting time in 89% and 88% patients. Two other antidotes, andexanet alfa (PRT064445 and ciraparantag (PER977 are also under development for reversal of NOACs. In this review, we discuss commonly encountered management issues with NOACs such as periprocedural management, laboratory monitoring of anticoagulation, and management of bleeding. We review currently available data regarding specific antidotes to NOACs with respect to pharmacology and clinical trials.Keywords: novel oral anticoagulant, dabigatran, idarucizumab, reversal

Biotransformation of uranium and transition metal citrate complexes by clostridia

International Nuclear Information System (INIS)

Francis, A.J.; Joshi-Tope, G.A.; Dodge, C.J.; Gillow, J.B.

2002-01-01

Clostridium sphenoides, which uses citric acid as its sole carbon source, metabolized equimolar Fe(III)-citrate with the degradation of citric acid and the reduction of Fe(III) to Fe(II), but not the U(VI)-citrate complex. However, in the presence of excess citric acid or added glucose it was reduced to U(IV)-citrate. In contrast, Clostridium sp., which ferments glucose but not citrate, reduced Fe(III)-citrate to Fe(II)-citrate and U(VI)-citrate to U(IV)-citrate only when supplied with glucose. These results show that complexed uranium is readily accessible as an electron acceptor despite the bacterium's inability to metabolize the organic ligand complexed to the actinide. These results also show that the metabolism of the metal-citrate complex depends upon the type of complex formed between the metal and citric acid. Fe(III) forms a bidentate complex with citric acid and was metabolized, whereas U forms a binuclear complex with citric acid and was recalcitrant. (author)

Anticoagulated patient's perception of their illness, their beliefs about the anticoagulant therapy prescribed and the relationship with adherence: impact of novel oral anticoagulant therapy - study protocol for The Switching Study: a prospective cohort study.

Science.gov (United States)

Auyeung, Vivian; Patel, Jignesh P; Abdou, John K; Vadher, Bipin; Bonner, Lynda; Brown, Alison; Roberts, Lara N; Patel, Raj K; Arya, Roopen

2016-01-01

Anticoagulant therapy is prescribed for millions of patients worldwide for the prevention and treatment of both arterial and venous thrombosis. Historically, only vitamin K antagonists have been available for clinicians to prescribe. The anticoagulation landscape is changing. The recent availability of the novel oral anticoagulants overcome many of the disadvantages associated with vitamin K antagonists. However the lack of formal monitoring and clinic follow-up is a concern for clinicians, as medication adherence is being assumed, which is known to decline in patients prescribed medications for chronic conditions. The switching study is a programme of work investigating the association between medication adherence and patient's beliefs about anticoagulation therapy (warfarin and subsequently novel oral anticoagulants), together with beliefs about their illness and anticoagulation related quality of life. The anticoagulation database at King's College Hospital will be interrogated and two groups of patients will be identified; those with a time in therapeutic range on warfarin of ≥75 % and those beliefs about medications compared. Those patients in the time in therapeutic range beliefs about medications, re-evaluated on the novel agent. The results from these sub-studies, will inform a clinical pathway to support patients on these novel agents, which will be evaluated in an independent group of patients. The results from the switching study will be used to develop a clinical pathway to support patient's prescribed novel oral anticoagulant therapy long-term.

Na/K citrate versus sodium bicarbonate in prevention of contrast-induced nephropathy

Directory of Open Access Journals (Sweden)

Sameh Mohamed Abouzeid

2016-01-01

Full Text Available Contrast-induced nephropathy (CIN is one of the important complications of radiographic procedures, especially in patients with chronic kidney disease. It is also one of the common causes of acute kidney injury. The pathogenesis is postulated to be the effect of oxygen- free radicals and hyperosmolar stress on the renal medulla. It is reported that the production of superoxide is most active at acid environment. K/Na citrate is well known as a urine alkalini- zation medium, and this has been evaluated earlier with standard hydration for reduction of CIN and was stated to be efficient. We aimed to determine the efficacy of Na/K citrate in reducing the frequency of CIN in comparison to sodium bicarbonate in patients after coronary angiography. Two hundred and ten patients with renal dysfunction [estimated glomerular filtration rate (eGFR, 60 mL/min/1.73 m2or less] who underwent elective or emergency coronary angiography (CAG with/without percutaneous coronary intervention (PCI at our institution were enrolled into the study. The patients were randomized into two groups, Group 1-Taking Na/K citrate and Group 2-Taking sodium bicarbonate. Radiographic contrast agent iohexol was used. Change in creatinine, percent change in creatinine, percent change in eGFR, change in serum potassium, and urine pH were all compared between the two groups. There was no significant difference for prevention of CIN when comparing the Na/K citrate with sodium bicarbonate solution in patients exposed to CAG with or without PCI. Mean absolute change in eGFR after 48 h after administration of contrast between sodium bicarbonate group and Na/K citrate group was −0.60 ± 1.58 versus −0.71 ± 1.38. Serum potassium decreased postprocedure in the sodium bicarbonate group than in the citrate group (3.90 ± 0.33 vs. 4.14 ± 0.39. Both agents are equally effective in reducing the incidence of CIN, but the citrate would possibly be a safer option for patients at risk of

The pharmacology of recombinant hirudin, a new anticoagulant ...

African Journals Online (AJOL)

A new anticoagulant, recombinant hirudin, was given to healthy volunteers (5 per test dose) in single .intravenous doses of 0,01, 0,02, 0,04, 0,07 and 0,1 mg/kg to study its anticoagulant effects, how it was tolerated and its pharmacokinetics. Hirudin proved to be a potent anticoagulant with important effects on thrombin ...

Hair sheep blood, citrated or defibrinated, fulfills all requirements of blood agar for diagnostic microbiology laboratory tests.

Science.gov (United States)

Yeh, Ellen; Pinsky, Benjamin A; Banaei, Niaz; Baron, Ellen Jo

2009-07-03

Blood agar is used for the identification and antibiotic susceptibility testing of many bacterial pathogens. In the developing world, microbiologists use human blood agar because of the high cost and inhospitable conditions for raising wool sheep or horses to supply blood. Many pathogens either fail to grow entirely or exhibit morphologies and hemolytic patterns on human blood agar that confound colony recognition. Furthermore, human blood can be hazardous to handle due to HIV and hepatitis. This study investigated whether blood from hair sheep, a hardy, low-maintenance variety of sheep adapted for hot climates, was suitable for routine clinical microbiology studies. Hair sheep blood obtained by jugular venipuncture was anticoagulated by either manual defibrination or collection in human blood bank bags containing citrate-phosphate-dextrose. Trypticase soy 5% blood agar was made from both forms of hair sheep blood and commercial defibrinated wool sheep blood. Growth characteristics, colony morphologies, and hemolytic patterns of selected human pathogens, including several streptococcal species, were evaluated. Specialized identification tests, including CAMP test, reverse CAMP test, and satellite colony formation with Haemophilus influenzae and Abiotrophia defectiva were also performed. Mueller-Hinton blood agar plates prepared from the three blood types were compared in antibiotic susceptibility tests by disk diffusion and E-test. The results of all studies showed that blood agar prepared from citrated hair sheep blood is suitable for microbiological tests used in routine identification and susceptibility profiling of human pathogens. The validation of citrated hair sheep blood eliminates the labor-intensive and equipment-requiring process of manual defibrination. Use of hair sheep blood, in lieu of human blood currently used by many developing world laboratories and as an alternative to cost-prohibitive commercial sheep blood, offers the opportunity to

Hair sheep blood, citrated or defibrinated, fulfills all requirements of blood agar for diagnostic microbiology laboratory tests.

Directory of Open Access Journals (Sweden)

Ellen Yeh

Full Text Available BACKGROUND: Blood agar is used for the identification and antibiotic susceptibility testing of many bacterial pathogens. In the developing world, microbiologists use human blood agar because of the high cost and inhospitable conditions for raising wool sheep or horses to supply blood. Many pathogens either fail to grow entirely or exhibit morphologies and hemolytic patterns on human blood agar that confound colony recognition. Furthermore, human blood can be hazardous to handle due to HIV and hepatitis. This study investigated whether blood from hair sheep, a hardy, low-maintenance variety of sheep adapted for hot climates, was suitable for routine clinical microbiology studies. METHODS AND FINDINGS: Hair sheep blood obtained by jugular venipuncture was anticoagulated by either manual defibrination or collection in human blood bank bags containing citrate-phosphate-dextrose. Trypticase soy 5% blood agar was made from both forms of hair sheep blood and commercial defibrinated wool sheep blood. Growth characteristics, colony morphologies, and hemolytic patterns of selected human pathogens, including several streptococcal species, were evaluated. Specialized identification tests, including CAMP test, reverse CAMP test, and satellite colony formation with Haemophilus influenzae and Abiotrophia defectiva were also performed. Mueller-Hinton blood agar plates prepared from the three blood types were compared in antibiotic susceptibility tests by disk diffusion and E-test. CONCLUSIONS: The results of all studies showed that blood agar prepared from citrated hair sheep blood is suitable for microbiological tests used in routine identification and susceptibility profiling of human pathogens. The validation of citrated hair sheep blood eliminates the labor-intensive and equipment-requiring process of manual defibrination. Use of hair sheep blood, in lieu of human blood currently used by many developing world laboratories and as an alternative to cost

Optimal duration of anticoagulation in patients with venous thromboembolism.

Science.gov (United States)

Prandoni, Paolo; Piovella, Chiara; Spiezia, Luca; Dalla Valle, Fabio; Pesavento, Raffaele

2011-07-01

The risk of recurrent venous thromboembolism (VTE) approaches 40 per cent of all patients after 10 yr of follow up. This risk is higher in patients with permanent risk factors of thrombosis such as active cancer, prolonged immobilization from medical diseases, and antiphospholipid syndrome; in carriers of several thrombophilic abnormalities, including deficiencies of natural anticoagulants; and in patients with unprovoked presentation. Patients with permanent risk factors of thrombosis should receive indefinite anticoagulation, consisting of subtherapeutic doses of low molecular weight heparin in cancer patients, and oral anticoagulants in all other conditions. Patients whose VTE is triggered by major surgery or trauma should be offered three months of anticoagulation. Patients with unprovoked VTE, including carriers of thrombophilia, and those whose thrombotic event is associated with minor risk factors (such as hormonal treatment, minor injuries, long travel) should receive at least three months of anticoagulation. The decision as to go on or discontinue anticoagulation after this period should be individually tailored and balanced against the haemorrhagic risk. Post-baseline variables, such as the D-dimer determination and the ultrasound assessment of residual thrombosis can help identify those patients in whom anticoagulation can be safely discontinued. As a few emerging anti-Xa and anti-IIa compounds seem to induce fewer haemorrhagic complications than conventional anticoagulation, while preserving at least the same effectiveness, these have the potential to open new scenarios for decisions regarding the duration of anticoagulation in patients with VTE.

Gallium-67 citrate localization in disseminated sporotrichosis

International Nuclear Information System (INIS)

Moreno, A.J.; Brazier, J.M.; Baker, F.J.; Fox, B.J.; Pittman, D.L.

1985-01-01

A 25-year-old woman demonstrated Ga-67 citrate accumulation within a facial cutaneous lesion and two subcutaneous nodules within the right lower extremity. Cultures of the facial lesion and one of the subcutaneous nodules grew Sporothrix schenckii. Ga-67 citrate uptake has not been reported previously with this fungal infection. Ga-67 citrate scintigraphy was helpful in defining the extent of the disease, following its course, and determining the response to therapy

SMART: self-management of anticoagulation, a randomised trial [ISRCTN19313375].

Science.gov (United States)

McCahon, Deborah; Fitzmaurice, David A; Murray, Ellen T; Fuller, Christopher J; Hobbs, Richard F D; Allan, Teresa F; Raftery, James P

2003-09-18

Oral anticoagulation monitoring has traditionally taken place in secondary care because of the need for a laboratory blood test, the international normalised ratio (INR). The development of reliable near patient testing (NPT) systems for INR estimation has facilitated devolution of testing to primary care. Patient self-management is a logical progression from the primary care model. This study will be the first to randomise non-selected patients in primary care, to either self-management or standard care. The study was a multi-centred randomised controlled trial with patients from 49 general practices recruited. Those suitable for inclusion were aged 18 or over, with a long term indication for oral anticoagulation, who had taken warfarin for at least six months. Patients randomised to the intervention arm attended at least two training sessions which were practice-based, 1 week apart. Each patient was assessed on their capability to undertake self management. If considered capable, they were given a near patient INR testing monitor, test strips and quality control material for home testing. Patients managed their own anticoagulation for a period of 12 months and performed their INR test every 2 weeks. Control patients continued with their pre-study care either attending hospital or practice based anticoagulant clinics. The methodology used in this trial will overcome concerns from previous trials of selection bias and relevance to the UK health service. The study will give a clearer understanding of the benefits of self-management in terms of clinical and cost effectiveness and patient preference.

SMART: Self-Management of Anticoagulation, a Randomised Trial [ISRCTN19313375

Directory of Open Access Journals (Sweden)

Murray Ellen T

2003-09-01

Full Text Available Abstract Background Oral anticoagulation monitoring has traditionally taken place in secondary care because of the need for a laboratory blood test, the international normalised ratio (INR. The development of reliable near patient testing (NPT systems for INR estimation has facilitated devolution of testing to primary care. Patient self-management is a logical progression from the primary care model. This study will be the first to randomise non-selected patients in primary care, to either self-management or standard care. Method The study was a multi-centred randomised controlled trial with patients from 49 general practices recruited. Those suitable for inclusion were aged 18 or over, with a long term indication for oral anticoagulation, who had taken warfarin for at least six months. Patients randomised to the intervention arm attended at least two training sessions which were practice-based, 1 week apart. Each patient was assessed on their capability to undertake self management. If considered capable, they were given a near patient INR testing monitor, test strips and quality control material for home testing. Patients managed their own anticoagulation for a period of 12 months and performed their INR test every 2 weeks. Control patients continued with their pre-study care either attending hospital or practice based anticoagulant clinics. Discussion The methodology used in this trial will overcome concerns from previous trials of selection bias and relevance to the UK health service. The study will give a clearer understanding of the benefits of self-management in terms of clinical and cost effectiveness and patient preference.

Evaluation of hematuria in anticoagulated patients

International Nuclear Information System (INIS)

Cuttino, J.T.; Clark, R.L.

1986-01-01

To determine the efficacy of investigating hematuria in anticoagulated patients the authors examined records of 25 consecutive patients with hematuria who were on an anticoagulation regimen with sodium warfarin (Coumadin) for various thromboembolic disorders. All had undergone intravenous urography (IVU) and 12 had undergone cystoscopy. Potential bleeding sources were discovered in 14 patients by IVU and in seven patients by cystoscopy. Disorders found were renal stones (4), transitional carcinoma (1), lymphoma (1), retroperitoneal hematoma (1), bladder tumors (2), calcified renal mass (1), hemorrhagic cystitis (2), and enlarged prostate (7). In 18 (72%) patients, the findings on IVU and/or cystoscopy were abnormal. Hematuria is a serious symptom that warrants investigation in anticoagulated as well as nonanticoagulated patients

Anticoagulation knowledge in patients with atrial fibrillation: An Australian survey.

Science.gov (United States)

Obamiro, Kehinde O; Chalmers, Leanne; Lee, Kenneth; Bereznicki, Bonnie J; Bereznicki, Luke R E

2018-03-01

Atrial fibrillation (AF) is the most commonly diagnosed arrhythmia in clinical practice, and is associated with a significant medical and economic burden. Anticoagulants reduce the risk of stroke and systemic embolism by approximately two-thirds compared with no therapy. Knowledge regarding anticoagulant therapy can influence treatment outcomes in patients with AF. To measure the level of anticoagulation knowledge in patients with AF taking oral anticoagulants (OACs), investigate the association between patient-related factors and anticoagulation knowledge, and compare these results in patients taking warfarin and direct-acting oral anticoagulant (DOACs). Participants were recruited for an online survey via Facebook. Survey components included the Anticoagulation Knowledge Tool, the Perception of Anticoagulant Treatment Questionnaires (assessing treatment expectations, convenience and satisfaction), a modified Cancer Information Overload scale and the Morisky Medication Adherence Scale. Treatment groups were compared and predictors of OAC knowledge were identified. Participants taking warfarin had a higher knowledge score compared with those taking DOACs (n = 386, 73% ± 13% vs 66% ± 14%, Pcounselling sessions to help identify and resolve knowledge deficits. © 2018 John Wiley & Sons Ltd.

Evidence-Based Management of Anticoagulant Therapy

Science.gov (United States)

Schulman, Sam; Witt, Daniel M.; Vandvik, Per Olav; Fish, Jason; Kovacs, Michael J.; Svensson, Peter J.; Veenstra, David L.; Crowther, Mark; Guyatt, Gordon H.

2012-01-01

Background: High-quality anticoagulation management is required to keep these narrow therapeutic index medications as effective and safe as possible. This article focuses on the common important management questions for which, at a minimum, low-quality published evidence is available to guide best practices. Methods: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. Results: Most practical clinical questions regarding the management of anticoagulation, both oral and parenteral, have not been adequately addressed by randomized trials. We found sufficient evidence for summaries of recommendations for 23 questions, of which only two are strong rather than weak recommendations. Strong recommendations include targeting an international normalized ratio of 2.0 to 3.0 for patients on vitamin K antagonist therapy (Grade 1B) and not routinely using pharmacogenetic testing for guiding doses of vitamin K antagonist (Grade 1B). Weak recommendations deal with such issues as loading doses, initiation overlap, monitoring frequency, vitamin K supplementation, patient self-management, weight and renal function adjustment of doses, dosing decision support, drug interactions to avoid, and prevention and management of bleeding complications. We also address anticoagulation management services and intensive patient education. Conclusions: We offer guidance for many common anticoagulation-related management problems. Most anticoagulation management questions have not been adequately studied. PMID:22315259

Comparison of the efficiency of clomiphene citrate and letrozole in combination with metformin in moderately obese clomiphene citrate-resistant polycystic ovarian syndrome patients.

Science.gov (United States)

Bjelica, Artur; Trninić-Pjević, Aleksandra; Mladenović-Segedi, Ljiljana; Cetković, Nenad; Petrović, Djordje

2016-01-01

Polycystic ovary syndrome is the most common endocrinopathy in women of reproductive-age. Therapy for those who want to get pregnant involves ovulation induction using clomiphene citrate, metformin, letrozole and gonadotropins. The aim of the study was to compare the efficacy of combinations of clomiphene citrate-metformin and letrozole-metformin in obese patients who are resistant to clomiphene citrate alone. The investigation was conducted as a retrospective study involving 60 moderately obese patients with polycystic ovary syndrome. Thirty-one of them received the clomiphene citrate-metformin, and 29 letrozole-metformin therapy. Stimulation was carried out for the procedures of intrauterine insemination (IUI). The age of patients, duration of infertility, and body mass index in both groups were similar. There was statistically significant difference in the thickness of the endometrium in favor of the group having the letrozole-metformin therapy (8.9 ± 1.7 mm) compared with the group receiving the clomiphene citrate-metformin treatment (6.3 ± 1.3 mm). The number of follicles was not statistically significantly different. Pregnancy rate in the first cycle of IUI in the clomiphene citrate group was 6.4%, and 17.2% in the letrozole group, which also was not statistically different. After the third IUI cycle, the pregnancy rate was significantly higher in the letrozole group (20.6%), while in the clomiphene citrate group it was (9.6%). This retrospective study demonstrated the advantages of the use of letrozole over clomiphene citrate in combination with metformin in moderately obese patients with polycystic ovary syndrome who are resistant to stimulation with clomiphene citrate alone.

INR targets and site-level anticoagulation control: results from the Veterans AffaiRs Study to Improve Anticoagulation (VARIA).

Science.gov (United States)

Rose, A J; Berlowitz, D R; Miller, D R; Hylek, E M; Ozonoff, A; Zhao, S; Reisman, J I; Ash, A S

2012-04-01

Not all clinicians target the same International Normalized Ratio (INR) for patients with a guideline-recommended target range of 2-3. A patient's mean INR value suggests the INR that was actually targeted. We hypothesized that sites would vary by mean INR, and that sites of care with mean values nearest to 2.5 would achieve better anticoagulation control, as measured by per cent time in therapeutic range (TTR). To examine variations among sites in mean INR and the relationship with anticoagulation control in an integrated system of care. We studied 103,897 patients receiving oral anticoagulation with an expected INR target between 2 and 3 at 100 Veterans Health Administration (VA) sites from 1 October 2006 to 30 September 2008. Key site-level variables were: proportion near 2.5 (that is, percentage of patients with mean INR between 2.3 and 2.7) and mean risk-adjusted TTR. Site mean INR ranged from 2.22 to 2.89; proportion near 2.5, from 30 to 64%. Sites' proportions of patients near 2.5, below 2.3 and above 2.7 were consistent from year to year. A 10 percentage point increase in the proportion near 2.5 predicted a 3.8 percentage point increase in risk-adjusted TTR (P < 0.001). Proportion of patients with mean INR near 2.5 is a site-level 'signature' of care and an implicit measure of targeted INR. This proportion varies by site and is strongly associated with site-level TTR. Our study suggests that sites wishing to improve TTR, and thereby improve patient outcomes, should avoid the explicit or implicit pursuit of non-standard INR targets. © 2012 International Society on Thrombosis and Haemostasis.

Reversal of target-specific oral anticoagulants

Science.gov (United States)

Siegal, D.M.; Cuker, Adam

2014-01-01

Target-specific oral anticoagulants (TSOACs) provide safe and effective anticoagulation for the prevention and treatment of thrombosis in a variety of clinical settings by interfering with the activity of thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban, edoxaban, betrixaban). Although TSOACs have practical advantages over vitamin K antagonists (VKAs), there are currently no antidotes to reverse their anticoagulant effect. Herein we summarize the available evidence for TSOAC reversal using nonspecific and specific reversal agents. We discuss important limitations of existing evidence, which is derived from studies in human volunteers, animal models and in vitro experiments. Studies evaluating the safety and efficacy of reversal agents on clinical outcomes such as bleeding and mortality in patients with TSOAC-associated bleeding are needed. PMID:24880102

Enclomiphene Citrate for the Treatment of Secondary Male Hypogonadism

Science.gov (United States)

Rodriguez, Katherine M.; Pastuszak, Alexander W.; Lipshultz, Larry I.

2016-01-01

Introduction Hypogonadism is a growing concern in an aging male population. Historically treated using exogenous testosterone, concerns about possible adverse effects of testosterone have led physicians to seek alternative treatment approaches. Areas Covered Enclomiphene citrate is the trans isomer of clomiphene citrate, a non-steroidal estrogen receptor antagonist that is FDA-approved for the treatment of ovarian dysfunction in women. Clomiphene citrate has also been used off-label for many years to treat secondary male hypogonadism, particularly in the setting of male infertility. Here we review the literature examining the efficacy and safety of enclomiphene citrate in the setting of androgen deficiency. Expert Opinion Initial results support the conclusion that enclomiphene citrate increases serum testosterone levels by raising luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, without negatively impacting semen parameters. The ability to treat testosterone deficiency in men while maintaining fertility supports a role for enclomiphene citrate in the treatment of men in whom testosterone therapy is not a suitable option. PMID:27337642

Risk of gastrointestinal bleeding during anticoagulant treatment.

Science.gov (United States)

Lanas-Gimeno, Aitor; Lanas, Angel

2017-06-01

Gastrointestinal bleeding (GIB) is a major problem in patients on oral anticoagulation therapy. This issue has become even more pressing since the introduction of direct oral anticoagulants (DOACs) in 2009. Areas covered: Here we review current evidence related to GIB associated with oral anticoagulants, focusing on randomized controlled trials, meta-analyses, and post-marketing observational studies. Dabigatran 150 mg twice daily and rivaroxaban 20 mg once daily increase the risk of GIB compared to warfarin. The risk increase with edoxaban is dose-dependent, while apixaban shows apparently, no increased risk. We summarize what is known about GIB risk factors for individual anticoagulants, the location of GIB in patients taking these compounds, and prevention strategies that lower the risk of GIB. Expert opinion: Recently there has been an important shift in the clinical presentation of GIB. Specifically, upper GIB has decreased with the decreased incidence of peptic ulcers due to the broad use of proton pump inhibitors and the decreased prevalence of H. pylori infections. In contrast, the incidence of lower GIB has increased, due in part to colonic diverticular bleeding and angiodysplasia in the elderly. In this population, the addition of oral anticoagulation therapy, especially DOACs, seems to increase the risk of lower GIB.

Antitumor effect and toxicity of free rhodium (II) citrate and rhodium (II) citrate-loaded maghemite nanoparticles in mice bearing breast cancer.

Science.gov (United States)

Carneiro, Marcella Lemos Brettas; Peixoto, Raphael C A; Joanitti, Graziela A; Oliveira, Ricardo G S; Telles, Luis A M; Miranda-Vilela, Ana L; Bocca, Anamélia L; Vianna, Leonora M S; da Silva, Izabel C R; de Souza, Aparecido R; Lacava, Zulmira G M; Báo, Sônia N

2013-02-16

Magnetic fluids containing superparamagnetic iron oxide nanoparticles represent an attractive platform as nanocarriers in chemotherapy. Recently, we developed a formulation of maghemite nanoparticles coated with rhodium (II) citrate, which resulted in in vitro cytotoxicity enhanced up to 4.6 times when compared to free rhodium (II) citrate formulation on breast carcinoma cells. In this work, we evaluate the antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Mice were evaluated with regard to the treatments' toxicity through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine; DNA fragmentation and cell cycle of bone marrow cells; and liver, kidney and lung histology. In addition, the antitumor activity of rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate was verified by tumor volume reduction, histology and immunohistochemistry. Regarding the treatments' toxicity, no experimental groups had alterations in levels of serum ALT or creatinine, and this suggestion was corroborated by the histopathologic examination of liver and kidney of mice. Moreover, DNA fragmentation frequency of bone marrow cells was lower than 15% in all experimental groups. On the other hand, the complexes rhodium (II) citrate-functionalized maghemite and free rhodium (II) citrate led to a marked growth inhibition of tumor and decrease in CD31 and Ki-67 staining. In summary, we demonstrated that both rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate formulations exhibited antitumor effects against 4T1 metastatic breast cancer cell line following intratumoral administration. This antitumor effect was followed by inhibition of both cell proliferation and microvascularization and by tumor tissue injury characterized as necrosis and fibrosis. Remarkably, this is the first published report demonstrating the therapeutic efficacy of maghemite

Cost Effectiveness of Implantable Cardiac Monitor-Guided Intermittent Anticoagulation for Atrial Fibrillation: An Analysis of the REACT.COM Pilot Study.

Science.gov (United States)

Steinhaus, Daniel A; Zimetbaum, Peter J; Passman, Rod S; Leong-Sit, Peter; Reynolds, Matthew R

2016-08-30

Anticoagulation guidelines for patients with atrial fibrillation (AF) disregard AF burden. A strategy of targeted anticoagulation with novel oral anticoagulants (NOACs) based on continuous rhythm assessment with an implantable cardiac monitor (ICM) has recently been explored. We evaluated the potential cost-effectiveness of this strategy versus projected outcomes with continuous anticoagulation. We developed a Markov model using data from the Rhythm Evaluation for AntiCoagulaTion With COntinuous Monitoring (REACT.COM) pilot study (N = 59) and prior NOAC trials to calculate the costs and quality-adjusted life years (QALYs) associated with ICM-guided intermittent anticoagulation for AF versus standard care during a 3-year time horizon. Health state utilities were estimated from the pilot study population using the SF-12. Costs were based on current Medicare reimbursement. Over 14 ± 4 months of follow-up, 18 of 59 patients had 35 AF episodes. The ICM-guided strategy resulted in a 94% reduction in anticoagulant use relative to continuous treatment. There were no strokes, 3 (5.1%) TIAs, 2 major bleeding events (on aspirin) and 3 minor bleeding events with the ICM-guided strategy. The projected total 3-year costs were $12,535 for the ICM-guided strategy versus $13,340 for continuous anticoagulation. Projected QALYs were 2.45 for both groups. Based on a pilot study, a strategy of ICM-guided anticoagulation with NOACs may be cost-saving relative to expected outcomes with continuous anticoagulation, with similar quality-adjusted survival. This strategy could be attractive from a health economic perspective if shown to be safe and effective in a rigorous clinical trial. © 2016 Wiley Periodicals, Inc.

In vitro anti-thrombotic and anti-coagulant properties of blacklip abalone (Haliotis rubra) viscera hydrolysate.

Science.gov (United States)

Suleria, Hafiz Ansar Rasul; Masci, Paul P; Addepalli, Rama; Chen, Wei; Gobe, Glenda C; Osborne, Simone A

2017-07-01

Abalone viscera contain sulphated polysaccharides with anti-thrombotic and anti-coagulant activities. In this study, a hydrolysate was prepared from blacklip abalone (Haliotis rubra) viscera using papain and bromelain and fractionated using ion exchange and size exclusion chromatography. Hydrolysates and fractions were investigated for in vitro thrombin inhibition mediated through heparin cofactor II (HCII) as well as anti-coagulant activity in plasma and whole blood. On the basis of sulphated polysaccharide concentration, the hydrolysate inhibited thrombin through HCII with an inhibitor concentration at 50% (IC50) of 16.5 μg/mL compared with 2.1 μg/mL for standard heparin. Fractionation concentrated HCII-mediated thrombin inhibition down to an IC50 of 1.8 μg/mL and improved anti-coagulant activities by significantly delaying clotting time. This study confirmed the presence of anti-thrombotic and anti-coagulant molecules in blacklip abalone viscera and demonstrated that these activities can be enriched with a simple chromatography regime. Blacklip abalone viscera warrant further investigation as a source of nutraceutical or functional food ingredients. Graphical abstract Schematic showing preparation of bioactive extracts and fractions from blacklip abalone.

Anticoagulant activity of ginger ( Zingiber officinale Rosc ...

African Journals Online (AJOL)

Background: Herbal medicines with anticoagulant therapeutic claims could serve as veritable sources of new oral anticoagulant drugs with possible wider safety margins than the currently available ones. Objectives: This work was aimed at evaluating a Ginger Rhizome Methanolic Extract in vivo in rats for its potential ...

Synthesis and characterization of the Rhodium (II) citrate complex

International Nuclear Information System (INIS)

Najjar, R.; Santos, F.S. dos; Seidel, W.

1987-01-01

The preparation and characterization of the rhodium (II) citrate is described. Rhodium citrate was prepared by reacting citric acid trihydrated (3,4 g, 16 mmols) with anhydrous rhodium acetate (0,44 g, 1 mmol). Th electronic instruments, thermogravimetric curve and spectrum of rhodium (II) citrate are analysed. (M.J.C.) [pt

Comparison of the efficiency of clomiphene citrate and letrozole in combination with metformin in moderately obese clomiphene citrate - resistant polycystic ovarian syndrome patients

Directory of Open Access Journals (Sweden)

Bjelica Artur

2016-01-01

Full Text Available Introduction. Polycystic ovary syndrome is the most common endocrinopathy in women of reproductiveage. Therapy for those who want to get pregnant involves ovulation induction using clomiphene citrate, metformin, letrozole and gonadotropins. Objective. The aim of the study was to compare the efficacy of combinations of clomiphene citrate-metformin and letrozole-metformin in obese patients who are resistant to clomiphene citrate alone. Methods. The investigation was conducted as a retrospective study involving 60 moderately obese patients with polycystic ovary syndrome. Thirty-one of them received the clomiphene citrate-metformin, and 29 letrozole-metformin therapy. Stimulation was carried out for the procedures of intrauterine insemination (IUI. Results. The age of patients, duration of infertility, and body mass index in both groups were similar. There was statistically significant difference in the thickness of the endometrium in favor of the group having the letrozole-metformin therapy (8.9 ± 1.7 mm compared with the group receiving the clomiphene citrate-metformin treatment (6.3 ± 1.3 mm. The number of follicles was not statistically significantly different. Pregnancy rate in the first cycle of IUI in the clomiphene citrate group was 6.4%, and 17.2% in the letrozole group, which also was not statistically different. After the third IUI cycle, the pregnancy rate was significantly higher in the letrozole group (20.6%, while in the clomiphene citrate group it was (9.6%. Conclusion. This retrospective study demonstrated the advantages of the use of letrozole over clomiphene citrate in combination with metformin in moderately obese patients with polycystic ovary syndrome who are resistant to stimulation with clomiphene citrate alone.

Postpartum wound and bleeding complications in women who received peripartum anticoagulation.

Science.gov (United States)

Limmer, Jane S; Grotegut, Chad A; Thames, Elizabeth; Dotters-Katz, Sarah K; Brancazio, Leo R; James, Andra H

2013-07-01

The objective of this study was to compare wound and bleeding complications between women who received anticoagulation after cesarean delivery due to history of prior venous thromboembolic disease, arterial disease, or being a thrombophilia carrier with adverse pregnancy outcome, to women not receiving anticoagulation. Women in the Duke Thrombosis Center Registry who underwent cesarean delivery during 2003-2011 and received postpartum anticoagulation (anticoagulation group, n=77), were compared with a subset of women who delivered during the same time period, but did not receive anticoagulation (no anticoagulation group, n=77). The no anticoagulation group comprised women who were matched to the anticoagulation group by age, body mass index, type of cesarean (no labor vs. labor), and date of delivery. Bleeding and wound complications were compared between the two groups. A multivariable logistic regression model was constructed to determine if anticoagulation was an independent predictor of wound complication. Women who received anticoagulation during pregnancy had a greater incidence of wound complications compared to those who did not (30% vs. 8%, p<0.001). Using multivariable logistic regression, while controlling for race, diabetes, chorioamnionitis, and aspirin use, anticoagulation predicted the development of any wound complication (OR 5.8, 95% CI 2.2, 17.6), but there were no differences in the mean estimated blood loss at delivery (782 vs. 778 ml, p=0.91), change in postpartum hematocrit (5.4 vs. 5.2%, p=0.772), or percent of women receiving blood products (6.5 vs. 1.3%, p=0.209) between the two groups. Anticoagulation following cesarean delivery is associated with an increased risk of post-cesarean wound complications, but not other postpartum bleeding complications. Copyright © 2013 Elsevier Ltd. All rights reserved.

Antithrombotic/anticoagulant and anticancer activities of selected ...

African Journals Online (AJOL)

Antithrombotic/anticoagulant and anticancer activities of selected medicinal plants from South Africa. NLA Kee, N Mnonopi, H Davids, RJ Naudé, CL Frost. Abstract. Nine plants available in the Eastern Cape Province of South Africa were tested for antithrombotic and/or anticoagulant activity. Organic (methanol) and aqueous ...

Clomiphene citrate-induced visual hallucinations: a case report

OpenAIRE

Venkatesh, Ramesh; Gujral, Gaganjeet Singh; Gurav, Prachi; Tibrewal, Shailja; Mathur, Umang

2017-01-01

Background Polycystic ovary syndrome is a common cause of chronic anovulation and infertility in otherwise healthy fertile couples. Clomiphene citrate is used as a first-line ovulation induction therapy in patients with polycystic ovary syndrome. Clomiphene citrate can cause both systemic and ocular side effects. We report a rare side effect of illusory palinopsias in a patient with polycystic ovary syndrome treated with ovulation induction therapy with clomiphene citrate, and emphasize the n...

Preparation of lead titanate zirconate from metal citrates

International Nuclear Information System (INIS)

Bastos, C.M.R.

1994-01-01

Lead titanate zirconate (PZT) preparation from its metal constituent citrates have been investigated. Metal citrates were obtained by forced precipitation using a dehydration alcohol mixture. Salt solutions of lead nitrate and octahydrated zirconyl chloride, and titanium tetrachloride were treated separately with citric acid and ammonium hydroxide. Zirconium, titanium and lead oxides resulted from thermal decomposition of corresponding citrates at 500 0 C, 450 0 C and 250 0 C, respectively. Lead titanate (PT) and lead zirconate (P Z) were obtained by calcining at 450 0 C and 500 0 C, respectively, after adequate heating of citrates mechanically mixed in ethyl ether. PZT samples were obtained with different starting stoichiometry. Rhombohedral PZT-1 53/47 sample was prepared from co precipitating zirconyl ammonium and ammonium lead citrates in presence of ethanolic titanium oxide dispersion, and calcinating at 800 0 C. Rhombohedral PZT-q 52/48 sample was obtained from heating at 500 0 C for 2 hours a mixture of metal citrates coprecipitated by dehydration mixture of acetone-ethanol-formic acid (2:1:0,06). Tetragonal PZT-m stoichiometry 53/47 sample were obtained by calcining at after 600 0 C for 2 hours after heating a mechanically mixed metal citrates. PT phase arose at 400 0 C. PZT-m powders obtained in a range of 400 0 C-800 0 C were isostatically pressed, and sintered at 1100 0 C and 1200 0 C in saturated Pb O atmosphere. Rhombohedral sintered PZT was obtained with 7,78 g.cm -3 at 1200 0 C. (author). 123 refs, 53 figs, 32 tabs

Honey Bee Venom (Apis mellifera) Contains Anticoagulation Factors and Increases the Blood-clotting Time.

Science.gov (United States)

Zolfagharian, Hossein; Mohajeri, Mohammad; Babaie, Mahdi

2015-12-01

Bee venom (BV) is a complex mixture of proteins and contains proteins such as phospholipase and melittin, which have an effect on blood clotting and blood clots. The mechanism of action of honey bee venom (HBV, Apis mellifera) on human plasma proteins and its anti-thrombotic effect were studied. The purpose of this study was to investigate the anti-coagulation effect of BV and its effects on blood coagulation and purification. Crude venom obtained from Apis mellifera was selected. The anti-coagulation factor of the crude venom from this species was purified by using gel filtration chromatography (sephadex G-50), and the molecular weights of the anti-coagulants in this venom estimated by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Blood samples were obtained from 10 rabbits, and the prothrombin time (PT) and the partial thromboplastin time (PTT) tests were conducted. The approximate lethal dose (LD) values of BV were determined. Crude BV increased the blood clotting time. For BV concentrations from 1 to 4 mg/mL, clotting was not observed even at more than 300 seconds, standard deviations (SDs) = ± 0.71; however, clotting was observed in the control group 13.8 s, SDs = ± 0.52. Thus, BV can be considered as containing anti-coagulation factors. Crude BV is composed 4 protein bands with molecular weights of 3, 15, 20 and 41 kilodalton (kDa), respectively. The LD50 of the crude BV was found to be 177.8 μg/mouse. BV contains anti-coagulation factors. The fraction extracted from the Iranian bees contains proteins that are similar to anti-coagulation proteins, such as phospholipase A2 (PLA2) and melittin, and that can increase the blood clotting times in vitro.

Honey Bee Venom (Apis mellifera Contains Anticoagulation Factors and Increases the Blood-clotting Time

Directory of Open Access Journals (Sweden)

Hossein Zolfagharian

2015-12-01

Full Text Available Objectives: Bee venom (BV is a complex mixture of proteins and contains proteins such as phospholipase and melittin, which have an effect on blood clotting and blood clots. The mechanism of action of honey bee venom (HBV, Apis mellifera on human plasma proteins and its anti-thrombotic effect were studied. The purpose of this study was to investigate the anti-coagulation effect of BV and its effects on blood coagulation and purification. Methods: Crude venom obtained from Apis mellifera was selected. The anti-coagulation factor of the crude venom from this species was purified by using gel filtration chromatography (sephadex G-50, and the molecular weights of the anti-coagulants in this venom estimated by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE. Blood samples were obtained from 10 rabbits, and the prothrombin time (PT and the partial thromboplastin time (PTT tests were conducted. The approximate lethal dose (LD values of BV were determined. Results: Crude BV increased the blood clotting time. For BV concentrations from 1 to 4 mg/mL, clotting was not observed even at more than 300 seconds, standard deviations (SDs = ± 0.71; however, clotting was observed in the control group 13.8 s, SDs = ± 0.52. Thus, BV can be considered as containing anti-coagulation factors. Crude BV is composed 4 protein bands with molecular weights of 3, 15, 20 and 41 kilodalton (kDa, respectively. The LD50 of the crude BV was found to be 177.8 μg/mouse. Conclusion: BV contains anti-coagulation factors. The fraction extracted from the Iranian bees contains proteins that are similar to anti-coagulation proteins, such as phospholipase A2 (PLA2 and melittin, and that can increase the blood clotting times in vitro.

Excessive anticoagulation with warfarin or phenprocoumon may have multiple causes

DEFF Research Database (Denmark)

Meegaard, Peter Martin; Holck, Line H V; Pottegård, Anton

2012-01-01

Excessive anticoagulation with vitamin K antagonists is a serious condition with a substantial risk of an adverse outcome. We thus found it of interest to review a large case series to characterize the underlying causes of excessive anticoagulation.......Excessive anticoagulation with vitamin K antagonists is a serious condition with a substantial risk of an adverse outcome. We thus found it of interest to review a large case series to characterize the underlying causes of excessive anticoagulation....

Anticoagulant therapy and its impact on dental patients: a review.

Science.gov (United States)

Thean, D; Alberghini, M

2016-06-01

Several new oral anticoagulants have been studied in the past decade, and have now started to enter the market. These drugs are reported to be as effective as, or more effective than, warfarin. In Australia, the Therapeutic Goods Administration has approved dabigatran, rivaroxaban and apixaban. The use of these newer anticoagulants is likely to increase in time, and it is important for dentists to have a sound understanding of the mechanisms of action, reversal strategies, and management guidelines for patients taking oral anticoagulants. This article discusses the process of coagulation, available anticoagulants and their monitoring and reversal, and provides clinical advice on the management of patients on anticoagulants who require dental treatment. © 2016 Australian Dental Association.

Pathology consultation on anticoagulation monitoring: factor X-related assays.

Science.gov (United States)

Wool, Geoffrey D; Lu, Chuanyi M

2013-11-01

To review various anticoagulation therapies and related laboratory monitoring issues, with a focus on factor X-related chromogenic assays. A case-based approach is used to review pertinent published literatures and product inserts of anticoagulation drugs and to look back on clinical use of factor X-related chromogenic assays. The number of anticoagulants available to clinicians has increased greatly in the past decade. Whether and how these anticoagulants should be monitored are areas of uncertainty for clinicians, which can lead to misuse of laboratory assays and suboptimal patient management. Factor X-related assays are of particular concern because of the similar and often confusing test names. Based on a common clinical case scenario and literature review regarding anticoagulant monitoring, an up-to-date discussion and review of the various factor X-related assays are provided, focusing on the differences in test designs and clinical utilities between the chromogenic anti-Xa and chromogenic factor X activity assays. Anticoagulation therapy and related laboratory monitoring are rapidly evolving areas of clinical practices. A good knowledge of relevant laboratory assays and their clinical applications is necessary to help optimize patient care.

Is automated kinetic measurement superior to end-point for advanced oxidation protein product?

Science.gov (United States)

Oguz, Osman; Inal, Berrin Bercik; Emre, Turker; Ozcan, Oguzhan; Altunoglu, Esma; Oguz, Gokce; Topkaya, Cigdem; Guvenen, Guvenc

2014-01-01

Advanced oxidation protein product (AOPP) was first described as an oxidative protein marker in chronic uremic patients and measured with a semi-automatic end-point method. Subsequently, the kinetic method was introduced for AOPP assay. We aimed to compare these two methods by adapting them to a chemistry analyzer and to investigate the correlation between AOPP and fibrinogen, the key molecule responsible for human plasma AOPP reactivity, microalbumin, and HbA1c in patients with type II diabetes mellitus (DM II). The effects of EDTA and citrate-anticogulated tubes on these two methods were incorporated into the study. This study included 93 DM II patients (36 women, 57 men) with HbA1c levels > or = 7%, who were admitted to the diabetes and nephrology clinics. The samples were collected in EDTA and in citrate-anticoagulated tubes. Both methods were adapted to a chemistry analyzer and the samples were studied in parallel. In both types of samples, we found a moderate correlation between the kinetic and the endpoint methods (r = 0.611 for citrate-anticoagulated, r = 0.636 for EDTA-anticoagulated, p = 0.0001 for both). We found a moderate correlation between fibrinogen-AOPP and microalbumin-AOPP levels only in the kinetic method (r = 0.644 and 0.520 for citrate-anticoagulated; r = 0.581 and 0.490 for EDTA-anticoagulated, p = 0.0001). We conclude that adaptation of the end-point method to automation is more difficult and it has higher between-run CV% while application of the kinetic method is easier and it may be used in oxidative stress studies.

Quality of Vitamin K Antagonist Anticoagulation in Spain: Prevalence of Poor Control and Associated Factors.

Science.gov (United States)

Anguita Sánchez, Manuel; Bertomeu Martínez, Vicente; Cequier Fillat, Ángel

2015-09-01

To study the prevalence of poorly controlled vitamin K antagonist anticoagulation in Spain in patients with nonvalvular atrial fibrillation, and to identify associated factors. We studied 1056 consecutive patients seen at 120 cardiology clinics in Spain between November 2013 and March 2014. We analyzed the international normalized ratio from the 6 months prior to the patient's visit, calculating the prevalence of poorly controlled anticoagulation, defined as < 65% time in therapeutic range using the Rosendaal method. Mean age was 73.6 years (standard deviation, 9.8 years); women accounted for 42% of patients. The prevalence of poorly controlled anticoagulation was 47.3%. Mean time in therapeutic range was 63.8% (25.9%). The following factors were independently associated with poorly controlled anticoagulation: kidney disease (odds ratio = 1.53; 95% confidence interval, 1.08-2.18; P = .018), routine nonsteroidal anti-inflammatory drugs (odds ratio = 1.79; 95% confidence interval, 1.20-2.79; P = .004), antiplatelet therapy (odds ratio = 2.16; 95% confidence interval, 1.49-3.12; P < .0001) and absence of angiotensin receptor blockers (odds ratio = 1.39; 95% confidence interval, 1.08-1.79; P = .011). There is a high prevalence of poorly controlled vitamin K antagonist anticoagulation in Spain. Factors associated with poor control are kidney disease, routine nonsteroidal anti-inflammatory drugs, antiplatelet use, and absence of angiotensin receptor blockers. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Citrate and succinate uptake by potato mitochondria

International Nuclear Information System (INIS)

Jung, D.W.; Laties, G.G.

1979-01-01

Potato mitochondria, in the absence of respiration, have a very low capacity for uptake by exchange with endogenous anions, taking up only 2.4 nanomoles citrate and 2.0 nanomoles succinate per milligram protein. Maximum citrate uptake of over 17 nanomoles per milligram protein occurs in the presence of inorganic phosphate, a dicarboxylic acid, and an external energy source (NADH), conditions where net anion accumulation proceeds, mediated by the interlinking of the inorganic phosphate, dicarboxylate, and tricarboxylate carriers. Maximum succinate uptake in the absence of respiratory inhibitors requires only added inorganic phosphate. Compounds which inhibit respiration (antimycin), the exchange carriers (mersalyl and benzylmalonate), or the establishment of the membrane proton motive force (uncouplers) reduce substrate accumulation. A potent inhibitor of the citrate carrier in animal mitochondria, 1,2,3-benzenetricarboxylic acid, does not inhibit citrate uptake in potato mitochondria. Citrate uptake is reduced by concurrent ADP phosphorylation and this reduction is sensitive to oligomycin. The initiation of state 3 after a 3-minute substrate state results in a reduction of the steady-state of citrate uptake by approximately 50%. Accumulation of succinate initially is inhibited by increasing sucrose concentration in the reaction medium from 50 to 400 millimolar. Limited substrate uptake is one of the factors responsible for the often observed depressed initial state 3 respiration rates in many mitochondrial preparations. Since nonlimiting levels of substrate in the matrix cannot be attained by energy-independent exchange, a dependence on respiration for adequate uptake results. Substrate limitation therefore occurs in the matrix for the period of time needed for energy-dependent accumulation of nonlimiting levels

[Secondary osteoporosis induced by anticoagulants?].

Science.gov (United States)

Riess, H; Loew, A; Himmelreich, G

2001-07-01

Generalized osteoporosis is a result of different causes and pathogenic mechanisms, which often combine forces to become clinically relevant. Among the different exogenic factors, drugs play an important role, frequently in connection with other factors such as immobilization or pregnancy. It has been suggested that anticoagulation therapy with heparins or coumarins may induce osteoporotic changes or enhance the development of osteoporosis for other reasons. According to in vitro experiments, preclinical trials, and clinical investigations, it seems reasonable to assume that heparins induce increased bone loss in a time- and dose-related manner. Low-molecular-weight heparins most likely have less effect on bone turnover when compared to unfractionated heparin. Oral anticoagulation therapy with vitamin K-antagonists is believed to have a weak effect on induction of osteoporosis, but clinical studies are contradictory. In spite of the fact that a relevant effect of these drugs on the induction of osteoporosis is questionable, it must be taken into consideration that anticoagulant drugs may enhance the negative effects on bone density of other risk factors capable of inducing osteoporosis such as immobilization, pregnancy, or endocrinological disorders.

Blood platelet kinetics and platelet transfusion

OpenAIRE

Aster, Richard H.

2013-01-01

The discovery of citrate anticoagulant in the 1920s and the development of plastic packs for blood collection in the 1960s laid the groundwork for platelet transfusion therapy on a scale not previously possible. A major limitation, however, was the finding that platelet concentrates prepared from blood anticoagulated with citrate were unsuitable for transfusion because of platelet clumping. We found that this could be prevented by simply reducing the pH of platelet-rich plasma to about 6.5 pr...

A single center retrospective cohort study comparing low-molecular-weight heparins to direct oral anticoagulants for the treatment of venous thromboembolism in patients with cancer - A real world experience.

Science.gov (United States)

Phelps, Megan K; Wiczer, Tracy E; Erdeljac, H Paige; Van Deusen, Kelsey R; Porter, Kyle; Philips, Gary; Wang, Tzu-Fei

2018-01-01

Introduction Low-molecular-weight heparins are the standard treatment for cancer-associated thrombosis. Recently, direct oral anticoagulants are a new option for thrombosis treatment; however, data supporting the use of direct oral anticoagulants for cancer-associated thrombosis are limited. Objectives The primary objective of this study was to determine the rate of recurrent cancer-associated thrombosis and major bleeding within 6 months of starting either low-molecular-weight heparin or direct oral anticoagulant for treatment of cancer-associated thrombosis. Secondary objectives were to determine the rates of clinically relevant-non-major bleeding and all-cause mortality. Patients/methods This is a retrospective cohort study including adults with cancer-associated thrombosis treated with low-molecular-weight heparin or direct oral anticoagulant between 2010 and 2016 at the Ohio State University. Medical records were reviewed for 6 months after initiation of anticoagulation or until the occurrence of recurrent cancer-associated thrombosis, major bleeding, cessation of anticoagulation of interest, or death, whichever occurred first. Results Four hundred and eighty patients were included (290 low-molecular-weight heparin and 190 direct oral anticoagulant). Patients treated with direct oral anticoagulant were found to carry "lower risk" features including cancer with lower VTE risk and lower rate of metastatic disease. After adjustment for baseline differences, there was no significant difference in the rate of recurrent cancer-associated thrombosis (7.2% low-molecular-weight heparin vs 6.3% direct oral anticoagulant, p = 0.71) or major bleeding (7.6% low-molecular-weight heparin vs 2.6% direct oral anticoagulant, p = 0.08). Conclusions Our study demonstrates that in a select population of cancer patients with VTE, direct oral anticoagulant use can be as effective and safe compared to the standard therapy with low-molecular-weight heparin.

A test of the citrate method of PMI estimation from skeletal remains.

Science.gov (United States)

Wilson, Sarah J; Christensen, Angi M

2017-01-01

Citrate content in bone has been shown to be associated with the postmortem interval (PMI), with citrate decreasing after death as a function of time. Here we test this method using porcine ribs for the period of 1-165days after death, and also assess citrate content and variation from samples placed into two different postmortem environments (terrestrial and aquatic). Higher citrate variation, lower citrate recovery, and a weaker association with time were found in this study as compared to others. Citrate content, however, was found to decrease with increasing PMI, and the method was found to be easy and inexpensive to apply. No significant differences were found in citrate loss between terrestrial and aquatic environments. Although more research is needed, citrate content appears to be a promising new approach in estimating PMI from skeletal remains. Published by Elsevier B.V.

Net clinical benefit of combination anticoagulant and antiplatelet therapy versus anticoagulation alone in atrial fibrillation patients: Results from the amadeus trial

NARCIS (Netherlands)

Lane, Deirdre; Kamphuisen, Pieter; Minini, Pascal; De Peuter, Olaf R.; Buller, Harry R.; Lip, Gregory Y. H.

2010-01-01

Background: To compare the effect of combination anticoagulant and antiplatelet (AP) therapy with anticoagulation alone on stroke and bleeding risk in atrial fibrillation (AF) patients and examine predictors of clinically relevant bleeding. Methods: Post-hoc analysis of 4576 AF patients [mean (SD)

FERRIC CITRATE: AN IRON-BASED ORAL PHOSPHATE BINDER

Directory of Open Access Journals (Sweden)

T. Christopher Bond

2012-06-01

Based on actual physician behavior in response to ferritin and TSAT increases and ferric citrate clinical trial results, and assuming equivalent pricing to other PBs, there would be cost savings with ferric citrate use through reduced ESA and iron use.

Preparation of electrocatalysts by reduction of precursors with sodium citrate

OpenAIRE

Briskeby, Stein Trygve; Tsypkin, Mikhail; Tunold, Reidar; Sunde, Svein

2014-01-01

In this work synthesis of Pt/C catalysts by reduction of H2PtCl6 with sodium citrate has been investigated. The strong pH-dependence of citrate as a reducing and stabilizing agent has been explored, and an optimum pH range for production of well dispersed catalysts is proposed. To achieve stabilizing and reducing conditions, the presence of both citrate anions and protonated citrates are required. This is achieved in an intermediate pH range between pKa2 and pKa3 (4.76 and 6.4) of citric acid...

Oral Anticoagulant Use After Bariatric Surgery: A Literature Review and Clinical Guidance.

Science.gov (United States)

Martin, Karlyn A; Lee, Craig R; Farrell, Timothy M; Moll, Stephan

2017-05-01

Bariatric surgery may alter the absorption, distribution, metabolism, or elimination (disposition) of orally administered drugs via changes to the gastrointestinal tract anatomy, body weight, and adipose tissue composition. As some patients who have undergone bariatric surgery will need therapeutic anticoagulation for various indications, appropriate knowledge is needed regarding anticoagulant drug disposition and resulting efficacy and safety in this population. We review general considerations about oral drug disposition in patients after bariatric surgery, as well as existing literature on oral anticoagulation after bariatric surgery. Overall, available evidence on therapeutic anticoagulation is very limited, and individual drug studies are necessary to learn how to safely and effectively use the direct oral anticoagulants. Given the sparsity of currently available data, it appears most prudent to use warfarin with international normalized ratio monitoring, and not direct oral anticoagulants, when full-dose anticoagulation is needed after bariatric surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

[Drug compliance of patients on anticoagulant treatment].

Science.gov (United States)

Gadó, Klára; Kocsis, Eszter; Zelkó, Romána; Hankó, Balázs; Kovácsné Balogh, Judit; Forczig, Mónika; Domján, Gyula

2015-08-09

Despite several therapeutic possibilities the morbidity and mortality of thromboembolic disorders remain high. Improving drug compliance - i. e. keeping up the doctor's prescriptions - may be an effective tool to reach better results. To improve patients' compliance, the risk factors of non-compliance should be recognized. Among these patients' fear of adverse effects of drugs, their lack of knowledge about their illness and medication, forgetfulness, and other social, economic factors may be the most important. Furthermore, adherence may be worsened when the patient feels that the decision has been made over his/her head. Sustained medical adherence is important because anticoagulation may be a life-long treatment. The new oral anticoagulants make the matter of compliance to be current. These new type of drugs do not need regular laboratory monitoring and, therefore, compliance cannot be strictly followed. There are several studies concerning drug compliance to anticoagulant medications. Improvement of adherence is based on regular patient education after reviewing the factors of non-compliance, which needs teamwork with important roles of doctors, pharmacists, dietetics and nurses. Careful and accurate work of the participants of primary care might be complemented by the activity of anticoagulant clinics.

Adherence to oral anticoagulant therapy in secondary stroke prevention – impact of the novel oral anticoagulants

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Luger S

2015-11-01

Full Text Available Sebastian Luger,1 Carina Hohmann,2 Daniela Niemann,1 Peter Kraft,3 Ignaz Gunreben,3 Tobias Neumann-Haefelin,2 Christoph Kleinschnitz,3 Helmuth Steinmetz,1 Christian Foerch,1 Waltraud Pfeilschifter1 1Department of Neurology, University Hospital Frankfurt, Frankfurt am Main, 2Department of Neurology, Klinikum Fulda gAG, Fulda, 3Department of Neurology, University Hospital Würzburg, Würzburg, Germany Background: Oral anticoagulant therapy (OAT potently prevents strokes in patients with atrial fibrillation. Vitamin K antagonists (VKA have been the standard of care for long-term OAT for decades, but non-VKA oral anticoagulants (NOAC have recently been approved for this indication, and raised many questions, among them their influence on medication adherence. We assessed adherence to VKA and NOAC in secondary stroke prevention. Methods: All patients treated from October 2011 to September 2012 for ischemic stroke or transient ischemic attack with a subsequent indication for OAT, at three academic hospitals were entered into a prospective registry, and baseline data and antithrombotic treatment at discharge were recorded. At the 1-year follow-up, we assessed the adherence to different OAT strategies and patients’ adherence to their respective OAT. We noted OAT changes, reasons to change treatment, and factors that influence persistence to the prescribed OAT. Results: In patients discharged on OAT, we achieved a fatality corrected response rate of 73.3% (n=209. A total of 92% of these patients received OAT at the 1-year follow-up. We observed good adherence to both VKA and NOAC (VKA, 80.9%; NOAC, 74.8%; P=0.243 with a statistically nonsignificant tendency toward a weaker adherence to dabigatran. Disability at 1-year follow-up was an independent predictor of lower adherence to any OAT after multivariate analysis, whereas the choice of OAT did not have a relevant influence. Conclusion: One-year adherence to OAT after stroke is strong (>90% and patients

Real-life Use of Anticoagulants in Venous Thromboembolism With a Focus on Patients With Exclusion Criteria for Direct Oral Anticoagulants.

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Moustafa, Farès; Pesavento, Raffaele; di Micco, Pierpaolo; González-Martínez, José; Quintavalla, Roberto; Peris, Maria-Luisa; Porras, José Antonio; Falvo, Nicolas; Baños, Pilar; Monreal, Manuel

2018-04-01

We assessed the real-life use of direct oral anticoagulants (DOACs) in patients with venous thromboembolism (VTE) and exclusion criteria for randomized trials. From 2013 to 2016, 3,578 of 18,853 patients (19%) had exclusion criteria. Irrespective of which anticoagulant was chosen, they had more VTE recurrences (hazard ratio (HR): 3.10; 95% confidence interval (CI): 2.47-3.88), major bleeds (HR: 4.10; 95% CI: 3.38-4.96), and deaths (HR: 9.47; 95% CI: 8.46-10.6) than those without exclusion criteria. During initial therapy, no patient with exclusion criteria on DOACs (n = 115) recurred, but those on rivaroxaban bled less often (adjusted HR: 0.18; 95% CI: 0.04-0.79) than those on unfractionated heparin (n = 224) and similar to those (n = 3,172) on low-molecular-weight (LMWH) heparin. For long-term therapy, patients on rivaroxaban (n = 151) had nonsignificantly fewer VTE recurrences (adjusted HR: 0.74; 95% CI: 0.08-1.32) and major bleeds (adjusted HR: 0.41; 95% CI: 0.15-1.15) than those on LMWH (n = 2,071). The efficacy and safety of DOACs were similar to standard therapy. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Underuse of Anticoagulation in Older Patients with Atrial Fibrillation and CHADS2 Score ≥ 2: Are We Doing Better Since the Marketing of Direct Oral Anticoagulants?

Science.gov (United States)

Henrard, Séverine; Vandenabeele, Caroline; Marien, Sophie; Boland, Benoit; Dalleur, Olivia

2017-11-01

Our objectives were to (1) describe the evolution of the underuse of anticoagulants in older people with atrial fibrillation (AF) and a CHADS 2 score ≥ 2 since direct oral anticoagulants (DOACs) were introduced to the market and (2) describe factors associated with this underuse. We conducted a retrospective cross-sectional study including geriatric patients admitted during the pre-DOAC (2008-2011) and post-DOAC (2013-2015) periods in an academic hospital in Belgium. Five inclusion criteria were met: age ≥ 75 years, diagnosis of AF, indication for anticoagulation (CHADS 2 score ≥ 2), risk of functional decline (Identification of Seniors At Risk [ISAR] score ≥ 2), and comprehensive geriatric assessment. The use of anticoagulants and antiplatelets at home before admission was recorded. Risks of stroke and bleeding were calculated using CHADS 2 and HEMORR 2 HAGES scores, respectively. Three different logistic regression models were performed to describe the evolution of and factors associated with the underuse of anticoagulants after DOAC marketing. Anticoagulant underuse, present in 209 of 614 (34%) geriatric patients with AF, was lower in patients with a history of stroke (28.5%) or congestive heart failure (26.9%) but higher in those receiving antiplatelets (56.2%) and in older individuals. Anticoagulant underuse decreased significantly from the pre-DOAC (37.3%) to the post-DOAC (29.7%) era, as shown by two analyses using propensity scores. In older patients with AF, anticoagulant underuse was mainly associated with antiplatelet use. Anticoagulant underuse and antiplatelet use have both decreased since DOAC marketing. Underuse of anticoagulants was still a concern for three in ten geriatric patients with AF at high risk of stroke (CHADS 2 score ≥ 2).

Self-monitoring and self-management of oral anticoagulation.

Science.gov (United States)

Heneghan, Carl J; Garcia-Alamino, Josep M; Spencer, Elizabeth A; Ward, Alison M; Perera, Rafael; Bankhead, Clare; Alonso-Coello, Pablo; Fitzmaurice, David; Mahtani, Kamal R; Onakpoya, Igho J

2016-07-05

The introduction of point-of-care devices for the management of patients on oral anticoagulation allows self-testing by the patient at home. Patients who self-test can either adjust their medication according to a pre-determined dose-INR (international normalized ratio) schedule (self-management), or they can call a clinic to be told the appropriate dose adjustment (self-monitoring). Increasing evidence suggests self-testing of oral anticoagulant therapy is equal to or better than standard monitoring. This is an updated version of the original review published in 2010. To evaluate the effects on thrombotic events, major haemorrhages, and all-cause mortality of self-monitoring or self-management of oral anticoagulant therapy compared to standard monitoring. For this review update, we re-ran the searches of the Cochrane Central Register of Controlled Trials (CENTRAL), 2015, Issue 6, the Cochrane Library, MEDLINE (Ovid, 1946 to June week 4 2015), Embase (Ovid, 1980 to 2015 week 27) on 1 July 2015. We checked bibliographies and contacted manufacturers and authors of relevant studies. We did not apply any language restrictions . Outcomes analysed were thromboembolic events, mortality, major haemorrhage, minor haemorrhage, tests in therapeutic range, frequency of testing, and feasibility of self-monitoring and self-management. Review authors independently extracted data and we used a fixed-effect model with the Mantzel-Haenzel method to calculate the pooled risk ratio (RR) and Peto's method to verify the results for uncommon outcomes. We examined heterogeneity amongst studies with the Chi(2) and I(2) statistics and used GRADE methodology to assess the quality of evidence. We identified 28 randomised trials including 8950 participants (newly incorporated in this update: 10 trials including 4227 participants). The overall quality of the evidence was generally low to moderate. Pooled estimates showed a reduction in thromboembolic events (RR 0.58, 95% CI 0.45 to 0

Applying standardized uptake values in gallium-67-citrate single-photon emission computed tomography/computed tomography studies and their correlation with blood test results in representative organs.

Science.gov (United States)

Toriihara, Akira; Daisaki, Hiromitsu; Yamaguchi, Akihiro; Yoshida, Katsuya; Isogai, Jun; Tateishi, Ukihide

2018-05-21

Recently, semiquantitative analysis using standardized uptake value (SUV) has been introduced in bone single-photon emission computed tomography/computed tomography (SPECT/CT). Our purposes were to apply SUV-based semiquantitative analytic method for gallium-67 (Ga)-citrate SPECT/CT and to evaluate correlation between SUV of physiological uptake and blood test results in representative organs. The accuracy of semiquantitative method was validated using an National Electrical Manufacturers Association body phantom study (radioactivity ratio of sphere : background=4 : 1). Thereafter, 59 patients (34 male and 25 female; mean age, 66.9 years) who had undergone Ga-citrate SPECT/CT were retrospectively enrolled in the study. A mean SUV of physiological uptake was calculated for the following organs: the lungs, right atrium, liver, kidneys, spleen, gluteal muscles, and bone marrow. The correlation between physiological uptakes and blood test results was evaluated using Pearson's correlation coefficient. The phantom study revealed only 1% error between theoretical and actual SUVs in the background, suggesting the sufficient accuracy of scatter and attenuation corrections. However, a partial volume effect could not be overlooked, particularly in small spheres with a diameter of less than 28 mm. The highest mean SUV was observed in the liver (range: 0.44-4.64), followed by bone marrow (range: 0.33-3.60), spleen (range: 0.52-2.12), and kidneys (range: 0.42-1.45). There was no significant correlation between hepatic uptake and liver function, renal uptake and renal function, or bone marrow uptake and blood cell count (P>0.05). The physiological uptake in Ga-citrate SPECT/CT can be represented as SUVs, which are not significantly correlated with corresponding blood test results.

A Comparative 68Ga-Citrate and 68Ga-Chloride PET/CT Imaging of Staphylococcus aureus Osteomyelitis in the Rat Tibia

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Petteri Lankinen

2018-01-01

Full Text Available There may be some differences in the in vivo behavior of 68Ga-chloride and 68Ga-citrate leading to different accumulation profiles. This study compared 68Ga-citrate and 68Ga-chloride PET/CT imaging under standardized experimental models. Methods. Diffuse Staphylococcus aureus tibial osteomyelitis and uncomplicated bone healing rat models were used (n=32. Two weeks after surgery, PET/CT imaging was performed on consecutive days using 68Ga-citrate or 68Ga-chloride, and tissue accumulation was confirmed by ex vivo analysis. In addition, peripheral quantitative computed tomography and conventional radiography were performed. Osteomyelitis was verified by microbiological analysis and specimens were also processed for histomorphometry. Results. In PET/CT imaging, the SUVmax of 68Ga-chloride and 68Ga-citrate in the osteomyelitic tibias (3.6 ± 1.4 and 4.7 ± 1.5, resp. were significantly higher (P=0.0019 and P=0.0020, resp. than in the uncomplicated bone healing (2.7 ± 0.44 and 2.5 ± 0.49, resp.. In osteomyelitic tibias, the SUVmax of 68Ga-citrate was significantly higher than the uptake of 68Ga-chloride (P=0.0017. In animals with uncomplicated bone healing, no difference in the SUVmax of 68Ga-chloride or 68Ga-citrate was seen in the operated tibias. Conclusions. This study further corroborates the use of 68Ga-citrate for PET imaging of osteomyelitis.

Bed rest versus early ambulation with standard anticoagulation in the management of deep vein thrombosis: a meta-analysis.

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Zhenlei Liu

Full Text Available Bed rest has been considered as the cornerstone of management of deep vein thrombosis (DVT for a long time, though it is not evidence-base, and there is growing evidence favoring early ambulation.Electronic databases including Medline, PubMed, Cochrane Library and three Chinese databases were searched with key words of "deep vein thrombosis", "pulmonary embolism", "venous thrombosis", "bed rest", "immobilization", "mobilization" and "ambulation". We considered randomized controlled trials, prospective or retrospective cohort studies that compared the outcomes of acute DVT patients managed with early ambulation versus bed rest, in addition to standard anticoagulation. Meta-analysis pertaining to the incidence of new pulmonary embolism (PE, progression of DVT, and DVT related deaths were conducted, as well as the extent of remission of pain and edema.13 studies were included with a total of 3269 patients. Compared to bed rest, early ambulation was not associated with a higher incidence of new PE, progression of DVT, or DVT related deaths (RD -0.03, 95% CI -0.05∼ -0.02; Z = 1.24, p = 0.22; random effect model, Tau2 = 0.01. Moreover, if the patients suffered moderate or severe pain initially, early ambulation was related to a better outcome, with respect to remission of acute pain in the affected limb (SMD 0.42, 95%CI 0.09∼0.74; Z = 2.52, p = 0.01; random effect model, Tau2 = 0.04. Meta-analysis of alleviation of edema cannot elicit a solid conclusion because of significant heterogeneity among the few studies.Compared to bed rest, early ambulation of acute DVT patients with anticoagulation was not associated with a higher incidence of new PE, progression of DVT, and DVT related deaths. Furthermore, for the patients suffered moderate or severe pain initially, a better outcome can be seen in early ambulation group, regarding to the remission of acute pain in the affected limb.

Minimizing Hemodialysis Catheter Dysfunction: An Ounce of Prevention

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Timmy Lee

2012-01-01

Full Text Available The maintenance of tunneled catheter (TC patency is critical for the provision of adequate hemodialysis in patients who are TC-dependent. TC dysfunction results in the need for costly and inconvenient interventions, and reduced quality of life. Since the introduction of TCs in the late 1980s, heparin catheter lock has been the standard prophylactic regimen for the prevention of TC dysfunction. More recently, alternative catheter locking agents have emerged, and in some cases have shown to be superior to heparin lock with respect to improving TC patency and reducing TC-associated infections. These include citrate, tissue plasminogen activator, and a novel agent containing sodium citrate, methylene blue, methylparaben, and propylparaben. In addition, prophylaxis using oral anticoagulants/antiplatelet agents, including warfarin, aspirin, ticlodipine, as well as the use of modified heparin-coated catheters have also been studied for the prevention of TC dysfunction with variable results. The use of oral anticoagulants and/or antiplatelet agents as primary or secondary prevention of TC dysfunction must be weighed against their potential adverse effects, and should be individualized for each patient.

Idarucizumab for Reversing Dabigatran-Induced Anticoagulation: A Systematic Review.

Science.gov (United States)

Thibault, Nathan; Morrill, Amanda M; Willett, Kristine C

The approval of the oral direct thrombin inhibitor, dabigatran etexilate, gave patients an alternative to oral anticoagulation with warfarin. Like all anticoagulants, the primary adverse event (AE) associated with dabigatran is bleeding. Until the FDA approval of idarucizumab, there had been no reversal agent for dabigatran-induced anticoagulation in patients with life-threatening or uncontrollable bleeding, or those requiring emergent procedures. The primary purpose of this review is to summarize the safety and efficacy of idarucizumab, a monoclonal antibody fragment, and its use as a reversal agent for dabigatran. A literature search was conducted through MEDLINE (1946 to November week 1 2015) and Embase (1980-2015 week 46) using the search term idarucizumab. Clinicaltrials.gov was consulted for a comprehensive list of ongoing and completed studies. Additional studies were identified through bibliographical citations. Clinical trials in animals and humans published in English evaluating the safety and efficacy of idarucizumab for reversal of anticoagulant treatment with dabigatran were included for review. Idarucizumab has been shown to significantly reverse the anticoagulant effects of dabigatran in both healthy volunteers and patients requiring a reversal agent because of either overt bleeding or an emergency surgery or invasive procedure. The most common AEs were headache, nasopharyngitis, back pain, skin irritation, hypokalemia, delirium, constipation, pyrexia, and pneumonia. Deaths reported in idarucizumab studies were attributed to either the index event or a preexisting comorbidity. Most adverse effects were minor, but 21 serious AEs have been reported in the published data including thrombotic events. Given the increased use of direct oral anticoagulants, such as dabigatran, a need for specific reversal agents exists. Idarucizumab has been shown to be safe and effective in the reversal of dabigatran-induced anticoagulation in patients requiring emergent

Reference range determination for whole-blood platelet aggregation using the Multiplate analyzer

NARCIS (Netherlands)

Peerschke, Ellinor I. B.; Castellone, Donna D.; Stroobants, A. K.; Francis, John

2014-01-01

To develop reference ranges for platelet aggregation using the Multiplate analyzer (Roche Diagnostics, Mannheim, Germany) in blood anticoagulated with sodium citrate (Na-citrate), lithium heparin (Li-heparin), or hirudin. The study was performed at three sites on consented, healthy adults (n = 193)

Whole-body retention studies of /sup 167/Tm--citrate. Estimation of radiation dose to humans from /sup 167/Tm--citrate

Energy Technology Data Exchange (ETDEWEB)

Hiraki, T; Ando, A [Kanazawa Univ. (Japan). School of Paramedicine; Mori, H; Ando, I; Sakamoto, K

1978-02-01

For the purpose of calculating absorbed dose to humans from /sup 167/Tm-citrate, the whole-body retention studies using 5 rats were carried out. Up to 40 days following intravenous injection of /sup 167/Tm-citrate, the whole-body counts were monitored with an animal counter. The whole-body retention curve was obtained with three exponential components. Namely, the 26% of the injected /sup 167/Tm-citrate had a biological half-time of 3.4 hours, 12.5% had a biological half-time of 99 hours and 61.5% had a biological half-time of 106 days. These results indicate, that three components consist of the rapid clearance from the kidneys, the retention in the liver and other soft tissues with relatively long half-time and the retention in the bones with long half-time. Based on these biological data and the MIRD Committee method, the average dose estimates to the bone and whole-body from intravenous administration of 1 mCi /sup 167/Tm-citrate were 7.08 rads and 1.28 rads, respectively.

Is it safe to prescribe clomiphene citrate without ultrasound monitoring facilities?

LENUS (Irish Health Repository)

Coughlan, C

2010-05-01

The majority of triplet and higher order multiple pregnancies now result from ovulation induction\\/superovulation rather than in vitro fertilisation. However, clomiphene citrate is still widely prescribed by gynaecologists and general practitioners who do not have access to ultrasound monitoring. The objective of our study was to determine the prevalence of multifollicular development with different doses of clomiphene citrate. A retrospective review of transvaginal ultrasound monitoring of 425 cycles in 182 women receiving clomiphene citrate from January 2002 to December 2003, was studied. Three or more follicles of >or= 14 mm were identified in 58 cycles (14%). Patients received 50 mg of clomiphene citrate in 52 of these 58 cycles and 25 mg in the remaining six. One patient was noted to have developed five follicles and 10 patients developed four follicles. One patient developed six follicles, despite receiving only 25 mg clomiphene citrate daily. It was concluded that a significant number of women (14%) developed three or more follicles, despite receiving low doses of clomiphene citrate.

Pathogenic mutations of the human mitochondrial citrate carrier SLC25A1 lead to impaired citrate export required for lipid, dolichol, ubiquinone and sterol synthesis.

Science.gov (United States)

Majd, Homa; King, Martin S; Smith, Anthony C; Kunji, Edmund R S

2018-01-01

Missense mutations of the human mitochondrial citrate carrier, encoded by the SLC25A1 gene, lead to an autosomal recessive neurometabolic disorder characterised by neonatal-onset encephalopathy with severe muscular weakness, intractable seizures, respiratory distress, and lack of psychomotor development, often resulting in early death. Here, we have measured the effect of all twelve known pathogenic mutations on the transport activity. The results show that nine mutations abolish transport of citrate completely, whereas the other three reduce the transport rate by >70%, indicating that impaired citrate transport is the most likely primary cause of the disease. Some mutations may be detrimental to the structure of the carrier, whereas others may impair key functional elements, such as the substrate binding site and the salt bridge network on the matrix side of the carrier. To understand the consequences of impaired citrate transport on metabolism, the substrate specificity was also determined, showing that the human citrate carrier predominantly transports citrate, isocitrate, cis-aconitate, phosphoenolpyruvate and malate. Although D-2- and L-2 hydroxyglutaric aciduria is a metabolic hallmark of the disease, it is unlikely that the citrate carrier plays a significant role in the removal of hydroxyglutarate from the cytosol for oxidation to oxoglutarate in the mitochondrial matrix. In contrast, computer simulations of central metabolism predict that the export of citrate from the mitochondrion cannot be fully compensated by other pathways, restricting the cytosolic production of acetyl-CoA that is required for the synthesis of lipids, sterols, dolichols and ubiquinone, which in turn explains the severe disease phenotypes. Copyright © 2017. Published by Elsevier B.V.

Best strategies for patient education about anticoagulation with warfarin: a systematic review

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Singh Sonal

2008-02-01

administered were located in anticoagulation clinics/centers. The number of questions ranged from as few as 4 to as many as 28, and questions were most often of multiple choice format. Three were self-administered, and 2 were completed over the telephone. Two reports described instruments along with formal testing of the validity and reliability of the instrument. Conclusion Published reports of patient education related to warfarin anticoagulation vary greatly in strategy, content, and patient testing. Prioritizing the educational domains, standardizing the educational content, and delivering the content more efficiently will be necessary to improve the quality of anticoagulation with warfarin.

New oral anticoagulant-induced bleeding: clinical presentation and management

NARCIS (Netherlands)

Levy, Jerrold H.; Levi, Marcel

2014-01-01

Bleeding is a significant complication of anticoagulant therapy. With the emergence of new oral anticoagulants (NOACs; ie, direct factor IIa or Xa inhibitors), this risk is further compounded by the lack of validated reversal strategies for these agents. Emerging postmarketing evidence suggests that

Retroperitoneal Bleeding: An Experience During Prophylactic Anticoagulation in a Patient With Nephrotic Syndrome

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Mari Okada

2017-07-01

Full Text Available The association between nephrotic syndrome (NS and a hypercoagulable state has been demonstrated. Controlling the blood clotting activity may therefore be attractive for patients with nephrosis in terms of thromboembolism prophylaxis. We herein report a 75-year-old woman with minimal change disease who developed pains in the right back, groin, and thigh because of retroperitoneal bleeding during prophylactic anticoagulation with unfractionated heparin. Although this procedure has not been accepted as the standard of care for patients with nephrosis, pharmacologic prophylaxis may already be practiced empirically, as in the present patient. We believe that our experience highlights the pitfalls of such a management in patients with nephrosis, implying the need for a diagnostic strategy for identifying those patients with NS who can benefit from prophylactic anticoagulation. Several concerns that emerged in this case are also discussed.

Citrate-Induced Nanocubes: A Re-Examination of the Role of Citrate as a Shape-Directing Capping Agent for Ag-Based Nanostructures.

Science.gov (United States)

Hajfathalian, Maryam; Gilroy, Kyle D; Hughes, Robert A; Neretina, Svetlana

2016-07-01

Seed-mediated syntheses utilizing facet-selective surface passivation provide the necessary chemical controls to direct noble metal nanostructure formation to a predetermined geometry. The foremost protocol for the synthesis of (111)-faceted Ag octahedra involves the reduction of metal ions onto pre-existing seeds in the presence of citrate and ascorbic acid. It is generally accepted that the capping of (111) facets with citrate dictates the shape while ascorbic acid acts solely as the reducing agent. Herein, a citrate-based synthesis is demonstrated in which the presence or absence of ascorbic acid is the shape-determining factor. Reactions are carried out in which Ag(+) ions are reduced onto substrate-immobilized Ag, Au, Pd, and Pt seeds. Syntheses lacking ascorbic acid, in which citrate acts as both the capping and the reducing agent, result in a robust nanocube growth mode able to withstand wide variations in the concentration of reactants, reaction rates, seed material, seed orientation and faceting, pH, and substrate material. If, however, ascorbic acid is included in these syntheses, then the growth mode reverts to one that advances the octahedral geometry. The implication of these results is that citrate, or one of its oxidation products, selectively caps (100) facets, but where this capability is compromised by ascorbic acid. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Disadvantages of VKA and requirements for novel anticoagulants.

Science.gov (United States)

Shameem, Raji; Ansell, Jack

2013-06-01

Vitamin K antagonists have been in wide use for over 70 years. Warfarin, the most commonly used vitamin K antagonist, has been shown to be highly effective in treating and preventing thrombosis. Despite this, warfarin has many disadvantages, which has led to the development of a new class of oral anticoagulants targeted to specific coagulation factors designated as target-specific oral anticoagulants (TSOAs). TSOAs include the thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban). This chapter reviews the disadvantages of warfarin and evaluates both the advantages and disadvantages of the new oral anticoagulants. © 2013 Elsevier Ltd. All rights reserved.

Medium intensity oral anticoagulants versus aspirin after cerebral ischaemia of arterial origin (ESPRIT): a randomised controlled trial.

Science.gov (United States)

Halkes, P H A; van Gijn, J; Kappelle, L J; Koudstaal, P J; Algra, A

2007-02-01

Oral anticoagulants are better than aspirin for secondary prevention after myocardial infarction and after cerebral ischaemia in combination with non-rheumatic atrial fibrillation. The European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) aimed to determine whether oral anticoagulation with medium intensity is more effective than aspirin in preventing future vascular events in patients with transient ischaemic attack or minor stroke of presumed arterial origin. In this international, multicentre trial, patients were randomly assigned within 6 months after a transient ischaemic attack or minor stroke of presumed arterial origin either anticoagulants (target INR range 2.0-3.0; n=536) or aspirin (30-325 mg daily; n=532). The primary outcome was the composite of death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction, or major bleeding complication, whichever occurred first. In a post hoc analysis anticoagulants were compared with the combination of aspirin and dipyridamole (200 mg twice daily). Treatment was open, but auditing of outcome events was blinded. Primary analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial (number ISRCTN73824458) and with ClinicalTrials.gov (NCT00161070). The anticoagulants versus aspirin comparison of ESPRIT was prematurely ended because ESPRIT reported previously that the combination of aspirin and dipyridamole was more effective than aspirin alone. Mean follow-up was 4.6 years (SD 2.2). The mean achieved INR was 2.57 (SD 0.86). A primary outcome event occurred in 99 (19%) patients on anticoagulants and in 98 (18%) patients on aspirin (hazard ratio [HR] 1.02, 95% CI 0.77-1.35). The HR for ischaemic events was 0.73 (0.52-1.01) and for major bleeding complications 2.56 (1.48-4.43). The HR for the primary outcome event comparing anticoagulants with the combination treatment of aspirin and dipyridamole was 1.31 (0.98-1.75). Oral

Hematometra secondary to anticoagulant rodenticide toxicity

International Nuclear Information System (INIS)

Padgett, S.L.; Stokes, J.E.; Tucker, R.L.; Wheaton, L.G.

1998-01-01

An adult, intact female Australian shepherd presented for frank vaginal bleeding of unknown duration. The only coagulation profile abnormality upon presentation was mild prolongation of the partial thromboplastin time (PTT). The uterus was removed at surgery and contained a large amount of coagulated blood. Clotting profiles were markedly abnormal48 hours postoperatively. Serum analysis was positive for brodifacoum, an anticoagulant rodenticide. Preoperative coagulation was most likely normalized by vitamin K-1 therapy administered prior to presentation. The only manifestation of anticoagulant rodenticide was hematometra. Rodenticide intoxication should be considered in the differential diagnosis list of hematometra or metrorrhagia

Vitamin K requirement in Danish anticoagulant-resistant Norway rats (Rattus norvegicus)

DEFF Research Database (Denmark)

Markussen, Mette D.; Heiberg, Ann-Charlotte; Nielsen, Robert

2003-01-01

Norway rats, Rattus norvegicus, Denmark, anticoagulant rodenticide resistance, vitamin K requirement......Norway rats, Rattus norvegicus, Denmark, anticoagulant rodenticide resistance, vitamin K requirement...

New anticoagulants for the prevention and treatment of venous thromboembolism

Directory of Open Access Journals (Sweden)

Simon J McRae

2005-04-01

Full Text Available Simon J McRae, Jeffrey S GinsbergDepartment of Medicine, McMaster University, Hamilton, ON, CanadaAbstract: Anticoagulant therapy is effective at preventing the development of venous thromboembolism in high-risk patients, and reduces morbidity and mortality in individuals with established thromboembolic disease. Vitamin K antagonists and heparins are currently the most commonly used anticoagulant drugs, but they have practical limitations. Therefore, new antithrombotic agents with predictable dose-responses (thereby decreasing the need for monitoring without compromising efficacy or safety, ideally available in an oral formulation and with a rapidly reversible anticoagulant effect, are needed. New drugs fulfilling some of the above criteria have been developed and have proven to be effective agents for the treatment and prevention of venous thromboembolism.Keywords: venous thromboembolism, anticoagulants, antithrombotic

Management of anticoagulation in hip fractures: A pragmatic approach.

Science.gov (United States)

Yassa, Rafik; Khalfaoui, Mahdi Yacine; Hujazi, Ihab; Sevenoaks, Hannah; Dunkow, Paul

2017-09-01

Hip fractures are common and increasing with an ageing population. In the United Kingdom, the national guidelines recommend operative intervention within 36 hours of diagnosis. However, long-term anticoagulant treatment is frequently encountered in these patients which can delay surgical intervention. Despite this, there are no set national standards for management of drug-induced coagulopathy pre-operatively in the context of hip fractures.The aim of this study was to evaluate the management protocols available in the current literature for the commonly encountered coagulopathy-inducing agents.We reviewed the current literature, identified the reversal agents used in coagulopathy management and assessed the evidence to determine the optimal timing, doses and routes of administration.Warfarin and other vitamin K antagonists (VKA) can be reversed effectively using vitamin K with a dose in the range of 2 mg to 10 mg intravenously to correct coagulopathy.The role of fresh frozen plasma is not clear from the current evidence while prothrombin complex remains a reliable and safe method for immediate reversal of VKA-induced coagulopathy in hip fracture surgery or failed vitamin K treatment reversal.The literature suggests that surgery should not be delayed in patients on classical antiplatelet medications (aspirin or clopidogrel), but spinal or regional anaesthetic methods should be avoided for the latter. However, evidence regarding the use of more novel antiplatelet medications (e.g. ticagrelor) and direct oral anticoagulants remains a largely unexplored area in the context of hip fracture surgery. We suggest treatment protocols based on best available evidence and guidance from allied specialties.Hip fracture surgery presents a common management dilemma where semi-urgent surgery is required. In this article, we advocate an evidence-based algorithm as a guide for managing these anticoagulated patients. Cite this article: EFORT Open Rev 2017;2:394-402. DOI: 10.1302/2058-5241.2.160083.

Alkali replacement raises urinary citrate excretion in patients with topiramate-induced hypocitraturia.

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Jhagroo, R Allan; Wertheim, Margaret L; Penniston, Kristina L

2016-01-01

The aims of this study were to assess (1) the magnitude and temporality of decreased urinary citrate excretion in patients just starting topiramate and (2) the effect of alkali replacement on topiramate-induced hypocitraturia. Study 1 was a prospective, non-intervention study in which patients starting topiramate for headache remediation provided pre- and post-topiramate 24 h urine collections for measurement of urine citrate. Study 2 was a clinical comparative effectiveness study in which patients reporting to our stone clinic for kidney stones and who were treated with topiramate were prescribed alkali therapy. Pre- and post-alkali 24 h urinary citrate excretion was compared. Data for 12 and 22 patients (studies 1 and 2 respectively) were evaluated. After starting topiramate, urinary citrate excretion dropped significantly by 30 days (P = 0.016) and 62% of patients had hypocitraturia (citrate alkali, urine citrate increased in stone-forming patients on topiramate (198 ± 120 to 408 ± 274 mg day(-1) ; P = 0.042 for difference). 85% of patients were hypocitraturic on topiramate alone vs. 40% after adding alkali. The increase in urinary citrate was greater in patients provided ≥ 90 mEq potassium citrate. Our study is the first to provide clinical evidence that alkali therapy can raise urinary citrate excretion in patients who form kidney stones while being treated with topiramate. Clinicians should consider alkali therapy for reducing the kidney stone risk of patients benefitting from topiramate treatment for migraine headaches or other conditions. © 2015 The British Pharmacological Society.

Sildenafil citrate (Viagra) enhances vasodilatation in fetal growth restriction.

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Wareing, Mark; Myers, Jenny E; O'Hara, Maureen; Baker, Philip N

2005-05-01

Fetal growth restriction (FGR) affects up to 8% of all pregnancies and has massive short-term (increased fetal morbidity and mortality) and long-term (increased incidence of cardiovascular disease in adulthood) health implications. Doppler waveform analysis of pregnancies complicated by FGR suggests compromised uteroplacental circulation and placental hypoperfusion. Our aim was to determine whether myometrial small artery function was aberrant in FGR and to assess whether sildenafil citrate could improve vasodilatation in FGR pregnancies. Small arteries dissected from myometrial biopsies obtained at cesarean section from normal pregnant women (n = 27) or women whose pregnancies were complicated by FGR (n = 12) were mounted on wire myographs. Vessels were constricted (with arginine vasopressin or U46619) and relaxed (with bradykinin) before and after incubation with a phosphodiesterase-5 inhibitor, sildenafil citrate. We demonstrated increased myometrial small artery vasoconstriction and decreased endothelium-dependent vasodilatation in vessels from women whose pregnancies were complicated by FGR. Sildenafil citrate significantly reduced vasoconstriction and significantly improved relaxation of FGR small arteries. We conclude that sildenafil citrate improves endothelial function of myometrial vessels from women whose pregnancies are complicated by intrauterine growth restriction. Sildenafil citrate may offer a potential therapeutic strategy to improve uteroplacental blood flow in FGR pregnancies.

Study of Np speciation in citrate medium

Energy Technology Data Exchange (ETDEWEB)

Bonin, L.; Den Auwer, C.; Ansoborlo, E.; Moisy, P. [CEA Valrho - DEN/DRCP/SCPS, Bagnols sur Ceze (France); Cote, G. [ENSP - LECA, UMR 7575, Paris (France)

2007-07-01

In the framework of the French Environmental Nuclear Toxicology program, additional experiments related to the decorporation of actinides are planned. Decorporation is the removal or release from target organs (bones, liver, kidney..), tissues or cells of radioactive material previously incorporated in them, using chelating agents or other administrated pharmaceutical agents. The contradictory data on the neptunium complexation behaviour within blood and its transfer to target organs, as well as the inefficiency of therapeutic treatments, led us to study the complexation of this element with biological constituents. Within this purpose, the in vitro behaviour of Np(IV) and Np(V) in simple media simulating biological fluids was studied. This study was more specifically focused on the behaviour of neptunium with citrate ion, which is an essential component in a number of metalloenzyme active sites. In order to determine the speciation of this system, spectrophotometry was more particularly used. Concerning the complexation phenomenon, the existence of several complexes of Np(V) with various acido-basic forms of the citrate anion was observed; regarding Np(IV), complexes with Cit{sup 3-} have been observed. From the quantitative study of these equilibria, the values of the absolute constants for the complexation of Np(IV) and Np(V) with citrate were determined. Concerning the stability of neptunium towards oxydo-reduction, it was confirmed that Np(VI) was very quickly reduced to Np(V) by the citrate anions, whereas Np(IV) was stable. In the case of Np(V), it was observed that, depending on the pH and the citrate concentration, Np(V) was unstable and was reduced to Np(IV). The E-pH diagrams, constructed using the stability constants determined in this study, showed that this instability was due to the Np(V) disproportionation. (orig.)

Adherence to a new oral anticoagulant treatment prescription: dabigatran etexilate

Directory of Open Access Journals (Sweden)

L Bellamy

2009-07-01

Full Text Available L Bellamy1, N Rosencher1, BI Eriksson21Anaesthesiology Department, Hôpital Cochin (AP-HP, René Descartes University, Paris 75014 France; 2Orthopaedic Department, University Hospital Sahlgrenska/Ostra, Gothenburg, SwedenAbstract: The recent development of new oral anticoagulants, of which dabigatran etexilate is currently at the most advanced stage of development, is the greatest advance in the provision of convenient anticoagulation therapy for many years. A new oral anticoagulation treatment, dabigatran etexilate, is already on the market in Europe. The main interest probably will be to improve the prescription and the adherence to an effective thromboprophylaxis in medical conditions such as atrial fibrillation without bleeding side effects, without the need for monitoring coagulation, and without drug and food interactions such as vitamin K anticoagulant (VKA treatment. Dabigatran is particularly interesting for extended thromboprophylaxis after major orthopedic surgery in order to avoid daily injection for a month. However, oral long-term treatments such as VKA are not systematically associated with a higher compliance level than injected treatments such as low-molecular-weight heparins. Indeed, adherence to an oral treatment, instead of the usual daily injection in major orthopedic surgery, is complex, and based not only on the frequency of dosing but also on patient motivation, understanding, and socio-economic status. New oral anticoagulants may be useful in this way but education and detection of risk factors of nonadherence to treatment are still essential.Keywords: oral anticoagulant, adherence, compliance, education, dabigatran

Scoring Systems for Estimating the Risk of Anticoagulant-Associated Bleeding.

Science.gov (United States)

Parks, Anna L; Fang, Margaret C

2017-07-01

Anticoagulant medications are frequently used to prevent and treat thromboembolic disease. However, the benefits of anticoagulants must be balanced with a careful assessment of the risk of bleeding complications that can ensue from their use. Several bleeding risk scores are available, including the Outpatient Bleeding Risk Index, HAS-BLED, ATRIA, and HEMORR 2 HAGES risk assessment tools, and can be used to help estimate patients' risk for bleeding on anticoagulants. These tools vary by their individual risk components and in how they define and weigh clinical factors. However, it is not yet clear how best to integrate bleeding risk tools into clinical practice. Current bleeding risk scores generally have modest predictive ability and limited ability to predict the most devastating complication of anticoagulation, intracranial hemorrhage. In clinical practice, bleeding risk tools should be paired with a formal determination of thrombosis risk, as their results may be most influential for patients at the lower end of thrombosis risk, as well as for highlighting potentially modifiable risk factors for bleeding. Use of bleeding risk scores may assist clinicians and patients in making informed and individualized anticoagulation decisions. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Pharmacology of new oral anticoagulants: mechanism of action, pharmacokinetics, pharmacodynamics

Directory of Open Access Journals (Sweden)

Luca Masotti

2013-12-01

Full Text Available Due to their mechanism of action, the new oral anticoagulants are named direct oral anticoagulants (DOACs. Dabigatran is a selective, competitive, direct inhibitor of thrombin (Factor IIa while rivaroxaban, apixaban and edoxaban act by directly inhibiting the activated Factor X (FXa in a selective and competitive manner. DOACs have a relatively short half-life and almost immediate anticoagulant activity, and rapidly reach the plasma peak concentration. Therefore, they do not need a phase of overlapping with parenteral anticoagulants. After their withdrawal, their removal is sufficiently rapid, although influenced by renal function. Dabigatran is the only DOACs to be administered as a pro-drug and becomes active after drug metabolization. The route of elimination of dabigatran is primarily renal, whereas FXa inhibitors are mainly eliminated by the biliary-fecal route. The drug interactions of DOACs are mainly limited to drugs that act on P-glycoprotein for dabigatran and on P-glycoprotein and/or cytochrome P3A4 for anti-Xa. DOACs have no interactions with food. Given their linear pharmacodynamics, with a predictable dose/response relationship and anticoagulant effect, DOACs are administered at a fixed dose and do not require routine laboratory monitoring.

New oral anticoagulant and antiplatelet agents for neurosurgeons.

Science.gov (United States)

Kimpton, George; Dabbous, Bassam; Leach, Paul

2015-01-01

Until recently, warfarin, clopidogrel and aspirin have provided the mainstay for prevention of thrombotic disease in cardiac patients. However, new classes of drugs have recently emerged that promise better clinical outcomes and lower risks. Use of such agents has increased, but increased risk and severity of intra-cranial haemorrhage (ICH) still remain. These cases of intra-cranial bleeds present as emergencies to neurosurgical units. It is of paramount importance that neurosurgical practitioners are aware of those new drugs, useful monitoring tests and available emergency reversal options in case the patient needs emergency intervention. In this review we survey newly available agents in the U.K. at the time of publication. We look at the data provided by the manufacturers, related publications and international guidelines for their use and reversal. New anticoagulants offer a lower incidence of ICH compared with warfarin. Advanced and accurate monitoring tests are emerging, as are prospective data on reversal of anticoagulation in bleeding. Some standard coagulation tests may be of use, whilst reversal agents are available and being evaluated. The trial data shows that new antiplatelet agents have similar or increased incidence and severity of intra-cranial ICH compared with clopidogrel. There is currently limited data on monitoring or reversal. We suggest they may be managed similarly to clopidogrel by using platelet reactivity assays, optimising platelet count and using platelet transfusion with adjunctive agents.

Atrial Fibrillation in Embolic Stroke: Anticoagulant Therapy at UNTH ...

African Journals Online (AJOL)

Objective: The decision to commence anticoagulation in a patient with embolic stroke and atrial fibrillation (AF) is often a difficult one for many clinicians. The result can have significant impact on the patient. This study was therefore undertaken to review the use of anticoagulation in embolic stroke in the setting of atrial ...

Effectiveness of ranitidine bismuth citrate and proton pump inhibitor ...

African Journals Online (AJOL)

Effectiveness of ranitidine bismuth citrate and proton pump inhibitor based triple therapies of Helicobacter pylori in Turkey. ... Results: When we look at the eradication rates of the treatment groups, only two groups (ranitidine bismuth citrate and rabeprazole groups) had eradication rates greater than 80%, both at intention to ...

Citrate increases glass transition temperature of vitrified sucrose preparations

NARCIS (Netherlands)

Kets, E.P.W.; Lipelaar, P.J.; Hoekstra, F.A.; Vromans, H.

2004-01-01

The aim of this study was to investigate the effect of sodium citrate on the properties of dried amorphous sucrose glasses. Addition of sodium citrate to a sucrose solution followed by freeze-drying or convective drying resulted in a glass transition temperature (T-g) that was higher than the

Bleeding events associated with novel anticoagulants: a case series.

Science.gov (United States)

Mirzaee, Sam; Tran, Tara Thi Thien; Amerena, John

2013-12-01

Until lately warfarin was the only valuable oral anticoagulant in stroke reduction in high risk cases with non valvular atrial fibrillation (NVAF). Although with warfarin the rate of stroke reduced notably, the major concern is the risk of serious bleeding and difficulty of establishing and maintaining the international normalised ratio (INR) within the therapeutic range. With the development of the novel anticoagulants we now have for the first time since the innovation of Warfarin feasible alternatives to it to decrease stroke rates in high risk patients with NVAF. To diminish adverse bleeding events with the novel anticoagulant proper selection of patients prior starting treatment is essential. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Synthesis and biological activity of the novel indanedione anticoagulant rodenticides containing fluorine.

Science.gov (United States)

Chen, Feng; Liu, Liping; Bai, Zengguo; Zhang, Tianhua; Zhao, Keke

2017-01-02

Here, 3 fluorinated intermediates of drug were synthesized: (M1), (M2), (M3). Three new anticoagulant rodenticides were designed which were based on 4-hydroxycoumarin or 1,3-indandione, added acute toxicity groups containing fluorine. The structures of synthesized compounds were analyzed and proved by FT-IR spectroscopy and 1 H nuclear magnetic resonance ( 1 H-NMR). The compounds were also evaluated for their anticoagulant and acute biologic activity. In addition, both the acute orally toxicity and the feeding indexes of R 1 and R 2 were tested. The result of the experiment proved that the new synthesis of 1, 3 - indan diketone for maternal new anticoagulant rodenticide can replace the current 4 - hydroxyl coumarin as the mother of the second generation anticoagulant rodenticide and 1, 3 - indan diketone for maternal new anticoagulant rodenticides will have a good development prospect.

Bleeding in patients using new anticoagulants or antiplatelet agents: Risk factors and management

NARCIS (Netherlands)

Levi, M.M.; Eerenberg, E.; Löwenberg, E.; Kamphuisen, P.W.

2010-01-01

The most important adverse effect of antithrombotic treatment is the occurrence of bleeding. in case of serious or even life-threatening bleeding in a patient who uses anticoagulant agents or when patient on anticoagulants needs to undergo an urgent invasive procedure, anticoagulant treatment can be

Structural and functional annotation of citrate synthase from Aspergillus niger ANJ-120.

Science.gov (United States)

Mustafa, Ghulam; Arif, Rawaba; Bukhari, Shazia Anwer; Ali, Muhammad; Sharif, Sumaira; Atta, Asia

2018-03-01

Citrate synthase (CS) is involved in citric acid biosynthesis which is a well-established metabolic pathway. The condensation of acetyl-CoA with oxaloacetate is catalyzed by CS. Citric acid (CA) has a number of applications in pharmaceutical industry. CA in combination with bicarbonates is used as an effervescent in the preparations of tablets and powders. It has also been used as an anticoagulant and acidulant to form mild astringent. In current study, detailed structural and functional analyses of CS protein were carried out using various bioinformatics tools. Structural modeling was also done by building 3D model of CS from Aspergillus niger ANJ-120 using Modeller 9.16 software. The 3D Model was then evaluated using different online approaches. Furthermore, superimposition of query and template structures, Root Mean Squared Deviation and visualization of generated model were done through UCSF Chimera 1.5.3. Even though various roles of CS protein were already known and verified experimentally, here we presented a structural analysis of CS protein. The structural investigation of CS protein will be helpful for protein engineering strategies and understanding the interactions among proteins. Due to large number of applications, the production of citric acid by A. niger and its bioinformatics studies will offer substantial improvement in commercial scale intensification of this useful product.

Anticoagulant rodenticides and wildlife: Introduction

Science.gov (United States)

van den Brink, Nico W.; Elliott, John E.; Shore, Richard F.; Rattner, Barnett A.; van den Brink, Nico W.; Elliott, John E.; Shore, Richard F.; Rattner, Barnett A.

2018-01-01

Rodents have interacted with people since the beginning of systematic food storage by humans in the early Neolithic era. Such interactions have had adverse outcomes such as threats to human health, spoiling and consumption of food sources, damage to human infrastructure and detrimental effects on indigenous island wildlife (through inadvertent anthropogenic assisted introductions). These socio/economic and environmental impacts illustrate the clear need to control populations of commensal rodents. Different methods have been applied historically but the main means of control in the last decades is through the application of rodenticides, mainly anticoagulant rodenticides (ARs) that inhibit blood clotting. The so-called First Generation Anticoagulant Rodenticides (FGARs) proved highly effective but rodents increasingly developed resistance. This led to a demand for more effective alternative compounds and paved the way to the development of Second Generation Anticoagulant Rodenticides (SGARs). These were more acutely toxic and persistent, making them more effective but also increasing the risks of exposure of non-target species and secondary poisoning of predatory species. SGARs often fail the environmental thresholds of different regulatory frameworks because of these negative side-effects, but their use is still permitted because of the overwhelming societal needs for rodent control and the lack of effective alternatives. This book provides a state-of-the-art overview of the scientific advancements in assessment of environmental exposure, effects and risks of currently used ARs. This is discussed in relation to the societal needs for rodent control, including risk mitigation and development of alternatives.

Cost-effectiveness of pharmacogenetics-guided warfarin therapy vs. alternative anticoagulation in atrial fibrillation.

Science.gov (United States)

Pink, J; Pirmohamed, M; Lane, S; Hughes, D A

2014-02-01

Pharmacogenetics-guided warfarin dosing is an alternative to standard clinical algorithms and new oral anticoagulants for patients with nonvalvular atrial fibrillation. However, clinical evidence for pharmacogenetics-guided warfarin dosing is limited to intermediary outcomes, and consequently, there is a lack of information on the cost-effectiveness of anticoagulation treatment options. A clinical trial simulation of S-warfarin was used to predict times within therapeutic range for different dosing algorithms. Relative risks of clinical events, obtained from a meta-analysis of trials linking times within therapeutic range with outcomes, served as inputs to an economic analysis. Neither dabigatran nor rivaroxaban were cost-effective options. Along the cost-effectiveness frontier, in relation to clinically dosed warfarin, pharmacogenetics-guided warfarin and apixaban had incremental cost-effectiveness ratios of £13,226 and £20,671 per quality-adjusted life year gained, respectively. On the basis of our simulations, apixaban appears to be the most cost-effective treatment.

In vivo examination of the anticoagulant effect of the Brassica oleracea methanol extract

Directory of Open Access Journals (Sweden)

Khan Rafeeq Alam

2015-01-01

Full Text Available The anticoagulant effect of the methanol extract of Brassica oleracea var. capitata (MEB was examined in rabbits. The animals were divided into five groups, each comprising seven animals. Three groups were administered increasing doses of MEB (200, 300, and 500 mg/kg, respectively; one group received warfarin (0.54 mg/kg; animals in the control group received saline (1 ml/day equivalent to the volume of doses applied to the treated and standard animals. Biochemical tests were performed on the 16th and 31st days of dosing. Animals that were administered MEB (500 mg MEB/kg 30 days displayed increases of 24.07 s, 28.79 s and 4.08 s in activated partial thromboplastin (aPTT, fibrinogen (Fg and thrombin time (TT. Compared to the control, the increase in aPTT and Fg was highly significant and the increase in TT was significant. The anticoagulant effect exhibited by MEB in rabbits may be due to inactivation or inhibition of factors affecting coagulation.

Diffuse abdominal gallium-67 citrate uptake in salmonella infections

International Nuclear Information System (INIS)

Garty, I.; Koren, A.

1987-01-01

Two pediatric patients with salmonella infections (one with typhoid fever and the second with salmonella C2 gastroenteritis), had a diffuse abdominal uptake of Ga-67 citrate. The possible explanation for this finding is discussed. Salmonella infection should be included as a cause in the differential diagnosis of diffuse accumulation of Ga-67 citrate

The effect of the amiodarone-warfarin interaction on anticoagulation quality in a single, high-quality anticoagulation center.

Science.gov (United States)

White, Ryan D; Riggs, Kyle W; Ege, Ed J; Petroski, Gregory F; Koerber, Scott M; Flaker, Greg

2016-03-01

Clinical trials have reported a low time in therapeutic range (TTR) in patients with atrial fibrillation treated with both warfarin andamiodarone. These trials included centers and countries with both high and low TTRs. What is the impact of amiodarone on the TTR in a single, high-quality anticoagulation clinic? TTR was assessed in amiodarone and nonamiodarone-treated patients from a University anticoagulation clinic. Baseline characteristics between patients ever-taking or never-taking amiodarone were similar, except more amiodarone patients were smokers (19.5 vs. 6.1%, P = 0.0031). The TTR calculated from 8901international normalized ratios (INRs) in 249 nonamiodarone patients with a mean follow-up of 34 ± 20 months (mean INR 36 ± 18) was 66 ± 16.6% compared with 61.3 ± 16.2% (P = 0.111) from 1455 INRs in 41 amiodarone-treated patients with a mean follow-up of 28 ± 20 months (mean INR 35 ± 22). Factors associated with a low TTR were male sex (P = 0.0013), smoker (P = 0.0048), and amiodarone use (P = 0.0374). A second on-treatment analysis, in which the TTR was calculated only during amiodarone therapy, resulted in similar findings; however, amiodarone did not emerge as a predictor of a low TTR. In 11 patients, the TTR prior to amiodarone (54.5 ± 22.2%) was not significantly different in the first 3 months (54.6 ± 33.4%) or after 3 months (67.2 ± 33.7%) of amiodarone. In a single high-quality anticoagulation center, anticoagulation quality, as measured by the TTR, can be comparable in amiodarone and nonamiodarone-treated patients.

A case report of uncompensated alkalosis induced by daily plasmapheresis in a patient with thrombotic thrombocytopenic purpura.

Science.gov (United States)

Nagai, Yoshiko; Itabashi, Mitsuyo; Mizutani, Mayuko; Ogawa, Tetsuya; Yumura, Wako; Tsuchiya, Ken; Nitta, Kosaku

2008-02-01

Plasmapheresis (PP) is widely known as the standard therapy for thrombotic thrombocytopenic purpura (TTP). Citrate is used as an anticoagulant in fresh frozen plasma, and the large amount of citrate infused during PP induces metabolic alkalosis. A 29-year-old woman was diagnosed with TTP associated with systemic lupus erythematosus, and was treated by daily PP in addition to a steroid, an immunosuppressant, vincristine, and cyclophosphamide. Uncompensated alkalosis caused by a combination of metabolic and respiratory alkalosis developed after artificial ventilation was discontinued. Her metabolic status improved after controlling her respiratory status and the activity of the TTP. Metabolic alkalosis is a common complication in TTP patients treated by frequent PP, but several factors that affect metabolic status may aggravate the alkalosis and induce uncompensated alkalosis.

Comparative genomics and transcriptome analysis of Aspergillus niger and metabolic engineering for citrate production

Science.gov (United States)

Yin, Xian; Shin, Hyun-dong; Li, Jianghua; Du, Guocheng; Liu, Long; Chen, Jian

2017-01-01

Despite a long and successful history of citrate production in Aspergillus niger, the molecular mechanism of citrate accumulation is only partially understood. In this study, we used comparative genomics and transcriptome analysis of citrate-producing strains—namely, A. niger H915-1 (citrate titer: 157 g L−1), A1 (117 g L−1), and L2 (76 g L−1)—to gain a genome-wide view of the mechanism of citrate accumulation. Compared with A. niger A1 and L2, A. niger H915-1 contained 92 mutated genes, including a succinate-semialdehyde dehydrogenase in the γ-aminobutyric acid shunt pathway and an aconitase family protein involved in citrate synthesis. Furthermore, transcriptome analysis of A. niger H915-1 revealed that the transcription levels of 479 genes changed between the cell growth stage (6 h) and the citrate synthesis stage (12 h, 24 h, 36 h, and 48 h). In the glycolysis pathway, triosephosphate isomerase was up-regulated, whereas pyruvate kinase was down-regulated. Two cytosol ATP-citrate lyases, which take part in the cycle of citrate synthesis, were up-regulated, and may coordinate with the alternative oxidases in the alternative respiratory pathway for energy balance. Finally, deletion of the oxaloacetate acetylhydrolase gene in H915-1 eliminated oxalate formation but neither influence on pH decrease nor difference in citrate production were observed. PMID:28106122

Effect of an interactive voice response system on oral anticoagulant management.

Science.gov (United States)

Oake, Natalie; van Walraven, Carl; Rodger, Marc A; Forster, Alan J

2009-04-28

Monitoring oral anticoagulants is logistically challenging for both patients and medical staff. We evaluated the effect of adding an interactive voice response system to computerized decision support for oral anticoagulant management. We developed an interactive voice response system to communicate to patients the results of international normalized ratio testing and their dosage schedules for anticoagulation therapy. The system also reminded patients of upcoming and missed appointments for blood tests. We recruited patients whose anticoagulation control was stable after at least 3 months of warfarin therapy. We prospectively examined clinical data and outcomes for these patients for an intervention period of at least 3 months. We also collected retrospective data for each patient for the 3 months before study enrolment. We recruited 226 patients between Nov. 23, 2006, and Aug. 1, 2007. The mean duration of the intervention period (prospective data collection) was 4.2 months. Anticoagulation control was similar for the periods during and preceding the intervention (mean time within the therapeutic range 80.3%, 95% confidence interval [CI] 77.5% to 83.1% v. 79.9%, 95% CI 77.3% to 82.6%). The interactive voice response system delivered 1211 (77.8%) of 1557 scheduled dosage messages, with no further input required from clinic staff. The most common reason for clinic staff having to deliver the remaining messages (accounting for 143 [9.2%] of all messages) was an international normalized ratio that was excessively high or low, (i.e., 0.5 or more outside the therapeutic range). When given the option, 76.6% of patients (164/214) chose to continue with the interactive voice response system for management of their anticoagulation after the study was completed. The system reduced staff workload for monitoring anticoagulation therapy by 48 min/wk, a 33% reduction from the baseline of 2.4 hours. Interactive voice response systems have a potential role in improving the

Scintiscanning of lung cancer with 67Ga-citrate

International Nuclear Information System (INIS)

Abe, Mitsunobu; Ohyama, Shiro; Ohtsuka, Hassau; Hoshina, Toshifumi; Takanashi, Shuko

1982-01-01

The clinical value of scintigram with 67 Ga-citrate in 58 patients with primary lung cancer was investigated and discussed. The results are as follows: 1) Positive 67 Ga-scintigram was obtained in 83% of patients with primary lung cancer. The histologically confirmed positive ratios were 74% in adenocarcinoma, 94% in squamous cell carcinoma, 80% in small cell carcinoma and 100% in large cell carcinoma. 2) The positive ratios according to T category of TNM classification was 0% (0/1) in T1, 83% (20/24) in T2 and 85% (28/33) in T3. 3) According to rules for classification of lung cancer (TNM UICC 1978,) T2 cases were divided into two groups. a) In patients with hilar involvements on chest X-ray, positive accumulation to the hilar region was 88% (7/8). b) In patients without the evidence of hilar involvements on chest X-ray, the positive accumulation to the hilar region was 81% (13/16). 4) All cases extending to the mediastinum showed abnormal 67 Ga-citrate accumulation regardless of histological type. 67 Ga-citrate scanning is useful in evaluating the extent of lung cancer, especially with hilar and mediastinal involvements. Therefore 67 Ga-citrate scanning seems to be very useful for planning the radiotherapy for lung cancer. (author)

Reproductive success of bromadiolone-resistant rats in absence of anticoagulant pressure

DEFF Research Database (Denmark)

Heiberg, Ann-Charlotte; Leirs, Herwig; Siegismund, Hans Redlef

2006-01-01

Resistance to anticoagulant rodenticides in brown rats (Rattus norvegicus Berk.) is associated with pleiotropic effects, notably with an increased dietary vitamin K requirement. Owing to this disadvantage, resistance is believed to be selected against if anticoagulant selection is absent. In small...... experimental populations of wild brown rats, an investigation was carried out to establish whether tolerance to anticoagulant exposure changed over a period of 2 years. In the same populations, DNA microsatellite markers were used to infer parentage, and this made it possible to estimate reproductive success...... of sensitive and resistant rats and estimate effective population size, Ne. Even though there was evidence for a selection against resistant rats with high vitamin K requirement, anticoagulant tolerance was not seen to be significantly influenced in the absence of bromadiolone selection. As the population size...

Effects of irradiation on red cells stored in CPDA-1 and CPD-ADSOL (AS-1)

International Nuclear Information System (INIS)

Jeter, E.K.; Gadsden, R.H.; Cate, J.

1991-01-01

Red blood cells (pRBC) collected in citrate, phosphate, dextrose, adenine-formula 1 (CPDA-1) and citrate, phosphate, dextrose-adenine, manitol saline solution (CPD-ADSOL [AS-1]) anticoagulants are increasingly being stored for variable periods in transfusion service inventories following irradiation. While anecdotal reports of increased K+ following irradiation and storage have recently appeared in the literature, concomitant in vitro biochemical changes resulting from differences in anticoagulants have not been reported. Utilizing two venipunctures, two units each of 225 mL of blood from five volunteers were collected in anticoagulant-adjusted CPDA-1 and AS-1 bags. Within two hours of collection, each unit was equally divided. One of each pair was irradiated (2000 rads). Samples were analyzed on Days 0, 1, 3, 7, and every seven days to expiration. Irradiation resulted in a 2.3 fold increase in K+ during the first seven days of storage for both anticoagulants, although significantly greater K+ levels were observed in the CPDA-1 pairs compared to the AS-1 pairs. Comparison of glucose utilization, plasma free hemoglobin, 2,3-diphosphoglycerate (2,3-DPG) and lactate dehydrogenase between control and irradiated CPDA-1 and AS-1 pairs and between anticoagulants were documented

Quantification of active pharmaceutical ingredient and impurities in sildenafil citrate obtained from the Internet.

Science.gov (United States)

Veronin, Michael A; Nutan, Mohammad T; Dodla, Uday Krishna Reddy

2014-10-01

The accessibility of prescription drugs produced outside of the United States, most notably sildenafil citrate (innovator product, Viagra®), has been made much easier by the Internet. Of greatest concern to clinicians and policymakers is product quality and patient safety. The US Food and Drug Administration (FDA) has issued warnings to potential buyers that the safety of drugs purchased from the Internet cannot be guaranteed, and may present a health risk to consumers from substandard products. The objective of this study was to determine whether generic sildenafil citrate tablets from international markets obtained via the Internet are equivalent to the US innovator product regarding major aspects of pharmaceutical quality: potency, accuracy of labeling, and presence and level of impurities. This will help identify aspects of drug quality that may impact public health risks. A total of 15 sildenafil citrate tablets were obtained for pharmaceutical analysis: 14 generic samples from international Internet pharmacy websites and the US innovator product. According to US Pharmacopeial guidelines, tablet samples were tested using high-performance liquid chromatography for potency of active pharmaceutical ingredient (API) and levels of impurities (impurities A, B, C, and D). Impurity levels were compared with International Conference on Harmonisation (ICH) limits. Among the 15 samples, 4 samples possessed higher impurity B levels than the ICH qualification threshold, 8 samples possessed higher impurity C levels than the ICH qualification threshold, and 4 samples possessed more than 1% impurity quantity of maximum daily dose (MDD). For API, 6 of the samples failed to fall within the 5% assay limit. Quality assurance tests are often used to detect formulation defects of drug products during the manufacturing and/or storage process. Results suggest that manufacturing standards for sildenafil citrate generic drug products compared with the US innovator product are not

Blood platelet kinetics and platelet transfusion.

Science.gov (United States)

Aster, Richard H

2013-11-01

The discovery of citrate anticoagulant in the 1920s and the development of plastic packs for blood collection in the 1960s laid the groundwork for platelet transfusion therapy on a scale not previously possible. A major limitation, however, was the finding that platelet concentrates prepared from blood anticoagulated with citrate were unsuitable for transfusion because of platelet clumping. We found that this could be prevented by simply reducing the pH of platelet-rich plasma to about 6.5 prior to centrifugation. We used this approach to characterize platelet kinetics and sites of platelet sequestration in normal and pathologic states and to define the influence of variables such as anticoagulant and ABO incompatibility on post-transfusion platelet recovery. The "acidification" approach enabled much wider use of platelet transfusion therapy until alternative means of producing concentrates suitable for transfusion became available.

Utilization of oral anticoagulation in a teaching hospital in Nigeria ...

African Journals Online (AJOL)

The mean age of the patients was 53.4 years and more females than males were on anticoagulation and monitoring (F14:M12). The most common indications for anticoagulation include deep venous thrombosis/pulmonary embolism, congestive heart failure with atrial fibrillation and mitral valve disease with atrial fibrillation.

Non-vitamin K antagonist oral anticoagulation agents in anticoagulant naïve atrial fibrillation patients

DEFF Research Database (Denmark)

Olesen, Jonas Bjerring; Sørensen, Rikke; Hansen, Morten Lock

2015-01-01

AIMS: Non-vitamin K antagonist oral anticoagulation (NOAC) agents have been approved for stroke prophylaxis in atrial fibrillation (AF). We investigated 'real-world' information on how these drugs are being adopted. METHODS AND RESULTS: Using Danish nationwide administrative registers, we identif...

Hemorrhagic stroke and oral anticoagulants: What is to be done?

Directory of Open Access Journals (Sweden)

M. A. Domashenko

2016-01-01

Full Text Available Hemorrhagic stroke (HS is associated with high mortality and disability rates. Due to the introduction of the current guidelines for the prevention of systemic thromboembolic events in patients with atrial fibrillations and to an increase in the number of older patients, there has been a rise in the incidence of intracranial hemorrhage (ICH associated with the use of oral anticoagulants. The paper discusses medical treatment in patients with HS during therapy with vitamin K antagonists (warfarin and novel oral anticoagulants (dabigatran. rivaroxaban, apixaban, as well as an anticoagulant resumption policy after prior ICH in patients at high risk for thromboembolic events.

77 FR 24461 - Citric Acid and Certain Citrate Salts From Canada: Final Results of Antidumping Duty...

Science.gov (United States)

2012-04-24

... that satisfies the standards set forth in the United States Pharmacopeia and has been mixed with a... meaning of 19 CFR 351.106(c)(1), in which case the cash deposit rate will be zero; (2) for previously.... See Citric Acid and Certain Citrate Salts from Canada and the People's Republic of China: Antidumping...

Sildenafil citrate (Viagra) enhances vasodilatation by atrial natriuretic peptide in normal dogs.

Science.gov (United States)

Ishikura, Fuminobu; Beppu, Shintaro; Asanuma, Toshihiko; Seward, James B; Khandheria, Bijoy K

2007-12-01

Sildenafil citrate (Viagra) is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5, which might enhance the vasorelaxant and natriuretic actions of atrial natriuretic peptide (ANP) in patients with heart failure. The objective of this study was to examine the combined effect of Viagra on hemodynamic changes during infusion of exogenous ANP. Healthy male beagles were used to assess systemic blood pressure, pulmonary artery pressure (PAP), and plasma levels of cGMP. After hemodynamic variables were measured, 0.1 microg.kg(-1).min(-1) of ANP was given during this study. One hour after initiating infusion of ANP, 2 mg/kg of sildenafil citrate or vehicle was given orally via a nasogastric tube. Hemodynamic changes were measured before and 1 h after these administrations. Mean systemic and PAP decreased during infusion of ANP, and further decreased after sildenafil citrate administration, however, mean systemic blood pressure decreased within 10 mmHg. Plasma levels of cGMP also increased after sildenafil citrate administration. In normal dogs, sildenafil citrate enhances the vasodilator effect of ANP by increasing the cGMP level, however, the concomitant use of sildenafil citrate with ANP will not induce severe hypotension.

Artificial citrate operon and Vitreoscilla hemoglobin gene enhanced mineral phosphate solubilizing ability of Enterobacter hormaechei DHRSS.

Science.gov (United States)

Yadav, Kavita; Kumar, Chanchal; Archana, G; Kumar, G Naresh

2014-10-01

Mineral phosphate solubilization by bacteria is mediated through secretion of organic acids, among which citrate is one of the most effective. To overproduce citrate in bacterial systems, an artificial citrate operon comprising of genes encoding NADH-insensitive citrate synthase of E. coli and Salmonella typhimurium sodium-dependent citrate transporter was constructed. In order to improve its mineral phosphate solubilizing (MPS) ability, the citrate operon was incorporated into E. hormaechei DHRSS. The artificial citrate operon transformant secreted 7.2 mM citric acid whereas in the native strain, it was undetectable. The transformant released 0.82 mM phosphate in flask studies in buffered medium containing rock phosphate as sole P source. In fermenter studies, similar phenotype was observed under aerobic conditions. However, under microaerobic conditions, no citrate was detected and P release was not observed. Therefore, an artificial citrate gene cluster containing Vitreoscilla hemoglobin (vgb) gene under its native promoter, along with artificial citrate operon under constitutive tac promoter, was constructed and transformed into E. hormaechei DHRSS. This transformant secreted 9 mM citric acid under microaerobic conditions and released 1.0 mM P. Thus, incorporation of citrate operon along with vgb gene improves MPS ability of E. hormaechei DHRSS under buffered, microaerobic conditions mimicking rhizospheric environment.

APPLICATIONS OF PHARMACOGENETIC TESTING FOR PERSONALIZATION OF THERAPY WITH ORAL ANTICOAGULANTS IN RUSSIA

Directory of Open Access Journals (Sweden)

D. A. Sychev

2013-01-01

Full Text Available The clinical significance of the patient genetic characteristics in the individual pharmacological response to oral anticoagulants is considered. Possible tactics of warfarin dosing and new oral anticoagulants choice on the basis of pharmacogenetic testing as well as indications for this approach in clinical practice are discussed. It should increase efficacy and safety of anticoagulant therapy.

The optimal duration of anticoagulant therapy after unprovoked venous thromboembolism - still a challenging issue.

Science.gov (United States)

Elmi, Giovanna; Di Pasquale, Giuseppe; Pesavento, Raffaele

2017-03-01

As about 50 % of patients with unprovoked venous thromboembolism (VTE) will develop new episodes after discontinuing therapy, indefinite treatment is suggested in patients with low or moderate bleeding risk. Baseline and post-baseline factors can help clinicians to identify patients at high risk of recurrence, who require extended treatment. Residual vein obstruction and D-dimer assay have been shown to be suitable methods for assessing the risk of VTE recurrences after a first unprovoked VTE. In treatment for VTE the use of direct oral anticoagulants (DOAC) is growing instead of the standard adjusted dose of vitamin K antagonists. The DOAC safety profile has recently been strengthened with systematic reviews and meta-analyses. Idarucizumab is only approved for the reversal of dabigatran etexilate; intravenous antidotes for factor Xa inhibitors are under development. Their advent is of great interest. In the extended treatment of VTE sulodexide has been demonstrated to significantly decrease the risk of recurrences with an excellent safety profile. Aspirin is substantially less effective than oral anticoagulants in preventing recurrences but could play a role among patients who decided to stop anticoagulants. In conclusion, for the secondary prevention of VTE several options are available, without a recognised best choice regarding the treatment duration and the choice of drugs. An individual strategy taking into account risk of recurrence, bleeding risk, therapeutic options, and patient preferences is appropriate.

SPECIFIC ASPECTS OF INTERACTION OF PLATELETS WITH THE HEPARINIZED MATERIALS

Directory of Open Access Journals (Sweden)

E.A. Nemets

2012-01-01

Full Text Available Comparative analysis of anticoagulant nature on medical materials testing was done. It was found that change of citrate by heparin is accompanied by significant changes in platelet adhesion and activation. This results allowed us to arrive at a conclusion about reasonability of heparin usage as anticoagulant in in vitro testing. 

Direct Oral Anticoagulants and Women

NARCIS (Netherlands)

Cohen, Hannah; Arachchillage, Deepa R. J.; Beyer-Westendorf, Jan; Middeldorp, Saskia; Kadir, Rezan A.

2016-01-01

Direct oral anticoagulants (DOACs) provide an effective, safe, and convenient therapeutic alternative to warfarin and other vitamin K antagonists (VKAs), and are now established for a wide range of indications. The use of DOACs in women merits special consideration due to two main situations: first,

D-dimer to guide the intensity of anticoagulation in Chinese patients after mechanical heart valve replacement: a randomized controlled trial.

Science.gov (United States)

Zhang, L; Zheng, X; Long, Y; Wu, M; Chen, Y; Yang, J; Liu, Z; Zhang, Z

2017-10-01

Essentials Low anticoagulation intensity reduces bleeding but increases thrombosis during warfarin therapy. Elevated D-dimer level is associated with increased thrombosis events. D-dimer can be used to find potential thrombosis in those receiving low intensity therapy. D-dimer-guided therapy may be the optimal strategy for those with mechanical heart valve replacement. Background Controversies remain regarding the optimal anticoagulation intensity for Chinese patients after mechanical heart valve replacement despite guidelines having recommended a standard anticoagulation intensity. Objectives To investigate whether D-dimer could be used to determine the optimal anticoagulation intensity in Chinese patients after mechanical heart valve replacement. Patients/Methods This was a prospective, randomized controlled clinical study. A total of 748 patients following mechanical heart valve replacement in Wuhan Asia Heart Hospital were randomized to three groups at a ratio of 1 : 1 : 1. Patients in two control groups received warfarin therapy based on constant standard intensity (international normalized ratio [INR], 2.5-3.5; n = 250) and low intensity (INR, 1.8-2.6; n = 248), respectively. In the experimental group (n = 250), warfarin therapy was initiated at low intensity, then those with elevated D-dimer levels were adjusted to standard intensity. All patients were followed-up for 24 months until the occurrence of endpoints, including bleeding events, thrombotic events and all-cause mortality. Results A total of 718 patients were included in the analysis. Fifty-three events occurred during follow-up. There was less hemorrhage (3/240 vs. 16/241; hazard ratio [HR], 0.18; 95% confidence interval [CI], 0.07-0.45) and all-cause mortality (4/240 vs. 12/241; HR, 0.33; 95% CI, 0.12-0.87) observed in the D-dimer-guided group than in the standard-intensity group. A lower incidence of thrombotic events was also observed in the D-dimer-guided group when compared with the

Direct-Acting Oral Anticoagulants: Practical Considerations for Emergency Medicine Physicians

Directory of Open Access Journals (Sweden)

W. Frank Peacock

2016-01-01

Full Text Available Nonvalvular atrial fibrillation- (NVAF- related stroke and venous thromboembolism (VTE are cardiovascular diseases associated with significant morbidity and economic burden. The historical standard treatment of VTE has been the administration of parenteral heparinoid until oral warfarin therapy attains a therapeutic international normalized ratio. Warfarin has been the most common medication for stroke prevention in NVAF. Warfarin use is complicated by a narrow therapeutic window, unpredictable dose response, numerous food and drug interactions, and requirements for frequent monitoring. To overcome these disadvantages, direct-acting oral anticoagulants (DOACs—dabigatran, rivaroxaban, apixaban, and edoxaban—have been developed for the prevention of stroke or systemic embolic events (SEE in patients with NVAF and for the treatment of VTE. Advantages of DOACs include predictable pharmacokinetics, few drug-drug interactions, and low monitoring requirements. In clinical studies, DOACs are noninferior to warfarin for the prevention of NVAF-related stroke and the treatment and prevention of VTE as well as postoperative knee and hip surgery VTE prophylaxis, with decreased bleeding risks. This review addresses the practical considerations for the emergency physician in DOAC use, including dosing recommendations, laboratory monitoring, anticoagulation reversal, and cost-effectiveness. The challenges of DOACs, such as the lack of specific laboratory measurements and antidotes, are also discussed.

Affinity for a malignant tumor and organs of sup(99m)Tc-citrate complex

Energy Technology Data Exchange (ETDEWEB)

Ando, A; Sanada, S; Hiraki, T [Kanazawa Univ. (Japan). School of Paramedicine; Hisada, K; Nakazawa, N

1976-12-01

In order to investigate the tumor affinity of sup(99m)Tc-citrate complex, it was synthesized in three different ways. By (1) reducing sup(99m)TcO/sub 4//sup -/ with FeCl/sub 3//sup -/ ascorbic acid in 0.15 M sodium citrate, (2) reducing sup(99m)TcO/sub 4//sup -/ with SnCl/sub 2/ solution in 0.15 M sodium citrate, and (3) reducing sup(99m)TcO/sub 4//sup -/ with NaBH/sub 4/ in 0.45 sodium citrate. It was presumed from thinlayer chromatography that the sup(99m)Tc-citrate complexes synthesized in three ways were chemically different. These sup(99m)Tc-citrate complexes were injected intravenously into the rats subcutaneously transplanted with Yoshida sarcoma. These rats were sacrificed at one hour and three hours after injection. The radioactivity of the tumor, blood, muscle, liver, kidney, spleen and urine was measured by well-type scintillation counter. The retention values in these organs and the excretion rates in the urine were calculated. sup(99m)Tc-citrate complex synthesized by reducing sup(99m)TcO/sub 4//sup -/ with SnCl/sub 2/ solution had very strong affinity for the malignant tumor but the other two sup(99m)Tc-citrate complexes had no affinity to the malignant tumor. Excretion rates (% dose) of sup(99m)Tc-citrate complexes in one hour were from 65% to 75%.

Anticoagulation Quality and Complications of using Vitamin K Antagonists in the Cardiac Surgery Outpatient Clinic

Directory of Open Access Journals (Sweden)

Mário Augusto Cray da Costa

Full Text Available ABSTRACT Introduction: In patients with mechanical prosthetic heart valves or atrial fibrillation requiring anticoagulation to prevent thromboembolic events, several factors influence adherence and anticoagulation complications. Objective: To evaluate the factors that interfere with the quality and complications of anticoagulation with vitamin K antagonists. Methods: A retrospective cohort study of 100 patients, in the period from 2011 to 2014, was performed. Anticoagulation conditions in the last year, regarding the presence of complications (embolisms/bleeding and inadequate treatment were assessed: achievement of less than 8 annual prothrombin times and International Normalized Ratio outside therapeutic target in more than 40% of prothrombin times. Results: There were 31 complications (22 minor bleeding without hospitalization and 9 major complications: 7 bleeding with hospitalization and two emboli; 70 were with International Normalized Ratio outside the target in more than 40% of the tests and 36 with insufficient number of prothrombin times. Socioeconomic factors, anticoagulant type and anticoagulation reason had no relationship with complications or with inadequate treatment. There were more complications in patients with longer duration of anticoagulation (P=0.001. Women had more International Normalized Ratio outside the target range (OR 2.61, CI:1.0-6.5; P=0.04. Patients with lower number of annual prothrombin times had longer times of anticoagulation (P=0.03, less annual consultations (P=0.02 and less dose adjustments (P=0.003. Patients with longer duration of anticoagulation have more complications (P=0.001. Conclusion: There was a high rate of major complications and International Normalized Ratio was outside the goal. Less annual prothrombin times was related to longer duration of anticoagulation, less annual consultations and less dose adjustments. More major complications occurred in patients with longer duration of

Clomiphene citrate therapy for male infertility.

Science.gov (United States)

Allag, I S; Alexander, N J

1979-11-01

We have summarized 697 reported cases of the use of clomiphene citrate for the improvement of semen quality. Basal levels of gonadotropins are useful criteria for the differential diagnosis of hypo- and hypergonadotropic hypogonadism. Patients with an intact hypothalamic-pituitary-gonadal axis are most likely to respond to clomiphene citrate. Twenty-five mg. per day, administered in a cyclic fashion for a period of six to nine months, caused the greatest improvement. A higher dose (50 mg. per day) may be effective in men who do not respond to 25 mg. During the course of therapy gonadotropin levels and semen samples should be analyzed periodically. This drug is not currently approved for use in men; the incidence of side effects, particularly with long-term treatment, is unknown.

Photoselective vaporization of the prostate in men with a history of chronic oral anti-coagulation

Directory of Open Access Journals (Sweden)

Omer F. Karatas

2010-04-01

Full Text Available PURPOSE: A considerable percentage of patients with benign prostatic hyperplasia (BPH also have additional cardiac pathologies, which often require anticoagulant therapy. The aim of this study was to evaluate the efficacy and safety of photoselective vaporization of the prostate (PVP for BPH in cardiac patients receiving anticoagulant therapy. MATERIALS AND METHODS: A total of 67 patients suffering from BPH and high risk cardiac pathologies were operated on using laser prostatectomy. All patients had cardiac pathologies with bleeding disorders requiring anticoagulant use, and underwent standard urologic evaluation for BPH. Patients were treated with laser prostatectomy for relief of the obstruction using the KTP/532 laser energy at 80 W. RESULTS: The mean patient age was 71.4 years (range 55-80. Mean prostate volume on transrectal ultrasonography was 73.2 mL (range 44-120. Operation time ranged from 40 to 90 min, with an average value of 55 min. The average hospital stay was 48 hours (range 12-72 and the Foley catheters were removed within 48 hours, with a mean catheterization time of 34.2 ± 5.9 hours (0-48. No patient required an additional procedure due to severe bleeding necessitating intervention during the early postoperative phase. Mean International symptoms scoring system (IPSS values and post voiding residual volume decreased and peak urinary flow rate increased (p < 0.001. Our results showed that the mean prostate volume had decreased by 53% at 6 months. CONCLUSIONS: High-power photo selective laser vaporization prostatectomy is a feasible, safe, and effective alternative for the minimal invasive management of BPH, particularly in cardiac patients receiving anticoagulant therapy.

nanoparticles synthesized by citrate precursor m

African Journals Online (AJOL)

user

(M=Co, Cu) nanoparticles synthesized by citrate precursor method ... The structural characterization was carried out using an X-ray Diffractometer (Rikagu Miniflex, Japan) ..... His current area of interest includes magnetic nanomaterials.

Effect of sildenafil citrate (Viagra) on coronary flow in normal subjects.

Science.gov (United States)

Ishikura, Fuminobu; Beppu, Shintaro; Ueda, Hiroaki; Nehra, Ajay; Khandheria, Bijoy K

2008-01-01

The purpose of this study was to evaluate the effect of sildenafil citrate (Viagra) on coronary function in normal subjects. The study assessed mean blood pressure, left anterior descending coronary artery (LAD) flow, and echocardiographic variables before and 30 and 60 minutes after taking 50 mg of sildenafil citrate. The mean velocity of LAD flow was assessed with Doppler flow imaging. The study subjects were 6 healthy male volunteers (mean age 37 years). The mean velocity of LAD flow increased 60 minutes after taking sildenafil citrate, but there were no other changes. Two volunteers felt mild flashing and one had mild headache during the study. Sildenafil citrate caused vasodilatation in a normal coronary artery without systemic pressure drops. These results suggest that the agent itself did not have negative effects on the heart in normal subjects.

SERS substrates fabricated using ceramic filters for the detection of bacteria: Eliminating the citrate interference

Science.gov (United States)

Mosier-Boss, P. A.; Sorensen, K. C.; George, R. D.; Sims, P. C.; O'braztsova, A.

2017-06-01

It was found that spectra obtained for bacteria on SERS substrates fabricated by filtering citrate-generated Ag nanoparticles (NPs) onto rigid, ceramic filters exhibited peaks due to citrate as well as the bacteria. In many cases the citrate spectrum overwhelmed that of the bacteria. Given the simplicity of the method to prepare these substrates, means of eliminating this citrate interference were explored. It was found that allowing a mixture of bacteria suspension and citrate-generated Ag NPs to incubate prior to filtering onto the ceramic filter eliminated this interference.

Effects of citrate on hexavalent chromium reduction by structural Fe(II) in nontronite

Energy Technology Data Exchange (ETDEWEB)

Liu, Xiaolei; Dong, Hailiang; Yang, Xuewei; Kovarik, Libor; Chen, Yu; Zeng, Qiang

2018-02-01

Iron-bearing clay minerals and organic matter are two important components in natural environments that influence hexavalent chromium (Cr(VI)) reduction. Previous studies have shown that organic ligands could influence Cr(VI) reduction by aqueous Fe2+ and pyrite. However, the effects of organic ligands on Cr(VI) reduction by structural Fe(II) in clays are not well understood. In this study, the effects of citrate on Cr(VI) reduction by nontronite (NAu-2) were investigated under near neutral pH condition (pH=6). Our results showed that the presence of citrate decreased the rate but increased the amount of Cr(VI) reduction by structural Fe(II) in NAu-2. The decreased reaction rate was likely due to competitive sorption of citrate and polyanionic dichromate (Cr2O7- ), because sorption of dichromate appeared to be the first step for subsequent Cr(VI) reduction. The increased amount of Cr(VI) reduction in the presence of citrate was likely because citrate provided additional reducing power through ligand-metal electron transfer in the presence of soluble Fe 3+ derived from dissolution of reduced NAu-2. Soluble Cr(III)-citrate complex was the possible form of reduced chromium when citrate was present. In contrast, nanometer-sized Cr2O3 particles were the product of Cr(VI) reduction by reduced NAu-2 without citrate. Our study highlights the importance of organic ligands on Cr(VI) reduction and immobilization when iron-bearing clay minerals are applied to treat Cr(VI) contaminant in organic matter rich environments.

Fall risk and anticoagulation for atrial fibrillation in the elderly: A delicate balance.

Science.gov (United States)

Hagerty, Tracy; Rich, Michael W

2017-01-01

Guidelines for managing atrial fibrillation recommend systemic anticoagulation for almost all patients age 65 and older, but in practice up to 50% of older patients do not receive maintenance anticoagulation therapy. The most common reason physicians cite for withholding anticoagulation in older patients with atrial fibrillation is a perception of a high risk of falling and associated bleeding, especially intracranial hemorrhage. Copyright © 2017 Cleveland Clinic.

Hematin-derived anticoagulant. Generation in vitro and in vivo

OpenAIRE

1986-01-01

Prolongation of clotting times produced by hematin was investigated both in vitro and in vivo. Hematin-derived anticoagulant (HDA) was found to be due to a degradative product or derivative of hematin, and was generated in vitro in standing (aging) aqueous solutions of the parent compound. Generation of HDA in vitro was inhibited by antioxidants. The anticoagulant effect of HDA was inhibited by freshly prepared hematin, fresh Sn-protoporphyrin, imidazole, or the iron chelator desferrioxamine....

The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines-Anticoagulation During Cardiopulmonary Bypass.

Science.gov (United States)

Shore-Lesserson, Linda; Baker, Robert A; Ferraris, Victor A; Greilich, Philip E; Fitzgerald, David; Roman, Philip; Hammon, John W

2018-02-01

Despite more than a half century of "safe" cardiopulmonary bypass (CPB), the evidence base surrounding the conduct of anticoagulation therapy for CPB has not been organized into a succinct guideline. For this and other reasons, there is enormous practice variability relating to the use and dosing of heparin, monitoring heparin anticoagulation, reversal of anticoagulation, and the use of alternative anticoagulants. To address this and other gaps, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiologists, and the American Society of Extracorporeal Technology developed an Evidence Based Workgroup. This was a group of interdisciplinary professionals gathered to summarize the evidence and create practice recommendations for various aspects of CPB. To date, anticoagulation practices in CPB have not been standardized in accordance with the evidence base. This clinical practice guideline was written with the intent to fill the evidence gap and to establish best practices in anticoagulation therapy for CPB using the available evidence. To identify relevant evidence, a systematic review was outlined and literature searches were conducted in PubMed using standardized medical subject heading (MeSH) terms from the National Library of Medicine list of search terms. Search dates were inclusive of January 2000 to December 2015. The search yielded 833 abstracts, which were reviewed by two independent reviewers. Once accepted into the full manuscript review stage, two members of the writing group evaluated each of 286 full papers for inclusion eligibility into the guideline document. Ninety-six manuscripts were included in the final review. In addition, 17 manuscripts published before 2000 were included to provide method, context, or additional supporting evidence for the recommendations as these papers were considered sentinel publications. Members of the writing group wrote and developed recommendations based on review of the articles obtained and achieved

Whole-body retention studies of /sup 169/Yb-citrate. Estimation of radiation dose to humans from /sup 169/Yb-citrate

Energy Technology Data Exchange (ETDEWEB)

Ando, A; Hiraki, T [Kanazawa Univ. (Japan). School of Paramedicine; Mori, H; Ando, I; Hisada, K

1977-09-01

For purpose of the estimation of the radiation dose to humans from /sup 169/Yb-citrate, the whole-body retention studies using five rats were carried out. Following intravenous administration of /sup 169/Yb-citrate, the whole-body activity was monitored for 40 days by the animal counter. The whole-body retention curve consisted of three components: the first with a 3.6 hours effective half-time, the second with an 154 hours effective half-time and the third with a 29.9 days effective half-time. Therefore it was assumed that 32% of the administered /sup 169/Yb-citrate clears from the kidney with a short biologic half-time (3.6 hours), 18% remains in the liver and other soft tissues with a relatively long biologic half-time (194 hours) and 50% remains in the bone with a long biologic half-time (850 days). Based on these biological data and the MIRD Committee method, the average dose to the bone and whole-body were 20.8 rads/mCi and 4.5 rads/mCi respectively.

[Effect of glucose and lactose on the utilization of citrate by Lactobacillus casei subsp. rhamnosus ATCC 7469].

Science.gov (United States)

Benito de Cárdenas, I L; Medina, R; Oliver, G

1992-01-01

The utilization of citrate by Lactobacillus casei subsp. rhamnosus ATCC 7469 in a complex medium containing glucose, lactose or citrate was investigated, as an approach to the question of the transport of this acid and the possible relationship with the production of flavour compounds (diacetyl and acetoin). This lactobacillus uses citrate as an energy source in the absence of carbohydrates. External pH and growth increases when citrate is added to complex medium. The presence of citrate does not affect glucose uptake. L. casei ATCC 7469 possibly uses a transport system for citrate utilization, and citrate uptake seems to be under glucose or lactose control. Lactose only inhibits the entrance of citrate at high concentration while the utilization of this acid was negatively regulated by low glucose concentration.

D-dimer: a useful tool in gauging optimal duration of oral anticoagulant therapy?

Directory of Open Access Journals (Sweden)

M. Silingardi

2013-05-01

Full Text Available BACKGROUND AND AIM OF THE STUDY Optimal duration of oral anticoagulant therapy (OAT in idiopathic venous thromboembolism (VTE is unknown. Indefinite OAT carries an unacceptable risk of major bleeding and prospective studies have demonstrated that OAT is no longer protective after its withdrawal. How to identify the patients at risk for recurrence? D-dimer is a marker of thrombin activity. Early prospective studies showed that elevated D-dimer levels after anticoagulation had a highly predictive value for a recurrent episode. Does D-dimer assay have a role in gauging the appropriate duration of anticoagulant therapy? The PROLONG study tries to answer this question. METHOD D-dimer assay was performed one month after stopping anticoagulation. Patiens with normal D-dimer levels did not resume anticoagulation while patients with elevated D-dimer levels were randomized to discontinue or resume anticoagulation. Study end-points was the composite of recurrent VTE and major bleeding during an average follow-up of 1.4 years. RESULTS The rate of recurrence is significantly higher in patients with elevated D-dimer levels who discontinued anticoagulation. Resuming anticoagulation in this cohort of patients markedly reduces recurrent events without increasing major bleeding. DISCUSSION AND CONCLUSIONS PROLONG study is provocative, because D-dimer assay is simple, thus not requiring dedicated laboratory facilities. D-dimer test has otherwise high sensitivity but low specificity in VTE diagnosis. Aspecifically elevated D-dimer levels are available in the elderly and the majority of patients included in the study were > 65 years old, thus introducing a possible selection bias. Nonetheless the results of the study are useful for the clinician. Prolongation of vitamin K antagonists in patients with elevated D-dimer levels one month after discontinuation of OAT for a first unprovoked episode of VTE results in a favourable risk-benefit relationship. Probably this

Oral Anticoagulation in Patients With Liver Disease.

Science.gov (United States)

Qamar, Arman; Vaduganathan, Muthiah; Greenberger, Norton J; Giugliano, Robert P

2018-05-15

Patients with liver disease are at increased risks of both thrombotic and bleeding complications. Many have atrial fibrillation (AF) or venous thromboembolism (VTE) necessitating oral anticoagulant agents (OACs). Recent evidence has contradicted the assumption that patients with liver disease are "auto-anticoagulated" and thus protected from thrombotic events. Warfarin and non-vitamin K-antagonist OACs have been shown to reduce thrombotic events safely in patients with either AF or VTE. However, patients with liver disease have largely been excluded from trials of OACs. Because all currently approved OACs undergo metabolism in the liver, hepatic dysfunction may cause increased bleeding. Thus, the optimal anticoagulation strategy for patients with AF or VTE who have liver disease remains unclear. This review discusses pharmacokinetic and clinical studies evaluating the efficacy and safety of OACs in patients with liver disease and provides a practical, clinically oriented approach to the management of OAC therapy in this population. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

POST-NOAC: Portuguese observational study of intracranial hemorrhage on non-vitamin K antagonist oral anticoagulants.

Science.gov (United States)

Marques-Matos, Cláudia; Alves, José Nuno; Marto, João Pedro; Ribeiro, Joana Afonso; Monteiro, Ana; Araújo, José; Silva, Fernando; Grenho, Fátima; Viana-Baptista, Miguel; Sargento-Freitas, João; Pinho, João; Azevedo, Elsa

2017-08-01

Background There is a lower reported incidence of intracranial hemorrhage with non-vitamin K antagonist oral anticoagulants compared with vitamin K antagonist. However, the functional outcome and mortality of intracranial hemorrhage patients were not assessed. Aims To compare the outcome of vitamin K antagonists- and non-vitamin K antagonist oral anticoagulants-related intracranial hemorrhage. Methods We included consecutive patients with acute non-traumatic intracranial hemorrhage on oral anticoagulation therapy admitted between January 2013 and June 2015 at four university hospitals. Clinical and demographic data were obtained from individual medical records. Intracranial hemorrhage was classified as intracerebral, extra-axial, or multifocal using brain computed tomography. Three-month functional outcome was assessed using the modified Rankin Scale. Results Among 246 patients included, 24 (9.8%) were anticoagulated with a non-vitamin K antagonist oral anticoagulants and 222 (90.2%) with a vitamin K antagonists. Non-vitamin K antagonist oral anticoagulants patients were older (81.5 vs. 76 years, p = 0.048) and had intracerebral hemorrhage more often (83.3% vs. 63.1%, p = 0.048). We detected a non-significant trend for larger intracerebral hemorrhage volumes in vitamin K antagonists patients ( p = 0.368). Survival analysis adjusted for age, CHA 2 DS 2 VASc, HAS-BLED, and anticoagulation reversal revealed that non-vitamin K antagonist oral anticoagulants did not influence three-month mortality (hazard ratio (HR) = 0.83, 95% confidence interval (CI) = 0.39-1.80, p = 0.638). Multivariable ordinal regression for three-month functional outcome did not show a significant shift of modified Rankin Scale scores in non-vitamin K antagonist oral anticoagulants patients (odds ratio (OR) 1.26, 95%CI 0.55-2.87, p = 0.585). Conclusions We detected no significant differences in the three-month outcome between non-vitamin K antagonist oral anticoagulants

The effect anticoagulation status on geriatric fall trauma patients.

Science.gov (United States)

Coleman, Julia; Baldawi, Mustafa; Heidt, David

2016-12-01

This research study aims to identify the effect of anticoagulation status on hospital course, complications, and outcomes among geriatric fall trauma patients. The study design is a retrospective cohort study, looking at fall trauma among patients aged 60 to 80 years from 2009 to 2013 at a university hospital in the United States. The statistical analysis, conducted with SPSS software with a threshold for statistical significance of P patients included in this study was 1,121. Compared with patients not on anticoagulation, there was a higher LOS among patients on anticoagulation (6.3 ± 6.2 vs 4.9 ± 5.2, P = .001). A higher LOS (7.2 ± 6.8 vs 5.0 ± 5.3, P = .001) and days in the ICU (2.1 ± 5.4 vs 1.1 ± 3.8, P = .010) was observed in patients on warfarin. A higher mortality (7.1% vs 2.8%, P = .013), LOS (6.3 ± 6.2 vs 5.1 ± 5.396, P = .036), and complication rate (49.1 vs 36.7, P = .010) was observed among patients on clopidogrel. In this study, a higher mortality and complication rate were seen among clopidogrel, and a greater LOS and number of days in the ICU were seen in patients on warfarin. These differences are important, as they can serve as a screening tool for triaging the severity of a geriatric trauma patient's condition and complication risk. For patients on clopidogrel, it is essential that these patients are recognized early as high-risk patients who will need to be monitored more closely. For patients on clopidogrel or warfarin, bridging a patient's anticoagulation should be initiated as soon as possible to prevent unnecessary increased LOS. At last, these data also provide support against prescribing patients clopidogrel when other anticoagulation options are available. Published by Elsevier Inc.

Free Rhodium (II) citrate and rhodium (II) citrate magnetic carriers as potential strategies for breast cancer therapy

Science.gov (United States)

2011-01-01

Background Rhodium (II) citrate (Rh2(H2cit)4) has significant antitumor, cytotoxic, and cytostatic activity on Ehrlich ascite tumor. Although toxic to normal cells, its lower toxicity when compared to carboxylate analogues of rhodium (II) indicates Rh2(H2cit)4 as a promising agent for chemotherapy. Nevertheless, few studies have been performed to explore this potential. Superparamagnetic particles of iron oxide (SPIOs) represent an attractive platform as carriers in drug delivery systems (DDS) because they can present greater specificity to tumor cells than normal cells. Thus, the association between Rh2(H2cit)4 and SPIOs can represent a strategy to enhance the former's therapeutic action. In this work, we report the cytotoxicity of free rhodium (II) citrate (Rh2(H2cit)4) and rhodium (II) citrate-loaded maghemite nanoparticles or magnetoliposomes, used as drug delivery systems, on both normal and carcinoma breast cell cultures. Results Treatment with free Rh2(H2cit)4 induced cytotoxicity that was dependent on dose, time, and cell line. The IC50 values showed that this effect was more intense on breast normal cells (MCF-10A) than on breast carcinoma cells (MCF-7 and 4T1). However, the treatment with 50 μM Rh2(H2cit)4-loaded maghemite nanoparticles (Magh-Rh2(H2cit)4) and Rh2(H2cit)4-loaded magnetoliposomes (Lip-Magh-Rh2(H2cit)4) induced a higher cytotoxicity on MCF-7 and 4T1 than on MCF-10A (p rhodium (II) citrate-loaded maghemite nanoparticles and magnetoliposomes induced more specific cytotoxicity on breast carcinoma cells than on breast normal cells, which is the opposite of the results observed with free Rh2(H2cit)4 treatment. Thus, magnetic nanoparticles represent an attractive platform as carriers in Rh2(H2cit)4 delivery systems, since they can act preferentially in tumor cells. Therefore, these nanopaticulate systems may be explored as a potential tool for chemotherapy drug development. PMID:21443799

Effects and mechanisms of action of sildenafil citrate in human chorionic arteries

Directory of Open Access Journals (Sweden)

Lynch Tadhg

2009-04-01

Full Text Available Abstract Objectives Sildenafil citrate, a specific phosphodiesterase-5 inhibitor, is increasingly used for pulmonary hypertension in pregnancy. Sildenafil is also emerging as a potential candidate for the treatment of intra-uterine growth retardation and for premature labor. Its effects in the feto-placental circulation are not known. Our objectives were to determine whether phosphodiesterase-5 is present in the human feto-placental circulation, and to characterize the effects and mechanisms of action of sildenafil citrate in this circulation. Study Design Ex vivo human chorionic plate arterial rings were used in all experiments. The presence of phosphodiesterase-5 in the feto-placental circulation was determined by western blotting and immunohistochemical staining. In a subsequent series of pharmacologic studies, the effects of sildenafil citrate in pre-constricted chorionic plate arterial rings were determined. Additional studies examined the role of cGMP and nitric oxide in mediating the effects of sildenafil. Results Phosphodiesterase-5 mRNA and protein was demonstrated in human chorionic plate arteries. Immunohistochemistry demonstrated phosphodiesterase-5 within the arterial muscle layer. Sildenafil citrate produced dose dependent vasodilatation at concentrations at and greater than 10 nM. Both the direct cGMP inhibitor methylene blue and the cGMP-dependent protein kinase inhibitor Rp-8-Br-PET-cGMPS significantly attenuated the vasodilation produced by sildenafil citrate. Inhibition of NO production with L-NAME did not attenuate the vasodilator effects of sildenafil. In contrast, sildenafil citrate significantly enhanced the vasodilation produced by the NO donor sodium nitroprusside. Conclusion Phosphodiesterase-5 is present in the feto-placental circulation. Sildenafil citrate vasodilates the feto-placental circulation via a cGMP dependent mechanism involving increased responsiveness to NO.

Effects and mechanisms of action of sildenafil citrate in human chorionic arteries.

LENUS (Irish Health Repository)

Maharaj, Chrisen H

2009-01-01

OBJECTIVES: Sildenafil citrate, a specific phosphodiesterase-5 inhibitor, is increasingly used for pulmonary hypertension in pregnancy. Sildenafil is also emerging as a potential candidate for the treatment of intra-uterine growth retardation and for premature labor. Its effects in the feto-placental circulation are not known. Our objectives were to determine whether phosphodiesterase-5 is present in the human feto-placental circulation, and to characterize the effects and mechanisms of action of sildenafil citrate in this circulation. STUDY DESIGN: Ex vivo human chorionic plate arterial rings were used in all experiments. The presence of phosphodiesterase-5 in the feto-placental circulation was determined by western blotting and immunohistochemical staining. In a subsequent series of pharmacologic studies, the effects of sildenafil citrate in pre-constricted chorionic plate arterial rings were determined. Additional studies examined the role of cGMP and nitric oxide in mediating the effects of sildenafil. RESULTS: Phosphodiesterase-5 mRNA and protein was demonstrated in human chorionic plate arteries. Immunohistochemistry demonstrated phosphodiesterase-5 within the arterial muscle layer. Sildenafil citrate produced dose dependent vasodilatation at concentrations at and greater than 10 nM. Both the direct cGMP inhibitor methylene blue and the cGMP-dependent protein kinase inhibitor Rp-8-Br-PET-cGMPS significantly attenuated the vasodilation produced by sildenafil citrate. Inhibition of NO production with L-NAME did not attenuate the vasodilator effects of sildenafil. In contrast, sildenafil citrate significantly enhanced the vasodilation produced by the NO donor sodium nitroprusside. CONCLUSION: Phosphodiesterase-5 is present in the feto-placental circulation. Sildenafil citrate vasodilates the feto-placental circulation via a cGMP dependent mechanism involving increased responsiveness to NO.

Adverse effects of anticoagulation treatment: clinically significant upper gastrointestinal hemorrhage

Directory of Open Access Journals (Sweden)

Pavel Skok

2006-12-01

Full Text Available Background: Over the last years, the use of oral anticoagulant treatment has increased dramatically, principally for the prevention of venous thrombosis and thrombembolic events. This treatment is demanding, especially among the elderly with concommitant diseases and different medication. Aim of the study to evaluate the rate of serious complications, clinically significant hemorrhage from upper gastointestinal tract in patients treated with oral antiocoagulants in a prospective cohort study.Patients and methods: Included were patients admitted to our institution between January 1, 1994 and December 31, 2003 due to gastrointestinal hemorrhage. Emergency endoscopy and laboratory testing was performed in all patients.Results: 6416 patients were investigated: 2452 women (38.2 % and 3964 men (61.8 %, mean age 59.1 years, SD 17.2. Among our patients, 55 % were aged over 60 years. In 86.4 % of patients the source of bleeding was confirmed in the upper gastrointestinal tract. In the last week prior to bleeding, 20.4 % (1309/6416 of all patients were regularly taking nonsteroidal anti-inflammatory drugs, anticoagulant therapy or antiplatelet agents in single daily doses at least. 6.3 % of patients (82/1309 with abundant hemorrhage from upper gastrointestinal tract were using oral anticoagulant therapy and had INR > 5 at admission, 25.6 % of them had INR > 10. The mortality of patients using oral anticoagulants and INR > 5 was 17.1 %.Conclusions: Upper gastrointestinal hemorrhage is a serious complication of different medications, particularly in elderly patients. Safe use of anticoagulant therapy is based on careful selection of patients and correct intake of the prescribed drugs.

Can we withdraw anticoagulation in patients with antiphospholipid syndrome after seroconvertion?

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Sciascia, S; Coloma-Bazán, E; Radin, M; Bertolaccini, M L; López-Pedrera, C; Espinosa, Gerard; Meroni, P L; Cervera, R; Cuadrado, M J

2017-11-01

The current mainstay of treatment in patients with thrombotic antiphospholipid syndrome (APS) is long-term anticoagulation, mainly with Vitamin K antagonist agents. Some recently available studies have created new ground for discussion about the possible discontinuation of anticoagulation therapy in patients with a history of thrombotic APS in whom antiphospholipid antibodies (aPL) are not detected any longer (i.e. aPL seroconversion). We report the main points discussed at the last CORA Meeting regarding the issue whether or not anticoagulation can be stopped after aPL seroconversion. In particular, we systematically reviewed the available evidence investigating the clinical outcome of APS patients with aPL seroconversion in whom anticoagulation was stopped when compared to those in whom therapy was continued regardless the aPL profile. Furthermore, the molecular basis for the aPL pathogenicity, the available evidence of non-criteria aPL and their association with thrombosis are addressed. To date, available evidence is still limited to support the indication to stop oral anticoagulation therapy in patients with a previous diagnosis of thrombotic APS who subsequently developed a negative aPL profile. The identification of the whole risk profile for cardiovascular manifestations and possibly of a second level aPL testing in selected patients with aPL might support the eventual clinical decision but further investigation is warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

A comparative assessment of efficacy of three anticoagulant rodenticides.

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Renapurkar, D M

1982-01-01

Results are presented of feeding tests carried out with three common anticoagulant rodenticides viz., coumatetralyl, fumarin and warfarin on three common species of commensal rodents i.e., Rattus rattus, Rattus norvegicus and Bandicota bengalensis. All three species of rodents were susceptible to anticoagulant rodenticides. However, the action of these compounds in B. bengalensis was comparatively slow. Coumatetralyl was found to be the most effective rodenticide followed by fumarin and warfarin. Liquid baits of these compounds are more effective in comparison to food baits.

Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial

NARCIS (Netherlands)

Moll, Etelka; Bossuyt, Patrick M. M.; Korevaar, Johanna C.; Lambalk, Cornelis B.; van der Veen, Fulco

2006-01-01

OBJECTIVE: To compare the effectiveness of clomifene citrate plus metformin and clomifene citrate plus placebo in women with newly diagnosed polycystic ovary syndrome. DESIGN: Randomised clinical trial. SETTING: Multicentre trial in 20 Dutch hospitals. PARTICIPANTS: 228 women with polycystic ovary

Acute management of stroke patients taking non-vitamin K antagonist oral anticoagulants Addressing Real-world Anticoagulant Management Issues in Stroke (ARAMIS) Registry: Design and rationale.

Science.gov (United States)

Xian, Ying; Hernandez, Adrian F; Harding, Tina; Fonarow, Gregg C; Bhatt, Deepak L; Suter, Robert E; Khan, Yosef; Schwamm, Lee H; Peterson, Eric D

2016-12-01

Non-vitamin K antagonist oral anticoagulants (NOACs, dabigatran, rivaroxaban, apixaban, and edoxaban) have been increasingly used as alternatives to warfarin for stroke prophylaxis in patients with atrial fibrillation. Yet there is substantial lack of information on how patients on NOACs are currently treated when they have an acute ischemic stroke and the best strategies for treating intracerebral hemorrhage for those on chronic anticoagulation with warfarin or a NOAC. These are critical unmet needs for real world clinical decision making in these emergent patients. The ARAMIS Registry is a multicenter cohort study of acute stroke patients who were taking chronic anticoagulation therapy prior to admission and are admitted with either an acute ischemic stroke or intracerebral hemorrhage. Built upon the existing infrastructure of American Heart Association/American Stroke Association Get With the Guidelines Stroke, the ARAMIS Registry will enroll a total of approximately 10,000 patients (5000 with acute ischemic stroke who are taking a NOAC and 5000 with anticoagulation-related intracerebral hemorrhage who are on warfarin or a NOAC). The primary goals of the ARAMIS Registry are to provide a comprehensive picture of current treatment patterns and outcomes of acute ischemic stroke patients on NOACs, as well as anticoagulation-related intracerebral hemorrhage in patients on either warfarin or NOACs. Beyond characterizing the index hospitalization, up to 2500 patients (1250 ischemic stroke and 1250 intracerebral hemorrhage) who survive to discharge will be enrolled in an optional follow-up sub-study and interviewed at 3 and 6 months after discharge to assess longitudinal medication use, downstream care, functional status, and patient-reported outcomes. The ARAMIS Registry will document the current state of management of NOAC treated patients with acute ischemic stroke as well as contemporary care and outcome of anticoagulation-related intracerebral hemorrhage. These

Abnormal uterine bleeding in women receiving direct oral anticoagulants for the treatment of venous thromboembolism.

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Godin, Richard; Marcoux, Violaine; Tagalakis, Vicky

2017-08-01

Abnormal uterine bleeding (AUB) is a common complication of anticoagulant therapy in premenopausal women affected with acute venous thromboembolism. AUB impacts quality of life, and can lead to premature cessation of anticoagulation. There is increasing data to suggest that the direct oral anticoagulants when used for the treatment of venous thromboembolism differ in their menstrual bleeding profile. This article aims to review the existing literature regarding the association between AUB and the direct oral anticoagulants and make practical recommendations. Copyright © 2017 Elsevier Inc. All rights reserved.

Management of Periprocedural Anticoagulation: A Survey of Contemporary Practice.

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Flaker, Greg C; Theriot, Paul; Binder, Lea G; Dobesh, Paul P; Cuker, Adam; Doherty, John U

2016-07-12

Interruption of oral anticoagulation (AC) for surgery or an invasive procedure is a complicated process. Practice guidelines provide only general recommendations, and care of such patients occurs across multiple specialties. The availability of direct oral anticoagulants further complicates decision making and guidance here is limited. To evaluate current practice patterns in the United States for bridging AC, a survey was developed by the American College of Cardiology Anticoagulation Work Group. The goal of the survey was to assess how general and subspecialty cardiologists, internists, gastroenterologists, and orthopedic surgeons currently manage patients who receive AC and undergo surgery or an invasive procedure. The survey was completed by 945 physicians involved in the periprocedural management of AC. The results provide a template for educational and research projects geared toward the development of clinical pathways and point-of-care tools to improve this area of health care. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

SILDENAFIL CITRATE INDUCED RETINAL TOXICITY-ELECTRORETINOGRAM, OPTICAL COHERENCE TOMOGRAPHY, AND ADAPTIVE OPTICS FINDINGS.

Science.gov (United States)

Yanoga, Fatoumata; Gentile, Ronald C; Chui, Toco Y P; Freund, K Bailey; Fell, Millie; Dolz-Marco, Rosa; Rosen, Richard B

2018-02-27

To report a case of persistent retinal toxicity associated with a high dose of sildenafil citrate intake. Single retrospective case report. A 31-year-old white man with no medical history presented with complaints of bilateral multicolored photopsias and erythropsia (red-tinted vision), shortly after taking sildenafil citrate-purchased through the internet. Patient was found to have cone photoreceptor damage, demonstrated using electroretinogram, optical coherence tomography, and adaptive optics imaging. The patient's symptoms and the photoreceptor structural changes persisted for several months. Sildenafil citrate is a widely used erectile dysfunction medication that is typically associated with transient visual symptoms in normal dosage. At high dosage, sildenafil citrate can lead to persistent retinal toxicity in certain individuals.

Use of antifibrinolytic mouthwash solution in anticoagulated oral surgery patients

OpenAIRE

Dimova, Cena; Evrosimovska, Biljana; Papakoca, Kiro; Georgiev, Zlatko; Angelovska, Bistra; Ristoska, Sonja

2012-01-01

Introduction:The ordinary treatment of anticoagulated patients includes the interruption of anticoagulant therapy for oral surgery interventions to prevent hemorrhage. However, this practice may logically increase the risk of a potentially life-threatening thromboembolism, so this issue is still controversial. The aim of the study was to evaluate the antifibrinolitic mouthwash solution (tranexamic acid) as a local haemostatic modality after oral surgery interventions. Methods:To realize the a...

Studies on sildenafil citrate (Viagra) interaction with DNA using electrochemical DNA biosensor.

Science.gov (United States)

Rauf, Sakandar; Nawaz, Haq; Akhtar, Kalsoom; Ghauri, Muhammad A; Khalid, Ahmad M

2007-05-15

The interaction of sildenafil citrate (Viagra) with DNA was studied by using an electrochemical DNA biosensor. The binding mechanism of sildenafil citrate was elucidated by using constant current potentiometry and differential pulse voltammetry at DNA-modified glassy carbon electrode. The decrease in the guanine oxidation peak area or peak current was used as an indicator for the interaction in 0.2M acetate buffer (pH 5). The binding constant (K) values obtained were 2.01+/-0.05 x 10(5) and 1.97+/-0.01 x 10(5)M(-1) with constant current potentiometry and differential pulse voltammetry, respectively. A linear dependence of the guanine peak area or peak current was observed within the range of 1-40 microM sildenafil citrate with slope=-2.74 x 10(-4)s/microM, r=0.989 and slope=-2.78 x 10(-3)microA/microM, r=0.995 by using constant current potentiometry and differential pulse voltammetry, respectively. Additionally, binding constant values for sildenafil citrate-DNA interaction were determined for the pH range of 4-8 and in biological fluids (serum and urine) at pH 5. The influence of sodium and calcium ions was also studied to elucidate the mechanism of sildenafil citrate-DNA interaction under different solution conditions. The present study may prove to be helpful in extending our understanding of the anticancer activity of sildenafil citrate from cellular to DNA level.

76 FR 19997 - Determination That FENTORA (Fentanyl Citrate) Buccal Tablet, 300 Micrograms, Was Not Withdrawn...

Science.gov (United States)

2011-04-11

...] Determination That FENTORA (Fentanyl Citrate) Buccal Tablet, 300 Micrograms, Was Not Withdrawn From Sale for... Food and Drug Administration (FDA) has determined that FENTORA (fentanyl citrate) buccal tablet, 300... allow FDA to approve abbreviated new drug applications (ANDAs) for fentanyl citrate buccal tablet, 300...

Hemorrhagic transformation in patients with acute ischaemic stroke and an indication for anticoagulation.

Science.gov (United States)

Marsh, E B; Llinas, R H; Hillis, A E; Gottesman, R F

2013-06-01

Intracerebral hemorrhage (ICH) can occur in patients following acute ischaemic stroke in the form of hemorrhagic transformation, and results in significant long-term morbidity and mortality. Anticoagulation theoretically increases risk. We evaluated stroke patients with an indication for anticoagulation to determine the factors associated with hemorrhagic transformation. Three-hundred and forty-five patients with ICD-9 codes indicating: (i) acute ischaemic stroke; and (ii) an indication for anticoagulation were screened. One-hundred and twenty-three met inclusion criteria. Data were collected retrospectively. Neuroimaging was reviewed for infarct volume and evidence of ICH. Hemorrhages were classified as: hemorrhagic conversion (petechiae) versus intracerebral hematoma (a space occupying lesion); symptomatic versus asymptomatic. Using multivariable logistic regression, we determined the hypothesized factors associated with intracerebral bleeding. Age [odds ratio (OR) = 1.50 per 10-year increment, 95% confidence interval (CI) 1.07-2.08], infarct volume (OR = 1.10 per 10 ccs, 95% CI 1.06-1.18) and worsening category of renal impairment by estimated glomerular filtration rate (eGFR; OR = 1.95, 95% CI 1.04-3.66) were predictors of hemorrhagic transformation. Ninety- nine out of 123 patients were anticoagulated. Hemorrhage rates of patients on and off anticoagulation did not differ (25.3% vs. 20.8%; P = 0.79); however, all intracerebral hematomas (n = 7) and symptomatic bleeds (n = 8) occurred in the anticoagulated group. The risk of hemorrhagic transformation in patients with acute ischaemic stroke and an indication for anticoagulation is multifactorial, and most closely associated with an individual's age, infarct volume and eGFR. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

Nitrate Protects Cucumber Plants Against Fusarium oxysporum by Regulating Citrate Exudation.

Science.gov (United States)

Wang, Min; Sun, Yuming; Gu, Zechen; Wang, Ruirui; Sun, Guomei; Zhu, Chen; Guo, Shiwei; Shen, Qirong

2016-09-01

Fusarium wilt causes severe yield losses in cash crops. Nitrogen plays a critical role in the management of plant disease; however, the regulating mechanism is poorly understood. Using biochemical, physiological, bioinformatic and transcriptome approaches, we analyzed how nitrogen forms regulate the interactions between cucumber plants and Fusarium oxysporum f. sp. cucumerinum (FOC). Nitrate significantly suppressed Fusarium wilt compared with ammonium in both pot and hydroponic experiments. Fewer FOC colonized the roots and stems under nitrate compared with ammonium supply. Cucumber grown with nitrate accumulated less fusaric acid (FA) after FOC infection and exhibited increased tolerance to chemical FA by decreasing FA absorption and transportation in shoots. A lower citrate concentration was observed in nitrate-grown cucumbers, which was associated with lower MATE (multidrug and toxin compound extrusion) family gene and citrate synthase (CS) gene expression, as well as lower CS activity. Citrate enhanced FOC spore germination and infection, and increased disease incidence and the FOC population in ammonium-treated plants. Our study provides evidence that nitrate protects cucumber plants against F. oxysporum by decreasing root citrate exudation and FOC infection. Citrate exudation is essential for regulating disease development of Fusarium wilt in cucumber plants. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Prediction of the risk of bleeding during anticoagulant treatment for venous thromboembolism

NARCIS (Netherlands)

Kuijer, P. M.; Hutten, B. A.; Prins, M. H.; Büller, H. R.

1999-01-01

OBJECTIVES: To construct and validate the bleeding risk prediction score, which is based on variables identified in the literature that can be easily obtained before the institution of anticoagulant therapy, in a large independent cohort of patients who were treated with anticoagulant therapy for

Anticoagulant rodenticide toxicity to non-target wildlife under controlled exposure conditions

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Rattner, Barnett A.; Mastrota, F. Nicholas; van den Brink, Nico; Elliott, J.; Shore, R.; Rattner, B.

2018-01-01

Much of our understanding of anticoagulant rodenticide toxicity to non-target wildlife has been derived from molecular through whole animal research and registration studies in domesticated birds and mammals, and to a lesser degree from trials with captive wildlife. Using these data, an adverse outcome pathway identifying molecular initiating and anchoring events (inhibition of vitamin K epoxide reductase, failure to activate clotting factors), and established and plausible linkages (coagulopathy, hemorrhage, anemia, reduced fitness) associated with toxicity, is presented. Controlled exposure studies have demonstrated that second-generation anticoagulant rodenticides (e.g., brodifacoum) are more toxic than first- and intermediate-generation compounds (e.g., warfarin, diphacinone), however the difference in potency is diminished when first- and intermediate-generation compounds are administered on multiple days. Differences in species sensitivity are inconsistent among compounds. Numerous studies have compared mortality rate of predators fed prey or tissue containing anticoagulant rodenticides. In secondary exposure studies in birds, brodifacoum appears to pose the greatest risk, with bromadiolone, difenacoum, flocoumafen and difethialone being less hazardous than brodifacoum, and warfarin, coumatetralyl, coumafuryl, chlorophacinone and diphacinone being even less hazardous. In contrast, substantial mortality was noted in secondary exposure studies in mammals ingesting prey or tissue diets containing either second- or intermediate-generation compounds. Sublethal responses (e.g., prolonged clotting time, reduced hematocrit and anemia) have been used to study the sequelae of anticoagulant intoxication, and to some degree in the establishment of toxicity thresholds or toxicity reference values. Surprisingly few studies have undertaken histopathological evaluations to identify cellular lesions and hemorrhage associated with anticoagulant rodenticide exposure in non

Effect of post-filter anticoagulation on mortality in patients with cancer-associated pulmonary embolism.

Science.gov (United States)

Kang, Jieun; Kim, Seon Ok; Oh, Yeon-Mok; Lee, Sang-Do; Lee, Jae Seung

2018-05-17

Malignancy is associated with an increased risk of venous thromboembolism. Inferior vena cava filters are a viable alternative when anticoagulation is infeasible because of the risk of bleeding. Although the current guidelines recommend that all patients with a vena cava filter be treated with anticoagulation treatment when the risk of bleeding is reduced, studies concerning the role of concomitant anticoagulation after vena cava filter insertion in high-risk patients are scarce. Since many cancer patients suffer from a high risk of hemorrhagic complications, we aimed to determine the effect of post-filter anticoagulation on mortality in patients with a malignant solid tumor. A retrospective cohort study of patients with pulmonary embolism was performed between January 2010 and May 2016. Patients with a solid tumor and vena cava filter inserted because of pulmonary embolism were included. Using Cox proportional hazards model, the prognostic effect of clinical variables was analyzed. A total of 180 patients were analyzed, with 143 patients receiving and 37 patients not receiving post-filter anticoagulation treatment. Mortality was not significantly different between the two groups. The presence of metastatic cancer and that of pancreatobiliary cancer were significant risk factors for mortality. However, post-filter anticoagulation did not show significant effect on mortality regardless of the stage of cancer. In patients with cancer-associated pulmonary embolism, the effect of post-filter anticoagulation on mortality may not be critical, especially in patients with a short life expectancy.

The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines-Anticoagulation During Cardiopulmonary Bypass.

Science.gov (United States)

Shore-Lesserson, Linda; Baker, Robert A; Ferraris, Victor A; Greilich, Philip E; Fitzgerald, David; Roman, Philip; Hammon, John W

2018-02-01

Despite more than a half century of "safe" cardiopulmonary bypass (CPB), the evidence base surrounding the conduct of anticoagulation therapy for CPB has not been organized into a succinct guideline. For this and other reasons, there is enormous practice variability relating to the use and dosing of heparin, monitoring heparin anticoagulation, reversal of anticoagulation, and the use of alternative anticoagulants. To address this and other gaps, The Society of Thoracic Surgeons, the Society of Cardiovascular Anesthesiologists, and the American Society of Extracorporeal Technology developed an Evidence Based Workgroup. This was a group of interdisciplinary professionals gathered to summarize the evidence and create practice recommendations for various aspects of CPB. To date, anticoagulation practices in CPB have not been standardized in accordance with the evidence base. This clinical practice guideline was written with the intent to fill the evidence gap and to establish best practices in anticoagulation therapy for CPB using the available evidence. To identify relevant evidence, a systematic review was outlined and literature searches were conducted in PubMed using standardized medical subject heading (MeSH) terms from the National Library of Medicine list of search terms. Search dates were inclusive of January 2000 to December 2015. The search yielded 833 abstracts, which were reviewed by two independent reviewers. Once accepted into the full manuscript review stage, two members of the writing group evaluated each of 286 full papers for inclusion eligibility into the guideline document. Ninety-six manuscripts were included in the final review. In addition, 17 manuscripts published before 2000 were included to provide method, context, or additional supporting evidence for the recommendations as these papers were considered sentinel publications. Members of the writing group wrote and developed recommendations based on review of the articles obtained and achieved

Laparoscopic electrocautery of the ovaries versus recombinant FSH in clomiphene citrate-resistant polycystic ovary syndrome. Impact on women's health-related quality of life

NARCIS (Netherlands)

van Wely, M.; Bayram, N.; Bossuyt, P. M. M.; van der Veen, F.

2004-01-01

BACKGROUND: Ovulation induction with gonadotrophins is the standard treatment strategy for women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). Laparoscopic electrocautery of the ovaries is an alternative treatment modality, leading to a comparable cumulative pregnancy

Electrospray ionization of uranyl-citrate complexes

Science.gov (United States)

Somogyi, Árpád; Pasilis, Sofie P.; Pemberton, Jeanne E.

2007-09-01

Results presented here demonstrate the usefulness of electrospray ionization and gas-phase ion-molecule reactions to predict structural and electronic differences in complex inorganic ions. Electrospray ionization of uranyl citrate solutions generates positively and negatively charged ions that participate in further ion-molecule reactions in 3D ion trap and FT-ICR mass analyzers. Most ions observed are derived from the major solution uranyl-citrate complexes and involve species of {(UO2)2Cit2}2-, (UO2)3Cit2, and {(UO2)3Cit3}3-, where Cit indicates the citrate trianion, C6H5O73-. In a 3D ion trap operated at relatively high pressure, complex adducts containing solvent molecules, alkali and ammonium cations, and nitrate or chloride anions are dominant, and proton/alkali cation (Na+, K+) exchange is observed for up to six exchangeable protons in an excess of alkali cations. Adduct formation in a FT-ICR cell that is operated at lower pressures is less dominant, and direct detection of positive and negative ions of the major solution complexes is possible. Multiply charged ions are also detected, suggesting the presence of uranium in different oxidation states. Changes in uranium oxidation state are detected by He-CID and SORI-CID fragmentation, and certain fragments undergo association reactions in trapping analyzers, forming "exotic" species such as [(UO2)4O3]-, [(UO2)4O4]-, and [(UO2)4O5]-. Ion-molecule reactions with D2O in the FT-ICR cell indicate substantial differences in H/D exchange rate and D2O accommodation for different ion structures and charge states. Most notably, the positively charged ions [H2(UO2)2Cit2(H)]+ and [(UO2)2(Cit)]+ accommodate two and three D2O molecules, respectively, which reflects well the structural differences, i.e., tighter uranyl-citrate coordination in the former ion than in the latter. The corresponding negatively charged ions accommodate zero or two D2O molecules, which can be rationalized using suggested solution phase structures

Direct anticoagulants and nursing: an approach from patient's safety.

Science.gov (United States)

Romero Ruiz, Adolfo; Romero-Arana, Adolfo; Gómez-Salgado, Juan

In recent years, a new line of treatment for the prevention of stroke in non-valvular atrial fibrillation, the so-called direct anticoagulants or new anticoagulants has appeared. The proper management and follow-up of these patients is essential to minimize their side effects and ensure patient safety. In this article, a description of these drugs is given, analyzing their characteristics, functioning and interactions together with the most habitual nursing interventions, as well as a reflection on the implications for the practice. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Isolation and characterization of anticoagulant compound from ...

African Journals Online (AJOL)

GIS

2013-10-02

Oct 2, 2013 ... The structural characterization of anticoagulant GAG was analyzed by Fourier transform infrared ... for pharmaceutical use are currently not available. However ... methods and sold live in the market for human consump- tion.

Anticoagulation in adults with congenital heart disease

DEFF Research Database (Denmark)

Jensen, A S; Idorn, L; Nørager, B

2015-01-01

Adults with congenital heart disease are a growing population. One of the major challenges in the care of these patients is to prevent thromboembolic episodes. Despite relative young age and no typical cardiovascular risk factors, this cohort has a high prevalence of thrombotic events....... Furthermore, there is a lack of scientific evidence regarding how to prevent thromboembolic events with anticoagulation in adults with congenital heart disease. The aim of this paper is to review the current literature pertaining to anticoagulation in adults with congenital heart disease and hence enable....... It is difficult to use treatment algorithms from the general adult population with acquired heart disease in this heterogeneous population due to special conditions such as myocardial scarring after previous surgery, atypical atrial flutter, prothrombotic conditions and the presence of interatrial shunts...

Control of anticoagulant therapy and quality of life of patients with atrial fibrillation (review

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Shvarts Y.G.

2012-06-01

Full Text Available The review presents the published data on the relevance of the problem of thromboembolic complications in atrial fibrillation, the peculiarities of anticoagulant therapy for this disease. The relationship of clinical characteristics of patients with anticoagulant dose adjustment algorithms has been described. The problem of ethical issues of out of clinical trials patients and the dynamics of their quality of life against the background of long-term use of anticoagulant have been considered.

Anticoagulant Treatment of Deep Vein Thrombosis and Pulmonary Embolism: The Present State of the Art.

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Thaler, Johannes; Pabinger, Ingrid; Ay, Cihan

2015-01-01

Venous thromboembolism (VTE), a disease entity comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a frequent and potentially life-threatening event. To date different agents are available for the effective treatment of acute VTE and the prevention of recurrence. For several years, the standard of care was the subcutaneous application of a low molecular weight heparin (LMWH) or fondaparinux, followed by a vitamin K antagonist (VKA). The so-called direct oral anticoagulants (DOAC) were introduced rather recently in clinical practice for the treatment of VTE. DOAC seem to have a favorable risk-benefit profile compared to VKA. Moreover, DOAC significantly simplify VTE treatment because they are administered in fixed doses and no routine monitoring is needed. Patients with objectively diagnosed DVT or PE should receive therapeutic anticoagulation for a minimum of 3 months. Whether a patient ought to receive extended treatment needs to be evaluated on an individual basis, depending mainly on risk factors determined by characteristics of the thrombotic event and patient-related factors. In specific patient groups (e.g., pregnant women, cancer patients, and elderly patients), treatment of VTE is more challenging than that in the general population and additional issues need to be considered in those patients. The aim of this review is to give an overview of the currently available treatment modalities of acute VTE and secondary prophylaxis. In particular, specific aspects regarding the initiation of VTE treatment, duration of anticoagulation, and specific patient groups will be discussed.

Study on the Antimicrobial Properties of Citrate-Based Biodegradable Polymers

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Lee-Chun eSu

2014-07-01

Full Text Available Citrate-based polymers possess unique advantages for various biomedical applications since citric acid is a natural metabolism product, which is biocompatible and antimicrobial. In polymer synthesis, citric acid also provides multiple functional groups to control the crosslinking of polymers and active binding sites for further conjugation of biomolecules. Our group recently developed a number of citrate-based polymers for various biomedical applications by taking advantage of their controllable chemical, mechanical, and biological characteristics. In this study, various citric acid derived biodegradable polymers were synthesized and investigated for their physicochemical and antimicrobial properties. Results indicate that citric acid derived polymers reduced bacterial proliferation to different degrees based on their chemical composition. Among the studied polymers, poly(octamethylene citrate (POC showed approximately 70-80% suppression to microbe proliferation, owing to its relatively higher ratio of citric acid contents. Crosslinked urethane-doped polyester elastomers (CUPEs and biodegradable photoluminescent polymers (BPLPs also exhibited significant bacteria reduction of ~20% and ~50% for Staphylococcus aureus and Escherichia coli, respectively. Thus, the intrinsic antibacterial properties in citrate-based polymers enable them to inhibit bacteria growth without incorporation of antibiotics, silver nanoparticles, and other traditional bacteria-killing agents suggesting that they are unique beneficial materials for wound dressing, tissue engineering, and other potential medical applications where antimicrobial property is desired.

Does novel oral anticoagulant improve anticoagulation for non-valvular atrial fibrillation associated stroke: An inpatient registration study in Shanghai

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Feng-Di Liu

2015-12-01

Full Text Available Abstracts: Objective: To summarize the use rate, safety, efficacy of antithrombotics in stroke/transient ischemic attack (TIA prevention, and reasons for not using dabigatran etexilate (DE in Shanghai, China. Methods: Non-valvular atrial fibrillation (NVAF-associated stroke patients were prospectively registered as an electronic database. Use rate of antithrombotics and reasons for not using DE were extracted during follow-up. Patients' baseline characteristics, recurrent ischemic stroke/TIA events and bleeding complications were analyzed. Patients: From April 2012 to August 2014, 110 inpatients with NVAF-associated stroke were studied in our hospital. NVAF was diagnosed by 12-lead electrocardiogram, 24 h Holter and echocardiography. Results: Before introduction of DE (April 2013, use rates of warfarin and antiplatelets were 28.9% (11/38 and 60.5% (23/38 respectively; after that, use rates of warfarin, DE, and antiplatelets were 20.8% (15/72, 12.5% (9/72, and 43.1% (31/72. The DE did not improve use of anticoagulants (P = 0.639. There were 19 (17.3% recurrent ischemic stroke events up to October 2015; two (9.5% in the non-user group, 10 (18.5% in the antiplatelet group, and seven (20.0% in the anticoagulants group (P = 0.570. Furthermore, recurrence rates were similar between the DE group (20.0% and the Warfarin group (20.0%, P = 1.000. The most common reason for not using DE was financial concerns (61.0%, followed by inconvenience to purchase (14.0% and hemorrhage concerns (11.0%. Two patients using warfarin found fecal occult blood so they stopped warfarin and began to use antiplatelet drugs. No bleeding event occurred in the other groups. Only one patient had side effects (dyspepsia and gastroesophageal reflux from DE. Conclusion: The use rate of either DE or warfarin in Shanghai was low; DE had not improved anticoagulation therapy for NVAF patients in Shanghai mainly because DE had not been covered by health insurance. Keywords

Inhibition of citric acid accumulation by manganese ions in Aspergillus niger mutants with reduced citrate control of phosphofructokinase

Energy Technology Data Exchange (ETDEWEB)

Schreferl, G.; Kubicek, C.P.; Roehr, M.

1986-03-01

Mutant strains of Aspergillus niger with reduced citrate control of carbohydrate catabolism (cic mutants) grow faster than the parent strain on media containing 5% (wt/vol) citrate. The mutants tolerated a higher intracellular citrate concentration than the parent strain. One mutant (cic-7/3) contained phosphofructokinase activity significantly less sensitive towards citrate than the enzyme from the parent strain. When this mutant was grown under citrate accumulating conditions, acidogenesis was far less sensitive to inhibition by Mn/sup 2 +/ than in the parent strain. Some of the cic mutants also showed altered citrate inhibition of NADP-specific isocitrate dehydrogenase.

Bio-inspired citrate functionalized apatite coating on rapid prototyped titanium scaffold

Energy Technology Data Exchange (ETDEWEB)

Yu, Peng [National engineering research center for tissue restoration and reconstruction, South China University of Technology, Guangzhou 510641 (China); Lu, Fang [School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006 (China); Zhu, Wenjun [Department of Prosthodontics, Guanghua School of Stomatology, Guang Dong Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Wang, Di [National engineering research center for tissue restoration and reconstruction, South China University of Technology, Guangzhou 510641 (China); Zhu, Xiaojing [Department of Prosthodontics, Guanghua School of Stomatology, Guang Dong Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Tan, Guoxin, E-mail: tanguoxin@126.com [Institute of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006 (China); Wang, Xiaolan [National engineering research center for tissue restoration and reconstruction, South China University of Technology, Guangzhou 510641 (China); Zhang, Yu; Li, Lihua [General Hospital of Guangzhou Military Command of PLA, Guangzhou 510010 (China); Ning, Chengyun, E-mail: imcyning@scut.edu.cn [National engineering research center for tissue restoration and reconstruction, South China University of Technology, Guangzhou 510641 (China)

2014-09-15

Highlights: • Designed and reproducible porous titanium scaffolds were produced. • Hydrophilic nanoporous film was built on scaffold. • Apatite coating was deposited on scaffold under the modulation of citrate ions. • Citrate ions could affect CO{sub 3}{sup 2−} incorporation in apatite coatings. - Abstract: Scaffold functionalized with appropriate osteogenic coatings can significantly improve implant-bone response. In this study, with designed model and optimized manufacture parameters, reproducible and precise titanium scaffolds were produced. Reconstructed three-dimensional image and sectional structure of the scaffold were examined by micro-computed tomography and relative software. Alkali treatment was carried out on these manufactured porous scaffolds to produce nanoporous hydrophilic film. After 6 days deposition in simulated body fluid (SBF) containing sodium citrate (SC-SBF), plate-like amorphous calcium phosphate (ACP) coating was deposited on scaffold surface. Ultrasonication tests qualitatively indicated an enhanced adhesion force of apatite coatings deposited in SC-SBF compared to that deposited in SBF. And the effect of citrate ions on the CO{sub 3}{sup 2−} incorporation rate in apatite coating was quantitatively examined by bending vibration of CO{sub 3}{sup 2−} at ∼874 cm{sup −1}. Results indicated the highest carbonate content was obtained at the citrate ion concentration of 6 × 10{sup −5} mol/L in SC-SBF. These three-dimensional porous titanium-apatite hybrid scaffolds are expected to find application in bone tissue regeneration.

Spontaneous pharyngo-laryngeal hematoma and anticoagulation. A case report

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Marleny CASASOLA-GIRÓN

2016-03-01

Full Text Available Introduction and Objective: Spontaneous pharyngeal-laryngeal hematoma shows the importance of a complete ENT examination in the face of symptoms of banal appearance and a correct history that, in the case reported, unveiled the therapeutic use of anticoagulants. Case description: A 55 year old woman comes to emergency because of unexplained dysphagia. The inspection shows the presence of a hematoma in the pharyngeal-laryngeal region that, after the anticoagulant therapy was reversed, evolved favorably with conservative treatment. Discussion: In this case, apart from medical management performed by the hematology department, we focus our therapeutic approach in the protection of the airway and the prevention of a possible massive bleeding. Determining which patients require endotracheal intubation or tracheostomy and hemostatic surgery is the key to treatment. Conclusions: The anticoagulant therapy involves several complications that ENT specialists must consider in the face of clinical symptoms of dysphagia, dysphonia, dyspnea or signs of bleeding and they must know the possibilities of performance depending on the severity of each case.

Anticoagulant and antimicrobial finishing of non-woven polypropylene textiles

International Nuclear Information System (INIS)

Degoutin, S; Jimenez, M; Casetta, M; Bellayer, S; Chai, F; Blanchemain, N; Neut, C; Kacem, I; Traisnel, M; Martel, B

2012-01-01

The aim of this work is to prepare non-woven polypropylene (PP) textile functionalized with bioactive molecules in order to improve its anticoagulation and antibacterial properties. This paper describes the optimization of the grafting process of acrylic acid (AA) on low-pressure cold-plasma pre-activated PP, the characterization of the modified substrates and the effect of these modifications on the in vitro biological response towards cells. Then, the immobilization of gentamicin (aminoglycoside antibiotic) and heparin (anticoagulation agent) has been carried out on the grafted samples by either ionic interactions or covalent linkages. Their bioactivity has been investigated and related to the nature of their interactions with the substrate. For gentamicin-immobilized AA-grafted samples, an inhibition radius and a reduction of 99% of the adhesion of Escherichia coli have been observed when gentamicin was linked by ionic interactions, allowing the release of the antibiotic. By contrast, for heparin-immobilized AA-grafted PP samples, a strong increase of the anticoagulant effect up to 35 min has been highlighted when heparin was covalently bonded on the substrate, by contact with the blood drop. (paper)

A Process-Based Model of TCA Cycle Functioning to Analyze Citrate Accumulation in Pre- and Post-Harvest Fruits.

Science.gov (United States)

Etienne, Audrey; Génard, Michel; Bugaud, Christophe

2015-01-01

Citrate is one of the most important organic acids in many fruits and its concentration plays a critical role in organoleptic properties. The regulation of citrate accumulation throughout fruit development, and the origins of the phenotypic variability of the citrate concentration within fruit species remain to be clarified. In the present study, we developed a process-based model of citrate accumulation based on a simplified representation of the TCA cycle to predict citrate concentration in fruit pulp during the pre- and post-harvest stages. Banana fruit was taken as a reference because it has the particularity of having post-harvest ripening, during which citrate concentration undergoes substantial changes. The model was calibrated and validated on the two stages, using data sets from three contrasting cultivars in terms of citrate accumulation, and incorporated different fruit load, potassium supply, and harvest dates. The model predicted the pre and post-harvest dynamics of citrate concentration with fairly good accuracy for the three cultivars. The model suggested major differences in TCA cycle functioning among cultivars during post-harvest ripening of banana, and pointed to a potential role for NAD-malic enzyme and mitochondrial malate carriers in the genotypic variability of citrate concentration. The sensitivity of citrate accumulation to growth parameters and temperature differed among cultivars during post-harvest ripening. Finally, the model can be used as a conceptual basis to study citrate accumulation in fleshy fruits and may be a powerful tool to improve our understanding of fruit acidity.

A novel prothrombin time method to measure all non-vitamin K-dependent oral anticoagulants (NOACs)

Science.gov (United States)

Lindahl, Tomas L.; Arbring, Kerstin; Wallstedt, Maria; Rånby, Mats

2017-01-01

Background There is a clinical need for point-of-care (POC) methods for non-vitamin K-dependent oral anticoagulants (NOACs). We modified a routine POC procedure: Zafena’s Simple Simon™ PT-INR, a room-temperature, wet-chemistry prothrombin time method of the Owren-type. Methods To either increase or decrease NOAC interference, two assay variants were devised by replacing the standard 10 µL end-to-end capillary used to add the citrated plasma sample to 200 µL of prothrombin time (PT) reagent by either a 20 µL or a 5 µL capillary. All assay variants were calibrated to show correct PT results in plasma samples from healthy and warfarin-treated persons. Results For plasmas spiked with dabigatran, apixaban, or rivaroxaban, the 20 µL variant showed markedly higher PT results than the 5 µL. The effects were even more pronounced at room temperature than at +37 °C. In plasmas from patients treated with NOACs (n = 30 for each) there was a strong correlation between the PT results and the concentration of NOACs as determined by the central hospital laboratory. For the 20 µL variant the PT response of linear correlation coefficient averaged 0.90. The PT range was INR 1.1–2.1 for dabigatran and apixaban, and INR 1.1–5.0 for rivaroxaban. Using an INR ratio between the 20 µL and 5 µL variants (PTr20/5) made the NOAC assay more robust and independent of the patient sample INR value in the absence of NOAC. Detection limits were 80 µg/L for apixaban, 60 µg/L for dabigatran, and 20 µg/L for rivaroxaban. Conclusions A wet-chemistry POC PT procedure was modified to measure the concentrations of three NOACs using a single reagent. PMID:28891412

A Role for the Krebs Cycle Intermediate Citrate in Metabolic Reprogramming in Innate Immunity and Inflammation

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Niamh C. Williams

2018-02-01

Full Text Available Metabolism in immune cells is no longer thought of as merely a process for adenosine triphosphate (ATP production, biosynthesis, and catabolism. The reprogramming of metabolic pathways upon activation is also for the production of metabolites that can act as immune signaling molecules. Activated dendritic cells (DCs and macrophages have an altered Krebs cycle, one consequence of which is the accumulation of both citrate and succinate. Citrate is exported from the mitochondria via the mitochondrial citrate- carrier. Cytosolic metabolism of citrate to acetyl-coenzyme A (acetyl-CoA is important for both fatty-acid synthesis and protein acetylation, both of which have been linked to macrophage and DC activation. Citrate-derived itaconate has a direct antibacterial effect and also has been shown to act as an anti-inflammatory agent, inhibiting succinate dehydrogenase. These findings identify citrate as an important metabolite for macrophage and DC effector function.

Combined oral administration of bovine collagen peptides with calcium citrate inhibits bone loss in ovariectomized rats.

Science.gov (United States)

Liu, JunLi; Wang, YiHu; Song, ShuJun; Wang, XiJie; Qin, YaYa; Si, ShaoYan; Guo, YanChuan

2015-01-01

Collagen peptides (CPs) and calcium citrate are commonly used as bone health supplements for treating osteoporosis. However, it remains unknown whether the combination of oral bovine CPs with calcium citrate is more effective than administration of either agent alone. Forty 12-week-old Sprague-Dawley rats were randomly divided into five groups (n = 8) for once-daily intragastric administration of different treatments for 3 months at 3 months after ovariectomy (OVX) as follows: sham + vehicle; OVX + vehicle; OVX + 750 mg/kg CP; OVX + CP-calcium citrate (75 mg/kg); OVX + calcium citrate (75 mg/kg). After euthanasia, the femurs were removed and analyzed by dual energy X-ray absorptiometry and micro-computed tomography, and serum samples were analyzed for bone metabolic markers. OVX rats supplemented with CPs or CP-calcium citrate showed osteoprotective effects, with reductions in the OVX-induced decreases in their femoral bone mineral density. Moreover, CP-calcium citrate prevented trabecular bone loss, improved the microarchitecture of the distal femur, and significantly inhibited bone loss with increased bone volume, connectivity density, and trabecular number compared with OVX control rats. CP or CP-calcium citrate administration significantly increased serum procollagen type I N-terminal propeptide levels and reduced serum bone-specific alkaline phosphatase, osteocalcin, and C-telopeptide of type I collagen levels. Our data indicate that combined oral administration of bovine CPs with calcium citrate inhibits bone loss in OVX rats. The present findings suggest that combined oral administration of bovine CPs with calcium citrate is a promising alternative for reducing bone loss in osteopenic postmenopausal women.

Combined oral administration of bovine collagen peptides with calcium citrate inhibits bone loss in ovariectomized rats.

Directory of Open Access Journals (Sweden)

JunLi Liu

Full Text Available Collagen peptides (CPs and calcium citrate are commonly used as bone health supplements for treating osteoporosis. However, it remains unknown whether the combination of oral bovine CPs with calcium citrate is more effective than administration of either agent alone.Forty 12-week-old Sprague-Dawley rats were randomly divided into five groups (n = 8 for once-daily intragastric administration of different treatments for 3 months at 3 months after ovariectomy (OVX as follows: sham + vehicle; OVX + vehicle; OVX + 750 mg/kg CP; OVX + CP-calcium citrate (75 mg/kg; OVX + calcium citrate (75 mg/kg. After euthanasia, the femurs were removed and analyzed by dual energy X-ray absorptiometry and micro-computed tomography, and serum samples were analyzed for bone metabolic markers.OVX rats supplemented with CPs or CP-calcium citrate showed osteoprotective effects, with reductions in the OVX-induced decreases in their femoral bone mineral density. Moreover, CP-calcium citrate prevented trabecular bone loss, improved the microarchitecture of the distal femur, and significantly inhibited bone loss with increased bone volume, connectivity density, and trabecular number compared with OVX control rats. CP or CP-calcium citrate administration significantly increased serum procollagen type I N-terminal propeptide levels and reduced serum bone-specific alkaline phosphatase, osteocalcin, and C-telopeptide of type I collagen levels.Our data indicate that combined oral administration of bovine CPs with calcium citrate inhibits bone loss in OVX rats. The present findings suggest that combined oral administration of bovine CPs with calcium citrate is a promising alternative for reducing bone loss in osteopenic postmenopausal women.

A light-up fluorescent probe for citrate detection based on bispyridinum amides with aggregation-induced emission feature.

Science.gov (United States)

Liu, Chenchen; Hang, Yandi; Jiang, Tao; Yang, Ji; Zhang, Xiao; Hua, Jianli

2018-02-01

Citrate is an important intermediate in the citric acid cycle, a vital metabolic pathway for animals, plants and bacteria. It is of great significance to detect its levels in human beings because several diseases may cause the abnormal of citrate. In this paper, a new turn-on fluorescent sensor (TPE-Py) using the classic tetraphenylethylene (TPE) as the aggregation-induced emission (AIE) fluorophore and bipyridinium-based amides as the recognition receptor has been synthesized for the detection of citrate. The probe exhibits good selectivity and sensitivity to citrate with a relatively low detection limit (1.0 × 10 -7 M). The enhancement of the fluorescence is relevant with the AIE property based on the complexation of TPE-Py with citrate caused by the hydrogen bonding and electrostatic interactions between the bipyridinium diamides and citrate, which has been proved by 1 H NMR and mass spectra titration, scanning electronic microscope and dynamic light scattering analyses. More importantly, the quantification of citrate in artificial urine may develop TPE-Py fluorometric probe for the citrate detection in real biosystems. Copyright © 2017 Elsevier B.V. All rights reserved.

Anticoagulant use for prevention of stroke in a commercial population with atrial fibrillation.

Science.gov (United States)

Patel, Aarti A; Lennert, Barb; Macomson, Brian; Nelson, Winnie W; Owens, Gary M; Mody, Samir H; Schein, Jeff

2012-07-01

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and patients with AF are at an increased risk for stroke. Thromboprophylaxis with vitamin K antagonists reduces the annual incidence of stroke by approximately 60%, but appropriate thromboprophylaxis is prescribed for only approximately 50% of eligible patients. Health plans may help to improve quality of care for patients with AF by analyzing claims data for care improvement opportunities. To analyze pharmacy and medical claims data from a large integrated commercial database to determine the risk for stroke and the appropriateness of anticoagulant use based on guideline recommendations for patients with AF. This descriptive, retrospective claims data analysis used the Anticoagulant Quality Improvement Analyzer software, which was designed to analyze health plan data. The data for this study were obtained from a 10% randomly selected sample from the PharMetrics Integrated Database. This 10% sample resulted in almost 26,000 patients with AF who met the inclusion criteria for this study. Patients with a new or existing diagnosis of AF between July 2008 and June 2010 who were aged ≥18 years were included in this analysis. The follow-up period was 1 year. Demographics, stroke risk level (CHADS2 and CHA2DS2-VASc scores), anticoagulant use, and inpatient stroke hospitalizations were analyzed through the analyzer software. Of the 25,710 patients with AF (CHADS2 score 0-6) who were eligible to be included in this study, 9093 (35%) received vitamin K antagonists and 16,617 (65%) did not receive any anticoagulant. Of the patients at high risk for stroke, as predicted by CHADS2, 39% received an anticoagulant medication. The rates of patients receiving anticoagulant medication varied by age-group-16% of patients aged <65 years, 22% of those aged 65 to 74 years, and 61% of elderly ≥75 years. Among patients hospitalized for stroke, only 28% were treated with an anticoagulant agent in the outpatient

Use of 67Ga citrate in the diagnosis of lung cancer

International Nuclear Information System (INIS)

Bogdasarov, Yu.B.; Zajtseva, T.I.; Gabuniya, R.I.; Abramov, V.F.

1981-01-01

A study was of the potentialities of 67 Ga citrate in the diagnosis of lung cancer, in differentiation from benign tumors and chronic inflammatory processes of the lungs. A total of 101 lung cancer patients were examined, of them 64 with central, and 37 with peripheral cancer. The results of radionuclide studies were correlated with those of surgery and with morphological findings. It has been established that in central cancer scintigraphy with 67 Ga citrate gives positive results in 87% of cases, and in peripheral cancer in 89%. This method is of great value for the diagnosis of cancer metastases to the mediastinal lymph nodes. No correlation between the intensity of 67 Ga citrate accumulation in lung tumors and their histological structure has been revealed [ru

Determination of radiation loads from examination of the colon by 67Ga citrate

International Nuclear Information System (INIS)

Mihalova, P.; Buncova, M.; Vrba, T.

2011-01-01

This paper deals with the determination of radiation loads from examination of the colon by gallium citrate. The average calculated committed effective dose after administration of 5 MBq of 67 Ga-citrate is 2.05 mSv.

Magnetic resonance venography to assess thrombus resolution with edoxaban monotherapy versus parenteral anticoagulation/warfarin for symptomatic deep vein thrombosis: A multicenter feasibility study.

Science.gov (United States)

Piazza, Gregory; Mani, Venkatesh; Goldhaber, Samuel Z; Grosso, Michael A; Mercuri, Michele; Lanz, Hans J; Schussler, Steven; Hsu, Ching; Chinigo, Amy; Ritchie, Bruce; Nadar, Venkatesh; Cannon, Kevin; Pullman, John; Concha, Mauricio; Schul, Marlin; Fayad, Zahi A

2016-08-01

The feasibility of magnetic resonance venography (MRV) for measuring change in thrombus volume with a novel anticoagulation regimen versus standard anticoagulation in patients with symptomatic deep vein thrombosis (DVT) has not been assessed. Our aim was to study the feasibility of MRV to measure change in thrombus volume in patients with acute symptomatic objectively confirmed proximal DVT in an open-label multicenter trial (edoxaban Thrombus Reduction Imaging Study, eTRIS). We randomized patients in a 2:1 allocation ratio to edoxaban 90 mg/day for 10 days followed by 60 mg/day versus parenteral anticoagulation bridging to warfarin for 3 months. The primary efficacy outcome was a surrogate end point of the relative change in MRV-quantified thrombus volume from baseline to Day 14-21. A total of 85 eligible patients from 26 study sites were randomized to edoxaban monotherapy (n=56) versus parenteral anticoagulation as a 'bridge' to warfarin (n=29). The mean relative change in MRV-quantified thrombus volume from baseline to Day 14-21 was similar in patients treated with edoxaban and parenteral anticoagulation as a 'bridge' to warfarin (-50.1% vs -58.9%; 95% confidence interval of treatment difference, -12.7%, 30.2%). However, thrombus extension was observed in eight patients in the edoxaban monotherapy group and in none in the warfarin group. Rates of recurrent venous thromboembolism (3.6% vs 3.6%, p=0.45) and clinically relevant non-major bleeding (5.4% vs 7.1%, p=0.34) were also similar. No major bleeds occurred in either on-treatment group during the study period. In conclusion, MRV can assess change in thrombus volume in patients with acute DVT randomized to two different anticoagulant regimens.ClinicalTrials.gov IDENTIFIER NCT01662908: INVESTIGATIONAL NEW DRUG IND APPLICATION EDOXABAN IND # 63266. © The Author(s) 2016.

Graves’ Disease and Treatment Effects on Warfarin Anticoagulation

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Amanda Howard-Thompson

2014-01-01

Full Text Available Background. Hyperthyroidism causes an increased hypoprothrombinemic response to warfarin anticoagulation. Previous studies have demonstrated that patients with hyperthyroidism require lower dosages of warfarin to achieve a therapeutic effect. As hyperthyroidism is treated and euthyroidism is approached, patients may require increasing warfarin dosages to maintain appropriate anticoagulation. We describe a patient’s varying response to warfarin during treatment of Graves’ disease. Case Presentation. A 48-year-old African American female presented to the emergency room with tachycardia, new onset bilateral lower extremity edema, gradual weight loss, palpable goiter, and generalized sweating over the prior 4 months. She was admitted with Graves’ disease and new onset atrial fibrillation. Primary stroke prophylaxis was started using warfarin; the patient developed a markedly supratherapeutic INR likely due to hyperthyroidism. After starting methimazole, her free thyroxine approached euthyroid levels and the INR became subtherapeutic. She remained subtherapeutic over several months despite steadily increasing dosages of warfarin. Immediately following thyroid radioablation and discontinuation of methimazole, the patient’s warfarin dose and INR stabilized. Conclusion. Clinicians should expect an increased response to warfarin in patients with hyperthyroidism and close monitoring of the INR is imperative to prevent adverse effects. As patients approach euthyroidism, insufficient anticoagulation is likely without vigilant follow-up, INR monitoring, and increasing warfarin dosages.

Unexpected disappearance of portal cavernoma on long-term anticoagulation.

Science.gov (United States)

Silva-Junior, Gilberto; Turon, Fanny; Hernandez-Gea, Virginia; Darnell, Anna; García-Criado, Ángeles; García-Pagán, Juan Carlos

2014-08-01

Idiopathic non-cirrhotic portal hypertension is a rare disease of unknown etiology. Patients with idiopathic non-cirrhotic portal hypertension have an increased risk of developing portal vein thrombosis and this is especially prevalent when HIV is also present. We describe a unique case of a patient with idiopathic non-cirrhotic portal hypertension associated to HIV, who developed acute portal vein thrombosis that despite anticoagulation transformed in portal cavernoma and disappeared completely after five years of follow-up on continuous anticoagulation. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

The impact of citrate introduction at UK syringe exchange programmes: a retrospective cohort study in Cheshire and Merseyside, UK

Directory of Open Access Journals (Sweden)

Wareing Michelle

2007-12-01

Full Text Available Abstract Background In 2003, it became legal in the UK for syringe exchange programmes (SEPs to provide citrate to injecting drug users to solubilise heroin. Little work has been undertaken on the effect of policy change on SEP function. Here, we examine whether the introduction of citrate in Cheshire and Merseyside SEPs has altered the number of heroin/crack injectors accessing SEPs, the frequency at which heroin/crack injectors visited SEPs and the number of syringes dispensed. Methods Eleven SEPs in Cheshire and Merseyside commenced citrate provision in 2003. SEP-specific data for the six months before and six months after citrate was introduced were extracted from routine monitoring systems relating to heroin and crack injectors. Analyses compared all individuals attending pre and post citrate and matched analyses only those individuals attending in both periods (defined as 'longitudinal attenders'. Non-parametric tests were used throughout. Results Neither new (first seen in either six months period nor established clients visited SEPs more frequently post citrate. New clients collected significantly less syringes per visit post citrate, than pre citrate (14.5,10.0; z = 1.992, P Conclusion The introduction of citrate did not negatively affect SEP attendance. 'Longitudinal attenders' visited SEPs more frequently post citrate, providing staff with greater opportunity for intervention and referral. As the number of syringes they collected each visit remained unchanged the total number of clean syringes made available to this group of injectors increased very slightly between the pre and post citrate periods. However, new clients collected significantly less syringes post citrate than pre citrate, possibly due to staff concerns regarding the amount of citrate (and thus syringes to dispense safely to new clients. These concerns should not be allowed to negatively impact on the number of syringes dispensed.

Hematology of Nile tilapia (Oreochromis niloticus subjected to anesthesia and anticoagulation protocols

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Nadia Cristine Weinert

2015-12-01

Full Text Available Clinical hematology facilitates the diagnosis of disease and can act as a prognostic indicator of pathological conditions in fish. The aim of the present study was to evaluate hematological parameters of Nile tilapia (Oreochromis niloticus subjected to different anesthetics and anticoagulants. Thirty apparently healthy fishes (average weight of 473 ± 35. 50 g and mean total length of 29. 33 ± 0. 37 cm, were selected from the local commercial fish farm in the Lages municipality (Santa Catarina, Brazil. The animals were randomly divided into three groups of 10. In two groups, anesthesia was induced with eugenol (70 mg·L- 1 (EG and Benzocaine hydrochloride (100 mg·L-1 (BG, respectively. Anesthesia was not administered to fish of the third group (CG/control group. Blood samples were obtained by venipuncture of the caudal vessels and placed into microtubes containing sodium heparin or Na2EDTA for further analysis. The results were analyzed by Sigma Stat for Windows, the paired t-test for significant differences between anticoagulants of the same group, and analysis of variance followed by the Tukey test for comparison of means between groups (p ? 0. 05. Most of the observed changes in the erythrogram were significantly higher for the anticoagulant heparin and benzocaine group in comparison to the control group. However, the values obtained for the leukogram were significantly higher for all groups subjected to the Na2EDTA anticoagulant, suggesting that heparin may cause cell clumping. The results suggest that the anesthetics under investigation effectively minimizes the effects of stress caused by handling and invasive procedures, and that the anticoagulant heparin causes less hemolysis in comparison to Na2EDTA for Nile tilapia. Thus, the hematological variations attributed to different anesthetic protocols and/or different anticoagulants should be considered for the species Oreochromis niloticus.

Direct oral anticoagulants: what can we learn?

Science.gov (United States)

Marongiu, Francesco; Barcellona, Doris

2018-03-02

Direct oral anticoagulants (DOACs) represent an innovation because they avoid periodic laboratory monitoring, and also reduce cerebral bleeding. An examination of the performance of DOACs versus warfarin in randomized clinical trials dedicated to atrial fibrillation would reveal the poor performance of warfarin because the percentage of major bleeding is always above 3%; however, the percentage of major bleeding is less than half of that when the management is done in anticoagulation clinics (ACs). Several years ago, a common opinion was that ACs would disappear as soon as DOACs enter the market. We proposed then that ACs could be transformed into thrombosis centres (TCs) because we envisaged many new activities in terms of diagnostic tools and therapeutic choices. After the introduction of DOACs, the role of the ACs has been re-evaluated because their role may be crucial in selecting both the most appropriate diagnostic approach and the best therapeutic option (including anti-vitamin K drugs) for the single patient. TCs can organize a regular follow-up to improve patient adherence to DOACs. Marketing might have a role in the decision making of the single doctor. Efforts should be made for limiting the relationships between doctors and pharmaceutical companies. It seems reasonable to better prepare doctors, during their university courses, for them to develop a greater scientific culture that would enable them to critically read clinical studies and acquire an independent opinion. Ideally, an expert in haemostasis and thrombosis should handle new and old anticoagulants.

Improved anticoagulant effect of fucosylated chondroitin sulfate orally administered as gastro-resistant tablets.

Science.gov (United States)

Fonseca, Roberto J C; Sucupira, Isabela D; Oliveira, Stephan Nicollas M C G; Santos, Gustavo R C; Mourão, Paulo A S

2017-04-03

Fucosylated chondroitin sulfate (FucCS) is a potent anticoagulant polysaccharide extracted from sea cucumber. Its anticoagulant activity is attributed to the presence of unique branches of sulfated fucose. Although this glycosaminoglycan exerts an antithrombotic effect following oral administration, high doses are necessary to achieve the maximum effect. The diminished activity of FucCS following oral administration is likely due to its degradation in the gastrointestinal tract and its limited ability to cross the intestinal cell membranes. The latter aspect is particularly difficult to overcome. However, gastro-resistant tablet formulation may help limit the degradation of FucCS in the gastrointestinal tract. In the present work, we found that the oral administration of FucCS as gastro-resistant tablets produces a more potent and prolonged anticoagulant effect compared with its administration as an aqueous solution, with no significant changes in the bleeding tendency or arterial blood pressure. Experiments using animal models of arterial thrombosis initiated by endothelial injury demonstrated that FucCS delivered as gastro-protective tablets produced a potent antithrombotic effect, whereas its aqueous solution was ineffective. However, there was no significant difference between the effects of FucCS delivered as gastro-resistant tablets or as aqueous solution in a venous thrombosis model, likely due to the high dose of thromboplastin used. New oral anticoagulants tested in these experimental models for comparison showed significantly increased bleeding tendencies. Our study provides a framework for developing effective oral anticoagulants based on sulfated polysaccharides from marine organisms. The present results suggest that FucCS is a promising oral anticoagulant.

Optimizing the use of oral anticoagulant therapy for atrial fibrilation in primary care: a pharmacist-led intervention.

Science.gov (United States)

Virdee, Mandeep S; Stewart, Derek

2017-02-01

Background Updated evidence-based guidelines for the management of atrial fibrillation (AF) necessitate patient review, particularly with respect to oral anticoagulants, to ensure maximum health gain around stroke prophylaxis. Objective To quantify the level of anticoagulation utilisation in patients with a CHA 2 DS 2 -VASc ≥1/≥2 (male/female) according to evidence-based guidelines and to assess the impact of a pharmacist-led intervention to optimise therapy. Setting Fifteen general medical practices in Liverpool, North-West England with a practice population of 99,129. Method GRASP-AF software was employed to interrogate patient electronic medical records to identify and risk stratify AF patients (using CHA 2 DS 2 -VASc). A pharmacist then reviewed the medical records of those of patients not anticoagulated and with a CHA 2 DS 2 -VASc ≥1/≥2 (male/female). Recommendations were discussed with a general practitioner (GP) and those patients in whom the need for anticoagulation was agreed were invited for a consultation with either the pharmacist or GP and therapy optimised where appropriate. The GPs were responsible for managing those patients referred for diagnosis confirmation or further specialist opinion. Main outcome measure Proportion of patients eligible/not eligible for anticoagulation; proportions in whom anticoagulants initiated, refused, antiplatelets discontinued. Results Five hundred and twenty-three patients (31% of patients identified with AF and a CHA 2 DS 2 -VASc ≥1/≥2 (male/female)) were not receiving an anticoagulant (26 subsequently died or left the practice leaving 497). Three hundred and eighty-two (77%) pharmacist recommendations to a GP were agreed without modification. Following outcomes of diagnostic investigations and specialist referrals, 202 (41%) patients were candidates for anticoagulation, 251 (51%) were not eligible for anticoagulation, 103 (21%) were anticoagulated (56 warfarin, 47 DOAC). Conclusion A pharmacist

Recent developments in separation of low molecular weight heparin anticoagulants.

Science.gov (United States)

Sadowski, Radosław; Gadzała-Kopciuch, Renata; Buszewski, Bogusław

2017-10-05

The general function of anticoagulants is to prevent blood clotting and growing of the existing clots in blood vessels. In recent years, there has been a significant improvement in developing methods of prevention as well as pharmacologic and surgical treatment of thrombosis. For over the last two decades, low molecular weight heparins (LMWHs) have found their application in the antithrombotic diseases treatment. These types of drugs are widely used in clinical therapy. Despite the biological and medical importance of LMWHs, they have not been completely characterized in terms of their chemical structure. Due to both, the structural complexity of these anticoagulants and the presence of impurities, their structural characterization requires the employment of advanced analytical techniques. Since separation techniques play the key role in these endeavors, this review will focus on the presentation of recent developments in the separation of LMWH anticoagulants. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A Process-Based Model of TCA Cycle Functioning to Analyze Citrate Accumulation in Pre- and Post-Harvest Fruits.

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Audrey Etienne

Full Text Available Citrate is one of the most important organic acids in many fruits and its concentration plays a critical role in organoleptic properties. The regulation of citrate accumulation throughout fruit development, and the origins of the phenotypic variability of the citrate concentration within fruit species remain to be clarified. In the present study, we developed a process-based model of citrate accumulation based on a simplified representation of the TCA cycle to predict citrate concentration in fruit pulp during the pre- and post-harvest stages. Banana fruit was taken as a reference because it has the particularity of having post-harvest ripening, during which citrate concentration undergoes substantial changes. The model was calibrated and validated on the two stages, using data sets from three contrasting cultivars in terms of citrate accumulation, and incorporated different fruit load, potassium supply, and harvest dates. The model predicted the pre and post-harvest dynamics of citrate concentration with fairly good accuracy for the three cultivars. The model suggested major differences in TCA cycle functioning among cultivars during post-harvest ripening of banana, and pointed to a potential role for NAD-malic enzyme and mitochondrial malate carriers in the genotypic variability of citrate concentration. The sensitivity of citrate accumulation to growth parameters and temperature differed among cultivars during post-harvest ripening. Finally, the model can be used as a conceptual basis to study citrate accumulation in fleshy fruits and may be a powerful tool to improve our understanding of fruit acidity.

Molecular characterization of microbial population dynamics during sildenafil citrate degradation.

Science.gov (United States)

De Felice, Bruna; Argenziano, Carolina; Guida, Marco; Trifuoggi, Marco; Russo, Francesca; Condorelli, Valerio; Inglese, Mafalda

2009-02-01

Little is known about pharmaceutical and personal care products pollutants (PPCPs), but there is a growing interest in how they might impact the environment and microbial communities. The widespread use of Viagra (sildenafil citrate) has attracted great attention because of the high usage rate, the unpredictable disposal and the unknown potential effects on wildlife and the environment. Until now information regarding the impact of Viagra on microbial community in water environment has not been reported. In this research, for the first time, the genetic profile of the microbial community, developing in a Viagra polluted water environment, was evaluated by means of the 16S and 18S rRNA genes, for bacteria and fungi, respectively, amplified by polymerase chain reaction (PCR) and separated using the denaturing gradient gel electrophoresis (DGGE) technique. The DGGE results revealed a complex microbial community structure with most of the population persisting throughout the experimental period. DNA sequences from bands observed in the different denaturing gradient gel electrophoresis profiles exhibited the highest degree of identity to uncultured bacteria and fungi found previously mainly in polluted environmental and treating bioreactors. Biotransformation ability of sildenafil citrate by the microbial pool was studied and the capability of these microorganisms to detoxify a polluted water ecosystem was assessed. The bacterial and fungal population was able to degrade sildenafil citrate entirely. Additionally, assays conducted on Daphnia magna, algal growth inhibition assay and cell viability determination on HepG2 human cells showed that biotransformation products obtained from the bacterial growth was not toxic. The higher removal efficiency for sildenafil citrate and the lack of toxicity by the biotransformation products obtained showed that the microbial community identified here represented a composite population that might have biotechnological relevance to

Citric complexes, neodymium citrate and americium citrate

International Nuclear Information System (INIS)

Bouhlassa, Saidati.

1981-06-01

The behaviour of neodymium and americium has been studied in citric aqueous medium by two methods: solvent extraction of elements at tracer scale as chelates and by potentiometry. So range of pH and concentrations of elements and citric acid never reached before have been explored: 10 -7 -1 M, 10 -10 -3 , Csub(H3 Cit) -1 M, 1 2 O; AmCit, xH 2 O; NdCit 2 Co(NH 3 ) 6 , 8H 2 O; AmCit 2 Co(NH 3 ) 6 , xH 2 O and Nd 3 (OH) 4 (Cit) 4 NH 4 (Co(NH 3 ) 6 ) 2 , 18H 2 O. Their spectroscopic and crystallographic characteristics have been listed and studied. The nephelauxetic effect has been estimated from citric complexes as well as from citrates of these elements. The structure of the complexes in solution has been discussed on the basis of analysis of hypersensitive transition in different complexes [fr

Artificial Citrate Operon Confers Mineral Phosphate Solubilization Ability to Diverse Fluorescent Pseudomonads

Science.gov (United States)

Adhikary, Hemanta; Sanghavi, Paulomi B.; Macwan, Silviya R.; Archana, Gattupalli; Naresh Kumar, G.

2014-01-01

Citric acid is a strong acid with good cation chelating ability and can be very efficient in solubilizing mineral phosphates. Only a few phosphate solubilizing bacteria and fungi are known to secrete citric acids. In this work, we incorporated artificial citrate operon containing NADH insensitive citrate synthase (gltA1) and citrate transporter (citC) genes into the genome of six-plant growth promoting P. fluorescens strains viz., PfO-1, Pf5, CHAO1, P109, ATCC13525 and Fp315 using MiniTn7 transposon gene delivery system. Comprehensive biochemical characterization of the genomic integrants and their comparison with plasmid transformants of the same operon in M9 minimal medium reveals the highest amount of ∼7.6±0.41 mM citric and 29.95±2.8 mM gluconic acid secretion along with ∼43.2±3.24 mM intracellular citrate without affecting the growth of these P. fluorescens strains. All genomic integrants showed enhanced citric and gluconic acid secretion on Tris-Cl rock phosphate (TRP) buffered medium, which was sufficient to release 200–1000 µM Pi in TRP medium. This study demonstrates that MPS ability could be achieved in natural fluorescent pseudomonads by incorporation of artificial citrate operon not only as plasmid but also by genomic integration. PMID:25259527

Alkali absorption and citrate excretion in calcium nephrolithiasis

Science.gov (United States)

Sakhaee, K.; Williams, R. H.; Oh, M. S.; Padalino, P.; Adams-Huet, B.; Whitson, P.; Pak, C. Y.

1993-01-01

The role of net gastrointestinal (GI) alkali absorption in the development of hypocitraturia was investigated. The net GI absorption of alkali was estimated from the difference between simple urinary cations (Ca, Mg, Na, and K) and anions (Cl and P). In 131 normal subjects, the 24 h urinary citrate was positively correlated with the net GI absorption of alkali (r = 0.49, p origin of hypocitraturia. However, the normal dependence was maintained in CDS and in idiopathic hypocitraturia, suggesting that reduced citrate excretion was largely dietary in origin as a result of low net alkali absorption (from a probable relative deficiency of vegetables and fruits or a relative excess of animal proteins).

Subdural hematoma and oral anticoagulant therapy

NARCIS (Netherlands)

Wintzen, A. R.; Tijssen, J. G.

1982-01-01

In a retrospective study of the period 1959 to 1978, the role of anticoagulant therapy (ACT) in the development of subdural hematoma (SH) was investigated. Of 212 cases, 46 were receiving ACT, a proportion highly in excess of the frequency of ACT in the general population of the Leiden area. In this

Evaluation of Oral Anticoagulant-Associated Intracranial Parenchymal Hematomas Using CT Findings.

Science.gov (United States)

Gökçe, E; Beyhan, M; Acu, B

2015-06-01

Intracranial hemorrhage (ICH) is one of the most serious and lethal complications of anticoagulants with a reported incidence of 5-18.5 %. Computed tomographic (CT) findings, should be carefully studied because early diagnosis and treatment of oral anticoagulant use-associated hematomas are vitally important. In the present study, CT findings of intraparenchymal hematomas associated with anticoagulant and antihypertensive use are presented. This study included 45 patients (25 men, 20 women) under anticoagulant (21 patients) or antihypertensive (24 patients) treatment who had brain CT examinations due to complaints and findings suggesting cerebrovascular disease during July 2010-October 2013 period. CT examinations were performed to determine hematoma volumes and presence of swirl sign, hematocrit effect, mid-line shift effect, and intraventricular extension. The patients were 40-89 years of age. In four cases, a total of 51 intraparenchymal hematomas (42 cerebral, 7 cerebellar and 2 brain stem) were detected in multiple foci. Hematoma volumes varied from 0.09 to 284.00 ml. Swirl sign was observed in 87.5 and 63.0 % of OAC-associated ICHs and non-OAC-associated ICHs, respectively. In addition, hematocrit effect was observed in 41.6 % of OAC-associated and in 3.7 % of non-OAC-associated ICHs. Volume increases were observed in all 19 hematomas where swirl sign was detected, and follow-up CT scanning was conducted. Mortality of OAC-associated ICHs was correlated with initial volumes of hematoma, mid-line shift amount, and intraventricular extension. Detection of hematocrit effect by CT scanning of intracranial hematomas should be cautionary in oral anticoagulant use, while detection of swirl sign should be suggestive of active hemorrhage.

[Use of non-vitamin K antagonist oral anticoagulants in Primary Care: ACTUA study].

Science.gov (United States)

Barrios, V; Escobar, C; Lobos, J M; Polo, J; Vargas, D

2017-10-01

Approximately 40% of patients with non-valvular auricular fibrillation (NVAF) who receive vitamin K antagonists (VKA) in Primary Care in Spain have poor anticoagulation control. The objective of the study Actuación en antiCoagulación, Tratamiento y Uso de anticoagulantes orales de acción directa (ACOD) en Atención primaria (ACTUA) (Action in Coagulation, Treatment and Use of direct oral anticoagulants [DOACs]) in Primary Care) was to analyse the current situation regarding the use of VKA and non-vitamin K antagonist oral anticoagulants (NOACs) in patients with NVAF in Primary Care in Spain and the possible issues arising from it. An online survey was created covering various aspects of the use of oral anticoagulants in NAFV. A two-round modified Delphi approach was used. Results were compiled as a set of practical guidelines. Forty-four experts responded to the survey. Consensus was reached in 62% (37/60) of the items. Experts concluded that a considerable number of patients with NVAF who receive VKA do not have a well-controlled INR and that a substantial group of patients who could benefit from being treated with NOACs do not receive them. The use of NOACs increases the probability of having good anticoagulation control and decreases the risk of severe and intracranial haemorrhage. Current limitations to the use of NOACs include administrative barriers, insufficient knowledge about the benefits and risks of NOACs, limited experience of doctors in using them, and their price. Renal insufficiency influences the choice of a particular anticoagulant. The ACTUA study highlights the existing controversies about the use of oral anticoagulants for the treatment of NVAF in Primary Care in Spain, and provides consensus recommendations that may help to improve the use of these medications. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Improvement in long-term ECMO by detailed monitoring of anticoagulation: a case report.

Science.gov (United States)

Sievert, Alicia; Uber, Walter; Laws, Stacey; Cochran, Joel

2011-01-01

The use of unfractionated heparin (UFH) as an anticoagulant during long-term extracorporeal support presents a unique challenge for the clinician in balancing the amount of anticoagulant to maintain adequate anticoagulation without causing excessive bleeding. Activated clotting times (ACT) and activated partial thromboplastin times (aPTT) are the most common modality to monitor UFH on extracorporeal membrane oxygenation (ECMO). Limitations to these tests include consumptive coagulopathies, clotting factor deficiencies, platelet dysfunction, and fibrinolysis. The following case report describes the use of alternative monitoring strategies to assess more accurately anticoagulation during ECMO. A 20-month-old female presented to the emergency department with a 5-6 day history of cough, fever, tachypnea, and respiratory distress. She was diagnosed with influenza A and B with pneumonia. The patient was placed on veno-venous ECMO (V-V ECMO) after mechanical ventilation failed. On ECMO day eight, the patient developed a thrombus in her inferior vena cava and pleural effusions, obstructing cannula flow. Laboratory tests revealed the ACT was within range, yet the aPTT was dropping, despite increased heparin. Heparin levels were low and antithrombin-III (AT) concentrations were 40%. Recombinant AT was given and subsequent aPTTs were within the therapeutic range. Later, the aPTT decreased to 475 mg/ dL, and Factor VIII >150 IU/dL, suggesting an acute phase reaction or ongoing systemic inflammation, increasing the risk for thrombosis. We maintained heparin assays between 0.5-0.7 IU/mL and AT >60% to assure heparin's effect. The patient showed no signs of excess bleeding, blood product administration, or clots in the circuit, suggesting proper anticoagulation. The patient was successfully weaned on day 33 and is currently alive and at home. Monitoring of anti-Xa UFH and AT proved effective for measuring anticoagulation and detecting inconsistencies in other anticoagulation

Statement on the safety of glucosamine for patients receiving coumarin anticoagulants

DEFF Research Database (Denmark)

Tetens, Inge

2011-01-01

The European Food Safety Authority (EFSA) asked the Panel on Dietetic Products, Nutrition and Allergies to provide a scientific statement on the safety of glucosamine for patients receiving coumarin anticoagulants. More than 40 case reports have been collected by drug-monitoring agencies...... cases haemorrhage occurred in a variety of organs, and in one case this resulted in a persistent vegetative state. The evidence for an interaction between glucosamine and coumarin anticoagulants is strengthened by the observation that in the majority of cases the INR began to fall to normal values when...... glucosamine intake was discontinued. There is insufficient information to conclude on a mechanism for an interaction between glucosamine and coumarin anticoagulants. There are also insufficient data in the case reports to derive a dose-response relationship for glucosamine and to assess the level of risk...

Oral anticoagulants for stroke prevention in atrial fibrillation.

Science.gov (United States)

Senoo, Keitaro; Lane, Deirdre A; Lip, Gregory Y H

2014-09-01

The availability of 4 non-vitamin K oral anticoagulants (NOACs), that is, dabigatran, rivaroxaban, apixaban, and edoxaban, has changed the landscape of stroke prevention in patients with atrial fibrillation. This review article provides an overview of the 4 phase III studies that have compared these NOACs, examining major outcomes of efficacy and safety. A range of practical questions relating to the NOACs have emerged, including topics such as patient selection, treating patients with renal impairment, treating elderly patients, and combining anticoagulant therapy with antiplatelet drugs. We also address the interaction of various patient characteristics with the treatments and suggest the features can assist the physician in the choice of a particular NOAC for a particular patient(s). Copyright © 2014 Elsevier B.V. All rights reserved.

Transportation cost of anticoagulation clinic visits in an urban setting.

Science.gov (United States)

Hwang, Jamie M; Clemente, Jennifer; Sharma, Krishna P; Taylor, Thomas N; Garwood, Candice L

2011-10-01

Patients being managed on warfarin make frequent or regular visits to anticoagulation monitoring appointments. International studies have evaluated transportation cost and associated time related to anticoagulation clinic visits. To our knowledge, no studies have evaluated the cost of transportation to such clinic visits in the United States. To describe the methods of transportation and estimate the average total cost of transportation to and from an anticoagulation clinic in an urban setting. We prospectively conducted a survey of patients treated at the Harper Anticoagulation Clinic located in Detroit, Michigan, during November 2010. The survey was given to patients while waiting at their regularly scheduled clinic appointments and included questions regarding mode of transportation, distance traveled in miles, parking payment, and time missed from work for clinic appointments. The mean distance traveled was translated into cost assuming 50 cents per mile based on 2010 estimates by the Internal Revenue Service. Sixty patients responded to the 11-item survey; response rates for individual items varied because participants were instructed to skip questions that did not pertain to them. Of the 47 participants responding to demographic questions, 70.2% were female, and 46.8% were older than 60 years. Transportation by private vehicle (80.0%), either driven by patients (41.7%) or someone else (38.3%), was the most common method reported. Use of private automobile translated into a cost of $11.19 per round trip. Other means of transportation identified include a ride from a medical transportation service (10.0%), bus (5.0%), walking (3.3%), and taxi (1.7%). The mean (SD) distance traveled to the clinic for all methods of transportation was 8.34 (7.7) miles. We estimated the average cost of round-trip transportation to be $10.78 weighted for all transportation modes. This is a direct nonmedical cost that is paid for by most patients out of pocket. However, 9 of 44 (20

Calcium citrate: a new biomaterial that can enhance bone formation in situ

Directory of Open Access Journals (Sweden)

WANG Li-ming

2012-11-01

Full Text Available 【Abstract】 Objective: To investigate the effect of a new biomaterial combining calcium citrate and recombinant human bone morphogenetic protein-2 (rhBMP-2 on bone regeneration in a bone defect rabbit model. Methods: Totally 30 male New Zealand white rabbits were randomly and equally divided into calcium citrate-rhBMP-2 (CC-rhBMP-2 group and rhBMP-2 only group. Two 10 mm-long and 5 mm-deep bone defects were respec-tively created in the left and right femoral condyles of the rabbits. Subsequently 5 pellets of calcium citrate (10 mg combined with rhBMP-2 (2 mg or rhBMP-2 alone were im-planted into the bone defects and compressed with cotton swab. Bone granules were obtained at 2, 4 and 6 weeks after procedure and received histological analysis. LSD t-test and a subsequent t-test were adopted for statistical analysis. Results: Histomorphometric analysis revealed newly formed bones, and calcium citrate has been absorbed in the treatment group. The percent of newly formed bone area in femoral condyle in control group and CC-rhBMP-2 group was respectively 31.73%±1.26% vs 48.21%±2.37% at 2 weeks; 43.40%±1.65% vs 57.32%±1.47% at 4 weeks, and 51.32%±7.80% vs 66.74%±4.05% at 6 weeks (P<0.05 for all. At 2 weeks, mature cancellous bone was observed to be already formed in the treatment group. Conclusion: From this study, it can be concluded that calcium citrate combined with rhBMP-2 signifcantly en-hances bone regeneration in bone defects. This synthetic gelatin matrix stimulates formation of new bone and bone marrow in the defect areas by releasing calcium ions. Key words: Bone morphogenetic protein-2; Biocompatible materials; Calcium citrate; Gelatin

Real life anticoagulation treatment of patients with atrial fibrillation in Germany

DEFF Research Database (Denmark)

Wilke, Thomas; Groth, Antje; Pfannkuche, Matthias

2015-01-01

Oral anticoagulation (OAC) with either new oral anticoagulants (NOACs) or Vitamin-K antagonists (VKAs) is recommended by guidelines for patients with atrial fibrillation (AF) and a moderate to high risk of stroke. Based on a claims-based data set the aim of this study was to quantify the stroke-r...... that both patient/disease characteristics and treatment environment/general prescribing behaviour of physicians may explain the OAC under-use in AF patients....

Non arteritic anterior ischemic optic neuropathy; does anticoagulation help?

International Nuclear Information System (INIS)

Aftab, A.M.; Iqbal, M.; Ali, A.; Rauf, A.

2017-01-01

Non Arteritic Anterior Ischemic Optic Neuropathy (NAION) is the most common acute optic neuropathy in patients over 50 years of age. This study was conducted to determine the beneficial effects of anticoagulation with Heparin and Warfarin in patients with NAION presenting within 4 weeks of onset of symptoms Methods: A prospective, interventional, pilot study was conducted in Eye- A unit of Khyber Teaching Hospital from July 2010 onwards on patients with NAION presenting within 4 weeks of onset of symptoms. Patients underwent complete ophthalmological examination including Snellen's visual acuity (latter converted to Log MAR), pupil examination, fundus examination and automated Humphrey visual field analysis. Hematologic tests, Thrombophilia screening, Echocardiography and carotid Doppler ultrasound were carried on patients. All patients were anticoagulated with Heparin and Warfarin after obtaining informed written consent. Patients were examined at 1 Month, 3 months and 6 months' time period. Primary parameter measured was improvement in visual acuity. Results: Total number of patients in our study was 24. Regarding visual outcome total number of patients having significant improvement of visual acuity in our study was 16 (66.6 percent), while 4 (16.7 percent) patients had marginal improvement of visual acuity. Three (12.5 percent) patients maintained stable visual acuity of 6/6 throughout the study period in presence of thrombophilic disorders. One patient (4.1 percent) suffered a decline in visual acuity compared to VA at baseline presentation. Conclusions: Anticoagulation using heparin and warfarin does benefit patients with NAION presenting within 4 weeks of onset of symptoms. In our study a higher proportion of patients experienced significant improvement of visual acuity following anticoagulation as compared to the highest reported spontaneous improvement in such patients. (author)

Anticoagulant factor V: factors affecting the integration of novel scientific discoveries into the broader framework.

Science.gov (United States)

LaBonte, Michelle L

2014-09-01

Since its initial discovery in the 1940s, factor V has long been viewed as an important procoagulant protein in the coagulation cascade. However, in the later part of the 20th century, two different scientists proposed novel anticoagulant roles for factor V. Philip Majerus proposed the first anticoagulant function for factor V in 1983, yet ultimately it was not widely accepted by the broader scientific community. In contrast, Björn Dahlbäck proposed a different anticoagulant role for factor V in 1994. While this role was initially contested, it was ultimately accepted and integrated into the scientific framework. In this paper, I present a detailed historical account of these two anticoagulant discoveries and propose three key reasons why Dahlbäck's anticoagulant role for factor V was accepted whereas Majerus' proposed role was largely overlooked. Perhaps most importantly, Dahlbäck's proposed anticoagulant role was of great clinical interest because the discovery involved the study of an important subset of patients with thrombophilia. Soon after Dahlbäck's 1994 work, this patient population was shown to possess the factor V Leiden mutation. Also key in the ultimate acceptance of the second proposed anticoagulant role was the persistence of the scientist who made the discovery and the interest in and ability of others to replicate and reinforce this work. This analysis of two different yet similar discoveries sheds light on factors that play an important role in how new discoveries are incorporated into the existing scientific framework. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

Does whole blood coagulation analysis reflect developmental haemostasis?

DEFF Research Database (Denmark)

Ravn, Hanne Berg; Andreasen, Jo Bønding; Hvas, Anne-Mette

2017-01-01

.05), but there was no sign of developmental changes in whole blood coagulation assessment when applying ROTEM, apart from clotting time in the EXTEM assay (P reach statistical significance. Citrate-anticoagulated blood showed...

Prevalence of Lupus Anticoagulant in Women with Spontaneous ...

African Journals Online (AJOL)

2017-10-26

Oct 26, 2017 ... ... pregnancy. Presence of lupus anticoagulant (LA), one of the antiphospholipid antibodies, ... pregnancy outcomes such as preeclampsia/eclampsia and small for date deliveries. ... changes in a background of APL syndrome.

Are pharmacological properties of anticoagulants reflected in pharmaceutical pricing and reimbursement policy? Out-patient treatment of venous thromboembolism and utilization of anticoagulants in Poland.

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Bochenek, T; Czarnogorski, M; Nizankowski, R; Pilc, A

2014-06-01

Pharmacotherapy with vitamin K antagonists (VKA) and low-molecular-weight heparins (LMWH) is a major cost driver in the treatment of venous thromboembolism (VTE). Major representatives of anticoagulants in Europe include: acenocoumarol and warfarin (VKA), enoxaparin, dalteparin, nadroparin, reviparin, parnaparin and bemiparin (LMWH). Aim of this report is to measure and critically assess the utilization of anticoagulants and other resources used in the out-patient treatment of VTE in Poland. To confront the findings with available scientific evidence on pharmacological and clinical properties of anticoagulants. The perspectives of the National Health Fund (NHF) and the patients were adopted, descriptive statistics methods were used. The data were gathered at the NHF and the clinic specialized in treatment of coagulation disorders. Non-pharmacological costs of treatment were for the NHF 1.6 times higher with VKA than with LMWH. Daily cost of pharmacotherapy with LMWH turned out higher than with VKA (234 times for the NHF, 42 times per patient). Within both LMWH and VKA the reimbursement due for the daily doses of a particular medication altered in the manner inversely proportional to the level of patient co-payment. Utilization of long-marketed and cheap VKA was dominated by LMWH, when assessed both through the monetary measures and by the actual volume of sales. Pharmaceutical reimbursement policy favored the more expensive equivalents among VKA and LMWH, whereas in the financial terms the patients were far better off when remaining on a more expensive alternative. The pharmaceutical pricing and reimbursement policy of the state should be more closely related to the pharmacological properties of anticoagulants.

Radiolabeled porphyrin versus gallium-67 citrate for the detection of human melanoma in athymic mice

International Nuclear Information System (INIS)

Maric, N.; Chan, S. Ming; Hoffer, P.B.; Duray, P.

1987-01-01

We performed the biodistribution and imaging studies of 111 In and 67 Ga labeled tetra(4-N-methylpyridyl) porphine, (T4NMPYP), and compared it to that of 67 Ga citrate in athymic mice bearing a human melanoma xenograft. The biodistribution results of both 111 In and 67 Ga labeled T4NMPYP (3, 6, 24, and 48 hours) were similar but differed from that of 67 Ga citrate (48 hours). The optimum tumor uptake of both radiolabeled porphyrins was at 6 hours postinjection and was lower than the tumor uptake of 67 Ga citrate at 48 hours postinjection. Kidney was the only organ showing higher uptake of radiolabeled porphyrin compared to that of 67 Ga citrate. The imaging studies performed with 111 In T4NMPYP and 67 Ga citrate correspond to the biodistribution results. Osteomyelitis present in one mouse showed good localization of 111 In T4NMPYP. 15 refs., 3 figs., 5 tabs

Treatment Changes among Users of Non-Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation

DEFF Research Database (Denmark)

Poulsen, Maja Hellfritzsch; Husted, Steen Elkjær; Grove, Erik Lerkevang

2017-01-01

Patients with atrial fibrillation discontinuing anticoagulant therapy are left unprotected against ischaemic stroke. Further, switching between oral anticoagulants may be associated with a transiently increased risk of bleeding or thromboembolism. However, there is a paucity of real-life data on ...

Antiplatelet and Anticoagulant Drugs in Interventional Radiology

International Nuclear Information System (INIS)

Altenburg, Alexander; Haage, Patrick

2012-01-01

In treating peripheral arterial disease, a profound knowledge of antiplatelet and anticoagulative drug therapy is helpful to assure a positive clinical outcome and to anticipate and avoid complications. Side effects and drug interactions may have fatal consequences for the patient, so interventionalists should be aware of these risks and able to control them. Aspirin remains the first-line agent for antiplatelet monotherapy, with clopidogrel added where dual antiplatelet therapy is required. In case of suspected antiplatelet drug resistance, the dose of clopidogrel may be doubled; prasugrel or ticagrelor may be used alternatively. Glycoprotein IIb/IIIa inhibitors (abciximab or eptifibatide) may help in cases of hypercoagulability or acute embolic complications. Desmopressin, tranexamic acid, or platelet infusions may be used to decrease antiplatelet drug effects in case of bleeding. Intraprocedurally, anticoagulant therapy treatment with unfractionated heparin (UFH) still is the means of choice, although low molecular-weight heparins (LMWH) are suitable, particularly for postinterventional treatment. Adaption of LMWH dose is often required in renal insufficiency, which is frequently found in elderly patients. Protamine sulphate is an effective antagonist for UFH; however, this effect is less for LMWH. Newer antithrombotic drugs, such as direct thrombin inhibitors or factor X inhibitors, have limited importance in periprocedural treatment, with the exception of treating patients with heparin-induced thrombocytopenia (HIT). Nevertheless, knowing pharmacologic properties of the newer drugs facilitate correct bridging of patients treated with such drugs. This article provides a comprehensive overview of antiplatelet and anticoagulant drugs for use before, during, and after interventional radiological procedures.

Practical recommendations for the choice of anticoagulants in the management of patients with atrial fibrillation on ibrutinib.

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Chai, Khai Li; Rowan, Gail; Seymour, John F; Burbury, Kate; Carney, Dennis; Tam, Constantine S

2017-12-01

The management of AF represents a major challenge in patients with CLL, especially in elderly patients with multiple comorbidities who are representative of the majority of patients with CLL. This is especially complex in the case of ibrutinib. Many anticoagulants have potential for pharmacological interaction with ibrutinib, and ibrutinib itself has antiplatelet properties. Use of ibrutinib therapy in these patients mandates review and revision of the need for anticoagulation and best anticoagulant to use. Herein, we review the current knowledge of the metabolism of common anticoagulants and how they may interact with ibrutinib.

A cost-analysis model for anticoagulant treatment in the hospital setting.

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Mody, Samir H; Huynh, Lynn; Zhuo, Daisy Y; Tran, Kevin N; Lefebvre, Patrick; Bookhart, Brahim

2014-07-01

Rivaroxaban is the first oral factor Xa inhibitor approved in the US to reduce the risk of stroke and blood clots among people with non-valvular atrial fibrillation, treat deep vein thrombosis (DVT), treat pulmonary embolism (PE), reduce the risk of recurrence of DVT and PE, and prevent DVT and PE after knee or hip replacement surgery. The objective of this study was to evaluate the costs from a hospital perspective of treating patients with rivaroxaban vs other anticoagulant agents across these five populations. An economic model was developed using treatment regimens from the ROCKET-AF, EINSTEIN-DVT and PE, and RECORD1-3 randomized clinical trials. The distribution of hospital admissions used in the model across the different populations was derived from the 2010 Healthcare Cost and Utilization Project database. The model compared total costs of anticoagulant treatment, monitoring, inpatient stay, and administration for patients receiving rivaroxaban vs other anticoagulant agents. The length of inpatient stay (LOS) was determined from the literature. Across all populations, rivaroxaban was associated with an overall mean cost savings of $1520 per patient. The largest cost savings associated with rivaroxaban was observed in patients with DVT or PE ($6205 and $2742 per patient, respectively). The main driver of the cost savings resulted from the reduction in LOS associated with rivaroxaban, contributing to ∼90% of the total savings. Furthermore, the overall mean anticoagulant treatment cost was lower for rivaroxaban vs the reference groups. The distribution of patients across indications used in the model may not be generalizable to all hospitals, where practice patterns may vary, and average LOS cost may not reflect the actual reimbursements that hospitals received. From a hospital perspective, the use of rivaroxaban may be associated with cost savings when compared to other anticoagulant treatments due to lower drug cost and shorter LOS associated with

The Need for Anticoagulation Following Inferior Vena Cava Filter Placement: Systematic Review

International Nuclear Information System (INIS)

Ray, Charles E.; Prochazka, Allan

2008-01-01

Purpose. To perform a systemic review to determine the effect of anticoagulation on the rates of venous thromboembolism (pulmonary embolus, deep venous thrombosis, inferior vena cava (IVC) filter thrombosis) following placement of an IVC filter. Methods. A comprehensive computerized literature search was performed to identify relevant articles. Data were abstracted by two reviewers. Studies were included if it could be determined whether or not subjects received anticoagulation following filter placement, and if follow-up data were presented. A meta-analysis of patients from all included studies was performed. A total of 14 articles were included in the final analysis, but the data from only nine articles could be used in the meta-analysis; five studies were excluded because they did not present raw data which could be analyzed in the meta-analysis. A total of 1,369 subjects were included in the final meta-analysis. Results. The summary odds ratio for the effect of anticoagulation on venous thromboembolism rates following filter deployment was 0.639 (95% CI 0.351 to 1.159, p = 0.141). There was significant heterogeneity in the results from different studies [Q statistic of 15.95 (p = 0.043)]. Following the meta-analysis, there was a trend toward decreased venous thromboembolism rates in patients with post-filter anticoagulation (12.3% vs. 15.8%), but the result failed to reach statistical significance. Conclusion. Inferior vena cava filters can be placed in patients who cannot receive concomitant anticoagulation without placing them at significantly higher risk of development of venous thromboembolism

[Retrospective analysis of correlative factors between digestive system injury and anticoagulant or antiplatelet-agents].

Science.gov (United States)

Cui, Ning; Luo, Hesheng

2014-05-27

To explore the correlative factors and clinical characteristics of digestive system injury during the treatment of anticoagulant and (or) antiplatelet-agents. A total of 1 443 hospitalized patients on anticoagulant and (or) antiplatelet-agents from January 2010 to December 2013 at Renmin Hospital of Wuhan University were analyzed retrospectively. Their length of hospital stay was from 5 to 27 days. Most of them were elderly males (n = 880, 61.0%) with an average age of (62 ± 6) years. 1 138 patients (78.9%) were farmers, workers or someone without a specific occupation. During the treatment of anticoagulant/antiplatelet-agents, statistical difference existed (P = 0.01) between positively and negatively previous digestive disease groups for actively newly occurring digestive system injury (16.0% (41/256) vs 15.9% (189/1 187)). After the dosing of anticoagulant and (or) antiplatelet-agents, 57 (66.3%, 57/86) patients were complicated by hemorrhage of digestive tract, taking 62.9% (61/97) of all positive result patients for Helicobacter pylori test. Comparing preventive PPI group with no PPI group, there was no marked statistical differences (P = 2.67) for digestive system complication (including hemorrhage of digestive tract) while receiving anticoagulant and (or) antiplatelet-agents (13.9% (74/533) vs 17.1% (156/910)). During anticoagulant and/or antiplatelet-agent therapy, 185 patients (12.8%) were complicated by peptic ulcer or peptic ulcer with bleeding, 40 patients (2.8%) had erosive gastritis and 5 (0.3%) developed acute gastric mucosal lesions. And 42 of 76 patients complicated by hemorrhage of digestive tract underwent endoscopic hemostasis while 2 patients were operated. Ninety-seven patients (6.7%) died, including 61 (62.9%, 61/97) from hemorrhage of digestive tract. The remainder became cured, improved and discharged. Moreover, no significant statistical differences existed (P = 2.29) among three combination group (aspirin, clopidogrel, warfarin), two

21 CFR 73.2110 - Bismuth citrate.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Bismuth citrate. 73.2110 Section 73.2110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR... paragraph (c)(1), effective April 27, 2010. For the convenience of the user, the revised text is set forth...

BIOQUIMICO PLASMÁTICO DE CÃES: EFEITOS DOS DIFERENTES ANTICOAGULANTES EM COMPARAÇÃO COM O SORO

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Bianca Ressetti da Silva

2015-06-01

Full Text Available Different types of anticoagulants are used in the routine of a veterinary clinic, which are chosen based on the exam to be performed. Agitated, aggressive, of hard contention and small size animals can be a limiting factor when it is wished to separate samples into tubes with different anticoagulants. Therefore, this study had as the objective evaluate the effects of anticoagulants: EDTA, sodium citrate and sodium fluorite associated with EDTA, in the results of routine plasma biochemistry performed in dogs and compare it with serum. Blood samples of 10 clinically healthy dogs were collected and placed in different tubes with each anticoagulant and one without to obtain serum. Albumin, alanine aminotransferase (ALT, calcium, total cholesterol, creatine, phosphorus, glucose, total protein (PT and urea concentrations were measured by spectophotometric. It was found that plasma obtained with EDTA anticoagulant resulted in dosage alterations for glucose, cholesterol and calcium. Samples obtained with sodium citrate presented results lower than serum in all analyzed parameters, except for ALT. The anticoagulant sodium 34 Colloquium Agrariae, v. 11, n.1, Jan-Jun. 2015, p.33-41. DOI: 10.5747/ca.2015.v11.n1.a116 fluorite with EDTA only didn’t result in statistical differences when compared to serum in the parameters of urea and glucose. Thus, serum is the most trustworthy sample to determine the biochemical profile of dogs, however some biochemical’s can be performed with plasma with EDTA such as creatine, ALT, urea, albumin, PT and phosphorus.

Rôle modeste du citrate comme transporteur d'acétyl-CoA chez l'animal vivant.

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Rous, S

1971-02-09

2,4-(14) C-Citrate incorporated to a far greater extent than 1,5-(14) C-citrate into liver, carcass or adipose tissue fatty acids of living mice. This finding excludes the possibility that the acetyl units emerge from the mitochondria in the form of citrate.

Healthcare resources and needs in anticoagulant therapy for patients with nonvalvular atrial fibrillation. SAMOA Study.

Science.gov (United States)

Barrios, V; Egocheaga-Cabello, M I; Gállego-Culleré, J; Ignacio-García, E; Manzano-Espinosa, L; Martín-Martínez, A; Mateo-Arranz, J; Polo-García, J; Vargas-Ortega, D

2017-05-01

To determine, in the various medical specialties, the healthcare process for anticoagulated patients with nonvalvular atrial fibrillation, to determine the available and necessary resources and to identify potential areas of improvement in the care of these patients. We performed a cross-sectional survey of primary care and specialised physicians involved in the care of anticoagulated patients. The questionnaires referred to the healthcare process, the indication and prescription of anticoagulant therapy and the barriers and deficiencies present for these patients. A total of 893 physicians participated in the study, 437 of whom worked in primary care and 456 of whom were specialists (mostly cardiologists). Forty-two percent of the family doctors indicated that they assessed and prescribed anticoagulant therapy, and 66% performed the regular follow-up of these patients. In both healthcare settings, the physicians noted the lack of standardised protocols. There was also a lack of quality control in the treatment. The role of primary care in managing anticoagulated patients has grown compared with previous reports. The responses of the participating physicians suggest marked gaps in the standardisation of the healthcare process and several areas for improvement in these patients' follow-up. The promotion of training in direct-acting anticoagulant drugs remains pivotal. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Could Some Geriatric Characteristics Hinder the Prescription of Anticoagulants in Atrial Fibrillation in the Elderly?

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Paule Denoël

2014-01-01

Full Text Available Several studies have reported underprescription of anticoagulants in atrial fibrillation (AF. We conducted an observational study on 142 out of a total of 995 consecutive ≥75 years old patients presenting AF (14% when admitted in an emergency unit of a general hospital, in search of geriatric characteristics that might be associated with the underprescription of anticoagulation therapy (mostly antivitamin K at the time of the study. The following data was collected from patients presenting AF: medical history including treatment and comorbidities, CHADS2 score, ISAR scale (frailty, Lawton’s scale (ADL, GDS scale (mood status, MUST (nutrition, and blood analysis (INR, kidney function, and albumin. Among those patients for who anticoagulation treatment was recommended (73%, only 61% were treated with it. In the group with anticoagulation therapy, the following characteristics were observed more often than in the group without such therapy: a recent (≤6 months hospitalization and medical treatment including digoxin or based on >3 different drugs. Neither the value of the CHADS2 score, nor the geriatric characteristics could be correlated with the presence or the absence of an anticoagulation therapy. More research is thus required to identify and clarify the relative importance of patient-, physician-, and health care system-related hurdles for the prescription of oral anticoagulation therapy in older patients with AF.

Nonoclusive thrombosis of mechanical mitral valve prosthesis caused by inadequate treatment of anticoagulant therapy resistance

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Ivanović Branislava

2008-01-01

Full Text Available Background. Oral anticoagulants have been used in the prevention of thromboembolic complications for over six decades. A rare, but possible problem in the application of these medications could be resistance to them. Case report. We presented a patient with nonocclusive thrombosis of the mechanical mitral prosthesis due to inadequately treated resistance to peroral anticoagulant therapy. Resistance to oral anticoagulant medications was proven by an increased dosage of warfarin up to 20 mg and, after that, acenokumarol to 15 mg over ten days which did not lead to an increase in the international normalized ratio (INR value over 1.2. On the basis of information that she did not take food rich in vitamin K or medications which could reduce effects of oral anticoagulants, and that she did not have additional illnesses and conditions that could cause an inadequate response to anticoagulant therapy, it was circumstantially concluded that this was a hereditary form of resistance. Because of the existing mechanical prosthetics on the mitral position, low molecular heparin has been introduced into the therapy. The patient reduced it on her own initiative, leading to nonocclusive valvular thrombosis. Conclusion. When associated complications like absolute arrhithmia does not exist, the finding of resistance to oral anticoagulant agents is an indication for the replacement of a mechanical prosthetic with a biological one which has been done in this patients.

Anti-Coagulant and Anti-Thrombotic Properties of Blacklip Abalone (Haliotis rubra): In Vitro and Animal Studies.

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Suleria, Hafiz Ansar Rasul; Masci, Paul P; Zhao, Kong-Nan; Addepalli, Rama; Chen, Wei; Osborne, Simone A; Gobe, Glenda C

2017-08-04

Sulphated polysaccharides with anti-thrombotic and anti-coagulant activities have been found in various marine biota. In this study, a previously characterised anti-thrombotic and anti-coagulant extract from blacklip abalone was fractionated by anion exchange chromatography (AEC), pooled (on a sulphated polysaccharide basis) and administered to Wistar rats via oral gavage (N = 8) for assessment as an oral therapeutic. To ensure that the preparation had anti-coagulant activity prior to oral administration, it was assessed in rat blood by thromboelastography (TEG) significantly increasing reaction (R) time (or time until clot formation). Following in vitro confirmation of anti-coagulant activity, 40 mg of the preparation was orally administered to rats with blood samples collected at 2, 4, and 6 h post-gavage. Assessment of all blood samples by TEG showed some prolongation of R time from 355 to 380 s after 4 h. Dosing of the post-gavage blood samples with the abalone preparation to confirm anti-thrombotic activity in vitro revealed residual anti-coagulant activity, further suggesting that oral administration did increase anti-coagulant potential in the collected blood but that bioavailability was low. Assessment of tissues and haematological parameters showed no obvious harmful effects of the abalone preparation in animals. In summary, even though oral administration of fractionated and pooled blacklip abalone extract to rats delayed clotting after 4 h, bioavailability of the preparation appeared to be low and may be more appropriate for intravenous administration as an anti-thrombotic or anti-coagulant therapeutic.

An economic comparison of a laparoscopic electrocautery strategy and ovulation induction with recombinant FSH in women with clomiphene citrate-resistant polycystic ovary syndrome

NARCIS (Netherlands)

van Wely, M.; Bayram, N.; van der Veen, F.; Bossuyt, P. M. M.

2004-01-01

BACKGROUND: Recombinant FSH (rFSH) is the current standard treatment for ovulation induction in women with polycystic ovary syndrome (PCOS) that do not respond to clomiphene citrate. Ovulation induction with rFSH is known to be costly due to the necessity of daily injections and intensive

Plasma Membrane Na+-Coupled Citrate Transporter (SLC13A5 and Neonatal Epileptic Encephalopathy

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Yangzom D. Bhutia

2017-02-01

Full Text Available SLC13A5 is a Na+-coupled transporter for citrate that is expressed in the plasma membrane of specific cell types in the liver, testis, and brain. It is an electrogenic transporter with a Na+:citrate3− stoichiometry of 4:1. In humans, the Michaelis constant for SLC13A5 to transport citrate is ~600 μM, which is physiologically relevant given that the normal concentration of citrate in plasma is in the range of 150–200 μM. Li+ stimulates the transport function of human SLC13A5 at concentrations that are in the therapeutic range in patients on lithium therapy. Human SLC13A5 differs from rodent Slc13a5 in two important aspects: the affinity of the human transporter for citrate is ~30-fold less than that of the rodent transporter, thus making human SLC13A5 a low-affinity/high-capacity transporter and the rodent Slc13a5 a high-affinity/low-capacity transporter. In the liver, SLC13A5 is expressed exclusively in the sinusoidal membrane of the hepatocytes, where it plays a role in the uptake of circulating citrate from the sinusoidal blood for metabolic use. In the testis, the transporter is expressed only in spermatozoa, which is also only in the mid piece where mitochondria are located; the likely function of the transporter in spermatozoa is to mediate the uptake of citrate present at high levels in the seminal fluid for subsequent metabolism in the sperm mitochondria to generate biological energy, thereby supporting sperm motility. In the brain, the transporter is expressed mostly in neurons. As astrocytes secrete citrate into extracellular medium, the potential function of SLC13A5 in neurons is to mediate the uptake of circulating citrate and astrocyte-released citrate for subsequent metabolism. Slc13a5-knockout mice have been generated; these mice do not have any overt phenotype but are resistant to experimentally induced metabolic syndrome. Recently however, loss-of-function mutations in human SLC13A5 have been found to cause severe epilepsy

Creatinine Versus Cystatin C: Differing Estimates of Renal Function in Hospitalized Veterans Receiving Anticoagulants.

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Wang, Christina Hao; Rubinsky, Anna D; Minichiello, Tracy; Shlipak, Michael G; Price, Erika Leemann

2018-05-31

Current practice in anticoagulation dosing relies on kidney function estimated by serum creatinine using the Cockcroft-Gault equation. However, creatinine can be unreliable in patients with low or high muscle mass. Cystatin C provides an alternative estimation of glomerular filtration rate (eGFR) that is independent of muscle. We compared cystatin C-based eGFR (eGFR cys ) with multiple creatinine-based estimates of kidney function in hospitalized patients receiving anticoagulants, to assess for discordant results that could impact medication dosing. Retrospective chart review of hospitalized patients over 1 year who received non-vitamin K antagonist anticoagulation, and who had same-day measurements of cystatin C and creatinine. Seventy-five inpatient veterans (median age 68) at the San Francisco VA Medical Center (SFVAMC). We compared the median difference between eGFR by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) study equation using cystatin C (eGFR cys ) and eGFRs using three creatinine-based equations: CKD-EPI (eGFR EPI ), Modified Diet in Renal Disease (eGFR MDRD ), and Cockcroft-Gault (eGFR CG ). We categorized patients into standard KDIGO kidney stages and into drug-dosing categories based on each creatinine equation and calculated proportions of patients reclassified across these categories based on cystatin C. Cystatin C predicted overall lower eGFR compared to creatinine-based equations, with a median difference of - 7.1 (IQR - 17.2, 2.6) mL/min/1.73 m 2 versus eGFR EPI , - 21.2 (IQR - 43.7, - 8.1) mL/min/1.73 m 2 versus eGFR MDRD , and - 25.9 (IQR - 46.8, - 8.7) mL/min/1.73 m 2 versus eGFR CG . Thirty-one to 52% of patients were reclassified into lower drug-dosing categories using cystatin C compared to creatinine-based estimates. We found substantial discordance in eGFR comparing cystatin C with creatinine in this group of anticoagulated inpatients. Our sample size was limited and included few women. Further

Differentiation of malignant and degenerative benign bone disease using 99mTc-citrate scintigraphy

International Nuclear Information System (INIS)

Guo Rui; Jin Jianhua; Li Sijin; Li Xianfeng; Zhang Xiaojuan; Ren Yuan

2008-01-01

Objective: To differentiate malignant and degenerative benign bone disease using 99m Tc- citrate scintigraphy. Methods: Thirty-nine patients (92 lesions) with confirmed malignant bone disease or degenerative benign bone disease were studied, for which the results of 99m Te-methylene diphosphonate( 99m Tc- MDP) scintigraphy were positive. 99m Tc-citrate scintigraphy was performed within a time interval of 2-7 days after 99m Tc-MDP scintigraphy. Visual analysis and semiquantitative analysis were applied. Each lesion was scored as malignant or benign, which was independently verified, using conventional techniques (histopathology, X-ray, CT, MRI and clinical follow up). Results: In visual analysis of 99m Tc-citrate imaging, most malignant lesions (35/48, 72.92%) clearly showed high radioactivity accumulation, while most benign lesions (39/44, 88.64%) had not obviously visible uptake of 99m Tc-citrate. In semiquantitative analysis of 99m Tc- citrate image, malignant lesions demonstrated a higher lesion-to-background radioisotope uptake ratio (RUR) than that of benign degenerative lesions (1.47 ± 0.42 vs. 1.09 ± 0.38, t=2.887, P 99m Tc-MDP in the two groups is of the same (1.96 ± 0.25 vs. 1.87 ± 0.21, t=1.178, P>0.20). Conclusion: 99m Tc- citrate scintigraphy is a promising method to differentiate malignant from benign degenerative lesions seen as areas of increased activity on 99m Tc-MDP bone scintigraphy. (authors)

Metformin-letrozole in comparison with Metformin-clomiphene citrate in clomiphene-resistance PCOS patients undergoing IUI

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Mohammad Hossein Fallahzadeh

2011-01-01

Full Text Available Background: Polycystic ovary syndrome (PCOS is associated with approximately 75% of women who suffer from infertility due to anovulation. Additionally, around 20– 25% of anovulatory women with PCOS do not respond at all to clomiphene citrate and are considered to be “clomiphene– resistant”. Aromatase inhibitors have been suggested as an alternative treatment to clomiphene as the discrepancy between ovulation and pregnancy rates with clomiphene citrate has been attributed to its anti-estrogenic action and estrogen receptor depletion. Objective: The aim of this study is to compare results of Metformin-letrozole with Metformin-clomiphene citrate in clomiphene resistance PCOS patients undergoing IUI.Materials and Methods: In this single blind randomized trial, ovarian cycles were studied in 100 clomiphene- resistant patients with PCOS. The inclusion criteria were patients who received 150mg clomiphene citrate daily for 3 cycles and failed to become pregnant. The patients were matched for their age, body mass index (BMI, and infertility period. They were randomly allocated to a metformin-letrozole group (n=50 and a metformin-clomiphene citrate group (n=50. Chemical and clinical pregnancies were assessed after IUI. Abortion rates were determined in both groups. Results: Regarding pregnancy rate, there was no significant difference between the two groups. One miscarriage (2% occurred in the metformin-clomiphene citrate group, whereas none was seen in the metformin-letrozole group. Conclusion: There is no significant difference in pregnancy rate between clomiphene citrate and letrozole groups although it has been 2% in the former and 5% in the latter.

Structural insights into the elevator-like mechanism of the sodium/citrate symporter CitS.

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Kim, Ji Won; Kim, Subin; Kim, Songwon; Lee, Haerim; Lee, Jie-Oh; Jin, Mi Sun

2017-05-31

The sodium-dependent citrate transporter of Klebsiella pneumoniae (KpCitS) belongs to the 2-hydroxycarboxylate transporter (2-HCT) family and allows the cell to use citrate as sole carbon and energy source in anaerobic conditions. Here we present crystal structures of KpCitS in citrate-bound outward-facing, citrate-bound asymmetric, and citrate-free inward-facing state. The structures reveal that the KpCitS dimerization domain remains stationary throughout the transport cycle due to a hydrogen bond network as well as extensive hydrophobic interactions. In contrast, its transport domain undergoes a ~35° rigid-body rotation and a ~17 Å translocation perpendicular to the membrane to expose the substrate-binding site alternately to either side of the membrane. Furthermore, homology models of two other 2-HCT proteins based on the KpCitS structure offer structural insights into their differences in substrate specificity at a molecular level. On the basis of our results and previous biochemical data, we propose that the activity of the 2-HCT CitS involves an elevator-like movement in which the transport domain itself traverses the lipid bilayer, carrying the substrate into the cell in a sodium-dependent manner.

Efficacy and safety of a pharmacist-managed inpatient anticoagulation service for warfarin initiation and titration.

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Wong, Y M; Quek, Y-N; Tay, J C; Chadachan, V; Lee, H K

2011-10-01

Anticoagulation consultations provided by a pharmacist-staffed inpatient service, similar to the experience reported in outpatient anticoagulation clinics, can potentially improve anticoagulation control and outcomes. At Tan Tock Seng Hospital, a 1200-bed acute care teaching hospital in Singapore, pharmacist-managed anticoagulation clinics have been in place since 1997. Pharmacist-managed services were extended to inpatient consultations in anticoagulation management from April 2006. Our objective was to assess the effect of implementing a pharmacist-managed inpatient anticoagulation service. This was a single-centre cohort study. Baseline data from 1 January 2006 to 31 March 2006 were collected and compared with post-implementation data from 1 April 2006 to 31 March 2007. Patients newly started on warfarin for deep vein thrombosis, pulmonary embolism or atrial fibrillation in general medicine and surgery departments were included. The three endpoints were as follows: (i) percentage of international normalized ratios (INRs) achieving therapeutic range within 5 days, (ii) INRs more than 4 during titration and (iii) subtherapeutic INRs on discharge. A total of 26 patients in the control period were compared with 144 patients who had received dosing consultations by a pharmacist during the initiation of warfarin. The provision of pharmacist consult resulted in 88% compared to 38% (P < 0·001) of INR values achieving therapeutic range within 5 days. There was a reduction in INR values of more than 4 during titration from 27% to 2% (P < 0·001), and subtherapeutic INR values on discharge without low molecular weight heparin from 15% to 0% (P < 0·001). The mean time to therapeutic INR was reduced from 6·5 to 3·9 days (P < 0·001) and mean length of stay after initiation of warfarin from 11 to 7·7 days (P = 0·004). Inpatient anticoagulation care and outcomes were significantly improved by a pharmacist-managed anticoagulation service. The time to therapeutic INR was

Trends in oral anticoagulant choice for acute stroke patients with nonvalvular atrial fibrillation in Japan: The SAMURAI‐NVAF Study

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Arihiro, Shoji; Todo, Kenichi; Yamagami, Hiroshi; Kimura, Kazumi; Furui, Eisuke; Terasaki, Tadashi; Shiokawa, Yoshiaki; Kamiyama, Kenji; Takizawa, Shunya; Okuda, Satoshi; Okada, Yasushi; Kameda, Tomoaki; Nagakane, Yoshinari; Hasegawa, Yasuhiro; Mochizuki, Hiroshi; Ito, Yasuhiro; Nakashima, Takahiro; Takamatsu, Kazuhiro; Nishiyama, Kazutoshi; Kario, Kazuomi; Sato, Shoichiro; Koga, Masatoshi; Nagatsuka, K; Minematsu, K; Nakagawara, J; Akiyama, H; Shibazaki, K; Maeda, K; Shibuya, S; Yoshimura, S; Endo, K; Miyagi, T; Osaki, M; Kobayashi, J; Okata, T; Tanaka, E; Sakamoto, Y; Takizawa, H; Takasugi, J; Tokunaga, K; Homma, K; Kinoshita, N; Matsuki, T; Higashida, K; Shiozawa, M; Kanai, H; Uehara, S

2015-01-01

Background Large clinical trials are lack of data on non‐vitamin K antagonist oral anticoagulants for acute stroke patients. Aim To evaluate the choice of oral anticoagulants at acute hospital discharge in stroke patients with nonvalvular atrial fibrillation and clarify the underlying characteristics potentially affecting that choice using the multicenter Stroke Acute Management with Urgent Risk‐factor Assessment and Improvement‐NVAF registry (ClinicalTrials.gov NCT01581502). Method The study included 1192 acute ischemic stroke/transient ischemic attack patients with nonvalvular atrial fibrillation (527 women, 77·7 ± 9·9 years old) between September 2011 and March 2014, during which three nonvitamin K antagonist oral anticoagulant oral anticoagulants were approved for clinical use. Oral anticoagulant choice at hospital discharge (median 23‐day stay) was assessed. Results Warfarin was chosen for 650 patients, dabigatran for 203, rivaroxaban for 238, and apixaban for 25. Over the three 10‐month observation periods, patients taking warfarin gradually decreased to 46·5% and those taking nonvitamin K antagonist oral anticoagulants increased to 48·0%. As compared with warfarin users, patients taking nonvitamin K antagonist oral anticoagulants included more men, were younger, more frequently had small infarcts, and had lower scores for poststroke CHADS 2, CHA 2 DS 2‐VASc, and HAS‐BLED, admission National Institutes of Health stroke scale, and discharge modified Rankin Scale. Nonvitamin K antagonist oral anticoagulants were started at a median of four‐days after stroke onset without early intracranial hemorrhage. Patients starting nonvitamin K antagonist oral anticoagulants earlier had smaller infarcts and lower scores for the admission National Institutes of Health stroke scale and the discharge modified Rankin Scale than those starting later. Choice of nonvitamin K antagonist oral anticoagulants was independently associated with 20‐day or

Influence of temperature on flavour compound production from citrate by Lactobacillus rhamnosus ATCC 7469.

Science.gov (United States)

De Figueroa, R M; Oliver, G; Benito de Cárdenas, I L

2001-03-01

The citrate utilization by Lactobacillus rhamnosus ATCC 7469 was found to be temperature-dependent. The maximum citrate utilization and incorporation of [1,5-14C]citrate rate were observed at 37 degreesC. At this temperature, maximum citrate lyase activity and specific diacetyl and acetoin production (Y(DA%)) were observed. The high levels of alpha-acetolactate synthase and low levels of diacetyl reductase, acetoin reductase and L-lactate dehydrogenase found at 37 degreesC led to an accumulation of diacetyl and acetoin. Optimum lactic acid production was observed at 45 degreesC, according to the high lactate dehydrogenase activity. The NADH oxidase activity increased with increasing culture temperature from 22 degreesC to 37 degreesC. Thus there are greater quantities of pyruvate available for the production of alpha-acetolactate, diacetyl and aceotin, and less diacetyl and acetoin are reduced.

Antitumor effect of free rhodium (II) citrate and rhodium (II) citrate-loaded maghemite nanoparticles on mice bearing breast cancer: a systemic toxicity assay.

Science.gov (United States)

Peixoto, Raphael Cândido Apolinário; Miranda-Vilela, Ana Luisa; de Souza Filho, José; Carneiro, Marcella Lemos' Brettas; Oliveira, Ricardo G S; da Silva, Matheus Oliveira; de Souza, Aparecido R; Báo, Sônia Nair

2015-05-01

Breast cancer is one of the most prevalent cancer types among women. The use of magnetic fluids for specific delivery of drugs represents an attractive platform for chemotherapy. In our previous studies, it was demonstrated that maghemite nanoparticles coated with rhodium (II) citrate (Magh-Rh2Cit) induced in vitro cytotoxicity and in vivo antitumor activity, followed by intratumoral administration in breast carcinoma cells. In this study, our aim was to follow intravenous treatment to evaluate the systemic antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Female Balb/c mice were evaluated with regard to toxicity of intravenous treatments through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine and liver, kidney, and lung histology. The antitumor activity of rhodium (II) citrate (Rh2Cit), Magh-Rh2Cit, and maghemite nanoparticles coated with citrate (Magh-Cit), used as control, was evaluated by tumor volume reduction, histology, and morphometric analysis. Magh-Rh2Cit and Magh-Cit promoted a significant decrease in tumor area, and no experimental groups presented hematotoxic effects or increased levels of serum ALT and creatinine. This observation was corroborated by the histopathological examination of the liver and kidney of mice. Furthermore, the presence of nanoparticles was verified in lung tissue with no morphological changes, supporting the idea that our nanoformulations did not induce toxicity effects. No studies about the systemic action of rhodium (II) citrate-loaded maghemite nanoparticles have been carried out, making this report a suitable starting point for exploring the therapeutic potential of these compounds in treating breast cancer.

Reference intervals of citrated-native whole blood thromboelastography in premature neonates.

Science.gov (United States)

Motta, Mario; Guaragni, Brunetta; Pezzotti, Elena; Rodriguez-Perez, Carmen; Chirico, Gaetano

2017-12-01

Bleeding due to acquired coagulation disorders is a common complication in premature neonates. In this clinical setting, standard coagulation laboratory tests might be unsuitable to investigate the hemostatic function as they reflect the concentration of pro-coagulant proteins but not of anti-coagulant proteins. Thromboelastography (TEG), providing a more complete assessment of hemostasis, may be able to overcome some of these limitations. Unfortunately, experience on the use of TEG in premature neonates is very limited and, in particular in this population, reference ranges of TEG parameters have not been yet evaluated. To evaluate TEG in preterm neonates, and to assess their reference ranges. One hundred and eighteen preterm neonates were analyzed for TEG in a retrospective cohort study. Double-sided 95% reference intervals were calculated using a bootstrap method after Box-Cox transformation. TEG parameters were compared between early-preterm and moderate-/late-preterm neonates and between bleeding and non-bleeding preterm neonates. Comparing early-preterm with moderate-/late-preterm neonates, TEG parameters were not statistically different, except for fibrinolysis which was significantly higher in early preterm neonates. Platelet count significantly correlated with α angle and MA parameters. Bleeding and non-bleeding neonates had similar TEG values. These results reinforce the concept that in stable preterm neonates, in spite of lower concentration of pro- and anti-coagulants proteins, the hemostasis is normally balanced and well functioning. Copyright © 2017 Elsevier B.V. All rights reserved.

Local hemostatic measures in anticoagulated patients undergoing oral surgery: a systematized literature review

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Fábio Wildson Gurgel Costa

2013-01-01

Full Text Available PURPOSE: To conduct a systematized review of the literature about the main local hemostatic measures to control postoperative bleeding in anticoagulated patients. METHODS: A systematized review of literature was performed in the electronic database Medline (PubMed without restriction of the publication date. The eligibility criteria were studies involving maintenance of the anticoagulant therapy, prospective studies, retrospective studies, randomized clinical trials, controlled clinical studies, comparative studies, multicentric studies or case-control studies. Studies discontinuing anticoagulant therapy, case reports, literature reviews, in vitro studies, animal experiments and articles written in language not compatible with the search strategy adopted in this work were excluded. RESULTS: Twenty-four articles that met the adopted eligibility criteria were selected, enrolling 3891 subjects under anticoagulant therapy. A total of 171 cases of hemorrhage was observed. Tranexamic acid was the main local hemostatic measure used to controlling of postoperative bleeding. CONCLUSION: The local hemostatic measures proved to be effective according to previously published studies. Nevertheless, further clinical studies should be conducted to confirm this effectiveness.

Effects of L-arginine immobilization on the anticoagulant activity and hemolytic property of polyethylene terephthalate films

International Nuclear Information System (INIS)

Liu Yun; Yang Yun; Wu Feng

2010-01-01

Surface modification of polyethylene terephthalate (PET) films was performed with L-arginine (L-Arg) to gain an improved anticoagulant surface. The surface chemistry changes of modified films were characterized by X-ray photoelectron spectroscopy (XPS) and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. The in vitro anticoagulant activities of the surface-modified PET films were evaluated by blood clotting test, hemolytic test, and the measurement of clotting time including plasma recalcification time (PRT), activated partial thromboplastin time (APTT), and prothrombin time (PT). The data of blood coagulation index (BCI) for L-arginine modified PET films (PET-Arg) was larger than that for PET at the same blood-sample contact time. The hemolysis ratio for PET-Arg was less than that for PET and within the accepted standard for biomaterials. The PRT and APTT for PET-Arg were significantly prolonged by 189 s and 25 s, respectively, compared to those for the unmodified PET. All results suggested that the currently described modification method could be a possible candidate to create antithrombogenic PET surfaces which would be useful for further medical applications.

Direct Oral Anticoagulants: An Overview for the Interventional Radiologist

Energy Technology Data Exchange (ETDEWEB)

Kumar, Pradesh, E-mail: pradeshkumar@doctors.org.uk; Ravi, Rajeev, E-mail: rajeev.ravi@aintree.nhs.uk; Sundar, Gaurav, E-mail: gaurav.sundar@aintree.nhs.uk [Aintree University Hospitals NHS Foundation Trust, Radiology Department (United Kingdom); Shiach, Caroline, E-mail: caroline.shiach@aintree.nhs.uk [Aintree University Hospitals NHS Foundation Trust, Haematology Department (United Kingdom)

2017-03-15

The direct oral anticoagulants (DOACs) have emerged as a good alternative for the treatment of thromboembolic diseases, and their use in clinical practice is increasing rapidly. The DOACs act by blocking the activity of one single step in the coagulation cascade. These drugs act downstream in the common pathway of the coagulation cascade by directly antagonising the action of thrombin or factor Xa. The development of DOACs represents a paradigm shift from the oral vitamin K antagonists such as warfarin. This article aims to describe the properties of the currently available DOACs including pharmacology and dosing. We also address the strategies for periprocedural management and reversal of anticoagulation of patients treated with these agents.

Direct Oral Anticoagulants: An Overview for the Interventional Radiologist

International Nuclear Information System (INIS)

Kumar, Pradesh; Ravi, Rajeev; Sundar, Gaurav; Shiach, Caroline

2017-01-01

The direct oral anticoagulants (DOACs) have emerged as a good alternative for the treatment of thromboembolic diseases, and their use in clinical practice is increasing rapidly. The DOACs act by blocking the activity of one single step in the coagulation cascade. These drugs act downstream in the common pathway of the coagulation cascade by directly antagonising the action of thrombin or factor Xa. The development of DOACs represents a paradigm shift from the oral vitamin K antagonists such as warfarin. This article aims to describe the properties of the currently available DOACs including pharmacology and dosing. We also address the strategies for periprocedural management and reversal of anticoagulation of patients treated with these agents.

Anticoagulation therapy a risk factor for the development of chronic subdural hematoma

DEFF Research Database (Denmark)

Aspegren, Oskar P.; Åstrand, Ramona; Lundgren, Maria I.

2013-01-01

Chronic subdural hematoma (CSDH) is a common disease among the elderly and with increasing incidence we have chosen to focus on associations between development and recurrence of CSDH and anticoagulation and/or antiplatelet agent therapy.......Chronic subdural hematoma (CSDH) is a common disease among the elderly and with increasing incidence we have chosen to focus on associations between development and recurrence of CSDH and anticoagulation and/or antiplatelet agent therapy....

Bioassay-guided fractionation of Melastoma malabathricum Linn. leaf solid phase extraction fraction and its anticoagulant activity.

Science.gov (United States)

Khoo, Li Teng; Abdullah, Janna Ong; Abas, Faridah; Tohit, Eusni Rahayu Mohd; Hamid, Muhajir

2015-02-24

The aims of this study were to examine the bioactive component(s) responsible for the anticoagulant activity of M. malabathricum Linn. leaf hot water crude extract via bioassay-guided fractionation and to evaluate the effect of bioactive component(s) on the intrinsic blood coagulation pathway. The active anticoagulant fraction of F3 was subjected to a series of chromatographic separation and spectroscopic analyses. Furthermore, the effect of the bioactive component(s) on the intrinsic blood coagulation pathway was studied through immediate and time incubation mixing studies. Through Activated Partial Thromboplastin Time (APTT) assay-guided fractionation, Subfraction B was considered the most potent anticoagulant fraction. Characterisation of Subfraction B indicated that anticoagulant activity could partly be due to the presence of cinnamic acid and a cinnamic acid derivative. APTT assays for both the immediate and time incubation mixing were corrected back into normal clotting time range (35.4-56.3 s). In conclusion, cinnamic acid and cinnamic acid derivative from Subfraction B were the first such compounds to be discovered from M. malabathricum Linn. leaf hot water crude extract that possess anticoagulant activity. This active anticoagulant Subfraction B prolonged blood clotting time by causing factor(s) deficiency in the intrinsic blood coagulation pathway.

Human METTL12 is a mitochondrial methyltransferase that modifies citrate synthase.

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Rhein, Virginie F; Carroll, Joe; Ding, Shujing; Fearnley, Ian M; Walker, John E

2017-06-01

The protein methylome in mammalian mitochondria has been little studied until recently. Here, we describe that lysine-368 of human citrate synthase is methylated and that the modifying enzyme, localized in the mitochondrial matrix, is methyltransferase-like protein 12 (METTL12), a member of the family of 7β-strand methyltransferases. Lysine-368 is near the active site of citrate synthase, but removal of methylation has no effect on its activity. In mitochondria, it is possible that some or all of the enzymes of the citric acid cycle, including citrate synthase, are organized in metabolons to facilitate the channelling of substrates between participating enzymes. Thus, possible roles for the methylation of Lys-368 are in controlling substrate channelling itself, or in influencing protein-protein interactions in the metabolon. © 2017 The Authors FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Physicochemical properties and anticoagulant activity of polyphenols derived from Lachnum singerianum

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Shuai Zong

2017-10-01

Full Text Available In this study, polyphenols (LSP were obtained from the fermentation broth of Lachnum singerianum. Two fractions were isolated by Sephadex LH-20 chromatographic column, and the primary fraction (LSP-1 was collected. The comprehensive physicochemical properties of phenolic acids and polyhydroxy phenolic compounds of LSP-1 were determined by UV-visible spectroscopy, Fourier transform infrared spectroscopy, and gas chromatography–mass spectrometry. Results of anticoagulant activity assay in vitro showed that LSP-1 could lengthen prothrombin time, activated partial thromboplastin time, and thrombin time of mouse plasma. In addition, anticoagulant activity results in vivo showed that high dose of LSP-1 could significantly prolong bleeding time, coagulation time, prothrombin time, activated partial thromboplastin time, and thrombin time of hypercoagulable mice induced by adrenaline, reduce the content of fibrinogen and enhance antithrombin III activity. All results indicated that the LSP-1 could serve well as an anticoagulant, and might be used as a potential natural drug candidate for thrombosis.

Effects of Citrate and Arginine on Sorption of Nickel to Yazd Sepiolite and Calcite

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Ahmadreza Sheikhhosseini

2017-03-01

Full Text Available Introduction: Pollution of soil and water environment by release of heavy metals is of great concerns of the last decades. Sorption of heavy metals by low cost materials is considered as an inexpensive and efficient method used for removal of heavy metals from soil-water systems. The presence of different ligands with various complexing abilities can change the sorption properties of heavy metals and their fate in the environment as well. In order to assess the effect of citrate and arginine as natural organic ligands in soil environment, in a batch study we investigated the effects of these ligands on equilibrium sorption of nickel to sepiolite and calcite minerals and also kinetics of Ni sorption by these minerals. Materials and Methods: Minerals used in this study included sepiolite from Yazd (Iran and pure calcite (Analytical grade, Merck, Germany. Sepiolite was purified, saturated with Ca using 0.5 M CaCl2, powdered in a mortar and sieved by non-metal 230 mesh standard wire sieve. For equilibrium sorption study, in a 50-mL polyethylene centrifuge tube,0.3 g sample of each mineral was suspended in 30 mL of a 0.01 M CaCl2 solution containing 0, 5, 10, 20, 40, 60, 80 and 100 mg L-1 Ni (NiCl2 and containing zero (as control or 0.1mmol L-1 citrate or arginine ligands. The applied concentrationsfor each ligand can naturally occur in soils. Preparedtubes were shaken (180±2 rpm, 25±1oC for 24 h using an orbital shaker and centrifuged (4000×g for 10 min and the supernatants were analyzed for Ni concentration using an atomic absorption spectrophotometer (AAnalyst 200 Perkin-Elmer at a wavelength of 232 nm and a detection limit of 0.05 mg L-1. The quantity of Ni retained by each mineral at equilibrium was calculated using equation qe = (Ci - CeV/W where qe was the amount of nickel retained by mineral surface at equilibrium. Ci and Ce were the initial and the equilibrium concentrations (mg L-1 of Ni, respectively, V was the volume (L of the solution

Citrate-coated silver nanoparticles interactions with effluent organic matter: influence of capping agent and solution conditions

KAUST Repository

Gutierrez, Leonardo

2015-07-31

Fate and transport studies of silver nanoparticles (AgNPs) discharged from urban wastewaters containing effluent organic matter (EfOM) into natural waters represent a key knowledge gap. In this study, EfOM interfacial interactions with AgNPs and their aggregation kinetics were investigated by atomic force microscopy (AFM) and time-resolved dynamic light scattering (TR-DLS), respectively. Two well-characterized EfOM isolates, i.e., wastewater humic (WW humic) and wastewater colloids (WW colloids, a complex mixture of polysaccharides-proteins-lipids), and a River humic isolate of different characteristics were selected. Citrate-coated AgNPs were selected as representative capped-AgNPs. Citrate-coated AgNPs showed a considerable stability in Na+ solutions. However, Ca2+ ions induced aggregation by cation bridging between carboxyl groups on citrate. Although the presence of River humic increased the stability of citrate-coated AgNPs in Na+ solutions due to electrosteric effects, they aggregated in WW humic-containing solutions, indicating the importance of humics characteristics during interactions. Ca2+ ions increased citrate-coated AgNPs aggregation rates in both humic solutions, suggesting cation bridging between carboxyl groups on their structures as a dominant interacting mechanism. Aggregation of citrate-coated AgNPs in WW colloids solutions was significantly faster than those in both humic solutions. Control experiments in urea solution indicated hydrogen bonding as the main interacting mechanism. During AFM experiments, citrate-coated AgNPs showed higher adhesion to WW humic than to River humic, evidencing a consistency between TR-DLS and AFM results. Ca2+ ions increased citrate-coated AgNPs adhesion to both humic isolates. Interestingly, strong WW colloids interactions with citrate caused AFM probe contamination (nanoparticles adsorption) even at low Na+ concentrations, indicating the impact of hydrogen bonding on adhesion. These results suggest the importance

Corrosion behavior of Ti and TI6Al4V in citrate buffers containing fluoride ions

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Anelise Marlene Schmidt

2010-03-01

Full Text Available The effect of fluoride ions concentration on the electrochemical behavior of Ti grade 2 and Ti6Al4V in citrate buffers was studied. Open circuit potential (OCP measurements and voltammetric studies of the samples in the fluoride containing citrate buffers revealed a dissolution process when the pH falls below 5.0 and the NaF content is higher than 0.01 M. However, in citrate pH 7.6 the materials showed a passive behavior even in 0.1 M NaF. Some micrographs of Ti grade 2 obtained after longer immersion times in citrate pH 5.0 with 0.01 M NaF showed a surface attack. EIS (Electrochemical Impedance Sprectroscopy data obtained at the OCP revealed that the film resistance decreases when the immersion time is increased in pH 5.0 containing 0.1 M NaF. In the citrate pH 7.6 the EIS data indicated a two-layer model of an oxide film consisting of a more compact inner layer and a porous outer layer. On the other hand, the EIS results in citrate pH 4.0 change significantly when the fluoride ions concentration increases from 0.01 to 0.05 M. The electrochemical data revealed that the corrosion behavior of Ti grade 2 and Ti6Al4V in the citrate buffers depends on the pH, the fluoride content and the exposure time.

Sildenafil citrate (Viagra) impairs fertilization and early embryo development in mice.

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Glenn, David R J; McClure, Neil; Cosby, S Louise; Stevenson, Michael; Lewis, Sheena E M

2009-03-01

To determine the effects of sildenafil citrate, a cyclic monophosphate-specific type 5 phosphodiesterase inhibitor known to affect sperm function, on fertilization and early embryo cleavage. This acute mammal study included male and female mice assigned randomly, the females sacrificed after mating and their oocytes/embryos evaluated at four time periods after treatment. Academic research environment. Male and female CBAB(6) mice. Female mice were injected intraperitoneally with 5 IU gonadotropin (hCG) to stimulate follicular growth and induce ovulation. They were each caged with a male that had been gavaged with sildenafil citrate (0.06 mg/0.05 mL) and allowed to mate. After 12, 36, 60, and 84 h, females were killed, their oviducts were dissected out, and retrieved embryos were assessed for blastomere number and quality. Fertilization rates and numbers of embryos were evaluated after treatment. Fertilization rates (day 1) were markedly reduced (-33%) in matings where the male had taken sildenafil citrate. Over days 2-4, the numbers of embryos developing in the treated group were significantly fewer than in the control group. There was also a trend for impaired cleavage rates within those embryos, although this did not reach significance. The impairments to fertility caused by sildenafil citrate have important implications for infertility centers and for couples who are using this drug precoitally while attempting to conceive.

Oral anticoagulation for stroke prevention amongst atrial fibrillation patients with valvular heart disease: an update.

Science.gov (United States)

Ha, Andrew C T; Verma, Atul; Verma, Subodh

2017-03-01

The majority of evidence on the safety and efficacy of oral anticoagulation for stroke prevention amongst patients with atrial fibrillation is derived from those without significant valvular heart disease. This article will review current knowledge, areas of uncertainty and controversy, and ongoing research on oral anticoagulation for stroke prevention amongst patients with valvular heart disease. The rates of stroke, systemic embolism, and major bleeding were similar for patients with and without significant native valvular disease when treated with direct oral anticoagulants (DOACs) or vitamin K antagonists. There are very limited prospective data on the safety and efficacy of DOAC use for patients with bioprosthetic valves or rheumatic mitral stenosis. Atrial fibrillation patients with concomitant valvulopathies constitute a group with high thromboembolic risk and should be treated with oral anticoagulation. There is good supportive evidence that DOAC is well tolerated and effective in preventing thromboembolism amongst patients with native valvular disease. Further research is underway to better define the risks and benefits of DOAC use among patients with bioprosthetic valves or rheumatic mitral stenosis in preventing thromboembolic events. Until then, vitamin K antagonists remain the oral anticoagulant of choice for these patient subsets.

Renal Localization of 67Ga Citrate in Noninfectious Nephritis

International Nuclear Information System (INIS)

Lee, Kang Wook; Jeong, Min Soo; Rhee, Sunn Kgoo; Kim, Sam Yong; Shin, Young Tai; Ro, Heung Kyu

1992-01-01

67 Ga citrate scan has been requested for detection or follow-up of inflammatory or neoplastic disease. Visualization of 67 Ga citrate in the kidneys at 48 and 72 hr post injection is usually interpreted as evidence of renal pathology. But precise mechanisms of abnormal 67 Ga uptake in kidneys were unknown. We undertook a study to determine the clinical value of 67 Ga citrate imaging of the kidneys in 68 patients with primary or secondary nephropathy confirmed by renal biopsy and 66 control patients without renal disease. Renal uptake in 48 to 72 hr images was graded as follows: Grade 0=background activity;1=faint uptake greater than background; 2=definite uptake, but less than lumbar vertebrae;3 same uptake as lumbar vertebrae, but less than liver; 4=same or higher uptake than liver. The results were as follows. 1) 42 of 68(62%) patients with noninfectious nephritis showed grade 2 or higher 67 Ga renal uptake but only 10 percent of control patients showed similar uptake. 2) In 14 patients with systemic lupus erythematosus, 8 of 9 (89%) patients with lupus nephritis exhibited marked renal uptake. 3) 36 of 41 patients (88%) with combined nephrotic syndrome showed Grade 2 or higher renal uptake. 4) Renal 67 Ga uptake was correlated with clinical severity of nephrotic syndrome determined by serum albumin level, 24 hr urine protein excretion and serum lipid levels. 5) After complete remission of nephrotic syndrome, renal uptake in all 8 patients who were initially Grade 3 or 4, decreased to Grade 1 or 0. In conclusion, we think that the mechanism of renal 67 Ga uptake in nephrotic syndrome might be related to the pathogenesis of nephrotic syndrome. In systemic lupus erythematosus, 67 Ga citrate scan is useful in predicting renal involvement.

Differential expression of cytochrome P450 genes between bromadiolone-resistant and anticoagulant-susceptible Norway rats:

DEFF Research Database (Denmark)

Markussen, Mette Drude; Heiberg, Ann-Charlotte; Fredholm, Merete

2008-01-01

Anticoagulant resistance in Norway rats (Rattus norvegicus) has been suggested to be due to mutations in the VKORC1 gene, encoding the target protein of anticoagulant rodenticides such as warfarin and bromadiolone. Other factors, e.g. pharmacokinetics, may however also contribute to resistance. We...... that bromadiolone resistance in Norway rats involves enhanced anticoagulant clearance and metabolism catalyzed by specific cytochrome P450 enzymes, such as Cyp2e1, Cyp3a2 and Cyp3a3. This pharmacokinetically based resistance varies to some extend between the genders....

Differential expression of cytochrome P450 genes between bromadiolone-resistant and anticoagulant-susceptible Norway rats

DEFF Research Database (Denmark)

Markussen, Mette Drude Kjær; Heiberg, Ann-Charlotte; Fredholm, Merete

2008-01-01

Background: Anticoagulant resistance in Norway rats, Rattus norvegicus (Berk.), has been suggested to be conferred by mutations in the VKORC1 gene, encoding the target protein of anticoagulant rodenticides. Other factors, e.g. pharmacokinetics, may also contribute to resistance, however. To examine......, Cyp3a2 and Cyp3a3 genes. On exposure to bromadiolone, females had higher Cyp2e1 expression than males, which possibly explains why female rats are generally more tolerant to anticoagulants than male rats. Conclusion: results suggest that bromadiolone resistance in a Danish strain of Norway rats...

The structure and binding mode of citrate in the stabilization of gold nanoparticles

KAUST Repository

Al-Johani, Hind; Abou-Hamad, Edy; Jedidi, Abdesslem; Widdifield, Cory M.; Viger-Gravel, Jasmine; Sangaru, Shiv; Gajan, David; Anjum, Dalaver H.; Ould-Chikh, Samy; Hedhili, Mohamed N.; Gurinov, Andrei; Kelly, Michael J.; El Eter, Mohamad; Cavallo, Luigi; Basset, Jean-Marie; Basset, Jean-Marie

2017-01-01

Elucidating the binding mode of carboxylate-containing ligands to gold nanoparticles (AuNPs) is crucial to understand their stabilizing role. A detailed picture of the three-dimensional structure and coordination modes of citrate, acetate, succinate and glutarate to AuNPs is obtained by 13C and 23Na solid-state NMR in combination with computational modelling and electron microscopy. The binding between the carboxylates and the AuNP surface is found to occur in three different modes. These three modes are simultaneously present at low citrate to gold ratios, while a monocarboxylate monodentate (1κO1) mode is favoured at high citrate:gold ratios. The surface AuNP atoms are found to be predominantly in the zero oxidation state after citrate coordination, although trace amounts of Auδ+ are observed. 23Na NMR experiments show that Na+ ions are present near the gold surface, indicating that carboxylate binding occurs as a 2e− L-type interaction for each oxygen atom involved. This approach has broad potential to probe the binding of a variety of ligands to metal nanoparticles.

The structure and binding mode of citrate in the stabilization of gold nanoparticles

KAUST Repository

Al-Johani, Hind

2017-03-27

Elucidating the binding mode of carboxylate-containing ligands to gold nanoparticles (AuNPs) is crucial to understand their stabilizing role. A detailed picture of the three-dimensional structure and coordination modes of citrate, acetate, succinate and glutarate to AuNPs is obtained by 13C and 23Na solid-state NMR in combination with computational modelling and electron microscopy. The binding between the carboxylates and the AuNP surface is found to occur in three different modes. These three modes are simultaneously present at low citrate to gold ratios, while a monocarboxylate monodentate (1κO1) mode is favoured at high citrate:gold ratios. The surface AuNP atoms are found to be predominantly in the zero oxidation state after citrate coordination, although trace amounts of Auδ+ are observed. 23Na NMR experiments show that Na+ ions are present near the gold surface, indicating that carboxylate binding occurs as a 2e− L-type interaction for each oxygen atom involved. This approach has broad potential to probe the binding of a variety of ligands to metal nanoparticles.

Contributions of citrate in redox potential maintenance and ATP production: metabolic pathways and their regulation in Lactobacillus panis PM1.

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Kang, Tae Sun; Korber, Darren R; Tanaka, Takuji

2013-10-01

Lactobacillus panis PM1 belongs to the group III heterofermentative lactobacilli and can utilize various NADH-reoxidizing routes (e.g., citrate, glycerol, and oxygen) according to environmental conditions. In this study, we investigated the ability of L. panis PM1 to produce succinate, acetate, and lactate via citrate utilization. Possible pathways, as well as regulation, for citrate metabolism were examined on the basis of the genome sequence data and metabolic profiles of L. panis PM1. The presence of citrate led to the up-regulation, at the transcriptional level, of the genes encoding for citrate lyase, malate dehydrogenase, and malic enzyme of the citrate pathways by 10- to 120-fold. The transcriptional regulator of the dha operon coding for glycerol dehydratase of L. panis PM1 repressed the expression of the citrate lyase gene (10-fold). Metabolite analyses indicated that the transcriptional enhancement by citrate stimulated succinate yield. Citrate metabolism contributed to energy production by providing a major alternate pathway for NAD(+) regeneration and allowed acetyl phosphate to yield acetate/ATP instead of ethanol/NAD(+). Additionally, a branching pathway from oxaloacetate to pyruvate increased the pool of lactate, which was then used to produce ATP during stationary phase. However, the redirection of NADH-to-citrate utilization resulted in stress caused by end-products (i.e., succinate and acetate). This stress reduced succinate production by up to 50 % but did not cause significant changes at transcriptional level. Overall, citrate utilization was beneficial for the growth of L. panis PM1 by providing a NAD(+) regeneration route and producing extra ATP.

Citrate effects on amorphous calcium carbonate (ACC) structure, stability, and crystallization

DEFF Research Database (Denmark)

Tobler, Dominique Jeanette; Rodriguez Blanco, Juan Diego; Dideriksen, Knud

2015-01-01

Understanding the role of citrate in the crystallization kinetics of amorphous calcium carbonate (ACC) is essential to explain the formation mechanisms, stabilities, surface properties, and morphologies of CaCO3 biominerals. It also contributes to deeper insight into fluid-mineral inte......Understanding the role of citrate in the crystallization kinetics of amorphous calcium carbonate (ACC) is essential to explain the formation mechanisms, stabilities, surface properties, and morphologies of CaCO3 biominerals. It also contributes to deeper insight into fluid...

Consensus recommendations for preventing and managing bleeding complications associated with novel oral anticoagulants in singapore.

Science.gov (United States)

Ng, Heng Joo; Chee, Yen Lin; Ponnudurai, Kuperan; Lim, Lay Cheng; Tan, Daryl; Tay, Jam Chin; Handa, Pankaj Kumar; Akbar Ali, Mufeedha; Lee, Lai Heng

2013-11-01

Novel oral anticoagulants (NOACs) have at least equivalent efficacy compared to standard anticoagulants with similar bleeding risk. Optimal management strategies for bleeding complications associated with NOACs are currently unestablished. A working group comprising haematologists and vascular medicine specialists representing the major institutions in Singapore was convened to produce this consensus recommendation. A Medline and EMBASE search was conducted for articles related to the 3 available NOACs (dabigatran, rivaroxaban, apixaban), bleeding and its management. Additional information was obtained from the product monographs and bibliographic search of articles identified. The NOACs still has substantial interactions with a number of drugs for which concomitant administration should best be avoided. As they are renally excreted, albeit to different degrees, NOACs should not be prescribed to patients with creatinine clearance of factor VIIa and prothrombin complex may be considered although their effectiveness is currently unsupported by firm clinical evidence. The NOACs have varying effect on the prothrombin time and activated partial thromboplastin time which has to be interpreted with caution. Routine monitoring of drug level is not usually required. NOACs are an important advancement in antithrombotic management and careful patient selection and monitoring will permit optimisation of their potential and limit bleeding events.

A study of 153Sm-citrate-hydroxyapatite synovectomy in knee synovitis with rheumatoid arthritis

International Nuclear Information System (INIS)

Fan Yanggang; Li Guohua; Yao Guozhong; Zhang Qingcheng; Li Guangming

2006-01-01

Objective: To investigate the efficacy and safety of 153 Sm-citrate-hydroxyapatite (HA) synovectomy in knee synovitis with rheumatoid arthritis (RA). Methods: In 43 RA patients ineffective to routine anti-rheumatic drugs (DMMARDs) therapy, radiation synovectomy was performed by 153 Sm-citrate-HA in 67 joints and its efficacy and safety were evaluated. Results: Radioactivity was evenly distributed as observed by gamma camera after injection. In 8 cases leakage of radioactivity was detected after 24 h, and accounted to 153 Sm-citrate-HA synovectomy is effective after short-term and medium-term follow-up and it is a safe procedure. (authors)

77 FR 47370 - Citric Acid and Certain Citrate Salts from the People's Republic of China: Intent To Rescind...

Science.gov (United States)

2012-08-08

... DEPARTMENT OF COMMERCE International Trade Administration [C-570-938] Citric Acid and Certain... citric acid and certain citrate salts from the People's Republic of China.\\1\\ On May 31, 2012, we... order includes all grades and granulation sizes of citric acid, sodium citrate, and potassium citrate in...

Impact of Anticoagulation in Elderly Patients With Pulmonary Embolism That Undergo IVC Filter Placement: A Retrospective Cohort Study.

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Falatko, John M; Dalal, Bhavinkumar; Qu, Lihua

2017-12-01

Anticoagulation is the primary treatment for pulmonary embolism (PE). Inferior vena cava (IVC) filters are an adjunctive intervention to prevent recurrent pulmonary embolism. Long-term outcomes in elderly patients with contraindications to anticoagulation after IVC filter placement for prevention of recurrent pulmonary embolism have yet to be assessed. Patients ≥60years of age, that had an IVC filter placed between 1 January, 2008 and 2 February, 2013, with a primary diagnosis of pulmonary embolism, were included. Patients that died during index hospitalisation, were discharged to hospice, or had active malignancy were excluded. The primary endpoint was overall survival. Patients were divided depending on whether they were treated with an approved anticoagulant for VTE or had no anticoagulant. Of the 152 patients identified, 55 were not anti-coagulated after IVC filter placement. The incidence of death was 0.4 per 1000 filter days and 0.7 per 1000 filter days in the anti-coagulated and untreated groups respectively (p-value=0.06). After statistical correction for co-morbid conditions, the effect of anticoagulation was not significant (HR 0.82 CI 0.49-1.37, p-value 0.46). Age was a significant confounder that was associated with death. Increased BMI was protective. Indications for IVC filter placement were numerous, but similar between the two groups. Treatment with an approved anticoagulant is recommended after IVC filter placement for prevention of recurrent PE, however its effect may be attenuated by advanced age. In elderly patients that have undergone IVC filter placement for prevention of recurrent PE, survival may be more dependent on age and co-morbid conditions than exposure to anticoagulation. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

[Anticoagulation in the aged patient with atrial fibrillation: What are prescribing cardiologists, geriatricians and general practitioners?].

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Fuchs, P; Vogel, T; Lang, P-O

2015-08-01

To assess prescribing of anticoagulants in atrial fibrillation (AF) in the elderly, both a quantitative point of view (rate of anticoagulation) and qualitative (type of anticoagulation). Determinants of prescribing and non-prescribing were also analysed. Prospective survey of practice, based on one clinical case and questionnaire conducted in 60 practitioners (20 cardiologists [C], 20 geriatricians [G] and 20 general practitioners [GP]). In reading the clinical case, 88.3% of physicians would have initiated a treatment; three types of treatments would have been chosen: AVK (68.3%), ODA (20.0%) and platelet antiaggregant (11.7%). Criteria taken into account to initiate anticoagulation varied according to the specialty. Cardiologists considered more the age criteria (C: 95.0%, G: 75.0%, MG: 60.0%; PC: 90.0%, G: 60.0%, MG: 55.0%; PC: 85.0%, G: 55.0%, MG: 60.0%; PC: 80.0%, G: 35.0%, MG: 25.0%; PC: 15.0%, G: 5.0%, MG: 0.0%; PC: 35.0%, G: 5.0%, MG: 45.0%; PC: 70.0%, G: 75.0%, MG: 85.0%; P<0.05). This survey confirms that the FA remains under anticoagulated in the elderly and the barriers to the prescription of oral anticoagulation are often without rational basis. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Quality of Life analysis of patients in chronic use of oral anticoagulant: an observational study

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Almeida Geisa

2011-10-01

Full Text Available Abstract Background Treatment with oral anticoagulant may influence the quality of life perception as it promotes changes in the patient's life, not offering an evident symptomatic relief and presenting well defined risks, such as bleeding. In this trial, the influence of chronic use of anticoagulants on the quality of life perception has been analyzed in patients assisted at the anticoagulation outpatient unit. Methods The health related quality of life was evaluated through a cross-section study with a sample composed of 72 patients seen from July 23, 2009 to September 2, 2010 at the Anticoagulation Outpatient Unit of the Federal University of Bahia's University Hospital. The study's population was composed by patients with atrial fibrillation and mechanical heart valve. The patients were submitted to two quality of life evaluation questionnaires: a generic questionnaire - the Medical Outcomes Study SF-36 Health Survey (SF36 - and a specific questionnaire - the Duke Anticoagulation Satisfaction Scale (DASS. Results The quality of life perception of the patients studied, based on both the DASS and the SF36, was positive regarding the treatment with oral anticoagulant. The SF36 presented an average score of 62.2 (± 20.0. Among the SF36 evaluated domains, the physical-emotional aspect was the most compromised one regarding life quality perception. The DASS presented an average score of 67.1 (± 18.2 and the domain presenting a greater compromise was the one related to the treatment inconveniences (annoyances, burdens and obligations. Previous hemorrhagic event, comorbidities, drug interactions with medicines that increase the anticoagulant effect, lower education level in the SF36 and younger age group influence a more negative perception of the quality of life, whereas lower education level in the DASS and the duration of treatment for more than 1 year offer a more positive perception. Conclusion Patients seen at the anticoagulation outpatient

Partial Purification and Characterization of Anticoagulant Factor from the Snake (Echis Carinatus) Venom

Science.gov (United States)

Amrollahi Byoki, Elham; Zare Mirakabadi, Abbas

2013-01-01

Objective(s): Snake venoms contain complex mixture of proteins with biological activities. Some of these proteins affect blood coagulation and platelet function in different ways. Snake venom toxin may serve as a starting material for drug design to combat several pathophysiological problems such as cardiovascular disorders. In the present study, purification of anticoagulation factor from venom of snake (Echis carinatus) was studied. Materials and Methods: Anticoagulation activity of crude venom, fractions and purified peptide were determined by using prothrombin time (PT) and thrombin time (TT). Three fractions were partially purified from the venom of E. Carinatus by gel filtration on sephadex G-75 and final purification was performed by high-performance liquid chromatography (HPLC) with C18 column. A purified anticoagulant factor was derived which showed a single protein band in SDS-PAGE electrophoresis under reducing condition. Results: Results of PT and TT tests for purified peptide (EC217) were found to be 102±4.242 and < 5 min. respectively. Determination of molecular weight revealed that the active purified peptide (EC217) was about 30 KD. Conclusion: The present study showed that the venom of E. carinatus contains at least one anticoagulant factor. PMID:24494065

Partial Purification and Characterization of Anticoagulant Factor from the Snake (Echis carinatus Venom

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Elham Amrollahi Byoki

2013-11-01

Full Text Available   Objective(s: Snake venoms contain complex mixture of proteins with biological activities. Some of these proteins affect blood coagulation and platelet function in different ways. Snake venom toxin may serve as a starting material for drug design to combat several pathophysiological problems such as cardiovascular disorders. In the present study, purification of anticoagulation factor from venom of snake (Echis carinatus was studied. Anticoagulation activity of crude venom, fractions and purified peptide were determined by using prothrombin time (PT and thrombin time (TT. Three fractions were partially purified from the venom of E. Carinatus by gel filtration on sephadex G-75 and final purification was performed by high-performance liquid chromatography (HPLC with C18 column. A purified anticoagulant factor was derived which showed a single protein band in SDS-PAGE electrophoresis under reducing condition. Results of PT and TT tests for purified peptide (EC217 were found to be 102±4.242 and < 5 min. respectively. Determination of molecular weight revealed that the active purified peptide (EC217 was about 30 KD. In conclusion, the present study showed that the venom of E. carinatus contains at least one anticoagulant factor.

Citrate, malate and alkali content in commonly consumed diet sodas: implications for nephrolithiasis treatment.

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Eisner, Brian H; Asplin, John R; Goldfarb, David S; Ahmad, Ardalanejaz; Stoller, Marshall L

2010-06-01

Citrate is a known inhibitor of calcium stone formation. Dietary citrate and alkali intake may have an effect on citraturia. Increasing alkali intake also increases urine pH, which can help prevent uric acid stones. We determined citrate, malate and total alkali concentrations in commonly consumed diet sodas to help direct dietary recommendations in patients with hypocitraturic calcium or uric acid nephrolithiasis. Citrate and malate were measured in a lemonade beverage commonly used to treat hypocitraturic calcium nephrolithiasis and in 15 diet sodas. Anions were measured by ion chromatography. The pH of each beverage was measured to allow calculation of the unprotonated anion concentration using the known pK of citric and malic acid. Total alkali equivalents were calculated for each beverage. Statistical analysis was done using Pearson's correlation coefficient. Several sodas contained an amount of citrate equal to or greater than that of alkali and total alkali as a lemonade beverage commonly used to treat hypocitraturic calcium nephrolithiasis (6.30 mEq/l citrate as alkali and 6.30 as total alkali). These sodas were Diet Sunkist Orange, Diet 7Up, Sprite Zero, Diet Canada Dry Ginger Ale, Sierra Mist Free, Diet Orange Crush, Fresca and Diet Mountain Dew. Colas, including Caffeine Free Diet Coke, Coke Zero, Caffeine Free Diet Pepsi and Diet Coke with Lime, had the lowest total alkali (less than 1.0 mEq/l). There was no significant correlation between beverage pH and total alkali content. Several commonly consumed diet sodas contain moderate amounts of citrate as alkali and total alkali. This information is helpful for dietary recommendations in patients with calcium nephrolithiasis, specifically those with hypocitraturia. It may also be useful in patients with low urine pH and uric acid stones. Beverage malate content is also important since malate ingestion increases the total alkali delivered, which in turn augments citraturia and increases urine pH. Copyright

Structure and anticoagulant activity of a sulfated galactan from the red alga, Gelidium crinale. Is there a specific structural requirement for the anticoagulant action?

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Pereira, Maria G; Benevides, Norma M B; Melo, Marcia R S; Valente, Ana Paula; Melo, Fábio R; Mourão, Paulo A S

2005-09-05

Marine red algae are an abundant source of sulfated galactans with potent anticoagulant activity. However, the specific structural motifs that confer biological activity remain to be elucidated. We have now isolated and purified a sulfated galactan from the marine red alga, Gellidium crinale. The structure of this polysaccharide was determined using NMR spectroscopy. It is composed of the repeating structure -4-alpha-Galp-(1-->3)-beta-Galp1--> but with a variable sulfation pattern. Clearly 15% of the total alpha-units are 2,3-di-sulfated and another 55% are 2-sulfated. No evidence for the occurrence of 3,6-anhydro alpha-galactose units was observed in the NMR spectra. We also compared the anticoagulant activity of this sulfated galactan with a polysaccharide from the species, Botryocladia occidentalis, with a similar saccharide chain but with higher amounts of 2,3-di-sulfated alpha-units. The sulfated galactan from G. crinale has a lower anticoagulant activity on a clotting assay when compared with the polysaccharide from B. occidentalis. When tested in assays using specific proteases and coagulation inhibitors, these two galactans showed significant differences in their activity. They do not differ in thrombin inhibition mediated by antithrombin, but in assays where heparin cofactor II replaces antithrombin, the sulfated galactan from G. crinale requires a significantly higher concentration to achieve the same inhibitory effect as the polysaccharide from B. occidentalis. In contrast, when factor Xa instead of thrombin is used as the target protease, the sulfated galactan from G. crinale is a more potent anticoagulant. These observations suggest that the proportion and/or the distribution of 2,3-di-sulfated alpha-units along the galactan chain may be a critical structural motif to promote the interaction of the protease with specific protease and coagulation inhibitors.

Cupric citrate as growth promoter for broiler chickens in different rearing stages

Energy Technology Data Exchange (ETDEWEB)

Brainer, Monica Maria de Almeida [EAFCe, Ceres, GO (Brazil). Dept. de Zootecnia; Menten, Jose Fernando Machado; Vale, Marcos Martinez do; Morais, Sonia Cristina Daroz de [Universidade de Sao Paulo (USP), Piracicaba, SP (Brazil). Escola Superior de Agricultura Luiz de Queiroz (ESALQ). Dept. de Zootecnia]. E-mail: jfmmente@esalq.usp.br

2003-07-01

Feeding cupric citrate as alternative to cupric sulfate to broilers has been suggested in the literature. Day-old male broiler chicks (1,200) were used in an experiment to evaluate the efficacy of cupric citrate supplementation (75 mg Cu kg-1) during the 1-21, 22-42 or 1-42 d periods in comparison to an unsupplemented diet and a diet supplemented with cupric sulfate (200 mg Cu kg-1, 1-42 d). A randomized block design was used, with five treatments, six replicates and 40 birds per pen. The diets, based on corn and soybean meal, and water were offered ad libitum during the 42-day experimental period. Over the entire period, there was no effect of copper supplementation (P > 0.05) on bird live weight, weight gain, feed intake, feed conversion and mortality. Cupric citrate supplementation on the 22-42 d period resulted in worse feed conversion as compared to broilers receiving cupric sulfate (2.014 vs. 1.967, P < 0.05). Copper residues in the litter were reduced when broilers were fed cupric citrate, as compared to cupric sulfate (P < 0.01). The absence of response to copper supplementation can be attributed to the environmental and sanitary rearing conditions.

Cupric citrate as growth promoter for broiler chickens in different rearing stages

International Nuclear Information System (INIS)

Brainer, Monica Maria de Almeida; Menten, Jose Fernando Machado; Vale, Marcos Martinez do; Morais, Sonia Cristina Daroz de

2003-01-01

Feeding cupric citrate as alternative to cupric sulfate to broilers has been suggested in the literature. Day-old male broiler chicks (1,200) were used in an experiment to evaluate the efficacy of cupric citrate supplementation (75 mg Cu kg-1) during the 1-21, 22-42 or 1-42 d periods in comparison to an unsupplemented diet and a diet supplemented with cupric sulfate (200 mg Cu kg-1, 1-42 d). A randomized block design was used, with five treatments, six replicates and 40 birds per pen. The diets, based on corn and soybean meal, and water were offered ad libitum during the 42-day experimental period. Over the entire period, there was no effect of copper supplementation (P > 0.05) on bird live weight, weight gain, feed intake, feed conversion and mortality. Cupric citrate supplementation on the 22-42 d period resulted in worse feed conversion as compared to broilers receiving cupric sulfate (2.014 vs. 1.967, P < 0.05). Copper residues in the litter were reduced when broilers were fed cupric citrate, as compared to cupric sulfate (P < 0.01). The absence of response to copper supplementation can be attributed to the environmental and sanitary rearing conditions

Synthesis and biological activity of the novel indanedione anticoagulant rodenticides containing fluorine

OpenAIRE

Chen, Feng; Liu, Liping; Bai, Zengguo; Zhang, Tianhua; Zhao, Keke

2016-01-01

Here, 3 fluorinated intermediates of drug were synthesized: (M1), (M2), (M3). Three new anticoagulant rodenticides were designed which were based on 4-hydroxycoumarin or 1,3-indandione, added acute toxicity groups containing fluorine. The structures of synthesized compounds were analyzed and proved by FT-IR spectroscopy and 1H nuclear magnetic resonance (1H-NMR). The compounds were also evaluated for their anticoagulant and acute biologic activity. In addition, both the acute orally toxicity ...

Sulfated modification and anticoagulant activity of pumpkin (Cucurbita pepo, Lady Godiva) polysaccharide.

Science.gov (United States)

Liang, Li; Ao, Le; Ma, Tao; Ni, Yuanying; Liao, Xiaojun; Hu, Xiaosong; Song, Yi

2018-01-01

Sulfated modification of pumpkin polysaccharide using CAS with pyridines as catalysts under different conditions was conducted to obtain different degrees of sulfation on a laboratory scale. Anticoagulant activities of pumpkin polysaccharide and its sulfated derivatives were also investigated employing various established in vitro systems. Results showed that addition of high ratio of CAS/pyridine under constant conditions could increase the degree of substitution. Sulfate substitution was further confirmed by the FT-IR and 13 C NMR analysis. The d f values between 2.11-2.73 indicated the relatively expanded conformation of the sulfated derivatives. The sulfated polysaccharides showed higher anticoagulant activities through activated partial thrombosis time (aPTT), thrombin time (TT), prothrombin time (PT) and anti-Xa activity assay, which revealed that better anticoagulant activities could be obtained when DS remained higher and M w maintained in a moderate range. Copyright © 2017 Elsevier B.V. All rights reserved.

Functional analysis of the citrate activator CitO from Enterococcus faecalis implicates a divalent metal in ligand binding

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Victor S. Blancato

2016-02-01

Full Text Available The regulator of citrate metabolism, CitO, from Enterococcus faecalis belongs to the FCD family within the GntR superfamily. In the presence of citrate, CitO binds to cis-acting sequences located upstream of the cit promoters inducing the expression of genes involved in citrate utilization. The quantification of the molecular binding affinities, performed by isothermal titration calorimetry (ITC, indicated that CitO has a high affinity for citrate (KD= 1.2±0.2 µM, while it did not recognize other metabolic intermediates. Based on a structural model of CitO where a putative small molecule and a metal binding site were identified, it was hypothesized that the metal ion is required for citrate binding. In agreement with this model, citrate binding to CitO sharply decreased when the protein was incubated with EDTA. This effect was reverted by the addition of Ni2+, and Zn2+ to a lesser extent. Structure-based site-directed mutagenesis was conducted and it was found that changes to alanine in residues Arg97 and His191 resulted in decreased binding affinities for citrate, as determined by EMSA and ITC. Further assays using lacZ fusions confirmed that these residues in CitO are involved in sensing citrate in vivo. These results indicate that the molecular modifications induced by a ligand and a metal binding in the C-terminal domain of CitO are required for optimal DNA binding activity, and consequently, transcriptional activation.

Impact of INR monitoring, reversal agent use, heparin bridging, and anticoagulant interruption on rebleeding and thromboembolism in acute gastrointestinal bleeding.

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Naoyoshi Nagata

Full Text Available Anticoagulant management of acute gastrointestinal bleeding (GIB during the pre-endoscopic period has not been fully addressed in American, European, or Asian guidelines. This study sought to evaluate the risks of rebleeding and thromboembolism in anticoagulated patients with acute GIB.Baseline, endoscopy, and outcome data were reviewed for 314 patients with acute GIB: 157 anticoagulant users and 157 age-, sex-, and important risk-matched non-users. Data were also compared between direct oral anticoagulants (DOACs and warfarin users.Between anticoagulant users and non-users, of whom 70% underwent early endoscopy, no endoscopy-related adverse events or significant differences were found in the rate of endoscopic therapy need, transfusion need, rebleeding, or thromboembolism. Rebleeding was associated with shock, comorbidities, low platelet count and albumin level, and low-dose aspirin use but not HAS-BLED score, any endoscopic results, heparin bridge, or international normalized ratio (INR ≥ 2.5. Risks for thromboembolism were INR ≥ 2.5, difference in onset and pre-endoscopic INR, reversal agent use, and anticoagulant interruption but not CHA2DS2-VASc score, any endoscopic results, or heparin bridge. In patients without reversal agent use, heparin bridge, or anticoagulant interruption, there was only one rebleeding event and no thromboembolic events. Warfarin users had a significantly higher transfusion need than DOACs users.Endoscopy appears to be safe for anticoagulant users with acute GIB compared with non-users. Patient background factors were associated with rebleeding, whereas anticoagulant management factors (e.g. INR correction, reversal agent use, and drug interruption were associated with thromboembolism. Early intervention without reversal agent use, heparin bridge, or anticoagulant interruption may be warranted for acute GIB.

Effective management of venous thromboembolism in the community: non-vitamin K antagonist oral anticoagulants

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Patel R

2016-05-01

Full Text Available Raj Patel Department of Haematological Medicine, King's Thrombosis Centre, King's College Hospital, London, UK Abstract: Anticoagulation therapy is essential for the effective treatment and secondary prevention of venous thromboembolism (VTE. For many years, anticoagulation for acute VTE was limited to the use of initial parenteral heparin, overlapping with and followed by a vitamin K antagonist. Although highly effective, this regimen has several limitations and is particularly challenging when given in an ambulatory setting. Current treatment pathways for most patients with deep-vein thrombosis typically involve initial hospital or community-based ambulatory care with subsequent follow-up in a secondary care setting. With the introduction of non-vitamin K antagonist oral anticoagulants (NOACs into routine clinical practice, it is now possible for the initial acute management of patients with deep-vein thrombosis to be undertaken by primary care. As hospital admissions associated with VTE become shorter, primary care will play an increasingly important role in the long-term management of these patients. Although the NOACs can potentially simplify patient management and improve clinical outcomes, primary care physicians may be less familiar with these new treatments compared with traditional therapy. To assist primary care physicians in further understanding the role of the NOACs, this article outlines the main differences between NOACs and traditional anticoagulation therapy and discusses the benefit–risk profile of the different NOACs in the treatment and secondary prevention of recurrent VTE. Key considerations for the use of NOACs in the primary care setting are highlighted, including dose transition, risk assessment and follow-up, duration of anticoagulant therapy, how to minimize bleeding risks, and the importance of patient education and counseling. Keywords: venous thromboembolism, oral anticoagulant, prevention, treatment, primary

Lupus anticoagulant-hypoprothrombinemia syndrome and catastrophic antiphospholipid syndrome in a patient with antidomain I antibodies.

Science.gov (United States)

Galland, Joris; Mohamed, Shirine; Revuz, Sabine; de Maistre, Emmanuel; de Laat, Bas; Marie, Pierre-Yves; Zuily, Stéphane; Lévy, Bruno; Regnault, Véronique; Wahl, Denis

2016-07-01

Lupus anticoagulant-hypoprothrombinemia syndrome is a rare condition characterized by the association of acquired factor II deficiency and lupus anticoagulant. Contrary to classical antiphospholipid syndrome, it may cause severe life-threatening bleeding (89% of published cases). We report a patient, positive for antidomain I antibodies, with initially primary lupus anticoagulant-hypoprothrombinemia syndrome without previous clinical manifestation or underlying systemic disease. Five years later, he experienced the first systemic lupus erythematous flare. Within a few days, catastrophic antiphospholipid syndrome was diagnosed with heart, liver and kidney involvement. The patient recovered under pulse steroids, intravenous heparin and intravenous immunoglobulins.

Anticoagulant Effect of Sugammadex: Just an In Vitro Artifact.

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Dirkmann, Daniel; Britten, Martin W; Pauling, Henning; Weidle, Juliane; Volbracht, Lothar; Görlinger, Klaus; Peters, Jürgen

2016-06-01

Sugammadex prolongs activated partial thromboplastin time (aPTT) and prothrombin time (PT) suggestive of anticoagulant effects. To pinpoint its presumed anticoagulant site of action, the authors assessed Sugammadex's impact on a panel of coagulation assays. Sugammadex, Rocuronium, Sugammadex and Rocuronium combined, or saline were added to blood samples from healthy volunteers and analyzed using plasmatic (i.e., aPTT, thrombin time, and fibrinogen concentration) (n = 8 each), PT (quick), activities of plasmatic coagulation factors, and whole blood (extrinsically and intrinsically activated thromboelastometry) assays (n = 18 each). Furthermore, dose-dependent effects of Sugammadex were also assessed (n = 18 each) in diluted Russel viper venom time (DRVVT) assays with low (DRVVT1) and high (DRVVT2) phospholipid concentrations and in a highly phospholipid-sensitive aPTT assay. Sugammadex increased PT (+9.1%; P Sugammadex dose-dependently prolonged both DRVVT1 and the highly phospholipid-sensitive aPTT assays, but additional phospholipids in the DRVVT2 assay almost abolished these prolongations. Thrombin time, a thromboelastometric thrombin generation assay, clot firmness, clot lysis, fibrinogen concentration, and activities of other coagulation factors were unaltered. Rocuronium, Sugammadex and Rocuronium combined, and saline exerted no effects. Sugammadex significantly affects various coagulation assays, but this is explainable by an apparent phospholipid-binding effect, suggesting that Sugammadex`s anticoagulant effects are likely an in vitro artifact.

New Direct Oral Anticoagulants (DOAC and Their Use Today

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Heike Schwarb

2016-03-01

Full Text Available The ideal anticoagulant is oral, has a wide therapeutic range, predictable pharmacokinetics and pharmacodynamics, a rapid onset of action, an available antidote, minimal side effects and minimal interactions with other drugs or food. With the development of the novel direct oral anticoagulants (DOAC, we now have an alternative to the traditional vitamin K antagonists (VKA for the prevention and treatment of thrombosis. DOACs have limited monitoring requirements and very predictable pharmacokinetic profiles. They were shown to be non-inferior or superior to VKA in the prophylaxis or treatment of thromboembolic events. Particularly in terms of safety they were associated with less major bleeding, including intracranial bleeding, thus providing a superior benefit for the prevention of stroke in patients with atrial fibrillation. Despite these advantages, there are remaining limitations with DOACs: their dependence on renal and hepatic function for clearance and the lack of an approved reversal agent, whereas such antidotes are successively being made available. DOACs do not need regular monitoring to assess the treatment effect but, on the other hand, they interact with other drugs and interfere with functional coagulation assays. From a practical point of view, the properties of oral administration, simple dosing without monitoring, a short half-life allowing for the possibility of uncomplicated switching or bridging, and proven safety overwhelm the disadvantages, making them an attractive option for short- or long-term anticoagulation.

Aneurysmal subarachnoid hemorrhage in patients taking direct oral anticoagulants: A case series and discussion of management

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Joseph H. McMordie, MD

2018-03-01

Full Text Available Direct oral anticoagulants are becoming more commonplace for the treatment of nonvalvular atrial fibrillation and deep vein thrombosis. Unfortunately, effective reversal agents are not widely available limiting options for neurosurgical intervention during active anticoagulation. We report a case series of 3 patients treated for aneurysmal subarachnoid hemorrhage while taking direct oral anticoagulants. All three underwent open surgical clipping after adequate time was allowed for drug metabolism. Decision-making must take into account timing of intervention, drug half-life, and currently available reversal agents.

Myositis ossificans with Ga-67 citrate positivity

International Nuclear Information System (INIS)

Moreno, A.J.; Yedinak, M.A.; Spicer, M.J.; Turnbull, G.L.; Byrd, B.F.; Brown, T.J.

1985-01-01

A 16 year-old boy presented with a firm mass within the left thigh. Ga-67 citrate and bone scintigraphy revealed soft tissue radiotracer accumulation within the mass lesion. Radiographs and xerography of the left thigh revealed calcification within the soft tissue mass typical of myositis ossificans. The patient's clinical course was uneventful

Clinical impact of a pharmacist-led inpatient anticoagulation service: a review of the literature

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Lee T

2016-05-01

Full Text Available Tiffany Lee, Erin Davis, Jason Kielly School of Pharmacy, Memorial University, St John's, NL, Canada Background: Anticoagulant therapies provide management options for potentially life-threatening thromboembolic conditions. They also carry significant safety risks, requiring careful consideration of medication dose, close monitoring, and follow-up. Inpatients are particularly at risk, considering the widespread use of anticoagulants in hospitals. This has prompted the introduction of safety goals for anticoagulants in Canada and the USA, which recommend increased pharmacist involvement to reduce patient harm. The goal of this review is to evaluate the efficacy and safety of pharmacist-led inpatient anticoagulation services compared to usual or physician-managed care. Methods: This narrative review includes articles identified through a literature search of PubMed, Embase, and International Pharmaceutical Abstracts databases, as well as hand searches of the references of relevant articles. Full publications of pharmacist-managed inpatient anticoagulation services were eligible if they were published in English and assessed clinical outcomes. Results: Twenty-six studies were included and further divided into two categories: 1 autonomous pharmacist-managed anticoagulation programs (PMAPs and 2 pharmacist recommendation. Pharmacist management of heparin and warfarin appears to result in improvements in some surrogate outcomes (international normalized ratio [INR] stability and time in INR goal range, while results for others are mixed (time to therapeutic INR, length of stay, and activated partial thromboplastin time [aPTT] measures. There is also some indication that PMAPs may be associated with reduced patient mortality. When direct thrombin inhibitors are managed by pharmacists, there seems to be a shorter time to therapeutic aPTT and a greater percentage of time in the therapeutic range, as well as a decrease in the frequency of medication

Citrate, a Ubiquitous Key Metabolite with Regulatory Function in the CNS

DEFF Research Database (Denmark)

Westergaard, Niels; Waagepetersen, Helle S; Belhage, Bo

2017-01-01

Citrate is key constituent of the tricarboxylic acid (TCA) cycle, serves as substrate for fatty acid and sterol biosynthesis, and functions as a key regulator of intermediary energy metabolism. Ursula Sonnewald had initiated studies using for the first time both proton- and 13C-NMR to investigate...... metabolic processes in cultured neurons and astrocytes resulting in the important observation that citrate was specifically synthesized in and released from astrocytes in large amounts which is in keeping with the high concentration found in the CSF. The aim of this review is to highlight the possible roles...

Comparison of technetium-99m methoxyisobutylisonitrile and gallium-67 citrate scanning in the assessment of lymphomas

International Nuclear Information System (INIS)

Ziegels, P.; Nocaudie, M.; Huglo, D.; Deveaux, M.; Detourmignies, L.; Wattel, E.; Marchandise, X.

1995-01-01

The aim of this study was to compare the value of scintigraphy using technetium-99m methoxy-isobutylisonitrile (MIBI) with that of scintigraphy using gallium-67 citrate in the assessment of Hodgkin's disease and non-Hodgkin's lymphoma and to relate these results with those of CT scan and MRI. Fifty-eight patients were included either for a follow-up examination or for monitoring of their treatment. Twenty-three residual masses were studied. A whole-body scan was performed, followed by single-photon emission computed tomography (SPET) 20 min after injection of 740 MBq of 99m Tc-MIBI and 72 h after injection of 185 MBq of 67 Ga citrate. The overall sensitivity of 99m Tc-MIBI and 67 Ga citrate was 71% and 68%, respectively, and the overall specificity was 76% and 44%, respectively. For residual masses, the sensitivity was 44% with both tracers and the specificity was 80% with 99m Tc-MIBI and 53% with 67 Ga citrate. The positive predictive values were 85% and 68% and the negative predictive values were 59% and 44%, respectively. The signal-to-background ratio was 1.5 for 99m Tc-MIBI and 2 for 67 Ga citrate. At present, 99m Tc-MIBI cannot replace 67 Ga citrate in the assessment of lymphomas. (orig.)

Evaluation of computerized decision support for oral anticoagulation management based in primary care.

OpenAIRE

Fitzmaurice, D A; Hobbs, F D; Murray, E T; Bradley, C P; Holder, R

1996-01-01

BACKGROUND: Increasing indications for oral anticoagulation has led to pressure on general practices to undertake therapeutic monitoring. Computerized decision support (DSS) has been shown to be effective in hospitals for improving clinical management. Its usefulness in primary care has previously not been investigated. AIM: To test the effectiveness of using DSS for oral anticoagulation monitoring in primary care by measuring the proportions of patients adequately controlled, defined as with...

Lupus anticoagulant, disease activity and low complement in the first trimester are predictive of pregnancy loss.

Science.gov (United States)

Mankee, Anil; Petri, Michelle; Magder, Laurence S

2015-01-01

Multiple factors, including proteinuria, antiphospholipid syndrome, thrombocytopenia and hypertension, are predictive of pregnancy loss in systemic lupus erythematosus (SLE). In the PROMISSE study of predictors of pregnancy loss, only a battery of lupus anticoagulant tests was predictive of a composite of adverse pregnancy outcomes. We examined the predictive value of one baseline lupus anticoagulant test (dilute Russell viper venom time) with pregnancy loss in women with SLE. From the Hopkins Lupus Cohort, there were 202 pregnancies from 175 different women after excluding twin pregnancies and pregnancies for which we did not have a first trimester assessment of lupus anticoagulant. We determined the percentage of women who had a pregnancy loss in groups defined by potential risk factors. The lupus anticoagulant was determined by dilute Russell viper venom time with appropriate mixing and confirmatory testing. Generalised estimating equations were used to calculate p values, accounting for repeated pregnancies in the same woman. The age at pregnancy was 40 (3%). 55% were Caucasian and 34% African-American. Among those with lupus anticoagulant during the first trimester, 6/16 (38%) experienced a pregnancy loss compared with only 16/186 (9%) of other pregnancies (p=0.003). In addition, those with low complement or higher disease activity had a higher rate of pregnancy loss than those without (p=0.049 and 0.005, respectively). In contrast, there was no association between elevated anticardiolipin in the first trimester and pregnancy loss. The strongest predictor of pregnancy loss in SLE in the first trimester is the lupus anticoagulant. In addition, moderate disease activity by the physician global assessment and low complement measured in the first trimester were predictive of pregnancy loss. These data suggest that treatment of the lupus anticoagulant could be considered, even in the absence of history of pregnancy loss.

The Italian START-Register on Anticoagulation with Focus on Atrial Fibrillation

Science.gov (United States)

2015-01-01

START-Register – Survey on anTicoagulated pAtients RegisTer – is an independent, inception-cohort, observational, collaborative database aimed at recording prospectively the clinical history of adult patients starting anticoagulant treatment for any reason and using whatever drug. In this article we present the START-Register and give cross section baseline data focusing on non valvular atrial fibrillation (NVAF). Participants are asked to insert prospectively consecutive patients recorded as electronic file on the web-site of the registry. Required data are: demographic and clinical characteristics of patients, associated risk factors for stroke and bleeding, laboratory routine data, clinical indication for treatment, expected therapeutic range (in cases of treatment with vitamin K antagonists -VKAs). The follow-up is carried out to record: quality of treatment (for patients on VKAs), bleeding complications, thrombotic events, and the onset of any type of associated disease. To date 5252 patients have been enrolled; 97.6% were on VKAs because direct oral anticoagulants (DOAC) have been available in Italy only recently. The median age was 74 years [interquartile range (IQR) 64-80]; males 53.7%. This analysis is focused on the 3209 (61.1%) NVAF patients. Mean CHADS2 score was 2.1±1.1, CHADSVASc score was 3.1±1.3;median age was 76 years (IQR 70-81); 168 patients (5.3%) had severe renal failure [Creatinine clearance (CrCl) START-Register data shows that two-third of patients who started chronic anticoagulant treatment had NVAF, one-third of them was > 80 years with high prevalence of renal failure. PMID:26001109

Platelet factor 4 impairs the anticoagulant activity of activated protein C.

LENUS (Irish Health Repository)

Preston, Roger J S

2012-02-01

Platelet factor 4 (PF4) is an abundant platelet alpha-granule chemokine released following platelet activation. PF4 interacts with thrombomodulin and the gamma-carboxyglutamic acid (Gla) domain of protein C, thereby enhancing activated protein C (APC) generation by the thrombin-thrombomodulin complex. However, the protein C Gla domain not only mediates protein C activation in vivo, but also plays a critical role in modulating the diverse functional properties of APC once generated. In this study we demonstrate that PF4 significantly inhibits APC anti-coagulant activity. PF4 inhibited both protein S-dependent APC anticoagulant function in plasma and protein S-dependent factor Va (FVa) proteolysis 3- to 5-fold, demonstrating that PF4 impairs protein S cofactor enhancement of APC anticoagulant function. Using recombinant factor Va variants FVa-R506Q\\/R679Q and FVa-R306Q\\/R679Q, PF4 was shown to impair APC proteolysis of FVa at position Arg(306) by 3-fold both in the presence and absence of protein S. These data suggest that PF4 contributes to the poorly understood APC resistance phenotype associated with activated platelets. Finally, despite PF4 binding to the APC Gla domain, we show that APC in the presence of PF4 retains its ability to initiate PAR-1-mediated cytoprotective signaling. In summary, we propose that PF4 acts as a critical regulator of APC generation, but also differentially targets APC toward cytoprotective, rather than anticoagulant function at sites of vascular injury with concurrent platelet activation.

Platelet factor 4 impairs the anticoagulant activity of activated protein C.

LENUS (Irish Health Repository)

Preston, Roger J S

2009-02-27

Platelet factor 4 (PF4) is an abundant platelet alpha-granule chemokine released following platelet activation. PF4 interacts with thrombomodulin and the gamma-carboxyglutamic acid (Gla) domain of protein C, thereby enhancing activated protein C (APC) generation by the thrombin-thrombomodulin complex. However, the protein C Gla domain not only mediates protein C activation in vivo, but also plays a critical role in modulating the diverse functional properties of APC once generated. In this study we demonstrate that PF4 significantly inhibits APC anti-coagulant activity. PF4 inhibited both protein S-dependent APC anticoagulant function in plasma and protein S-dependent factor Va (FVa) proteolysis 3- to 5-fold, demonstrating that PF4 impairs protein S cofactor enhancement of APC anticoagulant function. Using recombinant factor Va variants FVa-R506Q\\/R679Q and FVa-R306Q\\/R679Q, PF4 was shown to impair APC proteolysis of FVa at position Arg(306) by 3-fold both in the presence and absence of protein S. These data suggest that PF4 contributes to the poorly understood APC resistance phenotype associated with activated platelets. Finally, despite PF4 binding to the APC Gla domain, we show that APC in the presence of PF4 retains its ability to initiate PAR-1-mediated cytoprotective signaling. In summary, we propose that PF4 acts as a critical regulator of APC generation, but also differentially targets APC toward cytoprotective, rather than anticoagulant function at sites of vascular injury with concurrent platelet activation.

Generic switching of warfarin and risk of excessive anticoagulation

DEFF Research Database (Denmark)

Hellfritzsch, Maja; Rathe, Jette; Stage, Tore Bjerregaard

2016-01-01

PURPOSE: Generic switching of warfarin was recently repealed in Denmark, as adverse drug reaction (ADR) reports suggested risk of excessive anticoagulation following switches from branded to generic warfarin. We investigated this putative association in a formalized pharmacoepidemiological analysis....... METHODS: We conducted a nationwide cohort study based on Danish healthcare registries, including data from the introduction of generic warfarin until the repeal (January 2011-April 2015). We followed Danish warfarin users over time and compared the rate of incident hospitalizations due to excessive...... anticoagulation (i.e. increased INR or any bleeding requiring hospitalization) in periods following a recent switch to generic warfarin to the rate in periods without a recent switch. RESULTS: We included 105,751 warfarin users, filling a total of 1,539,640 prescriptions for warfarin (2.5% for generic warfarin...

Comparing new anticoagulants.

Science.gov (United States)

Wooten, James M

2012-12-01

For years, the pharmaceutical industry has been trying to find a safe and effective drug to replace warfarin. Although warfarin is an effective anticoagulant, its pharmacology, adverse effects, and risk profiles dictate that patients taking this medication must be monitored judiciously. The US Food and Drug Administration has approved two drugs for commercial use, dabigatran and rivaroxaban, that will compete directly with warfarin for use in specific indications. Because of direct marketing to patients, physicians are being asked to comment on these new medications. This brief review illustrates the data available for the two new drugs when compared to warfarin for the specified indications. For some patients, these drugs may be highly beneficial and offer an excellent alternative to warfarin. For others, warfarin may still be the preferred drug.

[Effects of sodium ethamsylate on anticoagulant and anti-aggregation activity of vascular endothelium in hemorrhagic fever patients with renal syndrome].

Science.gov (United States)

Davidovich, I M; Sirotin, B Z; Parshina, T A

1999-01-01

To elucidate effects of sodium ethamsylate (SE) on anticoagulant and antiaggregation activity of vascular endothelium in patients suffering from hemorrhagic fever with renal syndrome (HFRS). A trial of SE enrolled 70 HFRS patients (58 males, 12 females aged under 30 years) compatible by the disease severity. They were divided into two groups. 42 patients of the control group received standard therapy, 28 patients of the study group received adjuvant 12% solution of SE in daily dose 1500-2000 mg in the course of HFRS oliguria period. Hemostatic parameters were measured before and after the cuff test to investigate the condition of vascular wall with calculation of the athrombogenicity index (the ratio of the relevant indices before and after the cuff test). SE effects on vascular endothelium was assessed by a blind method. In oliguria, both groups had baseline antiaggregation indices significantly higher than in the control. After the cuff test, control patients' indices tended to an increase while in the study group there was a marked decrease. The trend in anticoagulant activity of microvascular endothelium did not differ much with the groups. This picture persisted also in polyuria. In convalescence hemostasis was similar in both groups. SE enhances antiaggregant activity of vascular endothelium in oliguria period of HFRS without affecting its anticoagulant properties. This is explained by a direct effect of SE on vascular endothelium.

Flexible biodegradable citrate-based polymeric step-index optical fiber.

Science.gov (United States)

Shan, Dingying; Zhang, Chenji; Kalaba, Surge; Mehta, Nikhil; Kim, Gloria B; Liu, Zhiwen; Yang, Jian

2017-10-01

Implanting fiber optical waveguides into tissue or organs for light delivery and collection is among the most effective ways to overcome the issue of tissue turbidity, a long-standing obstacle for biomedical optical technologies. Here, we report a citrate-based material platform with engineerable opto-mechano-biological properties and demonstrate a new type of biodegradable, biocompatible, and low-loss step-index optical fiber for organ-scale light delivery and collection. By leveraging the rich designability and processibility of citrate-based biodegradable polymers, two exemplary biodegradable elastomers with a fine refractive index difference and yet matched mechanical properties and biodegradation profiles were developed. Furthermore, we developed a two-step fabrication method to fabricate flexible and low-loss (0.4 db/cm) optical fibers, and performed systematic characterizations to study optical, spectroscopic, mechanical, and biodegradable properties. In addition, we demonstrated the proof of concept of image transmission through the citrate-based polymeric optical fibers and conducted in vivo deep tissue light delivery and fluorescence sensing in a Sprague-Dawley (SD) rat, laying the groundwork for realizing future implantable devices for long-term implantation where deep-tissue light delivery, sensing and imaging are desired, such as cell, tissue, and scaffold imaging in regenerative medicine and in vivo optogenetic stimulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ion exchange behaviour of citrate and EDTA anions on strong and weak base organic ion exchangers

International Nuclear Information System (INIS)

Askarieh, M.M.; White, D.A.

1988-01-01

The exchange of citrate and EDTA ions with two strong base and two weak base exchangers is considered. Citrate and EDTA analysis for this work was performed using a colorimetric method developed here. The ions most selectively exchanged on the resins are H 2 cit - and H 2 EDTA 2- , though EDTA is generally less strongly sorbed on strong base resins. In contact with weak base resins, deprotonation of the resin occurs during ion exchange with a noticeable drop in solution pH. Although EDTA sorption can be reversed by nitric acid, citrate ions are significantly held on the resin at low pH. The exchange of citrate can be made reversible if bicarbonate is added to the initial solutions. Alkaline regeneration of exchangers loaded with EDTA proved to be very effective. (author)

Atrial fibrillation and stroke prevention practices in patients with candidacy for anticoagulation therapy

International Nuclear Information System (INIS)

Ullah, I.; Ahmad, S.; Hayat, Y.

2015-01-01

Background: Stroke secondary to Atrial Fibrillation is usually due to thrombi formed in the left atrium and left atrial appendage embolizing to cause ischemic stroke. Therefore, in patients with Atrial Fibrillation, antithrombotic therapy is recommended to prevent stroke. Vitamin K antagonist therapy is most widely used antithrombotic therapy for patients with valvular and non valvular AF. Aspirin is recommended only in low risk patients. This study was conducted to determine the stroke prevention practices in local patients with atrial fibrillation who were candidates for anticoagulation therapy. Method: This was descriptive cross sectional study conducted at Cardiovascular Department Lady Reading Hospital Peshawar and Cardiology Department Hayatabad Medical Complex Peshawar. Sampling technique was non probability consecutive. Patients visiting OPD of respective hospitals with EKG evidence of AF and having CHADES VASC score 2 or more or having mitral stenosis and AF were included in the study. Patients with additional indications for anticoagulation were excluded from the study. Results: A total of 205 patients with atrial fibrillation were studied. Mean age was 60.7±14.7 years. Male were 55.6 percentage (n=114) while 44.4 percentage (n=91) were female. Of these 149 (72.7 percentage) were candidates for anticoagulation based on CHA2DS2 VASc score of 2 and more or mitral stenosis with AF. Only 27.5 percentage (n=41) patients were adequately treated with anticoagulant therapy using VKA or novel oral anticoagulant drugs. Majority of them were getting dual antiplatelet therapy (DAPT). Conclusion: Most patients with AF and high risk characteristics for thromboembolism are not receiving proper stroke prevention therapies. (author)

Does small mammal prey guild affect the exposure of predators to anticoagulant rodenticides?

International Nuclear Information System (INIS)

Tosh, D.G.; McDonald, R.A.; Bearhop, S.; Lllewellyn, N.R.; Fee, S.; Sharp, E.A.; Barnett, E.A.; Shore, R.F.

2011-01-01

Ireland has a restricted small mammal prey guild but still includes species most likely to consume anticoagulant rodenticide (AR) baits. This may enhance secondary exposure of predators to ARs. We compared liver AR residues in foxes (Vulpes vulpes) in Northern Ireland (NI) with those in foxes from Great Britain which has a more diverse prey guild but similar agricultural use of ARs. Liver ARs were detected in 84% of NI foxes, more than in a comparable sample of foxes from Scotland and similar to that of suspected AR poisoned animals from England and Wales. High exposure in NI foxes is probably due to greater predation of commensal rodents and non-target species most likely to take AR baits, and may also partly reflect greater exposure to highly persistent brodifacoum and flocoumafen. High exposure is likely to enhance risk and Ireland may be a sentinel for potential effects on predator populations. - Highlights: → Exposure of a predator to anticoagulant rodenticides was compared in Britain and Ireland. → Exposure was higher in Ireland. → Differences driven by small mammal prey guilds. → Ireland a potential sentinel for predator exposure to anticoagulants. - Restriction of the small mammal prey guild is associated with enhanced exposure of predators to anticoagulant rodenticides.

Sodium citrate blood contamination by K2 -ethylenediaminetetraacetic acid (EDTA): impact on routine coagulation testing.

Science.gov (United States)

Lima-Oliveira, G; Salvagno, G L; Danese, E; Favaloro, E J; Guidi, G C; Lippi, G

2015-06-01

The potential cross-contamination of additives between primary blood tubes is a well-known problem during sample collection. The aim of this study was to assess the impact of citrated blood contamination with different amounts of dipotassium ethylenediaminetetraacetic (K2 EDTA blood) on activated partial thromboplastin time (APTT), prothrombin time (PT), and fibrinogen. Blood was collected from 15 ostensibly healthy volunteers into four 0.109 m citrate blood tubes followed by one K2 EDTA blood tube. The citrate tubes of each subject were pooled and divided in five aliquots. The whole blood of the K2 EDTA tube was then added in scalar amounts to autologous citrated blood aliquots, to obtain K2 EDTA contamination ranging from 0% to 43%, and thus mimic potential pre-analytical contamination. A statistically and clinically significant prolongation was observed for both APTT and PT between 29% and 43% K2 EDTA contamination, whereas the decrease of fibrinogen values became statistically and clinically significant at 43% K2 EDTA contamination. The results of this investigation show that contamination of citrated blood with as much as 29% of K2 EDTA blood generates a significant bias in results of routine clotting assays. This has serious implications for patient safety and management. © 2014 John Wiley & Sons Ltd.

Practical considerations in emergency management of bleeding in the setting of target-specific oral anticoagulants.

Science.gov (United States)

Miller, Michael P; Trujillo, Toby C; Nordenholz, Kristen E

2014-04-01

The recent arrival of the target-specific oral anticoagulants (TSOACs) offers potential advantages in the field of anticoagulation. However, there are no rapid and accurate and routinely available laboratory assays to evaluate their contribution to clinical bleeding. With the expanding clinical indications for the TSOACs, and the arrival of newer reversal agents on the market, the emergency clinician will need to be familiar with drug specifics as well as methods for anticoagulation reversal. This review offers a summary of the literature and some practical strategies for the approach to the patient taking TSOACs and the management of bleeding in these cases. Copyright © 2014 Elsevier Inc. All rights reserved.

Biodegradation of metal citrate complexes and implications for toxic-metal mobility

International Nuclear Information System (INIS)

Francis, A.J.; Dodge, C.J.; Gillow, J.B.

1992-01-01

The presence of synthetic and naturally occurring chelating agents in nuclear and toxic-metal wastes is a major concern because of their potential to enhance mobilization of metal ions away from the disposal sites. Of particular interest is citric acid, which is present in low-level and transuranic radioactive wastes and in domestic and industrial wastes (as washing fluids, for instance), as well as being found naturally. Citrate ions form multidentate, stable complexes with a variety of toxic metals and radionuclides; but biodegradation of these complexes, precipitating the metal ions as insoluble hydroxides, oxides or other salts, may retard migration. Here we report a study of the biodegradation of citrate complexes of Ca, Fe(II), Fe(III), Cd, Cu, Ni, Pb and U. Several of these complexes were not readily degraded by bacteria, and the biodegradability depended on the chemical nature of the complex, not on the toxicity of the metal to the bacteria. This resistance to biodegradation implies that citrate complexation may play an important part in migration of these hazardous wastes. (author)

Highly selective and sensitive macrocycle-based dinuclear foldamer for fluorometric and colorimetric sensing of citrate in water.

Science.gov (United States)

Rhaman, Md Mhahabubur; Hasan, Mohammad H; Alamgir, Azmain; Xu, Lihua; Powell, Douglas R; Wong, Bryan M; Tandon, Ritesh; Hossain, Md Alamgir

2018-01-10

The selective detection of citrate anions is essential for various biological functions in living systems. A quantitative assessment of citrate is required for the diagnosis of various diseases in the human body; however, it is extremely challenging to develop efficient fluorescence and color-detecting molecular probes for sensing citrate in water. Herein, we report a macrocycle-based dinuclear foldamer (1) assembled with eosin Y (EY) that has been studied for anion binding by fluorescence and colorimetric techniques in water at neutral pH. Results from the fluorescence titrations reveal that the 1·EY ensemble strongly binds citrate anions, showing remarkable selectivity over a wide range of inorganic and carboxylate anions. The addition of citrate anions to the 1·EY adduct led to a large fluorescence enhancement, displaying a detectable color change under both visible and UV light in water up to 2 μmol. The biocompatibility of 1·EY as an intracellular carrier in a biological system was evaluated on primary human foreskin fibroblast (HF) cells, showing an excellent cell viability. The strong binding properties of the ensemble allow it to be used as a highly sensitive, detective probe for biologically relevant citrate anions in various applications.

Inhibitory effect of fentanyl citrate on the release of endothlin-1 induced by bradykinin in melanoma cells.

Science.gov (United States)

Andoh, Tsugunobu; Shinohara, Akira; Kuraishi, Yasushi

2017-02-01

Our previous study showed that the μ-opioid receptor agonist fentanyl citrate inhibits endothelin-1-and bradykinin-mediated pain responses in mice orthotopically inoculated with melanoma cells. We also demonstrated that bradykinin induces endothelin-1 secretion in melanoma cells. However, the analgesic mechanisms of fentanyl citrate remain unclear. Thus, the present study was conducted to determine whether fentanyl citrate affects bradykinin-induced endothelin-1 secretion in B16-BL6 melanoma cells. The amount of endothelin-1 in the culture medium was measured using an enzyme immunoassay. The expression of endothelin-1, kinin B 2 receptors, and μ-opioid receptors in B16-BL/6 melanoma cells was determined using immunocytochemistry. Fentanyl citrate inhibited bradykinin-induced endothelin-1 secretion. The inhibitory effect of fentanyl citrate on the secretion of endothelin-1 was attenuated by the μ-opioid receptor antagonist naloxone methiodide. The immunoreactivities of endothelin-1, kinin B 2 receptors, and μ-opioid receptors in B16-BL6 melanoma cells were observed. These results suggest that fentanyl citrate regulates bradykinin-induced endothelin-1 secretion through μ-opioid receptors in melanoma cells. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

21 CFR 172.370 - Iron-choline citrate complex.

Science.gov (United States)

2010-04-01

....370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Special Dietary and Nutritional Additives § 172.370 Iron-choline citrate complex. Iron-choline...

Gaps in monitoring during oral anticoagulation: insights into care transitions, monitoring barriers, and medication nonadherence.

Science.gov (United States)

Rose, Adam J; Miller, Donald R; Ozonoff, Al; Berlowitz, Dan R; Ash, Arlene S; Zhao, Shibei; Reisman, Joel I; Hylek, Elaine M

2013-03-01

Among patients receiving oral anticoagulation, a gap of > 56 days between international normalized ratio tests suggests loss to follow-up that could lead to poor anticoagulation control and serious adverse events. We studied long-term oral anticoagulation care for 56,490 patients aged 65 years and older at 100 sites of care in the Veterans Health Administration. We used the rate of gaps in monitoring per patient-year to predict percentage time in therapeutic range (TTR) at the 100 sites. Many patients (45%) had at least one gap in monitoring during an average of 1.6 years of observation; 5% had two or more gaps per year. The median gap duration was 74 days (interquartile range, 62-107). The average TTR for patients with two or more gaps per year was 10 percentage points lower than for patients without gaps (P < .001). Patient-level predictors of gaps included nonwhite race, area poverty, greater distance from care, dementia, and major depression. Site-level gaps per patient-year varied from 0.19 to 1.78; each one-unit increase was associated with a 9.2 percentage point decrease in site-level TTR (P < .001). Site-level gap rates varied widely within an integrated care system. Sites with more gaps per patient-year had worse anticoagulation control. Strategies to address and reduce gaps in monitoring may improve anticoagulation control.

Risk scores and geriatric profile: can they really help us in anticoagulation decision making among older patients suffering from atrial fibrillation?

Science.gov (United States)

Maes, Frédéric; Dalleur, Olivia; Henrard, Séverine; Wouters, Dominique; Scavée, Christophe; Spinewine, Anne; Boland, Benoit

2014-01-01

Anticoagulation for the prevention of cardio-embolism is most frequently indicated but largely underused in frail older patients with atrial fibrillation (AF). This study aimed at identifying characteristics associated with anticoagulation underuse. A cross-sectional study of consecutive geriatric patients aged ≥75 years, with AF and clear anticoagulation indication (CHADS₂ [Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior Stroke or transient ischemic attack] ≥2) upon hospital admission. All patients benefited from a comprehensive geriatric assessment. Their risks of stroke and bleeding were predicted using CHADS₂ and HEMORR2HAGES (Hepatic or renal disease, Ethanol abuse, Malignancy, Older (age >75 years), Reduced platelet count or function, Rebleed risk, Hypertension (uncontrolled), Anemia, Genetic factors, Excessive fall risk, and Stroke) scores, respectively. Anticoagulation underuse was observed in 384 (50%) of 773 geriatric patients with AF (median age 85 years; female 57%, cognitive disorder 33%, nursing home 20%). No geriatric characteristic was found to be associated with anticoagulation underuse. Conversely, anticoagulation underuse was markedly increased in the patients treated with aspirin (odds ratio [OR] [95% confidence interval]: 5.3 [3.8; 7.5]). Other independent predictors of anticoagulation underuse were ethanol abuse (OR: 4.0 [1.4; 13.3]) and age ≥90 years (OR: 2.0 [1.2; 3.4]). Anticoagulation underuse was not inferior in patients with a lower bleeding risk and/or a higher stroke risk and underuse was surprisingly not inferior either in the AF patients who had previously had a stroke. Half of this geriatric population did not receive any anticoagulation despite a clear indication, regardless of their individual bleeding or stroke risks. Aspirin use is the main characteristic associated with anticoagulation underuse.

Photometric determination of the composition and dissociation constants of niobium (5) citrate complexes

International Nuclear Information System (INIS)

Grigor'eva, V.V.; Golubeva, I.V.

1979-01-01

Niobium (5) citrate complexes in aqueous solution (pH 1-6) are investigated. To determine the complexes composition the metal-indicator method has been applied. Experimental data have been treated by the method of equilibrium shift using somewhat changed variant of the metal-indicator method. The complex ion charge in the solution has been determined by the ion-exchange method. Dissociation constants of citrate complexes have been determined photometrically

Renal Localization of {sup 67}Ga Citrate in Noninfectious Nephritis

Energy Technology Data Exchange (ETDEWEB)

Lee, Kang Wook; Jeong, Min Soo; Rhee, Sunn Kgoo; Kim, Sam Yong; Shin, Young Tai; Ro, Heung Kyu [Chungnam University College of Medicine, Deajeon (Korea, Republic of)

1992-07-15

{sup 67}Ga citrate scan has been requested for detection or follow-up of inflammatory or neoplastic disease. Visualization of {sup 67}Ga citrate in the kidneys at 48 and 72 hr post injection is usually interpreted as evidence of renal pathology. But precise mechanisms of abnormal {sup 67}Ga uptake in kidneys were unknown. We undertook a study to determine the clinical value of {sup 67}Ga citrate imaging of the kidneys in 68 patients with primary or secondary nephropathy confirmed by renal biopsy and 66 control patients without renal disease. Renal uptake in 48 to 72 hr images was graded as follows: Grade 0=background activity;1=faint uptake greater than background; 2=definite uptake, but less than lumbar vertebrae;3 same uptake as lumbar vertebrae, but less than liver; 4=same or higher uptake than liver. The results were as follows. 1) 42 of 68(62%) patients with noninfectious nephritis showed grade 2 or higher {sup 67}Ga renal uptake but only 10 percent of control patients showed similar uptake. 2) In 14 patients with systemic lupus erythematosus, 8 of 9 (89%) patients with lupus nephritis exhibited marked renal uptake. 3) 36 of 41 patients (88%) with combined nephrotic syndrome showed Grade 2 or higher renal uptake. 4) Renal {sup 67}Ga uptake was correlated with clinical severity of nephrotic syndrome determined by serum albumin level, 24 hr urine protein excretion and serum lipid levels. 5) After complete remission of nephrotic syndrome, renal uptake in all 8 patients who were initially Grade 3 or 4, decreased to Grade 1 or 0. In conclusion, we think that the mechanism of renal {sup 67}Ga uptake in nephrotic syndrome might be related to the pathogenesis of nephrotic syndrome. In systemic lupus erythematosus, {sup 67}Ga citrate scan is useful in predicting renal involvement.

Colon transit scintigraphy by 67 Ga citrate for idiopathic constitution

International Nuclear Information System (INIS)

Neshandar Asll, I.; Ehsani, M.J.; Javadi, H.

2005-01-01

Background/objective: segmental colonic transit studies are important in patients with severe constipation. This study is the first Iranian preliminary survey of colonic transit scintigraphy using 67 Ga -citrate as a new method in constipated patients with normal radiographic and colonoscopic evaluations. Patients and methods: thirteen patients with idiopathic constipation underwent colon transit scintigraphy. After oral administration of 6-7 MBq Ga-citrates, serial abdominal images were taken up to 72 hours. Pattern classification wa s performed visually according to the distribution of radioactivity, Scintigraphic parameters such as geometric mean center of seq mental retention of tracer, as well as mean ac activity profiles and colonic tracer half-clearance time were calculated Results: Three patterns of colonic transit scintigraphy were recognized. Nine patients had the normal pattern, i.e. excellent propagation of ac activity. Three patients had the colonic inertia pattern with marked retention of activity in the transverse colon and splenic flexure at 48 hours, One patient had significant retention of activity in the recto sigmoid at 72 hours, defined as functional recto sigmoid obstruction . No significant difference was seen in GMC24h between the normal pattern and colonic inertia (P4.053), but GMC48h and GMC72h markedly differed between the two groups (P50.0 16 and 0.025 respectively). 'The mean half clearance time of the two groups was di different (P4.017). Our results are well compatible with scintigraphic diagnostic criteria in different patterns of colonic transit defined by other studies with different radiotracer. Conclusion: oral 67 Ga -citrate colon transit scintigraphy is a feasible method to evaluate idiopathic constipation and seems to be a suitable surrogate for radio-opaque markers. Keywords: oral 67 Ga -citrate, colonic transit study, idiopathic constipation, scintigraphy

The role of tannic acid and sodium citrate in the synthesis of silver nanoparticles

Science.gov (United States)

Ranoszek-Soliwoda, Katarzyna; Tomaszewska, Emilia; Socha, Ewelina; Krzyczmonik, Pawel; Ignaczak, Anna; Orlowski, Piotr; Krzyzowska, Małgorzata; Celichowski, Grzegorz; Grobelny, Jaroslaw

2017-08-01

We describe herein the significance of a sodium citrate and tannic acid mixture in the synthesis of spherical silver nanoparticles (AgNPs). Monodisperse AgNPs were synthesized via reduction of silver nitrate using a mixture of two chemical agents: sodium citrate and tannic acid. The shape, size and size distribution of silver particles were determined by UV-Vis spectroscopy, dynamic light scattering (DLS) and scanning transmission electron microscopy (STEM). Special attention is given to understanding and experimentally confirming the exact role of the reagents (sodium citrate and tannic acid present in the reaction mixture) in AgNP synthesis. The oxidation and reduction potentials of silver, tannic acid and sodium citrate in their mixtures were determined using cyclic voltammetry. Possible structures of tannic acid and its adducts with citric acid were investigated in aqueous solution by performing computer simulations in conjunction with the semi-empirical PM7 method. The lowest energy structures found from the preliminary conformational search are shown, and the strength of the interaction between the two molecules was calculated. The compounds present on the surface of the AgNPs were identified using FT-IR spectroscopy, and the results are compared with the IR spectrum of tannic acid theoretically calculated using PM6 and PM7 methods. The obtained results clearly indicate that the combined use of sodium citrate and tannic acid produces monodisperse spherical AgNPs, as it allows control of the nucleation, growth and stabilization of the synthesis process. [Figure not available: see fulltext.

Women taking the “blue pill” (sildenafil citrate: such a big deal?

Directory of Open Access Journals (Sweden)

Lo Monte G

2014-11-01

Full Text Available Giuseppe Lo Monte, Angela Graziano, Isabella Piva, Roberto Marci Department of Morphology, Surgery, and Experimental Medicine, University of Ferrara, Ferrara, Italy Abstract: For years, phosphodiesterase type 5 inhibitors have been used for the treatment of erectile dysfunctions. Due to the similarities between male and female sexual response, several studies have assessed the effects of sildenafil citrate (Viagra® in women affected by female sexual arousal disorder. The results are still conflicting and the drug is not devoid of adverse effects. Furthermore, female sexual arousal disorder is a heterogeneous condition whose underlying causes are difficult to diagnose and appropriate treatment requires a thorough sexual, psychological, and medical history along with specialist consultations. The clinician should pursue a global approach to the patient with sexual difficulties, while non-hormonal treatment such as phosphodiesterase type 5 inhibitors (ie, sildenafil citrate should be kept as the last option. Keywords: phosphodiesterase type 5 inhibitors, female sexual arousal disorder (FSAD, sildenafil citrate

A fundamental study on brain scanning with sup(99m)Tc-citrate

International Nuclear Information System (INIS)

Ishii, Katsumi; Kobayashi, Takeshi; Yamada, Nobuaki; Horiike, Shigeharu; Nakazawa, Keiji

1978-01-01

We examined the sup(99m)Tc-citrate obtained by labelling citrate with sup(99m)Tc-pertechnetate using Solcocitran Kit. For our fundamental study--we measured the ratio of labelling by means of paper chromatography. By picking out each organs of each rats we also measured the velocity at which radiopharmaceuticals disappeared in each of their organs, and the distribution of radio-pharmaceuticals in their organs. For our clinical study--we performed brain scanning on 47 patients. The following are the results; Citrate was labelled as much as 99 - 95% into sup(99m)Tc-pertechnetate. The velocity of disappearance in each organ of the rats was quicker than in the case of sup(99m)TcO 4 - . Accumulation in the choroid plexus and salivary gland was not obserbed despite the fact that we did not use KClo 4 , and images of brain tumor were obtainable to a high degree. (author)

Scoring and psychometric validation of the Perception of Anticoagulant Treatment Questionnaire (PACT-Q©

Directory of Open Access Journals (Sweden)

Essers B

2009-04-01

Full Text Available Abstract Background The 'Perception of Anti-Coagulant Treatment Questionnaire' (PACT-Q was developed to assess patients' expectations of, and satisfaction with their anticoagulant treatment. This questionnaire needs to be finalised and psychometrically validated. Methods The PACT-Q was included in the United States, the Netherlands and France into three phase III multinational clinical trials conducted to evaluate efficacy and safety of a new long-acting anticoagulant drug (idraparinux compared to vitamin K antagonist (VKA. PACT-Q was administered to patients with deep venous thrombosis (DVT, atrial fibrillation (AF or pulmonary embolism (PE at Day 1, to assess patients' expectations, and at 3 and 6 months to assess patients' satisfaction and treatment convenience and burden. The final structure of the PACT-Q (Principal Component Analysis – PCA – with Varimax Rotation was first determined and its psychometric properties were then measured with validity of the structure (Multitrait analysis, internal consistency reliability (Cronbach's alpha coefficients and known-group validity. Results PCA and multitrait analyses showed the multidimensionality of the "Treatment Expectations" dimension, comprising 7 items that had to be scored independently. The "Convenience" and "Burden of Disease and Treatment" dimensions of the hypothesised original structure of the questionnaire were combined, thus resulting in 13 items grouped into the single dimension "Convenience". The "Anticoagulant Treatment Satisfaction" dimension remained unchanged and included 7 items. All items of the "Convenience" and "Anticoagulant Treatment Satisfaction" dimensions displayed good convergent and discriminant validity. The internal consistency reliability was good, with a Cronbach's alpha of 0.84 for the "Convenience" dimension, and 0.76 for the "Anticoagulant Treatment Satisfaction" dimension. Known-group validity was good, especially with regard to occurrence of

Multicentre randomised placebo-controlled trial of oral anticoagulation with apixaban in systemic sclerosis-related pulmonary arterial hypertension: the SPHInX study protocol.

Science.gov (United States)

Calderone, Alicia; Stevens, Wendy; Prior, David; Nandurkar, Harshal; Gabbay, Eli; Proudman, Susanna M; Williams, Trevor; Celermajer, David; Sahhar, Joanne; Wong, Peter K K; Thakkar, Vivek; Dwyer, Nathan; Wrobel, Jeremy; Chin, Weng; Liew, Danny; Staples, Margaret; Buchbinder, Rachelle; Nikpour, Mandana

2016-12-08

Systemic sclerosis (SSc) is a severe and costly multiorgan autoimmune connective tissue disease characterised by vasculopathy and fibrosis. One of the major causes of SSc-related death is pulmonary arterial hypertension (PAH), which develops in 12-15% of patients with SSc and accounts for 30-40% of deaths. In situ thrombosis in the small calibre peripheral pulmonary vessels resulting from endothelial dysfunction and an imbalance of anticoagulant and prothrombotic mediators has been implicated in the complex pathophysiology of SSc-related PAH (SSc-PAH), with international clinical guidelines recommending the use of anticoagulants for some types of PAH, such as idiopathic PAH. However, anticoagulation has not become part of standard clinical care for patients with SSc-PAH as only observational evidence exists to support its use. Therefore, we present the rationale and methodology of a phase III randomised controlled trial (RCT) to evaluate the efficacy, safety and cost-effectiveness of anticoagulation in SSc-PAH. This Australian multicentre RCT will compare 2.5 mg apixaban with placebo, in parallel treatment groups randomised in a 1:1 ratio, both administered twice daily for 3 years as adjunct therapy to stable oral PAH therapy. The composite primary outcome measure will be the time to death or clinical worsening of PAH. Secondary outcomes will include functional capacity, health-related quality of life measures and adverse events. A cost-effectiveness analysis of anticoagulation versus placebo will also be undertaken. Ethical approval for this RCT has been granted by the Human Research Ethics Committees of all participating centres. An independent data safety monitoring board will review safety and tolerability data for the duration of the trial. The findings of this RCT are to be published in open access journals. ACTRN12614000418673, Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence

Using Artificial Intelligence to Reduce the Risk of Nonadherence in Patients on Anticoagulation Therapy.

Science.gov (United States)

Labovitz, Daniel L; Shafner, Laura; Reyes Gil, Morayma; Virmani, Deepti; Hanina, Adam

2017-05-01

This study evaluated the use of an artificial intelligence platform on mobile devices in measuring and increasing medication adherence in stroke patients on anticoagulation therapy. The introduction of direct oral anticoagulants, while reducing the need for monitoring, have also placed pressure on patients to self-manage. Suboptimal adherence goes undetected as routine laboratory tests are not reliable indicators of adherence, placing patients at increased risk of stroke and bleeding. A randomized, parallel-group, 12-week study was conducted in adults (n=28) with recently diagnosed ischemic stroke receiving any anticoagulation. Patients were randomized to daily monitoring by the artificial intelligence platform (intervention) or to no daily monitoring (control). The artificial intelligence application visually identified the patient, the medication, and the confirmed ingestion. Adherence was measured by pill counts and plasma sampling in both groups. For all patients (n=28), mean (SD) age was 57 years (13.2 years) and 53.6% were women. Mean (SD) cumulative adherence based on the artificial intelligence platform was 90.5% (7.5%). Plasma drug concentration levels indicated that adherence was 100% (15 of 15) and 50% (6 of 12) in the intervention and control groups, respectively. Patients, some with little experience using a smartphone, successfully used the technology and demonstrated a 50% improvement in adherence based on plasma drug concentration levels. For patients receiving direct oral anticoagulants, absolute improvement increased to 67%. Real-time monitoring has the potential to increase adherence and change behavior, particularly in patients on direct oral anticoagulant therapy. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02599259. © 2017 American Heart Association, Inc.

Safety and efficacy of anticoagulation for secondary stroke prevention in atrial fibrillation patients: The AMADEUS trial

NARCIS (Netherlands)

Lane, D.A.; Kamphuisen, P.W.; Minini, P.; Buller, H.R.; Lip, G.Y.H.

2010-01-01

ackground: Patients with atrial fibrillation (AF) and previous ischemic stroke are at high risk of recurrent stroke, but are also perceived to be at increased bleeding risk while treated with anticoagulants. Methods: Post-hoc analyses examined the efficacy and safety of anticoagulation of 4576 AF

Major cerebral events in Staphylococcus aureus infective endocarditis: is anticoagulant therapy safe?

DEFF Research Database (Denmark)

Rasmussen, Rasmus V; Snygg-Martin, Ulrika; Olaison, Lars

2009-01-01

OBJECTIVES: To study the impact of anticoagulation on major cerebral events in patients with left-sided Staphylococcus aureus infective endocarditis (IE). METHODS: A prospective cohort study; the use of anticoagulation and the relation to major cerebral events was evaluated separately at onset...... of admission and during hospitalization. RESULTS: Overall, 70 out of 175 patients (40%; 95% CI: 33-47%) experienced major cerebral events during the course of the disease, cerebral ischaemic stroke occured in 59 patients (34%; 95% CI: 27-41%), cerebral infection in 23 patients (14%; 95% CI: 9...

The first pharmacist-managed anticoagulation clinic under a collaborative practice agreement in Qatar: clinical and patient-oriented outcomes.

Science.gov (United States)

Elewa, H F; AbdelSamad, O; Elmubark, A E; Al-Taweel, H M; Mohamed, A; Kheir, N; Mohamed Ibrahim, M I; Awaisu, A

2016-08-01

Optimal outpatient anticoagulation management requires a systematic and coordinated approach. Extensive evidence regarding the benefits of pharmacist-managed anticoagulation services has been reported in the literature. The quality and outcomes associated with pharmacist-managed anticoagulation clinics under collaborative practice agreements in the Middle East have rarely been reported. The first pharmacist-managed ambulatory anticoagulation clinic in Qatar was launched at Al-Wakrah Hospital in March 2013. The objectives of this study were to: (i) describe the practice model of the clinic, (ii) evaluate the quality of the clinic [i.e. the time in therapeutic range (TTR)] and the clinical outcomes (i.e. the efficacy and safety), and (iii) determine the patients' satisfaction and overall quality of life (QoL). Clinical outcome data were collected through a retrospective chart review of all patients managed from March 2013 to October 2014 at the pharmacist-managed anticoagulation clinic. Furthermore, the patient-oriented outcomes data were prospectively collected using the 24-item Duke Anticoagulation Satisfaction Scale (DASS). Each item was assessed using a 7-point Likert-type scale on which lower scores indicated better QoL and greater satisfaction. The clinical outcome data analyses included 119 patients who were enrolled at the clinic during the 19-month study period. The mean number of international normalized ratio (INR) tests/month was 65 ± 9, the average testing frequency was 2·7 ± 1·6 weeks, and the average %TTR was 76·8 ± 22·9%. There was one major bleeding event (0·67%/year), 12 minor bleeding events (8%/year) and two thromboembolic events (1·35%/year) recorded during the study period. Of the 119 patients, 50 participated in the satisfaction and QoL survey. The median (IQR) total QoL score of these subjects was 63 (48) (minimum-maximum achievable score: 24-168). Seventy-six per cent of the patients indicated 'a lot to very much' in terms of their

The Effect of Polymer Molecular Weight on Citrate Crosslinked ...

African Journals Online (AJOL)

Erah

Purpose: To develop citrate crosslinked chitosan films using chitosan of different molecular weights. (MW) in .... left to stand until trapped air bubbles ... blotted out carefully with filter paper from the .... potential as biodegradable stent coatings. J.

The risk of venous thromboembolism with aspirin compared to anticoagulants after hip and knee arthroplasty.

Science.gov (United States)

Chu, Janet N; Maselli, Judith; Auerbach, Andrew D; Fang, Margaret C

2017-07-01

Recent guidelines include aspirin as an option to prevent venous thromboembolism (VTE) in selected patients undergoing hip or knee replacement surgery. However, the efficacy of aspirin after arthroplasty has not been well-defined, particularly in more contemporary patient populations. We compared rates of post-operative VTE between patients who received aspirin-only versus anticoagulants after hip or knee arthroplasty, using data from a large US-based administrative database. We conducted a retrospective cohort study of 231,780 adults who underwent total knee arthroplasty and 110,621 who underwent total hip arthroplasty in 2009-2012 and who received pharmacologic VTE prophylaxis (aspirin or anticoagulant) within the first 7days after surgery. We compared the risk of post-operative VTE between patients receiving aspirin-only vs. anticoagulants, controlling for clinical and hospital characteristics using multivariable logistic regression with propensity score adjustment. Aspirin-only prophylaxis was administered to 7.5% of patients after knee arthroplasty and 8.0% after hip arthroplasty. Post-operative VTE was diagnosed in 2217 (0.96%) patients after knee arthroplasty and 454 (0.41%) after hip arthroplasty. Compared to anticoagulants, aspirin was not associated with a higher risk for post-operative VTE either after knee arthroplasty (adjusted odds ratio and 95% confidence interval [OR] 0.34 [0.24-0.48]) or hip arthroplasty (OR 0.82 [0.45-1.51]). Aspirin was uncommonly administered as the sole prophylactic agent after hip or knee arthroplasty in this study. However, patients who received aspirin-only had similar rates of post-operative VTE compared to patients who received anticoagulants. Further research should focus on distinguishing which patients benefit more from anticoagulants versus aspirin after arthroplasty. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Comparison of Secondary Polycythemia in Hypogonadal Men Treated with Clomiphene Citrate versus Testosterone Replacement: A Multi-Institutional Study.

Science.gov (United States)

Wheeler, Karen M; Smith, Ryan P; Kumar, Raj A; Setia, Shaan; Costabile, Raymond A; Kavoussi, Parviz K

2017-04-01

We evaluated the relative prevalence of secondary polycythemia in hypogonadal men treated with clomiphene citrate or testosterone replacement therapy. In this retrospective, multi-institutional study, we included 188 men who received clomiphene citrate and 175 who received testosterone replacement therapy with symptomatic hypogonadism. The overall prevalence and ORs of secondary polycythemia for clomiphene citrate treatment vs testosterone replacement were primarily measured, as were baseline characteristics. Subset analysis included polycythemia rates for different types of testosterone replacement therapy. Overall, men on testosterone replacement therapy were older than clomiphene citrate treated men (age 51.5 vs 38 years). Men on testosterone replacement had longer treatment duration than clomiphene citrate treated men (19.6 vs 9.2 months). For testosterone replacement therapy and clomiphene citrate the mean change in hematocrit was 3.0% and 0.6%, and the mean change in serum testosterone was 333.1 and 367.6 ng/dl, respectively. The prevalence of polycythemia in men on testosterone replacement was 11.2% vs 1.7% in men on clomiphene citrate (p = 0.0003). This significance remained on logistic regression after correcting for age, site, smoking history and pretreatment hematocrit. The prevalence of polycythemia in men treated with clomiphene citrate was markedly lower than that in men on testosterone replacement therapy. The improvement in absolute serum testosterone levels was similar to that in men on testosterone replacement. There is no significant risk of polycythemia in men treated with clomiphene citrate for hypogonadism. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Citrate biodegradation. Mid-year status report, [January 1994--June 1994

International Nuclear Information System (INIS)

Francis, A.J.; Dodge, C.J.; Chatterjee, S.; Landry, M.F.

1994-07-01

The Uranium Soils Integrated Demonstration (USID) Program was established to demonstrate advanced technologies for the remediation of uranium contaminated soils. This program, managed by the Fernald Environmental Restoration Management Corporation (FERMCO), focuses on the development and demonstration of new soil remediation processes which are faster, safer, and more economical for use at the Fernald site and throughout the DOE complex for cleanup of similar contaminants. Brookhaven National Laboratory (BNL) has developed a process which uses citric acid to treat contaminated soils and wastes with the subsequent recovery of toxic metals and uranium. Citric acid, a naturally occurring organic chelating agent, forms multidentate stable complexes with the transition metals and actinides, and has been effectively used to extract uranium and other metals from solid wastes via the formation of soluble metal citrate complexes. Further studies have also shown that several of the metal citrate complexes are readily biodegraded by microorganisms. During this process, the metals form a precipitate or become associated with the biomass and are recovered at the end of the biodegradation. Although uranyl citrate is recalcitrant to biodegradation, upon exposure to visible light it undergoes photochemical degradation resulting in the formation of an insoluble, stable polymeric form of uranium

Fatal rebleeding following coil embolization of cerebral aneurysms: the role of long-term systemic anticoagulation

International Nuclear Information System (INIS)

Sinson, G.; Bagley, L.J.; Hurst, R.W.; Flamm, E.S.

2001-01-01

Embolization of cerebral aneurysms has become a common technique. Its impact on subsequent medical management of the patient is not well known. We report two patients who presented in a poor neurological grade after subarachnoid hemorrhage from posterior communicating artery aneurysms. Both were treated by coil embolization and both developed subclavian vein thrombosis, requiring systemic anticoagulation, initiated 11 and 21 days after embolization, respectively. Both developed a large, fatal intracranial hemorrhage adjacent to the embolized aneurysm in the fourth week of anticoagulation. Systemic anticoagulation of patients who have had a ruptured aneurysm treated by coil embolization may carry a significant risk of rebleeding. Alternate management strategies should be considered in these patients. (orig.)

Fatal rebleeding following coil embolization of cerebral aneurysms: the role of long-term systemic anticoagulation

Energy Technology Data Exchange (ETDEWEB)

Sinson, G. [Dept. of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, PA (United States); Bagley, L.J.; Hurst, R.W. [Dept. of Radiology-Neuroradiology, University of Pennsylvania School of Medicine, Philadelphia, PA (United States); Flamm, E.S. [Hyman-Newman Institute for Neurology and Neurosurgery, New York, NY (United States)

2001-05-01

Embolization of cerebral aneurysms has become a common technique. Its impact on subsequent medical management of the patient is not well known. We report two patients who presented in a poor neurological grade after subarachnoid hemorrhage from posterior communicating artery aneurysms. Both were treated by coil embolization and both developed subclavian vein thrombosis, requiring systemic anticoagulation, initiated 11 and 21 days after embolization, respectively. Both developed a large, fatal intracranial hemorrhage adjacent to the embolized aneurysm in the fourth week of anticoagulation. Systemic anticoagulation of patients who have had a ruptured aneurysm treated by coil embolization may carry a significant risk of rebleeding. Alternate management strategies should be considered in these patients. (orig.)

Intermittent vs. Continuous Anticoagulation theRapy in patiEnts with Atrial Fibrillation (iCARE-AF): a randomized pilot study.

Science.gov (United States)

Stavrakis, Stavros; Stoner, Julie A; Kardokus, Joel; Garabelli, Paul J; Po, Sunny S; Lazzara, Ralph

2017-01-01

We hypothesized that intermittent anticoagulation based on daily rhythm monitoring using the novel oral anticoagulants (NOACs) is feasible and safe among patients with paroxysmal atrial fibrillation (AF). Patients with paroxysmal AF and ≥1 risk factors for stroke were randomized to either intermittent or continuous anticoagulation. Those in the intermittent group were instructed to transmit a daily ECG using an iPhone-based rhythm monitoring device. If AF was detected, patients received one of the NOACs for 48 h-1 week. Patients who failed to transmit an ECG for three consecutive days or more than 7 days total were crossed over to continuous anticoagulation. Patients in the continuous group received one of the NOACs. Fifty-eight patients were randomized to either intermittent (n = 29) or continuous anticoagulation (n = 29). Over a median follow-up of 20 months, 20 patients in the intermittent group failed to submit a daily ECG at least once (median three failed submissions). Four patients (14 %) crossed over to continuous anticoagulation due to failure to submit an ECG for three consecutive days. One stroke (continuous group) occurred during the study. Major bleeding occurred in two patients in the continuous and one patient in the intermittent group, after crossing over to continuous anticoagulation. In a prespecified per-protocol analysis, gastrointestinal bleeding was more frequent in the continuous group (16 vs. 0 %; p = 0.047). Intermittent anticoagulation based on daily rhythm monitoring is feasible and may decrease bleeding in low-risk patients with paroxysmal AF. A larger trial, adequately powered to detect clinical outcomes, is warranted.

[Clinical scores for the risk of bleeding with or without anticoagulation].

Science.gov (United States)

Junod, Alain

2016-09-14

The assessment of hemorragic risk related to therapeutic anticoagulation is made difficult because of the variety of existing drugs, the heterogeneity of treatment strategies and their duration. Six prognostic scores have been analyzed. For three of them, external validations have revealed a marked decrease in the discrimination power. One British study, Qbleed, based on the data of more than 1 million of ambulatory patients, has repeatedly satisfied quality criteria. Two scores have also studied the bleeding risk during hospital admission for acute medical disease. The development of new and effective anticoagulants with fewer side-effects is more likely to solve this problem than the production of new clinical scores.

78 FR 34648 - Citric Acid and Certain Citrate Salts: Preliminary Results of Countervailing Duty Administrative...

Science.gov (United States)

2013-06-10

... citric acid and citrate salts from the People's Republic of China for the period January 1, 2011, through... and Certain Citrate Salts from the People's Republic of China: Notice of Countervailing Duty Order, 74... subsidy, i.e., a government-provided financial contribution that gives rise to a benefit to the recipient...

Neptunium speciation (complexation and redox behaviour) in aqueous citrate medium

International Nuclear Information System (INIS)

Bonin, L.; Ansoborlo, E.; Moisy, Ph.

2005-01-01

Full text of publication follows: In the framework of the French Environmental Nuclear Toxicology programme, additional experiments related to the decorporation of actinides are planned. The lack of information on the neptunium behaviour within blood and the inefficiency of therapeutic treatments, led us to study the complexation of this element with basic anions. Within this purpose, the in vitro behaviour of Np IV and Np V in simple media simulating biological media was studied: blood plasma is one of the media of interest and it can be simulated, from a chemical point of view, by an aqueous solution with pH 7.4, containing ions such as citrate (1.6 10 -4 mol/L), lactate (1.5 10 -3 mol/L), CO 3 2- (2.5 10 -2 mol/L), PO 4 3- (1.1 10 -3 mol/L), SO 4 2- (3.3 10 -4 mol/L) and Cl - (9 10 -2 mol/L). This study was more specifically focused on the behaviour of neptunium with citrate ion, which is also a basic ligand to consider when one wishes to study the migration of actinides in the environment, since it exists in significant amounts in the ground due to its production by the plants. In order to determine the speciation of this system, spectrophotometry was more particularly used. Concerning the complexation phenomenon, the existence of several complexes of Np V with various acid-basic forms of the citrate anion was observed; regarding Np IV , two complexes, with 1:1 and 1:2 stoichiometry, have been respectively observed. The reactivity of Np VI is probably similar to the behaviour of U VI , which is reported in literature to form a complex with a 1:1 stoichiometry with the Cit 3- anion From the quantitative study of these equilibria, it has been possible to determine the values of various equilibrium constants. Concerning the stability of neptunium towards oxido-reduction, it was confirmed that Np VI was very quickly reduced to Np V by the citrate anions, whereas Np IV was stable. In the case of Np V , it was observed that, depending on the pH and the citrate

Bleeding complications during anticoagulant treatment in patients with cancer

NARCIS (Netherlands)

Kamphuisen, Pieter W.; Beyer-Westendorf, Jan

Patients with cancer have an increased risk of bleeding complications, of which some are fatal. This risk is influenced by chemotherapy, cancer type and stage, thrombocytopenia, renal function, and previous bleeding. Since many cancer patients receive anticoagulant treatment for prophylaxis or

Self-management of oral anticoagulant therapy in two centers

DEFF Research Database (Denmark)

Nilsson, Hanna; Grove, E; Larsen, Torben Bjerregaard

of Cardiology, Aarhus University Hospital, Aarhus; 3Department of Cardiology, Aalborg Hospital & Department of Health Science and Technology, Aalborg University, Aalborg, Denmark haana_86@hotmail.com Objectives: Patient-self-management (PSM) of oral anticoagulant therapy with vitamin K antagonists have...

Synthesis of Fucosylated Chondroitin Sulfate Glycoclusters: A Robust Route to New Anticoagulant Agents.

Science.gov (United States)

Zhang, Xiao; Yao, Wang; Xu, Xiaojiang; Sun, Huifang; Zhao, Jinhua; Meng, Xiangbao; Wu, Mingyi; Li, Zhongjun

2018-02-01

Fucosylated chondroitin sulfate (FuCS) is a structurally distinct glycosaminoglycan with excellent anticoagulant activity. Studies show that FuCS and its depolymerized fragments exhibit a different anticoagulant mechanism from that of heparin derivatives, with decreased risks of adverse effects and bleeding. However, further exploitation has been hindered by the scarcity of structurally defined oligosaccharides. Herein, facile method is reported for the synthesis of the repeating trisaccharide unit of FuCS based on the degradation of chondroitin sulfate polymers. A series of simplified FuCS glycomimetics that have highly tunable structures, controllable branches, and defined sulfation motifs were generated by copper-catalyzed alkyne-azide cycloaddition. Remarkable improvement in activated partial thromboplastin time (APTT) assay activities was observed as the branches increased, but no significant influences were observed for prothrombin time (PT) and thrombin time (TT) assay activities. Further FXase inhibition tests suggested that glycoclusters 33 b-40 b selectively inhibited intrinsic anticoagulant activities, but had little effect on the extrinsic and common coagulation pathways. Notably, glycoclusters with the 2,4-di-O-sulfated fucosyl residue displayed the most potency, which was in consistent with that of natural polysaccharides. These FuCS clusters demonstrated potency to mimic linear glycosaminoglycans and offer a new framework for the development of novel anticoagulant agents. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bright luminescence of Vibrio fischeri aconitase mutants reveals a connection between citrate and the Gac/Csr regulatory system.

Science.gov (United States)

Septer, Alecia N; Bose, Jeffrey L; Lipzen, Anna; Martin, Joel; Whistler, Cheryl; Stabb, Eric V

2015-01-01

The Gac/Csr regulatory system is conserved throughout the γ-proteobacteria and controls key pathways in central carbon metabolism, quorum sensing, biofilm formation and virulence in important plant and animal pathogens. Here we show that elevated intracellular citrate levels in a Vibrio fischeri aconitase mutant correlate with activation of the Gac/Csr cascade and induction of bright luminescence. Spontaneous or directed mutations in the gene that encodes citrate synthase reversed the bright luminescence of aconitase mutants, eliminated their citrate accumulation and reversed their elevated expression of CsrB. Our data elucidate a correlative link between central metabolic and regulatory pathways, and they suggest that the Gac system senses a blockage at the aconitase step of the tricarboxylic acid cycle, either through elevated citrate levels or a secondary metabolic effect of citrate accumulation, and responds by modulating carbon flow and various functions associated with host colonization, including bioluminescence. © 2014 John Wiley & Sons Ltd.

Vitamin K and stability of oral anticoagulant therapy

NARCIS (Netherlands)

Rombouts, Eva Karolien

2011-01-01

One of the causes of unstable anticoagulation is a variable vitamin K intake. The main objective of this thesis was to test the hypothesis that the INR is particularly sensitive to changes in vitamin K intake when vitamin K status is low, and that patients with a low vitamin K intake would therefore

Non-vitamin K antagonist oral anticoagulants (NOAC) in the treatment of venous thromboembolism

OpenAIRE

Sebastian Werth; Jan Beyer-Westendorf

2015-01-01

In case of venous thromboembolism (VTE) e ective anticoagulation is needed. The introduction of non-vitamin K antagonist oral anticoagulants (NOACs) for VTE therapy o ers new treatment options and, in general, simpli es VTE therapy compared to the concept of LMWH/ VKA. At the same time, NOACs may help to improve the clinical outcome of patients with VTE as trial results consistently indicated the reduction in major bleeding complications. There are several reasons to use NOAC in special p...

Is magnesium citrate treatment effective on pain, clinical parameters and functional status in patients with fibromyalgia?

Science.gov (United States)

Bagis, Selda; Karabiber, Mehmet; As, Ismet; Tamer, Lülüfer; Erdogan, Canan; Atalay, Ayçe

2013-01-01

The aims of this study were to investigate the relationship between magnesium levels and fibromyalgia symptoms and to determine the effect of magnesium citrate treatment on these symptoms. Sixty premenopausal women diagnosed with fibromyalgia according to the ACR criteria and 20 healthy women whose age and weight matched the premenopausal women were evaluated. Pain intensity, pain threshold, the number of tender points, the tender point index, the fibromyalgia impact questionnaire (FIQ), the Beck depression and Beck anxiety scores and patient symptoms were evaluated in all the women. Serum and erythrocyte magnesium levels were also measured. The patients were divided into three groups. The magnesium citrate (300 mg/day) was given to the first group (n = 20), amitriptyline (10 mg/day) was given to the second group (n = 20), and magnesium citrate (300 mg/day) + amitriptyline (10 mg/day) treatment was given to the third group (n = 20). All parameters were reevaluated after the 8 weeks of treatment. The serum and erythrocyte magnesium levels were significantly lower in patients with fibromyalgia than in the controls. Also there was a negative correlation between the magnesium levels and fibromyalgia symptoms. The number of tender points, tender point index, FIQ and Beck depression scores decreased significantly with the magnesium citrate treatment. The combined amitriptyline + magnesium citrate treatment proved effective on all parameters except numbness. Low magnesium levels in the erythrocyte might be an etiologic factor on fibromyalgia symptoms. The magnesium citrate treatment was only effective tender points and the intensity of fibromyalgia. However, it was effective on all parameters when used in combination with amitriptyline.

Diagnostic imaging of severe rectus sheath hematoma complicating anticoagulant therapy

International Nuclear Information System (INIS)

Blum, A.; Bui, P.; Boccaccini, H.; Bresler, L.; Claudon, M.; Boissel, P.; Regent, D.

1995-01-01

CT were performed in thirteen patients (12 women, 1 man) aged from 53 to 90 (mean age, 74) with severe RSH. Five patients also underwent ultrasound examination and three MR examination. Nine patients (69%) were receiving subcutaneous injection of heparin, three (23%) oral anticoagulant therapy and one continuous IV infusion of heparin. Clinical diagnosis was reached in 6 cases. Excessive activity of anticoagulant therapy was noted in 4 cases. The location of the RSH, their densities and their signals were analysed. All the RSH were mostly developed in the lower third of the abdominal wall, had a large spreading into the Retzius space and compressed the bladder and/or the bowels. RSH were all hyperdense and in 8 cases (61%) a fluid-fluid level due to the hematocrit effect was noted. In one case, a retroperitoneal hematoma was discovered. The extension of the RSH was well delineated with MRI. The RSH showed itself with heterogeneous signal intensities with areas of high-signal-intensity on T1-weighted images. Fluid-fluid levels and a concentric ring sign were also noted. Older women with subcutaneous injection of heparin are especially prone to RSH even though there is no overall excessive activity of anticoagulant therapy. Clinical and biological diagnosis may be difficult. CT scan is the exam of choice to reach a precise and acute diagnosis of RSH. (authors). 34 refs., 8 figs

Renal Infarction during Anticoagulant Therapy after Living Donor Liver Transplantation

Directory of Open Access Journals (Sweden)

Shinji Onda

2018-04-01

Full Text Available Introduction: Liver transplant recipients are at risk for complications of vascular thrombosis. The reconstructed hepatic artery and portal vein thrombosis potentially result in hepatic failure and graft loss. Renal infarction is a rare clinical condition, but in severe cases, it may lead to renal failure. We herein report a case of renal infarction after living donor liver transplantation (LDLT during anticoagulant therapy. Case Presentation: A 60-year-old woman with end-stage liver disease due to primary biliary cholangitis underwent LDLT with splenectomy. Postoperatively, tacrolimus, mycophenolate mofetil, and steroid were used for initial immunosuppression therapy. On postoperative day (POD 5, enhanced computed tomography (CT revealed splenic vein thrombosis, and anticoagulant therapy with heparin followed by warfarin was given. Follow-up enhanced CT on POD 20 incidentally demonstrated right renal infarction. The patient’s renal function was unchanged and the arterial flow was good, and the splenic vein thrombosis resolved. At 4 months postoperatively, warfarin was discontinued, but she developed recurrent splenic vein thrombosis 11 months later, and warfarin was resumed. As of 40 months after transplantation, she discontinued warfarin and remains well without recurrence of splenic vein thrombosis or renal infarction. Conclusion: Renal infarction is a rare complication of LDLT. In this case, renal infarction was incidentally diagnosed during anticoagulant therapy and was successfully treated.

76 FR 34044 - Citric Acid and Certain Citrate Salts From Canada: Final Results of Antidumping Duty...

Science.gov (United States)

2011-06-10

... DEPARTMENT OF COMMERCE International Trade Administration [A-122-853] Citric Acid and Certain... the antidumping duty order on citric acid and certain citrate salts (citric acid) from Canada. The... order on citric acid from Canada. See Citric Acid and Certain Citrate Salts From Canada: Preliminary...

Acute effect of citrate bath on postdialysis alkalaemia

Directory of Open Access Journals (Sweden)

Patricia De Sequera Ortiz

2015-03-01

Conclusion: Dialysis with citrate provides better control of postdialysis acid-base balance, decreases/avoids postdialysis alkalaemia, and lowers the increase in Cac and Cai. This finding is of special interest in patients with predisposing factors for arrhythmia and patients with respiratory failure, carbon dioxide retention, calcifications and advanced liver disease.

Emergency management of major bleeding in a case of maxillofacial trauma and anticoagulation: utility of prothrombin complex concentrates in the shock room

Directory of Open Access Journals (Sweden)

Alessandro Morotti

2015-03-01

Full Text Available Life-threatening bleeding in anticoagulation with Warfarin is an emergency challenging issue. Several approaches are available to treat bleeding in either over-anticoagulation or propeanticoagulation, including vitamin K, fresh frozen plasma and prothrombin complex concentrates (PCC administration. In coexisting trauma-induced bleeding and anticoagulation, reversal of anticoagulation must be a rapid and highly effective procedure. Furthermore the appropriate treatment must be directly available in each shock rooms to guarantee the rapid management of the emergency. PCC require a simple storage, rapid accessibility, fast administration procedures and high effectiveness. Here we report the utility of PCC in management of a craniofacial trauma in proper-anticoagulation.

Safety of percutaneous nephrolithotomy in patients on chronic anticoagulant or antiplatelet therapy.

Science.gov (United States)

Fernández-Baltar, C; Pérez-Fentes, D; Sánchez-García, J F; García-Freire, C

2018-01-22

In developed countries, the incidence of cardiovascular disease is increasing, therefore, anticoagulant and antiplatelet drugs are a widespread treatment nowadays. Percutaneous nephrolithotomy (PNL) is the first-line treatment for large or complex stones (> 2 cm) and remains an alternative for the smaller ones. The objective of this study is to analyze whether PNL surgery is a safe procedure in patients under a treatment discontinuation protocol for anticoagulant or antiplatelet therapies. We retrospectively studied 301 patients who underwent PNL in our hospital between 2008 and 2016 and identified 46 patients on chronic antiplatelet or anticoagulation treatment. With respect to PNL outcomes, the stone-free rate was similar (78 vs 74%, p = 0.762) in both groups, without any significant differences in the overall postoperative complications (17 vs 26%, p = 0.203). The incidence of hemorrhagic complications was similar between groups (12 vs 9%, p = 0.492), as demonstrated by the mean drop in hemoglobin (Hb), which was comparable in both cohorts (2.2 ± 1.3 vs 2.0 ± 1.4 p = 0.270) and the blood transfusion rate (14% in group A and 8% in group B, p = 0.205). No thromboembolic events were found within the year after the PNL procedure. PNL is a safe and effective intervention in patients under a treatment discontinuation protocol for anticoagulant or antiplatelet therapies. Although our study demonstrates the feasibility of this protocol, new scientific evidence aims to stratify the thromboembolic and bleeding risk of each patient to individualize the perioperative management thereafter.

Target specific oral anticoagulants in the management of thromboembolic disease in the elderly.

Science.gov (United States)

Maddula, Surekha; Ansell, Jack

2013-08-01

The elderly population represents a population at highest risk of thromboembolism, but also the most vulnerable to hemorrhage. In the community setting there is a general tendency to under- treat this patient group. Specific consideration must be taken with elderly patients because they have reduced renal function, co-morbidities and risk of falls, altered pharmacodynamics, and challenges with adherence. Vitamin K antagonists, most often warfarin, have been the first line choice of therapy for long-term anticoagulation and enjoyed an unopposed position in the market for the last 70 years. Recently several new oral anticoagulants have been developed and found to be equally effective as warfarin in phase III studies and may provide an optimal treatment option in the elderly population. In this review we explore the target-specific oral anticoagulants and the pharmacological differences between them with a focus on the elderly population in whom these new drugs would constitute a possible alternative to warfarin therapy.

Developmental toxicity of orally administered sildenafil citrate (Viagra) in SWR/J mice.

Science.gov (United States)

Abou-Tarboush, Faisal Mohamed; Abdel-Samad, Mohamed Fathy; Al-Meteri, Mokhlid Hamed

2011-04-01

Normal adult inbred SWR/J mice were used to investigate the teratogenic and other possible toxic effects of various dose levels of sildenafil citrate (Viagra) on fetuses. Multiple dose levels of 6.5, 13.0, 19.5, 26.0, 32.5 or 40.0 mg of sildenafil citrate/kg body weight (which correspond to the multiples of 1, 2, 3, 4, 5 or 6 of human 50 mg Viagra, respectively) were orally administered into pregnant mice on days 7-9, 10-12 or 13-15 of gestation. On day 17 of pregnancy, all fetuses were removed and examined for toxic phenomena (embryo-fetal toxicity) and for external, internal and skeletal malformations. A total of 285 pregnant mice were used in the present study. None of the dams treated with sildenafil citrate at any of the oral dose levels used in the present study died during the experimental period and all dams treated with the drug failed to reveal overt signs of maternal toxicity. Moreover, the results of the present study clearly demonstrate that none of the multiple oral dose levels of the drug at any time interval used has induced any external, internal or skeletal malformations in the fetuses obtained from treated females. However, the dose level of 40 mg/kg body weight of sildenafil citrate has a growth suppressing effect on alive fetuses when it was administered at all the time intervals used in the present study. Furthermore, the dose levels 26.0, 32.5 and 40 mg/kg of the drug have embryo-fetal toxicity when the drug is applied on days 13-15 of gestation. The possible mechanisms involved in the embryo-fetal toxicity and fetal growth suppressing effects of sildenafil citrate were discussed. The results of this study have important implications for the widespread use of this drug.

The "Janus face" of the thrombin binding aptamer: Investigating the anticoagulant and antiproliferative properties through straightforward chemical modifications.

Science.gov (United States)

Esposito, Veronica; Russo, Annapina; Amato, Teresa; Vellecco, Valentina; Bucci, Mariarosaria; Mayol, Luciano; Russo, Giulia; Virgilio, Antonella; Galeone, Aldo

2018-02-01

The thrombin binding aptamer (TBA) is endowed with both anticoagulant and antiproliferative activities. Its chemico-physical and/or biological properties can be tuned by the site-specific replacement of selected residues. Four oligodeoxynucleotides (ODNs) based on the TBA sequence (5'-GGTTGGTGTGGTTGG-3') and containing 2'-deoxyuridine (U) or 5-bromo-2'-deoxyuridine (B) residues at positions 4 or 13 have been investigated by NMR and CD techniques. Furthermore, their anticoagulant (PT assay) and antiproliferative properties (MTT assay) have been tested and compared with two further ODNs containing 5-hydroxymethyl-2'-deoxyuridine (H) residues in the same positions, previously investigated. The CD and NMR data suggest that all the investigated ODNs are able to form G-quadruplexes strictly resembling that of TBA. The introduction of B residues in positions 4 or 13 increases the melting temperature of the modified aptamers by 7 °C. The replacement of thymidines with U in the same positions results in an enhanced anticoagulant activity compared to TBA, also at low ODN concentration. Although all ODNs show antiproliferative properties, only TBA derivatives containing H in the positions 4 and 13 lose the anticoagulant activity and remarkably preserve the antiproliferative one. All ODNs have shown antiproliferative activities against two cancer cell lines but only those with U and B are endowed with anticoagulant activities similar or improved compared to TBA. The appropriate site-specific replacement of the residues in the TT loops of TBA with commercially available thymine analogues is a useful strategy either to improve the anticoagulant activity or to preserve the antiproliferative properties by quenching the anticoagulant ones. Copyright © 2017 Elsevier Inc. All rights reserved.

The Effect of Polymer Molecular Weight on Citrate Crosslinked ...

African Journals Online (AJOL)

SEM), dissolution studies and differential scanning calorimetry (DSC) for surface ... Conclusion: The citrate-crosslinked chitosan films can be modulated to vary swelling and drug release at pH 3.5 and 6.2; this feature makes them useful tools for ...

Shifting to a non-vitamin K antagonist oral anticoagulation agent from vitamin K antagonist in atrial fibrillation

DEFF Research Database (Denmark)

Fosbøl, Emil L; Vinding, Naja Emborg; Lamberts, Morten

2017-01-01

Aims: After non-vitamin K antagonist (VKA) oral anticoagulation agents (NOAC) have been approved for thrombo-embolic prophylaxis in non-valvular atrial fibrillation (NVAF), utilization of oral anticoagulants (OAC) in NVAF has changed. Contemporary shifting from a VKA to a NOAC (dabigatran...

An excess of topical calcium and magnesium reverses the therapeutic effect of citrate on the development of corneal ulcers after alkali injury.

Science.gov (United States)

Haddox, J L; Pfister, R R; Slaughter, S E

1996-03-01

Our purpose was to determine whether chelation of Ca2+ and Mg2+ is the mechanism by which sodium citrate inhibits corneal ulceration in the alkali-injured rabbit eye. The right eyes of 60 albino rabbits (2-2.5 kg) were alkali-injured by filling a 12-mm-diameter plastic well placed on the corneal surface with 0.4 ml of 1 N NaOH. After 35 s the alkali was aspirated, and the well was rinsed with physiological saline. Animals were randomly distributed to three treatment groups of equal size. Two drops of the following topical medications were administered on the hour (14 times per day) for 35 days: physiological saline, 10% citrate in saline, and 346 mM Ca2+, 346 mM Mg2+, and 10% citrate in saline. During the experiment, significantly fewer ulcerations occurred in the citrate-treated eyes (five of 20, 25%) than in the saline-treated eyes (13 of 20, 65%) or in the calcium-magnesium-citrate-treated eyes (15 of 20, 75%). When ulcerations did develop in the citrate group, they occurred significantly later and were less severe than those in the saline and calcium-magnesium-citrate groups. There was a significant increase in the number of eyes with signs of band keratopathy and translucent areas in the calcium-magnesium-citrate group when compared with the other two groups. As in previous studies, sodium citrate significantly inhibited the development of corneal ulcers after alkali injury. The annullment of the favorable effect of citrate on ulceration in the alkali-injured eye by the addition of calcium and magnesium shows that the mechanism of action of citrate is the chelation of these divalent cations.

Adherence rates to ferric citrate as compared to active control in patients with end stage kidney disease on dialysis.

Science.gov (United States)

Jalal, Diana; McFadden, Molly; Dwyer, Jamie P; Umanath, Kausik; Aguilar, Erwin; Yagil, Yoram; Greco, Barbara; Sika, Mohammed; Lewis, Julia B; Greene, Tom; Goral, Simin

2017-04-01

Oral phosphate binders are the main stay of treatment of hyperphosphatemia. Adherence rates to ferric citrate, a recently approved phosphate binder, are unknown. We conducted a post-hoc analysis to evaluate whether adherence rates were different for ferric citrate vs. active control in 412 subjects with end stage kidney disease (ESKD) who were randomized to ferric citrate vs. active control (sevelamer carbonate and/or calcium acetate). Adherence was defined as percent of actual number of pills taken to total number of pills prescribed. There were no significant differences in baseline characteristics including gender, race/ethnicity, and age between the ferric citrate and active control groups. Baseline phosphorus, calcium, and parathyroid hormone levels were similar. Mean (SD) adherence was 81.4% (17.4) and 81.7% (15.9) in the ferric citrate and active control groups, respectively (P = 0.88). Adherence remained similar between both groups after adjusting for gender, race/ethnicity, age, cardiovascular disease (CVD), and diabetic nephropathy (mean [95% CI]: 81.4% [78.2, 84.6] and 81.5% [77.7, 85.2] for ferric citrate and active control, respectively). Gender, race/ethnicity, age, and diagnosis of diabetic nephropathy did not influence adherence to the prescribed phosphate binder. Subjects with CVD had lower adherence rates to phosphate binder; this was significant only in the active control group. Adherence rates to the phosphate binder, ferric citrate, were similar to adherence rates to active control. Similar adherence rates to ferric citrate are notable since tolerance to active control was an entry criteria and the study was open label. Gender, race/ethnicity, nor age influenced adherence. © 2016 International Society for Hemodialysis.

Beliefs and social norms about sildenafil citrate (Viagra) misuse and perceived consequences among Houstonian teenage males.

Science.gov (United States)

Peters, Ronald J; Johnson, Regina J; Kelder, Steve; Meshack, Angela F; Jefferson, Troy

2007-09-01

In the current study, a qualitative approach was used to investigate relevant beliefs and norms associated with sildenafil citrate (Viagra) consumption, initiation, and perceived consequences. Focus groups were conducted with 43 young men aged 18 and 19 years who identified themselves as lifetime sildenafil citrate users. The majority of focus group participants believed that "curiosity" and "peer pressure" contributed to their initial use. Most revealed that they first heard about sildenafil citrate from television advertisements, family members, friends, or sporting events, and they were able to obtain the drug from their friends and family members or they stole it from their father or grandfather. These findings may highlight the relative importance of exposure to prescription drug messages among those to whom the message is not specifically targeted, that is, young men. It is possible that the sildenafil citrate television messages are recalled by not only older male audiences but also by teenagers and younger men, producing similar cognitive processing and curiosity in both age cohorts.

Potassium citrate prevents increased osteoclastogenesis resulting from acidic conditions: Implication for the treatment of postmenopausal bone loss.

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Donatella Granchi

Full Text Available The extracellular acidic milieu in bones results in activation of osteoclasts (OC and inhibition of osteoblasts (OB causing a net loss of calcium from the skeleton and the deterioration of bone microarchitecture. Alkalinization through supplementation with potassium citrate (K citrate has been proposed to limit the osteopenia progression, even though its pharmacological activity in bone microenvironment is not well defined. We evaluated if K citrate was able to prevent the adverse effects that acidic milieu induces on bone cells. OC and OB were maintained in neutral (pH 7.4 versus acidic (pH 6.9 culture medium, and treated with different K citrate concentrations. We evaluated the OC differentiation at seven days, by counting of multinucleated cells expressing tartrate-resistant acid phosphatase, and the activity of mature OC at 14 days, by quantifying of collagen degradation. To evaluate the effects on OB, we analyzed proliferation, mineralization, and expression of bone-related genes. We found that the low pH increased OC differentiation and activity and decreased OB function. The osteoclastogenesis was also promoted by RANKL concentrations ineffective at pH 7.4. Non-cytotoxic K citrate concentrations were not sufficient to steadily neutralize the acidic medium, but a inhibited the osteoclastogenesis, the collagen degradation, and the expression of genes involved in RANKL-mediated OC differentiation, b enhanced OB proliferation and alkaline phosphatase expression, whereas it did not affect the in vitro mineralization, and c were effective also in OC cultures resistant to alendronate, i.e. the positive control of osteoclastogenesis inhibition. In conclusion, K citrate prevents the increase in OC activity induced by the acidic microenvironment, and the effect does not depend exclusively on its alkalizing capacity. These data provide the biological basis for the use of K citrate in preventing the osteopenia progression resulting from low

Effects of heating atmosphere on formation of crystalline citrate-derived LaAlO3 nanoparticles

International Nuclear Information System (INIS)

Yu, Hsuan-Fu; Guo, Yu-Man

2011-01-01

Research highlights: → LaAlO 3 can be crystallized at 550 deg. C in an oxygen-enriched atmosphere. → Calcining the citrate precursor in oxygen atmosphere lowers the reaction temperatures to form crystalline LaAlO 3 . → In oxygen atmosphere, pure citrate-derived LaAlO 3 nanoparticles can be produced at 700 deg. C. - Abstract: Crystalline LaAlO 3 nanoparticles were synthesized at relative low temperatures, using a citrate-precursor technique. La(NO 3 ) 3 , Al(NO 3 ) 3 , and C 3 H 4 (OH)(COOH) 3 , in a molar ratio of 1:1:1, were dissolved in deionized water. NH 4 OH was used to adjust the aqueous solution to pH 7. After drying, the citrate precursors were charred at 350 deg. C, followed by calcination at different temperatures, in air or oxygen atmosphere. The thermochemical properties of the resultant particles were analyzed using thermogravimetric and differential thermal analysis, X-ray diffractometry, infrared spectroscopy, scanning electron microscopy, and transmission electron microscopy. Effects of calcination temperature and heating atmosphere on the formation of crystalline LaAlO 3 nanoparticles were investigated. In O 2 atmosphere, clacining the citrate-derived charred solid precursor at 700 deg. C for 3 h can decompose all intermediates to produce pure LaAlO 3 nanoparticles (particle sizes ≤ 100 nm) with an average crystallite size of about 24 nm and possessing high sinterability.

Evaluation of hilar 67Ga-citrate uptake in bronchogenic carcinoma

International Nuclear Information System (INIS)

Matsuno, Noriyo; Kuyama, Junpei; Uchida, Yoshitaka; Hatano, Osamu; Imai, Yasunori; Uno, Kimiichi; Minoshima, Satoshi.

1995-01-01

We evaluated hilar uptake on 67 Ga-citrate scintigraphy and correlated with hilar lymph node metastases in one-hundred seventeen cases (two-hundred thirty four hila) of bronchogenic carcinoma. Hilar uptake was classified into three grades independently on anterior and posterior chest views: no uptake (grade 0), uptake equal to that in the thoracic vertebrae (grade 1), and uptake higher than that in the thoracic vertebrae (grade 2). If a summed grade of anterior and posterior view was larger than 3, hilar uptake was considered as positive. In forty-four cases (forty-nine hila) with hilar lymph node metastases, positive hilar uptake was found in ten cases (eleven hila), resulting in sensitivity of 22% based on cases and 23% based on hila. In seventy-three cases (one-hundred forty-six hila) without hilar lymph node metastases, positive hilar uptake was found in six cases (ten hila), resulting in specificity of 91% based on cases and 93% based on hila. In comparison to scintigraphic findings of unilaterally positive hilar uptake, findings of bilaterally positive hilar uptake showed significantly lower accuracy in determining presence of hilar lymph node metastases. No definite correlation between hilar uptake and histopathology or 67 Ga-citrate uptake in a primary tumor was observed. The results indicate that usefulness of 67 Ga-citrate scintigraphy is limited when evaluating hilar lymph node metastases in bronchogenic carcinoma. (author)

Dynamics of meso and thermo citrate synthases with implicit solvation

Science.gov (United States)

Cordeiro, J. M. M.

The dynamics of hydration of meso and thermo citrate synthases has been investigated using the EEF1 methodology implemented with the CHARMM program. The native enzymes are composed of two identical subunits, each divided into a small and large domain. The dynamics behavior of both enzymes at 30°C and 60°C has been compared. The results of simulations show that during the hydration process, each subunit follows a different pathway of hydration, in spite of the identical sequence. The hydrated structures were compared with the crystalline structure, and the root mean square deviation (RMSD) of each residue along the trajectory was calculated. The regions with larger and smaller mobility were identified. In particular, helices belonging to the small domain are more mobile than those of the large domain. In contrast, the residues that constitute the active site show a much lower displacement compared with the crystalline structure. Hydration free energy calculations point out that Thermoplasma acidophilum citrate synthase (TCS) is more stable than chicken citrate synthase (CCS), at high temperatures. Such result has been ascribed to the higher number of superficial charges in the thermophilic homologue, which stabilizes the enzyme, while the mesophilic homologue denatures. These results are in accord with the experimental found that TCS keeps activity at temperatures farther apart from the catalysis regular temperature than the CCS.

Enhanced citrate production through gene insertion in Aspergillus niger

DEFF Research Database (Denmark)

Jongh, Wian de; Nielsen, Jens

2007-01-01

The effect of inserting genes involved in the reductive branch of the tricarboxylic acid (TCA) cycle on citrate production by Aspergillus niger was evaluated. Several different genes were inserted individually and in combination, i.e. malate dehydrogenase (mdh2) from Saccharomyces cerevisiae, two...

Ovarian capsular drilling in the treatment of clomiphene citrate ...

African Journals Online (AJOL)

Background: Laparoscopic Ovarian Drilling (LOD) is an effective and a well evaluated surgical Treatment of Clomiphene Citrate resistant Polycystic ovarian syndrome. Transvaginal hydrolaparoscopy (TVHL) is a relatively new simple method of exploring the pelvis and has recently been introduced as a transvaginal ...

78 FR 34338 - Citric Acid and Certain Citrate Salts From Canada: Preliminary Results of Antidumping Duty...

Science.gov (United States)

2013-06-07

... DEPARTMENT OF COMMERCE International Trade Administration [A-122-853] Citric Acid and Certain... on citric acid and certain citrate salts (citric acid) from Canada. The period of review (POR) is May... INFORMATION: Scope of the Order The merchandise covered by this order is citric acid and certain citrate salts...

Pyrolytic citrate synthesis and ozone annealing

International Nuclear Information System (INIS)

Celani, F.; Saggese, A.; Giovannella, C.; Messi, R.; Merlo, V.

1988-01-01

A pyrolytic procedure is described that via a citrate synthesis allowed us to obtain very fine grained YBCO powders that, after a first furnace thermal treatment in ozone, results already to contain a large amount of superconducting microcrystals. A second identical thermal treatment gives a final product strongly textured, as shown by magnetic torque measurements. Complementary structural and diamagnetic measurement show the high quality of these sintered pellets. The role covered by both the pyrolytic preparation and the ozone annealing are discussed

Standardisation of the Laboratory Control of Anticoagulant Therapy

African Journals Online (AJOL)

1974-09-11

Sep 11, 1974 ... Anticoagulant therapy with the coumarin group of drugs has been used in clinical practice for more than a quarter of a century. The most widely used form of laboratory control of the treatment is the Quick one-stage prothrom·- bin time. I. This simple test proved to be satisfactory in most cases, but discrepant ...

Effect of tartarate and citrate based food additives on the micellar properties of sodium dodecylsulfate for prospective use as food emulsifier.

Science.gov (United States)

Banipal, Tarlok S; Kaur, Harjinder; Kaur, Amanpreet; Banipal, Parampaul K

2016-01-01

Citrate and tartarate based food preservatives can be used to enhance the emulsifying properties of sodium dodecylsulfate (SDS) based micellar system and thus making it appropriate for food applications. Exploration of interactions between the two species is the key constraint for execution of such ideas. In this work various micellar and thermodynamic parameters of SDS like critical micellar concentration (CMC), standard Gibbs free energy of micellization (ΔG(0)mic.) etc. have been calculated in different concentrations of disodium tartarate (DST) and trisodium citrate (TSC) in the temperature range (288.15-318.15)K from the conductivity and surface tension measurements. The parameters obtained from these studies reveal the competitive nature of both the additives with SDS for available positions at the air/water interface. TSC is found to be more effective additive in order to make SDS micellar system better for its potential applications as food emulsifier. Copyright © 2015 Elsevier Ltd. All rights reserved.

Factors Affecting Outcome in Treatment of Chronic Subdural Hematoma in ICU Patients: Impact of Anticoagulation.

Science.gov (United States)

Szczygielski, Jacek; Gund, Sina-Maria; Schwerdtfeger, Karsten; Steudel, Wolf-Ingo; Oertel, Joachim

2016-08-01

The use of anticoagulants and older age are the main risk factors for chronic subdural hematoma (CSDH). Because the age of the population and use of anticoagulants are increasing, a growing number of CSDH cases is expected. To address this issue, we analyzed the impact of anticoagulants on postsurgical outcome in patients in the intensive care unit (ICU). Demographic data, coagulation parameters, surgical details, radiologic appearance of hematoma, Glasgow Coma Scale (GCS) score on admission, and Glasgow Outcome Scale (GOS) score on discharge were retrieved and retrospectively analyzed in 98 patients with CSDH treated in the neurosurgical ICU using correlation coefficient tests and multivariate analysis test. Overall outcome was good (GOS score 4 and 5) in 55.1% of patients. Overall mortality was 9.1%. There was a correlation between GCS score on admission and GOS score. There was no correlation between hematoma thickness/radiologic appearance and impaired coagulation. Disturbance in thrombocyte function (usually resulting from aspirin intake) correlated with improved outcome, whereas warfarin-related coagulopathy correlated with poor recovery. Nevertheless, patients with thrombocytopathy presented with better initial GCS scores. Neither hematoma size nor recurrence rate affected the outcome. The size of CSDH was not associated with poor outcome and is not necessarily determined by the use of anticoagulants. Coagulopathy does not rule out a good outcome, but the impact of anticoagulation on treatment results in CSDH varies between the main groups of drugs (warfarin vs. antiplatelet drugs). Patients in good neurologic condition on ICU admission have better chances of recovery. Copyright © 2016 Elsevier Inc. All rights reserved.

Pulsed electric field extraction enhanced anti-coagulant effect of fungal polysaccharide from Jew's ear (Auricularia auricula).

Science.gov (United States)

Li, Changtian; Mao, Xinxin; Xu, Baojun

2013-01-01

As a Chinese herbal medicine, Jew's ear has been known for its anti-coagulant effects. Hence it is worthwhile developing an effective technique to extract active components. To find the optimal extraction condition and to identify the best strain to yield fungal polysaccharide with anti-coagulant activity. Three strains of Jew's ear from Jilin Province, named as 988, DY 18 and FS 02, and three extraction techniques, namely, high intensity pulsed electric fields (HIPEF), microwave-assisted extraction method (MAEM) and ultrasonic-assisted extraction method (UAEM), were applied to optimise the extraction conditions. The crude extracts and polysaccharides were further determined for anti-coagulant activities. All extracts prolonged blood clotting time as compared to reagent control. The HIPEF exhibited the most remarkable effect among the three extraction techniques. The anti-coagulant activities of extracts were enhanced with increasing electric field strength when the field strength reached 24 kV/cm. Current results suggest that the HIPEF technique will be an effective method in the manufacture of bioactive natural polysaccharide. Copyright © 2012 John Wiley & Sons, Ltd.

Anticoagulant and Antiplatelet Prescribing Patterns for Patients with Atrial Fibrillation after Percutaneous Coronary Intervention.

Science.gov (United States)

Woods, Erin A; Ackman, Margaret L; Graham, Michelle M; Koshman, Sheri L; Boswell, Rosaleen M; Barry, Arden R

2016-01-01

Current guidelines recommend triple antithrombotic therapy (TAT), defined as acetylsalicylic acid (ASA), clopidogrel, and warfarin, for patients with nonvalvular atrial fibrillation who have undergone percutaneous coronary intervention with stent implantation. The choice of anticoagulant/antiplatelet therapy in this population is ambiguous and complex, and prescribing patterns are not well documented. To characterize local prescribing patterns for anticoagulant/antiplatelet therapy after percutaneous coronary intervention in patients with nonvalvular atrial fibrillation. A chart review was conducted at a single quaternary cardiology centre. Patients with nonvalvular atrial fibrillation were identified via medical records, and those who underwent percutaneous coronary intervention were identified using a local clinical patient registry. Adult inpatients with nonvalvular atrial fibrillation and a CHADS2 score (based on congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke) of 1 or higher who underwent percutaneous coronary intervention from 2011 to 2013 were included. Patients undergoing cardiovascular surgery or transcatheter aortic valve replacement, those with mechanical devices requiring anticoagulation, and those with an allergy to any component of TAT were excluded. Seventy patients were included. The median age was 75 years, and 52 (74%) were men. At discharge, 30 (43%) were receiving TAT and 27 (39%) were receiving dual antiplatelet therapy (clopidogrel and ASA). No patients received the combination of warfarin and clopidogrel. Among those who received TAT, 90% (19 of 21) who received a bare metal stent had a recommended duration of 1 month, and 75% (6 of 8) who received a drug-eluting stent had a recommended duration of 1 year. Direct-acting oral anticoagulants with 2 antiplatelet drugs were prescribed for 9% (6 of 70) of the patients, and 10% (7 of 70) received ticagrelor and ASA with or without warfarin. Overall, the

The Anticoagulation of Calf Thrombosis (ACT project: study protocol for a randomized controlled trial

Directory of Open Access Journals (Sweden)

Horner Daniel

2012-04-01

Full Text Available Abstract Background Half of all lower limb deep vein thrombi (DVT in symptomatic ambulatory patients are located in the distal (calf veins. While proximal disease warrants therapeutic anticoagulation to reduce the associated risks, distal DVT often goes untreated. However, a proportion of untreated distal disease will undoubtedly propagate or embolize. Concern also exists that untreated disease could lead to long-term post thrombotic changes. Currently, it is not possible to predict which distal thrombi will develop such complications. Whether these potential risks outweigh those associated with unrestricted anticoagulation remains unclear. The Anticoagulation of Calf Thrombosis (ACT trial aims to compare therapeutic anticoagulation against conservative management for patients with acute symptomatic distal deep vein thrombosis. Methods ACT is a pragmatic, open-label, randomized controlled trial. Adult patients diagnosed with acute distal DVT will be allocated to either therapeutic anticoagulation or conservative management. All patients will undergo 3 months of clinical and assessor blinded sonographic follow-up, followed by 2-year final review. The project will commence initially as an external pilot study, recruiting over a 16-month period at a single center to assess feasibility measures and clinical event rates. Primary outcome measures will assess feasibility endpoints. Secondary clinical outcomes will be collected to gather accurate data for the design of a definitive clinical trial and will include: (1 a composite endpoint combining thrombus propagation to the popliteal vein or above, development of symptomatic pulmonary embolism or sudden death attributable to venous thromboembolic disease; (2 the incidence of major and minor bleeding episodes; (3 the incidence of post-thrombotic leg syndrome at 2 years using a validated screening tool; and (4 the incidence of venous thromboembolism (VTE recurrence at 2 years. Discussion The ACT trial

Transport of citrate-coated silver nanoparticles in unsaturated sand

Science.gov (United States)

Kumahor, Samuel; Hron, Pavel; Metreveli, George; Schaumann, Gabriele; Vogel, Hans-Jörg

2015-04-01

Chemical factors and physical constraints lead to coupled effects during particle transport in unsaturated porous media. Unlike for saturated transport, studies on unsaturated transport as typical for soil are currently scarce. We investigated the mobility of citrate-coated Ag NPs in unsaturated sand (grain diameter: 0.1-0.3 mm). For three flux rates and a given pore-water ionic strength (1 mM KNO3), the citrate-coated Ag NPs were less mobile at pH = 5 compared to pH = 9. The classic Derjaguin-Landau-Verwey-Overbeek (DLVO) theory suggests unfavorable deposition conditions at both, the air-water interface and solid-water interface. Breakthrough curves measured under quasi-steady state unsaturated flow showed retardation of the citrate-coated Ag NPs compared to inert solute (KBr). After flushing with nanoparticle-free 1 mM KNO3 solution (pH-adjusted), retention was much lower in deeper depths compared to the surface where the particles entered the flow field. The results show a non-linear dependence of nanoparticle (NP) mobility on flux rate and water content. Especially the observed retardation similar to equilibrium sorption is in contrast to observations under saturated flow conditions. A convection-dispersion and reaction model that combines a reversible equilibrium process and a non-equilibrium interaction process reproduced the measured breakthrough curves reasonably well. From comparison between saturated and unsaturated experiments we conclude that the air-water interface is responsible for the reversible equilibrium process while the water-solid interface accounts for irreversible soption.

Development of Fourier transform mid-infrared calibrations to predict acetone, β-hydroxybutyrate, and citrate contents in bovine milk through a European dairy network.

Science.gov (United States)

Grelet, C; Bastin, C; Gelé, M; Davière, J-B; Johan, M; Werner, A; Reding, R; Fernandez Pierna, J A; Colinet, F G; Dardenne, P; Gengler, N; Soyeurt, H; Dehareng, F

2016-06-01

To manage negative energy balance and ketosis in dairy farms, rapid and cost-effective detection is needed. Among the milk biomarkers that could be useful for this purpose, acetone and β-hydroxybutyrate (BHB) have been proved as molecules of interest regarding ketosis and citrate was recently identified as an early indicator of negative energy balance. Because Fourier transform mid-infrared spectrometry can provide rapid and cost-effective predictions of milk composition, the objective of this study was to evaluate the ability of this technology to predict these biomarkers in milk. Milk samples were collected in commercial and experimental farms in Luxembourg, France, and Germany. Acetone, BHB, and citrate contents were determined by flow injection analysis. Milk mid-infrared spectra were recorded and standardized for all samples. After edits, a total of 548 samples were used in the calibration and validation data sets for acetone, 558 for BHB, and 506 for citrate. Acetone content ranged from 0.020 to 3.355mmol/L with an average of 0.103mmol/L; BHB content ranged from 0.045 to 1.596mmol/L with an average of 0.215mmol/L; and citrate content ranged from 3.88 to 16.12mmol/L with an average of 9.04mmol/L. Acetone and BHB contents were log-transformed and a part of the samples with low values was randomly excluded to approach a normal distribution. The 3 edited data sets were then randomly divided into a calibration data set (3/4 of the samples) and a validation data set (1/4 of the samples). Prediction equations were developed using partial least square regression. The coefficient of determination (R(2)) of cross-validation was 0.73 for acetone, 0.71 for BHB, and 0.90 for citrate with root mean square error of 0.248, 0.109, and 0.70mmol/L, respectively. Finally, the external validation was performed and R(2) obtained were 0.67 for acetone, 0.63 for BHB, and 0.86 for citrate, with respective root mean square error of validation of 0.196, 0.083, and 0.76mmol/L. Although

Value of gallium 67 citrate scintigraphy in ophthalmology

International Nuclear Information System (INIS)

Ivanez-Alloschery, Monique.

1978-01-01

For ophthalmologists scintigraphy appears as a simple method to detect endoocular or endoorbital abnormalities. However none of the many scintigraphic methods described seems reliable enough to be used alone. One of the latest isotopic explorations using gallium 67 citrate, a tracer considered tumour-tropic might be able to solve this problem. The aim of this work is to judge the value of the method in the diagnosis of malignant endoocular and endoorbital tumours on the basis of 24 anatomoclinical observations. It may be concluded from this study that ocular gallium 67 citrate scintigraphy, which gave no clearly positive results at all but some doubtful results in the case of endoocular tumours more than 5 mm in diameter, is to be rejected; fluorescein angiography and ocular echograhy provide more elements for an accurate etiological diagnosis. Orbital scintigraphy on the other hand seems to be a necessary complement to a tomodensitometric examination since both methods offer diagnostic information without systematic recurse to carotid arteriography or orbital phlebography, sometimes dangerous for the patient [fr

Diffuse abdominal uptake of Ga-67 citrate in a patient with hypoproteinemia

International Nuclear Information System (INIS)

Kim, E.E.; Gobuty, A.; Gutierrez, C.

1983-01-01

A 3-wk-old male, with abdominal distention and severe hypoproteinemia from poor nutrition, underwent a study that showed a persistent diffuse abdominal uptake of Ga-67 citrate, indicating pyogenic or tuberculous peritonitis. However, there were no corresponding clinical or laboratory findings. After a 1-wk course of hyperalimentation with albumin, furosemide, and protein, repeat radiographs showed reduction in bowel gas. It is suggested that hypoproteinemia should be considered as a possibility in the differential diagnosis when there is diffuse abdominal uptake of Ga-67 citrate, with careful clinical correlation. Possible mechanism of Ga-67 uptake in the peritoneal cavity is suggested

Neptunium speciation (complexation and redox behaviour) in aqueous citrate medium

Energy Technology Data Exchange (ETDEWEB)

Bonin, L.; Ansoborlo, E.; Moisy, Ph. [CEA Marcoule (France)

2005-07-01

Full text of publication follows: In the framework of the French Environmental Nuclear Toxicology programme, additional experiments related to the decorporation of actinides are planned. The lack of information on the neptunium behaviour within blood and the inefficiency of therapeutic treatments, led us to study the complexation of this element with basic anions. Within this purpose, the in vitro behaviour of Np{sup IV} and Np{sup V} in simple media simulating biological media was studied: blood plasma is one of the media of interest and it can be simulated, from a chemical point of view, by an aqueous solution with pH 7.4, containing ions such as citrate (1.6 10{sup -4} mol/L), lactate (1.5 10{sup -3} mol/L), CO{sub 3}{sup 2-} (2.5 10{sup -2} mol/L), PO{sub 4}{sup 3-} (1.1 10{sup -3} mol/L), SO{sub 4}{sup 2-} (3.3 10{sup -4} mol/L) and Cl{sup -} (9 10{sup -2} mol/L). This study was more specifically focused on the behaviour of neptunium with citrate ion, which is also a basic ligand to consider when one wishes to study the migration of actinides in the environment, since it exists in significant amounts in the ground due to its production by the plants. In order to determine the speciation of this system, spectrophotometry was more particularly used. Concerning the complexation phenomenon, the existence of several complexes of Np{sup V} with various acid-basic forms of the citrate anion was observed; regarding Np{sup IV}, two complexes, with 1:1 and 1:2 stoichiometry, have been respectively observed. The reactivity of Np{sup VI} is probably similar to the behaviour of U{sup VI}, which is reported in literature to form a complex with a 1:1 stoichiometry with the Cit{sup 3-}anion From the quantitative study of these equilibria, it has been possible to determine the values of various equilibrium constants. Concerning the stability of neptunium towards oxido-reduction, it was confirmed that Np{sup VI} was very quickly reduced to Np{sup V} by the citrate anions

Early detection of interstitial pneumonia by 67Ga-citrate scintigraphy

International Nuclear Information System (INIS)

Ito, Shinsaku; Mikami, Riichiro; Ryujin, Yoshitada

1985-01-01

In this paper we report our recent experience indicating usefulness of 67 Ga-citrate scintigraphy in 4 cases with inflammatory pulmonary diseases. These cases showed abnormal pulmonary 67 Ga uptake with normal chest radiographs. The first case with malignant lymphoma and the second one with lung cancer suffered from pulmonary infection following secondary immuno-insufficiency due to radiotherapy and chemotherapy. Pneumocystis carinii was suspected as causative agent in the first case, and gram negative bacilli in the second case. The third case with lung cancer developed radiation pneumonia after radiotherapy. The fourth case with acute bronchitis developed drug induced interstitial pneumonia presumably due to minocycline administration. It is concluded that 67 Ga-citrate scintigraphy is more sensitive for early detection of interstitial pneumonia than routine chest radiography. (author)

Evaluation of oral abdominal contrast agent containing ferric ammonium citrate

International Nuclear Information System (INIS)

Shiga, Toshiko; Kawamura, Yasutaka; Iwasaki, Toshiko

1991-01-01

We evaluated the effectiveness of oral MRI contrast agent containing ferric ammonium citrate. Twenty patients were arbitrarily divided into 2 groups according to the given dose of 100 and 200 mg Fe of oral MRI contrast agent. MRI was performed before and immediately after ingesting 300 ml solution of oral MRI contrast agent using a 1.5 T superconducting system (GE: Signa). Each dose of 100 and 200 mg Fe of oral MRI contrast agent produced sufficient enhancement of gastrointestinal tract, enough to make clear the pancreatic contour and porta hepatis. There was no significant change in blood and urine analysis observed after taking oral MRI contrast agent. The use of ferric ammonium citrate as an oral MRI contrast agent seems to add valuable information in performing upper abdominal MRI imaging. (author)

Combined administration of antibiotics and direct oral anticoagulants: a renewed indication for laboratory monitoring?

Science.gov (United States)

Lippi, Giuseppe; Favaloro, Emmanuel J; Mattiuzzi, Camilla

2014-10-01

The recent development and marketing of novel direct oral anticoagulants (DOACs) represents a paradigm shift in the management of patients requiring long-term anticoagulation. The advantages of these compounds over traditional therapy with vitamin K antagonists include a reportedly lower risk of severe hemorrhages and the limited need for laboratory measurements. However, there are several scenarios in which testing should be applied. The potential for drug-to-drug interaction is one plausible but currently underrecognized indication for laboratory assessment of the anticoagulant effect of DOACs. In particular, substantial concern has been raised during Phase I studies regarding the potential interaction of these drugs with some antibiotics, especially those that interplay with permeability glycoprotein (P-gp) and cytochrome 3A4 (CYP3A4). A specific electronic search on clinical trials published so far confirms that clarithromycin and rifampicin significantly impair the bioavailability of dabigatran, whereas clarithromycin, erythromycin, fluconazole, and ketoconazole alter the metabolism of rivaroxaban in vivo. Because of their more recent development, no published data were found for apixaban and edoxaban, or for potential interactions of DOACs with other and widely used antibiotics. It is noteworthy, however, that an online resource based on Food and Drug Administration and social media information, reports several hemorrhagic and thrombotic events in patients simultaneously taking dabigatran and some commonly used antibiotics such as amoxicillin, cephalosporin, and metronidazole. According to these reports, the administration of antibiotics in patients undergoing therapy with DOACs would seem to require accurate evaluation as to whether dose adjustments (personalized or antibiotic class driven) of the anticoagulant drug may be advisable. This might be facilitated by direct laboratory assessments of their anticoagulant effect ex vivo. Thieme Medical Publishers

Structural, spectroscopic and Thermal Studies of Potassium Di-hydrogen Citrate Crystal

Directory of Open Access Journals (Sweden)

N.D. Pandya

2017-04-01

Full Text Available Potassium dihydrogen citrate (KDC finds wide applications in food products. Pure potassium dihydrogen citrate crystal was grown by slow solvent evaporation technique at room temperature. Grown crystal exhibited needle like morphology. The powder XRD shows triclinic structure symmetry with lattice parameters a=11.820 Å, b=14.970 Å, c=9.442 Å with angles α = 91.60°, β = 93.35°, γ = 110°. The presence of various functional groups of grown crystal was confirmed by using FT-IR spectroscopy. The thermogram indicates the thermal stability of the sample up to 100oC and then decomposes slowly into oxide stage through two stages. The results are discussed here.

Personalized prophylactic anticoagulation decision analysis in patients with membranous nephropathy

Science.gov (United States)

Lee, Taewoo; Biddle, Andrea K.; Lionaki, Sofia; Derebail, Vimal K.; Barbour, Sean J.; Tannous, Sameer; Hladunewich, Michelle A.; Hu, Yichun; Poulton, Caroline J.; Mahoney, Shannon L.; Jennette, J. Charles; Hogan, Susan L.; Falk, Ronald J.; Cattran, Daniel C.; Reich, Heather N.; Nachman, Patrick H.

2014-01-01

Primary membranous nephropathy is associated with increased risk of venous thromboembolic events, which are inversely correlated with serum albumin levels. To evaluate the potential benefit of prophylactic anticoagulation (venous thromboembolic events prevented) relative to the risk (major bleeds), we constructed a Markov decision model. The venous thromboembolic event risk according to serum albumin was obtained from an inception cohort of 898 patients with primary membranous nephropathy. Risk estimates of hemorrhage were obtained from a systematic literature review. Benefit-to-risk ratios were predicted according to bleeding risk and serum albumin. This ratio increased with worsening hypoalbuminemia from 4.5:1 for an albumin under 3 g/dl to 13.1:1 for an albumin under 2 g/dl in patients at low bleeding risk. Patients at intermediate bleeding risk with an albumin under 2 g/dl have a moderately favorable benefit-to-risk ratio (under 5:1). Patients at high bleeding risk are unlikely to benefit from prophylactic anticoagulation regardless of albuminemia. Probabilistic sensitivity analysis, to account for uncertainty in risk estimates, confirmed these trends. From these data, we constructed a tool to estimate the likelihood of benefit based on an individual’s bleeding risk profile, serum albumin level, and acceptable benefit-to-risk ratio (http://www.gntools.com). This tool provides an approach to the decision of prophylactic anticoagulation personalized to the individual’s needs and adaptable to dynamic changes in health status and risk profile. PMID:24336031

Electroconvulsive therapy and anticoagulation after pulmonary embolism: a case report

Directory of Open Access Journals (Sweden)

Julio Cesar Lazaro

2014-07-01

Full Text Available Introduction Electroconvulsive therapy (ECT is considered the most effective treatment for catatonia regardless its underlying condition. The rigid fixed posture and immobility observed in catatonia may lead to several clinical complications, of which, pulmonary embolism (PE is one of the most severe. The rapid improvement of the psychiatric condition in catatonia-related PE is essential, since immobility favors the occurrence of new thromboembolic events and further complications. In that scenario, ECT should be considered, based on a risk-benefit analysis, aiming at the faster resolution of the catatonia. Methods Case report and literature review. Results A 66-years-old woman admitted to the psychiatric ward with catatonia due to a depressive episode presented bilateral PE. Clinically stable, but still severely depressed after a trial of antidepressants, she was treated with ECT in the course of full anticoagulation with enoxaparin. After five ECT sessions, her mood was significantly better and she was walking and eating spontaneously. She did not present complications related either to PE or to anticoagulation. After the eighth ECT session, she evolved with hypomania, which was managed with oral medication adjustments. The patient was completely euthymic at discharge. Conclusion The case we presented provides further evidence to the anecdotal case reports on the safety of ECT in the course of concomitant full anticoagulant therapy after PE, and illustrates how, with the proper precautions, the benefits of ECT in such condition might outweigh its risks.

Enclomiphene citrate stimulates testosterone production while preventing oligospermia: a randomized phase II clinical trial comparing topical testosterone.

Science.gov (United States)

Wiehle, Ronald D; Fontenot, Gregory K; Wike, Jenny; Hsu, Kuang; Nydell, Jennifer; Lipshultz, Larry

2014-09-01

To determine the effect of enclomiphene citrate in men with secondary hypogonadism. Phase II clinical trial. Community dwelling men making visits to physician offices. Men with secondary hypogonadism. Oral administration of enclomiphene citrate or 1% topical T gel. Luteinizing hormone, FSH, T, and semen analysis. Treatment with enclomiphene citrate resulted in increased morning serum T, E2, and LH levels similar to those obtained with a topical T gel in men with secondary hypogonadism. Follicle-stimulating hormone and LH were increased with enclomiphene, and sperm counts were conserved. Enclomiphene citrate reverses the two hallmarks of secondary hypogonadism, namely, low serum total T and low or inappropriately normal LH while preserving sperm production. NCT01270841 (ClinicalTrials.gov Identifier NCT01270841). Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Effects of oversulfated and fucosylated chondroitin sulfates on coagulation. Challenges for the study of anticoagulant polysaccharides.

Science.gov (United States)

Fonseca, Roberto J C; Oliveira, Stephan-Nicollas M C G; Pomin, Vitor H; Mecawi, André S; Araujo, Iracema G; Mourão, Paulo A S

2010-05-01

We report the effects of a chemically oversulfated chondroitin sulfate and a naturally fucosylated chondroitin sulfate on the coagulation system. The former has been recently identified as a contaminant of heparin preparations and the latter has been proposed as an alternative anticoagulant. The mechanism of action of these polymers on coagulation is complex and target different components of the coagulation system. They have serpin-independent anticoagulant activity, which preponderates in plasma. They also have serpin-dependent anticoagulant activity but differ significantly in the target coagulation protease and preferential serpin. Their anticoagulant effects differ even more markedly when tested as inhibitors of coagulation proteases using plasma as a source of serpins. It is possible that the difference is due to the high availability of fucosylated chondroitin sulfate whereas oversulfated chondroitin sulfate has strong unspecific binding to plasma protein and low availability for the binding to serpins. When tested using a venous thrombosis experimental model, oversulfated chondroitin sulfate is less potent as an antithrombotic agent than fucosylated chondroitin sulfate. These highly sulfated chondroitin sulfates activate factor XII in in vitro assays, based on kallikrein release. However, only fucosylated chondroitin sulfate induces hypotension when intravenously injected into rats. In conclusion, the complexity of the regulatory mechanisms involved in the action of highly sulfated polysaccharides in coagulation requires their analysis by a combination of in vitro and in vivo assays. Our results are relevant due to the urgent need for new anticoagulant drugs or alternative sources of heparin.

Structural and Thermodynamic Analysis of the First Mononuclear Aqueous Aluminum Citrate Complex Using DFT Calculations.

Science.gov (United States)

de Noronha, Antonio Luiz Oliveira; Guimarães, Luciana; Duarte, Hélio Anderson

2007-05-01

Structural and thermodynamic properties of the mononuclear Al/citrate complexes have been theoretically investigated aiming to understand the coordination mechanism at an atomic level. GGA-DFT/PCM calculations have been performed for the different conformations and tautomers arising from the Al(3+) and citric acid (H3L) interaction in aqueous solution. The Gibbs reaction energies were estimated based on the reaction of the trigonal planar Al(OH)3 and H3L to form different Al-citrate complexes. The estimated Gibbs free reaction energies for the [AlL], [AlHL](+), and [Al(OH)L](-) species are in good agreement with the experimental values. In these species, the Al(3+) center is coordinated by two carboxylic and the tertiary hydroxyl groups of the citrate. Conversely to what has been proposed based on the experiments, the present theoretical calculations indicate that the citric acid hydroxyl group remains protonated upon the coordination of Al(3+). In fact, our model turns out to be more consistent with the relative pKa values of citrate protonation groups and with the hydrolysis constant of the H2O bound to Al(3+) leading to better agreement with the available experimental data.

Anticoagulant drugs increase natural killer cell activity in lung cancer

Czech Academy of Sciences Publication Activity Database

Bobek, M.; Boubelík, Michael; Fišerová, Anna; Luptovcová, Martina; Vannucci, Luca; Kacprzak, G.; Kolodzej, J.; Majewski, A.M.; Hoffman, R. M.

2005-01-01

Roč. 47, č. 2 (2005), s. 215-223 ISSN 0169-5002 Institutional research plan: CEZ:AV0Z5052915 Keywords : anticoagulant drugs * lung cancer * NK cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.172, year: 2005

On the nature of citrate-derived surface species on Ag nanoparticles: Insights from X-ray photoelectron spectroscopy

Science.gov (United States)

Mikhlin, Yuri L.; Vorobyev, Sergey A.; Saikova, Svetlana V.; Vishnyakova, Elena A.; Romanchenko, Alexander S.; Zharkov, Sergey M.; Larichev, Yurii V.

2018-01-01

Citrate is an important stabilizing, reducing, and complexing reagent in the wet chemical synthesis of nanoparticles of silver and other metals, however, the exact nature of adsorbates, and its mechanism of action are still uncertain. Here, we applied X-ray photoelectron spectroscopy, soft X-ray absorption near-edge spectroscopy, and other techniques in order to determine the surface composition and to specify the citrate-related species at Ag nanoparticles immobilized from the dense hydrosol prepared using room-temperature reduction of aqueous Ag+ ions with ferrous ions and citrate as stabilizer (Carey Lea method). It was found that, contrary to the common view, the species adsorbed on the Ag nanoparticles are, in large part, products of citrate decomposition comprising an alcohol group and one or two carboxylate bound to the surface Ag, and minor unbound carboxylate group; these may also be mixtures of citrate with lower molecular weight anions. No ketone groups were specified, and very minor surface Ag(I) and Fe (mainly, ferric oxyhydroxides) species were detected. Moreover, the adsorbates were different at AgNPs having various size and shape. The relation between the capping and the particle growth, colloidal stability of the high-concentration sol and properties of AgNPs is briefly considered.

Injuries and outcomes associated with traumatic falls in the elderly population on oral anticoagulant therapy.

Science.gov (United States)

Boltz, Melissa M; Podany, Abigail B; Hollenbeak, Christopher S; Armen, Scott B

2015-09-01

Fall risk for older adults is a multi-factorial public health problem as 90% of geriatric injuries are caused by traumatic falls. The CDC estimated 33% of adults >65 years incurred a fall in 2011, with 30% resulting in moderate injury. While much has been written about overall risk to trauma patients on oral anticoagulant (OAC) therapy, less has been reported on outcomes in the elderly trauma population. We used data from the National Trauma Data Bank (NTDB) to identify the types of injury and complications incurred, length of stay, and mortality associated with OACs in elderly patients sustaining a fall. Using standard NTDB practices, data were collected on elderly patients (≥65 years) on OACs with diagnosis of fall as the primary mechanism of injury from 2007 to 2010. Univariate analysis was used to determine patient variables influencing risk of fall on OACs. Odds ratios were calculated for types of injury sustained and post-trauma complications. Logistic regression was used to determine mortality associated with type of injury incurred. Of 118,467 elderly patients sampled, OAC use was observed in 444. Predisposing risk factors for fall on OACs were >1 comorbidity (p3 complications (p<0.0001); the most significant being ARDS and ARF (p<0.0001). The mortality rate on OACs was 16%. Injuries to the GI tract, liver, spleen, and kidney (p<0.0002) were more likely to occur. However, if patients suffered a mortality, the most significant injuries were skull fractures and intracranial haemorrhage (p<0.0001). Risks of anticoagulation in elderly trauma patients are complex. While OAC use is a predictor of 30-day mortality after fall, the injuries sustained are markedly different between the elderly who die and those who do not. As a result there is a greater need for healthcare providers to identify preventable and non-preventable risks factors indicative of falls in the anti-coagulated elderly patient. Copyright © 2015 Elsevier Ltd. All rights reserved.

Clinical efficacy of toothpaste containing potassium citrate in treating dentin hypersensitivity

Directory of Open Access Journals (Sweden)

Shih-Ya Shen

2009-12-01

Conclusion: The prevalence of dentin hypersensitivity in this study was 38%. The use of desensitizing toothpaste containing potassium citrate with oral hygiene instruction can effectively reduce dentin hypersensitivity.

Serum and plasma for total and free anticonvulsant drug analyses: effects on EMIT assays and ultrafiltration devices.

Science.gov (United States)

Godolphin, W; Trepanier, J; Farrell, K

1983-01-01

The suitability of serum and plasma anticoagulated with heparin, EDTA, citrate, or oxalate was assessed for analysis of free and total phenytoin, carbamazepine, and valproic acid. The free fraction was isolated by ultrafiltration through FreeLevel devices (Syva, Palo Alto, CA). Serum, heparin, and EDTA plasma were satisfactory for both free and total phenytoin and carbamazepine. EDTA could not be used for EMIT (Syva) analysis of valproate. Citrate and, to a lesser degree, oxalate cause a significant negative interference in the concentration of these three drugs as measured both by EMIT and gas-liquid chromatography.

Congenital Malformations Associated with the Administration of Oral Anticoagulants During Pregnancy

Science.gov (United States)

Pettifor, J. M.; Benson, R.

1975-01-01

Reported are case histories of three infants with congenital malformations (including defective formation of the nose and hands) associated with ingestion of oral anticoagulants during the first trimester of pregnancy. (CL)

Use of Percutaneous Aspiration Thrombectomy vs. Anticoagulation Therapy to Treat Acute Iliofemoral Venous Thrombosis: 1-year Follow-up Results of a Randomised, Clinical Trial

Energy Technology Data Exchange (ETDEWEB)

Cakir, Volkan, E-mail: drvolkancakir@gmail.com [Katip Celebi University, Ataturk Training and Research Hospital, Department of Radiology, Division of İnterventional Radiology (Turkey); Gulcu, Aytac, E-mail: aytac.gulcu@deu.edu.tr [Dokuz Eylul University Hospital, Department of Radiology (Turkey); Akay, Emrah, E-mail: emrahakay@hotmail.com [Sakarya University Hospital, Department of Radiology (Turkey); Capar, Ahmet E., E-mail: ahmetergina@gmail.com [Dokuz Eylul University Hospital, Department of Radiology (Turkey); Gencpinar, Tugra, E-mail: tugra01@hotmail.com [Dokuz Eylul University Hospital, Department of Cardiovascular Surgery (Turkey); Kucuk, Banu, E-mail: banu.kucuk@deu.edu.tr [Dokuz Eylul University Hospital, Department of Radiology (Turkey); Karabay, Ozalp, E-mail: ozalp.karabay@deu.edu.tr [Dokuz Eylul University Hospital, Department of Cardiovascular Surgery (Turkey); Goktay, A. Yigit, E-mail: yigit.goktay@deu.edu.tr [Dokuz Eylul University Hospital, Department of Radiology (Turkey)

2014-08-15

PurposeThe purpose of this study was to compare the efficacy of percutaneous aspiration thrombectomy (PAT) followed by standard anticoagulant therapy, with anticoagulation therapy alone, for the treatment of acute proximal lower extremity deep vein thrombosis.MethodsIn this randomised, prospective study, 42 patients with acute proximal iliofemoral deep vein thrombosis documented via Doppler ultrasound examination, were separated into an interventional treatment group (16 males, 5 females, average age 51 years) and a medical treatment group (13 males, 8 females, average age 59 years). In the interventional group, PAT with large-lumen 9-F diameter catheterisation was applied, after initiation of standard anticoagulant therapy. Balloon angioplasty (n 19) and stent implementation (n: 14) were used to treat patients with residual stenosis (>50 %) after PAT. Prophylactic IVC filters were placed in two patients. The thrombus clearance status of the venous system was evaluated by venography. In both the medical and interventional groups, venous patency rates and clinical symptom scores were evaluated at months 1, 3, and 12 after treatment.ResultsDeep venous systems became totally cleared of thrombi in 12 patients treated with PAT. The venous patency rates in month 12 were 57.1 and 4.76 % in the interventional and medical treatment groups, respectively. A statistically significant improvement was observed in clinical symptom scores of the interventional group (PAT) with or without stenting (4.23 ± 0.51 before treatment; 0.81 ± 0.92 at month 12) compared with the medical treatment group (4.00 ± 0.63 before treatment; 2.43 ± 0.67 at month 12). During follow-up, four patients in the medical treatment and one in the interventional group developed pulmonary embolisms.ConclusionsFor treatment of acute deep vein thrombosis, PAT with or without stenting is superior to anticoagulant therapy alone in terms of both ensuring venous patency and improving clinical

Utilization of Oral Anticoagulation in a Teaching Hospital in Nigeria

African Journals Online (AJOL)

optimal antithrombotic effect. The oral drugs ... vitamin K-dependent clotting factors, which include factors. II, VII, IX, and X, ... hyperthyroidism) and those that decrease INR (pharmacokinetic: Barbiturates ... of anticoagulation, drug dosing, treatment outcome and .... national guidelines, and performance on quality measures.

Upsetting the apple cart: a community anticoagulation clinic survey of life event factors that undermine safe therapy.

Science.gov (United States)

Edmundson, Sarah; Stuenkel, Diane L; Connolly, Phyllis M

2005-09-01

Anticoagulation therapy is a life-enhancing therapy for patients who are at risk for embolic events secondary to atrial fibrillation, valve replacement, and other comorbidities. Clinicians are motivated to decrease the amount of time that patients are either under- or over-anticoagulated, common conditions that decrease patient safety at either extreme. The primary purpose of this descriptive study was to examine the relationship between personal life event factors as measured by Norbeck's Life Events Questionnaire, core demographics such as age and income, and anticoagulation regulation. Although many factors affect anticoagulation therapy, the precise impact of life events, positive or negative, is unknown. The salient findings of this study (n = 202) showed a small, though statistically significant, inverse relationship (r = -0.184, P < .01) between negative life events and decreased time within therapeutic international normalized ratio. Total Life Event scores showed a statistically significant inverse relationship (r = -0.159, P < .05) to international normalized ratio time within therapeutic level. Lower income was inversely associated with higher negative Life Event scores (r = -0.192, P < .01). The findings demonstrate the need for strategies that address the potential impact of life events in conjunction with coexisting screening measures used in anticoagulation clinics. Implications for this study are limited by lack of methodology documenting concurrent social support factors and limitations of the research tool to reflect life event issues specific to outpatient seniors.

Removal of radioactive cesium from soil by ammonium citrate solution and ionic liquid

International Nuclear Information System (INIS)

Ishiwata, Shunji; Kitakouji, Manabu; Taga, Atsushi; Ogata, Fumihiko; Ouchi, Hidekazu; Yamanishi, Hirokuni; Inagaki, Masayo

2015-01-01

Radioactive cesium has strongly bound soil as time proceeded, which could not be cleaved in mild condition. We have found that serial treatment of ammonium citrate solution and ionic liquid removed radioactive cesium from soil effectively. The sequence of the treatment is crucial, since inverse serial treatment or mixture of two kinds of solution did not show such an effect, which suggested that ammonium citrate unlocked trapped cesium in soil and ionic liquid solved it. We also found that repeating serial treatment and prolonged treatment time additively removed cesium from soil. (author)

FecB, a periplasmic ferric-citrate transporter from E. coli, can bind different forms of ferric-citrate as well as a wide variety of metal-free and metal-loaded tricarboxylic acids.

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Banerjee, Sambuddha; Paul, Subrata; Nguyen, Leonard T; Chu, Byron C H; Vogel, Hans J

2016-01-01

The Escherichia coli Fec system, consisting of an outer membrane receptor (FecA), a periplasmic substrate binding protein (FecB) and an inner membrane permease-ATPase type transporter (FecC/D), plays an important role in the uptake and transport of Fe(3+)-citrate. Although several FecB sequences from various organisms have been reported, there are no biophysical or structural data available for this protein to date. In this work, using isothermal titration calorimetry (ITC), we report for the first time the ability of FecB to bind different species of Fe(3+)-citrate as well as other citrate complexes with trivalent (Ga(3+), Al(3+), Sc(3+) and In(3+)) and a representative divalent metal ion (Mg(2+)) with low μM affinity. Interestingly, ITC experiments with various iron-free di- and tricarboxylic acids show that FecB can bind tricarboxylates with μM affinity but not biologically relevant dicarboxylates. The ability of FecB to bind with metal-free citrate is also observed in (1)H,(15)N HSQC-NMR titration experiments reported here at two different pH values. Further, differential scanning calorimetry (DSC) experiments indicate that the ligand-bound form of FecB has greater thermal stability than ligand-free FecB under all pH and ligand conditions tested, which is consistent with the idea of domain closure subsequent to ligand binding for this type of periplasmic binding proteins.

Fabrication of anticoagulation layer on titanium surface by sequential immobilization of poly (ethylene glycol) and albumin.

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Pan, Chang-Jiang; Hou, Yan-Hua; Zhang, Bin-Bin; Zhang, Lin-Cai

2014-01-01

This paper presents a simple method to sequentially immobilize poly (ethylene glycol) (PEG) and albumin on titanium surface to enhance the blood compatibility. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) analysis indicated that PEG and albumin were successfully immobilized on the titanium surface. Water contact angle results showed a better hydrophilic surface after the immobilization. The immobilized PEG or albumin can not only obviously prevent platelet adhesion and activation but also prolong activated partial thromboplastin time (APTT), leading to the improved anticoagulation. Moreover, immobilization of albumin on PEG-modified surface can further improve the anticoagulation. The approach in the present study provides an effective and efficient method to improve the anticoagulation of blood-contact biomedical devices such as coronary stents.

Current practice of antiplatelet and anticoagulation management in post-cardiac surgery patients: a national audit.

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Hosmane, Sharath; Birla, Rashmi; Marchbank, Adrian

2012-04-01

The Audit and Guidelines Committee of the European Association for Cardio-Thoracic Surgery recently published a guideline on antiplatelet and anticoagulation management in cardiac surgery. We aimed to assess the awareness of the current guideline and adherence to it in the National Health Service through this National Audit. We designed a questionnaire consisting of nine questions covering various aspects of antiplatelet and anticoagulation management in post-cardiac surgery patients. A telephonic survey of the on-call cardiothoracic registrars in all the cardiothoracic centres across the UK was performed. All 37 National Health Service hospitals in the UK with 242 consultants providing adult cardiac surgical service were contacted. Twenty (54%) hospitals had a unit protocol for antiplatelet and anticoagulation management in post-cardiac surgery. Only 23 (62.2%) registrars were aware of current European Association for Cardio-Thoracic Surgery guidelines. Antiplatelet therapy is variable in the cardiac surgical units across the country. Low-dose aspirin is commonly used despite the recommendation of 150-300 mg. The loading dose of aspirin within 24 h as recommended by the guideline is followed only by 60.7% of surgeons. There was not much deviation from the guideline with respect to the anticoagulation therapy.

Purification, structural characterization and anticoagulant properties of fucosylated chondroitin sulfate isolated from Holothuria mexicana.

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Mou, Jiaojiao; Wang, Cong; Li, Wenjing; Yang, Jie

2017-05-01

A novel fucosylated chondroitin sulfate (HmG) was isolated from sea cucumber Holothuria mexicana, the structure of which was characterized by monosaccharide composition, disaccharide composition, IR, 1 H and 13 C NMR spectrum, additionally with two dimensional NMR spectrum of degraded HmG (DHmG). The backbone of HmG was identified as chondroitin 6-O sulfate, while the major O-4 sulfated fucose branches linked to O-3 position of glucuronic acid in almost every disaccharide unit. The anticoagulant activities of HmG and DHmG were assessed and compared with heparin and low molecular weight heparin. The results indicated that HmG and DHmG both could significantly prolong the activated partial thrombo-plastin time, and the properties were well related to its molecular weight. DHmG showed similar anticoagulant properties to low molecular weight heparin with less bleeding risks, making it a safer anticoagulant drug. Copyright © 2017 Elsevier B.V. All rights reserved.

Defective enamel and bone development in sodium-dependent citrate transporter (NaCT Slc13a5 deficient mice.

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Armando R Irizarry

Full Text Available There has been growing recognition of the essential roles of citrate in biomechanical properties of mineralized tissues, including teeth and bone. However, the sources of citrate in these tissues have not been well defined, and the contribution of citrate to the regulation of odontogenesis and osteogenesis has not been examined. Here, tooth and bone phenotypes were examined in sodium-dependent citrate transporter (NaCT Slc13a5 deficient C57BL/6 mice at 13 and 32 weeks of age. Slc13a5 deficiency led to defective tooth development, characterized by absence of mature enamel, formation of aberrant enamel matrix, and dysplasia and hyperplasia of the enamel organ epithelium that progressed with age. These abnormalities were associated with fragile teeth with a possible predisposition to tooth abscesses. The lack of mature enamel was consistent with amelogenesis imperfecta. Furthermore, Slc13a5 deficiency led to decreased bone mineral density and impaired bone formation in 13-week-old mice but not in older mice. The findings revealed the potentially important role of citrate and Slc13a5 in the development and function of teeth and bone.

Educational Level, Anticoagulation Quality, and Clinical Outcomes in Elderly Patients with Acute Venous Thromboembolism: A Prospective Cohort Study.

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Hofmann, Eveline; Faller, Nicolas; Limacher, Andreas; Méan, Marie; Tritschler, Tobias; Rodondi, Nicolas; Aujesky, Drahomir

2016-01-01

Whether the level of education is associated with anticoagulation quality and clinical outcomes in patients with acute venous thromboembolism (VTE) is uncertain. We thus aimed to investigate the association between educational level and anticoagulation quality and clinical outcomes in elderly patients with acute VTE. We studied 817 patients aged ≥65 years with acute VTE from a Swiss prospective multicenter cohort study (09/2009-12/2013). We defined three educational levels: 1) less than high school, 2) high school, and 3) post-secondary degree. The primary outcome was the anticoagulation quality, expressed as the percentage of time spent in the therapeutic INR range (TTR). Secondary outcomes were the time to a first recurrent VTE and major bleeding. We adjusted for potential confounders and periods of anticoagulation. Overall, 56% of patients had less than high school, 25% a high school degree, and 18% a post-secondary degree. The mean percentage of TTR was similar across educational levels (less than high school, 61%; high school, 64%; and post-secondary, 63%; P = 0.36). Within three years of follow-up, patients with less than high school, high school, and a post-secondary degree had a cumulative incidence of recurrent VTE of 14.2%, 12.9%, and 16.4%, and a cumulative incidence of major bleeding of 13.3%, 15.1%, and 15.4%, respectively. After adjustment, educational level was neither associated with anticoagulation quality nor with recurrent VTE or major bleeding. In elderly patients with VTE, we did not find an association between educational level and anticoagulation quality or clinical outcomes.

Cost evaluation of two methods of post tooth extraction hemostasis in patients on anticoagulant therapy.

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Zusman, S P; Lustig, J P; Bin Nun, G

1993-06-01

The classical management of patients on oral anticoagulant therapy included hospitalisation, cessation of the anticoagulant agent, and extraction of teeth when the prothrombine levels rise. This method was substituted in the High Risk Dental Clinic at Barzilai Medical Center in Ashkelon by use of a tissue sealant (Tisseel) which does not need hospitalisation nor cessation of the anticoagulant therapy. In comparing the last 23 sessions employing the former method to the first 23 sessions using the new method there were significant differences in the cost effectiveness for the health system, provider, insurer and patient. Despite the fact that from the health system point of view the new method is much more cost effective, there is no financial incentive for the provider (hospital) nor awareness on the part of the insurer (General Sick Fund) to embrace it and 'market' it.

Sulfated polysaccharides with antioxidant and anticoagulant activity from the sea cucumber Holothuria fuscogliva

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Li, Rongfeng; Yu, Huahua; Yue, Yang; Liu, Song; Xing, Rong'e.; Chen, Xiaolin; Li, Pengcheng

2017-07-01

Sea cucumber is a traditional nutritional food and medicinal resource with many bioactive components in China. Holothuria fuscogliva is a big sea cucumber with a rich of bioactive polysaccharides. To investigate the bioactivities of the polysaccharides from sea cucumber H. fuscogliva, we prepared the sulfated polysaccharides (HfP) from sea cucumber H. fuscogliva using a protease hydrolysis method. Antioxidant activities of HfP were investigated, including hydroxyl radical scavenging activity and superoxide radical scavenging activity. And, the anticoagulant activities of HfP were studied, including the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT). The average molecular weight was 1 867.1 Da, with a sulfate content of 20.7%. In addition, the molar ratio of monosaccharide composition of HfP was Man: Rha: Glc A: Glc: Gal: Xyl: Fuc=0.083 6: 0.437: 0.134: 0:1.182: 0.748: 1. It had a strong antioxidant activity, the hydroxyl and superoxide radical scavenging activity EC50 of HfP was 3.74 and 0.037 mg/mL, respectively. It also showed a good anticoagulant activity in our study. The APTT of HfP was much higher than that of heparin sodium, and the PT and TT of HfP was close to that of heparin sodium at a low concentration. Therefore, HfP shows a good antioxidant and anticoagulant activity and it may become a potential candidate of the natural antioxidant and anticoagulant and will have a good application future in health product or medicine industry.

Delphi-RAND consensus of the Spanish Society of Internal Medicine on the controversies in anticoagulant therapy and prophylaxis in medical diseases. INTROMBIN Project (Uncertainty in thromboprophylaxis in internal medicine).

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Ruiz-Ruiz, F; Medrano, F J; Navarro-Puerto, M A; Rodríguez-Torres, P; Romero-Alonso, A; Santos-Lozano, J M; Alonso-Ortiz Del Rio, C; Varela-Aguilar, J M; Calderón, E J; Marín-León, I

2018-05-21

The aim of this study was to determine the opinion of internists on the management of anticoagulation and thromboembolism prophylaxis in complex clinical scenarios in which the risk-benefit ratio of surgery is narrow and to develop a consensus document on the use of drugs anticoagulant therapy in this patient group. To this end, we identified by consensus the clinical areas of greatest uncertainty, a survey was created with 20 scenarios laid out in 40 clinical questions, and we reviewed the specific literature. The survey was distributed among the internists of the Spanish Society of Internal Medicine (SEMI) and was completed by 290 of its members. The consensus process was implemented by changing the Delphi-RAND appropriateness method in an anonymous, double-round process that enabled an expert panel to identify the areas of agreement and uncertainty. In our case, we also added the survey results to the panel, a methodological innovation that helps provide additional information on the standard clinical practice. The result of the process is a set of 19 recommendations formulated by SEMI experts, which helps establish guidelines for action on anticoagulant therapy in complex scenarios (high risk or active haemorrhage, short life expectancy, coexistence of antiplatelet therapy or comorbidities such as kidney disease and liver disease), which are not uncommon in standard clinical practice. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Enhancing anticoagulation and endothelial cell proliferation of titanium surface by sequential immobilization of poly(ethylene glycol) and collagen

International Nuclear Information System (INIS)

Pan, Chang-Jiang; Hou, Yan-Hua; Ding, Hong-Yan; Dong, Yun-Xiao

2013-01-01

In the present study, poly(ethylene glycol) (PEG) and collagen I were sequentially immobilized on the titanium surface to simultaneously improve the anticoagulation and endothelial cell proliferation. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy analysis confirmed that PEG and collagen I were successfully immobilized on the titanium surface. Water contact angle results suggested the excellent hydrophilic surface after the immobilization. The anticoagulation experiments demonstrated that the immobilized PEG and collagen I on the titanium surface could not only obviously prevent platelet adhesion and aggregation but also prolong activated partial thromboplastin time (APTT), leading to the improved blood compatibility. Furthermore, immobilization of collagen to the end of PEG chain did not abate the anticoagulation. As compared to those on the pristine and PEG-modified titanium surfaces, endothelial cells exhibited improved proliferative profiles on the surface modified by the sequential immobilization of PEG and collagen in terms of CCK-8 assay, implying that the modified titanium may promote endothelialization without abating the blood compatibility. Our method may be used to modify the surface of blood-contacting biomaterials such as titanium to promote endothelialization and improve the anticoagulation, it may be helpful for development of the biomedical devices such as coronary stents, where endothelializaton and excellent anticoagulation are required.

Anticoagulant Prairie Dog Bait Risk Mitigation Measures to Protect Endangered Species

Science.gov (United States)

This Web page contains information on how certified pesticide applicators can use anticoagulant prairie dog bait products such as Rozol and Kaput-D while minimizing exposure risks to listed and non-target species.

Women taking the "blue pill" (sildenafil citrate): such a big deal?

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Lo Monte, Giuseppe; Graziano, Angela; Piva, Isabella; Marci, Roberto

2014-01-01

For years, phosphodiesterase type 5 inhibitors have been used for the treatment of erectile dysfunctions. Due to the similarities between male and female sexual response, several studies have assessed the effects of sildenafil citrate (Viagra(®)) in women affected by female sexual arousal disorder. The results are still conflicting and the drug is not devoid of adverse effects. Furthermore, female sexual arousal disorder is a heterogeneous condition whose underlying causes are difficult to diagnose and appropriate treatment requires a thorough sexual, psychological, and medical history along with specialist consultations. The clinician should pursue a global approach to the patient with sexual difficulties, while non-hormonal treatment such as phosphodiesterase type 5 inhibitors (ie, sildenafil citrate) should be kept as the last option.

Use of Non-Vitamin K Antagonist Oral Anticoagulants 2008-2016

DEFF Research Database (Denmark)

Haastrup, Simone; Hellfritzsch, Maja; Rasmussen, Lotte

2018-01-01

We aimed to provide detailed utilization data on the total use of non-vitamin K antagonist oral anticoagulants (NOACs) since their introduction in 2008. Using the nationwide Danish National Prescription Registry, we identified all individuals filling prescriptions for NOACs 2008-2016. We reported...

Stratifying the risks of oral anticoagulation in patients with liver disease.

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Efird, Lydia M; Mishkin, Daniel S; Berlowitz, Dan R; Ash, Arlene S; Hylek, Elaine M; Ozonoff, Al; Reisman, Joel I; Zhao, Shibei; Jasuja, Guneet K; Rose, Adam J

2014-05-01

Chronic liver disease presents a relative contraindication to warfarin therapy, but some patients with liver disease nevertheless require long-term anticoagulation. The goal is to identify which patients with liver disease might safely receive warfarin. Among 102 134 patients who received warfarin from the Veterans Affairs from 2007 to 2008, International Classification of Diseases-Ninth Revision codes identified 1763 patients with chronic liver disease. Specific diagnoses and laboratory values (albumin, aspartate aminotransferase, alanine aminotransferase, creatinine, and cholesterol) were examined to identify risk of adverse outcomes, while controlling for available bleeding risk factors. Outcomes included percent time in therapeutic range, a measure of anticoagulation control, and major hemorrhagic events, by International Classification of Diseases-Ninth Revision codes. Patients with liver disease had lower mean time in therapeutic range (53.5%) when compared with patients without (61.7%; P<0.001) and more hemorrhages (hazard ratio, 2.02; P<0.001). Among patients with liver disease, serum albumin and creatinine levels were the strongest predictors of both outcomes. We created a 4-point score system: patients received 1 point each for albumin (2.5-3.49 g/dL) or creatinine (1.01-1.99 mg/dL), and 2 points each for albumin (<2.5 g/dL) or creatinine (≥2 mg/dL). This score predicted both anticoagulation control and hemorrhage. When compared with patients without liver disease, those with a score of zero had modestly lower time in therapeutic range (56.7%) and no increase in hemorrhages (hazard ratio, 1.16; P=0.59), whereas those with the worst score (4) had poor control (29.4%) and high hazard of hemorrhage (hazard ratio, 8.53; P<0.001). Patients with liver disease receiving warfarin have poorer anticoagulation control and more hemorrhages. A simple 4-point scoring system using albumin and creatinine identifies those at risk for poor outcomes. © 2014 American

Caffeine Citrate Dosing Adjustments to Assure Stable Caffeine Concentrations in Preterm Neonates.

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Koch, Gilbert; Datta, Alexandre N; Jost, Kerstin; Schulzke, Sven M; van den Anker, John; Pfister, Marc

2017-12-01

To identify dosing strategies that will assure stable caffeine concentrations in preterm neonates despite changing caffeine clearance during the first 8 weeks of life. A 3-step simulation approach was used to compute caffeine doses that would achieve stable caffeine concentrations in the first 8 weeks after birth: (1) a mathematical weight change model was developed based on published weight distribution data; (2) a pharmacokinetic model was developed based on published models that accounts for individual body weight, postnatal, and gestational age on caffeine clearance and volume of distribution; and (3) caffeine concentrations were simulated for different dosing regimens. A standard dosing regimen of caffeine citrate (using a 20 mg/kg loading dose and 5 mg/kg/day maintenance dose) is associated with a maximal trough caffeine concentration of 15 mg/L after 1 week of treatment. However, trough concentrations subsequently exhibit a clinically relevant decrease because of increasing clearance. Model-based simulations indicate that an adjusted maintenance dose of 6 mg/kg/day in the second week, 7 mg/kg/day in the third to fourth week and 8 mg/kg/day in the fifth to eighth week assures stable caffeine concentrations with a target trough concentration of 15 mg/L. To assure stable caffeine concentrations during the first 8 weeks of life, the caffeine citrate maintenance dose needs to be increased by 1 mg/kg every 1-2 weeks. These simple adjustments are expected to maintain exposure to stable caffeine concentrations throughout this important developmental period and might enhance both the short- and long-term beneficial effects of caffeine treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Preparation of lead titanate zirconate from metal citrates; Preparacao do titanato zirconato de chumbo a partir dos citratos metalicos

Energy Technology Data Exchange (ETDEWEB)

Bastos, C M.R.

1994-12-31

Lead titanate zirconate (PZT) preparation from its metal constituent citrates have been investigated. Metal citrates were obtained by forced precipitation using a dehydration alcohol mixture. Salt solutions of lead nitrate and octahydrated zirconyl chloride, and titanium tetrachloride were treated separately with citric acid and ammonium hydroxide. Zirconium, titanium and lead oxides resulted from thermal decomposition of corresponding citrates at 500{sup 0} C, 450{sup 0} C and 250{sup 0} C, respectively. Lead titanate (PT) and lead zirconate (P Z) were obtained by calcining at 450{sup 0} C and 500{sup 0} C, respectively, after adequate heating of citrates mechanically mixed in ethyl ether. PZT samples were obtained with different starting stoichiometry. Rhombohedral PZT-1 53/47 sample was prepared from co precipitating zirconyl ammonium and ammonium lead citrates in presence of ethanolic titanium oxide dispersion, and calcinating at 800{sup 0} C. Rhombohedral PZT-q 52/48 sample was obtained from heating at 500{sup 0} C for 2 hours a mixture of metal citrates coprecipitated by dehydration mixture of acetone-ethanol-formic acid (2:1:0,06). Tetragonal PZT-m stoichiometry 53/47 sample were obtained by calcining at after 600{sup 0} C for 2 hours after heating a mechanically mixed metal citrates. PT phase arose at 400{sup 0} C. PZT-m powders obtained in a range of 400{sup 0} C-800{sup 0} C were isostatically pressed, and sintered at 1100{sup 0} C and 1200{sup 0} C in saturated Pb O atmosphere. Rhombohedral sintered PZT was obtained with 7,78 g.cm{sup -3} at 1200{sup 0} C. (author). 123 refs, 53 figs, 32 tabs.

Aluminum-activated citrate and malate transporters from the MATE and ALMT families function independently to confer Arabidopsis aluminum tolerance.

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Liu, Jiping; Magalhaes, Jurandir V; Shaff, Jon; Kochian, Leon V

2009-02-01

Aluminum-activated root malate and citrate exudation play an important role in plant Al tolerance. This paper characterizes AtMATE, a homolog of the recently discovered sorghum and barley Al-tolerance genes, shown here to encode an Al-activated citrate transporter in Arabidopsis. Together with the previously characterized Al-activated malate transporter, AtALMT1, this discovery allowed us to examine the relationship in the same species between members of the two gene families for which Al-tolerance genes have been identified. AtMATE is expressed primarily in roots and is induced by Al. An AtMATE T-DNA knockdown line exhibited very low AtMATE expression and Al-activated root citrate exudation was abolished. The AtALMT1 AtMATE double mutant lacked both Al-activated root malate and citrate exudation and showed greater Al sensitivity than the AtALMT1 mutant. Therefore, although AtALMT1 is a major contributor to Arabidopsis Al tolerance, AtMATE also makes a significant but smaller contribution. The expression patterns of AtALMT1 and AtMATE and the profiles of Al-activated root citrate and malate exudation are not affected by the presence or absence of the other gene. These results suggest that AtALMT1-mediated malate exudation and AtMATE-mediated citrate exudation evolved independently to confer Al tolerance in Arabidopsis. However, a link between regulation of expression of the two transporters in response to Al was identified through work on STOP1, a transcription factor that was previously shown to be necessary for AtALMT1 expression. Here we show that STOP1 is also required for AtMATE expression and Al-activated citrate exudation.

Aqueous solubility of calcium citrate and interconversion between the tetrahydrate and the hexahydrate as a balance between endothermic dissolution and exothermic complex formation

DEFF Research Database (Denmark)

Hedegaard, Martina Vavrusova; Skibsted, Leif Horsfelt

2016-01-01

Aqueous solubility of calcium citrate tetrahydrate was found to decrease with increasing temperature, while solubility of hexahydrate increased with a transition temperature at 51.6 °C. Excess citrate increased calcium citrate solubility but decreased the calcium ion activity of the saturated sol...

Na2EDTA anticoagulant impaired blood samples from the teleost Piaractus mesopotamicus

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Thaís Heloisa Vaz Farias

2016-05-01

Full Text Available Abstract: The present study aimed to evaluate the effects of Na heparin and Na2EDTA on blood of Piaractus mesopotamicus (360.7±42.4g, 26.4±1.0cm. Twenty fishes were sampled in two experiment trials, ten for erythrocyte fragility analysis and ten for hematologic and plasma biochemical study. The blood collected by venous-caudal puncture was fractioned and stored in anticoagulants solution: Na2EDTA 10%, Na2EDTA 3%, Na heparin 5000 IU and Na heparin 100 IU. Plasmatic levels of calcium presented in the Na2EDTA stored samples were about 80% lower than both heparin groups. Blood samples of P. mesopotamicus stored with Na2EDTA demonstrated increase in the hematocrit and MCV, and decrease in MCHC. The dose-response effect was observed in this study. The results are reinforced by the higher levels of plasmatic protein and hemolysis presented in the Na2EDTA 10% stored blood, confirming the deleterious effect of this anticoagulant treatment on the quality of blood samples. Na2EDTA is not indicated to store P. mesopotamicus blood samples, but sodium heparin at 100 IU is the most recommended anticoagulant, since this treatment presented the lower rate of alterations in the stored blood.

[Pathogenesis and Laboratory Findings in Antiphospholipid Syndrome, Especially Associated with Lupus Anticoagulant].

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Ieko, Masahiro; Naito, Sumiyoshi; Yoshida, Mika; Takahashi, Nobuhiko

2015-10-01

Antiphospholipid syndrome (APS), an acquired thrombotic condition, is a complex clinical state characterized by the presence of circulating antiphospholipid antibodies in patients with thrombosis or pregnancy morbidity. Revised APS classification criteria are used for diagnosis, which include at least one clinical criterion (thrombosis or pregnancy loss) and at least one of the laboratory criteria [anticardiolipin antibodies, anti-β2GPI antibodies, lupus anticoagulant (LA)]. LA is also an independent risk factor for developing thrombosis, though some LA-positive cases have been reported to have a bleeding symptom. Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare disorder characterized by a bleeding tendency due to low prothrombin activity in patients with LA, and has recently been reported not only in children but also in adults We have encountered LA cases with bleeding and low coagulation factor activities except for prothrombin. Based on our findings, we propose that LA-positive cases with a bleeding symptom and characterized by low coagulation factor activity including prothrombin be termed lupus anticoagulant-associated coagulopathy (LAAC). Furthermore, coagulation factor autoantibodies are often detected in LAAC patients; thus, correct measurement of LA is important to distinguish LAAC patients from those possessing an inhibitor to coagulation factors such as acquired hemophilia A as well as to select the optimal therapeutic strategy.

Practice points in gynecardiology: Abnormal uterine bleeding in premenopausal women taking oral anticoagulant or antiplatelet therapy.

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Maas, Angela H E M; Euler, Mia von; Bongers, Marlies Y; Rolden, Herbert J A; Grutters, Janneke P C; Ulrich, Lian; Schenck-Gustafsson, Karin

2015-12-01

A growing number of premenopausal women are currently using antithrombotic and/or (dual) antiplatelet therapy for various cardiovascular indications. These may induce or exacerbate abnormal uterine bleeding and more awareness and knowledge among prescribers is required. Heavy and irregular menstrual bleeding is common in women in their forties and may have a variety of underlying causes that require different treatment options. Thus using anticoagulants in premenopausal women demands specific expertise and close collaboration between cardiovascular physicians and gynecologists. In this article we summarize the scope of the problem and provide practical recommendations for the care for young women taking anticoagulants and/or (dual) antiplatelet therapy. We also recommend that more safety data on uterine bleeding with novel anticoagulants in premenopausal women should be obtained. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Concurrent use of tramadol and oral vitamin K antagonists and the risk of excessive anticoagulation

DEFF Research Database (Denmark)

Pottegård, Anton; Meegaard, P. M.; Holck, L. H.

2013-01-01

.9-5.2). This corresponds to, on average, one excess case per 250 treatment years (CI 125-584). The result is potentially confounded by concomitant paracetamol use and the presence of acute illness. CONCLUSION: Caution is advised when using tramadol in patients using VKA, and if possible, an alternative pain......OBJECTIVES: The objective was to assess whether the concurrent use of tramadol and vitamin K antagonists (VKAs) leads to an increased risk of excessive anticoagulation. DESIGN: The study was designed as a case-control study, nested within users of VKA and with tramadol use as our main exposure. We...... anticoagulation attributable to the use of tramadol. RESULTS: A total of 178 patients were included, 30 of which were exposed to tramadol, along with 2643 controls, 114 of which were exposed to tramadol. The adjusted odds-ratio for experiencing excessive anticoagulation during use of tramadol was 3.1 (1...

Tofacitinib Citrate for Ulcerative Keratitis in a Patient with Rheumatoid Arthritis

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Philip B. Meadow

2014-01-01

Full Text Available Purpose. To report a case of a patient with rheumatoid arthritis (RA treated with tofacitinib citrate. Methods. Observational case report. Results. A 59-year-old patient, with a history of rheumatoid arthritis, on methotrexate 10 mg PO qwk and IV abatacept 750 mg/month, presented with photosensitivity, foreign body sensation, pain, redness, and blurry vision of her right eye (RE. Visual acuity of the RE was 20/200 and 20/20 of the left eye (LE. The slit lamp examination of the RE revealed dryness, 2+ injection of the conjunctiva, and pericentral ulceration of the cornea with 20–30% stromal thinning, pannus, and diffuse punctate epithelial erosions. The anterior chamber appeared normal. Laboratory values revealed elevated levels of rheumatoid factor, anticyclic citrullinated peptide antibodies, and C-reactive protein. The patient was switched to tofacitinib citrate 5 mg PO b.i.d, underwent corneal gluing, and was given prednisone acetate 1% gt TID, polytrim gt TID, neomycin-polymyxin-dexameth gt QD, FreshKote lubricant 1.8% gt QID, moxifloxacin 0.5% gt QID, and preservative free artificial tears Q1H. Within one week, laboratory values normalized, symptoms diminished, and the cornea reepithelialized. Conclusion. RA can present with ulcerative keratitis. Tofacitinib citrate, steroids, and corneal gluing were found to halt the progression of keratolysis and promote reepithelialization.

Does adding metformin to clomifene citrate lead to higher pregnancy rates in a subset of women with polycystic ovary syndrome?

OpenAIRE

Moll, E.; Korevaar, J.C.; Bossuyt, P.M.M.; van der Veen, F.

2008-01-01

BACKGROUND An RCT among newly diagnosed, therapy naive women with polycystic ovary syndrome (PCOS) showed no significant differences in ovulation rate, ongoing pregnancy rate or spontaneous abortion rate in favour of clomifene citrate plus metformin compared with clomifene citrate. We wanted to assess whether there are specific subgroups of women with PCOS in whom clomifene citrate plus metformin leads to higher pregnancy rates. METHODS Subgroup analysis based on clinical and biochemical para...

Anticoagulant use for the prevention of stroke in patients with atrial fibrillation: findings from a multi-payer analysis.

Science.gov (United States)

Lang, Kathleen; Bozkaya, Duygu; Patel, Aarti A; Macomson, Brian; Nelson, Winnie; Owens, Gary; Mody, Samir; Schein, Jeff; Menzin, Joseph

2014-07-28

Oral anticoagulation is recommended for stroke prevention in intermediate/high stroke risk atrial fibrillation (AF) patients. The objective of this study was to demonstrate the usefulness of analytic software tools for descriptive analyses of disease management in atrial AF; a secondary objective is to demonstrate patterns of potential anticoagulant undertreatment in AF. Retrospective data analyses were performed using the Anticoagulant Quality Improvement Analyzer (AQuIA), a software tool designed to analyze health plan data. Two-year data from five databases were analyzed: IMS LifeLink (IMS), MarketScan Commercial (MarketScanCommercial), MarketScan Medicare Supplemental (MarketScanMedicare), Clinformatics™ DataMart, a product of OptumInsight Life Sciences (Optum), and a Medicaid Database (Medicaid). Included patients were ≥ 18 years old with a new or existing diagnosis of AF. The first observed AF diagnosis constituted the index date, with patient outcomes assessed over a one year period. Key study measures included stroke risk level, anticoagulant use, and frequency of International Normalized Ratio (INR) monitoring. High stroke risk (CHADS2 ≥ 2 points) was estimated in 54% (IMS), 22% (MarketScanCommercial), 64% (MarketscanMedicare), 42% (Optum) and 62% (Medicaid) of the total eligible population. Overall, 35%, 29%, 38%, 39% and 16% of all AF patients received an anticoagulant medication in IMS, MarketScanCommercial, MarketScanMedicare, Optum and Medicaid, respectively. Among patients at high risk for stroke, 19% to 51% received any anticoagulant. The AQuIA provided a consistent platform for analysis across multiple AF populations with varying baseline characteristics. Analyzer results show that many high-risk AF patients in selected commercial, Medicare-eligible, and Medicaid populations do not receive appropriate thromboprophylaxis, as recommended by treatment guidelines.

Cross-cultural adaptation and psychometric properties of the Brazilian-Portuguese version of the Duke Anticoagulation Satisfaction Scale.

Science.gov (United States)

Pelegrino, Flávia M; Dantas, Rosana A S; Corbi, Inaiara S A; da Silva Carvalho, Ariana R; Schmidt, André; Pazin Filho, Antônio

2012-09-01

The aim of this study was to evaluate the internal reliability and validity of the Brazilian-Portuguese version of Duke Anticoagulation Satisfaction Scale (DASS) among cardiovascular patients. Oral anticoagulation is widely used to prevent and treat thromboembolic events in several conditions, especially in cardiovascular diseases; however, this therapy can induce dissatisfaction and reduce the quality of life. Methodological and cross-sectional research design. The cultural adaptation of the DASS included the translation and back-translation, discussions with healthcare professionals and patients to ensure conceptual equivalence, semantic evaluation and instrument pretest. The Brazilian-Portuguese version of the DASS was tested among subjects followed in a university hospital anticoagulation outpatient clinic. The psychometric properties were assessed by construct validity (convergent, known groups and dimensionality) and internal consistency/reliability (Cronbach's alpha). A total of 180 subjects under oral anticoagulation formed the baseline validation population. DASS total score and SF-36 domain correlations were moderate for General health (r=-0.47, pDASS score and most of the subscales, except Limitation (r=-0.375, pscale, and it ranged from 0.76 (hassles and burdens)-0.46 (psychological impact) among the domains, confirming the internal consistency reliability. The Brazilian-Portuguese version of the DASS has shown levels of reliability and validity comparable with the original English version. Healthcare practitioners and researchers need internationally validated measurement tools to compare outcomes of interventions in clinical management and research tools in oral anticoagulation therapy. © 2011 Blackwell Publishing Ltd.

The protein C omega-loop substitution Asn2Ile is associated with reduced protein C anticoagulant activity.

LENUS (Irish Health Repository)

Preston, Roger J S

2012-02-01

We report a kindred with heritable protein C (PC) deficiency in which two siblings with severe thrombosis showed a composite type I and IIb PC deficiency phenotype, identified using commercial PC assays (proband: PC antigen 42 u\\/dl, amidolytic activity 40 u\\/dl, anticoagulant activity 9 u\\/dl). The independent PROC nucleotide variations c.669C>A (predictive of Ser181Arg) and c.131C>T (predictive of Asn2Ile) segregated with the type I and type IIb PC deficiency phenotypes respectively, but co-segregated in the siblings with severe thrombosis. Soluble thrombomodulin (sTM)-mediated inhibition of plasma thrombin generation from an individual with PC-Asn2Ile was lower (endogenous thrombin potential (ETP) 56 +\\/- 1% that of ETP determined without sTM) than control plasma (ETP 15 +\\/- 2%) indicating reduced PC anticoagulant activity. Recombinant APC-Asn2Ile exhibited normal amidolytic activity but impaired anticoagulant activity. Protein S (PS)-dependent anticoagulant activity of recombinant APC-Asn2Ile and binding of recombinant APC-Asn2Ile to endothelial protein C receptor (EPCR) were reduced compared to recombinant wild-type APC. Asn2 lies within the omega-loop of the PC\\/APC Gla domain and this region is critical for calcium-induced folding and subsequent interactions with anionic phospholipids, EPCR and PS. The disruption of these interactions in this naturally-occurring PC variant highlights their collective importance in mediating APC anticoagulant activity in vivo.

A study of the effects of citrate-coated silver nanoparticles on RAW 264.7 cells using a toolbox of cytotoxic endpoints