A Novel Role of Eruca sativa Mill. (Rocket Extract: Antiplatelet (NF-κB Inhibition and Antithrombotic Activities

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Eduardo Fuentes

2014-12-01

Full Text Available Background: Epidemiological studies have shown the prevention of cardiovascular diseases through the regular consumption of vegetables. Eruca sativa Mill., commonly known as rocket, is a leafy vegetable that has anti-inflammatory activity. However, its antiplatelet and antithrombotic activities have not been described. Methods: Eruca sativa Mill. aqueous extract (0.1 to 1 mg/mL, was evaluated on human platelets: (i P-selectin expression by flow cytometry; (ii platelet aggregation induced by ADP, collagen and arachidonic acid; (iii IL-1β, TGF-β1, CCL5 and thromboxane B2 release; and (iv activation of NF-κB and PKA by western blot. Furthermore, (v antithrombotic activity (200 mg/kg and (vi bleeding time in murine models were evaluated. Results: Eruca sativa Mill. aqueous extract (0.1 to 1 mg/mL inhibited P-selectin expression and platelet aggregation induced by ADP. The release of platelet inflammatory mediators (IL-1β, TGF-β1, CCL5 and thromboxane B2 induced by ADP was inhibited by Eruca sativa Mill. aqueous extract. Furthermore, Eruca sativa Mill. aqueous extract inhibited NF-κB activation. Finally, in murine models, Eruca sativa Mill. aqueous extract showed significant antithrombotic activity and a slight effect on bleeding time. Conclusion: Eruca sativa Mill. presents antiplatelet and antithrombotic activity.

Isolation and chemical identification of lipid derivatives from avocado (Persea americana) pulp with antiplatelet and antithrombotic activities.

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Rodriguez-Sanchez, Dariana Graciela; Flores-García, Mirthala; Silva-Platas, Christian; Rizzo, Sheryl; Torre-Amione, Guillermo; De la Peña-Diaz, Aurora; Hernández-Brenes, Carmen; García-Rivas, Gerardo

2015-01-01

Platelets play a pivotal role in physiological hemostasis. However, in coronary arteries damaged by atherosclerosis, enhanced platelet aggregation, with subsequent thrombus formation, is a precipitating factor in acute ischemic events. Avocado pulp (Persea americana) is a good source of bioactive compounds, and its inclusion in the diet as a source of fatty acid has been related to reduced platelet aggregability. Nevertheless, constituents of avocado pulp with antiplatelet activity remain unknown. The present study aims to characterize the chemical nature of avocado constituents with inhibitory effects on platelet aggregation. Centrifugal partition chromatography (CPC) was used as a fractionation and purification tool, guided by an in vitro adenosine diphosphate (ADP), arachidonic acid or collagen-platelet aggregation assay. Antiplatelet activity was initially linked to seven acetogenins that were further purified, and their dose-dependent effects in the presence of various agonists were contrasted. This process led to the identification of Persenone-C (3) as the most potent antiplatelet acetogenin (IC₅₀=3.4 mM) among the evaluated compounds. In vivo evaluations with Persenone A (4) demonstrated potential protective effects against arterial thrombosis (25 mg kg⁻¹ of body weight), as coagulation times increased (2-fold with respect to the vehicle) and thrombus formation was attenuated (71% versus vehicle). From these results, avocado may be referred to as a functional food containing acetogenin compounds that inhibit platelet aggregation with a potential preventive effect on thrombus formation, such as those that occur in ischaemic diseases.

Prevalence of antiplatelet therapy in patients with diabetes

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Littenberg Benjamin

2005-12-01

Full Text Available Abstract Objective To determine the prevalence of, and patient characteristics associated with, antiplatelet therapy in a cohort of primary care patients with Type 1 or Type2 diabetes. Methods Subjects participating in a randomized trial of a decision support system were interviewed at home and medication usage verified by a research assistant. Eligibility for antiplatelet therapy was determined by American Diabetes Association criteria and clinical contraindications. The association between antiplatelet use and patient characteristics was examined using bivariate and multivariate logistic regression. Results The mean age of subjects was 64 years (range 31–93. The prevalence of antiplatelet use was 54% overall; 45% for subjects without known CVD vs. 78% for those with CVD; 46% for women vs. 63% for men; and 45% for younger subjects (age = 65 (OR 1.9 [1.3, 2.7]. The prevalence of antiplatelet therapy for younger women without CVD was 32.8% compared to a prevalence of 90.3% for older men with CVD. Conclusion Despite clinical practice guidelines recommending antiplatelet therapy for patients with diabetes, there are still many eligible patients not receiving this beneficial therapy, particularly patients under 65, women, and patients without known CVD. Effective methods to increase antiplatelet use should be considered at the national, community, practice and provider level.

Antiplatelet effects of Rhus verniciflua stokes heartwood and its active constituents--fisetin, butein, and sulfuretin--in rats.

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Lee, Jun-Hyeong; Kim, Mikyung; Chang, Kyung-Hwa; Hong, Cheol Yi; Na, Chun-Soo; Dong, Mi-Sook; Lee, Dongho; Lee, Moo-Yeol

2015-01-01

Rhus verniciflua stokes (RVS) is known to promote blood circulation by preventing blood stasis, although the active ingredients and the underlying mechanism are unclear. Platelets are the primary cells that regulate circulation and contribute to the development of diverse cardiovascular diseases by aggregation and thrombosis. The study assessed the antiplatelet activity of RVS and sought to identify the active constituents. Pretreatment of washed platelets with RVS heartwood extract blunted the aggregatory response of platelets to collagen. In the subfractions, fisetin, butein, and sulfuretin were identified as effective inhibitors of platelet aggregation by collagen, thrombin, and adenosine-5'-diphosphate. Antiplatelet activities of all three compounds were concentration dependent, and fisetin had longer in vitro duration of action compared with butein or sulfuretin. Extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase activation by collagen was prevented by fisetin, whereas butein and sulfuretin failed to inhibit ERK and p38 activation was not affected by any of the compounds. Rats orally administered 100 mg/(kg·day(-1)) fisetin for 7 days were resistant to arterial thrombosis, although total extract of RVS heartwood exhibited little effect at a dose of 1000 mg/(kg·day(-1)). RVS heartwood may have cardiovascular protective activity by inhibiting platelet aggregation. The active constituents are fisetin, butein, and sulfuretin, and fisetin is orally effective against thrombosis.

Novel direct factor Xa inhibitory compounds from Tenebrio molitor with anti-platelet aggregation activity.

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Lee, Wonhwa; Kim, Mi-Ae; Park, InWha; Hwang, Jae Sam; Na, MinKyun; Bae, Jong-Sup

2017-11-01

Tenebrio molitor is an edible insect that has antimicrobial, anticancer, and antihypertensive effects. The aim of this study was to identify the unreported bioactive compounds from T. molitor larvae with inhibitory activities against factor Xa (FXa) and platelet aggregation. Isolated compounds were evaluated for their anti-FXa and anti-platelet aggregation properties by monitoring clotting time, platelet aggregation, FXa activity, and thrombus formation. A diketopiperazine (1, cyclo( L -Pro- L -Tyr)) and a phenylethanoid (2, N-acetyltyramine) were isolated and inhibited the catalytic activity of FXa in a mixed inhibition model and inhibited platelet aggregation induced by adenosine diphosphate (ADP) and U46619. They inhibited ADP- and U46619-induced phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) and the expression of P-selectin and PAC-1 in platelets. They also improved the production of nitric oxide and inhibited the oversecretion of endothelin-1 compared to that of the ADP- or U46619-treated group. In an animal model of arterial and pulmonary thrombosis, the isolated compounds showed enhanced antithrombotic effects. They also elicited anticoagulant effects in mice. Compounds 1-2 inhibited ADP-, collagen-, or U46619-induced platelet aggregation and showed similar anti-thrombotic efficacy to rivaroxaban, a positive control. Therefore, 1-2 could serve as candidates and provide scaffolds for the development of new anti-FXa and anti-platelet drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

TIPdb: A Database of Anticancer, Antiplatelet, and Antituberculosis Phytochemicals from Indigenous Plants in Taiwan

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Ying-Chi Lin

2013-01-01

Full Text Available The unique geographic features of Taiwan are attributed to the rich indigenous and endemic plant species in Taiwan. These plants serve as resourceful bank for biologically active phytochemicals. Given that these plant-derived chemicals are prototypes of potential drugs for diseases, databases connecting the chemical structures and pharmacological activities may facilitate drug development. To enhance the utility of the data, it is desirable to develop a database of chemical compounds and corresponding activities from indigenous plants in Taiwan. A database of anticancer, antiplatelet, and antituberculosis phytochemicals from indigenous plants in Taiwan was constructed. The database, TIPdb, is composed of a standardized format of published anticancer, antiplatelet, and antituberculosis phytochemicals from indigenous plants in Taiwan. A browse function was implemented for users to browse the database in a taxonomy-based manner. Search functions can be utilized to filter records of interest by botanical name, part, chemical class, or compound name. The structured and searchable database TIPdb was constructed to serve as a comprehensive and standardized resource for anticancer, antiplatelet, and antituberculosis compounds search. The manually curated chemical structures and activities provide a great opportunity to develop quantitative structure-activity relationship models for the high-throughput screening of potential anticancer, antiplatelet, and antituberculosis drugs.

TIPdb: a database of anticancer, antiplatelet, and antituberculosis phytochemicals from indigenous plants in Taiwan.

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Lin, Ying-Chi; Wang, Chia-Chi; Chen, Ih-Sheng; Jheng, Jhao-Liang; Li, Jih-Heng; Tung, Chun-Wei

2013-01-01

The unique geographic features of Taiwan are attributed to the rich indigenous and endemic plant species in Taiwan. These plants serve as resourceful bank for biologically active phytochemicals. Given that these plant-derived chemicals are prototypes of potential drugs for diseases, databases connecting the chemical structures and pharmacological activities may facilitate drug development. To enhance the utility of the data, it is desirable to develop a database of chemical compounds and corresponding activities from indigenous plants in Taiwan. A database of anticancer, antiplatelet, and antituberculosis phytochemicals from indigenous plants in Taiwan was constructed. The database, TIPdb, is composed of a standardized format of published anticancer, antiplatelet, and antituberculosis phytochemicals from indigenous plants in Taiwan. A browse function was implemented for users to browse the database in a taxonomy-based manner. Search functions can be utilized to filter records of interest by botanical name, part, chemical class, or compound name. The structured and searchable database TIPdb was constructed to serve as a comprehensive and standardized resource for anticancer, antiplatelet, and antituberculosis compounds search. The manually curated chemical structures and activities provide a great opportunity to develop quantitative structure-activity relationship models for the high-throughput screening of potential anticancer, antiplatelet, and antituberculosis drugs.

Dual antiplatelet treatment in patients candidates for abdominal surgery.

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Illuminati, Giulio; Ceccanei, Gianluca; Pacilè, Maria A; Pizzardi, Giulia; Palumbo, Piergaspare; Vietri, Francesco

2013-01-01

With the increasing diffusion of percutaneous interventions (PCI), surgeons are often faced with the problem of operating on patients under dual antiplatelet treatment. Replacing dual antiplatelet regiment with low molecular weight heparin may expose to the abrupt thrombosis of coronary stent and massive myocardial infarction. The purpose of this study was to test the hypothesis that abdominal operations can be safely performed under dual antiplatelet treatment. Eleven patients underwent 5 colectomies, 3 nefrectomies, 2 gastrectomies and 1 hysterectomy under aspirin and plavix without any significant perioperative hemorrhage. These preliminary results show that abdominal operations can be safely performed under dual antiplatelet regimen. Abdominal surgery, Dual antiplatelet treatment.

Application of Feedback System Control Optimization Technique in Combined Use of Dual Antiplatelet Therapy and Herbal Medicines

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Wang Liu

2018-05-01

Full Text Available Aim: Combined use of herbal medicines in patients underwent dual antiplatelet therapy (DAPT might cause bleeding or thrombosis because herbal medicines with anti-platelet activities may exhibit interactions with DAPT. In this study, we tried to use a feedback system control (FSC optimization technique to optimize dose strategy and clarify possible interactions in combined use of DAPT and herbal medicines.Methods: Herbal medicines with reported anti-platelet activities were selected by searching related references in Pubmed. Experimental anti-platelet activities of representative compounds originated from these herbal medicines were investigated using in vitro assay, namely ADP-induced aggregation of rat platelet-rich-plasma. FSC scheme hybridized artificial intelligence calculation and bench experiments to iteratively optimize 4-drug combination and 2-drug combination from these drug candidates.Results: Totally 68 herbal medicines were reported to have anti-platelet activities. In the present study, 7 representative compounds from these herbal medicines were selected to study combinatorial drug optimization together with DAPT, i.e., aspirin and ticagrelor. FSC technique first down-selected 9 drug candidates to the most significant 5 drugs. Then, FSC further secured 4 drugs in the optimal combination, including aspirin, ticagrelor, ferulic acid from DangGui, and forskolin from MaoHouQiaoRuiHua. Finally, FSC quantitatively estimated the possible interactions between aspirin:ticagrelor, aspirin:ferulic acid, ticagrelor:forskolin, and ferulic acid:forskolin. The estimation was further verified by experimentally determined Combination Index (CI values.Conclusion: Results of the present study suggested that FSC optimization technique could be used in optimization of anti-platelet drug combinations and might be helpful in designing personal anti-platelet therapy strategy. Furthermore, FSC analysis could also identify interactions between different

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.

Antiplatelet Activity of Morus alba Leaves Extract, Mediated via Inhibiting Granule Secretion and Blocking the Phosphorylation of Extracellular-Signal-Regulated Kinase and Akt

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Rhee, Man Hee; Sung, Yoon-Young; Yang, Won-Kyung; Kim, Seung Hyung; Kim, Ho-Kyoung

2014-01-01

Ethnopharmacological Relevance. Morus alba L. leaves (MAE) have been used in fork medicine for the treatment of beriberi, edema, diabetes, hypertension, and atherosclerosis. However, underlying mechanism of MAE on cardiovascular protection remains to be elucidated. Therefore, we investigated whether MAE affect platelet aggregation and thrombosis. Materials and Methods. The anti-platelet activity of MAE was studied using rat platelets. The extent of anti-platelet activity of MAE was assayed in collagen-induced platelet aggregation. ATP and serotonin release was carried out. The activation of integrin α IIb β 3 and phosphorylation of signaling molecules, including MAPK and Akt, were investigated with cytofluorometer and immunoblotting, respectively. The thrombus formation in vivo was also evaluated in arteriovenous shunt model of rats. Results. HPLC chromatographic analysis revealed that MAE contained rutin and isoquercetin. MAE dose-dependently inhibited collagen-induced platelet aggregation. MAE also attenuated serotonin secretion and thromboxane A2 formation. In addition, the extract in vivo activity showed that MAE at 100, 200, and 400 mg/kg significantly and dose-dependently attenuated thrombus formation in rat arterio-venous shunt model by 52.3% (P < 0.001), 28.3% (P < 0.01), and 19.1% (P < 0.05), respectively. Conclusions. MAE inhibit platelet activation, TXB2 formation, serotonin secretion, aggregation, and thrombus formation. The plant extract could be considered as a candidate to anti-platelet and antithrombotic agent. PMID:24701244

Antiplatelet activity of Allium ursinum and Allium sativum.

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Hiyasat, Bahi; Sabha, Dina; Grotzinger, Kristina; Kempfert, Joerg; Rauwald, Johann-Wilhelm; Mohr, Friedrich-Wilhelm; Dhein, Stefan

2009-01-01

Garlic (Allium sativum) has a well-established reputation as a protective agent against cardiovascular disease, while nearly nothing is known about its cousin Allium ursinum. The aim of this study was to evaluate the antiaggregatory mechanism of garlic and to compare the effects of A. ursinum and A. sativum. In a prospective study, extracts were prepared from A. sativum powder made from fresh A. sativum bulbs and fresh A. ursinum leaves by maceration. The extracts were characterized by thin layer chromatography. Their in vitro effects on human platelet aggregation were examined by light transmission aggregometry after induction by adenosine diphosphate (ADP), collagen, A23187, epinephrine and arachidonic acid (ARA) in platelets from healthy volunteers. A. ursinum and A. sativum exert similar antiaggregatory effects: they inhibit platelet aggregation induced via the ADP pathway and to a lesser extent aggregation induced by epinephrine, whereas ARA-, collagen- and A23187-induced aggregation was not affected. It became clear that the alcoholic extract of A. ursinum is the potent form, while the aqueous extract exerted an unspecific activity. The effects were strictly dose related. A. ursinum and A. sativum extracts exhibited similar potencies. Both A. ursinum and A. sativum exert antiaggregatory effects. Garlic extracts are acting by inhibition of the ADP pathway; their mechanisms of action are comparable to that of the clinically used drug clopidogrel. The pharmacologically active component of the extracts appears to be lipophilic rather than hydrophilic, but the precise chemical substance is still unknown. This is the first report on the antiplatelet activity of A. ursinum. Copyright 2009 S. Karger AG, Basel.

Strokes attributable to underuse of warfarin and antiplatelets

DEFF Research Database (Denmark)

Olsen, Tom Skyhøj; Rasmussen, Berit Hammershaimb; Kammersgaard, Lars Peter

2007-01-01

atrial fibrillation, prior myocardial infarction, angina, or prior stroke transient ischemic attack (TIA). Sufficient information on cardiovascular risk factors before stroke was available in 404 patients. A total of 54 patients had atrial fibrillation known before the stroke. Of these, 16 had...... fibrillation could have been prevented if warfarin or antiplatelets had been given before stroke. A total of 147 patients had known stroke/TIA and/or myocardial infarction/angina before stroke (41 patients had not received antiplatelets on admission). If antiplatelet therapy had been given before stroke, 10...

ANTIPLATELET THERAPY IN THE PREVENTION OF CEREBROVASCULAR ACCIDENTS

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O. V. Rodionova

2017-01-01

Full Text Available Currently the problem of preventing cerebrovascular disorders, in which antiplatelet therapy takes one of the leading places, remains relevant. The efficiency of the therapy depends on a large number of modifiable and non-modifiable factors. There are many methods to assess the severity of the response to antiplatelet therapy, but there is no common approach to the assessment of the results and their prognostic significance. Further studies of this issue are essential with the aim of individualization of antiplatelet therapy thereby increasing its efficiency and safety.

Tailored antiplatelet therapy can overcome clopidogrel and aspirin resistance - The BOchum CLopidogrel and Aspirin Plan (BOCLA-Plan to improve antiplatelet therapy

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Pepinghege Fenena

2011-01-01

initial ALRs had an adequate antiplatelet response. The results for clopidogrel revealed that 69% of the CLR were treated effectively by increasing the clopidogrel dose to 150 mg daily. When prasugrel was not available or contraindicated, 12.7% of the remaining low responders showed an adequate result after being switched to ticlopidine. Consequently, by applying the therapy algorithm, we were able to reduce the CLR prevalence by 86.6%. On including prasugrel in the therapy plan, we were finally able to eliminate thienopyridine low response. In addition, no ADP receptor defect was found in this study as a potential reason for CLR. We identified the following factors associated with both CLR and ALR status: acute coronary syndromes, positive troponin values as well as diabetes mellitus and elevated HbA1C values and a higher platelet count. Furthermore, our data revealed for CLR elevated C-reactive protein values and a high PREDICT-score (including an age >65 years, acute coronary syndrome, diabetes mellitus, renal failure, and reduced left ventricular function as risk factors. The following factors correlated with the risk of ASA low response: patients with elevated hemoglobin, serum creatinine and C-reactive protein values. In addition, medication with nitrates reduced the risk of being CLR. As also holds true for CLR, we found the PREDICT-score to be correlated to the risk of being ALR. However, by far the strongest risk factor for CLR or ALR was the fact of dual resistance. Conclusion Following a structured therapy plan based on a "test and treat" strategy, the prevalence of clopidogrel or aspirin low response can be significantly reduced and the risk of inadequate dual antiplatelet therapy minimized. Trial Registration NCT01212302 (Clinicaltrials.gov

Static platelet adhesion, flow cytometry and serum TXB2 levels for monitoring platelet inhibiting treatment with ASA and clopidogrel in coronary artery disease: a randomised cross-over study

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Eriksson, Andreas C; Jonasson, Lena; Lindahl, Tomas L; Hedbäck, Bo; Whiss, Per A

2009-01-01

Background Despite the use of anti-platelet agents such as acetylsalicylic acid (ASA) and clopidogrel in coronary heart disease, some patients continue to suffer from atherothrombosis. This has stimulated development of platelet function assays to monitor treatment effects. However, it is still not recommended to change treatment based on results from platelet function assays. This study aimed to evaluate the capacity of a static platelet adhesion assay to detect platelet inhibiting effects of ASA and clopidogrel. The adhesion assay measures several aspects of platelet adhesion simultaneously, which increases the probability of finding conditions sensitive for anti-platelet treatment. Methods With a randomised cross-over design we evaluated the anti-platelet effects of ASA combined with clopidogrel as well as monotherapy with either drug alone in 29 patients with a recent acute coronary syndrome. Also, 29 matched healthy controls were included to evaluate intra-individual variability over time. Platelet function was measured by flow cytometry, serum thromboxane B2 (TXB2)-levels and by static platelet adhesion to different protein surfaces. The results were subjected to Principal Component Analysis followed by ANOVA, t-tests and linear regression analysis. Results The majority of platelet adhesion measures were reproducible in controls over time denoting that the assay can monitor platelet activity. Adenosine 5'-diphosphate (ADP)-induced platelet adhesion decreased significantly upon treatment with clopidogrel compared to ASA. Flow cytometric measurements showed the same pattern (r2 = 0.49). In opposite, TXB2-levels decreased with ASA compared to clopidogrel. Serum TXB2 and ADP-induced platelet activation could both be regarded as direct measures of the pharmacodynamic effects of ASA and clopidogrel respectively. Indirect pharmacodynamic measures such as adhesion to albumin induced by various soluble activators as well as SFLLRN-induced activation measured by flow

An investigation of the antiplatelet effects of succinobucol (AGI-1067).

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Houston, Stephanie A; Ugusman, Azizah; Gnanadesikan, Sukanya; Kennedy, Simon

2017-05-01

Succinobucol is a phenolic antioxidant with anti-inflammatory and antiplatelet effects. Given the importance of oxidant stress in modulating platelet-platelet and platelet-vessel wall interactions, the aim of this study was to establish if antioxidant activity was responsible for the antiplatelet activity of succinobucol. Platelet aggregation in response to collagen and adenosine diphosphate (ADP) was studied in rabbit whole blood and platelet-rich plasma using impedance aggregometry. The effect of oxidant stress on aggregation, platelet lipid peroxides, and vascular tone was studied by incubating platelets, washed platelets or preconstricted rabbit iliac artery rings respectively with a combination of xanthine and xanthine oxidase (X/XO). To study the effect of succinobucol in vivo, anaesthetized rats were injected with up to 150 mg/kg succinobucol and aggregation measured in blood removed 15 mins later. Succinobucol (10 -5 -10 -4 M) significantly attenuated platelet aggregation to collagen and ADP in whole blood and platelet-rich plasma. X/XO significantly increased aggregation to collagen and platelet lipid peroxides and this was reversed by succinobucol. Addition of X/XO to denuded rabbit iliac arteries caused a dose-dependent relaxation which was significantly inhibited by succinobucol. In vivo administration up to 150 mg/kg had no effect on heart rate or mean arterial blood pressure but significantly inhibited platelet aggregation to collagen ex vivo. In conclusion, succinobucol displays anti-platelet activity in rabbit and rat blood and reverses the increase in platelet aggregation in response to oxidant stress.

Patent Foramen Ovale Closure or Antiplatelet Therapy for Cryptogenic Stroke

DEFF Research Database (Denmark)

Søndergaard, Lars; Kasner, Scott E; Rhodes, John F

2017-01-01

BACKGROUND: The efficacy of closure of a patent foramen ovale (PFO) in the prevention of recurrent stroke after cryptogenic stroke is uncertain. We investigated the effect of PFO closure combined with antiplatelet therapy versus antiplatelet therapy alone on the risks of recurrent stroke and new...... brain infarctions. METHODS: In this multinational trial involving patients with a PFO who had had a cryptogenic stroke, we randomly assigned patients, in a 2:1 ratio, to undergo PFO closure plus antiplatelet therapy (PFO closure group) or to receive antiplatelet therapy alone (antiplatelet-only group......). Imaging of the brain was performed at the baseline screening and at 24 months. The coprimary end points were freedom from clinical evidence of ischemic stroke (reported here as the percentage of patients who had a recurrence of stroke) through at least 24 months after randomization and the 24-month...

NP-184[2-(5-methyl-2-furyl) benzimidazole], a novel orally active antithrombotic agent with dual antiplatelet and anticoagulant activities.

Science.gov (United States)

Kuo, Heng-Lan; Lien, Jin-Cherng; Chung, Ching-Hu; Chang, Chien-Hsin; Lo, Shyh-Chyi; Tsai, I-Chun; Peng, Hui-Chin; Kuo, Sheng-Chu; Huang, Tur-Fu

2010-06-01

The established antiplatelet and anticoagulant agents show beneficial effects in the treatment of thromboembolic diseases; however, these drugs still have considerable limitations. The effects of NP-184, a synthetic compound, on platelet functions, plasma coagulant activity, and mesenteric venule thrombosis in mice were investigated. NP-184 concentration-dependently inhibited the human platelet aggregation induced by collagen, arachidonic acid (AA), and U46619, a thromboxane (TX)A(2) mimic, with IC(50) values of 4.5 +/- 0.2, 3.9 +/- 0.1, and 9.3 +/- 0.5 microM, respectively. Moreover, NP-184 concentration-dependently suppressed TXA(2) formations caused by collagen and AA. In exploring effects of NP-184 on enzymes involved in TXA(2) synthesis, we found that NP-184 selectively inhibited TXA(2) synthase activity with an IC(50) value of 4.3 +/- 0.2 microM. Furthermore, NP-184 produced a right shift of the concentration-response curve of U46619, indicating a competitive antagonism on TXA(2)/prostaglandin H(2) receptor. Intriguingly, NP-184 also caused a concentration-dependent prolongation of the activated partial thromboplastin time (aPTT) with no changes in the prothrombin and thrombin time, indicating that it selectively impairs the intrinsic coagulation pathway. Oral administration of NP-184 significantly inhibited thrombus formation of the irradiated mesenteric venules in fluorescein sodium-treated mice without affecting the bleeding time induced by tail transection. However, after oral administration, NP-184 inhibited the ex vivo mouse platelet aggregation triggered by collagen and U46619 and also prolonged aPTT. Taken together, the dual antiplatelet and anticoagulant activities of NP-184 may have therapeutic potential as an oral antithrombotic agent in the treatment of thromboembolic disorders.

Protease-Activated Receptor 4 (PAR4): A Promising Target for Antiplatelet Therapy.

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Rwibasira Rudinga, Gamariel; Khan, Ghulam Jilany; Kong, Yi

2018-02-14

Cardiovascular diseases (CVDs) are currently among the leading causes of death worldwide. Platelet aggregation is a key cellular component of arterial thrombi and major cause of CVDs. Protease-activated receptors (PARs), including PAR1, PAR2, PAR3 and PAR4, fall within a subfamily of seven-transmembrane G-protein-coupled receptors (GPCR). Human platelets express PAR1 and PAR4, which contribute to the signaling transduction processes. In association with CVDs, PAR4 not only contributes to platelet activation but also is a modulator of cellular responses that serve as hallmarks of inflammation. Although several antiplatelet drugs are available on the market, they have many side effects that limit their use. Emerging evidence shows that PAR4 targeting is a safer strategy for preventing thrombosis and consequently may improve the overall cardiac safety profile. Our present review summarizes the PAR4 structural characteristics, activation mechanism, role in the pathophysiology of diseases and understanding the association of PAR4 targeting for improved cardiac protection. Conclusively, this review highlights the importance of PAR4 antagonists and its potential utility in different CVDs.

Synthesis and Antiplatelet Activity of Antithrombotic Thiourea Compounds: Biological and Structure-Activity Relationship Studies

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André Luiz Lourenço

2015-04-01

Full Text Available The incidence of hematological disorders has increased steadily in Western countries despite the advances in drug development. The high expression of the multi-resistance protein 4 in patients with transitory aspirin resistance, points to the importance of finding new molecules, including those that are not affected by these proteins. In this work, we describe the synthesis and biological evaluation of a series of N,N'-disubstituted thioureas derivatives using in vitro and in silico approaches. New designed compounds inhibit the arachidonic acid pathway in human platelets. The most active thioureas (compounds 3d, 3i, 3m and 3p displayed IC50 values ranging from 29 to 84 µM with direct influence over in vitro PGE2 and TXA2 formation. In silico evaluation of these compounds suggests that direct blockage of the tyrosyl-radical at the COX-1 active site is achieved by strong hydrophobic contacts as well as electrostatic interactions. A low toxicity profile of this series was observed through hemolytic, genotoxic and mutagenic assays. The most active thioureas were able to reduce both PGE2 and TXB2 production in human platelets, suggesting a direct inhibition of COX-1. These results reinforce their promising profile as lead antiplatelet agents for further in vivo experimental investigations.

Long-term use of antiplatelet drugs by stroke patients

DEFF Research Database (Denmark)

Ostergaard, Kamilla; Hallas, Jesper; Bak, Søren

2012-01-01

PURPOSE: Treatment with antiplatelet drugs is a key element of secondary stroke prevention. We investigated long-term antiplatelet drug use in stroke patients with a focus on non-persistence. METHODS: Population-based prescription register data were used to determine antiplatelet drug use...... the dosage of a previous prescription had run out, or within 180 days after discharge. Cox regression was used to identify risk factors for non-persistence. RESULTS: The cohort comprised 503 patients with ischaemic stroke discharged in 1999-2001. During follow-up (median 2.8 years, interquartile range 0......-persistent. Stroke severity was inversely associated with the risk of non-persistence [NIHSS score on admission 0-3 (reference); 4-6: hazard risk (HR) 0.87, 95 % confidence interval (CI) 0.61-1.25; 7+: HR 0.47, 95 % CI 0.29-0.74]. CONCLUSIONS: Long-term non-persistence with antiplatelet treatment was high and more...

In Vivo antiplatelet activity aggregation assay of bromelain fractionate by ethanol from extract pineapple core (Ananas comosus [l.] merr.)

Science.gov (United States)

Musfiroh, F. F.; Setiasih, S.; Handayani, S.; Hudiyono, S.; Ilyas, N. M.

2018-01-01

Processed fruit from pineapple is one of largest commodities tropical fruit production in Indonesia and will bring the waste from the skin and core. This study aims to isolate bromelain from the pineapple core (Ananas comusus) are purified by fractionation using ethanol and continued by activity test as an antiplatelets agent by in vivo method using white mice male ddy type with acetosal as positive control. Fractionation of crude enzyme bromelain with ethanol produces highest specific activity on ethanol 30-60% fraction (fraction 2) 3.107 Unit/mg and the protein content 61.25 mg with the degree of purity of 155 times compared to crude enzyme. Antiplatelet aggregation tests from in vivo method shows that faction of bromelain with doses 70 μg/KgBW, 140 μg/KgBW, and 210 μg/KgBW can increase a meaningful bleeding time. The highest percentage of increase shown by the isolate at a dose of 210 μg/KgBW in the amount of 515.10 ± 182.23%, when compared to aspirin (231.20 ± 140.66), the value is relatively higher.

The peri-operative management of anti-platelet therapy in elective, non-cardiac surgery.

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Alcock, Richard F; Naoum, Chris; Aliprandi-Costa, Bernadette; Hillis, Graham S; Brieger, David B

2013-07-31

Cardiovascular complications are important causes of morbidity and mortality in patients undergoing elective non-cardiac surgery, with adverse cardiac outcomes estimated to occur in approximately 4% of all patients. Anti-platelet therapy withdrawal may precede up to 10% of acute cardiovascular syndromes, with withdrawal in the peri-operative setting incompletely appraised. The aims of our study were to determine the proportion of patients undergoing elective non-cardiac surgery currently prescribed anti-platelet therapy, and identify current practice in peri-operative management. In addition, the relationship between management of anti-platelet therapy and peri-operative cardiac risk was assessed. We evaluated consecutive patients attending elective non-cardiac surgery at a major tertiary referral centre. Clinical and biochemical data were collected and analysed on patients currently prescribed anti-platelet therapy. Peri-operative management of anti-platelet therapy was compared with estimated peri-operative cardiac risk. Included were 2950 consecutive patients, with 516 (17%) prescribed anti-platelet therapy, primarily for ischaemic heart disease. Two hundred and eighty nine (56%) patients had all anti-platelet therapy ceased in the peri-operative period, including 49% of patients with ischaemic heart disease and 46% of patients with previous coronary stenting. Peri-operative cardiac risk score did not influence anti-platelet therapy management. Approximately 17% of patients undergoing elective non-cardiac surgery are prescribed anti-platelet therapy, the predominant indication being for ischaemic heart disease. Almost half of all patients with previous coronary stenting had no anti-platelet therapy during the peri-operative period. The decision to cease anti-platelet therapy, which occurred commonly, did not appear to be guided by peri-operative cardiac risk stratification. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Protease-Activated Receptor 4 (PAR4: A Promising Target for Antiplatelet Therapy

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Gamariel Rwibasira Rudinga

2018-02-01

Full Text Available Cardiovascular diseases (CVDs are currently among the leading causes of death worldwide. Platelet aggregation is a key cellular component of arterial thrombi and major cause of CVDs. Protease-activated receptors (PARs, including PAR1, PAR2, PAR3 and PAR4, fall within a subfamily of seven-transmembrane G-protein-coupled receptors (GPCR. Human platelets express PAR1 and PAR4, which contribute to the signaling transduction processes. In association with CVDs, PAR4 not only contributes to platelet activation but also is a modulator of cellular responses that serve as hallmarks of inflammation. Although several antiplatelet drugs are available on the market, they have many side effects that limit their use. Emerging evidence shows that PAR4 targeting is a safer strategy for preventing thrombosis and consequently may improve the overall cardiac safety profile. Our present review summarizes the PAR4 structural characteristics, activation mechanism, role in the pathophysiology of diseases and understanding the association of PAR4 targeting for improved cardiac protection. Conclusively, this review highlights the importance of PAR4 antagonists and its potential utility in different CVDs.

Static platelet adhesion, flow cytometry and serum TXB2 levels for monitoring platelet inhibiting treatment with ASA and clopidogrel in coronary artery disease: a randomised cross-over study

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Hedbäck Bo

2009-06-01

Full Text Available Abstract Background Despite the use of anti-platelet agents such as acetylsalicylic acid (ASA and clopidogrel in coronary heart disease, some patients continue to suffer from atherothrombosis. This has stimulated development of platelet function assays to monitor treatment effects. However, it is still not recommended to change treatment based on results from platelet function assays. This study aimed to evaluate the capacity of a static platelet adhesion assay to detect platelet inhibiting effects of ASA and clopidogrel. The adhesion assay measures several aspects of platelet adhesion simultaneously, which increases the probability of finding conditions sensitive for anti-platelet treatment. Methods With a randomised cross-over design we evaluated the anti-platelet effects of ASA combined with clopidogrel as well as monotherapy with either drug alone in 29 patients with a recent acute coronary syndrome. Also, 29 matched healthy controls were included to evaluate intra-individual variability over time. Platelet function was measured by flow cytometry, serum thromboxane B2 (TXB2-levels and by static platelet adhesion to different protein surfaces. The results were subjected to Principal Component Analysis followed by ANOVA, t-tests and linear regression analysis. Results The majority of platelet adhesion measures were reproducible in controls over time denoting that the assay can monitor platelet activity. Adenosine 5'-diphosphate (ADP-induced platelet adhesion decreased significantly upon treatment with clopidogrel compared to ASA. Flow cytometric measurements showed the same pattern (r2 = 0.49. In opposite, TXB2-levels decreased with ASA compared to clopidogrel. Serum TXB2 and ADP-induced platelet activation could both be regarded as direct measures of the pharmacodynamic effects of ASA and clopidogrel respectively. Indirect pharmacodynamic measures such as adhesion to albumin induced by various soluble activators as well as SFLLRN

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

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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

24-hour antiplatelet effect of aspirin in patients with previous definite stent thrombosis

DEFF Research Database (Denmark)

Würtz, Morten; Hvas, Anne-Mette; Jensen, Lisette O

2014-01-01

OBJECTIVE: Once-daily aspirin is standard treatment, but recent studies point towards increased platelet function at the end of the dosing interval. Stent thrombosis (ST) has been linked with reduced antiplatelet effect of aspirin, so we investigated if platelet inhibition by aspirin declines...... with 100 patients with stable coronary artery disease and 50 healthy volunteers. All participants were on aspirin 75 mg/day mono antiplatelet therapy. Platelet aggregation was measured 1 and 24 h after aspirin intake using platelet aggregometry (Multiplate® Analyzer). Cyclooxygenase-1 activity, platelet...... activation, immature platelets, and thrombopoietin were measured. RESULTS: Platelet aggregation increased by 109±150 (arachidonic acid) and 47±155 (collagen) aggregation units per minute from 1 to 24 h after aspirin intake (p-values

Prospective observational study of the effect of dual antiplatelet therapy with tranexamic acid treatment on platelet function and bleeding after cardiac surgery.

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Amour, J; Garnier, M; Szymezak, J; Le Manach, Y; Helley, D; Bertil, S; Ouattara, A; Riou, B; Gaussem, P

2016-12-01

The bleeding impact of dual antiplatelet therapy (DAPT), aspirin and clopidogrel, maintained until coronary artery bypass graft surgery (CABG), is still a matter of debate. The lack of preoperative antiplatelet activity measurement and heterogeneity of antifibrinolytic protocols in prior studies make the conclusions questionable. The aim of this prospective study was to determine, after preoperative antiplatelet activity measurement, if the maintenance of DAPT until CABG increases bleeding in patients treated with tranexamic acid (TA). This observational study included 150 consecutive patients, 89 treated with aspirin and 61 treated with DAPT, undergoing a first-time planned on-pump CABG with TA treatment. Antiplatelet activity was measured with platelet aggregation tests and quantification of VASP phosphorylation. Postoperative bleeding at 24 h was recorded and propensity score analysis was performed. Based on VASP assay, 54% of patients showed high on-clopidogrel platelet activity inhibition. Postoperative bleeding at 24 h increased by 22% in the DAPT group, compared with the aspirin group (680 [95% CI: 360-1670] vs 558 [95%CI: 267-1270] ml, P < 0.01), consistent with increased blood transfusion (21% vs 7%, P = 0.01); a higher incidence of mediastinitis did not reach statistical significance (15% vs 4%, P = 0.05). Bleeding correlated with the extent of clopidogrel antiplatelet effect, with the best correlation for the VASP assay. Maintenance of DAPT until the day of CABG in patients treated with TA, increased postoperative bleeding at 24 h in parallel with preoperative antiplatelet activity induced by clopidogrel. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cost-effectiveness of oral antiplatelet agents--current and future perspectives.

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Arnold, Suzanne V; Cohen, David J; Magnuson, Elizabeth A

2011-08-09

Cardiovascular disease is both highly prevalent and exceedingly costly to treat. Several novel antiplatelet agents have been found to be effective in reducing the morbidity and mortality associated with cardiovascular disease. Understanding both the economic and the clinical implications of these novel therapies is particularly important. In this article, the results of published evaluations of the cost-effectiveness of oral antiplatelet strategies for use across a range of clinical conditions and treatment settings are reviewed. The results of these studies support the use of aspirin for primary prevention in high-risk patients and for secondary prevention in all patients with previous cardiovascular events. Although the optimal duration of dual antiplatelet therapy after an event remains uncertain, favorable cost-effectiveness estimates have been demonstrated for aspirin plus clopidogrel versus aspirin alone after a myocardial infarction or percutaneous coronary intervention. Moreover, prasugrel has been shown to be more cost-effective than clopidogrel for patients with an acute coronary syndrome and planned percutaneous coronary intervention. As novel antiplatelet agents emerge and existing agents are tested in different patient populations, the evaluation of the relative economic efficiency of these oral antiplatelet treatment strategies will continue to be instrumental to optimally inform clinical and health-policy decision-making.

Pattern and predictors of dual antiplatelet use after coronary artery bypass graft surgery.

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Mori, Makoto; Shioda, Kayoko; Yun, James J; Mangi, Abeel A; Darr, Umer; Geirsson, Arnar

2018-02-01

Resumption of dual antiplatelet therapy after coronary artery bypass grafting in patients presenting with acute coronary syndrome is recommended, but the current practice pattern in the United States remains unknown. We aimed to investigate the current pattern of dual antiplatelet therapy use after coronary artery bypass grafting at the Yale-New Haven Hospital. We conducted a single-center retrospective review of patients who presented with acute coronary syndrome and underwent coronary artery bypass grafting between 2014 and 2016. The primary outcome was hospital discharge with dual antiplatelet therapy. Mixed-effect multivariate logistic regression was used to evaluate predictors of dual antiplatelet therapy use or nonuse, accounting for surgeon-specific preference. The discriminatory ability of the model was evaluated with receiver operating characteristics analysis. Of 572 patients included, only 29% were discharged with dual antiplatelet therapy. In the mixed-effect multivariate model isolating surgeon preferences, increase in age (odds ratio, 0.95; 95% confidence interval, 0.92-0.98; P dual antiplatelet therapy use. Off-pump coronary artery bypass grafting compared with on-pump coronary artery bypass grafting was associated with increased odds of dual antiplatelet therapy use (odds ratio, 31.5; 95% confidence interval, 12.8-77.2; P dual antiplatelet therapy use in patients with acute coronary syndrome who underwent coronary artery bypass grafting was low and variable among surgeons. The use or nonuse was guided by previously established risk factors of recurrent ischemia and bleeding, along with surgeon preference. Published by Elsevier Inc.

Urological surgery and antiplatelet drugs after cardiac and cerebrovascular accidents.

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Eberli, Daniel; Chassot, Pierre-Guy; Sulser, Tullio; Samama, Charles Marc; Mantz, Jean; Delabays, Alain; Spahn, Donat R

2010-06-01

The perioperative treatment of patients on dual antiplatelet therapy after myocardial infarction, cerebrovascular event or coronary stent implantation represents an increasingly frequent issue for urologists and anesthesiologists. We assess the current scientific evidence and propose strategies concerning treatment of these patients. A MEDLINE and PubMed search was conducted for articles related to antiplatelet therapy after myocardial infarction, coronary stents and cerebrovascular events, as well as the use of aspirin and/or clopidogrel in the context of surgery. Early discontinuation of antiplatelet therapy for secondary prevention is associated with a high risk of coronary thrombosis, which is further increased by the hypercoagulable state induced by surgery. Aspirin has recently been recommended as a lifelong therapy. Clopidogrel is mandatory for 6 weeks after myocardial infarction and bare metal stents, and for 12 months after drug-eluting stents. Surgery must be postponed beyond these waiting periods or performed with patients receiving dual antiplatelet therapy because withdrawal therapy increases 5 to 10 times the risk of postoperative myocardial infarction, stent thrombosis or death. The shorter the waiting period between revascularization and surgery the greater the risk of adverse cardiac events. The risk of surgical hemorrhage is increased approximately 20% by aspirin and 50% by clopidogrel. The risk of coronary thrombosis when antiplatelet agents are withdrawn before surgery is generally higher than the risk of surgical hemorrhage when antiplatelet agents are maintained. However, this issue has not yet been sufficiently evaluated in urological patients and in many instances during urological surgery the risk of bleeding can be dangerous. A thorough dialogue among surgeon, cardiologist and anesthesiologist is essential to determine all risk factors and define the best possible strategy for each patient. Copyright 2010 American Urological Association

Comparison of antiplatelet activity of garlic tablets with cardio-protective dose of aspirin in healthy volunteers: a randomized clinical trial

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Mojtaba Shafiekhani

2016-08-01

Full Text Available Objective: Some of the adverse effects of aspirin including peptic ulcers, gastrointestinal bleeding and aspirin resistance compelled researchers to find a suitable alternative with fewer adverse effects. In this clinical trial, we aimed to find the effective antiplatelet dose of garlic. Materials and Methods: This randomized controlled clinical trial (RCT was conducted on 62 healthy volunteers of 20-50 years old. All volunteers used 80 mg aspirin per day for 1 week and at the end of this time, platelet aggregation (PA induced by 4 agonists acting in aggregation pathway including adenosinediphosphate (20 μmol/l, epinephrine (20 μmol/l, collagen(0.19 mg/ ml and arachidonic acid (0.5mg/ ml was measured by Light Transmittance Aggregometry (LTA in all participants. After one month washout period, volunteers were randomized into 3 groups and each received 1, 2 or 3 garlic tablets (1250 mg a day for 1 month. After one month, PA was examined in all groups. Results: The mean ±SD of the age of all volunteers was 28.60 ± 9.00 years. In addition, 52.00 % of our volunteers were male and 48.00% of them were female. Garlic tablet didnot have significant effect on PA at any dose. However, 30% of volunteers in the group that used 3 garlic tablets/day reported adverse effect (i.e. bleeding. No significant association between sex, age and PA was observed. Conclusion:  In this study, we were unable to determine the effective anti-platelet dose of garlic which that could be equal to that of aspirin anti-platelet activity, as assessed LTA method.

Mauritia flexuosa Presents In Vitro and In Vivo Antiplatelet and Antithrombotic Activities

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Eduardo Fuentes

2013-01-01

Full Text Available Fruit from the palm Mauritia flexuosa is one of the most important species in Peru, Venezuela, Brazil, Colombia, Bolivia, and Guyana. The present study aimed to investigate the antiplatelet and antithrombotic activities of oil extracted from Mauritia flexuosa. The fatty acid contents were determined by gas chromatography—mass spectrometry. Oil extract of peel of Mauritia flexuosa was extracted by soxhlet extraction. The oil extract inhibited platelet secretion and aggregation induced by ADP, collagen, and TRAP-6 by a concentration-dependent way (0.1 to 1 mg/mL without the participation of the adenylyl cyclase pathway and diminished platelet rolling and firm adhesion under flow conditions. Furthermore, the oil extract induced a marked increase in the rolling speed of leukocytes retained on the platelet surface, reflecting a reduction of rolling and less adhesion. At the concentrations used, the oil extract significantly decreased platelet release of sP-selectin, an atherosclerotic-related inflammatory mediator. Oil extract inhibited thrombus growth at the same concentration as that of aspirin, a classical reference drug. Finally, the data presented herein also demonstrate for the first time to our knowledge the protective effect of oil extracted from Mauritia flexuosa on platelet activation and thrombosis formation.

Discovery and antiplatelet activity of a selective PI3Kβ inhibitor (MIPS-9922).

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Zheng, Zhaohua; Pinson, Jo-Anne; Mountford, Simon J; Orive, Stephanie; Schoenwaelder, Simone M; Shackleford, David; Powell, Andrew; Nelson, Erin M; Hamilton, Justin R; Jackson, Shaun P; Jennings, Ian G; Thompson, Philip E

2016-10-21

A series of amino-substituted triazines were developed and examined for PI3Kβ inhibition and anti-platelet function. Structural adaptations of a morpholine ring of the prototype pan-PI3K inhibitor ZSTK474 yielded PI3Kβ selective compounds, where the selectivity largely derives from an interaction with the non-conserved Asp862 residue, as shown by site directed mutagenesis. The most PI3Kβ selective inhibitor from the series was studied in detail through a series of in vitro and in vivo functional studies. MIPS-9922, 10 potently inhibited ADP-induced washed platelet aggregation. It also inhibited integrin αIIbβ3 activation and αIIbβ3 dependent platelet adhesion to immobilized vWF under high shear. It prevented arterial thrombus formation in the in vivo electrolytic mouse model of thrombosis without inducing prolonged bleeding or excess blood loss. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Is anti-platelet therapy interruption a real clinical issue? Its implications in dentistry and particularly in periodontics

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Kumar A

2009-01-01

Full Text Available The use of anti-platelet therapy has reduced the mortality and morbidity of cardiovascular disease remarkably. A considerable number of patients presenting before a dentist or periodontist give a history of anti-platelet therapy. A clinical dilemma whether to discontinue the anti-platelet therapy or continue the same always confronts the practitioner. Diverse opinions exist regarding the management of such patients. While one group of researchers advise continuation of anti-platelet therapy rather than invite remote, but possible, thromboembolic events, another group encourages discontinuation for variable periods. This study aims at reviewing the current rationale of anti-platelet therapy and the various options available to a clinician, with regard to the management of a patient under anti-platelet therapy. Current recommendations and consensus favour no discontinuation of anti-platelet therapy. This recommendation, however, comes with a rider to use caution and consider other mitigating factors as well. With a large number of patients giving a history of anti-platelet therapy, the topic is of interest and helps a clinician to arrive at a decision.

SERUM PARAOXONASE ACTIVITY IN RENAL TRANSPLANT RECIPIENTS

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Saritha Gadicherla

2017-12-01

Full Text Available BACKGROUND Serum paraoxonase is an enzyme synthesised in the liver. It is known to prevent atherosclerosis by inhibiting oxidation of lowdensity lipoprotein. Renal transplant recipients have increased tendency for developing atherosclerosis and cardiovascular disease. Reduced activity of serum paraoxonase contributes to accelerated atherosclerosis and increased cardiovascular complications in these patients. The aim of this study was to estimate serum paraoxonase activity in renal transplant recipients and compare it with healthy controls. MATERIALS AND METHODS 30 renal transplant recipients and 30 age and sex matched healthy controls were taken for the study. Serum paraoxonase activity, blood urea, serum creatinine and uric acid were estimated in these groups. The serum paraoxonase activity was correlated with urea, creatinine and uric acid levels. RESULTS Serum paraoxonase activity was reduced in renal transplant recipients compared to healthy controls. There was a negative correlation between paraoxonase activity and the levels of urea, creatinine and uric acid levels. CONCLUSION In this study, the paraoxonase activity was reduced in renal transplant recipients compared to controls. The increased cardiovascular disease in these patients could be due to reduced paraoxonase activity.

Individual patient data meta-analysis of antiplatelet regimens after noncardioembolic stroke or TIA : Rationale and design

NARCIS (Netherlands)

Greving, Jacoba P.; Diener, Hans Christoph; Csiba, László; Hacke, Werner; Kappelle, L. Jaap; Koudstaal, Peter J.; Leys, Didier; Mas, Jean Louis; Sacco, Ralph L.; Sivenius, Juhani; Algra, Ale

2015-01-01

Background: The Cerebrovascular Antiplatelet Trialists' Collaborative Group was formed to obtain and analyze individual patient data from the major randomized trials of common antiplatelet regimens after cerebral ischemia. Although the risk of stroke can be reduced by antiplatelet drugs, there

Awareness of antiplatelet resistance in patient with repeated episodes of thrombotic events

Science.gov (United States)

Dalimunthe, N. N.; Hamonangan, R.; Antono, D.; Prasetya, I.; Rusdi, L.

2018-03-01

Antiplatelet has been the cornerstones management of acute coronary syndrome. However, numbers of patients on these agents had episodes of adverse cardiovascular events. A 65-year-old woman post cardiac coronary bypass surgery on dual antiplatelet therapy, Aspirin, and Clopidogrel underwent several episodes of thrombotic events despite good adhered to thedailyantiplatelet regimen.These recurrent events had led to clinical suspicious of antiplatelet resistance. Platelet function test was performed which indicates a poor platelet response to Clopidogrel. Clopidogrelwas discontinued and Ticagrelor was prescribed together with Aspirin. During two months of follow up, there is no episode of chest discomfort.

The clinical value of antiplatelet therapy for patients with hemorrhage after thrombolysis based on susceptibility-weighted imaging: A prospective pilot study

International Nuclear Information System (INIS)

Lu, Jing; Li, Yue-Hua; Li, Yong-Dong; Li, Ming-Hua; Zhao, Jun-Gong; Chen, Shi-Wen

2012-01-01

Purpose: To evaluate treatment decision-making based on susceptibility-weighted imaging (SWI) in patients with hemorrhage after thrombolysis. Materials and methods: One hundred and forty-six patients without intracranial hemorrhage on CT after receiving recombinant tissue plasminogen activator (rt-PA) were allocated to two groups: antiplatelets (n = 72), who received antiplatelet therapy 24 h after rt-PA for 10 days; and non-antiplatelets (n = 74), who received no antiplatelet therapy. Twenty-two patients with SWI-detected microbleeds (MBs) or hemorrhagic transformation (HT) in the antiplatelets group (Group A) and 28 with MB or HT in the non-antiplatelets group (Group B) were included in this study. Results: Sixteen patients had MB and six HT in Group A; 18 had MB, six HT, and four parenchymal hemorrhage (PH) in Group B. National Institutes of Health Stroke Scale (NIHSS) scores at 7 and 14 days and the Modified Rankin Scale (mRS) at 90 days post-rt-PA were significantly lower in Group B than in Group A, duration of hospitalization was significantly shorter, and the favorable outcome rate was higher at 90 days (P < 0.05). There were no other significant differences. SWI evaluation at 14 days revealed eight patients with MB, 11 HT, and three PH in Group A; in Group B, 16 had MB, five HT, and one PH, with resolution of hemorrhage in six patients. Conclusions: Treatment decision-making based on SWI in acute stroke after thrombolysis was validated by the significantly reduced NIHSS score after 7/14 days, improved outcome, and reduced mRS in hemorrhage patients without antiplatelet therapy.

Antiplatelet therapy in STEMI undergoing primary PCI, when, which one and how long.

Science.gov (United States)

Baralis, Giorgio; Rossini, Roberta; Musumeci, Giuseppe

2018-02-19

Reperfusion therapy for patients presenting with an acute ST-segment elevation myocardial infarction (STEMI) involves primary percutaneous coronary intervention (PPCI) and concomitant dual antiplatelet therapy (DAPT) with combination of a P2Y12 inhibitor and acetylsalicylic acid (ASA). Decision regarding DAPT can be challenging clinically in the modern era with the evolution of newer stents, more potent antiplatelet agents and novel anticoagulant drugs in addition to an older patient population with multiple comorbidities. This review outlines the currently available antiplatelet treatments, and their place within the therapeutic timeline of a patient presenting with STEMI.

Synthesis of Analogues of Gingerol and Shogaol, the Active Pungent Principles from the Rhizomes of Zingiber officinale and Evaluation of Their Anti-Platelet Aggregation Effects

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Shih, Hung-Cheng; Chern, Ching-Yuh; Kuo, Ping-Chung; Wu, You-Cheng; Chan, Yu-Yi; Liao, Yu-Ren; Teng, Che-Ming; Wu, Tian-Shung

2014-01-01

The present study was aimed at discovering novel biologically active compounds based on the skeletons of gingerol and shogaol, the pungent principles from the rhizomes of Zingiber officinale. Therefore, eight groups of analogues were synthesized and examined for their inhibitory activities of platelet aggregation induced by arachidonic acid, collagen, platelet activating factor, and thrombin. Among the tested compounds, [6]-paradol (5b) exhibited the most significant anti-platelet aggregation activity. It was the most potent candidate, which could be used in further investigation to explore new drug leads. PMID:24599082

Synthesis of Analogues of Gingerol and Shogaol, the Active Pungent Principles from the Rhizomes of Zingiber officinale and Evaluation of Their Anti-Platelet Aggregation Effects

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Hung-Cheng Shih

2014-03-01

Full Text Available The present study was aimed at discovering novel biologically active compounds based on the skeletons of gingerol and shogaol, the pungent principles from the rhizomes of Zingiber officinale. Therefore, eight groups of analogues were synthesized and examined for their inhibitory activities of platelet aggregation induced by arachidonic acid, collagen, platelet activating factor, and thrombin. Among the tested compounds, [6]-paradol (5b exhibited the most significant anti-platelet aggregation activity. It was the most potent candidate, which could be used in further investigation to explore new drug leads.

A review of the use of common antiplatelet agents in orthopaedic practice.

LENUS (Irish Health Repository)

Dineen, P F

2010-09-01

Antiplatelet agents are widely prescribed for the primary and secondary prevention of cardiovascular events. A common clinical problem facing orthopaedic and trauma surgeons is how to manage patients receiving these agents who require surgery, either electively or following trauma. The dilemma is to balance the risk of increased blood loss if the antiplatelet agents are continued peri-operatively against the risk of coronary artery\\/stent thrombosis and\\/or other vascular event if the drugs are stopped. The traditional approach of stopping these medications up to two weeks before surgery appears to pose significant danger to patients and may require review. This paper covers the important aspects regarding the two most commonly prescribed antiplatelet agents, aspirin and clopidogrel.

Ristocetin induces phosphorylated-HSP27 (HSPB1) release from the platelets of type 2 DM patients: Anti-platelet agent-effect on the release.

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Tokuda, Haruhiko; Kuroyanagi, Gen; Onuma, Takashi; Enomoto, Yukiko; Doi, Tomoaki; Iida, Hiroki; Otsuka, Takanobu; Ogura, Shinji; Iwama, Toru; Kojima, Kumi; Kozawa, Osamu

2018-04-01

It has been previously reported that HSP27 is released from platelets in type 2 diabetes mellitus (DM) patients according to phosphorylation. In the present study, we investigated the effect of ristocetin, a glycoprotein (GP)Ib/IX/V activator, on the release of HSP27 and the effect of anti-platelet agents, such as acetylsalicylic acid (ASA), on this release. Forty-six patients with type 2 DM were recruited, and classified into two groups depending on administration of anti-platelet agents, resulting in 31 patients without these agents (control group) and 15 patients with them (anti-platelet group). Ristocetin potently induced the aggregation of platelets in the two groups. Ristocetin-induced changes of the area under the curve of light transmittance and the ratio of the size of platelet aggregates in the anti-platelet group were slightly different from those in the control group. On the other hand, the levels of phosphorylated-HSP27 induced by ristocetin in the platelets from a patient of the anti-platelet group taking ASA were significantly lower than those from a patient of the control group. The levels of HSP27 release from the ristocetin-stimulated platelets were significantly correlated with the levels of phosphorylated-HSP27 in the platelets from patients in the two groups. The levels of HSP27 release and those of platelet-derived growth factor-AB (PDGF-AB) secretion stimulated by ristocetin in the anti-platelet group were lower than those in the control group. In addition, the levels of HSP27 release and those of PDGF-AB secretion stimulated by ADP in the anti-platelet group were lower than those in the control group. These results strongly suggest that anti-platelet agents inhibit the HSP27 release from platelets stimulated by ristocetin but not the aggregation in type 2 DM patients.

Microfluidic thrombosis under multiple shear rates and antiplatelet therapy doses.

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Melissa Li

Full Text Available The mainstay of treatment for thrombosis, the formation of occlusive platelet aggregates that often lead to heart attack and stroke, is antiplatelet therapy. Antiplatelet therapy dosing and resistance are poorly understood, leading to potential incorrect and ineffective dosing. Shear rate is also suspected to play a major role in thrombosis, but instrumentation to measure its influence has been limited by flow conditions, agonist use, and non-systematic and/or non-quantitative studies. In this work we measured occlusion times and thrombus detachment for a range of initial shear rates (500, 1500, 4000, and 10000 s(-1 and therapy concentrations (0-2.4 µM for eptifibatide, 0-2 mM for acetyl-salicylic acid (ASA, 3.5-40 Units/L for heparin using a microfluidic device. We also measured complete blood counts (CBC and platelet activity using whole blood impedance aggregometry. Effects of shear rate and dose were analyzed using general linear models, logistic regressions, and Cox proportional hazards models. Shear rates have significant effects on thrombosis/dose-response curves for all tested therapies. ASA has little effect on high shear occlusion times, even at very high doses (up to 20 times the recommended dose. Under ASA therapy, thrombi formed at high shear rates were 4 times more prone to detachment compared to those formed under control conditions. Eptifibatide reduced occlusion when controlling for shear rate and its efficacy increased with dose concentration. In contrast, the hazard of occlusion from ASA was several orders of magnitude higher than that of eptifibatide. Our results show similar dose efficacy to our low shear measurements using whole blood aggregometry. This quantitative and statistically validated study of the effects of a wide range of shear rate and antiplatelet therapy doses on occlusive thrombosis contributes to more accurate understanding of thrombosis and to models for optimizing patient treatment.

Mucorales species activation of a serum leukotactic factor.

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Marx, R S; Forsyth, K R; Hentz, S K

1982-01-01

Previous studies have suggested that the focal accumulation of phagocytic leukocytes is an important feature of the host response in mucormycosis. To ascertain the basis for this influx of inflammatory cells, we evaluated the effect of members of the order Mucorales, including species from the genera Rhizopus, Absidia, and Mucor, on the chemotactic activity of normal human serum for neutrophils and monocytes. Both hyphae and spores produced concentration-dependent chemotaxigenesis in serum to a maximum level equivalent to that produced by zymosan activation of serum. Chemotactic activity was similar for live and heat-killed hyphae. No leukotactic activity was demonstrated in the absence of serum. The pretreatment of serum with anti-C3 antibody, heating at 56 degrees C, or 0.01 M EDTA abolished the activity. The pretreatment of serum with 0.01 M ethylene glycol-bis(beta-aminoethyl ether)-N,N-tetraacetic acid did not abolish the activity. These data provide evidence that the leukotactic activity of Mucorales species is generated through the alternative complement pathway. PMID:6759409

Risk and benefit of dual antiplatelet treatment among non-revascularized myocardial infarction patients in different age groups.

Science.gov (United States)

Juul, Nikolai; Gislason, Gunnar; Olesen, Jonas Bjerring; Lamberts, Morten; Hansen, Morten Lock; Karasoy, Deniz; Christiansen, Christine Benn; Torp-Pedersen, Christian; Sorensen, Rikke

2017-09-01

Dual anti-platelet treatment with clopidogrel and aspirin is indicated for most patients after myocardial infarction. We examined the risk/benefit relationship of dual anti-platelet treatment according to age in a nationwide cohort of 30,532 myocardial infarction patients without revascularization. Patients admitted with first-time myocardial infarction in 2002-2010, not undergoing revascularization, were identified from nationwide Danish registers. Dual anti-platelet treatment use was assessed by claimed prescriptions. Stratified into age groups, risk of bleeding, all-cause mortality and a combined endpoint of cardiovascular death, recurrent myocardial infarction and ischaemic stroke was analysed by Cox proportional-hazard models and tested in a propensity-score matched population. A total of 21,302 users and 9230 non-users of dual anti-platelet treatment were included (mean age 67.02 (±13.8) years and 64.7% males). Use of dual anti-platelet treatment decreased with age: 80% (79 years). We found a reduced risk of cardiovascular death, recurrent myocardial infarction and ischaemic stroke in users 79 years (HR=0.92; 95% CI 0.84-1.01, NS). Risk of bleeding increased with dual anti-platelet treatment use in patients aged 79 years (HR=1.46; 95% CI 1.22-1.74). Similar tendencies in all four age groups were found in the propensity-matched population. Dual anti-platelet treatment use was less likely among elderly patients although similar effects regarding both risk and benefit were found in all age groups. Increased focus on initiating dual anti-platelet treatment in elderly, non-invasively treated myocardial infarction patients is warranted.

Update: Acute coronary syndromes (V). Personalized antiplatelet therapy.

Science.gov (United States)

Gurbel, Paul A; Rafeedheen, Rahil; Tantry, Udaya S

2014-06-01

It is well established that high on-treatment platelet reactivity to adenosine diphosphate during clopidogrel therapy is an independent risk factor for ischemic event occurrences in a postpercutaneous coronary intervention patients. However, the precise role of platelet function testing remains debated. Platelet function testing to ensure optimal platelet inhibition has been recommended by some authorities to improve outcomes in patients treated with clopidogrel. Recent prospective, randomized trials of personalized antiplatelet therapy have failed to demonstrate a benefit of platelet function testing in improving outcomes. In this review article, we discuss the mechanisms responsible for clopidogrel nonreponsiveness, recent trials of platelet function testing, and other new developments in the field of personalized antiplatelet therapy. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Serum paraoxonase 1 activity in dogs

DEFF Research Database (Denmark)

Rossi, Gabriele; Giordano, Alessia; Pezzia, Francesca

2013-01-01

Serum activity of paraoxonase (PON1) decreases during inflammation in many species. Little information is available on paraoxon-based tests and the possible role of PON1 in dogs.......Serum activity of paraoxonase (PON1) decreases during inflammation in many species. Little information is available on paraoxon-based tests and the possible role of PON1 in dogs....

Spontaneous subdural hematoma and antiplatelet therapy: Does efficacy of Ticagrelor come with added risk?

Directory of Open Access Journals (Sweden)

Pattanagere Manjunatha Suryanarayana Sharma

2015-12-01

Full Text Available Antiplatelet therapy has established clinical benefit on cardiovascular outcome and has reduced the rates of re-infarction/in stent thrombosis following percutaneous coronary intervention in acute coronary syndromes. Major bleeding episodes can occur with antiplatelet therapy and intracranial hemorrhage (ICH is one of the most feared complications resulting in significant morbidity and mortality. Identification of high risk groups and judicious use of antiplatelet therapy reduces the bleeding risk. Ticagrelor is a newer P2Y12 receptor antagonist with established clinical benefit. However, risks of having an ICH with these newer molecules cannot be ignored. Here, we report a case of spontaneous acute subdural hematoma developing in a patient on antiplatelet therapy with aspirin and ticagrelor. Early recognition, discontinuation of the medication and appropriate management resulted in resolution of hematoma and good clinical outcome. Authors have reviewed the antithrombotic drugs and their tendencies in causing intracranial bleeds from a neurophysicians perspective.

Elemental analysis of human serum and serum protein fractions by thermal neutron activation

International Nuclear Information System (INIS)

Woittiez, J.R.W.

1984-01-01

Some applications of thermal neutron activation for the determination of elemental contents in human serum and human serum protein fractions are presented. Firstly total serum is dealt with, secondly serum protein fractions obtained by gel filtration are described. A brief review on the role of (trace) elements in human health and disease and a compilation of literature data for elemental contents in human serum, as obtained by neutron activation techniques, are given. The most important sources of statistical and systematic errors are evaluated. Results for the contents of sodium, potassium, magnesium, bromine, iron, copper, zinc, selenium, rubidium, cesium and antimony in serum are given, with emphasis on control of accuracy and precision. The possible relation between selenium in blood and cancer occurrence in humans is discussed. The results of elemental analyses from cancer patients and from a patient receiving a cytostatic treatment are presented. A survey of literature results for the determination of protein-bound elemental contents in serum is presented. Subsequently, results from a study on the behaviour of elements during gel filtration are discussed. Gel-element and protein-element interactions are studied. Finally the protein-bound occurrence of trace elements in human serum is determined by gel filtration and neutron activation analysis. Results for both desalting and fractionation are given, for the elements bromine, copper, manganese, vanadium, selenium, zinc, rubidium, iron and iodine. (Auth.)

Antiplatelet therapy and the effects of B vitamins in patients with previous stroke or transient ischaemic attack: a post-hoc subanalysis of VITATOPS, a randomised, placebo-controlled trial.

Science.gov (United States)

Hankey, Graeme J; Eikelboom, John W; Yi, Qilong; Lees, Kennedy R; Chen, Christopher; Xavier, Denis; Navarro, Jose C; Ranawaka, Udaya K; Uddin, Wasim; Ricci, Stefano; Gommans, John; Schmidt, Reinhold

2012-06-01

Previous studies have suggested that any benefits of folic acid-based therapy to lower serum homocysteine in prevention of cardiovascular events might be offset by concomitant use of antiplatelet therapy. We aimed to establish whether there is an interaction between antiplatelet therapy and the effects of folic acid-based homocysteine-lowering therapy on major vascular events in patients with stroke or transient ischaemic attack enrolled in the vitamins to prevent stroke (VITATOPS) trial. In the VITATOPS trial, 8164 patients with recent stroke or transient ischaemic attack were randomly allocated to double-blind treatment with one tablet daily of placebo or B vitamins (2 mg folic acid, 25 mg vitamin B(6), and 500 μg vitamin B(12)) and followed up for a median 3·4 years (IQR 2·0-5·5) for the primary composite outcome of stroke, myocardial infarction, or death from vascular causes. In our post-hoc analysis of the interaction between antiplatelet therapy and the effects of treatment with B vitamins on the primary outcome, we used Cox proportional hazards regression before and after adjusting for imbalances in baseline prognostic factors in participants who were and were not taking antiplatelet drugs at baseline and in participants assigned to receive B vitamins or placebo. We also assessed the interaction in different subgroups of patients and different secondary outcomes. The VITATOPS trial is registered with ClinicalTrials.gov, number NCT00097669, and Current Controlled Trials, number ISRCTN74743444. At baseline, 6609 patients were taking antiplatelet therapy and 1463 were not. Patients not receiving antiplatelet therapy were more likely to be younger, east Asian, and disabled, to have a haemorrhagic stroke or cardioembolic ischaemic stroke, and to have a history of hypertension or atrial fibrillation. They were less likely to be smokers and to have a history of peripheral artery disease, hypercholesterolaemia, diabetes, ischaemic heart disease, and a

Evaluation of the antioxidant properties of N-acetylcysteine in human platelets: prerequisite for bioconversion to glutathione for antioxidant and antiplatelet activity.

Science.gov (United States)

Gibson, Kyle R; Neilson, Ilene L; Barrett, Fiona; Winterburn, Tim J; Sharma, Sushma; MacRury, Sandra M; Megson, Ian L

2009-10-01

N-Acetylcysteine (NAC) is a frequently used "antioxidant" in vitro, but the concentrations applied rarely correlate with those encountered with oral dosing in vivo. Here, we investigated the in vitro antioxidant and antiplatelet properties of NAC at concentrations (10-100 microM) that are achievable in plasma with tolerable oral dosing. The impact of NAC pretreatment (2 hours) on aggregation of platelets from healthy volunteers in response to thrombin and adenosine diphosphate and on platelet-derived nitric oxide (NO) was examined. NAC was found to be a weak reducing agent and a poor antioxidant compared with glutathione (reduced form) (GSH). However, platelets treated with NAC showed enhanced antioxidant activity and depression of reactive oxygen species generation associated with increases in intraplatelet GSH levels. An approximately 2-fold increase in NO synthase-derived nitrite was observed with 10 microM NAC treatment, but the effect was not concentration dependent. Finally, NAC significantly reduced both thrombin-induced and adenosine diphosphate-induced platelet aggregation. NAC should be considered a weak antioxidant that requires prior conversion to GSH to convey antioxidant and antithrombotic benefit at therapeutically relevant concentrations. Our results suggest that NAC might be an effective antiplatelet agent in conditions where increased oxidative stress contributes to heightened risk of thrombosis but only if the intraplatelet machinery to convert it to GSH is functional.

Apixaban with antiplatelet therapy after acute coronary syndrome

NARCIS (Netherlands)

Alexander, J.H.; Lopes, R.D.; James, S.; Kilaru, R.; He, Y.; Mohan, P.; Bhatt, D.L.; Goodman, S.; Verheugt, F.W.A.; Flather, M.; Huber, K.; Liaw, D.; Husted, S.E.; Lopez-Sendon, J.; De Caterina, R.; Jansky, P.; Darius, H.; Vinereanu, D.; Cornel, J.H.; Cools, F.; Atar, D.; Leiva-Pons, J.L.; Keltai, M.; Ogawa, H.; Pais, P.; Parkhomenko, A.; Ruzyllo, W.; Diaz, R.; White, H.; Ruda, M.; Geraldes, M.; Lawrence, J.; Harrington, R.A.; Wallentin, L.

2011-01-01

BACKGROUND: Apixaban, an oral, direct factor Xa inhibitor, may reduce the risk of recurrent ischemic events when added to antiplatelet therapy after an acute coronary syndrome. METHODS: We conducted a randomized, double-blind, placebo-controlled clinical trial comparing apixaban, at a dose of 5 mg

In vitro toxicity, antiplatelet and acetylcholinesterase inhibition of Buddleja thyrsoides Lam. leaves.

Science.gov (United States)

Mahlke, Janaína Dorneles; Boligon, Aline Augusti; Machado, Michel Mansur; Athayde, Margareth Linde

2012-01-01

Alzheimer's disease (AD) is a neurodegenerative disorder resulting in impaired memory and behaviour of remarkable socio-economic impact. A decrease in cholinergic activity is a key event in the biochemical of AD. Buddleja thyrsoides is a plant widely distributed in Southern parts of South America. In Brazilian traditional medicine, the infusion of its leaves and flowers is used for the treatment of bronchitis and cough. Crude ethanolic (70%) extract and fractions (dichloromethane, ethyl acetate and n-butanolic) were investigated regarding their toxicities in vitro and antiplatelet action. The enzyme acetylcholinesterase inhibition was evaluated to study the crude extract. The crude extract and fractions were evaluated by means of Brine Shrimp Lethality test and they showed low activities with LC(50) values 1698, 2818, 2187 and 3672 µg mL(-1) for dichloromethane, ethyl acetate, n-butanolic fractions and crude extract, respectively. Buddleja thyrsoides presented great antiplatelet action. The IC(50) values obtained for crude extract and dichloromethane, ethyl acetate and n-butanolic fractions were 361.29, 354.23, 368.75 and 344.30, respectively, while the IC(50) for the standard AAS was 257.01 µg mL(-1). The crude extract showed an inhibition of 22.8% of the acetylcholinesterase enzyme in 24 h.

Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients

NARCIS (Netherlands)

Baigent, C; Sudlow, C; Collins, R; Peto, R

2002-01-01

Objective To determine the effects of antiplatelet therapy among patients at high risk of occlusive vascular events. Design Collaborative meta-analyses (systematic overviews). Inclusion criteria Randomised trials of an antiplatelet regimen versus control or of one antiplatelet regimen versus another

Contemporary Parenteral Antiplatelet Bridging Strategies: A Single-Center Real-World Experience at a Tertiary Care Center.

Science.gov (United States)

Stern, Gretchen; Rimsans, Jessica; Qamar, Arman; Vaduganathan, Muthiah; Bhatt, Deepak L

2018-03-13

Oral antiplatelet therapy may require interruption soon after percutaneous coronary intervention (PCI) or acute coronary syndrome. The optimal parenteral antiplatelet bridge strategy with glycoprotein IIb/IIIa inhibitors or cangrelor, a P2Y12 inhibitor, is unclear. We explore real-world use of cangrelor or eptifibatide for antiplatelet bridging at a large tertiary-care center. Thirty-one patients (9 eptifibatide, 20 cangrelor, and 2 both) received bridge therapy from October 2015 to June 2017. Primary bridge therapy indications included surgery (68%), limited enteral access/absorption (16%), and high-perceived bleed risk (16%). Median duration of bridge therapy was 61 (20-100) hours for cangrelor and 83 (19-98) hours for eptifibatide. Severe/life-threatening bleeding or stent thrombosis was not observed. GUSTO-defined bleeding occurred in 30% (cangrelor) and 27% (eptifibatide). Initial dosing errors occurred in 23% of patients. Death during hospitalization occurred in 16% of patients. Parenteral antiplatelet bridging was used for ~3 days in this single-center, tertiary care experience, commonly for unplanned surgery following PCI. Despite high-risk presentations with >15% in-hospital mortality, efficacy profiles were reassuring with no identified stent thrombosis, but bleeding and dosing errors were common. Antiplatelet bridging should only be used in well-selected patients at the appropriate dose for the minimal necessary duration.

Titration of antiplatelet treatment in pregnant women at risk of preeclampsia.

Science.gov (United States)

Sullivan, M H; Clark, N A; de Swiet, M; Nelson-Piercy, C; Elder, M G

1998-04-01

We recruited 111 patients who were considered to be at significantly increased risk of preeclampsia on the basis of previous obstetric history or preexisting medical disorders. All patients were treated with low dose aspirin (75 mg/day) from the first occasion the patient attended the antenatal clinic, regardless of gestational age. If the maternal mean platelet volume (MPV) increased significantly (by > 0.8 fl) from the baseline, antiplatelet treatment was increased. Five pregnancies were lost during the second trimester and 106 of the treated patients had live infants. The incidence of neonatal death (3/106 infants) was much lower than in the previous pregnancies in these patients (32/134 infants). Patients who were treated from the first trimester of pregnancy (group A, 89 patients) did substantially better than those treated from the second trimester (group B, 17 patients) as assessed by the incidence of pre-eclampsia or intrauterine growth restriction (IUGR), gestational age and birthweight at delivery. These data suggest that longitudinal monitoring of the MPV may identify the women who could benefit from increased antiplatelet treatment, and that antiplatelet treatment may be more effective when initiated in the first trimester rather than later in pregnancy.

Discontinuation of antiplatelet treatment and risk of recurrent stroke and all-cause death

DEFF Research Database (Denmark)

Ostergaard, Kamilla; Pottegård, Anton; Hallas, Jesper

2014-01-01

use and followed them up for stroke recurrence, or all-cause death. Person-time was classified by antiplatelet drug use into current use, recent use (≤150 days after last use), and non-use (>150 days after last use). Lipid-lowering drug (LLD) use was classified by the same rules. We used Cox......BACKGROUND: We wished to examine the impact of antiplatelet drug discontinuation on recurrent stroke and all-cause mortality. METHODS: We identified a cohort of incident ischaemic stroke patients in a Danish stroke registry, 2007-2011. Using population-based registries we assessed subjects' drug...... proportional hazard models to calculate the adjusted hazard ratio (HR) and corresponding 95% confidence intervals (CIs) for the risk of recurrent stroke or death associated with discontinuation of antiplatelet or LLD drugs. RESULTS: Among 4,670 stroke patients followed up for up a median of 1.5 years, 237...

Hypolipidaemic and antiplatelet activity of phenoxyacetic acid derivatives related to alpha-asarone.

Science.gov (United States)

Pérez-Pastén, Ricardo; García, Rosa Virginia; Garduño, Leticia; Reyes, Elba; Labarrios, Fernando; Tamariz, Joaquín; Chamorro, Germán

2006-10-01

The phenoxyacetic acid derivatives 1-6 [2-methoxy-4-(2-propenyl)phenoxyacetic acid (1); 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetic acid (2); methyl 2-methoxy-4-(2-propenyl)phenoxyacetate (3); ethyl 2-methoxy-4-(2-propenyl)phenoxyacetate (4); methyl 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetate (5); ethyl 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetate (6)] related to alpha-asarone have been reported previously as hypolipidaemic agents in diet-induced hyperlipidaemic mice. We have aimed to expand the pharmacological profile of these derivatives by investigating their hypolipidaemic activity in rats and mice under different experimental conditions. The antiplatelet activity was tested also in-vitro from blood derived from consenting healthy volunteers. In normolipidaemic rats, compounds 2, 3 and 5 at oral doses of 40 and 80 mg kg(-1) significantly decreased total cholesterol and LDL-cholesterol levels. Moreover, analogues 3 and 5 administered to hypercholesterolaemic rats at the same doses for seven days also produced a reduction in the content of these same lipoproteins. In neither case were the high-density lipoprotein cholesterol and triglyceride concentrations affected. However, practically all tested compounds were found to be hypocholesterolaemic agents, and were shown to effectively lower low-density lipoprotein cholesterol and triglyceride levels in Triton-induced hyperlipidaemic mice at oral doses of 50 and 100 mg kg(-1). In all tests, all animals appeared to be healthy throughout the experimental period in their therapeutic ranges. Triton-induced hypercholesterolaemic mice appeared to be a desirable model for this class of hypolipidaemic drugs. On the other hand, compounds 1, 2, 4 and 5 significantly inhibited ADP-induced aggregation in-vitro. These findings indicated that all of these compounds appeared to be promising for the treatment of human hyperlipidaemia and thrombotic diseases.

Antiplatelet therapy and vascular disease: an update.

Science.gov (United States)

Buch, Mamta H; Prendergast, Bernard D; Storey, Robert F

2010-08-01

Atherosclerosis is a diffuse, systemic disorder of the large and medium-sized arterial vessels, affecting the coronary, cerebral and peripheral circulation. Chronic inflammatory processes are the central pathophysiological mechanism largely driven by lipid accumulation, and provide the substrate for occlusive thrombus formation. The clinical sequelae of acute arterial thrombosis, heart attack and stroke, are the most common causes of morbidity and mortality in the industrialized world. Such acute events are characterized by rupture or erosion of the atherosclerotic plaque leading to acute thrombosis. The atherosclerotic process and associated thrombotic complications are collectively termed atherothrombosis. The platelet is a pivotal mediator of various endothelial, immune, thrombotic and inflammatory responses and therefore a key player in the initiation and progression of atherothrombosis. A robust evidence base supports the clear clinical benefits of antiplatelet agents in the primary and secondary therapy of atherothrombotic disorders. Percutaneous coronary and peripheral interventions have an established central role in the management of atherothrombotic disease and demand a greater understanding of platelet biology. In this article, we provide a clinically orientated overview of the pathophysiology of arterial thrombosis and the evidence supporting the use of the various established antiplatelet therapies, and discuss new and future agents.

Iliac artery mural thrombus formation. Effect of antiplatelet therapy on 111In-platelet deposition in baboons

International Nuclear Information System (INIS)

Hanson, S.R.; Paxton, L.D.; Harker, L.A.

1986-01-01

To measure the rate, extent, and time course of arterial mural thrombus formation in vivo and to assess the effects of antiplatelet therapy in that setting, we have studied autologous 111 In-platelet deposition induced by experimental iliac artery aneurysms in baboons. Scintillation camera imaging analyses were performed at 1, 24, 48, and 72 hours after implantation of the device. Correction for tissue attenuation was determined by using a small, comparably located 111 In source implanted at the time of surgery. In five animals, 111 In-platelet activity accumulated progressively after device implantation, reaching a maximum after the third day. Repeat image analysis carried out 2 weeks after the surgical procedure also showed progressive accumulation of 111 In-platelets over 3 days but at markedly reduced amounts as compared with the initial study. In five additional animals, treatment with a combination of aspirin and dipyridamole begun 1 hour after surgical implantation reduced 111 In-platelet deposition to negligible levels by the third day. Although platelet survival time was shortened and platelet turnover was reciprocally increased in all operated animals, platelet survival and turnover were not affected by antiplatelet therapy. We conclude that, in contrast to platelet survival and turnover measurements, 111 In-platelet imaging is a reliable and sensitive method for localizing and quantifying focal arterial thrombi and for assessing the effects of antiplatelet therapy

HMG-CoA reductase inhibitors, other lipid-lowering medication, antiplatelet therapy, and the risk of venous thrombosis

NARCIS (Netherlands)

Ramcharan, A.S.; van Stralen, K.J.; Snoep, J.D.; Mantel-Teeuwisse, A.K.; Doggen, Catharina Jacoba Maria

2009-01-01

Background: Statins [3-hydroxymethyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors] and antiplatelet therapy reduce the risk of atherosclerotic disease. Besides a reduction of lipid levels, statins might also have antithrombotic and anti-inflammatory properties, and anti-platelet

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.

Spontaneous pulmonary hematoma in a patient with sepsis treated with dual antiplatelet therapy.

Science.gov (United States)

Vlaović, Janko; Voga, Gorazd

2016-12-01

A 72-year-old patient was admitted to the medical intensive care unit due to a right-sided, hospital-acquired pneumonia and septic shock with respiratory failure and deterioration of chronic renal failure. During hospitalization the patient required hemodynamic support with norepinephrine and dobutamine, mechanical ventilation and hemodialysis. The patient suffered a non-ST segment elevation myocardial infarction (NSTEMI) and received dual antiplatelet therapy. After 14 days an acute intrapulmonary infiltrate of unknown origin developed, accompanied by fever and a significant increase of the C‑reactive protein (CRP) level. Chest radiography and a computed tomography (CT) scan showed a well-defined, round, high-attenuation lesion in the lungs and a suspected infected pulmonary hematoma, which was confirmed by percutaneous aspiration biopsy. There was no evidence of trauma and it is believed that the hematoma occurred spontaneously, probably because of the dual antiplatelet therapy. Double antibiotic treatment was started but no surgery was performed after consultation with a thoracic surgeon. The antiplatelet drugs were temporarily withdrawn until the size of the hematoma showed no further increase and then antiplatelet therapy was continued. After stabilization the patient was discharged from hospital and 6 months later a follow-up chest X‑ray showed almost complete resolution of the hematoma.

Dentists' approach to patients on anti-platelet agents and warfarin: a survey of practice.

LENUS (Irish Health Repository)

Murphy, James

2010-04-23

In everyday practice, dentists are confronted with the dilemma of patients on anti-platelet agents and warfarin who require invasive dental procedures and, more pertinently, dental extractions. There may be a divergence of opinion among dentists regarding how they manage these patients. AIMS: To assess general dental practitioners\\' approach to the management of patients taking anti-platelet agents and\\/or warfarin who are undergoing invasive dental procedures. METHODS AND DATA: A semi-structured questionnaire was designed to survey general dental practitioners in a large Irish urban area. RESULTS: A response rate of 89% was achieved in a study population of 54 general dental practitioners. A total of 25% of respondents who carry out extractions on warfarinised patients do not check the INR prior to invasive dental procedures. Some 90% of respondents stop anti-platelet agents prior to extractions. CONCLUSIONS: A significant proportion of respondents fail to check warfarinised patients\\' INR prior to invasive dental procedures. Furthermore, a trend of stopping anti-platelet agents was noted, which is in contrast with current recommendations in the dental literature. Certain practices in this small study population proved alarming and highlight the need for improved awareness of current guidelines. A further large-scale study may be justified, as variation in practice may have clinical and medico-legal repercussions.

Subdural haematoma complicating shunting for normal pressure hydrocephalus in the setting of concomitant antiplatelet medication

DEFF Research Database (Denmark)

Birkeland, Peter; Lauritsen, Jens; Poulsen, Frantz Rom

2016-01-01

OBJECTIVE: To report on the occurrence and management of subdural haematoma after shunt implantation for normal pressure hydrocephalus and to determine the risk of recurrence in the setting of antiplatelet medication. METHODS: From a consecutive series of 80 patients implanted with a cerebrospinal...... fluid shunt for normal pressure hydrocephalus, records from 11 patients taking antiplatelet drugs, who subsequently had surgery for subdural haematoma were extracted and retrospectively reviewed. RESULTS: Patients were followed up for a mean of 1819 days after shunt implantation. Subdural haematomas...... reoperations done before the subdural collection disappeared. Only one patient had a late recurrence almost 11 years after shunt implantation. CONCLUSIONS: Subdural haematoma in the setting of a ventriculoperitoneal implantation for normal pressure hydrocephalus and concomitant antiplatelet medication can...

Serum amylase and lipase activities after exploratory laparotomy in dogs.

Science.gov (United States)

Bellah, J R; Bell, G

1989-09-01

Serum amylase and lipase activities and creatinine concentration were determined before surgery, and at 1 and 2 days after exploratory laparotomy in 24 dogs. Examination of all viscera was done during each laparotomy, but a surgical procedure was not performed. The mean serum activities for lipase were: before surgery, 0.71 (0.0 to 2.0) Cherry Crandall units (CCU)/L; 1 day after surgery, 2.1 (0.0 to 4.5) CCU/L; and 2 days after surgery, 1.19 (0.0 to 3.9) CCU/L. The mean serum activities for amylase were: before surgery, 1,958 (1,027 to 3,426) IU/L; 1 day after surgery, 1,538 (937 to 2,659) IU/L; and 2 days after surgery, 1,663 (1,066 to 2,274) IU/L. Serum creatinine concentrations before surgery, 1 day after surgery, and 2 days after surgery were 0.88 (0.2 to 1.7) mg/dl, 0.78 (0.4 to 1.3) mg/dl, and 0.78 (0.3 to 1.3) mg/dl, respectively. Mean preoperative, day-1, and day-2 serum amylase activities and serum creatinine concentrations did not differ significantly from each other. Mean preoperative and day-2 serum lipase activities did not differ significantly; however, mean serum lipase activity was significantly greater when day 1 activities were compared with preoperative activities (P = 0.0002). Post-mortem examinations revealed no gross or histologic evidence of pancreatitis in any dog. The results of this study show that a 3 or more fold increase in serum lipase activity may occur after routine exploratory laparotomy in dogs without clinical signs or gross evidence of pancreatitis. Histologic evidence of pancreatitis was not found in the right pancreatic lobes in any dog.

Dual Antiplatelet Therapy in Secondary Prevention of Ischemic Stroke: A Ghost from the Past or a New Frontier?

Directory of Open Access Journals (Sweden)

Clotilde Balucani

2010-01-01

Full Text Available With majority of ischemic strokes attributable to atherothrombosis and many being predictable after transient ischemic attacks (TIA, the role of early secondary prevention with antiplatelet agents is under renewed investigation. Prior major clinical trials of various secondary stroke prevention regimens pointed to a greater efficacy of dual antiplatelet agents if initiated early from symptom onset. This paper examines data and rationale behind dual antiplatelet regimens across the completed clinical trials. The safety of dual antiplatelets approach is of concern, but it could be outweighed, at least in early management, by a greater reduction in recurrence of ischemic events since this risk is “front loaded” after minor stroke or TIA. Aspirin monotherapy, though considered standard of care, is compared to aspirin-extended release dipiridamole and its combination with clopidogrel in early-phase completed and efficacy-phase ongoing clinical trials.

Antiplatelet therapy for recurrent stroke prevention: newer perspectives based on (MATCH), (CHARISMA), and (ESPRIT).

Science.gov (United States)

Gorelick, Philip B

2008-01-01

Antiplatelet therapy is an important component of our armamentarium for recurrent stroke prevention. Aspirin is a safe and effective antiplatelet drug for recurrent stroke prevention, however, it has been challenged recently by the thienopyridine derivative, clopidogrel, and the combination agent, aspirin plus extended release dipyridamole. In this review, we discuss recent studies of thienopyridine derivatives and aspirin plus extended-release dipyridamole in stroke prevention and evidence-based guidelines for the administration of these agents in practice for recurrent stroke prevention.

Current practice of antiplatelet and anticoagulation management in post-cardiac surgery patients: a national audit.

Science.gov (United States)

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.

Baseline characteristics of the 3096 patients recruited into the 'Triple Antiplatelets for Reducing Dependency after Ischemic Stroke' trial

DEFF Research Database (Denmark)

Bath, Philip Mw; Appleton, Jason P; Beridze, Maia

2017-01-01

Background The risk of recurrence following ischemic stroke or transient ischemic attack is highest immediately after the event. Antiplatelet agents are effective in reducing the risk of recurrence and two agents are superior to one in the early phase after ictus. Design The triple antiplatelets...

Activation of lipoprotein lipase by lipoprotein fractions of human serum.

Science.gov (United States)

Bier, D M; Havel, R J

1970-11-01

Triglycerides in fat emulsions are hydrolyzed by lipoprotein lipase only when they are "activated" by serum lipoproteins. The contribution of different lipoprotein fractions to hydrolysis of triglycerides in soybean oil emulsion was assessed by determining the quantity of lipoprotein fraction required to give half-maximal hydrolysis. Most of the activator property of whole serum from normolipidemic, postabsorptive subjects was in high density lipoproteins. Low density lipoproteins and serum from which all lipoprotein classes were removed had little or no activity. Also, little activator was present in guinea pig serum or in very low density poor serum from an individual with lecithin:cholesterol acyltransferase deficiency, both of which are deficient in high density lipoproteins. Human very low density lipoproteins are potent activators and are much more active than predicted from their content of high density lipoprotein-protein. Per unit weight of protein, very low density lipoproteins had 13 times the activity of high density lipoproteins. These observations suggest that one or more of the major apoproteins of very low density lipoproteins, present as a minor constituent of high density lipoproteins, may be required for the activation process.

Serum Renalase Levels Correlate with Disease Activity in Lupus Nephritis.

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Chaojun Qi

Full Text Available Lupus nephritis (LN is among the most serious complications of systemic lupus erythematosus (SLE, which causes significant morbidity and mortality. Renalase is a novel, kidney-secreted cytokine-like protein that promotes cell survival. Here, we aimed to investigate the relationship of serum renalase levels with LN and its role in the disease progression of LN.For this cross-sectional study, 67 LN patients and 35 healthy controls were enrolled. Seventeen active LN patients who received standard therapies were followed up for six months. Disease activity was determined by the SLE Disease Activity-2000 (SLEDAI-2K scoring system and serum renalase amounts were determined by ELISA. Predictive value of renalase for disease activity was assessed. Furthermore, the expression of renalase in the kidneys of patients and macrophage infiltration was assessed by immunohistochemistry.Serum renalase amounts were significantly higher in LN patients than in healthy controls. Moreover, patients with proliferative LN had more elevated serum renalase levels than Class V LN patients. In proliferative LN patients, serum renalase levels were significantly higher in patients with active LN than those with inactive LN. Serum renalase levels were positively correlated with SLEDAI-2K, 24-h urine protein excretion, ds-DNA and ESR but inversely correlated with serum albumin and C3. Renalase amounts decreased significantly after six-months of standard therapy. The performance of renalase as a marker for diagnosis of active LN was 0.906 with a cutoff value of 66.67 μg/ml. We also observed that the amount of renalase was significantly higher in glomerular of proliferative LN along with the co-expression of macrophages.Serum renalase levels were correlated with disease activity in LN. Serum renalase might serve as a potential indicator for disease activity in LN. The marked increase of glomerular renalase and its association with macrophages suggest that it might play an

Antiplatelet Regimen for Patients With Breakthrough Strokes While on Aspirin: A Systematic Review and Meta-Analysis.

Science.gov (United States)

Lee, Meng; Saver, Jeffrey L; Hong, Keun-Sik; Rao, Neal M; Wu, Yi-Ling; Ovbiagele, Bruce

2017-09-01

Optimal antiplatelet therapy after an ischemic stroke or transient ischemic attack while on aspirin is uncertain. We, therefore, conducted a systematic review and meta-analysis. We searched PubMed (1966 to August 2016) and bibliographies of relevant published original studies to identify randomized trials and cohort studies reporting patients who were on aspirin at the time of an index ischemic stroke or transient ischemic attack and reported hazard ratio for major adverse cardiovascular events or recurrent stroke associated with a switch to or addition of another antiplatelet agent versus maintaining aspirin monotherapy. Estimates were combined using a random effects model. Five studies with 8723 patients with ischemic stroke or transient ischemic attack were identified. Clopidogrel was used in 4 cohorts, and ticagrelor was used in 1 cohort. Pooling results showed that addition of or a switch to another antiplatelet agent, versus aspirin monotherapy, was associated with reduced risks of major adverse cardiovascular events (hazard ratio, 0.68; 95% confidence interval, 0.54-0.85) and recurrent stroke (hazard ratio, 0.70; 95% confidence interval, 0.54-0.92). Each of the strategies of addition of and switching another antiplatelet agent showed benefit versus continued aspirin monotherapy, and studies with regimen initiation in the first days after index event showed more homogenous evidence of benefit. Among patients who experience an ischemic stroke or transient ischemic attack while on aspirin monotherapy, the addition of or a switch to another antiplatelet agent, especially in the first days after index event, is associated with fewer future vascular events, including stroke. © 2017 American Heart Association, Inc.

Trends in Ambulatory Prescribing of Antiplatelet Therapy among US Ischemic Stroke Patients: 2000–2007

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Sudeep Karve

2012-01-01

Full Text Available Objective. Study objectives were to assess temporal trends and identify patient- and practice-level predictors of the prescription of antiplatelet medications in a national sample of ischemic stroke (IS patients seeking ambulatory care. Methods. IS-related outpatient visits by adults were identified using the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey for the years 2000–2007. We assessed prescribing of antiplatelet medications using the generic drug code and drug entry codes in these data. Temporal trends in antiplatelet prescribing were assessed using the Cochran-Mantel-Haenszel test for trend. Results. We identified 9.5 million IS-related ambulatory visits. Antiplatelet medications were prescribed at 35.5% of visits. Physician office prescribing of the clopidogrel-aspirin combination increased significantly from 0.5% in 2000 to 22.0% in 2007 (P=0.05, whereas prescribing of aspirin decreased from 17.9% to 7.0% (P=0.50 during the same period. Conclusion. We observed a continued increase in prescription of the aspirin-clopidogrel combination from 2000 to 2007. Clinical trial evidence suggests that the aspirin-clopidogrel combination does not provide any additional benefit compared with clopidogrel alone; however, our study findings indicate that even with lack of adequate clinical evidence physician prescribing of this combination has increased in real-world community settings.

Smoking Discriminately Changes the Serum Active and Non-Active Forms of Vitamin B12

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Niloofar Shekoohi

2017-08-01

Full Text Available Smoking may modify the appetite, and consequently affect nutrient intake and serum micronutrients. The effect of smoking on vitamin B12 status has been considered in several studies. The research proposed that organic nitrites, nitro oxide, cyanides, and isocyanides of cigarette smoke interfere with vitamin B12 metabolism, and convert it to inactive forms. This research was carried out to determine the serum level of active and inactive forms of vitamin B12 in male smokers in comparison with male nonsmokers. This is a case-control study, in which the participants were 85 male smokers and 85 male nonsmokers. The serum levels of total and active form of vitamin B12 were measured. Dietary intake was recorded by a quantitative food frequency questionnaire and one-day 24-hour dietary recall method. Independent two sample T test was used to compare quantitative variables between the case and control groups. The serum level of total vitamin B12 was not significantly different between two groups, but serum level of active form of vitamin B12 in the smoking group was significantly lower than non-smoking group (P<0.001. This is one of the first studies that evaluated the serum level of active form of vitamin B12 in smokers in the Iranian community. The results of this study identified that serum level of total vitamin B12 might be not different between smoking and non-smoking people, but the function of this vitamin is disturbed in the body of smokers through the reduction of serum level of active form of vitamin B12.

Anti-Platelet Aggregation and Vasorelaxing Effects of the Constituents of the Rhizomes of Zingiber officinale

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Tian-Shung Wu

2012-07-01

Full Text Available In the present study, the chemical investigation of the bioactive fractions of the rhizomes of Zingiber officinale has resulted in the identification of twenty-nine compounds including one new compound, O-methyldehydrogingerol (1. Some of the isolates were subjected into the evaluation of their antiplatelet aggregation and vasorelaxing bioactivities. Among the tested compounds, [6]-gingerol (13 and [6]-shogaol (17 exhibited potent anti-platelet aggregation bioactivity. In addition, [10]-gingerol (15 inhibited the Ca²⁺-dependent contractions in high K⁺ medium. According to the results in the present research, the bioactivity of ginger could be related to the anti-platelet aggregation and vasorelaxing mechanism.

Risk and benefit of dual antiplatelet treatment among nonrevascularized myocardial infarction patients in different age groups

DEFF Research Database (Denmark)

Juul, Nikolai; Gislason, Gunnar; Olesen, Jonas Bjerring

2017-01-01

revascularization. METHODS: Patients admitted with first-time myocardial infarction in 2002-2010, not undergoing revascularization, were identified from nationwide Danish registers. Dual anti-platelet treatment use was assessed by claimed prescriptions. Stratified into age groups, risk of bleeding, all.......63; 95% CI 1.17-2.26), 60-69 years (HR=1.22; 95% CI 0.97-1.59, NS), 70-79 years (HR=1.42; 95% CI 1.17-1.72) and >79 years (HR=1.46; 95% CI 1.22-1.74). Similar tendencies in all four age groups were found in the propensity-matched population. CONCLUSION: Dual anti-platelet treatment use was less likely...... among elderly patients although similar effects regarding both risk and benefit were found in all age groups. Increased focus on initiating dual anti-platelet treatment in elderly, non-invasively treated myocardial infarction patients is warranted....

High prevalence of ulcer bleeding risk factors in dual antiplatelet-treated patients after percutaneous coronary intervention

DEFF Research Database (Denmark)

Jensen, Berit Elin S; Hansen, Jane M; Junker, Anders B

2015-01-01

INTRODUCTION: Dual antiplatelet therapy is standard treatment following percutaneous coronary intervention (PCI) and stenting. However, such therapy increases the risk of upper gastrointestinal bleeding (UGIB). The risk factors of UGIB are well-documented and proton pump inhibitor (PPI) treatment...... reduces the risk. The aim was to describe the prevalence of risk factors of UGIB in dual antiplatelet-treated patients. METHODS: A questionnaire was used to assess the prevalence of risk factors of upper gastrointestinal bleeding among dual antiplatelet-treated first-time PCI patients in Western Denmark......: A total of 1,358 patients with a mean age of 64.1 years (range: 33-92 years) were included. The distribution of risk factors was as follows: dyspepsia: 681 patients (50.1%); previous ulcer: 110 (8.1%; 2.3% with bleeding); use of NSAIDs: 214 (15.8%); corticosteroids (2.9%), SSRIs (5.8%) and anticoagulants...

Semiquantitative dynamic computed tomography to predict response to anti-platelet therapy in acute cerebral infarction

International Nuclear Information System (INIS)

Chokyu, K.; Shimizu, K.; Fukumoto, M.; Mori, T.; Mokudai, T.; Mori, K.

2002-01-01

We investigated whether dynamic computed tomography (CT) in patients with acute cerebral infarction could identify patients likely to respond to anti-platelet therapy. Seventy patients underwent semiquantitative dynamic CT within 6 h as well as cerebral angiography. All then received anti-platelet therapy with a thromboxane A2 synthetase inhibitor. Peak value (pv) and time-to-peak (tp) (time-density curves) for the Sylvian fissure were extracted from dynamic CT data and standardizing interpatient data, two indices, PV/TP index and TP index, were prepared following a standard semiquantitative manner. Both PV/TP index and TP index were effective in discriminating between 48 responders (modified Rankin scale (mRS): 0 to 2) and 22 non-responders (mRS: 3 to 5, or death: 6; both P 1.1) and non-compensated rCBF. Intermediate PV/TP values could not predict outcome. Dynamic CT prior to therapy can identify patients with acute cerebral infarction who are treatable with anti-platelet therapy alone. (orig.)

Initiation and persistence with dual antiplatelet therapy after acute myocardial infarction

DEFF Research Database (Denmark)

Green, Anders; Pottegård, Anton; Broe, Anne

2016-01-01

OBJECTIVES: The study investigated dual antiplatelet therapy (DAPT) patterns over time and patient characteristics associated with the various treatments in a myocardial infarction (MI) population. DESIGN: A registry-based observational cohort study was performed using antecedent data. SETTING: T...

Smoking Discriminately Changes the Serum Active and Non-Active Forms of Vitamin B12.

Science.gov (United States)

Shekoohi, Niloofar; Javanbakht, Mohammad Hassan; Sohrabi, Marjan; Zarei, Mahnaz; Mohammadi, Hamed; Djalali, Mahmoud

2017-06-01

Smoking may modify the appetite, and consequently affect nutrient intake and serum micronutrients. The effect of smoking on vitamin B12 status has been considered in several studies. The research proposed that organic nitrites, nitro oxide, cyanides, and isocyanides of cigarette smoke interfere with vitamin B12 metabolism, and convert it to inactive forms. This research was carried out to determine the serum level of active and inactive forms of vitamin B12 in male smokers in comparison with male nonsmokers. This is a case-control study, in which the participants were 85 male smokers and 85 male nonsmokers. The serum levels of total and active form of vitamin B12 were measured. Dietary intake was recorded by a quantitative food frequency questionnaire and one-day 24-hour dietary recall method. Independent two sample T test was used to compare quantitative variables between the case and control groups. The serum level of total vitamin B12 was not significantly different between two groups, but serum level of active form of vitamin B12 in the smoking group was significantly lower than non-smoking group (Psmokers in the Iranian community. The results of this study identified that serum level of total vitamin B12 might be not different between smoking and non-smoking people, but the function of this vitamin is disturbed in the body of smokers through the reduction of serum level of active form of vitamin B12.

Prehospital antiplatelet use and functional status on admission of patients with non-haemorrhagic moyamoya disease: a nationwide retrospective cohort study (J-ASPECT study)

Science.gov (United States)

Onozuka, Daisuke; Hagihara, Akihito; Nishimura, Kunihiro; Kada, Akiko; Nakagawara, Jyoji; Ogasawara, Kuniaki; Ono, Junichi; Shiokawa, Yoshiaki; Aruga, Toru; Miyachi, Shigeru; Nagata, Izumi; Toyoda, Kazunori; Matsuda, Shinya; Suzuki, Akifumi; Kataoka, Hiroharu; Nakamura, Fumiaki; Kamitani, Satoru; Nishimura, Ataru; Kurogi, Ryota; Sayama, Tetsuro; Iihara, Koji

2016-01-01

Objectives To elucidate the association between antiplatelet use in patients with non-haemorrhagic moyamoya disease before hospital admission and good functional status on admission in Japan. Design Retrospective, multicentre, non-randomised, observational study. Setting Nationwide registry data in Japan. Participants A total of 1925 patients with non-haemorrhagic moyamoya disease admitted between 1 April 2012 and 31 March 2014 in Japan. Main outcome measure We performed propensity score-matched analysis to examine the association between prehospital antiplatelet use and no significant disability on hospital admission, as defined by a modified Rankin Scale score of 0 or 1. Results Propensity-matched patients who received prehospital antiplatelet drugs were associated with a good outcome on hospital admission (OR adjusted for all covariates, 3.82; 95% CI 1.22 to 11.99) compared with those who did not receive antiplatelet drugs prior to hospital admission. Conclusions Prehospital antiplatelet use was significantly associated with good functional status on hospital admission among patients with non-haemorrhagic moyamoya disease in Japan. Our results suggest that prehospital antiplatelet use should be considered when evaluating outcomes of patients with non-haemorrhagic moyamoya disease. PMID:27008684

Epidemiology and Management of Patients With Acute Coronary Syndromes in Contemporary Real-World Practice: Evolving Trends From the EYESHOT Study to the START-ANTIPLATELET Registry.

Science.gov (United States)

Calabrò, Paolo; Gragnano, Felice; di Maio, Marco; Patti, Giuseppe; Antonucci, Emilia; Cirillo, Plinio; Gresele, Paolo; Palareti, Gualtiero; Pengo, Vittorio; Pignatelli, Pasquale; Pennacchi, Mauro; Granatelli, Antonino; De Servi, Stefano; De Luca, Leonardo; Marcucci, Rossella

2018-01-01

The epidemiology and management of patients with acute coronary syndromes (ACSs) have evolved. We aimed to describe recent demographics and therapeutic changes in the Italian ACS population. We analyzed data from 2 multicenter consecutive Italian registries (the EYESHOT [EmploYEd antithrombotic therapies in patients with acute coronary Syndromes HOspitalised in iTalian cardiac care units] and START-ANTIPLATELET registries) enrolling patients with ACS between December 2013 and June 2016. An overall population of 3756 patients with ACS was enrolled: 2585 in the EYESHOT and 1171 in the START-ANTIPLATELET. Compared with the EYESHOT, patients in the START-ANTIPLATELET registry presented more frequently with ST-segment elevation myocardial infarction and were more often smokers and dyslipidemic (all P START-ANTIPLATELET (all P START-ANTIPLATELET compared with the EYESHOT. The START-ANTIPLATELET and EYESHOT registries provide consecutive snapshots in the contemporary management of patients with ACS in Italy, showing important changes in both demographic characteristics and treatment strategies.

Degalactosylated/desialylated human serum containing GcMAF induces macrophage phagocytic activity and in vivo antitumor activity.

Science.gov (United States)

Kuchiike, Daisuke; Uto, Yoshihiro; Mukai, Hirotaka; Ishiyama, Noriko; Abe, Chiaki; Tanaka, Daichi; Kawai, Tomohito; Kubo, Kentaro; Mette, Martin; Inui, Toshio; Endo, Yoshio; Hori, Hitoshi

2013-07-01

The group-specific component protein-derived macrophage-activating factor (GcMAF) has various biological activities, such as macrophage activation and antitumor activity. Clinical trials of GcMAF have been carried out for metastatic breast cancer, prostate cancer, and metastatic colorectal cancer. In this study, despite the complicated purification process of GcMAF, we used enzymatically-treated human serum containing GcMAF with a considerable macrophage-stimulating activity and antitumor activity. We detected GcMAF in degalactosylated/desialylated human serum by western blotting using an anti-human Gc globulin antibody, and Helix pomatia agglutinin lectin. We also found that GcMAF-containing human serum significantly enhanced the phagocytic activity of mouse peritoneal macrophages and extended the survival time of mice bearing Ehrlich ascites tumors. We demonstrated that GcMAF-containing human serum can be used as a potential macrophage activator for cancer immunotherapy.

Prior antiplatelet therapy and outcome following intracerebral hemorrhage: a systematic review

DEFF Research Database (Denmark)

Thompson, B B; Béjot, Y; Caso, V

2010-01-01

Antiplatelet therapy (APT) promotes bleeding; therefore, APT might worsen outcome in patients with intracerebral hemorrhage (ICH). We performed a systematic review and meta-analysis to address the hypothesis that pre-ICH APT use is associated with mortality and poor functional outcome following ICH....

Serum creatine kinase and lactate dehydrogenase activities in ...

African Journals Online (AJOL)

Background and Objectives: There is the recognition of a pattern of elevations of serum enzymes in hyperthyroid and hypothyroid patients. The aims of this study were to determine the activities of serum creatine kinase (CK) and lactate deydrogenase (LDH) in thyroid disorders, and to evaluate the relationship between CK, ...

The stability of complement-mediated bactericidal activity in human serum against Salmonella.

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Colette M O'Shaughnessy

Full Text Available The complement cascade includes heat-labile proteins and care is required when handling serum in order to preserve its functional integrity. We have previously used a whole human serum bactericidal assay to show that antibody and an intact complement system are required in blood for killing of invasive isolates of Salmonella. The aim of the present study was to evaluate the conditions under which human serum can be stored and manipulated while maintaining complement integrity. Serum bactericidal activity against Salmonella was maintained for a minimum of 35 days when stored at 4°C, eight days at 22°C and 54 hours at 37°C. Up to three freeze-thaw cycles had no effect on the persistence of bactericidal activity and hemolytic complement assays confirmed no effect on complement function. Delay in the separation of serum for up to four days from clotted blood stored at 22°C did not affect bactericidal activity. Dilution of serum resulted in an increased rate of loss of bactericidal activity and so serum should be stored undiluted. These findings indicate that the current guidelines concerning manipulation and storage of human serum to preserve complement integrity and function leave a large margin for safety with regards to bactericidal activity against Salmonella. The study provides a scheme for determining the requirements for serum handling in relation to functional activity of complement in other systems.

A Comparative Study of Molecular Structure, pKa, Lipophilicity, Solubility, Absorption and Polar Surface Area of Some Antiplatelet Drugs

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Milan Remko

2016-03-01

Full Text Available Theoretical chemistry methods have been used to study the molecular properties of antiplatelet agents (ticlopidine, clopidogrel, prasugrel, elinogrel, ticagrelor and cangrelor and several thiol-containing active metabolites. The geometries and energies of most stable conformers of these drugs have been computed at the Becke3LYP/6-311++G(d,p level of density functional theory. Computed dissociation constants show that the active metabolites of prodrugs (ticlopidine, clopidogrel and prasugrel and drugs elinogrel and cangrelor are completely ionized at pH 7.4. Both ticagrelor and its active metabolite are present at pH = 7.4 in neutral undissociated form. The thienopyridine prodrugs ticlopidine, clopidogrel and prasugrel are lipophilic and insoluble in water. Their lipophilicity is very high (about 2.5–3.5 logP values. The polar surface area, with regard to the structurally-heterogeneous character of these antiplatelet drugs, is from very large interval of values of 3–255 Å2. Thienopyridine prodrugs, like ticlopidine, clopidogrel and prasugrel, with the lowest polar surface area (PSA values, exhibit the largest absorption. A high value of polar surface area (PSA of cangrelor (255 Å2 results in substantial worsening of the absorption in comparison with thienopyridine drugs.

Serum prolidase activity and oxidative status in Helicobacter pylori infection.

Science.gov (United States)

Aslan, Mehmet; Nazligul, Yasar; Horoz, Mehmet; Bolukbas, Cengiz; Bolukbas, Fusun F; Aksoy, Nurten; Celik, Hakim; Erel, Ozcan

2007-01-01

During the course of Helicobacter pylori infection, increased oxidative stress plays an important role in the pathogenesis of gastroduodenal mucosal inflammation, which can cause gastric mucosal atrophy that characterized by the replacement of the gastric mucosal glands by collagen fibers. In the present study, we aimed to determine serum prolidase activity and oxidative status, and to find out if there is any association between serum prolidase activity and oxidative status in H. pylori infection. Forty H. pylori-positive and 32 H. pylori-negative subjects were enrolled. Serum prolidase activity was measured spectrophotometrically. Oxidative status was determined using total antioxidant capacity and total oxidant status measurement and calculation of oxidative stress index. Total antioxidant capacity level was lower in H. pylori-positive group than H. pylori-negative group (ptotal oxidant status, oxidative stress index and prolidase activity were higher (all ptotal antioxidant capacity, total oxidant status and oxidative stress index (p<0.01, r=-0.367; p<0.05, r=0.283; p<0.01, r=0.379; respectively) in H. pylori-positive subjects. H. pylori infection may be associated with increased oxidative stress and increased serum prolidase activity. Increased oxidative stress seems to be associated with increased serum prolidase activity and this association may help to provide a better understanding about the pathogenesis of H. pylori infection.

Prehospital antiplatelet use and functional status on admission of patients with non-haemorrhagic moyamoya disease: a nationwide retrospective cohort study (J-ASPECT study).

Science.gov (United States)

Onozuka, Daisuke; Hagihara, Akihito; Nishimura, Kunihiro; Kada, Akiko; Nakagawara, Jyoji; Ogasawara, Kuniaki; Ono, Junichi; Shiokawa, Yoshiaki; Aruga, Toru; Miyachi, Shigeru; Nagata, Izumi; Toyoda, Kazunori; Matsuda, Shinya; Suzuki, Akifumi; Kataoka, Hiroharu; Nakamura, Fumiaki; Kamitani, Satoru; Nishimura, Ataru; Kurogi, Ryota; Sayama, Tetsuro; Iihara, Koji

2016-03-15

To elucidate the association between antiplatelet use in patients with non-haemorrhagic moyamoya disease before hospital admission and good functional status on admission in Japan. Retrospective, multicentre, non-randomised, observational study. Nationwide registry data in Japan. A total of 1925 patients with non-haemorrhagic moyamoya disease admitted between 1 April 2012 and 31 March 2014 in Japan. We performed propensity score-matched analysis to examine the association between prehospital antiplatelet use and no significant disability on hospital admission, as defined by a modified Rankin Scale score of 0 or 1. Propensity-matched patients who received prehospital antiplatelet drugs were associated with a good outcome on hospital admission (OR adjusted for all covariates, 3.82; 95% CI 1.22 to 11.99) compared with those who did not receive antiplatelet drugs prior to hospital admission. Prehospital antiplatelet use was significantly associated with good functional status on hospital admission among patients with non-haemorrhagic moyamoya disease in Japan. Our results suggest that prehospital antiplatelet use should be considered when evaluating outcomes of patients with non-haemorrhagic moyamoya disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Oxidative status and serum PON1 activity in beta-thalassemia minor.

Science.gov (United States)

Selek, Sahbettin; Aslan, Mehmet; Horoz, Mehmet; Gur, Mustafa; Erel, Ozcan

2007-03-01

Paraoxonase-1 (PON1) deficiency is related to increased susceptibility to low density lipoprotein oxidation and development of atherosclerosis. The aim of this study was to investigate paraoxonase and arylesterase activities along with oxidative status parameters, and to find out if there is any increased susceptibility to atherogenesis, which might be reflected with increased oxidative stress and decreased serum PON1 activity in beta-thalassemia minor (BTM) subjects. Thirty-two subjects with BTM and 28 healthy subjects as control were enrolled in the study. Serum paraoxonase and arylesterase activities, lipid hydroperoxide (LOOH) levels, total antioxidant capacity (TAC), total oxidant status (TOS) and oxidative stress index (OSI) were determined. Serum TAC, paraoxonase and arylesterase activities were significantly lower in BTM subjects than controls (for all p<0.001), while TOS, LOOH levels and OSI were significantly higher (p<0.001, p<0.05 and p<0.001; respectively). In BTM subjects, OSI, TOS, LOOH levels and TAC were significantly correlated with serum paraoxonase (r=-0.245, p<0.05; r=-0.231, p<0.05; r=-0.264, p<0.05 and, r=0.342, p<0.05, respectively) and arylesterase activities (r=-0.332, p<0.05, r=-0.308, p<0.05; r=-0.320, p<0.05 and r=0.443, p<0.05). Additionally, hemoglobin level was also correlated with serum paraoxonase (r=0.501, p<0.001) and arylesterase activities (r=0.501, p<0.001), TAC (r=0.402, p<0.05), TOS (r=-0.274, p<0.05) and OSI (r=-0.352, p<0.05). Oxidative stress is increased, while serum PON1 activity is decreased in BTM subjects. Decrease in PON1 activity seems to be associated with both the degree of oxidative stress and anemia. BTM subjects may be more prone to development of atherogenesis due to low serum PON1 activity.

ANALYZES OF ANTIPLATELETS AND ANTICOAGULANTS UTILIZATION IN PATIENTS TREATED IN CARDIOVASCULAR REHABILITATION CENTER FROM CROATIA

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Boban Marko

2016-07-01

Full Text Available Purpose: Discordance with the guidelines and underutilization of pharmacotherapy for secondary prevention frequently exists in clinical practice. Aim of our study was to assess the prescription routine and drug utilization patterns for antiplatelets and peroral anticoagulants in tertiary medical center specialized for cardiovascular rehabilitation. Methods: study included 96 consecutive patients scheduled for cardiovascular rehabilitation in period 1-6 months after the acute treatment for ischemic 87(80.2% and valvular heart disease 18(19.8%. Patients were divided according to etiology of heart disease and type of acute cardiovascular treatments (conservative, percutaneous coronary interventions (PCI and surgery. Results: Dual antiplatelet therapy was the most commonly applied regimen in 84(87.5% of conservatively treated myocardial infarctions, 47(61.9% of percutaneous coronary interventions (PCI and 13(58.9% of surgically treated group (p>0.05. Among studied group of patients significant differences in utilization were found for warfarin, or combinations of antiplatelets with warfarin(p0.05. All four of patients that received triple therapy (4.17% were from surgical group. Underutilization of antiplatelets in ischemic heart disease was at 11(14.3% what was congruent with the developed industrial nations. Conclusions: Acute cardiovascular treatment type, but not heart disease etiology, had significant influence on subsequent prescription routine. Decreased use of pharmacological agents for secondary prevention in surgical patients was revealed. Drug utilization analyzes can offer improvement in optimizing medical treatments, quality of care and decrease unnecessary polypragmasia, as well as improve economical efficiency of medical management.

Comparison on Anticoagulation and Antiplatelet Aggregation Effects of Puerarin with Heparin Sodium and Tirofiban Hydrochloride: An In Vitro Study.

Science.gov (United States)

Li, Si-Wei; Feng, Xue; Xu, Hao; Chen, Ke-Ji

2018-02-01

To detect the anticoagulation and antiplatelet effects of different concentrations of puerarin, heparin sodium and tirofiban hydrochloride on the blood samples of healthy volunteers by Sonoclot coagulation and platelet function analyzer. Peripheral blood samples were extracted from 20 healthy volunteers, followed by adding different concentrations of puerarin, heparin sodium and tirofiban hydrochloride. Samples were detected for activated clotting time (ACT), clot rate (CR) and platelet function (PF) by Sonoclot coagulation and platelet function analyzer instrument. For puerarin and heparin sodium, the values of ACT gradually increased, and the values of CR and PF gradually decreased with increasing in drug concentration. There was a linear (or log linear) relationship between ACT, CR, PF value and drug concentration (Phydrochloride, the values of ACT and CR had no significant changes, while PF values gradually decreased with concentration increasing. There was also a linear relationship between PF values and concentrations of tirofiban hydrochloride (Psodium. For high concentrations of puerarin (e.g. 3.8 mg/600 μL) and tirofiban hydrochloride (e.g. 0.8 μg/600 μL), PF values had no significant difference. However, PF values for high puerarin concentration had a larger variance. Puerarin has similar anticoagulant and antiplatelet effects with the heparin sodium, and may have a lower hemorrhage risk than heparin sodium when obtained the same anticoagulation effect in the concentration range of this experiment. In addition, for high concentration, puerarin had the same antiplatelet function as tirofiban hydrochloride but with a larger individual variability.

Dual antiplatelet therapy with prasugrel or ticagrelor versus clopidogrel in interventional cardiology

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Clemmensen, Peter; Dridi, Nadia Paarup; Holmvang, Lene

2013-01-01

For several years, clopidogrel plus aspirin has been the dual antiplatelet therapy (DAPT) of choice for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) with stent implantation. More recently, prasugrel and ticagrelor have demonstrated greater effica...

Arylesterase Phenotype-Specific Positive Association Between Arylesterase Activity and Cholinesterase Specific Activity in Human Serum

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Yutaka Aoki

2014-01-01

Full Text Available Context: Cholinesterase (ChE specific activity is the ratio of ChE activity to ChE mass and, as a biomarker of exposure to cholinesterase inhibitors, has a potential advantage over simple ChE activity. Objective: To examine the association of several potential correlates (serum arylesterase/paraoxonase activity, serum albumin, sex, age, month of blood collection, and smoking with plasma ChE specific activity. Methods: We analyzed data from 195 cancer-free controls from a nested case-control study, accounting for potential confounding. Results: Arylesterase activity had an independent, statistically significant positive association with ChE specific activity, and its magnitude was the greatest for the arylesterase phenotype corresponding to the QQ PON1192 genotype followed by phenotypes corresponding to QR and RR genotypes. Serum albumin was positively associated with ChE specific activity. Conclusions: Plasma arylesterase activity was positively associated with plasma ChE specific activity. This observation is consistent with protection conferred by a metabolic phenotype resulting in reduced internal dose.

Baseline characteristics of the 3096 patients recruited into the 'Triple Antiplatelets for Reducing Dependency after Ischemic Stroke' trial.

Science.gov (United States)

Bath, Philip Mw; Appleton, Jason P; Beridze, Maia; Christensen, Hanne; Dineen, Robert A; Duley, Lelia; England, Timothy J; Heptinstall, Stan; James, Marilyn; Krishnan, Kailash; Markus, Hugh S; Pocock, Stuart; Ranta, Annemarei; Robinson, Thompson G; Flaherty, Katie; Scutt, Polly; Venables, Graham S; Woodhouse, Lisa J; Sprigg, Nikola

2017-07-01

Background The risk of recurrence following ischemic stroke or transient ischemic attack is highest immediately after the event. Antiplatelet agents are effective in reducing the risk of recurrence and two agents are superior to one in the early phase after ictus. Design The triple antiplatelets for reducing dependency after ischemic stroke trial was an international multicenter prospective randomized open-label blinded-endpoint trial that assessed the safety and efficacy of short-term intensive antiplatelet therapy with three agents (combined aspirin, clopidogrel and dipyridamole) as compared with guideline treatment in acute ischemic stroke or transient ischemic attack. The primary outcome was stroke recurrence and its severity, measured using the modified Rankin Scale at 90 days. Secondary outcomes included recurrent vascular events, functional measures (cognition, disability, mood, quality of life), and safety (bleeding, death, serious adverse events). Data are number (%) or mean (standard deviation, SD). Results Recruitment ran from April 2009 to March 2016; 3096 patients were recruited from 106 sites in four countries (Denmark 1.6%, Georgia 2.7%, New Zealand 0.2%, UK 95.4%). Randomization characteristics included: age 69.0 (10.1) years; male 1945 (62.8%); time onset to randomization 29.4 (11.9) h; stroke severity (National Institutes for Health Stroke Scale) 2.8 (3.6); blood pressure 143.5 (18.2)/79.5 (11.4) mmHg; IS 2143 (69.2%), transient ischemic attack 953 (30.8%). Conclusion Triple antiplatelets for reducing dependency after ischemic stroke was a large trial of intensive/triple antiplatelet therapy in acute ischemic stroke and transient ischemic attack, and included participants from four predominantly Caucasian countries who were representative of patients in many western stroke services.

Complex nature of serum lysozyme activity: evidence of thermolability in inflammatory bowel disease

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Ward, M; Mitchell, W D; Eastwood, M [Western General Hospital, Edinburgh (UK)

1978-01-01

In patients with Crohn's disease and ulcerative colitis, alterations in serum storage temperature produced significant changes in serum lysozyme activity (SLA) as measured by the lysoplate method. This was not the case in healthy controls or in a group with other gastrointestinal disorders. Electrophoretic separation of serum revealed two components of lysozyme-type lytic activity but only one in extracts of gut mucosa, leucocytes, and egg white. The major lytic component of serum migrated towards the cathode and reacted with specific antilysozyme serum, but the minor component which migrated towards the anode did not. Although the cause of this anionic lytic activity is uncertain, it contributes to total serum activity as estimated by any method utilizing the lysis of Micrococcus lysodeikticus, and may possibly be related to the observed thermolability.

Efficacy And Safety of Dabigatran Etexilate Utilization With Concomitant Dual Antiplatelet Therapy In Atrial Fibrillation.

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Centurión Md PhD Facc, Osmar Antonio

2014-01-01

The necessity to add two antiplatelet agents to an oral anticoagulant (OAC) often arises in patients with atrial fibrillation (AF) in routine clinical practice. The majority of AF patients have an indication for continuous OAC, and coronary artery disease co-exists in 25% of these patients. The increasing use of drug-eluting stents to minimize intrastent restenosis necessitates long-term dual antiplatelet therapy with Aspirin plus Clopidogrel to reduce the risk of early and late stent thrombosis. Combined aspirin-clopidogrel therapy, however, is less effective in preventing stroke compared with OAC alone in AF patients, and OAC alone is insufficient to prevent stent thrombosis. The management of AF patients presenting with an acute coronary syndrome poses similar management complexities. Since AF and coronary artery disease with stent placement are common, it is relatively frequent to treat patients with both these conditions, where triple antithrombotic therapy with Aspirin, Clopidogrel and an OAC would be needed. Dabigatran etexilate, an oral direct thrombin inhibitor, has shown that compared with Warfarin given at a dose of 150 mg twice daily significantly reduces stroke with less intracranial bleeding, and at a dose of 110 mg twice daily has similar efficacy with less bleeding. Although, Dabigatran maintained its overall favorable profile compared with Warfarin in patients on dual antiplatelet therapy, we should always bear in mind for the sake of our AF patients that combining dual antiplatelet therapy with chronic anticoagulation with Dabigatran, as well as with Warfarin, significantly increases bleeding risk. This triple therapy association should be evaluated in the individual patient after carefully balancing bleeding versus thrombotic risk.

Increased serum cortisol binding in chronic active hepatitis

International Nuclear Information System (INIS)

Orbach, O.; Schussler, G.C.

1989-01-01

A high serum cortisol concentration, apparently due to increased cortisol-binding globulin (CBG), was found in a patient (index case) with chronic active hepatitis (CAH). We therefore performed further studies to determine whether increased cortisol binding is generally associated with CAH. Serum samples were obtained from 15 hospitalized patients with long-term liver function test elevations but no evidence of cirrhosis, 15 normal subjects without a history of hepatitis, four healthy pregnant women, and 10 alcoholic patients with stigmata of cirrhosis. Serum cortisol binding was measured by an adaptation of a previously described charcoal uptake method. Thyroxine-binding globulin (TBG) and sex hormone-binding globulin were determined by radioimmunoassays. Charcoal uptake of 125I cortisol from sera of normal subjects and additional patients with CAH revealed that increased serum cortisol binding by a saturable site, presumably CBG, was associated with CAH. Cortisol binding was significantly correlated with immunoassayable TBG, suggesting that in CAH, similar mechanisms may be responsible for increasing the serum concentrations of CBG and TBG

Stent Thrombosis in Drug-Eluting or Bare-Metal Stents in Patients Receiving Dual Antiplatelet Therapy.

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Kereiakes, Dean J; Yeh, Robert W; Massaro, Joseph M; Driscoll-Shempp, Priscilla; Cutlip, Donald E; Steg, P Gabriel; Gershlick, Anthony H; Darius, Harald; Meredith, Ian T; Ormiston, John; Tanguay, Jean-François; Windecker, Stephan; Garratt, Kirk N; Kandzari, David E; Lee, David P; Simon, Daniel I; Iancu, Adrian Corneliu; Trebacz, Jaroslaw; Mauri, Laura

2015-10-01

This study sought to compare rates of stent thrombosis and major adverse cardiac and cerebrovascular events (MACCE) (composite of death, myocardial infarction, or stroke) after coronary stenting with drug-eluting stents (DES) versus bare-metal stents (BMS) in patients who participated in the DAPT (Dual Antiplatelet Therapy) study, an international multicenter randomized trial comparing 30 versus 12 months of dual antiplatelet therapy in subjects undergoing coronary stenting with either DES or BMS. Despite antirestenotic efficacy of coronary DES compared with BMS, the relative risk of stent thrombosis and adverse cardiovascular events is unclear. Many clinicians perceive BMS to be associated with fewer adverse ischemic events and to require shorter-duration dual antiplatelet therapy than DES. Prospective propensity-matched analysis of subjects enrolled into a randomized trial of dual antiplatelet therapy duration was performed. DES- and BMS-treated subjects were propensity-score matched in a many-to-one fashion. The study design was observational for all subjects 0 to 12 months following stenting. A subset of eligible subjects without major ischemic or bleeding events were randomized at 12 months to continued thienopyridine versus placebo; all subjects were followed through 33 months. Among 10,026 propensity-matched subjects, DES-treated subjects (n = 8,308) had a lower rate of stent thrombosis through 33 months compared with BMS-treated subjects (n = 1,718, 1.7% vs. 2.6%; weighted risk difference -1.1%, p = 0.01) and a noninferior rate of MACCE (11.4% vs. 13.2%, respectively, weighted risk difference -1.8%, p = 0.053, noninferiority p stent thrombosis that are lower than BMS-treated subjects. (The Dual Antiplatelet Therapy Study [DAPT study]; NCT00977938). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Relation of serum γ-glutamyl transferase activity with copper in an adult population.

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Peng, You-Fan; Wang, Chun-Fang; Pan, Guo-Gang

2017-10-26

The aim of this study was to evaluate the relationship between serum γ-glutamyl transferase (γ-GGT) activity and serum copper in an adult population. We analyzed 281 adult subjects who regularly attended the physical examination center at the Affiliated Hospital of Youjiang Medical University for Nationalities. The demographic and laboratory data of the participants were divided into two groups according to the median of serum γ-GGT activity. Serum copper concentrations in individuals with higher γ-GGT levels were significantly increased compared with those with lower γ-GGT concentrations (9.9±2.41 vs. 11.2±3.36 μmol/L, pcopper in all eligible subjects (r=0.198, p=0.001). Further, serum γ-GGT maintained a positive correlation with serum copper in both males and females (r=0.322, pcopper after adjusting for multiple potential confounders (b=0.464, p=0.001). This study suggests that serum γ-GGT activity is correlated with copper in the study population, indicating that serum γ-GGT may be a biomarker to evaluate serum copper levels in an adult population.

When is the Best Time for the Second Antiplatelet Agent in Non-St Elevation Acute Coronary Syndrome?

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Pedro Gabriel Melo de Barros e Silva

2016-03-01

Full Text Available Abstract Dual antiplatelet therapy is a well-established treatment in patients with non-ST elevation acute coronary syndrome (NSTE-ACS, with class I of recommendation (level of evidence A in current national and international guidelines. Nonetheless, these guidelines are not precise or consensual regarding the best time to start the second antiplatelet agent. The evidences are conflicting, and after more than a decade using clopidogrel in this scenario, benefits from the routine pretreatment, i.e. without knowing the coronary anatomy, with dual antiplatelet therapy remain uncertain. The recommendation for the upfront treatment with clopidogrel in NSTE-ACS is based on the reduction of non-fatal events in studies that used the conservative strategy with eventual invasive stratification, after many days of the acute event. This approach is different from the current management of these patients, considering the established benefits from the early invasive strategy, especially in moderate to high-risk patients. The only randomized study to date that specifically tested the pretreatment in NSTE-ACS in the context of early invasive strategy, used prasugrel, and it did not show any benefit in reducing ischemic events with pretreatment. On the contrary, its administration increased the risk of bleeding events. This study has brought the pretreatment again into discussion, and led to changes in recent guidelines of the American and European cardiology societies. In this paper, the authors review the main evidence of the pretreatment with dual antiplatelet therapy in NSTE-ACS.

Implementation of pharmacogenetics: the University of Maryland Personalized Anti-platelet Pharmacogenetics Program.

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Shuldiner, Alan R; Palmer, Kathleen; Pakyz, Ruth E; Alestock, Tameka D; Maloney, Kristin A; O'Neill, Courtney; Bhatty, Shaun; Schub, Jamie; Overby, Casey Lynnette; Horenstein, Richard B; Pollin, Toni I; Kelemen, Mark D; Beitelshees, Amber L; Robinson, Shawn W; Blitzer, Miriam G; McArdle, Patrick F; Brown, Lawrence; Jeng, Linda Jo Bone; Zhao, Richard Y; Ambulos, Nicholas; Vesely, Mark R

2014-03-01

Despite a substantial evidence base, implementation of pharmacogenetics into routine patient care has been slow due to a number of non-trivial practical barriers. We implemented a Personalized Anti-platelet Pharmacogenetics Program (PAP3) for cardiac catheterization patients at the University of Maryland Medical Center and the Baltimore Veterans Administration Medical Center Patients' are offered CYP2C19 genetic testing, which is performed in our Clinical Laboratory Improvement Amendment (CLIA)-certified Translational Genomics Laboratory. Results are returned within 5 hr along with clinical decision support that includes interpretation of results and prescribing recommendations for anti-platelet therapy based on the Clinical Pharmacogenetics Implementation Consortium guidelines. Now with a working template for PAP3, implementation of other drug-gene pairs is in process. Lessons learned as described in this article may prove useful to other medical centers as they implement pharmacogenetics into patient care, a critical step in the pathway to personalized and genomic medicine. © 2014 Wiley Periodicals, Inc.

Xeno-oestrogenic activity in serum as marker of occupational pesticide exposure

DEFF Research Database (Denmark)

Andersen, Helle Raun; Nielsen, Flemming; Nielsen, Jesper Bo

2007-01-01

-oestrogenic activity in serum was statistically significant for women who had been at work within the last week, while no association was observed for women who had not been at work during the most recent week. Conclusions: The study illustrates the usefulness of this biomarker for qualitative assessment...... with oestrogen-like properties in an occupational setting. Methods: Serum samples were obtained from two separate cohorts representing non-pregnant and pregnant female greenhouse workers in Denmark. Serum samples from 270 non-pregnant women and 173 pregnant women were analysed for xeno-oestrogenic activity......, medium or high based on information collected by detailed interviews of the women and the employers. Results: In both cohorts, an exposure-associated increase in the xeno-oestrogenic activity in serum was demonstrated. Among the pregnant women, the association between pesticide exposure and xeno...

Risk of bleeding in patients undergoing percutaneous endoscopic gastrotrostomy (PEG tube insertion under antiplatelet therapy: a systematic review with a meta-analysis

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Alfredo J. Lucendo

2015-03-01

Full Text Available Background and aim: Patients undergoing percutaneous endoscopic gastrostomy (PEG tube placement often are under antiplatelet therapy with a potential thromboembolic risk if these medications are discontinued. This systematic review aims to assess if maintaining aspirin and/or clopidogrel treatment increases the risk of bleeding following PEG placement. Methods: A systematic search of the MEDLINE, EMBASE, and SCOPUS databases was developed for studies investigating the risk of bleeding in patients on antiplatelet therapy undergoing PEG tube insertion. Summary estimates, including 95 % confidence intervals (CI, were calculated. A fixed or random effects model was used depending on heterogeneity (I². Publication bias risks were assessed by means of funnel plot analysis. Results: Eleven studies with a total of 6,233 patients (among whom 3,665 were undergoing antiplatelet treatment, met the inclusion criteria and were included in the quantitative summary. Any PEG tube placement-related bleeding was found in 2.67 % (95 % CI 1.66 %, 3.91 % of the entire population and in 2.7 % (95 % CI 1.5 %, 4.1 % of patients not receiving antiplatelet therapy. Pooled relative risk (RR for bleeding in patients under aspirin, when compared to controls, was 1.43 (95 % CI 0.89, 2.29; I² = 0 %; pooled RR for clopidogrel was 1.21 (95 % CI 0.48, 3.04; I² = 0 % and for dual antiplatelet therapy, 2.13; (95 % CI 0.77, 5.91; I² = 47 %. No significant publication bias was evident for the different medications analyzed. Conclusion: Antiplatelet therapy was safe among patients undergoing PEG tube insertion. Future prospective and randomized studies with larger sample sizes are required to confirm the results of this study.

Increased serum erythropoietin activity in rats following intrarenal injection of nickel subsulfide

International Nuclear Information System (INIS)

Hopfer, S.M.; Sunderman, F.W. Jr.; Fredrickson, T.N.; Morse, E.E.

1979-01-01

To investigate the pathopysiologic mechanisms of nickel-induced erythocytosis, serum erythropoietin activities were measured in (a) pooled serum from rats at 2 wk after intrarenal injection of αNi 3 S 2 (5 mg/rat), and (b) pooled serum from control rats at 2 wk after intrarenal injection of sterile NaCl vehicle (0.4 ml/rat). A sensitive erythropoietin bioassay was employed, which entailed repetitive administration of test serums to post-hypoxic polycythemic mice in divided doses (12 s.c. injections of 0.5 ml of serum at 6 h intervals for 3 da; total dose = 6 ml of serum/mouse). The erythropoietin detection limit was approx. = 20 I.U./liter of serum. In mice which received pooled serum from αNi 3 S 2 -treated rats, erythrocyte 59 Fe-uptake averaged 28% (S.D. +- 5) (vs 3.7 +- 1.1% in control rats; P 3 S 2 -treated rats averaged 130 I.U./liter (S.D. +- 18) (vs 27 +- 6 I.U./liter in control rats; P 3 S 2 is mediated by increased serum erythropoietin activity

Serum components and clinical efficacies of autologous serum eye drops in dry eye patients with active and inactive Sjogren syndrome.

Science.gov (United States)

Ma, I-Hsin; Chen, Lily Wei; Tu, Wen-Hui; Lu, Chia-Ju; Huang, Chien-Jung; Chen, Wei-Li

2017-01-01

Autologous serum eye drops are considered safe and efficient for the treatment of various ocular surface disorders, including dry eye diseases (DED) caused by the primary and secondary Sjogren syndrome (SS). However, the serum components in patients of SS may be different from those of normal patients and can thus lead to unpredictable therapeutic effects. This study divided the SS patients into active and inactive types based on the erythrocyte sedimentation rate and the presence or absence of active rheumatoid arthritis. We compared the serum components of these two groups with standard and multiplex enzyme linked immunosorbent assay arrays and predicted the therapeutic effects of topical autologous serum for the treatment of DED with ocular surface disease index (OSDI) and Oxford Schema scale (OSS). Hyaluronic acid and transforming growth factor b1 levels were significantly higher in the active SS group compared to the inactive SS group ( P Sjogren dry eye patients into active and inactive groups may appear as a reasonable method to predict the quality of autologous serum eye drops, but there seems to be no significant predictability to the therapeutic effects.

[Neurosurgery in a patient on dual antiplatelet therapy. Case report and the review of the literature].

Science.gov (United States)

Lubnin, A Yu; Karnaukhov, V V; Moshkin, A V; Rylova, A V; Shimansky, V N

A neurosurgical intervention in a patient on dual antiplatelet therapy is a serious challenge for both the neurosurgeon and anesthesiologist.. The article describes a clinical case of a successful urgent neurosurgical intervention (ventriculoperitoneostomy for obstructive hydrocephalus caused by a large meningioma of the posterior surface of the petrous pyramid) in a patient on dual antiplatelet therapy (DAT) due to a recently placed coronary stent.. Given a high risk of coronary stent thrombosis, the surgery was performed in the presence of ongoing DAT. There were no intracranial hemorrhagic complications, but subcutaneous hemorrhagic complications developed. The article discusses the features of managing similar patients whose number is growing.

In vitro demonstration of anti-lipogenic activity in serum from obese rats

International Nuclear Information System (INIS)

Harris, R.B.S.; Martin, R.J.

1986-01-01

Studies with parabiosed rats provide evidence for a humoral factor, originating in obese animals, that specifically inhibits adipose lipogenesis. A bioassay was developed that allows serum from obese rats to be tested for this factor in vitro. Adipocytes are isolated from epididymal fat of 250g Sprague-Dawley rats. The cells are preincubated at 37 0 C for 1 or 12 hrs, in TC199 media containing 1.1 mg/ml glucose, 0.1 M Hepes and 2% serum. Following preincubation, the cells are washed 3 times and resuspended in serum-free media. Aliquots of cells are tested for metabolic activity in a subsequent 2 hour radiolabelled incubation in serum-free media with the addition of 0.5 μCi/ml U- 14 C-glucose. Basal, insulin (100 μU/ml) and norepinephrine (0.1 μg/ml) stimulated rates of glucose oxidation and conversion to triglyceride fatty acids are measured. Using serum from ad libitum fed rats as control, preincubation with serum from obese rats (20 days at 2 x normal intake) depressed basal and insulin stimulated glucose oxidation, and basal fatty acid synthesis. Serum from obese parabiotic rats and parabiotic partners of obese rats depressed basal fatty acid synthesis. This assay allows us to test serum for anti-lipogenic activity and may be used to identify the factor responsible for this activity in obese animals

New Insights into Butyrylcholinesterase Activity Assay: Serum Dilution Factor as a Crucial Parameter.

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Joanna Jońca

Full Text Available Butyrylcholinesterase (BChE activity assay and inhibitor phenotyping can help to identify patients at risk of prolonged paralysis following the administration of neuromuscular blocking agents. The assay plays an important role in clinical chemistry as a good diagnostic marker for intoxication with pesticides and nerve agents. Furthermore, the assay is also commonly used for in vitro characterization of cholinesterases, their toxins and drugs. There is still lack of standardized procedure for measurement of BChE activity and many laboratories use different substrates at various concentrations. The purpose of this study was to validate the BChE activity assay to determine the best dilution of human serum and the most optimal concentration of substrates and inhibitors. Serum BChE activity was measured using modified Ellman's method applicable for a microplate reader. We present our experience and new insights into the protocol for high-throughput routine assays of human plasma cholinesterase activities adapted to a microplate reader. During our routine assays used for the determination of BChE activity, we have observed that serum dilution factor influences the results obtained. We show that a 400-fold dilution of serum and 5mM S-butyrylthiocholine iodide can be successfully used for the accurate measurement of BChE activity in human serum. We also discuss usage of various concentrations of dibucaine and fluoride in BChE phenotyping. This study indicates that some factors of such a multicomponent clinical material like serum can influence kinetic parameters of the BChE. The observed inhibitory effect is dependent on serum dilution factor used in the assay.

Anti-platelet and anti-thrombotic effect of a traditional herbal medicine Kyung-Ok-Ko.

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Kim, Tae-Ho; Lee, Kyoung Mee; Hong, Nam Doo; Jung, Yi-Sook

2016-02-03

Kyung-Ok-Ko (KOK), a traditional herbal prescription, contains six main ingredients; Rehmannia glutinosa var. purpurae, Lycium chinense, Aquillaria agallocha, Poria cocos, Panax ginseng, and honey. KOK has been widely taken as a traditional oriental medicine for improving blood circulation or age-related symptoms, such as dementia and stroke. However, the effect of KOK on platelet activity has not been clarified. To evaluate the effect of KOK on platelet function, we evaluated its effect on functional markers of platelet activation such as aggregation and shape change. As a mechanism study for the effect of KOK, we examined its effect on granule secretion, intracellular Ca(2+) increase, and PLCγ and Akt activation. To investigate the effect of orally administered KOK (0.5, 1, 2 g/kg), we examined its ex vivo effect on platelet aggregation in rat, and its in vivo anti-thrombotic effect in mice thromboembolism model. Furthermore, the effect of KOK on bleeding time was examined to estimate its potential side effect. KOK (0.3, 1, 3, 10 mg/ml) inhibited collagen-induced platelet aggregation and shape change in rat platelets in a concentration-dependent manner. The mechanism for the anti-platelet effect of KOK seems to involve the inhibition of ATP release, intracellular Ca(2+) elevation, and the phosphorylation of PLCγ and Akt. In rat ex vivo study, KOK (2 g/kg, p.o. for 1 day, and 0.5, 1, 2 g/kg, p.o. for 7 days) also had significant inhibitory effects on collagen-induced platelet aggregation. In addition, KOK showed a significant protective effect against thrombosis attack in mice. The prolongation of bleeding time by KOK was much less than that by ASA, suggesting a beneficial potential of KOK than ASA in view of side effect. These findings suggest that KOK elicits remarkable anti-platelet and anti-thrombotic effects with less side effect of bleeding, and therefore, it may have a therapeutic potential for the prevention of platelet-associated cardiovascular diseases

Duration of dual antiplatelet therapy in acute coronary syndrome.

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Wilson, Simon John; Newby, David E; Dawson, Dana; Irving, John; Berry, Colin

2017-04-01

Despite a large volume of evidence supporting the use of dual antiplatelet therapy in patients with acute coronary syndrome, there remains major uncertainty regarding the optimal duration of therapy. Clinical trials have varied markedly in the duration of therapy, both across and within trials. Recent systematic reviews and meta-analyses suggest that shorter durations of dual antiplatelet therapy are superior because the avoidance of atherothrombotic events is counterbalanced by the greater risks of excess major bleeding with apparent increases in all-cause mortality with longer durations. These findings did not show significant heterogeneity according to whether patients had stable or unstable coronary heart disease. Moreover, the potential hazards and benefits may differ when applied to the general broad population of patients encountered in everyday clinical practice who have markedly higher bleeding and atherothrombotic event rates. Clinicians lack definitive information regarding the duration of therapy in patients with acute coronary syndrome and risk scores do not appear to be sufficiently robust to address these concerns. We believe that there is a pressing need to undertake a broad inclusive safety trial of shorter durations of therapy in real world populations of patients with acute coronary syndrome. The clinical evidence would further inform future research into strategies for personalised medicine. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Safety and efficacy of intensive vs. guideline antiplatelet therapy in high-risk patients with recent ischemic stroke or transient ischemic attack

DEFF Research Database (Denmark)

Christensen, Hanne Krarup

2015-01-01

RATIONALE: The risk of recurrence following a stroke or transient ischemic attack is high, especially immediately after the event. HYPOTHESIS: Because two antiplatelet agents are superior to one in patients with non-cardioembolic events, more intensive treatment might be even more effective. SAMPLE...... SIZE ESTIMATES: The sample size of 4100 patients will allow a shift to less recurrence, and less severe recurrence, to be detected (odds ratio 0·68) with 90% power at 5% significance. METHODS AND DESIGN: Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (ISRCTN47823388) is comparing...... the safety and efficacy of intensive (combined aspirin, clopidogrel, and dipyridamole) vs. guideline antiplatelet therapy, both given for one-month. This international collaborative parallel-group prospective randomized open-label blinded-end-point phase III trial plans to recruit 4100 patients with acute...

Serum nitric oxide metabolites and disease activity in patients with systemic sclerosis.

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Mok, Mo Yin; Fung, Peter Chin Wah; Ooi, Clara; Tse, Hung Fat; Wong, Yik; Lam, Yui Ming; Wong, Woon Sing; Lau, Chak Sing

2008-03-01

There is no surrogate marker in serum for defining disease activity in scleroderma (SSc). Nitric oxide (NO), which regulates vasodilation and possesses pro-inflammatory actions, has been implicated in the pathogenesis of SSc. We compared serum NO(x) (total nitrate and nitrite) level in SSc patients to healthy controls and evaluated its correlation with detailed symptomatology and scoring systems for various organ involvement. Symptoms and physical findings that suggested disease activity in regard to various organs were documented. Lung function test, high-resolution computed tomographic (HRCT) scan of thorax and echocardiography were performed. Serum NO(x) was measured by chemiluminescence. Serum NO(x) levels in SSc (n = 43) were significantly higher (72.4 +/- 47.8 microM) than age- and sex-matched controls (n = 41; 37.1 +/- 13.5 microM; p n = 9; OR 145.3, p = 0.01) were predictive factors for elevated serum NO(x). Prednisolone use was associated with lower serum NO(x) level (OR 0.06, p = 0.04). Elevated PAP of increasing severity was found to be associated with higher level of serum NO(x) (p = 0.004 by trend). Serum NO(x) in SSc patients were elevated compared to healthy controls. Serum NO(x) level was determined by multiple factors including age, prednisolone use, and elevated PAP.

In-hospital mortality after pre-treatment with antiplatelet agents or oral anticoagulants and hematoma evacuation of intracerebral hematomas.

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Stein, Marco; Misselwitz, Björn; Hamann, Gerhard F; Kolodziej, Malgorzata; Reinges, Marcus H T; Uhl, Eberhard

2016-04-01

Pre-treatment with antiplatelet agents is described to be a risk factor for mortality after spontaneous intracerebral hemorrhage (ICH). However, the impact of antithrombotic agents on mortality in patients who undergo hematoma evacuation compared to conservatively treated patients with ICH remains controversial. This analysis is based on a prospective registry for quality assurance in stroke care in the State of Hesse, Germany. Patients' data were collected between January 2008 and December 2012. Only patients with the diagnosis of spontaneous ICH were included (International Classification of Diseases 10th Revision codes I61.0-I61.9). Predictors of in-hospital mortality were determined by univariate analysis. Predictors with Phematoma evacuation (odds ratio [OR]: 2.5; 95% confidence interval [CI]: 1.24-4.97; P=0.010) compared to patients without antiplatelet pre-treatment treatment (OR: 0.9; 95% CI: 0.79-1.09; P=0.376). In conclusion a higher rate of in-hospital mortality after pre-treatment with antiplatelet agents in combination with hematoma evacuation after spontaneous ICH was observed in the presented cohort. Copyright © 2015 Elsevier Ltd. All rights reserved.

Serum elastase activity, serum elastase inhibitors, and occurrence of carotid atherosclerotic plaques: the Etude sur le Vieillissement Artériel (EVA) study.

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Zureik, Mahmoud; Robert, Ladislas; Courbon, Dominique; Touboul, Pierre-Jean; Bizbiz, Latifa; Ducimetière, Pierre

2002-06-04

In the last decades, interest has increased in the potential deleterious atherogenic effects of some cellular elastase activities. The results of experimental and clinical investigations were inconsistent. In this report, we assessed the associations of serum elastase activity and serum elastase inhibitors with carotid plaque occurrence during the 4-year follow-up in a population of 859 subjects free of coronary heart disease and stroke (age, 59 to 71 years). Serum elastase activity and serum elastase inhibitors were measured at baseline examination. Carotid B-mode ultrasound examination was performed at baseline and 2 years and 4 years later. The occurrence of carotid plaques in subjects with the lowest serum elastase activity values (quartile 1), in those with the intermediate values (quartiles 2 to 3), and in those with the highest values (quartile 4) was, respectively, 24.6%, 18.9%, and 12.2% (P<0.001 for trend). The multivariate odds ratios of carotid plaque occurrence associated with the three groups (adjusted for major known cardiovascular risk factors) were, respectively, 1.00, 0.67 (CI, 0.44 to 1.02; P<0.06), and 0.40 (CI, 0.23 to 0.70, P<0.001). For serum elastase inhibitors, the occurrence of carotid plaques in quartile 1 (lowest values), quartiles 2 to 3, and quartile 4 (highest values) was, respectively, 11.7%, 18.8%, and 25.2% (P for trend<0.001). The corresponding multivariate adjusted odds ratios were 1.00, 1.98 (CI, 1.19 to 3.31, P<0.01), and 3.18 (CI, 1.80 to 5.60, P<0.001). Low values of serum elastase activity and high values of serum elastase inhibitors were strongly and independently associated with increased 4-year carotid plaque occurrence. Further studies are necessary to elucidate the nature of the associations between elastase parameters and atherosclerosis.

Effect of B-vitamins on stroke risk among individuals with vascular disease who are not on antiplatelets: A meta-analysis.

Science.gov (United States)

Park, Jong-Ho; Saposnik, Gustavo; Ovbiagele, Bruce; Markovic, Daniela; Towfighi, Amytis

2016-02-01

Retrospective analyses of randomized controlled trials suggest that antiplatelet therapy may modify the potential cerebrovascular benefits of lowering homocysteine with B-vitamins among individuals with cardiovascular disease. We evaluated the effects of B-vitamin supplementation on risk of subsequent stroke among high cardiovascular risk individuals who are not taking antiplatelet medications. We systematically searched the Cochrane Central Register of controlled trials, PubMed, the Internet Stroke Center stroke trials, and the clinical trials.gov website from 1966 to April 2015. Inclusion criteria included: randomized controlled trials of homocysteine-lowering therapy with B-vitamins; high cardiovascular risk population and follow-up ≥1 year. We considered stroke as the primary outcome. Among 11 randomized controlled trials meeting inclusion criteria, three studies assessed stroke as an outcome and reported event rates according to whether or not individuals were taking antiplatelets: Vitamin Intervention for Stroke Prevention (VISP), VITAmins TO Prevent Stroke (VITATOPS), and Heart Outcomes Prevention Evaluation 2 (HOPE-2). A total of 4643 high vascular risk subjects not taking antiplatelets were evaluated. The overall effect size across studies was summarized using the fixed effects model after confirming there was no significant heterogeneity. Heterogeneity was assessed using the Cochran's Q and I(2) statistics. Compared with the control group, those taking B-vitamin supplementation had a lower risk of recurrent stroke (HR 0.86, 95% CI 0.62 to 1.19 for VISP; 0.65, 0.46 to 0.91 for VITATOPS; and 0.60, 0.39 to 0.92 for HOPE-2; overall HR 0.71, 0.58 to 0.88). Homocysteine lowering with B-vitamins among high vascular risk patients who are not taking antiplatelet therapy is related to a significant reduction (29%) in overall stroke risk. A clinical trial of B-vitamins in this group may be warranted. © 2016 World Stroke Organization.

Anticoagulant and Antiplatelet Prescribing Patterns for Patients with Atrial Fibrillation after Percutaneous Coronary Intervention.

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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

Characterization of Serum Phospholipase A2 Activity in Three Diverse Species of West African Crocodiles

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Mark Merchant

2011-01-01

Full Text Available Secretory phospholipase A2, an enzyme that exhibits substantial immunological activity, was measured in the serum of three species of diverse West African crocodiles. Incubation of different volumes of crocodile serum with bacteria labeled with a fluorescent fatty acid in the sn-2 position of membrane lipids resulted in a volume-dependent liberation of fluorescent probe. Serum from the Nile crocodile (Crocodylus niloticus exhibited slightly higher activity than that of the slender-snouted crocodile (Mecistops cataphractus and the African dwarf crocodile (Osteolaemus tetraspis. Product formation was inhibited by BPB, a specific PLA2 inhibitor, confirming that the activity was a direct result of the presence of serum PLA2. Kinetic analysis showed that C. niloticus serum produced product more rapidly than M. cataphractus or O. tetraspis. Serum from all three species exhibited temperature-dependent PLA2 activities but with slightly different thermal profiles. All three crocodilian species showed high levels of activity against eight different species of bacteria.

[Randomised comparative study of early versus delayed surgery in hip-fracture patients on concomitant treatment with antiplatelet drugs. Determination of platelet aggregation, perioperative bleeding and a review of annual mortality].

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Mas-Atance, J; Marzo-Alonso, C; Matute-Crespo, M; Trujillano-Cabello, J J; Català-Tello, N; de Miguel-Artal, M; Forcada-Calvet, P; Fernández-Martínez, J J

2013-01-01

A review of the perioperative management of patients with hip fractures and concomitant therapy with antiplatelet agents, and to analyse the differences in mortality and perioperative bleeding in early surgery (5 days). Platelet aggregation was measured on admission and immediately before surgery in all patients included in the study A total of 175 patients over 65 years old, with low energy hip fracture were randomised into 3 groups: Patients on antiplatelet therapy undergoing early surgery, patients on antiplatelet therapy undergoing delayed surgery, and patients not on antiplatelet therapy undergoing early surgery. The same clinical and laboratory data were collected prospectively up to 12 months for all the patients. The platelet aggregation was determined by a semi-quantitative computerised system based on impedance aggregometry in whole blood. Bleeding, transfusion requirements and analytical results showed no significant differences between groups. More than half (59.8%) of the patients not taking antiplatelet therapy had normal platelet aggregation on admission, while 13.5% of those taking antiplatelet agents did not. Multivariate analysis showed increased mortality at 12 months for the variables, low Barthel index before hip fracture (OR: 0.9-0.9) and number of transfusions (OR: 1.1-1.5). The average lenth of stay was 4.1 days greater in the delayed surgery group. Early surgery for patients receiving antiplatelet therapy has similar clinical outcomes to the delayed, but improves hospital efficiency by reducing the average length of stay. The antiplatelet drug reported by the patient showed low concordance with the determination of the platelet aggregation. Copyright © 2011 SECOT. Published by Elsevier Espana. All rights reserved.

[Soluble interleukin 2 receptor as activity parameter in serum of systemic and discoid lupus erythematosus].

Science.gov (United States)

Blum, C; Zillikens, D; Tony, H P; Hartmann, A A; Burg, G

1993-05-01

The evaluation of disease activity in systemic lupus erythematosus (SLE) is important for selection of the appropriate therapeutic regimen. In addition to the clinical picture, various laboratory parameters are taken into account. However, no validated criteria for the evaluation of the disease activity in SLE have yet been established. Recently, serum levels of soluble interleukin-2 receptor (sIL-2R) have been proposed as a potential parameter for disease activity in SLE. However, the studies reported on this subject so far have focused mainly on certain subsets of the disease, and the evaluation of the disease activity was based on a very limited number of parameters. In the present study, we determined serum levels of sIL-2R in 23 patients with SLE and 30 patients with discoid LE (DLE). Evaluation of disease activity in SLE was based on a comprehensive scale which considered numerous clinical signs and laboratory parameters. In SLE, serum levels of sIL-2R showed a better correlation with disease activity than all the other parameters investigated, including proteinuria, erythrocyte sedimentation rate, serum globulin concentration, titre of antibodies against double-stranded DNA, serum albumin concentration, serum complement levels and white blood cell count. For the first time, we report on elevated serum levels of sIL-2R in DLE, which also correlated with disease activity.

Pneumatic tube system transport does not alter platelet function in optical and whole blood aggregometry, prothrombin time, activated partial thromboplastin time, platelet count and fibrinogen in patients on anti-platelet drug therapy

Science.gov (United States)

Enko, Dietmar; Mangge, Harald; Münch, Andreas; Niedrist, Tobias; Mahla, Elisabeth; Metzler, Helfried; Prüller, Florian

2017-01-01

Introduction The aim of this study was to assess pneumatic tube system (PTS) alteration on platelet function by the light transmission aggregometry (LTA) and whole blood aggregometry (WBA) method, and on the results of platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen. Materials and methods Venous blood was collected into six 4.5 mL VACUETTE® 9NC coagulation sodium citrate 3.8% tubes (Greiner Bio-One International GmbH, Kremsmünster, Austria) from 49 intensive care unit (ICU) patients on dual anti-platelet therapy and immediately hand carried to the central laboratory. Blood samples were divided into 2 Groups: Group 1 samples (N = 49) underwent PTS (4 m/s) transport from the central laboratory to the distant laboratory and back to the central laboratory, whereas Group 2 samples (N = 49) were excluded from PTS forces. In both groups, LTA and WBA stimulated with collagen, adenosine-5’-diphosphate (ADP), arachidonic acid (AA) and thrombin-receptor-activated-peptide 6 (TRAP-6) as well as platelet count, PT, APTT, and fibrinogen were performed. Results No statistically significant differences were observed between blood samples with (Group 1) and without (Group 2) PTS transport (P values from 0.064 – 0.968). The AA-induced LTA (bias: 68.57%) exceeded the bias acceptance limit of ≤ 25%. Conclusions Blood sample transportation with computer controlled PTS in our hospital had no statistically significant effects on platelet aggregation determined in patients with anti-platelet therapy. Although AA induced LTA showed a significant bias, the diagnostic accuracy was not influenced. PMID:28392742

The correlation of serum bilirubin levels with disease activity in patients with rheumatoid arthritis.

Science.gov (United States)

Peng, You-Fan; Wang, Jun-Li; Pan, Guo-Gang

2017-06-01

We investigated the relationship between serum bilirubin and disease activity in patients with rheumatoid arthritis (RA). We included a total of 173 consecutive RA patients without steroid treatment and 346 healthy subjects; the disease activity score in 28 joints (DAS28) was used to assess disease activity in patients with RA. Serum bilirubin concentrations were significantly lower in RA patients than in controls. Serum bilirubin was found to be negatively correlated with C-reactive protein (CRP) concentration and erythrocyte sedimentation rate (ESR) (r=-0.165, P=0.030; r=-192, P=0.012) in patients with RA. There was a negative correlation between the serum bilirubin and DAS28 score (r=-0.331, Pbilirubin was independently associated with the DAS28 score (b=-0.225, P=0.001) in the multiple linear regression analysis. Serum bilirubin concentrations are lower in patients with RA compared to controls and correlate with disease activity in patients with RA. Copyright © 2017. Published by Elsevier B.V.

Serum creatine kinase and lactate dehydrogenase activities in ...

African Journals Online (AJOL)

... in thyroid function are common endocrine disorders affecting 5-10% of individuals over ... Key words: Hyperthyroidism, hypothyroidism, lactate dehydrogenase, serum creatine kinase ... individuals depends on age, race, lean body mass and physical activity. ... measured by radioimmunoassay on AXSYM System (Abbott.

Comparative evaluation of antiplatelet effect of lycopene with aspirin and the effect of their combination on platelet aggregation: An in vitro study.

Science.gov (United States)

Sawardekar, Swapna B; Patel, Tejal C; Uchil, Dinesh

2016-01-01

The objective was to compare antiplatelet effect of lycopene with aspirin and to study effect of combination of the two on platelet aggregation in vitro, using platelets from healthy volunteers. Platelets were harvested; platelet count of platelet-rich plasma adjusted to 2.5 Χ 10(5)/μL. Aspirin (140 μmol/L) and lycopene (4, 6, 8, 10, and 12 μmol/L) were studied in vitro against adenosine-5'- diphosphate (ADP) (2.5 μM/L) and collagen. All the concentrations of lycopene (4-12 μmol/L) exhibited reduction in maximum platelet aggregation induced by aggregating agents ADP and collagen (P Lycopene at concentration 10 μmol/L showed maximum platelet inhibition (47.05% ± 19.56%) against ADP, whereas lycopene at concentration 8 μmol/L showed maximum platelet inhibition (54.26% ± 30.71%) against collagen. Four μmol/L of lycopene combined with 140 μmol/L and 70 μmol/L aspirin showed greater inhibition of platelets as compared to aspirin 140 μmol/L alone, against both ADP and collagen. The study favorably compares lycopene and aspirin with respect to their antiplatelet activities against ADP and collagen. Lycopene can be considered as a potential target for modifying the thrombotic and pro-inflammatory events associated with platelet activation.

Serum paraoxonase activity and lipid hydroperoxide levels in adult ...

African Journals Online (AJOL)

EB

2013-09-03

Sep 3, 2013 ... Objectives: In this study, we aimed to investigate serum PON1 activity and lipid hydroperoxide (LOOH) levels in adult football players after three days ... oxidative stress after three days football tournament. In addition, physical activity for a ... polymorphism, gender, and exercise. Furthermore, it has been ...

Effects of aerobic activity on serum IgG concentration in male physical education students

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Arshadi Arshadi

2012-12-01

Full Text Available The aim of this study was to investigate the effects of aerobic activity on Serum IgG concentration. Consequently, 10 male physical education students with age ranging from 21 to 24 years old and mean body mass index 22.22 kg m2 volunteered to participate in this study. Aerobic activity was performed on bicycle ergometer for 30 minutes at intensity of 70 to 75 percent of maximum heart rate. Blood samples were obtained from subjects before and after aerobic activity. Changes in serum IgG concentration in pre-test and post-test were analyzed by dependent t-test using spss software. The results showed that aerobic activity not significantly effect on Serum IgG concentration (p=0.357. This study concludes that sub maximal aerobic activity does not affect on serum IgG concentration and there is no concern for athletes and coaches that sub maximal aerobic activity can impair immune function.

Practice points in gynecardiology: Abnormal uterine bleeding in premenopausal women taking oral anticoagulant or antiplatelet therapy.

Science.gov (United States)

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.

Effect of gamma radiation on tissue elastin content and serum elastolytic activity in rats

International Nuclear Information System (INIS)

Drozdz, M.; Olczyk, K.; Piwowarczyk, B.; Stawiarska, B.

1981-01-01

The elastin content of aorta, heart, skin and lungs as well as the serum elastolytic activity were determined in rats exposed to radiation. It was found that a single irradiation of rats with gamma rays (500 r) caused a decrease of the elastin content in all examined tissues. The serum elastolytic activity in the irradiated rats was increased. It is suggested that elastin degradation following radiation may be caused by changes in its molecular structure and possibly, due to increased serum elastolytic activity. (author)

Lowered serum dipeptidyl peptidase IV activity in patients with anorexia and bulimia nervosa.

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van West, D; Monteleone, P; Di Lieto, A; De Meester, I; Durinx, C; Scharpe, S; Lin, A; Maj, M; Maes, M

2000-01-01

The aim of this study was to examine whether anorexia nervosa and bulimia nervosa are accompanied by lower serum activity of dipeptidyl peptidase IV (DPP IV, EC 3.4.14.5), a membrane-bound serine protease that catalyses the cleavage of dipeptides from the amino-terminus of oligo- and polypeptides. Substrates of DPP IV are, amongst others, neuroactive eptides, such as substance P, growth hormone releasing hormone, neuropeptide Y, and peptide YY. DPP IV activity was measured in the serum of 21 women with anorexia nervosa, 21 women with bulimia nervosa and 18 normal women. Serum DPP IV activity was significantly lower in patients with anorexia nervosa and bulimia nervosa than in the normal controls. In the total study group, there were significant and inverse relationships between serum DPP IV activity and the total scores on the Bulimic Investigatory Test, Edinburgh, the Eating Disorder Inventory (EDI) and the Hamilton Depression Rating Scale. In the total study group no significant correlations between DPP IV and age, body weight or body mass index could be found. It is concluded that lowered serum DPP IV activity takes part in the pathophysiology of anorexia and bulimia nervosa. It is hypothesised that a combined dysregulation of DPP IV and neuroactive peptides, which are substrates of DPP IV, e.g. neuropeptide Y and peptide YY, could be an integral component of eating disorders.

Serum lipoproteins attenuate macrophage activation and Toll-Like Receptor stimulation by bacterial lipoproteins

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James Richard W

2010-09-01

Full Text Available Abstract Background Chlamydia trachomatis was previously shown to express a lipoprotein, the macrophage infectivity potentiator (Mip, exposed at the bacterial surface, and able to stimulate human primary monocytes/macrophages through Toll Like Receptor (TLR2/TLR1/TLR6, and CD14. In PMA-differentiated THP-1 cells the proinflammatory activity of Mip was significantly higher in the absence than in the presence of serum. The present study aims to investigate the ability of different serum factors to attenuate Mip proinflammatory activity in PMA-differentiated THP-1 cells and in primary human differentiated macrophages. The study was also extend to another lipoprotein, the Borrelia burgdorferi outer surface protein (OspA. The proinflammatory activity was studied through Tumor Necrosis Factor alpha (TNF-α and Interleukin (IL-8 release. Finally, TLR1/2 human embryonic kidney-293 (HEK-293 transfected cells were used to test the ability of the serum factors to inhibit Mip and OspA proinflammatory activity. Results In the absence of any serum and in the presence of 10% delipidated FBS, production of Mip-induced TNF-α and IL-8 in PMA-differentiated THP-1 cells were similar whereas they were significantly decreased in the presence of 10% FBS suggesting an inhibiting role of lipids present in FBS. In the presence of 10% human serum, the concentrations of TNF-α and IL-8 were 2 to 5 times lower than in the presence of 10% FBS suggesting the presence of more potent inhibitor(s in human serum than in FBS. Similar results were obtained in primary human differentiated macrophages. Different lipid components of human serum were then tested (total lipoproteins, HDL, LDL, VLDL, triglyceride emulsion, apolipoprotein (apoA-I, B, E2, and E3. The most efficient inhibitors were LDL, VLDL, and apoB that reduced the mean concentration of TNF-α release in Mip-induced macrophages to 24, 20, and 2%, respectively (p Conclusions These results demonstrated the ability of

Effect of benazepril and pimobendan on serum angiotensin-converting enzyme activity in dogs.

Science.gov (United States)

King, J N; Christinaz, C; Strehlau, G; Hornfeld, J

2018-06-01

To support their combined use, the objective of the study was to evaluate the effects of benazepril and pimobendan on serum angiotensin-converting enzyme (ACE) activity in dogs. A total of 48 healthy beagle dogs were randomized into four groups (n = 12 per group) in a parallel-group design study: A (control, placebo twice daily (BID)); B (0.5-1.0 mg/kg benazepril once daily (SID) in the morning, placebo in the evening); C (0.25-0.5 mg/kg benazepril BID); D (0.25-0.5 mg/kg benazepril and 0.125-0.25 mg/kg pimobendan, both BID). The test items were administered orally for 15 days. Serum ACE activity was measured on days 1 and 15. Groups B, C and D had significantly lower average serum ACE activity compared to baseline and to the control group, on both days 1 and 15. There were no significant differences in average ACE activity between groups B, C and D. Noninferiority of group C to B was demonstrated. In conclusion, 0.25-0.5 mg/kg benazepril administered BID produced noninferior inhibition of serum ACE activity compared to 0.5-1.0 mg/kg benazepril dosed SID. Pimobendan had no significant effect on benazepril's action on serum ACE activity. The results support the use of benazepril BID in dogs and in combination with pimobendan. © 2018 John Wiley & Sons Ltd.

Evaluation of bleeding following dental extraction in patients on long-term antiplatelet therapy: A clinical trial

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K George Varghese

2015-01-01

Conclusion: Hence, we recommend routine single tooth extractions in patients on long-term antiplatelet medication, without interruption or alteration of their medication. Such patients do not have an increased risk of prolonged or excessive postoperative bleeding.

Serum bactericidal activity as indicator of innate immunity in pacu Piaractus mesopotamicus (Holmberg, 1887

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J.D. Biller-Takahashi

2013-12-01

Full Text Available The immune system of teleost fish has mechanisms responsible for the defense against bacteria through protective proteins in several tissues. The protein action can be evaluated by serum bactericidal activity and this is an important tool to analyze the immune system. Pacu, Piaractus mesopotamicus, is one of the most important fish in national aquaculture. However there is a lack of studies on its immune responses. In order to standardize and assess the accuracy of the serum bactericidal activity assay, fish were briefly challenged with Aeromonas hydrophila and sampled one week after the challenge. The bacterial infection increased the concentration of protective proteins, resulting in a decrease of colony-forming unit values expressed as well as an enhanced serum bactericidal activity. The protocol showed a reliable assay, appropriate to determine the serum bactericidal activity of pacu in the present experimental conditions.

A time course study on prothrombotic parameters and their modulation by anti-platelet drugs in hyperlipidemic hamsters.

Science.gov (United States)

Singh, Vishal; Jain, Manish; Prakash, Prem; Misra, Ankita; Khanna, Vivek; Tiwari, Rajiv Lochan; Keshari, Ravi Shankar; Singh, Shivendra; Dikshit, Madhu; Barthwal, Manoj Kumar

2011-06-01

The present study was undertaken to assess the chronology of major pathological events associated with high cholesterol (HC) diet and their modulation by anti-platelet drugs. Male Golden Syrian hamsters were fed HC diet up to 90 days. Plasma lipid, glucose and coagulation parameters (commercial kits), platelet activation (whole blood aggregation and static adhesion), endothelial dysfunction (aortic ring vasoreactivity), splenocyte TNF-α, IFN-γ and iNOS mRNA transcripts (RT-PCR), and ferric chloride (time to occlusion) induced thrombosis were monitored at 15, 30, 60, and 90 days after HC feeding and compared with normolipidemic hamsters. A significant increase in plasma lipid levels was observed at 15 days of HC feeding, but other parameters remain unaltered. Enhanced ADP, collagen, and thrombin-induced platelet aggregation, splenocyte TNF-α expression along with endothelial dysfunction were observed from 30 to 90 days of HC feeding. Platelet adhesion on collagen-/fibrinogen-coated surface and IFN-γ expression were augmented only after 60 days, while enhanced iNOS expression, reduction in thrombin time, and potentiation of ferric chloride-induced thrombosis was observed only at 90 days of HC feeding. Thus, pathological changes induced by HC diet depend on the duration and extent of hyperlipidemia. Moreover, hamsters treated with anti-platelet drugs aspirin (5 mg/kg) or clopidogrel (10 mg/kg) along with HC feeding exhibited reduction in platelet activation as well as subsequent changes observed in the abovementioned parameters following HC feeding. Since reduction in TNF-α was associated with reversion in endothelial dysfunction and prothrombotic state, the role of platelets is implicated in the pathological changes associated with HC feeding.

Longitudinal assessment of thrombin generation potential in response to alteration of antiplatelet therapy after TIA or ischaemic stroke.

LENUS (Irish Health Repository)

Tobin, W O

2013-02-01

The impact of changing antiplatelet therapy on thrombin generation potential in patients with ischaemic cerebrovascular disease (CVD) is unclear. We assessed patients within 4 weeks of TIA or ischaemic stroke (baseline), and then 14 days (14d) and >90 days (90d) after altering antiplatelet therapy. Thrombin generation was assessed in platelet poor plasma. Ninety-one patients were recruited. Twenty-four were initially assessed on no antiplatelet therapy, and then after 14d (N = 23) and 90d (N = 8) on aspirin monotherapy; 52 were assessed on aspirin monotherapy, and after 14 and 90 days on aspirin and dipyridamole combination therapy; 21 patients were assessed on aspirin and after 14 days (N = 21) and 90 days (N = 19) on clopidogrel. Peak thrombin generation and endogenous thrombin potential were reduced at 14 and 90 days (p ≤ 0.04) in the overall cohort. We assessed the impact of individual antiplatelet regimens on thrombin generation parameters to investigate the cause of this effect. Lag time and time-to-peak thrombin generation were unchanged at 14 days, but reduced 90 days after commencing aspirin (p ≤ 0.009). Lag time, peak thrombin generation and endogenous thrombin potential were reduced at both 14 and 90 days after adding dipyridamole to aspirin (p ≤ 0.01). Lag time was reduced 14 days after changing from aspirin to clopidogrel (p = 0.045), but this effect was not maintained at 90 days (p = 0.2). This pilot study did not show any consistent effects of commencing aspirin, or of changing from aspirin to clopidogrel on thrombin generation potential during follow-up. The addition of dipyridamole to aspirin led to a persistent reduction in peak and total thrombin generation ex vivo, and illustrates the diverse, potentially beneficial, newly recognised \\'anti-coagulant\\' effects of dipyridamole in ischaemic CVD.

Risk of bleeding and stroke with oral anticoagulation and antiplatelet therapy in patients with atrial fibrillation in Taiwan: a nationwide cohort study.

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Pei-Chun Chen

Full Text Available Data on the use of oral anticoagulation (OAC and antiplatelet therapy and the risk of bleeding and stroke amongst Asian patients with atrial fibrillation (AF are limited. We investigated the risks of bleeding and stroke with use of oral anticoagulation (OAC and antiplatelet therapy as mono- or combination therapy, in patients with AF from a Chinese nationwide cohort study.We studied a cohort of 10384 patients (57.2% men, age 67.8 ± 13.2 yrs between 1999 and 2010 from the National Health Insurance Research Database in Taiwan. Records of prescriptions were obtained during follow-up. The main outcome was a recurrent stroke during the follow-up period. Time-dependent Cox proportional hazards models were used for this analysis.We documented 1009 events for bleeding, as well as 224 hemorrhagic stroke and 1642 ischemic stroke events during a median 3.2 (interquartile range, 1.05-6.54 years' follow-up. Compared with warfarin users, patients with antiplatelet therapy had a lower risk of bleeding (adjusted relative risk [RR], 0.59, 95% confidence interval [CI], 0.49-0.71, p<0.001 whilst combination therapy had a non-statistically significant higher bleeding risk (RR, 1.33, 95%, 0.91-1.94, p = 0.20. Patients on antiplatelet monotherapy had a similar risk for ischemic stroke compared with OAC (RR 1.05, 95% CI, 0.89-1.25, p = 0.50, whilst those on combination therapy had a significantly higher risk (RR 1.90, 95% CI, 1.34-2.70, p<0.001.In a national representative cohort, antiplatelet therapy had no significant difference in ischemic stroke risk to warfarin. For bleeding, aspirin had a lower risk compared to warfarin. This may reflect poor anticoagulation control, highlighting important missed opportunities for improved stroke prevention, especially in countries where anticoagulation management is suboptimal.

Antiplatelet Agents and the Prevention of Spontaneous Preterm Birth A Systematic Review and Meta-analysis

NARCIS (Netherlands)

van Vliet, Elvira O. G.; Askie, Lisa A.; Mol, Ben W. J.; Oudijk, Martijn A.

2017-01-01

OBJECTIVE: Spontaneous preterm birth is an important cause of neonatal mortality and morbidity. An increasing body of evidence suggests that uteroplacental ischemia plays an important role in the etiology of spontaneous preterm birth. We aimed to study whether antiplatelet agents reduce the risk of

Antiplatelet effect of phloroglucinol is related to inhibition of cyclooxygenase, reactive oxygen species, ERK/p38 signaling and thromboxane A2 production

International Nuclear Information System (INIS)

Chang, Mei-Chi; Chang, Hsiao-Hua; Chan, Chiu-Po; Chou, Han-Yi; Chang, Bei-En; Yeung, Sin-Yuet; Wang, Tong-Mei; Jeng, Jiiang-Huei

2012-01-01

Platelet dysfunction is a major risk factor of cardiovascular diseases such as atherosclerosis, stroke and myocardial infarction. Many antiplatelet agents are used for prevention and treatment of these diseases. In this study, phloroglucinol (2.5–25 μM) suppressed AA-induced platelet aggregation and thromboxane B 2 (TXB 2 ) production, but not U46619-induced platelet aggregation. Phloroglucinol (100–250 μM) showed little cytotoxicity to platelets. Phloroglucinol inhibited the COX-1 and COX-2 activities by 45–74% and 49–72% respectively at concentrations of 10–50 μM. At concentrations of 1 and 5 μM, phloroglucinol attenuated the AA-induced ROS production in platelets by 30% and 53%, with an IC 50 of 13.8 μM. Phloroglucinol also inhibited the PMA-stimulated ROS production in PMN. Preincubation of platelets by phloroglucinol (10–25 μM) markedly attenuated the AA-induced ERK and p38 phosphorylation. Intravenous administration of phloroglucinol (2.5 and 5 μmol/mouse) suppressed the ex vivo AA-induced platelet aggregation by 57–71%. Phloroglucinol administration also elevated the mice tail bleeding time. Moreover, phloroglucinol inhibited the IL-1β-induced PGE 2 production in pulp fibroblasts. These results indicate that antiplatelet and anti-inflammatory effects of phloroglucinol are related to inhibition of COX, ROS and TXA2 production as well as ERK/p38 phosphorylation in platelets. Phloroglucinol further suppress PMA-induced ROS production in PMN. The antiplatelet effect of phloroglucinol was confirmed by ex vivo study. Clinically, the consumption of phloroglucinol-containing food/natural products as nutritional supplement may be helpful to cardiovascular health. Phloroglucinol has potential pharmacological use. -- Highlights: ► Phloroglucinol suppressed AA-induced platelet aggregation and thromboxane production. ► Phloroglucinol inhibited COX activity and IL-1b-induced PGE2 production in fibroblast. ► Phloroglucinol declined platelet and

Dioxin-like activities in serum across European and Inuit populations

Science.gov (United States)

Long, Manhai; Andersen, Birgitte S; Lindh, Christian H; Hagmar, Lars; Giwercman, Aleksander; Manicardi, Gian-Carlo; Bizzaro, Davide; Spanò, Marcello; Toft, Gunnar; Pedersen, Henning S; Zvyezday, Valentyna; Bonde, Jens Peter; Bonefeld-Jorgensen, Eva C

2006-01-01

Background Persistent organic pollutants (POPs) such as polychlorinated dibenzo-p-dioxins/furans, polychlorinated biphenyls (PCBs) and organochlorine pesticides can cause a series of adverse effects on e.g. reproduction in animals and humans, many of which involve the aryl hydrocarbon receptor (AhR). The aim of the present study was to compare the integrated serum level of AhR mediated activity among European and Inuit populations, and evaluate whether the activity was associated to the selected POP markers, 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE). Methods The study included 338 males from Greenland (Inuit's), Sweden, Warsaw (Poland) and Kharkiv (Ukraine). The AhR transactivity of serum extracts alone (AhRag) and competitive AhR activity (AhRcomp) upon co-exposure with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were determined in the lipophilic serum fraction containing the POPs using the AhR mediated luciferase reporter Hepa1.12cR cell assay. Results The European groups showed higher median level of AhR-TEQ (TCDD toxic equivalents) compared to the Inuit's, whereas higher incidence of Inuits sample further induced AhRcomp activity. Neither AhRag nor AhR-TEQ were correlated to CB-153 or p,p'-DDE for any of the study groups. Multiple regressions showed a significant heterogeneity of association between the CB-153 and the AhRcomp across the study groups, and accordingly a negative association between AhRcomp and CB-153 was found for the Kharkiv group. Conclusion No consistent correlation between AhR activities and two POP markers was found. Although the difference of AhRag between European and Inuit men could not be explained by CB-153 or p,p'-DDE levels alone, we believe that the variation of AhR serum activity reflects different pattern of POP exposure, genetics and/or life style factors. PMID:16725033

Dual or Single Antiplatelet Therapy After Transcatheter Aortic Valve Implantation? A Systematic Review and Meta-Analysis.

Science.gov (United States)

Vavuranakis, Manolis; Siasos, Gerasimos; Zografos, Theodoros; Oikonomou, Evangelos; Vrachatis, Dimitris; Kalogeras, Konstantinos; Papaioannou, Theodoros; Kolokathis, Michail-Aggelos; Moldovan, Carmen; Tousoulis, Dimitrios

2016-01-01

Transcatheter aortic valve implantation (TAVI) has undeniably earned a prestigious post in the quiver of interventional cardiologists against symptomatic severe aortic stenosis. Cerebrovascular events are listed within the most frequent complications. We performed a systematic search of EMBASE, MEDLINE, and the Cochrane library from inception to March 2016 for the following search terms (transcatheter AND antiplatelet) OR (transcatheter AND antithrombotic) to retrieve studies of dual antiplatelet treatment (DAPT) and single antiplatelet treatment (SAPT) in patients after TAVI to study thrombotic, hemorrhagic and cardiovascular events at 30 days post procedure. From a total of 208 records 4 studies met inclusion criteria. In the included studies, 286 patients were enrolled in the DAPT group and 354 patients in the SAPT group. There was no difference in all-cause mortality, cardiovascular mortality, stroke, and myocardial infraction 30 days post TAVI between DAPT and SAPT. However, patients in the DAPT group had a significantly increased incidence of lethal and major bleeding at 30 days of follow-up and the incidence of the combined end-point of stroke, spontaneous MI, all-cause mortality and major bleeding was significantly higher in the DAPT group in comparison to the SAPT group. DAPT compared to SAPT in patients after TAVI increases incidence of hemorrhagic events with no benefits in terms of thrombotic events and cardiovascular mortality. However, these data must be interpreted cautiously and the choice of DAPT over SAPT must be based on an individual patient characteristic according to medical practice criteria.

Prospective evaluation of dermatologic surgery complications including patients on multiple antiplatelet and anticoagulant medications.

Science.gov (United States)

Bordeaux, Jeremy S; Martires, Kathryn J; Goldberg, Dori; Pattee, Sean F; Fu, Pingfu; Maloney, Mary E

2011-09-01

Few prospective studies have evaluated the safety of dermatologic surgery. We sought to determine rates of bleeding, infection, flap and graft necrosis, and dehiscence in outpatient dermatologic surgery, and to examine their relationship to type of repair, anatomic location of repair, antibiotic use, antiplatelet use, or anticoagulant use. Patients presenting to University of Massachusetts Medical School Dermatology Clinic for surgery during a 15-month period were prospectively entered. Medications, procedures, and complications were recorded. Of the 1911 patients, 38% were on one anticoagulant or antiplatelet medication, and 8.0% were on two or more. Risk of hemorrhage was 0.89%. Complex repair (odds ratio [OR] = 5.80), graft repair (OR = 7.58), flap repair (OR = 11.93), and partial repair (OR = 43.13) were more likely to result in bleeding than intermediate repair. Patients on both clopidogrel and warfarin were 40 times more likely to have bleeding complications than all others (P = .03). Risk of infection was 1.3%, but was greater than 3% on the genitalia, scalp, back, and leg. Partial flap necrosis occurred in 1.7% of flaps, and partial graft necrosis occurred in 8.6% of grafts. Partial graft necrosis occurred in 20% of grafts on the scalp and 10% of grafts on the nose. All complications resolved without sequelae. The study was limited to one academic dermatology practice. The rate of complications in dermatologic surgery is low, even when multiple oral anticoagulant and antiplatelet medications are continued, and prophylactic antibiotics are not used. Closure type and use of warfarin or clopidogrel increase bleeding risk. However, these medications should be continued to avoid adverse thrombotic events. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Elevation of Serum Acid Sphingomyelinase Activity in Children with Acute Respiratory Syncytial Virus Bronchiolitis.

Science.gov (United States)

Yoshida, Shuichiro; Noguchi, Atsuko; Kikuchi, Wataru; Fukaya, Hiroshi; Igarashi, Kiyoshi; Takahashi, Tsutomu

2017-12-01

Acid sphingomyelinase (ASM) is a lysosomal enzyme that hydrolyzes sphingomyelin into ceramide, a bioactive lipid to regulate cellular physiological functions. Thus, ASM activation has been reported as a key event in pathophysiological reactions including inflammation, cytokine release, oxidative stress, and endothelial damage in human diseases. Since ASM activation is associated with extracellular ASM secretion through unknown mechanisms, it can be detected by recognizing the elevation of secretory ASM (S-ASM) activity. Serum S-ASM activity has been reported to increase in chronic diseases, acute cardiac diseases, and systemic inflammatory diseases. However, the serum S-ASM has not been investigated in common acute illness. This study was designed to evaluate serum S-ASM activity in children with common acute illness. Fifty children with common acute illness and five healthy children were included in this study. The patients were categorized into five groups based on clinical diagnoses: acute respiratory syncytial virus (RSV) bronchiolitis, adenovirus infection, streptococcal infection, asthma, and other infections due to unknown origin. The serum S-ASM activity was significantly elevated at 6.9 ± 1.6 nmol/0.1 mL/6 h in the group of acute RSV bronchiolitis patients compared with healthy children who had a mean level of 1.8 ± 0.8 nmol/0.1 mL/6 h (p ASM activity was not significantly elevated. The results suggest an association of ASM activation with RSV infection, a cause for common acute illness. This is the first report to describe the elevation of serum S-ASM activity in respiratory tract infection.

Practice points in gynecardiology: Abnormal uterine bleeding in premenopausal women taking oral anticoagulant or antiplatelet therapy

NARCIS (Netherlands)

Maas, A.H.E.M.; Euler, M.; Bongers, M.Y.; Rolden, H.J.A.; Grutters, J.P.C.; Ulrich, L.; Schenck-Gustafsson, K.

2015-01-01

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

Concomitant nitrates enhance clopidogrel response during dual anti-platelet therapy.

Science.gov (United States)

Lee, Dong Hyun; Kim, Moo Hyun; Guo, Long Zhe; De Jin, Cai; Cho, Young Rak; Park, Kyungil; Park, Jong Sung; Park, Tae-Ho; Serebruany, Victor

2016-01-15

Despite advances in modern anti-platelet strategies, clopidogrel still remains the cornerstone of dual anti-platelet therapy (DAPT) in patients undergoing percutaneous coronary interventions (PCI). There is some inconclusive evidence that response after clopidogrel may be impacted by concomitant medications, potentially affecting clinical outcomes. Sustained released nitrates (SRN) are commonly used together with clopidogrel in post-PCI setting for mild vasodilatation and nitric oxide-induced platelet inhibition. We prospectively enrolled 458 patients (64.5 ± 9.6 years old, and 73.4% males) following PCI undergoing DAPT with clopidogrel and aspirin. Platelet reactivity was assessed by the VerifyNow™ P2Y12 assay at the maintenance outpatient setting. Concomitant SRN (n=266) significantly (p=0.008) enhanced platelet inhibition after DAPT (251.6 ± 80.9PRU) when compared (232.1 ± 73.5PRU) to the SRN-free (n=192) patients. Multivariate logistic regression analysis with the cut-off value of 253 PRU for defining heightened platelet reactivity confirmed independent correlation of more potent platelet inhibition during DAPT and use of SRN (Relative risk=1.675; Odds ratio [1.059-2.648]; p=0.027). In contrast, statins, calcium-channel blockers, beta blockers, angiotensin receptor blockers, ACE-inhibitors, diuretics, and anti-diabetic agents did not significantly impact platelet inhibition following DAPT. The synergic ability of SRN to enhance response during DAPT may have important clinical implications with regard to better cardiovascular protection, but extra bleeding risks, requiring further confirmation in a large randomized study. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Serum vaspin levels are associated with physical activity or physical fitness in Japanese: a pilot study.

Science.gov (United States)

Miyatake, Nobuyuki; Wada, Jun; Nakatsuka, Atsuko; Sakano, Noriko; Teshigawara, Sanae; Miyachi, Motohiko; Tabata, Izumi; Numata, Takeyuki

2014-05-01

To investigate the link between serum vaspin levels and physical activity and/or physical fitness in Japanese. A total of 156 subjects (81 men and 75 women) was enrolled in this cross-sectional study. Serum vaspin levels, physical activity by uniaxial accelerometers, peak oxygen uptake, and metabolic risk parameters were evaluated. We also assessed anthropometric and body composition parameters. Serum vaspin levels were over the level of 10 ng/mL in 15 subjects (9.6 %: Vaspin High group). In Vaspin Low group (men and 67 women), serum vaspin levels were 0.12 ± 0.18 ng/mL in men and 0.39 ± 0.70 ng/mL in women. Peak oxygen uptake was significantly and positively correlated with serum vaspin levels even after adjusting for age, physical activity evaluated by Σ[metabolic equivalents × h per week (METs[Symbol: see text]h/w)], BMI, and other confounding factors in men. In turn, physical activity was significantly and positively correlated with serum vaspin levels even after adjusting for confounding factors in women. Serum vaspin levels were closely associated with physical fitness in men and physical activity in women independent of body composition in this Japanese cohort.

Human serum activates CIDEB-mediated lipid droplet enlargement in hepatoma cells

Energy Technology Data Exchange (ETDEWEB)

Singaravelu, Ragunath [Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1N 6N5 (Canada); National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada); Lyn, Rodney K. [Department of Chemistry, University of Ottawa, Ottawa, Ontario K1N 6N5 (Canada); National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada); Srinivasan, Prashanth [National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada); Delcorde, Julie [Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1N 6N5 (Canada); National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada); Steenbergen, Rineke H.; Tyrrell, D. Lorne [Department of Medical Microbiology and Immunology, University of Alberta (Canada); Li Ka Shing Institute of Virology, Katz Centre for Pharmacy and Health Research, Edmonton, Alberta T6G 2S2 (Canada); Pezacki, John P., E-mail: John.Pezacki@nrc-cnrc.gc.ca [Department of Chemistry, University of Ottawa, Ottawa, Ontario K1N 6N5 (Canada); National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada)

2013-11-15

Highlights: •Human serum induced differentiation of hepatoma cells increases cellular lipid droplet (LD) size. •The observed increase in LD size correlates with increased PGC-1α and CIDEB expression. •Induction of CIDEB expression correlates with rescue of VLDL secretion and loss of ADRP. •siRNA knockdown of CIDEB impairs the human serum mediated increase in LD size. •This system represents a cost-efficient model to study CIDEB’s role in lipid biology. -- Abstract: Human hepatocytes constitutively express the lipid droplet (LD) associated protein cell death-inducing DFFA-like effector B (CIDEB). CIDEB mediates LD fusion, as well as very-low-density lipoprotein (VLDL) maturation. However, there are limited cell culture models readily available to study CIDEB’s role in these biological processes, as hepatoma cell lines express negligible levels of CIDEB. Recent work has highlighted the ability of human serum to differentiate hepatoma cells. Herein, we demonstrate that culturing Huh7.5 cells in media supplemented with human serum activates CIDEB expression. This activation occurs through the induced expression of PGC-1α, a positive transcriptional regulator of CIDEB. Coherent anti-Stokes Raman scattering (CARS) microscopy revealed a correlation between CIDEB levels and LD size in human serum treated Huh7.5 cells. Human serum treatment also resulted in a rapid decrease in the levels of adipose differentiation-related protein (ADRP). Furthermore, individual overexpression of CIDEB was sufficient to down-regulate ADRP protein levels. siRNA knockdown of CIDEB revealed that the human serum mediated increase in LD size was CIDEB-dependent. Overall, our work highlights CIDEB’s role in LD fusion, and presents a new model system to study the PGC-1α/CIDEB pathway’s role in LD dynamics and the VLDL pathway.

Human serum activates CIDEB-mediated lipid droplet enlargement in hepatoma cells

International Nuclear Information System (INIS)

Singaravelu, Ragunath; Lyn, Rodney K.; Srinivasan, Prashanth; Delcorde, Julie; Steenbergen, Rineke H.; Tyrrell, D. Lorne; Pezacki, John P.

2013-01-01

Highlights: •Human serum induced differentiation of hepatoma cells increases cellular lipid droplet (LD) size. •The observed increase in LD size correlates with increased PGC-1α and CIDEB expression. •Induction of CIDEB expression correlates with rescue of VLDL secretion and loss of ADRP. •siRNA knockdown of CIDEB impairs the human serum mediated increase in LD size. •This system represents a cost-efficient model to study CIDEB’s role in lipid biology. -- Abstract: Human hepatocytes constitutively express the lipid droplet (LD) associated protein cell death-inducing DFFA-like effector B (CIDEB). CIDEB mediates LD fusion, as well as very-low-density lipoprotein (VLDL) maturation. However, there are limited cell culture models readily available to study CIDEB’s role in these biological processes, as hepatoma cell lines express negligible levels of CIDEB. Recent work has highlighted the ability of human serum to differentiate hepatoma cells. Herein, we demonstrate that culturing Huh7.5 cells in media supplemented with human serum activates CIDEB expression. This activation occurs through the induced expression of PGC-1α, a positive transcriptional regulator of CIDEB. Coherent anti-Stokes Raman scattering (CARS) microscopy revealed a correlation between CIDEB levels and LD size in human serum treated Huh7.5 cells. Human serum treatment also resulted in a rapid decrease in the levels of adipose differentiation-related protein (ADRP). Furthermore, individual overexpression of CIDEB was sufficient to down-regulate ADRP protein levels. siRNA knockdown of CIDEB revealed that the human serum mediated increase in LD size was CIDEB-dependent. Overall, our work highlights CIDEB’s role in LD fusion, and presents a new model system to study the PGC-1α/CIDEB pathway’s role in LD dynamics and the VLDL pathway

Antiplatelet and anticoagulation regimen in patients with mechanical valve undergoing PCI - State-of-the-art review.

Science.gov (United States)

Gajanana, Deepakraj; Rogers, Toby; Iantorno, Micaela; Buchanan, Kyle D; Ben-Dor, Itsik; Pichard, Augusto D; Satler, Lowell F; Torguson, Rebecca; Okubagzi, Petros G; Waksman, Ron

2018-04-02

A common clinical dilemma regarding treatment of patients with a mechanical valve is the need for concomitant antiplatelet therapy for a variety of reasons, referred to as triple therapy. Triple therapy is when a patient is prescribed aspirin, a P2Y12 antagonist, and an oral anticoagulant. Based on the totality of the available evidence, best practice in 2017 for patients with mechanical valves undergoing percutaneous coronary intervention (PCI) is unclear. Furthermore, the optimal duration of dual antiplatelet therapy after PCI is evolving. With better valve designs that are less thrombogenic, the thromboembolic risks can be reduced at a lower international normalized ratio target, thus decreasing the bleeding risk. This review will offer an in-depth survey of current guidelines, current evidence, suggested approach for PCI in this cohort, and future studies regarding mechanical valve patients undergoing PCI. Copyright © 2017 Elsevier B.V. All rights reserved.

The relationship between serum adiponectin and postpartum luteal activity in high-producing dairy cows.

Science.gov (United States)

Kafi, Mojtaba; Tamadon, Amin; Saeb, Mehdi

2015-05-01

The aims of the present study were to initially determine the pattern of serum adiponectin concentrations during a normal estrous cycle in high-producing postpartum dairy cows and then evaluate the relationship between the serum concentrations of adiponectin and insulin with the commencement of postpartum luteal activity and ovarian activities in clinically healthy high-producing Holstein dairy cows. During a normal estrous cycle of cows (n = 6), serum adiponectin concentrations gradually decreased (P Cows with higher peak of milk yield had lower serum adiponectin concentrations by week 7 postpartum (P = 0.01). Serum adiponectin and insulin concentrations in cows with different postpartum luteal activity (based on the progesterone profile) were evaluated using the following class of cows: normal (≤45 days, n = 11) and delayed (>45 days, n = 11) commencement of luteal activity (C-LA) and four different profiles of normal luteal activity (NLA, n = 5), prolonged luteal phase (n = 6), delayed first ovulation (n = 6), and anovulation (AOV, n = 5). Serum adiponectin concentrations decreased gradually by week 3 postpartum in NLA and then increased; whereas in AOV and delayed first ovulation, they were decreased after week 3 postpartum (P cows was more than that of NLA cows. Insulin concentrations were almost maintained at a stable level in NLA cows (P > 0.05), whereas they increased in the other groups (P cows with C-LA greater than 45 days decreased more than those with C-LA 45 days or less after week 3 postpartum (P = 0.002). Serum adiponectin concentrations at week 7 postpartum were lower in delayed C-LA (P = 0.01). Milk yield in cows with C-LA greater than 45 days increased more than cows with C-LA 45 days or less postpartum (P = 0.002). Insulin concentrations increased relatively in parallel from weeks 1 to 7 postpartum in cows either with C-LA greater than 45 or with C-LA 45 days or less. We showed for the first time the profile of serum adiponectin concentrations

Lower Serum Paraoxonase-1 Activity Is Related to Higher Serum Amyloid A Levels in Metabolic Syndrome

NARCIS (Netherlands)

Kappelle, Paul Jan Willem Herman; Bijzet, Johan; Hazenberg, Bouke Pier; Dullaart, Robin Pieter Frank

Background and Aims. High-density lipoproteins (HDL) contain the anti-oxidative enzyme, paraoxonase-1 (PON-1), which is important for atheroprotection. The acute phase reactant, serum amyloid A (SAA), an HDL-associated apolipoprotein, may impair PON-1 activity, whereas SAA and PON-1 are reciprocally

Comparison of antiplatelet regimens in secondary stroke prevention

DEFF Research Database (Denmark)

Christiansen, Christine Benn; Pallisgaard, Jannik; Gerds, Thomas Alexander

2015-01-01

BACKGROUND: In patients with ischemic stroke of non-cardioembolic origin, acetylsalicylic acid, clopidogrel, or a combination of acetylsalicylic acid and dipyridamole are recommended for the prevention of a recurrent stroke. The purpose of this study was to examine the risk of bleeding or recurrent...... stroke associated with these three treatments. METHODS: Patients who were discharged with first-time ischemic stroke from 2007-2010, with no history of atrial fibrillation were identified from Danish nationwide registries. Hazard ratios (HRs) and 1-year risks of recurrent ischemic stroke and bleeding...... were calculated for each antiplatelet regimen. RESULTS: Among patients discharged after first-time ischemic stroke, 3043 patients were treated with acetylsalicylic acid, 12,295 with a combination of acetylsalicylic acid and dipyridamole, and 3885 with clopidogrel. Adjusted HRs for clopidogrel versus...

Serum protease activity in chronic kidney disease patients: The GANI_MED renal cohort.

Science.gov (United States)

Wolke, Carmen; Teumer, Alexander; Endlich, Karlhans; Endlich, Nicole; Rettig, Rainer; Stracke, Sylvia; Fiene, Beate; Aymanns, Simone; Felix, Stephan B; Hannemann, Anke; Lendeckel, Uwe

2017-03-01

Serum or plasma proteases have been associated with various diseases including cancer, inflammation, or reno-cardiovascular diseases. We aimed to investigate whether the enzymatic activities of serum proteases are associated with the estimated glomerular filtration rate (eGFR) in patients with different stages of chronic kidney disease (CKD). Our study population comprised 268 participants of the "Greifswald Approach to Individualized Medicine" (GANI_MED) cohort. Enzymatic activity of aminopeptidase A, aminopeptidase B, alanyl (membrane) aminopeptidase, insulin-regulated aminopeptidase, puromycin-sensitive aminopeptidase, leucine aminopeptidase 3, prolyl-endopeptidase (PEP), dipeptidyl peptidase 4 (DPP4), angiotensin I-converting enzyme, and angiotensin I-converting enzyme 2 (ACE2) proteases was measured in serum. Linear regression of the respective protease was performed on kidney function adjusted for age and sex. Kidney function was modeled either by the continuous Modification of Diet in Renal Disease (MDRD)-based eGFR or dichotomized by eGFR < 15 mL/min/1.73 m 2 or <45 mL/min/1.73 m 2 , respectively. Results with a false discovery rate below 0.05 were deemed statistically significant. Among the 10 proteases investigated, only the activities of ACE2 and DPP4 were correlated with eGFR. Patients with lowest eGFR exhibited highest DPP4 and ACE2 activities. DPP4 and PEP were correlated with age, but all other serum protease activities showed no associations with age or sex. Our data indicate that ACE2 and DPP4 enzymatic activity are associated with the eGFR in patients with CKD. This finding distinguishes ACE2 and DPP4 from other serum peptidases analyzed and clearly indicates that further analyses are warranted to identify the precise role of these serum ectopeptidases in the pathogenesis of CKD and to fully elucidate underlying molecular mechanisms. Impact statement • Renal and cardiac diseases are very common and often occur concomitantly

Serum prolidase enzyme activity in obese subjects and its relationship with oxidative stress markers.

Science.gov (United States)

Aslan, Mehmet; Duzenli, Ufuk; Esen, Ramazan; Soyoral, Yasemin Usul

2017-10-01

The relationship between increased serum enzyme activity of prolidase and increased rate of collagen turnover in the arterial wall has been asserted in previous studies. Collagen reflects much of the strength to the connective tissue involved in the arterial wall. Atherosclerosis is very common vessel disease and oxidative stress plays a pivotal role in the etiopathogenesis. Our objective was to examine the serum enzyme activity of prolidase and its possible relationships with oxidative stress parameters in obese subjects. Our present study was conducted 27 obese subjects and 26 age-matched healthy control subjects. The serum enzyme activity of prolidase in all study population was evaluated spectrophotometrically. Oxidative stress levels in obese subjects were analyzed with total antioxidant capacity (TAC) and total oxidant status (TOS) as well as oxidative stress index (OSI). Obese subjects have higher serum TOS and OSI indicators as well as prolidase activity than those in control subjects (for all; pstress levels in obese subjects. The significantly correlation between increased oxidative stress and increased prolidase activity may play a pivotal role in etiopathogenesis of atherosclerotic cardiovascular diseases in obese subjects. Copyright © 2017 Elsevier B.V. All rights reserved.

Apixaban Plus Mono Versus Dual Antiplatelet Therapy in Acute Coronary Syndromes: Insights From the APPRAISE-2 Trial

NARCIS (Netherlands)

Hess, C.N.; James, S.; Lopes, R.D.; Wojdyla, D.M.; Neely, M.L.; Liaw, D.; Hagstrom, E.; Bhatt, D.L.; Husted, S.; Goodman, S.G.; Lewis, B.S.; Verheugt, F.W.A.; Caterina, R. De; Ogawa, H.; Wallentin, L.; Alexander, J.H.

2015-01-01

BACKGROUND: Bleeding limits anticoagulant treatment in patients with acute coronary syndromes (ACS). OBJECTIVES: We investigated whether background concomitant antiplatelet therapy influences the effects of apixaban after ACS. METHODS: This study examined high-risk ACS patients who were treated with

The effect of pre-injury anti-platelet therapy on the development of complications in isolated blunt chest wall trauma: a retrospective study.

Directory of Open Access Journals (Sweden)

Ceri Battle

Full Text Available INTRODUCTION: The difficulties in the management of the blunt chest wall trauma patient in the Emergency Department due to the development of late complications are well recognised in the literature. Pre-injury anti-platelet therapy has been previously investigated as a risk factor for poor outcomes following traumatic head injury, but not in the blunt chest wall trauma patient cohort. The aim of this study was to investigate pre-injury anti-platelet therapy as a risk factor for the development of complications in the recovery phase following blunt chest wall trauma. METHODS: A retrospective study was completed in which the medical notes were analysed of all blunt chest wall trauma patients presenting to a large trauma centre in Wales in 2012 and 2013. Using univariate and multivariable logistic regression analysis, pre-injury platelet therapy was investigated as a risk factor for the development of complications following blunt chest wall trauma. Previously identified risk factors were included in the analysis to address the influence of confounding. RESULTS: A total of 1303 isolated blunt chest wall trauma patients presented to the ED in Morriston Hospital in 2012 and 2013 with complications recorded in 144 patients (11%. On multi-variable analysis, pre-injury anti-platelet therapy was found to be a significant risk factor for the development of complications following isolated blunt chest wall trauma (odds ratio: 16.9; 95% confidence intervals: 8.2-35.2. As in previous studies patient age, number of rib fractures, chronic lung disease and pre-injury anti-coagulant use were also found to be significant risk factors. CONCLUSIONS: Pre-injury anti-platelet therapy is being increasingly used as a first line treatment for a number of conditions and there is a concurrent increase in trauma in the elderly population. Pre-injury anti-platelet therapy should be considered as a risk factor for the development of complications by clinicians managing

Effect of Physical Activity on Serum Homocysteine Levels in Obese and Overweight Women

Directory of Open Access Journals (Sweden)

R. Soori

2016-09-01

Full Text Available Aims: Recently, homocysteine has been noticed as the major pathogenesis factor of the cardiovascular diseases. The aim of the study was to investigate the effects of physical activities on the serum homocysteine levels, as well as other cardiovascular risk factors in either obese or overweight women. Materials & Methods: In the controlled pretest-posttest semi-experimental study, 18 women referred to the Alzahra sport complexes in districts 3 and 4 of Tehran were studied in 2015. The subjects were selected via random sampling method and randomly divided into two groups; physical activity and control groups. And the intervention program was conducted in the former, while the latter received no intervention. The exercise protocol consisted of 10-week (5 sessions a week stretching exercises and aerobic activities (60 to 75% of the maximum heart beat. The serum homocystein level and lipids were measured both at the start and 48 hours after the exercises. Data was analyzed by SPSS 16 software using paired T and independent T tests. Findings: After the exercises, the mean serum homocysteine level in physical activity group significantly decreased than control group (p=0.001. Nevertheless, the difference between the lipid levels of physical activity and control groups was not significant (p>0.05. Conclusion: Reducing the serum homocysteine concentration, 10-week physical activity might also reduce the risk factors of cardiovascular diseases in either obese or overweight women.

The relationship between cerebrovascular complications and previously established use of antiplatelet therapy in left-sided infective endocarditis

DEFF Research Database (Denmark)

Snygg-Martin, Ulrika; Rasmussen, Rasmus Vedby; Hassager, Christian

2011-01-01

Cerebrovascular complications (CVC) in infective endocarditis (IE) are common. The only established treatments to reduce the incidence of CVC in IE are antibiotics and in selected cases early cardiac surgery. Potential effects of previously established antiplatelet therapy are under debate....

Serum lysozyme activity in coeliac disease: a possible aid to athe diagnosis of malignant change.

OpenAIRE

Cooper, B T; Ukabam, S O; Barry, R E; Read, A E

1981-01-01

Serum lysozyme activities were measured in 34 control subjects, 13 untreated adult coeliac patients, 21 adult coeliac patients on gluten-free diet, and eight coeliac patients with a histiocytic lymphoma. Serum lysozyme activities were raised in three untreated patients, three patients treated with a gluten-free diet, and in only two patients with coeliac disease and lymphoma. Serum lysozyme estimations cannot be recommended as an aid to the diagnosis of lymphoma in patients with coeliac disease.

Gender difference of serum angiotensin-converting enzyme (ACE) activity in DD genotype of ACE insertion/deletion polymorphism in elderly Chinese.

Science.gov (United States)

Zhang, Ya-Feng; Cheng, Qiong; Tang, Nelson L S; Chu, Tanya T W; Tomlinson, Brian; Liu, Fan; Kwok, Timothy C Y

2014-12-01

In this study we investigated the gender difference of serum angiotensin-converting enzyme (ACE) activity in a population of Hong Kong-dwelling elderly Chinese. A total of 1767 (843 male, 924 female) Hong Kong-dwelling elderly Chinese were recruited. ACE I/D genotypes were identified by polymerase chain reaction amplification and serum ACE activity was determined using a commercially available kinetic kit. ACE I/D genotype distribution was compared by chi-square test, the correlation between ACE I/D polymorphism and serum ACE activity was analysed by ANOVA test and gender difference of serum ACE activity of different genotypes was compared by independent sample t-test. No statistically significant difference of genotype distribution between male and female subjects was found. Serum ACE activity was significantly correlated with ACE genotype. Overall, there was no gender difference of serum ACE activity; however, when sub-grouping the subjects by ACE I/D genotype, male subjects with DD genotype had higher serum ACE activity than female subjects with DD genotype. No significant gender difference of genotype distribution was found in elderly Chinese. Serum ACE activity was significantly correlated with ACE I/D polymorphism in elderly Chinese. Male subjects with DD genotype had higher serum ACE activity than female subjects with DD genotype. © The Author(s) 2013.

Dual antiplatelet therapy in patients with aspirin resistance following coronary artery bypass grafting: study protocol for a randomized controlled trial [NCT01159639

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Gasparovic Hrvoje

2012-08-01

Full Text Available Abstract Background Coronary artery disease remains the dominant cause of mortality in developed countries. While platelets have been recognized to play a pivotal role in atherothrombosis, the ideal antiplatelet regime after coronary artery surgery remains elusive. The evolution of CABG has presently moved beyond technical improvements to involve modulation of pharmacologic management designed to improve patient outcomes. The aim of this trial will be to test the hypothesis that the addition of clopidogrel to patients with documented postoperative aspirin resistance will reduce the incidence of major cardiovascular events. Methods Patients scheduled for isolated coronary artery surgery will be eligible for the study. Patients in whom postoperative multiple electrode aggregometry documents aspirin resistance will be randomized into two groups. The control group will receive 300 mg of aspirin. The dual antiplatelet group will receive 75 mg of clopidogrel in addition to 300 mg of aspirin. Patients will be followed for 6 months. Major adverse cardiac and cerebrovascular events (death from any cause, myocardial infarction, stroke, hospitalization due to cardiovascular pathology as well as bleeding events will be recorded. Discussion This will be the first trial that will specifically address the issue of dual antiplatelet therapy in patients undergoing coronary artery surgery who have been found to be aspirin resistant. In the event that the addition of clopidogrel proves to be beneficial in this subset of surgical patients, this study could significantly impact their future antiplatelet management. This randomized controlled trial has been registered at the ClinicalTrials.gov website (Identifier NCT01159639.

THE BACTERICIDAL ACTIVITY OF NORMAL GUINEA PIG SERUM AGAINST LISTERIA MONOCYTOGENES AND ITS INHIBITION BY A LISTERIAL CELL EXTRACT,

Science.gov (United States)

Normal guinea pig serum contains bactericidins active against Listeria monocytogenes. The listeriocidal activity of the serum did not increase after...factor. Lysozyme was not implicated in the bactericidal system. It was suggested that the bactericidal activity of guinea pig serum might be due either to

Gelatinases A and B activities in the serum of patients with various coronary artery disease stages

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Radenković Sandra

2010-01-01

Full Text Available Background/Aim. The main characteristic of matrix metalloproteinases (MMPs is the degradation of extracellular matrix. Synthesis of MMPs has been reported in coronary atherosclerotic lesions in patients with coronary disease (CD suggesting a pathogenic role of MMPs in its development. Recently there is increasing evidence that gelatinase A (pro MMP-2 and gelatinase B (proMMP-9 play a pathogenic role in the development of the atherosclerotic plaques. The aim of the study was to determine, by the use of a gel image system, a possible presence of active gelatinases in the serum of the patients with CD, as well as if their activity is higher in these patients than in healthy people. Methods. By gelatin zymography we analyzed the activity of proMMP-2 and proMMP-9 in the serum of 50 patients with various coronary artery disease stages and in the serum of 15 healthy controls. The activity was measured by using a gel image system (Kodak Image 1D 3.6.. Results. ProMMP-2 and proMMP-9 activity was significantly higher in the serum of patients with CD compared to controls. There was higher activity of MMP-2 and MMP-9 in the serum of patients with acute myocardial infarction (AMI compared to patients with stable angina pectoris, as well as higher proMMP-9 activity in patients with unstable angina pectoris compared to patients with stable angina pectoris. Conclusion. ProMMP-2 and proMMP-9 participate in processes associated with destabilizing plaques and understanding the processes of MMPs activation and regulation may have significant benefits in clinical interpretation. The reported higher proMMP-2 and proMMP-9 activity in the serum of patients with CD suggests a role of proMMP-2 and proMMP-9 in prognostic stratification of these patients and in designing new drugs.

Continuous recording of long-chain acyl-coenzyme A synthetase activity using fluorescently labeled bovine serum albumin

DEFF Research Database (Denmark)

Demant, Erland J.F.; Nystrøm, Birthe T.

2001-01-01

acyl-Coenzyme A, synthetase, activity assay, fluorescence recording, fatty acid probe, serum albumin, hydroxycoumarin, detergent, micelles, Pseudomonas fragi, rat liver microsomes......acyl-Coenzyme A, synthetase, activity assay, fluorescence recording, fatty acid probe, serum albumin, hydroxycoumarin, detergent, micelles, Pseudomonas fragi, rat liver microsomes...

The changes in amount and activity of matrix metalloproteinases in rat's serum irradiated by γ-rays

International Nuclear Information System (INIS)

Le Chen; Li Haijun; Cheng Ying; Min Rui

2009-01-01

Rats were whole body irradiated by γ-rays with different doses. A commercial ELISA kit was used to analyze the concentration of MMP-2 and MMP-9 in rat's serum. And Gelatin zymography electrophoresis was used to test the activity of serum MMPs at 24 h after irradiation. The results show that the amount and the activity of MMP-2 in rat's serum increase with increment of irradiation doses. Compared with 1∼4 Gy exposed groups a significant rising of MMP-2 has been found in 5 Gy and 6 Gy exposed groups (p<0.01). On the contrast, the amount and activity of MMP-9 in rat's serum have a little change at 24 hours after irradiation in all of exposed groups. It can be deduced that the changes with amount and activity of MMP-2 may be used as a potential indicator of exposed dose in organisms. (authors)

Tympanic membrane bleeding complications during hyperbaric oxygen treatment in patients with or without antiplatelet and anticoagulant drug treatment

NARCIS (Netherlands)

Fijen, Valerie A.; Westerweel, Peter E.; van Ooij, Pieter Jan A. M.; van Hulst, Rob A.

2016-01-01

Middle ear barotrauma (MEBt) is a frequently occurring complication of hyperbaric oxygen treatment (HBOT). High-grade MEBt may involve tympanic membrane (TM) haemorrhaging. Although many patients undergoing HBOT use antiplatelet or anticoagulant drugs, it is unknown whether these drugs increase the

Antiplatelet therapy: aspirin resistance and all that jazz!

Science.gov (United States)

Divani, Afshin A; Zantek, Nicole D; Borhani-Haghighi, Afshin; Rao, Gundu H R

2013-01-01

Platelets play a crucial role in the pathogenesis of atherosclerosis, thrombosis, and stroke. Aspirin used alone or in combination with other antiplatelet drugs has been shown to offer significant benefit to patients at high risk of vascular events. Resistance to the action of aspirin may decrease this benefit. Aspirin resistance has been defined by clinical and/or laboratory criteria; however, detection by laboratory methods prior to experiencing a clinical event will likely provide the greatest opportunity for intervention. Numerous laboratory methods with different cutoff points have been used to evaluate the resistance. Noncompliance with aspirin treatment has also confounded studies. A single assay is currently insufficient to establish resistance. Combinations of results to confirm compliance and platelet inhibition may identify "at-risk" individuals who truly have aspirin resistance. The most effective strategy for managing patients with aspirin resistance is unknown; however, studies are currently underway to address this issue.

Interaction of Silver Nanoparticles with Serum Proteins Affects Their Antimicrobial Activity In Vivo

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Gnanadhas, Divya Prakash; Ben Thomas, Midhun; Thomas, Rony; Raichur, Ashok M.

2013-01-01

The emergence of multidrug-resistant bacteria is a global threat for human society. There exist recorded data that silver was used as an antimicrobial agent by the ancient Greeks and Romans during the 8th century. Silver nanoparticles (AgNPs) are of potential interest because of their effective antibacterial and antiviral activities, with minimal cytotoxic effects on the cells. However, very few reports have shown the usage of AgNPs for antibacterial therapy in vivo. In this study, we deciphered the importance of the chosen methods for synthesis and capping of AgNPs for their improved activity in vivo. The interaction of AgNPs with serum albumin has a significant effect on their antibacterial activity. It was observed that uncapped AgNPs exhibited no antibacterial activity in the presence of serum proteins, due to the interaction with bovine serum albumin (BSA), which was confirmed by UV-Vis spectroscopy. However, capped AgNPs [with citrate or poly(vinylpyrrolidone)] exhibited antibacterial properties due to minimized interactions with serum proteins. The damage in the bacterial membrane was assessed by flow cytometry, which also showed that only capped AgNPs exhibited antibacterial properties, even in the presence of BSA. In order to understand the in vivo relevance of the antibacterial activities of different AgNPs, a murine salmonellosis model was used. It was conclusively proved that AgNPs capped with citrate or PVP exhibited significant antibacterial activities in vivo against Salmonella infection compared to uncapped AgNPs. These results clearly demonstrate the importance of capping agents and the synthesis method for AgNPs in their use as antimicrobial agents for therapeutic purposes. PMID:23877702

Contribution of Helicobacter pylori infection to the risk of peptic ulcer bleeding in patients on nonsteroidal anti-inflammatory drugs, antiplatelet agents, anticoagulants, corticosteroids and selective serotonin reuptake inhibitors.

Science.gov (United States)

Venerito, M; Schneider, C; Costanzo, R; Breja, R; Röhl, F-W; Malfertheiner, P

2018-06-01

Nonsteroidal anti-inflammatory drugs, low-dose aspirin, non-aspirin antiplatelet agents, anticoagulants, selective serotonin reuptake inhibitors and corticosteroids increase the risk of gastroduodenal bleeding. To determine in a retrospective cohort study the contribution of Helicobacter pylori infection to the risk of peptic ulcer bleeding in patients taking these drugs. Among patients with peptic ulcer disease diagnosed by endoscopy from 01/2004 to 12/2014 (N = 1719, 60% males, age 65.8 ± 14.5), 56.9% had peptic ulcer bleeding (cases) and 43.1% uncomplicated peptic ulcer disease (controls). Demographics, intake of nonsteroidal anti-inflammatory drugs, aspirin, non-aspirin antiplatelet agents, anticoagulants, selective serotonin reuptake inhibitors, proton pump inhibitors and corticosteroids were documented. H. pylori status was determined by histology, rapid urease test or serology. Adjusted odds ratios (OR) were estimated by logistic regression analysis. Helicobacter pylori infection increased the risk of peptic ulcer bleeding in nonsteroidal anti-inflammatory drug and aspirin users (OR = 2.91, 95% CI = 1.71-4.98 and OR = 2.23, 95% CI = 1.52-3.28, respectively), but not in patients on anticoagulants, selective serotonin reuptake inhibitor or corticosteroid therapy. H. pylori-positive status substantially increased the risk of peptic ulcer bleeding in patients on non-aspirin antiplatelet agents (OR = 4.37, 95% CI = 1.28-14.99), concomitant aspirin/nonsteroidal anti-inflammatory drug intake (OR = 5.85, 95% CI = 1.68-20.36) and combined antiplatelet therapy (OR = 8.43, 95% CI = 1.09-65.17). After further adjustment for proton pump inhibitor intake, H. pylori infection was still a risk factor for peptic ulcer bleeding in nonsteroidal anti-inflammatory drug and aspirin users. Helicobacter pylori infection increases the risk of peptic ulcer bleeding in peptic ulcer disease patients on nonsteroidal anti-inflammatory drugs, aspirin and non

The Emerging Role of miR-223 in Platelet Reactivity: Implications in Antiplatelet Therapy

Science.gov (United States)

Shi, Rui; Zhou, Xin; Ji, Wen-Jie; Zhang, Ying-Ying; Ma, Yong-Qiang; Zhang, Jian-Qi

2015-01-01

Platelets are anuclear cells and are devoid of genomic DNA, but they are capable of de novo protein synthesis from mRNA derived from their progenitor cells, megakaryocytes. There is mounting evidence that microRNA (miRNA) plays an important role in regulating gene expression in platelets. miR-223 is the most abundant miRNAs in megakaryocytes and platelets. One of the miR-223-regulated genes is ADP P2Y12, a key target for current antiplatelet drug therapy. Recent studies showed that a blunted response to P2Y12 antagonist, that is, high on-treatment platelet reactivity (HTPR), is a strong predictor of major cardiovascular events (MACEs) in coronary heart disease (CHD) patients receiving antiplatelet treatment. Recent clinical cohort study showed that the level of circulating miR-223 is inversely associated with MACE in CHD patients. In addition, our recent data demonstrated that the level of both intraplatelet and circulating miR-223 is an independent predictor for HTPR, thus providing a link between miR-223 and MACE. These lines of evidence indicate that miR-223 may serve as a potential regulatory target for HTPR, as well as a diagnostic tool for identification of HTPR in clinical settings. PMID:26221610

Splenic TFH expansion participates in B-cell differentiation and antiplatelet-antibody production during immune thrombocytopenia.

Science.gov (United States)

Audia, Sylvain; Rossato, Marzia; Santegoets, Kim; Spijkers, Sanne; Wichers, Catharina; Bekker, Cornelis; Bloem, Andries; Boon, Louis; Flinsenberg, Thijs; Compeer, Ewoud; van den Broek, Theo; Facy, Olivier; Ortega-Deballon, Pablo; Berthier, Sabine; Leguy-Seguin, Vanessa; Martin, Laurent; Ciudad, Marion; Samson, Maxime; Trad, Malika; Lorcerie, Bernard; Janikashvili, Nona; Saas, Philippe; Bonnotte, Bernard; Radstake, Timothy R D J

2014-10-30

Antiplatelet-antibody-producing B cells play a key role in immune thrombocytopenia (ITP) pathogenesis; however, little is known about T-cell dysregulations that support B-cell differentiation. During the past decade, T follicular helper cells (TFHs) have been characterized as the main T-cell subset within secondary lymphoid organs that promotes B-cell differentiation leading to antibody class-switch recombination and secretion. Herein, we characterized TFHs within the spleen of 8 controls and 13 ITP patients. We show that human splenic TFHs are the main producers of interleukin (IL)-21, express CD40 ligand (CD154), and are located within the germinal center of secondary follicles. Compared with controls, splenic TFH frequency is higher in ITP patients and correlates with germinal center and plasma cell percentages that are also increased. In vitro, IL-21 stimulation combined with an anti-CD40 agonist antibody led to the differentiation of splenic B cells into plasma cells and to the secretion of antiplatelet antibodies in ITP patients. Overall, these results point out the involvement of TFH in ITP pathophysiology and the potential interest of IL-21 and CD40 as therapeutic targets in ITP. © 2014 by The American Society of Hematology.

Proteolytic activity of IgGs from blood serum of wistar rats at experimental rheumatoid arthritis

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Yu. Ya. Kit

2014-10-01

Full Text Available The aim of this work was to study the proteolytic activity of IgGs purified from blood serum of Wistar rats at experimental rheumatoid arthritis (ERA induced by an injection of bovine collagen of type II. Twenty rats were immunized with a preparation of bovine collagen II (Sigma-Aldrich, USA in the presence of complete Freund’s adjuvant. ERA development was determined by inflammation in limbs of treated animals. IgG preparations were isolated from blood serum of immunized and non-immunized animals by precipitation of antibodies with 33% ammonium sulfate followed by chromatography on the Protein G-Sepharose column. Human histone H1, bovine collagen II, calf thymus histones, myelin basic protein (MBP, bovine serum albumin (BSA, and bovine casein were used as substrates of the proteolytic activity of IgGs. It was found that IgG preparations from blood serum of rats with ERA were capable of cleaving histone H1 and MBP, however, they were catalytically inactive towards collagen II, casein, BSA, and core histones. IgGs from blood serum of non-immunized rats were proteolytically inactive towards all used protein substrates. Thus, we demonstrated that immunization of rats with bovine collagen II induced IgG-antibodies possessing the proteolytic activity towards histone H1 and MBP. This activity might be associated with the development of inflammatory processes in the immunized rats.

Comparing the Effect of Fasting and Physical Activity on Active and Non-active Males’ Body Composition, Serum Osmolarity Levels and Some Parameters of Electrolytes

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M Nematy

2012-08-01

Full Text Available Introduction: Ever since there is insufficient and incoherent information about the effect of the Ramadan Fasting together with regular exercise on levels of serum osmolarity, and electrolytes concentration. The aim of this study was to compare the effect of fasting and physical activity on active and non-active males’ body composition, serum osmolarity levels and some parameters of electrolytes. Methods: Twenty six healthy males, who were selected by convenience sampling method, were divided into two (active and non-active groups. The Active group participated in football training for three sessions per week during the fasting month. All measurements were repeated on the first and last day of fasting month and were used to analyze the test results. Results: The average differences were significantly decreased in weight, BMI, WHR, mineral, total water in two groups (P≤0.05. There was a significant difference in average of BMI, WHR, body fat, mineral and total water between two groups (P≤0.05. Within-group mean differences in glucose, potassium, urine and albumin in both groups were significant (P≤0.05. Differences of serum osmolarity in between- and within-groups were not significant in both groups. While, glucose decreased significantly, the levels of the protein decreased, and urea increased significantly only in non active fasting group. Conclusion: According to these results, regular exercise together with the Ramadan fasting result in change in some serum osmolarity index, electrolytes and water. Therefore, it is necessary to protect the athletics against the malnutrition in Ramadan fasting by using the diet schedule and enough water.

SPE-HPLC purification of endocrine disrupting compounds from human serum for assessment of xenoestrogenic activity

DEFF Research Database (Denmark)

Hjelmborg, P.S.; Ghisari, Mandana; Bonefeld-Jørgensen, Eva

2006-01-01

Assessment of xenoestrogenic activity in human serum samples requires the removal of endogenous sex hormones to assure that the activity measured originates from xenobiotic compounds only. Serum samples representing high, medium and lower accumulation of persistent organic pollutants (POPs) were...... measured by ERE-CALUX was validated and considered to be a valuable tool to assess the combined ER effect of lipophilic serum POPs where additive/synergistic and agonistic/antagonistic effects are integrated giving an overall estimate of exposure and bioactivity....... for the study. MVLN cells, stably transfected with an estrogen receptor (ER) luciferase reporter vector (ERE-CALUX), were exposed to the reconstituted SPE-HPLC extracts for determination of the integrated estrogenic activity. The effects of PCBs were analyzed by direct in vitro exposure of PCBs (138, 153...

Antiplatelet treatment for prevention of cerebrovascular events in patients with vascular diseases: a systematic review and meta-analysis

NARCIS (Netherlands)

Gouya, G.; Arrich, J.; Wolzt, M.; Huber, K.; Verheugt, F.W.A.; Gurbel, P.A.; Pirker-Kees, A.; Siller-Matula, J.M.

2014-01-01

BACKGROUND AND PURPOSE: The efficacy and safety of different antiplatelet regimes for prevention of stroke in patients at high risk were investigated in a systematic review and meta-analysis. METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Web of Science.

Trace element analysis of human blood serum by neutron activation analysis

International Nuclear Information System (INIS)

Nakahara, H.; Nagame, Y.; Yoshizawa, Y.; Oda, H.; Gotoh, S.; Murakami, Y.

1979-01-01

An attempt was made to determine if there is any correlation between trace element concentrations in human blood serum and some specific diseases. The serum samples of the patients suffering from cancer, Down syndrome, and Banti syndrome were analyzed by the neutron activation method and compared with the trace element concentrations observed among clinically healthy men. The cancer patients had concentrations in Rb, Mn, Fe, Co, Cu, Zn, Al and Se below normal. The Down syndrome patients were found to have similar deficiencies in Cr, Mn, Fe, Co, Zn, Cu and Sb. (author)

Dioxin-like activities in serum across European and Inuit populations

DEFF Research Database (Denmark)

Long, Manhai; Andersen, Birgitte S; Lindh, Christian H

2006-01-01

Background: Persistent organic pollutants (POPs) such as polychlorinated dibenzo--dioxins/furans, polychlorinatedbiphenyls (PCBs) and organochlorine pesticides can cause a series of adverse effects on e.g. reproduction in animals andhumans, many of which involve the aryl hydrocarbon receptor (Ah......,p'-DDE).Methods: The study included 338 males from Greenland (Inuit's), Sweden, Warsaw (Poland) and Kharkiv (Ukraine). TheAhR transactivity of serum extracts alone (AhRag) and competitive AhR activity (AhRcomp) upon co-exposure with2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were determined in the lipophilic serum fraction...

Seasonal disease activity and serum vitamin D levels in rheumatoid ...

African Journals Online (AJOL)

Background: Vitamin D is a steroid hormone that plays essential roles in calcium and phosphorus metabolism, bone formation and mineralization homeostasis, also has a role in the maintenance of immune-homeostasis. Objective: We aimed to investigate seasonal serum vitamin D levels and seasonal disease activity in ...

The 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE trial: study protocol for a randomized controlled trial

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Park Kyung

2012-03-01

Full Text Available Abstract Background Second-generation drug-eluting stents (DES have raised the bar of clinical performance. These stents are mostly made from cobalt chromium alloy. A newer generation DES has been developed from platinum chromium alloy, but clinical data regarding the efficacy and safety of the platinum chromium-based everolimus-eluting stent (PtCr-EES is limited, with no comparison data against the cobalt chromium-based zotarolimus-eluting stent (CoCr-ZES. In addition, an antiplatelet regimen is an integral component of medical therapy after percutaneous coronary intervention (PCI. A 1-week duration of doubling the dose of clopidogrel (double-dose antiplatelet therapy (DDAT was shown to improve outcome at 1 month compared with conventional dose in acute coronary syndrome (ACS patients undergoing PCI. However in Asia, including Korea, the addition of cilostazol (triplet antiplatelet therapy (TAT is used more commonly than doubling the dose of clopidogrel in high-risk patients. Methods In the 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE trial, approximately 3,750 patients are being prospectively and randomly assigned in a 2 × 2 factorial design according to the type of stent (PtCr-EES vs CoCr-ZES and antiplatelet regimen (TAT vs DDAT. The first primary endpoint is target lesion failure at 1 year for the stent comparison, and the second primary endpoint is net clinical outcome at 1 month for comparison of antiplatelet therapy regimen. Discussion The HOST-ASSURE trial is the largest study yet performed to directly compare the efficacy and safety of the PtCr-EES versus CoCr-ZES in an 'all-comers' population. In addition, this study will also compare the clinical outcome of TAT versus DDAT for 1-month post PCI. Trial registration ClincalTrials.gov number NCT01267734.

Continuing versus discontinuing antiplatelet drugs, vasodilators, and/or cerebral ameliorators on perioperative total blood loss in total knee arthroplasty without pneumatic tourniquet

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Sachiyuki Tsukada, MD

2018-03-01

Full Text Available Background: Although studies have supported the utility of perioperative continuation of antiplatelet drugs, vasodilators, and cerebral ameliorators in most procedures, no study compared total volume of blood loss after total knee arthroplasty (TKA in patients continuing and discontinuing these drugs. Methods: We retrospectively reviewed 266 consecutive patients undergoing TKA, and included 67 patients (25.2% taking antiplatelet drugs, vasodilators, or cerebral ameliorators in this study. All TKAs were performed without a pneumatic tourniquet. The primary outcome was perioperative total blood loss calculated from blood volume and change in hemoglobin. As subgroup analysis, we compared perioperative total blood loss in patients taking antiplatelet drugs. Results: There was no significant difference between the continuing group (n = 38 and discontinuing group (n = 29 in terms of the perioperative total blood loss (1025 ± 364 vs 1151 ± 327 mL, respectively; mean difference 126 mL; 95% confidence interval −45 to 298 mL; P = .15. No major bleeding or thrombotic events occurred in either group until postoperative 3-month follow-up. In patients taking antiplatelet drugs (n = 51, no significant difference was observed in the total blood loss between the continuing group (n = 30 and discontinuing group (n = 21 (1056 ± 287 vs 1151 ± 305 mL, respectively; mean difference 95 mL; 95% confidence interval −75 to 264 mL; P = .27. Conclusions: No significant differences in terms of perioperative total blood loss were observed between patients continuing and discontinuing study drugs. Continuing these drugs may be preferable in the perioperative period of TKA. Keywords: Knee, Primary arthroplasty, Bleeding events, Thrombotic events, Noncardiac surgery

Lumbar puncture in patients using anticoagulants and antiplatelet agents

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Renan Domingues

2016-08-01

Full Text Available ABSTRACT The use of anticoagulants and antiplatelet agents has largely increased. Diagnostic lumbar puncture in patients taking these drugs represents a challenge considering the opposing risks of bleeding and thrombotic complications. To date there are no controlled trials, specific guidelines, nor clear recommendations in this area. In the present review we make some recommendations about lumbar puncture in patients using these drugs. Our recommendations take into consideration the pharmacology of these drugs, the thrombotic risk according to the underlying disease, and the urgency in cerebrospinal fluid analysis. Evaluating such information and a rigorous monitoring of neurological symptoms after lumbar puncture are crucial to minimize the risk of hemorrhage associated neurological deficits. An individualized patient decision-making and an effective communication between the assistant physician and the responsible for conducting the lumbar puncture are essential to minimize potential risks.

Patent foramen ovale closure with GORE HELEX or CARDIOFORM Septal Occluder vs. antiplatelet therapy for reduction of recurrent stroke or new brain infarct in patients with prior cryptogenic stroke

DEFF Research Database (Denmark)

Kasner, Scott E; Thomassen, Lars; Søndergaard, Lars

2017-01-01

Rationale The utility of patent foramen ovale (PFO) closure for secondary prevention in patients with prior cryptogenic stroke is uncertain despite multiple randomized trials completed to date. Aims The Gore REDUCE Clinical Study (REDUCE) aims to establish superiority of patent foramen ovale...... with truly cryptogenic strokes. Medical therapy is limited to antiplatelet agents in both arms thereby reducing confounding. The trial should determine whether patent foramen ovale closure with the Gore septal occluders is safe and more effective than medical therapy alone for the prevention of recurrent...... closure in conjunction with antiplatelet therapy over antiplatelet therapy alone in reducing the risk of recurrent clinical ischemic stroke or new silent brain infarct in patients who have had a cryptogenic stroke. Methods and design This controlled, open-label trial randomized 664 subjects...

Site-specific RNase A activity was dramatically reduced in serum from multiple types of cancer patients.

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Weiyan Huang

Full Text Available Potent RNase activities were found in the serum of mammals but the physiological function of the RNases was never well illustrated, largely due to the caveats in methods of RNase activity measurement. None of the existing methods can distinguish between RNases with different target specificities. A systematic study was recently carried out in our lab to investigate the site-specificity of serum RNases on double-stranded RNA substrates, and found that serum RNases cleave double-stranded RNAs predominantly at 5'-U/A-3' and 5'-C/A-3' dinucleotide sites, in a manner closely resembling RNase A. Based on this finding, a FRET assay was developed in the current study to measure this site-specific serum RNase activity in human samples using a double stranded RNA substrate. We demonstrated that the method has a dynamic range of 10(-5 mg/ml- 10(-1 mg/ml using serial dilution of RNase A. The sera of 303 cancer patients were subjected to comparison with 128 healthy controls, and it was found that serum RNase activities visualized with this site-specific double stranded probe were found to be significantly reduced in patients with gastric cancer, liver cancer, pancreatic cancer, esophageal cancer, ovary cancer, cervical cancer, bladder cancer, kidney cancer and lung cancer, while only minor changes were found in breast and colon cancer patients. This is the first report using double stranded RNA as probe to quantify site-specific activities of RNase A in a serum. The results illustrated that RNase A might be further evaluated to determine if it can serve as a new class of biomarkers for certain cancer types.

Site-Specific RNase A Activity Was Dramatically Reduced in Serum from Multiple Types of Cancer Patients

Science.gov (United States)

Huang, Weiyan; Zhao, Mei; Wei, Na; Wang, Xiaoxia; Cao, Huqing; Du, Quan; Liang, Zicai

2014-01-01

Potent RNase activities were found in the serum of mammals but the physiological function of the RNases was never well illustrated, largely due to the caveats in methods of RNase activity measurement. None of the existing methods can distinguish between RNases with different target specificities. A systematic study was recently carried out in our lab to investigate the site-specificity of serum RNases on double-stranded RNA substrates, and found that serum RNases cleave double-stranded RNAs predominantly at 5′-U/A-3′ and 5′-C/A-3′ dinucleotide sites, in a manner closely resembling RNase A. Based on this finding, a FRET assay was developed in the current study to measure this site-specific serum RNase activity in human samples using a double stranded RNA substrate. We demonstrated that the method has a dynamic range of 10−5 mg/ml- 10−1 mg/ml using serial dilution of RNase A. The sera of 303 cancer patients were subjected to comparison with 128 healthy controls, and it was found that serum RNase activities visualized with this site-specific double stranded probe were found to be significantly reduced in patients with gastric cancer, liver cancer, pancreatic cancer, esophageal cancer, ovary cancer, cervical cancer, bladder cancer, kidney cancer and lung cancer, while only minor changes were found in breast and colon cancer patients. This is the first report using double stranded RNA as probe to quantify site-specific activities of RNase A in a serum. The results illustrated that RNase A might be further evaluated to determine if it can serve as a new class of biomarkers for certain cancer types. PMID:24805924

Effect of psoriasis activity and topical treatment on serum lipocalin-2 levels.

Science.gov (United States)

Baran, A; Świderska, M; Myśliwiec, H; Flisiak, I

2017-03-01

Psoriasis has been considered as systemic disorder. Lipocalin-2 might be a link between psoriasis and its comorbidities. Aim of the study was to investigate the associations between serum lipocalin-2 levels and the disease activity, markers of inflammation or metabolic disturbances and changes after topical treatment in psoriatic patients. Thirty-seven individuals with active plaque-type psoriasis and 15 healthy controls were recruited. Blood samples were collected before and after 14 days of therapy. Serum lipocalin-2 concentrations were examined by enzyme-linked immunosorbent assay. The results were correlated with Psoriasis Area and Severity Index (PASI), body mass index (BMI), inflammatory and biochemical markers, lipid profile and with effectiveness of topical treatment. Lipocalin-2 serum levels were significantly increased in psoriatic patients in comparison to the controls (p = 0.023). No significant correlations with indicators of inflammation, nor BMI or PASI were noted. A statistical association between lipocalin-2 and low-density lipoprotein-cholesterol was shown. After topical treatment serum lipocalin-2 level did not significantly change (p = 0.9), still remaining higher than in the controls, despite clinical improvement. Lipocalin-2 might be a marker of psoriasis and convey cardiovascular or metabolic risk in psoriatic patients, but may not be a reliable indicator of inflammation, severity of psoriasis nor efficacy of antipsoriatic treatment.

Preventive Aspirin and Other Antiplatelet Medication Use Among U.S. Adults Aged ≥40 Years: Data from the National Health and Nutrition Examination Survey, 2011–2012

Science.gov (United States)

Dillon, Charles F.; Eberhardt, Mark S.; Wright, Jacqueline D.; Burt, Vicki L.

2015-01-01

Objective We estimated the prevalence of preventive aspirin and/or other antiplatelet medication use and the dosage of aspirin use in the U.S. adult population. Methods We conducted cross-sectional analyses of a representative sample (n=3,599) of U.S. adults aged ≥40 years from the National Health and Nutrition Examination Survey, 2011–2012. Results In 2011–2012, one-third of U.S. adults aged ≥40 years reported taking preventive aspirin and/or other antiplatelet medications, 97% of whom indicated preventive aspirin use. Preventive aspirin use increased with age (from 11% of those aged 40–49 years to 54% of those ≥80 years of age, paspirin than non-Hispanic Asian (20%, paspirin. Among those with cardiovascular disease, 76% reported taking preventive aspirin and/or other antiplatelet medications, of whom 91% were taking preventive aspirin. Among adults without cardiovascular disease, 28% reported taking preventive aspirin. Adherence rates to medically recommended aspirin use were 82% overall, 91% for secondary prevention, and 79% for primary prevention. Among current preventive aspirin users, 70% were taking 81 milligrams (mg) of aspirin daily and 13% were taking 325 mg of aspirin daily. Conclusion The vast majority of antiplatelet therapy is preventive aspirin use. A health-care provider's recommendation to take preventive aspirin is an important determinant of current preventive aspirin use. PMID:26556936

Serum Paraoxonase 1 Activity Is Associated with Fatty Acid Composition of High Density Lipoprotein

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Maryam Boshtam

2013-01-01

Full Text Available Introduction. Cardioprotective effect of high density lipoprotein (HDL is, in part, dependent on its related enzyme, paraoxonase 1 (PON1. Fatty acid composition of HDL could affect its size and structure. On the other hand, PON1 activity is directly related to the structure of HDL. This study was designed to investigate the association between serum PON1 activity and fatty acid composition of HDL in healthy men. Methods. One hundred and forty healthy men participated in this research. HDL was separated by sequential ultracentrifugation, and its fatty acid composition was analyzed by gas chromatography. PON1 activity was measured spectrophotometrically using paraxon as substrate. Results. Serum PON1 activity was directly correlated with the amount of stearic acid and dihomo-gamma-linolenic acid (DGLA. PON1/HDL-C was directly correlated with the amount of miristic acid, stearic acid, and DGLA and was inversely correlated with total amount of ω6 fatty acids of HDL. Conclusion. The fatty acid composition of HDL could affect the activity of its associated enzyme, PON1. As dietary fats are the major determinants of serum lipids and lipoprotein composition, consuming some special dietary fatty acids may improve the activity of PON1 and thereby have beneficial effects on health.

Serum paraoxonase 1 activity is associated with fatty acid composition of high density lipoprotein.

Science.gov (United States)

Boshtam, Maryam; Razavi, Amirnader Emami; Pourfarzam, Morteza; Ani, Mohsen; Naderi, Gholam Ali; Basati, Gholam; Mansourian, Marjan; Dinani, Narges Jafari; Asgary, Seddigheh; Abdi, Soheila

2013-01-01

Cardioprotective effect of high density lipoprotein (HDL) is, in part, dependent on its related enzyme, paraoxonase 1 (PON1). Fatty acid composition of HDL could affect its size and structure. On the other hand, PON1 activity is directly related to the structure of HDL. This study was designed to investigate the association between serum PON1 activity and fatty acid composition of HDL in healthy men. One hundred and forty healthy men participated in this research. HDL was separated by sequential ultracentrifugation, and its fatty acid composition was analyzed by gas chromatography. PON1 activity was measured spectrophotometrically using paraxon as substrate. Serum PON1 activity was directly correlated with the amount of stearic acid and dihomo-gamma-linolenic acid (DGLA). PON1/HDL-C was directly correlated with the amount of miristic acid, stearic acid, and DGLA and was inversely correlated with total amount of ω 6 fatty acids of HDL. The fatty acid composition of HDL could affect the activity of its associated enzyme, PON1. As dietary fats are the major determinants of serum lipids and lipoprotein composition, consuming some special dietary fatty acids may improve the activity of PON1 and thereby have beneficial effects on health.

The clinical significance and risk factors of anti-platelet factor 4/heparin antibody on maintenance hemodialysis patients: a two-year prospective follow-up.

Directory of Open Access Journals (Sweden)

Delong Zhao

Full Text Available BACKGROUND: Heparin-induced thrombocytopenia is an immune response mediated by anti-PF4/heparin antibody, which is clinically characterized by thrombocytopenia and thromboembolic events. In this study, a prospective and multi-center clinical investigation 1 determined the positive rate of anti-PF4/heparin antibody in maintenance hemodialysis patients in China, 2 identified the related risk factors, and 3 further explored the effect of the anti-PF4/heparin antibody on bleeding, thromboembolic events, and risk of death in the patients. METHODS: The serum anti-PF4/heparin antibody was measured in 661 patients from nine hemodialysis centers, detected by IgG-specific ELISA and followed by confirmation with excess heparin. Risk factors of these patients were analyzed. Based on a two-year follow-up, the association between the anti-PF4/heparin antibody and bleeding, thromboembolic events, and risk of death in the patients was investigated. RESULTS: 1 The positivity rate of the anti-PF4/heparin antibody in maintenance hemodialysis patients was 5.6%. With diabetes as an independent risk factor, the positivity rate of the anti-PF4/heparin antibody decreased in the patients undergoing weekly dialyses ≥3 times. 2 The positivity rate of the anti-PF4/heparin antibody was not related to the occurrence of clinical thromboembolic events and was not a risk factor for death within two years in maintenance hemodialysis patients. 3 Negativity for the anti-PF4/heparin antibody combined with a reduction of the platelet count or combined with the administration of antiplatelet drugs yielded a significant increase in bleeding events. However, the composite determination of the anti-PF4/heparin antibody and thrombocytopenia, as well as the administration of antiplatelet drugs, was not predictive for the risk of thromboembolic events in the maintenance hemodialysis patients. CONCLUSIONS: A single detection of the anti-PF4/heparin antibody did not predict the occurrence

Relationship between changed alveolar-capillary permeability and angiotensin converting enzyme activity in serum in sarcoidosis.

OpenAIRE

Eklund, A; Blaschke, E

1986-01-01

The effect of altered alveolar-capillary permeability on angiotensin converting enzyme (ACE) activity in serum (SACE) was studied in 45 patients with sarcoidosis and 21 healthy controls. In sarcoidosis increased albumin concentrations in the bronchoalveolar lavage fluid (L albumin) and increased ratios of L albumin to albumin in serum (S albumin) indicated an increased permeability of the alveolar-capillary membrane. ACE activity in the lavage fluid (LACE) was correlated with the number of al...

Mechanism of anti-HIV activity of succinylated human serum albumin

NARCIS (Netherlands)

Kuipers, ME; Berg, HVD; Swart, PJ; Laman, Jon; Meijer, DKF; Kopelman, MHGM; Huisman, H

1999-01-01

In the present study, we described the interaction of succinylated human serum albumin (Suc-HSA), a negatively charged anti-HIV-1 active protein, with HIV-1 gp120 and in detail with the third variable domain of gp120 (V3 loop). To this end, different assay formats were tested in which gp120- and

Antiplatelet therapy at the time of coronary artery bypass grafting

DEFF Research Database (Denmark)

Kremke, Michael; Jensen, Mariann Tang; Bak, Mikkel

2013-01-01

OBJECTIVES: The purpose of this multicentre cohort study was to examine the relationship between antiplatelet therapy (APT) at the time of coronary artery bypass grafting (CABG) and postoperative bleeding complications, transfusion requirements and adverse cardiovascular events. METHODS: A matched...... Denmark Heart Registry. RESULTS: Of the 6350 patients enrolled, 1846 (29%) had been exposed to aspirin or clopidogrel within 5 days prior to CABG (the APT group). Matching with the remaining 4504 (71%) patients of the control group resulted in 1132 pairs of patients. Patients in the APT group had greater...... postoperative bleeding (OR: 2.08, 95% CI: 1.55-2.80). Overall, preoperative APT had no significant effect on postoperative 30-day mortality, incidence of myocardial infarction, stroke or need for dialysis. CONCLUSIONS: Preoperative APT is associated with increased bleeding and greater transfusion requirements...

Increased serum YKL-40 in patients with pulmonary sarcoidosis—a potential marker of disease activity?

DEFF Research Database (Denmark)

Johansen, JS; Milman, N; Hansen, M

2005-01-01

macrophages and giant cells in the granulomatous sarcoid lesions of patients with pulmonary sarcoidosis produce YKL-40 and to determine whether serum YKL-40 in these patients were associated with disease activity. Methods: Serum YKL-40 was determined by radioimmunoassay in 27 patients with a histological...

Characteristics of patients with atrial fibrillation prescribed antiplatelet monotherapy compared with those on anticoagulants: insights from the GARFIELD-AF registry

NARCIS (Netherlands)

Verheugt, F.W.A.; Gao, H.; Mahmeed, W. Al; Ambrosio, G.; Angchaisuksiri, P.; Atar, D.; Bassand, J.P.; Camm, A.J.; Cools, F.; Eikelboom, J.; Kayani, G.; Lim, T.W.; Misselwitz, F.; Pieper, K.S.; Eickels, M. van; Kakkar, A.K.

2018-01-01

Aims: Current atrial fibrillation (AF) guidelines discourage antiplatelet (AP) monotherapy as alternative to anticoagulants (ACs). Why AP only is still used is largely unknown. Methods and results: Factors associated with AP monotherapy prescription were analysed in GARFIELD-AF, a registry of

Significance of determination of serum cytidine deaminase (CD) levels for diagnosis of active rheumatoid arthritis (RA)

International Nuclear Information System (INIS)

Xiao Chuangqing; Jang Xiaogong; He Yunnan

2005-01-01

Objective: To determine the clinical value of measurement of serum cytidine deaminase (CD) levels in patients with active rheumatoid arthritis (RA). Methods: Serum levels of CD were detected with spectrophotometry, in 33 patients with active RA and 60 controls. The erythrocyte sedimentation rate (ESR) and CRP content were also determined in both groups. Results: The ser- um CD contents in patients with active RA(14.80 ± 2.11U/ml) were significantly higher than those in controls(4.86±1.86 U/ml,P<0.01). The CRP contents (51.46 ± 20.43mg/L) and ESR readings(85.03 ± 27.6mm/h) in the patients were also significantly higher than those in the controls(3.40 ± 2.21mg/L and 13.04 ± 4.89mm/h respectively, all P<0.01). In the patients, the serum CD contents were linearly positively correlated with the ESR contents and CRP readings (r=0.6324 and 0.8013 respectively, P <0.01). Conclusion: Serum CD is an early biochemical marker for diagnosis of active rheumatoid arthritis and is also of prognostic value. (authors)

Platelets Express Activated P2Y12 Receptor in Patients With Diabetes Mellitus.

Science.gov (United States)

Hu, Liang; Chang, Lin; Zhang, Yan; Zhai, Lili; Zhang, Shenghui; Qi, Zhiyong; Yan, Hongmei; Yan, Yan; Luo, Xinping; Zhang, Si; Wang, Yiping; Kunapuli, Satya P; Ye, Hongying; Ding, Zhongren

2017-08-29

Platelets from patients with diabetes mellitus are hyperactive. Hyperactivated platelets may contribute to cardiovascular complications and inadequate responses to antiplatelet agents in the setting of diabetes mellitus. However, the underlying mechanism of hyperactivated platelets is not completely understood. We measured P2Y 12 expression on platelets from patients with type 2 diabetes mellitus and on platelets from rats with diabetes mellitus. We also assayed platelet P2Y 12 activation by measuring cAMP and VASP phosphorylation. The antiplatelet and antithrombotic effects of AR-C78511 and cangrelor were compared in rats. Finally, we explored the role of the nuclear factor-κB pathway in regulating P2Y 12 receptor expression in megakaryocytes. Platelet P2Y 12 levels are 4-fold higher in patients with type 2 diabetes mellitus compared with healthy subjects. P2Y 12 expression correlates with ADP-induced platelet aggregation (r=0.89, P diabetes mellitus is constitutively activated. Although both AR-C78511, a potent P2Y 12 inverse agonist, and cangrelor have similar antiplatelet efficacy on platelets from healthy subjects, AR-C78511 exhibits more powerful antiplatelet effects on diabetic platelets than cangrelor (aggregation ratio 36±3% versus 49±5%, respectively, P diabetes mellitus than cangrelor (thrombus weight 4.9±0.3 mg versus 8.3±0.4 mg, respectively, P diabetes mellitus. Platelet P2Y 12 receptor expression is significantly increased and the receptor is constitutively activated in patients with type 2 diabetes mellitus, which contributes to platelet hyperactivity and limits antiplatelet drug efficacy in type 2 diabetes mellitus. © 2017 American Heart Association, Inc.

Serum diamine oxidase activity in patients with histamine intolerance.

Science.gov (United States)

Manzotti, G; Breda, D; Di Gioacchino, M; Burastero, S E

2016-03-01

Intolerance to various foods, excluding bona fide coeliac disease and lactose intolerance, represents a growing cause of patient visits to allergy clinics.Histamine intolerance is a long-known, multifaceted clinical condition triggered by histamine-rich foods and alcohol and/or by drugs that liberate histamine or block diamine oxidase (DAO), the main enzyme involved in the metabolism of ingested histamine. Histamine limitation diets impose complex, non-standardized restrictions that may severely impact the quality of life of patients. We retrospectively evaluated 14 patients who visited allergy outpatient facilities in northern Italy with a negative diagnosis for IgE-mediated food hypersensitivity, coeliac disease, conditions related to gastric hypersecretion, and systemic nickel hypersensitivity, and who previously underwent a histamine limitation diet with benefits for their main symptoms. Serum diamine oxidase levels and the clinical response to diamine oxidase supplementation were investigated. We found that 10 out of 14 patients had serum DAO activityintolerance. Moreover, 13 out of 14 patients subjectively reported a benefit in at least one of the disturbances related to food intolerances following diamine oxidase supplementation. The mean value (±SD) of diamine oxidase activity in the cohort of patients with histamine intolerance symptoms was 7.04±6.90 U/mL compared to 39.50±18.16 U/mL in 34 healthy controls (P=0.0031). In patients with symptoms triggered by histamine-rich food, measuring the serum diamine oxidase activity can help identify subjects who can benefit from a histamine limitation diet and/or diamine oxidase supplementation.Properly designed, controlled studies investigating histamine intolerance that include histamine provocation are indispensable for providing insights into the area of food intolerances, which are currently primarily managed with non-scientific approaches in Italy. © The Author(s) 2015.

Determination of mercury in human serum and packed blood cells by neutron activation analysis

International Nuclear Information System (INIS)

Versieck, J.; Vanballenberghe, L.; Wittoek, A.; Vermeir, G.; Vandecasteele, C.

1990-01-01

A method is described for the determination of mercury in human blood serum and packed blood cells employing neutron activation analysis. Great attention was devoted to the collection and manipulation of the samples. The accuracy and precision of the method were tested by analyzing biological reference materials and by comparing the concentrations measured in a number of serum samples to those obtained by another, independent technique (cold vapor atomic absorption spectrometry) in the same samples. The article reports the levels measured in blood serum and packed blood cells samples from 15 adult volunteers, as well as the figures determined in a open-quotes second-generationclose quotes biological reference material (freeze-dried human serum), prepared and conditioned at the University of Ghent

Percutaneous coronary intervention and antiplatelet therapy in patients with atrial fibrillation receiving apixaban or warfarin: Insights from the ARISTOTLE trial

NARCIS (Netherlands)

Kopin, D.; Jones, W.S.; Sherwood, M.W.; Wojdyla, D.M.; Wallentin, L.; Lewis, B.S.; Verheugt, F.W.A.; Vinereanu, D.; Bahit, M.C.; Halvorsen, S.; Huber, K.; Parkhomenko, A.; Granger, C.B.; Lopes, R.D.; Alexander, J.H.

2018-01-01

BACKGROUND: We assessed antiplatelet therapy use and outcomes in patients undergoing percutaneous coronary intervention (PCI) during the ARISTOTLE trial. METHODS: Patients were categorized based on the occurrence of PCI during follow-up (median 1.8 years); PCI details and outcomes post-PCI are

Frequency of "Pocket" Hematoma in Patients Receiving Vitamin K Antagonist and Antiplatelet Therapy at the Time of Pacemaker or Cardioverter Defibrillator Implantation (from the POCKET Study).

Science.gov (United States)

Malagù, Michele; Trevisan, Filippo; Scalone, Antonella; Marcantoni, Lina; Sammarco, Giuseppe; Bertini, Matteo

2017-04-01

In patients undergoing cardiac device implantation, anticoagulant and antiplatelet therapy are associated with an increased risk of pocket hematoma. In case of vitamin K antagonist therapy, a strategy of continued warfarin with no heparin bridge showed a reduction of pocket hematoma. Evidence regarding antiplatelet therapy management is limited. This is a single-center observational study which reflects our systematic approach to the problem. In 2012, we proposed an improved management protocol for anticoagulant and antiplatelet therapy (no-bridge protocol) based on individual thromboembolic risk stratification, noninterruption of oral anticoagulation, no bridge with heparin and elastic adherence compression bandage. The primary end point was the incidence of clinically significant pocket hematoma in the first 30 days after implantation. A total of 1,035 patients were enrolled, of whom 522 received the standard management and 513 the new protocol. The primary end point occurred in 34 patients of the standard management group and 8 patients of the no-bridge protocol group (6.5% vs 1.6%, p hematoma (relative risk [RR] 3.48, 95% confidence interval [CI] 1.55 to 7.83 and RR 2.43, 95% CI 1.25 to 4.76, respectively), whereas the no-bridge protocol was associated with a reduction of pocket hematoma (RR 0.33, 95% CI 0.14 to 0.76). New anticoagulant and antiplatelet therapy management protocol was associated with a reduced incidence of clinically significant pocket hematomas, thromboembolic events, pocket infections, and lead dislodgements. Copyright © 2017 Elsevier Inc. All rights reserved.

FREE-RADICAL OXIDATION ACTIVITY IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION WITHOUT Q WAVE TREATED WITH EPROSARTAN OR ENALAPRIL ADDITIONALLY TO THE BASIC THERAPY

Directory of Open Access Journals (Sweden)

O. G. Zaylobidinov

2009-01-01

Full Text Available Aim. To compare effects of eprosartan and enalapril on free-radical oxidation in patients with acute myocardial infarction (AMI without Q wave.Material and methods. 50 patients (aged 52,8±3,3 y.o. with AMI without Q were involved into the study. Patients were randomized on 2 groups. The first group consisted of 24 patients (51,1±2,4 y.o. which received basic therapy and enalapril (10 mg daily. The second group consisted of 26 patients (53,1±3,0 y.o. which received basic therapy and eprosartan (600 mg daily. Basic therapy included anticoagulants, antiplatelets, beta-blockers, nitrates and statins. Intensity of free-radical oxidation was evaluated by change of serum malonic dialdehyde (MDD concentration. Functional activity of serum enzymes of antioxidatic system (AOS was evaluated by rate of reaction of superoxide dismutase (SOD and catalase (CT.Results. The intensity of free-radical oxidation increased in patients with AMI without Q: high level of MDD and peroxinitrite (ONOO-. Besides activity of AOS enzymes (SOD and CT decreased. Eprosartan reduced intensity of peroxide oxidation more prominently in comparison with enalapril. Both drugs preserved low activity of SOD and CT.Conclusion. Eprosartan was significantly more effective than enalapril in reduction of serum free-radical oxidation in patients with AMI without Q wave during 10 days after hospital admission.

18F-Fluorodeoxyglucose positron emission tomography and serum cytokines and matrix metalloproteinases in the assessment of disease activity in Takayasu's arteritis

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Anne E.D. Arraes

Full Text Available ABSTRACT Objective: To evaluate 18F-fluorodeoxyglucose (18F-FDG uptake on positron emission tomography–computed tomography (PET–CT and serum levels of different cytokines and matrix metalloproteinases (MMPs in patients with Takayasu arteritis (TA and associations with disease activity. Methods: Serum levels of tumor necrosis factor-α (TNF-α, interleukin (IL-2, IL-6, IL-8, IL-12, IL-18, MMP-3 and MMP-9 were measured in 36 TA patients and 36 controls. Maximum standard uptake value (SUVmax of 18F-FDG in arterial walls was determined by PET–CT scans. TA patients were classified as active disease, inactive disease and possible active disease. Results: Serum IL-6 and MMP-3 levels were higher in TA patients than in controls (p < 0.001. Serum IL-6 was higher in patients with active disease and in patients with possible active disease than in inactive disease (p < 0.0001. Patients with active disease had higher serum TNFα levels than patients with inactive disease (p = 0.049 while patients with possible active disease presented higher IL-18 levels than patients with inactive disease (p = 0.046. Patients with active disease had higher SUVmax values than those with inactive disease (p = 0.042. By receiver operating characteristic (ROC curve SUVmax was predictive of active disease in TA and values ≥1.3 were associated with disease activity (p = 0.039. Serum TNF-α levels were higher in patients with SUVmax ≥ 1.3 than <1.3 (p = 0.045 and controls (p = 0.012. Serum IL-6 levels were higher in patients with SUVmax ≥ 1.3 than in controls (p < 0.001. No differences regarding other biomarkers were found between TA patients and controls. Conclusions: Higher serum IL-6 and TNFα levels as well as higher 18F-FDG uptake in arterial wall are associated with active TA.

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS)

DEFF Research Database (Denmark)

Bath, Philip M; Woodhouse, Lisa J; Appleton, Jason P

2018-01-01

, and dipyridamole) with that of guideline-based antiplatelet therapy. METHODS: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using...... was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using...... therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did...

Relationships between serum 25-hydroxycalciferol, vitamin D intake and disease activity in patients with rheumatoid arthritis--TOMORROW study.

Science.gov (United States)

Matsumoto, Yoshinari; Sugioka, Yuko; Tada, Masahiro; Okano, Tadashi; Mamoto, Kenji; Inui, Kentaro; Habu, Daiki; Koike, Tatsuya

2015-03-01

The effect of serum 25-hydroxycalciferol [25(OH)D] on rheumatoid arthritis (RA) activity remains controversial. This study was undertaken with an aim to clarify the relationship between serum 25(OH)D and RA activity, and to determine the effects of dietary vitamin D intake and age on serum 25(OH)D level. A total of 208 outpatients with RA were matched according to age and sex with 205 individuals without RA (controls) from the TOMORROW study (UMIN000003876). We excluded 27 patients with RA and 19 control subjects who had been prescribed vitamin D medication or were taking vitamin D supplements. Vitamin D intake was assessed in the remaining 181 patients and 186 controls using the brief-type dietary history questionnaire. Serum 25(OH)D levels were measured using a radioimmunoassay. Serum 25(OH)D levels were significantly lower in patients with RA than in the controls (p < 0.001). There was a significant and positive correlation between age and 25(OH)D in the patients (r = 0.283, p < 0.001), as with vitamin D intake and 25(OH)D, even after adjusting for age (r = 0.313, p < 0.001). Disease activity and 25(OH)D did not significantly correlate. Patients with RA were observed to have serum 25(OH)D levels which correlated with vitamin D intake and age but not disease activity.

Topical diclofenac does not affect the antiplatelet properties of aspirin as compared to the intermediate effects of oral diclofenac: A prospective, randomized, complete crossover study.

Science.gov (United States)

Rowcliffe, M; Nezami, B; Westphal, E S; Rainka, M; Janda, M; Bates, V; Gengo, F

2016-04-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) adversely interact with aspirin, diminishing its antiplatelet effect and potentially placing patients at an increased risk for recurrent thrombotic events. This crossover study aimed to determine whether the topical NSAID diclofenac epolamine 1.3% patch or oral diclofenac 50 mg interfered with the antiplatelet effects of aspirin 325 mg. Twelve healthy men and women aged 18-50 were included. Participants were randomized into 5 treatment arms: aspirin, diclofenac potassium 50 mg, diclofenac patch, diclofenac potassium plus ASA 325 mg, and diclofenac patch plus aspirin. Platelet responsiveness was determined using whole-blood impedance aggregation (WBA) to collagen 1 μg/mL and arachidonic acid (AA) 0.5 mM and was sampled every 2 hours. No significant difference in platelet function was observed following the diclofenac patch and aspirin vs aspirin alone. Oral diclofenac produced a mixed effect with significant reduction in platelet inhibition at hour 2 and hour 8 following aspirin administration. Topical diclofenac does not significantly interfere with the antiplatelet effects of aspirin and may be a safer alternative to the oral formulation. © 2015, The American College of Clinical Pharmacology.

[Serum calcium and phosphorus concentration and alkaline phosphatase activity in healthy children during growth and development].

Science.gov (United States)

Savić, Ljiljana; Savić, Dejan

2008-01-01

Many changes happen during growth and development in an organism as a result of important hormon changes, especially biohumoral ones. These changes make a problem when interpreting biochemical results in pediatric population. The most important changes are intensive calcium and phosphorus metabolic turnover in bone tissue with changes in alkaline phosphatase activity as a result of osteoblast activity. The aim of this study was to follow the serum calcium and phosphorus concentration and alkaline phosphatase activity in children 1-15 years old in different growth and development period and of different sexes and to fortify the influence of growth and development dynamics on biohumoral status in healthy male and female children. We evaluated 117 healthy children of both sexes from 1-15 years of age and divided them into three age groups: 1-5, 6-10 and 11-15 years. We followed the serum calcium and phosphorus concentration and alkaline phosphatase activity in different groups and in different sexes. Our investigation found significantly higher values of serum calcium in boys than in girls with no important changes between the age groups and significantly higher values of serum phosphorus in the youngest age group in all children and in different sexes with no important sex differences. Alkaline phosphatase activity followed the growth spurt and was the biggest in 6-10 years group in girls and in 11-15 years group in boys.

Relationship between elevated serum gamma-glutamyltransferase activity and slow coronary flow

DEFF Research Database (Denmark)

Sen, Nihat; Ozlü, Mehmet F; Basar, Nurcan

2009-01-01

OBJECTIVES: We evaluated the relationship between coronary blood flow and serum gamma-glutamyltransferase (GGT) activity in patients with slow coronary flow (SCF). STUDY DESIGN: The study included 90 patients (47 men, 43 women; mean age 50.8+/-9.4 years) with SCF and 88 patients (45 men, 43 women...

Effect of citric acid and microbial phytase on serum enzyme activities ...

African Journals Online (AJOL)

Effect of citric acid and microbial phytase on serum enzyme activities and plasma minerals retention in broiler chicks. ... African Journal of Biotechnology ... An experiment was conducted to study the effect of microbial phytase supplementation and citric acid in broiler chicks fed corn-soybean meal base diets on enzyme ...

Preoperative Serum Thymidine Kinase Activity as Novel Monitoring, Prognostic, and Predictive Biomarker in Pancreatic Cancer.

Science.gov (United States)

Felix, Klaus; Hinz, Ulf; Dobiasch, Sophie; Hackert, Thilo; Bergmann, Frank; Neumüller, Magnus; Gronowitz, Simon; Bergqvist, Mattias; Strobel, Oliver

2018-01-01

The aim of the study was to investigate serum thymidine kinase 1 (S-TK) activity as a diagnostic and prognostic marker for patients with pancreatic ductal adenocarcinoma (PDAC). Using the sensitive TK activity assay DiviTum, preoperative serum samples from 404 PDAC, 28 chronic pancreatitis, and 25 autoimmune pancreatitis patients and 83 healthy volunteers were analyzed. The preoperative S-TK activities of 54 PDAC patients who received neoadjuvant therapy (nTx) were also compared with those of 258 PDAC patients who did not receive nTx. The preoperative S-TK activities of PDAC patients were significantly higher and discriminatory from autoimmune and chronic pancreatitis patients and control groups. The S-TK activity in PDAC patients was associated with overall survival. Patients with S-TK activity of less than 80 Du (DiviTum units)/L demonstrated median survival of 20.3 months with an estimated 18.0% 5-year survival rate; for S-TK activity of 80 Du/L or greater, median survival was 15.1 months with a 6.8% 5-year survival rate. For early-stage PDAC, these differences were even more pronounced. The S-TK activity in the nTx group was significantly higher than that in the group not receiving nTx. Pancreatic ductal adenocarcinomas reveal a significant increase in S-TK activity, which is associated with overall survival, especially in early tumor stages. Serum thymidine kinase 1 activity may be a useful parameter for monitoring nTx efficacy.

Serum Is Not Necessary for Prior Pharmacological Activation of AMPK to Increase Insulin Sensitivity of Mouse Skeletal Muscle

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Nicolas O. Jørgensen

2018-04-01

Full Text Available Exercise, contraction, and pharmacological activation of AMP-activated protein kinase (AMPK by 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR have all been shown to increase muscle insulin sensitivity for glucose uptake. Intriguingly, improvements in insulin sensitivity following contraction of isolated rat and mouse skeletal muscle and prior AICAR stimulation of isolated rat skeletal muscle seem to depend on an unknown factor present in serum. One study recently questioned this requirement of a serum factor by showing serum-independency with muscle from old rats. Whether a serum factor is necessary for prior AICAR stimulation to increase insulin sensitivity of mouse skeletal muscle is not known. Therefore, we investigated the necessity of serum for this effect of AICAR in mouse skeletal muscle. We found that the ability of prior AICAR stimulation to improve insulin sensitivity of mouse skeletal muscle did not depend on the presence of serum during AICAR stimulation. Although prior AICAR stimulation did not enhance proximal insulin signaling, insulin-stimulated phosphorylation of Tre-2/BUB2/CDC16- domain family member 4 (TBC1D4 Ser711 was greater in prior AICAR-stimulated muscle compared to all other groups. These results imply that the presence of a serum factor is not necessary for prior AMPK activation by AICAR to enhance insulin sensitivity of mouse skeletal muscle.

Activation of the human complement system by cholesterol-rich and pegylated liposomes - Modulation of cholesterol-rich liposome-mediated complement activation by elevated serum LDL and HDL levels

DEFF Research Database (Denmark)

Moghimi, S.M.; Hamad, I.; Bunger, R.

2006-01-01

level of S-protein-bound form of the terminal complex (SC5b-9). However, liposome-induced rise of SC5b-9 was significantly suppressed when serum HDL cholesterol levels increased by 30%. Increase of serum LDL to levels similar to that observed in heterozygous familial hypercholesterolemia also suppressed......Intravenously infused liposomes may induce cardiopulmonary distress in some human subjects, which is a manifestation of "complement activation-related pseudoallergy." We have now examined liposome-mediated complement activation in human sera with elevated lipoprotein (LDL and HDL) levels, since...... abnormal or racial differences in serum lipid profiles seem to modulate the extent of complement activation and associated adverse responses. In accordance with our earlier observations, cholesterol-rich (45 mol% cholesterol) liposomes activated human complement, as reflected by a significant rise in serum...

Management of antiplatelet therapy in patients undergoing elective invasive procedures. Proposals from the French Working Group on perioperative haemostasis (GIHP) and the French Study Group on thrombosis and haemostasis (GFHT). In collaboration with the French Society for Anaesthesia and Intensive Care Medicine (SFAR).

Science.gov (United States)

Godier, Anne; Fontana, Pierre; Motte, Serge; Steib, Annick; Bonhomme, Fanny; Schlumberger, Sylvie; Lecompte, Thomas; Rosencher, Nadia; Susen, Sophie; Vincentelli, André; Gruel, Yves; Albaladejo, Pierre; Collet, Jean-Philippe

2018-01-05

The French Working Group on Perioperative Haemostasis (GIHP) and the French Study Group on Haemostasis and Thrombosis (GFHT) in collaboration with the French Society for Anaesthesia and Intensive Care Medicine (SFAR) drafted up-to-date proposals for the management of antiplatelet therapy in patients undergoing elective invasive procedures. The proposals were discussed and validated by a vote; all proposals but one could be assigned with a high strength. The management of antiplatelet therapy is based on their indication and the procedure. The risk of bleeding related to the procedure can be divided into high, moderate and low categories depending on the possibility of performing the procedure in patients receiving antiplatelet agents (none, monotherapy and dual antiplatelet therapy respectively). If discontinuation of antiplatelet therapy is indicated before the procedure, a last intake of aspirin, clopidogrel, ticagrelor and prasugrel 3, 5, 5 and 7 days before surgery respectively is proposed. The thrombotic risk associated with discontinuation should be assessed according to each specific indication of antiplatelet therapy and is higher for patients receiving dual therapy for coronary artery disease (with further refinements based on a few well-accepted items) than for those receiving monotherapy for cardiovascular prevention, for secondary stroke prevention or for lower extremity arterial disease. These proposals also address the issue of the potential role of platelet functional tests and consider management of antiplatelet therapy for regional anaesthesia, including central neuraxial anaesthesia and peripheral nerve blocks, and for coronary artery surgery. Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

BaltDC: purification, characterization and infrared spectroscopy of an antiplatelet DC protein isolated from Bothrops alternatus snake venom.

Science.gov (United States)

Matias, Mariana Santos; de Sousa, Bruna Barbosa; da Cunha Pereira, Déborah Fernanda; Dias, Edigar Henrique Vaz; Mamede, Carla Cristine Neves; de Queiroz, Mayara Ribeiro; Silva, Anielle Christine Almeida; Dantas, Noelio Oliveira; Soares, Andreimar Martins; de Oliveira Costa, Júnia; de Oliveira, Fábio

2017-01-01

Snake venoms are a complex mixture of proteins, organic and inorganic compounds. Some of these proteins, enzymatic or non-enzymatic ones, are able to interact with platelet receptors, causing hemostatic disorders. The possible therapeutic potential of toxins with antiplatelet properties may arouse interest in the pharmacological areas. The present study aimed to purify and characterize an antiplatelet DC protein from Bothrops alternatus snake venom. The protein, called BaltDC (DC protein from B. alternatus snake venom), was purified by a combination of ion-exchange chromatography on DEAE-Sephacel column and gel filtration on Sephadex G-75. The molecular mass was estimated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE). The amino acid sequence of the N-terminal region was carried out by Edman degradation method. Platelet aggregation assays were performed in human platelet-rich plasma (PRP). Infrared (IR) spectroscopy was used in order to elucidate the interactions between BaltDC and platelet membrane. BaltDC ran as a single protein band on SDS-PAGE and showed apparent molecular mass of 32 kDa under reducing or non-reducing conditions. The N-terminal region of the purified protein revealed the amino acid sequence IISPPVCGNELLEVGEECDCGTPENCQNECCDA, which showed identity with other snake venom metalloproteinases (SVMPs). BaltDC was devoid of proteolytic, hemorrhagic, defibrinating or coagulant activities, but it showed a specific inhibitory effect on platelet aggregation induced by ristocetin and epinephrine in PRP. IR analysis spectra strongly suggests that PO 3 2- groups, present in BaltDC, form hydrogen bonds with the PO 2 - groups present in the non-lipid portion of the membrane platelets. BaltDC may be of medical interest since it was able to inhibit platelet aggregation.

Common HEXB polymorphisms reduce serum HexA and HexB enzymatic activities, potentially masking Tay-Sachs disease carrier identification.

Science.gov (United States)

Vallance, Hilary; Morris, Tara J; Coulter-Mackie, Marion; Lim-Steele, Joyce; Kaback, Michael

2006-02-01

A DNA-proven Tay-Sachs disease (TSD) carrier and his brother were found to have serum percent Hexosaminidase A (%HexA) enzymatic activities in the non-carrier range, while the leukocyte %HexA profiles clearly identified them as TSD heterozygotes. Both their serum HexA and HexB enzymatic activities were below reference range, suggesting inheritance of mutations in both the HEXA (alpha-subunit) and HEXB (beta-subunit) genes. DNA sequencing revealed that both individuals, carried the common HEXA 1277_1278insTATC mutation, and two common HEXB polymorphisms: [619A>G (+) delTG]. To determine if these HEXB polymorphisms reduce HexA and HexB enzymatic activities, 69 DNA samples from subjects previously screened enzymatically in both serum and leukocytes for TSD carrier status were selected for either high, mid-range or low serum Total Hex (defined as the sum of HexA and HexB) activities and were tested for the HEXB mutations. Further, three additional TSD carriers ascertained by the atypical pattern of normal serum %HexA but carrier leukocyte %HexA, were found to have the [delTG (+) 619A>G] genotype. In addition, the frequency of the [delTG (+) 619A>G] genotype was significantly higher (P G] haplotype in the Ashkenazi Jewish population (approximately 10%), up to 10% of TSD carriers may have normal serum %HexA values with low total Hex. Accordingly, serum %HexA should not be the sole criterion used for carrier status determination. Where total Hex activity is reduced, further testing with leukocyte Hex profiles is indicated.

NRF2 activation is involved in ozonated human serum upregulation of HO-1 in endothelial cells

International Nuclear Information System (INIS)

Pecorelli, Alessandra; Bocci, Velio; Acquaviva, Alessandra; Belmonte, Giuseppe; Gardi, Concetta; Virgili, Fabio; Ciccoli, Lucia; Valacchi, Giuseppe

2013-01-01

During the last decade, it has been shown that the activation of NRF2 and the binding to electrophile-responsive element (EpREs), stimulates the expression of a great number of genes responsible for the synthesis of phase I and phase II proteins, including antioxidants enzymes and heme oxygenase-1 (HO-1). This critical cell response occurs in cardiovascular, degenerative and chronic infective diseases aggravated by a chronic oxidative stress. In our previous reports we have shown that ozonated plasma is able to up-regulate HO-1 expression in endothelial cells. In the present work we investigated a candidate mechanism involved in this process. After treatment with increasing doses of ozonated serum (20, 40 and 80 μg/mL O 3 per mL of serum), a clear dose dependent activation of NRF2 and the subsequent induction of HO-1 and NAD(P)H quinone oxidoreductase 1(NQO1) was observed. This effect was also present when cells were treated with serum and hydrogen peroxide (H 2 O 2 ) or serum and 4-hydroxynonenal (4HNE). Moreover, the treatment with ozonated serum was associated with a dose-dependent activation of extracellular-signal-regulated kinases (ERK1/2) and p38 MAP kinases (p38), not directly involved in NRF2 activation. These data, provide a new insight on the mechanism responsible for the induction of HO-1 expression by ozonated serum in the endothelium, and have a practical importance as an expedient approach to the treatment of patients with both effective orthodox drugs and ozonated autohemotherapy, targeted to the restoration of redox homeostasis. - Highlights: ► Endothelial HO1 is upregulated by ozonated plasma ► This activation is induced by NRF2 and it is ERK independent. ► 4HNE and H 2 O 2 are the main molecules involved in this process. ► Ozonated plasma induced a hormetic effect ► Combination of orthodox medicine and ozonated plasma can be a useful treatment

NRF2 activation is involved in ozonated human serum upregulation of HO-1 in endothelial cells

Energy Technology Data Exchange (ETDEWEB)

Pecorelli, Alessandra [Department of Molecular and Developmental Medicine, University of Siena (Italy); Child Neuropsychiatry Unit, University Hospital, AOUS, Siena (Italy); Bocci, Velio [Department of Physiology, University of Siena (Italy); Acquaviva, Alessandra [Department of Molecular and Developmental Medicine, University of Siena (Italy); Belmonte, Giuseppe [Department of Biomedical Sciences, University of Siena (Italy); Gardi, Concetta [Department of Molecular and Developmental Medicine, University of Siena (Italy); Virgili, Fabio [INRAN, Rome (Italy); Ciccoli, Lucia [Department of Molecular and Developmental Medicine, University of Siena (Italy); Valacchi, Giuseppe, E-mail: giuseppe.valacchi@unife.it [Department of Life Sciences and Biotechnology, University of Ferrara (Italy); Department of Food and Nutrition, Kyung Hee University, Seoul (Korea, Republic of)

2013-02-15

During the last decade, it has been shown that the activation of NRF2 and the binding to electrophile-responsive element (EpREs), stimulates the expression of a great number of genes responsible for the synthesis of phase I and phase II proteins, including antioxidants enzymes and heme oxygenase-1 (HO-1). This critical cell response occurs in cardiovascular, degenerative and chronic infective diseases aggravated by a chronic oxidative stress. In our previous reports we have shown that ozonated plasma is able to up-regulate HO-1 expression in endothelial cells. In the present work we investigated a candidate mechanism involved in this process. After treatment with increasing doses of ozonated serum (20, 40 and 80 μg/mL O{sub 3} per mL of serum), a clear dose dependent activation of NRF2 and the subsequent induction of HO-1 and NAD(P)H quinone oxidoreductase 1(NQO1) was observed. This effect was also present when cells were treated with serum and hydrogen peroxide (H{sub 2}O{sub 2}) or serum and 4-hydroxynonenal (4HNE). Moreover, the treatment with ozonated serum was associated with a dose-dependent activation of extracellular-signal-regulated kinases (ERK1/2) and p38 MAP kinases (p38), not directly involved in NRF2 activation. These data, provide a new insight on the mechanism responsible for the induction of HO-1 expression by ozonated serum in the endothelium, and have a practical importance as an expedient approach to the treatment of patients with both effective orthodox drugs and ozonated autohemotherapy, targeted to the restoration of redox homeostasis. - Highlights: ► Endothelial HO1 is upregulated by ozonated plasma ► This activation is induced by NRF2 and it is ERK independent. ► 4HNE and H{sub 2}O{sub 2} are the main molecules involved in this process. ► Ozonated plasma induced a hormetic effect ► Combination of orthodox medicine and ozonated plasma can be a useful treatment.

Relationship between serum adiponectin level and ATPase activity of erythrocyte membrance in patients with 2-type diabetes

International Nuclear Information System (INIS)

Song Jiejin

2008-01-01

Objective: To explore the possible mechanism of development nephrosis as related to changes of serum adiponectin levels and alteration of activities of Na + ·K + -ATPase and Ca +2 ·Mg +2 -ATPase of erythrocyte membrance in patients with 2-type diabetes. Methods: Serum adiponectin levels (with RIA) and erythrocyte membrance (prepared with Reilnila method) Na + ·K + - ATPase and Ca +2 ·Mg +2 -ATPase activity were determined in 45 DM2 patients without nephropathy, 31 DM2 patients with nephropathy and 30 controls. Results: Serum adiponectin levels in the diabetic patients were significantly lower than those in controls (P + ·K + -ATPase and Ca +2 ·Mg +2 -ATPase activities were also significantly lower than those in controls (P + ·K + -ATPase and Ca +2 ·Mg +2 -ATPase activities of erythrocyte membrance. (authors)

Clonogenic growth of human breast cancer cells co-cultured in direct contact with serum-activated fibroblasts

International Nuclear Information System (INIS)

Samoszuk, Michael; Tan, Jenny; Chorn, Guillaume

2005-01-01

Accumulating evidence suggests that fibroblasts play a pivotal role in promoting the growth of breast cancer cells. The objective of the present study was to characterize and validate an in vitro model of the interaction between small numbers of human breast cancer cells and human fibroblasts. We measured the clonogenic growth of small numbers of human breast cancer cells co-cultured in direct contact with serum-activated, normal human fibroblasts. Using DNA microarrays, we also characterized the gene expression profile of the serum-activated fibroblasts. In order to validate the in vivo relevance of our experiments, we then analyzed clinical samples of metastatic breast cancer for the presence of myofibroblasts expressing α-smooth muscle actin. Clonogenic growth of human breast cancer cells obtained directly from in situ and invasive tumors was dramatically and consistently enhanced when the tumor cells were co-cultured in direct contact with serum-activated fibroblasts. This effect was abolished when the cells were co-cultured in transwells separated by permeable inserts. The fibroblasts in our experimental model exhibited a gene expression signature characteristic of 'serum response' (i.e. myofibroblasts). Immunostaining of human samples of metastatic breast cancer tissue confirmed that myofibroblasts are in direct contact with breast cancer cells. Serum-activated fibroblasts promote the clonogenic growth of human breast cancer cells in vitro through a mechanism that involves direct physical contact between the cells. This model shares many important molecular and phenotypic similarities with the fibroblasts that are naturally found in breast cancers

Relationship between serum leptin levels, ATPase activity of erythrocyte membrance and development of diabetic nephropathy in patients with DM2

International Nuclear Information System (INIS)

Wang Yuming

2009-01-01

Objective: To study the possible mechanism of development of nephrosis affected by changes of serum leptin levels and alteration of activities of Na + K + -ATPase and Ca 2+ Mg 2+ -ATPase of erythrocyte membrane in patients with type 2 diabetes(DM2). Methods: Serum leptin levels (with RIA) and erythrocyte membrane Na + K + -ATPase and Ca 2+ Mg 2+ -ATPase activitities (with Reinila method) were determined in 40 DM2 patients without nephropathy, 32 DM2 patients with nephropathy and 35 controls. Results Serum leptin levels were significantly higher in the diabetics as a whole than those in controls (P + K + -ATPase and Ca 2+ Mg 2+ -ATPase activities were significantly lower (P<0.01). Among the diabetic patients, the serum leptin levels in patients without nephrosis (P<0.05), but the RBC membrance ATPase activities were significantly lower(P<0.05). Conclusion: Development of type 2 diabetes nephrosis might be correlated with the high serum leptin level and decreased ATPase activities of erythrocite membrane. (authors)

Relationship of serum resistin level to traits of metabolic syndrome and serum paraoxonase 1 activity in a population with a broad range of body mass index.

Science.gov (United States)

Bajnok, L; Seres, I; Varga, Z; Jeges, S; Peti, A; Karanyi, Z; Juhasz, A; Csongradi, E; Mezosi, E; Nagy, E V; Paragh, G

2008-11-01

The relationship between resistin, one of the adipokines, and metabolic syndrome is not fully elucidated. Altered activity of the HDL-associated antioxidant enzyme paraoxonase 1 (PON1) that participates in the antioxidant defense mechanisms of HDL may have an important role in the obesity-related accelerated atherosclerosis. Inverse associations of PON1 with obesity and serum levels of leptin have been demonstrated. Our aim was to investigate the association of serum levels of resistin with (i) PON1 activity, and (ii) parameters of metabolic syndrome, including some that are additional for research. A total of 74 Caucasian subjects were recruited into the study and divided into 3 age and sex-matched groups. Group 1, 25 non-diabetic overweight/obese subjects with BMI of 28-39.9 kg/m (2); group 2, 25 non-diabetic obese patients with BMI >or=40 kg/m (2); and the control group 3, 24 healthy, normal-weight control subjects. Serum levels of resistin were correlated negatively with BMI (r=-0.27, Pcorrelated positively with PON1 (r=0.24, PHDL-C. During multiple regression analyses BMI and TBARS were independent predictors of PON1, while age, gender, blood pressure, HOMA-IR, LDL-C, HDL-C, and resistin were not. Among the study subjects, serum levels of resistin showed a positive, although not independent correlation with serum PON1, and a negative correlation with numerous parameters of the metabolic syndrome (i.e. adiposity, blood pressure, levels of leptin, free fatty acid, glycosylated hemoglobin, and lipid peroxidation). BMI and TBARS are independent predictors of PON1 activity.

The effect on serum myeloperoxidase activity and oxidative status of eradication treatment in patients Helicobacter pylori infected.

Science.gov (United States)

Nazligul, Yaşar; Aslan, Mehmet; Horoz, Mehmet; Celik, Yilmaz; Dulger, Ahmet Cumhur; Celik, Hakim; Erel, Ozcan

2011-06-01

Myeloperoxidase activity has been investigated after eradication of Helicobacter pylori (H. pylori) in infected patients in previous studies but the results are controversial. The aim of this study was to investigate effect on serum myeloperoxidase activity and oxidative status of eradication treatment in H. pylori-infected patients. Gastric biopsy specimens were obtained from 30 H. pylori infected patients. Serum myeloperoxidase activity was measured by enzyme-linked immunoassay. Oxidative status was determined using total antioxidant capacity (TAC) and total oxidant status (TOS) measurement and calculation of oxidative stress index (OSI). After 2 weeks of the eradication treatment, serum myeloperoxidase activity, TOS and OSI values were significantly lower (all; p<0.001), while TAC was significantly higher (p<0.001). Our results indicate that eradication treatment in H. pylori-infected patients may affect both oxidative stress and myeloperoxidase activity which is an important biomarker in pathogenesis of atherosclerosis. Copyright © 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Effect of copper intrauterine device vs. injectable contraceptive on serum hormone levels and cell mitotic activity in endometrium

Directory of Open Access Journals (Sweden)

Ebtesam Moustafa Kamal

2013-09-01

Conclusion: Either copper intrauterine device or injectable contraceptive usage for more than 9 months results in significant decrease in endometrial proliferative or cell mitotic activity. While copper IUD has no effect on serum estradiol or progesterone levels, DMPA usage increased serum progesterone level with no effect on serum estradiol.

Serum IP-10 is useful for identifying renal and overall disease activity in pediatric systemic lupus erythematosus.

Science.gov (United States)

Zhang, Chen-Xing; Cai, Li; Shao, Kang; Wu, Jing; Zhou, Wei; Cao, Lan-Fang; Chen, Tong-Xin

2018-05-01

Traditional serological biomarkers often fail to assess systemic lupus erythematosus (SLE) disease activity and discriminate lupus nephritis (LN). The aim of this study was to identify novel markers for evaluating renal and overall disease activity in Chinese patients with pediatric systemic lupus erythematosus (pSLE). The study included 46 patients with pSLE (35 girls, 11 boys; average age 13.3 ± 2.6 years) and 31 matched healthy controls (22 girls, 9 boys; average age 12.3 ± 2.4 years). The SLE Disease Activity Index (SLEDAI) and renal SLEDAI were used to assess disease activity. Nine different soluble mediators in plasma, including tumor necrosis factor alpha (TNF-α), platelet-derived growth factor-BB (PDGF-BB), interferon (IFN) gamma inducible protein 10 (IP-10), interleukin (IL)-1β, IFN-γ, IL-17A, IL-2, Fas and Fas ligand, were measured by Luminex assay and compared between patients with active and inactive pSLE as well as between patients with pSLE with active and inactive renal disease. Receiver operating characteristic curve analysis was used to measure the discrimination accuracy. Of the 46 patients with pSLE, 30 (65.2%) had LN. These patients had significantly elevated levels of serum TNF-α, PDGF-BB, IP-10 and Fas. The serum levels of IP-10 were also significantly higher in patients with active pSLE. We found that IP-10 was also more sensitive and specific than conventional laboratory parameters, including anti-double-stranded DNA and complement components C3 and C4, for distinguishing active lupus from quiescent lupus. The serum level of IP-10 was also significantly increased in children with pSLE with active renal disease relative to those with inactive renal disease. There was also a positive correlation between serum IP-10 levels and renal SLEDAI scores as well as with 24 h urine protein. Serum IP-10 is useful for identifying renal and overall disease activity in children with pSLE.

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)

Fetal bovine serum and human constitutive androstane receptor: Evidence for activation of the SV23 splice variant by artemisinin, artemether, and arteether in a serum-free cell culture system

Energy Technology Data Exchange (ETDEWEB)

Lau, Aik Jiang; Chang, Thomas K.H., E-mail: thomas.chang@ubc.ca

2014-06-01

The naturally occurring SV23 splice variant of human constitutive androstane receptor (hCAR-SV23) is activated by di-(2-ethylhexyl)phthalate (DEHP), which is detected as a contaminant in fetal bovine serum (FBS). In our initial experiment, we compared the effect of dialyzed FBS, charcoal-stripped, dextran-treated FBS (CS-FBS), and regular FBS on the basal activity and ligand-activation of hCAR-SV23 in a cell-based reporter gene assay. In transfected HepG2 cells cultured in medium supplemented with 10% FBS, basal hCAR-SV23 activity varied with the type of FBS (regular > dialyzed > CS). DEHP increased hCAR-SV23 activity when 10% CS-FBS, but not regular FBS or dialyzed FBS, was used. With increasing concentrations (1–10%) of regular FBS or CS-FBS, hCAR-SV23 basal activity increased, whereas in DEHP-treated cells, hCAR-SV23 activity remained similar (regular FBS) or slightly increased (CS-FBS). Subsequent experiments identified a serum-free culture condition to detect DEHP activation of hCAR-SV23. Under this condition, artemisinin, artemether, and arteether increased hCAR-SV23 activity, whereas they decreased it in cells cultured in medium supplemented with 10% regular FBS. By comparison, FBS increased the basal activity of the wild-type isoform of hCAR (hCAR-WT), whereas it did not affect the basal activity of the SV24 splice variant (hCAR-SV24) or ligand activation of hCAR-SV24 and hCAR-WT by 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime (CITCO). The use of serum-free culture condition was suitable for detecting CITCO activation of hCAR-WT and hCAR-SV24. In conclusion, FBS leads to erroneous classification of pharmacological ligands of hCAR-SV23 in cell-based assays, but investigations on functional ligands of hCAR isoforms can be conducted in serum-free culture condition. - Highlights: • FBS leads to erroneous pharmacological classification of hCAR-SV23 ligands. • Artemisinin, artemether, and arteether activate h

Comparison of digoxin concentration in plastic serum tubes with clot activator and heparinized plasma tubes.

Science.gov (United States)

Dukić, Lora; Simundić, Ana-Maria; Malogorski, Davorin

2014-01-01

Sample type recommended by the manufacturer for the digoxin Abbott assay is either serum collected in glass tubes or plasma (sodium heparin, lithium heparin, citrate, EDTA or oxalate as anticoagulant) collected in plastic tubes. In our hospital samples are collected in plastic tubes. Our hypothesis was that the serum sample collected in plastic serum tube can be used interchangeably with plasma sample for measurement of digoxin concentration. Our aim was verification of plastic serum tubes for determination of digoxin concentration. Concentration of digoxin was determined simultaneously in 26 venous blood plasma (plastic Vacuette, LH Lithium heparin) and serum (plastic Vacuette, Z Serum Clot activator; both Greiner Bio-One GmbH, Kremsmünster, Austria) samples, on Abbott AxSYM analyzer using the original Abbott Digoxin III assay (Abbott, Wiesbaden, Germany). Tube comparability was assessed using the Passing Bablok regression and Bland-Altman plot. Serum and plasma digoxin concentrations are comparable. Passing Bablok intercept (0.08 [95% CI = -0.10 to 0.20]) and slope (0.99 [95% CI = 0.92 to 1.11]) showed there is no constant or proportional error. Blood samples drawn in plastic serum tubes and plastic plasma tubes can be interchangeably used for determination of digoxin concentration.

Effects of soy bean on serum paraoxonase 1 activity and lipoproteins in hyperlipidemic postmenopausal women.

Science.gov (United States)

Shidfar, Farzad; Ehramphosh, Elham; Heydari, Iraj; Haghighi, Ladan; Hosseini, Sharieh; Shidfar, Shahrzad

2009-05-01

Because of an unfavorable serum lipoprotein profile, postmenopausal women are at risk of cardiovascular disease. Soy protein may help protect against these risk factors, although its effect on paraoxonase 1 (PON1) is not clear. The aim of the present study was to determine the effects of soy protein on serum concentration of lipoproteins and PON1 activity in hypercholesterolemic postmenopausal women. In a double-blind randomized clinical trial with a parallel design, 52 hypercholesterolemic postmenopausal women were randomly assigned to 50 g/day soy protein containing 164 mg isoflavones or placebo, for 10 weeks. Serum lipoproteins and PON1 activity were measured at baseline and at the 10th week. There was significant increase in PON1 activity (P=0.029) and a significant decrease in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), LDL-C/high-density lipoprotein cholesterol (HDL-C), triacylglycerol/HDL-C and TC/HDL-C in the soy group compared with the placebo group (P=0.001, P=0.008, P=0.012, P=0.04 and P=0.029, respectively) at the end of the study. Similarly, PON1 activity was significantly increased (P=0.015) and LDL-C, TC, LDL-C/HDL-C, triacylglycerol/HDL-C and TC/HDL-C were significantly decreased (P=0.001, P=0.002, P=0.001, P=0.016 and P=0.001) at the end of the study compared with the beginning value in soy group. Soy protein reduces the cardiovascular disease risk in postmenopausal women because of both modest reductions in serum lipoproteins and an increase in PON1 activity.

2018 Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology Focused Update of the Guidelines for the Use of Antiplatelet Therapy.

Science.gov (United States)

Mehta, Shamir R; Bainey, Kevin R; Cantor, Warren J; Lordkipanidzé, Marie; Marquis-Gravel, Guillaume; Robinson, Simon D; Sibbald, Matthew; So, Derek Y; Wong, Graham C; Abunassar, Joseph G; Ackman, Margaret L; Bell, Alan D; Cartier, Raymond; Douketis, James D; Lawler, Patrick R; McMurtry, Michael S; Udell, Jacob A; van Diepen, Sean; Verma, Subodh; Mancini, G B John; Cairns, John A; Tanguay, Jean-François

2018-03-01

Antiplatelet therapy (APT) has become an important tool in the treatment and prevention of atherosclerotic events, particularly those associated with coronary artery disease. A large evidence base has evolved regarding the relationship between APT prescription in various clinical contexts and risk/benefit relationships. The Guidelines Committee of the Canadian Cardiovascular Society and Canadian Association of Interventional Cardiology publishes regular updates of its recommendations, taking into consideration the most recent clinical evidence. The present update to the 2011 and 2013 Canadian Cardiovascular Society APT guidelines incorporates new evidence on how to optimize APT use, particularly in situations in which few to no data were previously available. The recommendations update focuses on the following primary topics: (1) the duration of dual APT (DAPT) in patients who undergo percutaneous coronary intervention (PCI) for acute coronary syndrome and non-acute coronary syndrome indications; (2) management of DAPT in patients who undergo noncardiac surgery; (3) management of DAPT in patients who undergo elective and semiurgent coronary artery bypass graft surgery; (4) when and how to switch between different oral antiplatelet therapies; and (5) management of antiplatelet and anticoagulant therapy in patients who undergo PCI. For PCI patients, we specifically analyze the particular considerations in patients with atrial fibrillation, mechanical or bioprosthetic valves (including transcatheter aortic valve replacement), venous thromboembolic disease, and established left ventricular thrombus or possible left ventricular thrombus with reduced ejection fraction after ST-segment elevation myocardial infarction. In addition to specific recommendations, we provide values and preferences and practical tips to aid the practicing clinician in the day to day use of these important agents. Copyright © 2018. Published by Elsevier Inc.

Spray-dried Eudragit® L100 microparticles containing ferulic acid: Formulation, in vitro cytoprotection and in vivo anti-platelet effect

International Nuclear Information System (INIS)

Nadal, Jessica Mendes; Gomes, Mona Lisa Simionatto; Borsato, Débora Maria; Almeida, Martinha Antunes; Barboza, Fernanda Malaquias; Zawadzki, Sônia Faria; Kanunfre, Carla Cristine; Farago, Paulo Vitor; Zanin, Sandra Maria Warumby

2016-01-01

This paper aimed to obtain new spray-dried microparticles containing ferulic acid (FA) prepared by using a methacrylic polymer (Eudragit® L100). Microparticles were intended for oral use in order to provide a controlled release, and improved in vitro and in vivo biological effects. FA-loaded Eudragit® L100 microparticles were obtained by spray-drying. Physicochemical properties, in vitro cell-based effects, and in vivo platelet aggregation were investigated. FA-loaded Eudragit® L100 microparticles were successfully prepared by spray-drying. Formulations showed suitable encapsulation efficiency, i.e. close to 100%. Microparticles were of spherical and almost-spherical shape with a smooth surface and a mean diameter between 2 and 3 μm. Fourier-transformed infrared spectra demonstrated no chemical bond between FA and polymer. X-ray diffraction and differential scanning calorimetry analyses indicated that microencapsulation led to drug amorphization. FA-loaded microparticles showed a slower dissolution rate than pure drug. The chosen formulation demonstrated higher in vitro cytoprotection, anti-inflammatory and immunomodulatory potential and also improved in vivo anti-platelet effect. These results support an experimental basis for the use of FA spray-dried microparticles as a feasible oral drug delivery carrier for the controlled release of FA and improved cytoprotective and anti-platelet effects. - Highlights: • Ferulic acid-loaded Eudragit® L100 microparticles with high drug-loading were obtained. • Spray-dried Eudragit® L100 microparticles containing ferulic acid showed improved in vitro cytoprotective effect. • Ferulic acid spray-dried microparticles had potential as in vitro anti-inflammatory and immunomodulatory. • In vivo studies demonstrated an enhanced antiplatelet effect for ferulic acid-loaded Eudragit® L100 microparticles.

Spray-dried Eudragit® L100 microparticles containing ferulic acid: Formulation, in vitro cytoprotection and in vivo anti-platelet effect

Energy Technology Data Exchange (ETDEWEB)

Nadal, Jessica Mendes; Gomes, Mona Lisa Simionatto [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmacy, Federal University of Paraná (Brazil); Borsato, Débora Maria [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa (Brazil); Almeida, Martinha Antunes [Postgraduate Program in Chemistry, Department of Chemistry, Federal University of Paraná (Brazil); Barboza, Fernanda Malaquias [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa (Brazil); Zawadzki, Sônia Faria [Postgraduate Program in Chemistry, Department of Chemistry, Federal University of Paraná (Brazil); Kanunfre, Carla Cristine [Postgraduate Program in Biomedical Science, Department of General Biology, State University of Ponta Grossa (Brazil); Farago, Paulo Vitor, E-mail: pvfarago@gmail.com [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmaceutical Sciences, State University of Ponta Grossa (Brazil); Zanin, Sandra Maria Warumby [Postgraduate Program in Pharmaceutical Sciences, Department of Pharmacy, Federal University of Paraná (Brazil)

2016-07-01

This paper aimed to obtain new spray-dried microparticles containing ferulic acid (FA) prepared by using a methacrylic polymer (Eudragit® L100). Microparticles were intended for oral use in order to provide a controlled release, and improved in vitro and in vivo biological effects. FA-loaded Eudragit® L100 microparticles were obtained by spray-drying. Physicochemical properties, in vitro cell-based effects, and in vivo platelet aggregation were investigated. FA-loaded Eudragit® L100 microparticles were successfully prepared by spray-drying. Formulations showed suitable encapsulation efficiency, i.e. close to 100%. Microparticles were of spherical and almost-spherical shape with a smooth surface and a mean diameter between 2 and 3 μm. Fourier-transformed infrared spectra demonstrated no chemical bond between FA and polymer. X-ray diffraction and differential scanning calorimetry analyses indicated that microencapsulation led to drug amorphization. FA-loaded microparticles showed a slower dissolution rate than pure drug. The chosen formulation demonstrated higher in vitro cytoprotection, anti-inflammatory and immunomodulatory potential and also improved in vivo anti-platelet effect. These results support an experimental basis for the use of FA spray-dried microparticles as a feasible oral drug delivery carrier for the controlled release of FA and improved cytoprotective and anti-platelet effects. - Highlights: • Ferulic acid-loaded Eudragit® L100 microparticles with high drug-loading were obtained. • Spray-dried Eudragit® L100 microparticles containing ferulic acid showed improved in vitro cytoprotective effect. • Ferulic acid spray-dried microparticles had potential as in vitro anti-inflammatory and immunomodulatory. • In vivo studies demonstrated an enhanced antiplatelet effect for ferulic acid-loaded Eudragit® L100 microparticles.

Significant Risk Factors for Postoperative Enlargement of Basal Ganglia Hematoma after Frameless Stereotactic Aspiration: Antiplatelet Medication and Concomitant IVH.

Science.gov (United States)

Son, Wonsoo; Park, Jaechan

2017-09-01

Frameless stereotactic aspiration of a hematoma can be the one of the treatment options for spontaneous intracerebral hemorrhage in the basal ganglia. Postoperative hematoma enlargement, however, can be a serious complication of intracranial surgery that frequently results in severe neurological deficit and even death. Therefore, it is important to identify the risk factors of postoperative hematoma growth. During a 13-year period, 101 patients underwent minimally invasive frameless stereotactic aspiration for basal ganglia hematoma. Patients were classified into two groups according to whether or not they had postoperative hematoma enlargement in a computed tomography scan. Baseline demographic data and several risk factors, such as hypertension, preoperative hematoma growth, antiplatelet medication, presence of concomitant intraventricular hemorrhage (IVH), were analysed via a univariate statistical study. Nine of 101 patients (8.9%) showed hematoma enlargement after frameless stereotactic aspiration. Among the various risk factors, concomitant IVH and antiplatelet medication were found to be significantly associated with postoperative enlargement of hematomas. In conclusion, our study revealed that aspirin use and concomitant IVH are factors associated with hematoma enlargement subsequent to frameless stereotactic aspiration for basal ganglia hematoma.

The Intracranial-B2LEED3S Score and the Risk of Intracranial Hemorrhage in Ischemic Stroke Patients Under Antiplatelet Treatment

NARCIS (Netherlands)

Amarenco, Pierre; Sissani, Leila; Labreuche, Julien; Vicaut, Eric; Bousser, Marie Germaine; Chamorro, Angel; Fisher, Marc; Ford, Ian; Fox, Kim M; Hennerici, Michael G; Mattle, Heinrich; Rothwell, Peter M; Steg, Philippe Gabriel; Diener, Hans-Christoph; Sacco, Ralph L; Greving, Jacoba P; Algra, Ale

2017-01-01

BACKGROUND: Chronic antiplatelet therapy in the post-acute phase of non-cardioembolic ischemic stroke is limited by the risk of intracranial hemorrhage (ICH) complications. METHODS: We developed an ICH risk score based on the PERFORM trial cohort (n = 19,100), which included patients with a

Low Serum Paraoxonase-1 Lactonase and Arylesterase Activities in Obese Children and Adolescents

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Sandor Raluca

2015-12-01

Full Text Available Serum paraoxonase-1 (PON1 binds mainly to high density lipoproteins (HDLs and protects low density lipoproteins (LDLs against oxidation. While paraoxonase and arylesterase activities are traditionally assayed, lactonase activity, accounting for protection against LDL oxidation, was less investigated in obese children and adolescents. Therefore, we aimed to measure lactonase, paraoxonase and arylesterase activities, oxidized LDL (ox-LDL and malondialdehyde (MDA levels in obese children and adolescents.

Management of patients taking antiplatelet or anticoagulant medication requiring invasive breast procedures: United Kingdom survey of radiologists' and surgeons' current practice

International Nuclear Information System (INIS)

Pritchard, M.G.; Townend, J.N.; Lester, W.A.; England, D.W.; Kearins, O.; Bradley, S.A.

2008-01-01

Aim: To determine the current practice in the UK National Health Service Breast Screening Programme for invasive diagnostic procedures and surgery in patients taking anticoagulant and antiplatelet medication. Materials and methods: Lead radiologists and surgeons at each breast screening service were surveyed to determine current practice. One hundred and five respondents provided information regarding their services, protocols, and willingness to proceed with combinations of procedures and anti-haemostatic medications. Results: Between units there was wide variation in practice. Within 21 services providing more than one response, 10 (48%) disagreed on whether protocols existed. Decisions to perform biopsies were unrelated to professional group. The taking of a drug history was variable. Surgeons reported more adverse effects than radiologists [21 (48%) versus 12 (26%)], but no difference in self-assessment of knowledge. Conclusion: Both radiologists and surgeons have expressed uncertainty about their understanding of anticoagulant and antiplatelet treatment. This is reflected in a wide range of practice. Guidance regarding the management of these patients is suggested

Association analysis of PON2 genetic variants with serum paraoxonase activity and systemic lupus erythematosus

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Manzi Susan

2011-01-01

Full Text Available Abstract Background Low serum paraoxonase (PON activity is associated with the risk of coronary artery disease, diabetes and systemic lupus erythematosus (SLE. Our prior studies have shown that the PON1/rs662 (p.Gln192Arg, PON1/rs854560 (p.Leu55Met, PON3/rs17884563 and PON3/rs740264 SNPs (single nucleotide polymorphisms significantly affect serum PON activity. Since PON1, PON2 and PON3 share high degree of structural and functional properties, in this study, we examined the role of PON2 genetic variation on serum PON activity, risk of SLE and SLE-related clinical manifestations in a Caucasian case-control sample. Methods PON2 SNPs were selected from HapMap and SeattleSNPs databases by including at least one tagSNP from each bin defined in these resources. A total of nineteen PON2 SNPs were successfully genotyped in 411 SLE cases and 511 healthy controls using pyrosequencing, restriction fragment length polymorphism (RFLP or TaqMan allelic discrimination methods. Results Our pair-wise linkage disequilibrium (LD analysis, using an r2 cutoff of 0.7, identified 14 PON2 tagSNPs that captured all 19 PON2 variants in our sample, 12 of which were not in high LD with known PON1 and PON3 SNP modifiers of PON activity. Stepwise regression analysis of PON activity, including the known modifiers, identified five PON2 SNPs [rs6954345 (p.Ser311Cys, rs13306702, rs987539, rs11982486, and rs4729189; P = 0.005 to 2.1 × 10-6] that were significantly associated with PON activity. We found no association of PON2 SNPs with SLE risk but modest associations were observed with lupus nephritis (rs11981433, rs17876205, rs17876183 and immunologic disorder (rs11981433 in SLE patients (P = 0.013 to 0.042. Conclusions Our data indicate that PON2 genetic variants significantly affect variation in serum PON activity and have modest effects on risk of lupus nephritis and SLE-related immunologic disorder.

Is anti-platelet therapy needed in continuous flow left ventricular assist device patients? A single-centre experience.

Science.gov (United States)

Litzler, Pierre-Yves; Smail, Hassiba; Barbay, Virginie; Nafeh-Bizet, Catherine; Bouchart, François; Baste, Jean-Marc; Abriou, Caroline; Bessou, Jean-Paul

2014-01-01

We report our 5-year experience of continuous flow left ventricular assist device (LVAD) implantation without the use of anti-platelet therapy. Between February 2006 and September 2011, 27 patients (26 men; 1 woman) were implanted with a continuous flow LVAD (HeartMate II, Thoratec Corporation, Pleasanton, CA, USA). The mean age was 55.7 ± 9.9 years. The mean duration of support was 479 ± 436 (1-1555) days with 35.4 patient-years on support. Twenty-one patients were implanted as a bridge to transplantation and 6 for destination therapy. The anticoagulation regimen was fluindione for all patients, with aspirin for only 4 patients. At the beginning of our experience, aspirin was administered to 4 patients for 6, 15, 60 and 460 days. Due to gastrointestinal (GI) bleeding and epistaxis, aspirin was discontinued, and since August 2006, no patients have received anti-platelet therapy. At 3 years, the survival rate during support was 76%. The most common postoperative adverse event was GI bleeding (19%) and epistaxis (30%) (median time: 26 days) for patients receiving fluindione and aspirin. The mean International Normalized Ratio (INR) was 2.58 ± 0.74 during support. Fifteen patients have been tested for acquired Von Willebrand disease. A diminished ratio of collagen-binding capacity and ristocetin cofactor activity to Von Willebrand factor antigen was observed in 7 patients. In the postoperative period, 2 patients presented with ischaemic stroke at 1 and 8 months. One of these 2 patients had a previous history of carotid stenosis with ischaemic stroke. There were no patients with haemorrhagic stroke, transient ischaemic attack or pump thrombosis. The event rate of stroke (ischaemic and haemorrhagic) per patient-year was 0.059 among the patients without aspirin with fluindione regimen only. A fluindione regimen without aspirin in long-duration LVAD support appears to not increase thromboembolic events and could lead to a diminished risk of haemorrhagic stroke.

Progesterone production requires activation of caspase-3 in preovulatory granulosa cells in a serum starvation model.

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An, Li-Sha; Yuan, Xiao-Hua; Hu, Ying; Shi, Zi-Yun; Liu, Xiao-Qin; Qin, Li; Wu, Gui-Qing; Han, Wei; Wang, Ya-Qin; Ma, Xu

2012-11-01

Granulosa cells proliferate, differentiate, and undergo apoptosis throughout follicular development. Previous studies have demonstrated that stimulation of progesterone production is accompanied by caspase-3 activation. Moreover, we previously reported that arsenic enhanced caspase-3 activity coupled with progesterone production. Inhibition of caspase-3 activity can significantly inhibit progesterone production induced by arsenic or follicle-stimulating hormone (FSH). Here, we report that serum starvation induces caspase-3 activation coupled with augmentation of progesterone production. Serum starvation also increased the levels of cytochrome P450 cholesterol side chain cleavage enzyme (P450scc) and steroidogenic acute regulatory (StAR) protein, both of which may contribute to progesterone synthesis in preovulatory granulosa cells. Inhibition of caspase-3 activity resulted in a decrease in progesterone production. Deactivation of caspase-3 activity by caspase-3 specific inhibitor also resulted in decreases in P450scc and StAR expression, which may partly contribute to the observed decrease in progesterone production. Our study demonstrates for the first time that progesterone production in preovulatory granulosa cells is required for caspase-3 activation in a serum starvation model. Inhibition of caspase-3 activity can result in decreased expression of the steroidogenic proteins P450scc and StAR. Our work provides further details on the relationship between caspase-3 activation and steroidogenesis and indicates that caspase-3 plays a critical role in progesterone production by granulosa cells. Copyright © 2012 Elsevier Inc. All rights reserved.

Glaucocalyxin A inhibits platelet activation and thrombus formation preferentially via GPVI signaling pathway.

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Wei Li

Full Text Available Platelets play a pivotal role in atherothrombosis and the antiplatelet agents have been proved to be useful in preventing onset of acute clinical events including myocardial infarction and stroke. Increasing number of natural compounds has been identified to be potential antiplatelet agents. Here we report the antiplatelet effect of glaucocalyxin A (GLA, an ent-diterpenoid that we isolated and purified from the aerial parts of Rabdosia japonica (Burm. f. var. glaucocalyx (Maxim. Hara, and investigate the molecular mechanisms by which GLA inhibits platelet activation and thrombus formation. The effect of GLA on platelet activation was measured using platelets freshly isolated from peripheral blood of healthy donors. Results showed that pretreatment of human platelets with lower concentrations of GLA (0.01 μg/ml, 0.1 μg/ml significantly inhibited platelet aggregation induced by collagen (P<0.001 and CRP (P<0.01, a synthetic GPVI ligand, but not by ADP and U46619. Accordingly, GLA inhibited collagen-stimulated tyrosine phosphorylation of Syk, LAT, and phospholipase Cγ2, the signaling events in collagen receptor GPⅥ pathway. GLA also inhibited platelet p-selectin secretion and integrin activation by convulxin, a GPVI selective ligand. Additionally, GLA was found to inhibit low-dose thrombin-induced platelet activation. Using a flow chamber device, GLA was found to attenuate platelet adhesion on collagen surfaces in high shear condition. In vivo studies showed that GLA administration increased the time for complete occlusion upon vascular injury in mice, but did not extend tail-bleeding time when mice were administered with relatively lower doses of GLA. Therefore, the present results provide the molecular basis for the inhibition effect of GLA on platelet activation and its in vivo effect on thrombus formation, suggesting that GLA could potentially be developed as an antiplatelet and antithrombotic agent.

Serum thymidine kinase activity of various cancer and HBV positive liver diseases

Energy Technology Data Exchange (ETDEWEB)

Torizumi, Kazutami; Aibata, Hirofumi; Kiji, Shigeyuki; Ohta, Kiichiro; Okamoto, Yukiharu; Ohshiro, Iwao; Hirose, Tetsuhito

1987-03-01

Clinical utility of determination of serum deoxythymidine kinase (TK) activity is described. It is well known that elevated TK level is observed in leukemia and other malignant diseases, or some viral infectious diseases. The TK activity was assayed on normal subjects, hepatitis B virus (HBV) positive liver diseases and various cancer by a newly developed high sensitive method, radioenzyme assay (REA) utilizing /sup 125/I-iododeoxyuridine as the substrate. Measurement of TK activity by the REA is revealed to be useful for ''the marker of DNA metabolism anomaly'' in leukemia, etc.

Decreased serum paraoxonase 1 (PON1) activity: an additional risk factor for atherosclerotic heart disease in patients with PCOS?

Science.gov (United States)

Dursun, Polat; Demirtaş, Ezgi; Bayrak, Ahmet; Yarali, Hakan

2006-01-01

Patients with polycystic ovary syndrome (PCOS) may have an increased risk for the development of hypertension and atherosclerotic heart disease (AHD), the pathophysiological mechanisms of which are not clear. Paraoxonase1 (PON1) is a high-density lipoprotein-associated enzyme that prevents oxidative modification of low-density lipoprotein. The aim of this study was to measure the serum levels of PON1 activity in patients with PCOS and to compare with those of regularly cycling controls. Serum lipid parameters, malondialdehyde (MDA) levels and PON1 activity, were measured in PCOS patients (n = 23) and regularly cycling, age-, body mass index- and smoking status-matched controls (n = 23). All patients had normal glucose tolerance test as assessed by a 75 g oral glucose tolerance test. None of the patients had clinically evident hypertension or AHD. Apart from the mean serum PON1 activity, all parameters in the lipid profile including serum MDA levels were comparable between the two groups. There were no significant differences in respect to fasting glucose (4.64 +/- 0.5 versus 4.43 +/- 0.83 mmol/l) and fasting glucose insulin ratio (11.06 +/- 8.26 versus 11.49 +/- 4.90) among the two groups (P > 0.05). However, HOMA insulin resistance index was significantly higher in patients with PCOS compared with the controls (2.06 +/- 0.86 versus 1.51 +/- 0.49; P = 0.01). Also, mean serum PON1 activity was significantly lower in the PCOS group compared with the controls (151.2 +/- 90.8 versus 217.7 +/- 101.6, respectively; P = 0.027). Reduced serum PON1 activity might contribute to the increased susceptibility for the development of AHD in women with PCOS.

Antioxidant and antiplatelet activity by polyphenol-rich nutrients: focus on extra virgin olive oil and cocoa.

Science.gov (United States)

Loffredo, Lorenzo; Perri, Ludovica; Nocella, Cristina; Violi, Francesco

2017-01-01

Cardiovascular disease is the most common cause of death in the Western world. In the last decades nutraceutical approaches have been proposed to counteract atherosclerotic complications. In particular, polyphenols, a class of bio-active molecules prevalently contained in foods such as cocoa, fruits, vegetables, wine and tea, have been widely studied for their beneficial properties. Several epidemiological and interventional studies have shown that polyphenol-rich nutrients, as in extra virgin olive oil (EVOO) and cocoa, are associated with a risk reduction of cardiovascular events and/or modulation of cardiovascular risk factors. Definition of the mechanisms accounting for this putative cardio-protective effect is still elusive. This review focuses on the mechanisms that may be implicated in the beneficial effects of EVOO and cocoa, including down-regulation of oxidative stress and platelet aggregation, improvement of endothelial function and cardiovascular risk factor such as blood pressure, serum cholesterol and insulin sensitivity. © 2016 The British Pharmacological Society.

[Effect of low-intensity 900 MHz frequency electromagnetic radiation on rat liver and blood serum enzyme activities].

Science.gov (United States)

Nersesova, L S; Petrosian, M S; Gazariants, M G; Mkrtchian, Z S; Meliksetian, G O; Pogosian, L G; Akopian, Zh I

2014-01-01

The comparative analysis of the rat liver and blood serum creatine kinase, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and purine nucleoside phosphorylase post-radiation activity levels after a total two-hour long single and fractional exposure of the animals to low-intensity 900 MHz frequency electromagnetic field showed that the most sensitive enzymes to the both schedules of radiation are the liver creatine kinase, as well as the blood serum creatine kinase and alkaline phosphatase. According to the comparative analysis of the dynamics of changes in the activity level of the liver and blood serum creatine kinase, alanine aminotransferase, aspartate aminotransferase and purine nucleoside phosphorylase, both single and fractional radiation schedules do not affect the permeability of a hepatocyte cell membrane, but rather cause changes in their energetic metabolism. The correlation analysis of the post-radiation activity level changes of the investigated enzymes did not reveal a clear relationship between them. The dynamics of post-radiation changes in the activity of investigated enzyme levels following a single and short-term fractional schedules of radiation did not differ essentially.

Increased serum YKL-40 in patients with pulmonary sarcoidosis--a potential marker of disease activity?

DEFF Research Database (Denmark)

Johansen, Julia S; Milman, Nils; Hansen, Michael

2005-01-01

YKL-40, a growth factor for fibroblasts and vascular endothelial cells, is secreted by macrophages and neutrophils. Elevated serum YKL-40 is found in patients with diseases characterized by inflammation, tissue remodelling and ongoing fibrosis. The aim was to evaluate whether macrophages and giant...... cells in the granulomatous sarcoid lesions of patients with pulmonary sarcoidosis produce YKL-40 and to determine whether serum YKL-40 in these patients were associated with disease activity....

Antiplatelet Treatment After Transient Ischemic Attack and Ischemic Stroke in Patients With Cerebral Microbleeds in 2 Large Cohorts and an Updated Systematic Review.

Science.gov (United States)

Lau, Kui Kai; Lovelock, Caroline E; Li, Linxin; Simoni, Michela; Gutnikov, Sergei; Küker, Wilhelm; Mak, Henry Ka Fung; Rothwell, Peter M

2018-06-01

In patients with transient ischemic attack/ischemic stroke, microbleed burden predicts intracerebral hemorrhage (ICH), and ischemic stroke, but implications for antiplatelet treatment are uncertain. Previous cohort studies have had insufficient follow-up to assess the time course of risks, have not stratified risks by antithrombotic use, and have not reported extracranial bleeds or functional outcome of ICH versus ischemic stroke. In 2 independent prospective cohorts with transient ischemic attack/ischemic stroke (Oxford Vascular Study/mainly white; University of Hong Kong/mainly Chinese), antiplatelet treatment was started routinely irrespective of microbleed burden. Risks, time course and outcome of ICH, extracranial bleeds, and recurrent ischemic events were determined and stratified by microbleed burden (0 versus 1, 2-4, and ≥5), adjusting for age, sex, and vascular risk factors. Microbleeds were more frequent in the Chinese cohort (450 of 1003 versus 165 of 1080; P <0.0001), but risk associations were similar during 7433 patient-years of follow-up. Among 1811 patients on antiplatelet drugs, risk of major extracranial bleeds was unrelated to microbleed burden ( P trend =0.87), but the 5-year risk of ICH was steeply related ( P trend <0.0001), with 11 of 15 (73%) of ICH in 140 of 1811 (7.7%) patients with ≥5 microbleeds. However, risk of ischemic stroke also increased with microbleed burden ( P trend =0.013), such that risk of ischemic stroke and coronary events exceeded ICH and major extracranial bleeds during the first year, even among patients with ≥5 microbleeds (11.6% versus 3.9%). However, this ratio changed over time, with risk of hemorrhage (11.2%) matching that of ischemic events (12.0%) after 1 year. Moreover, whereas the association between microbleed burden and risk of ischemic stroke was due mainly to nondisabling events ( P trend =0.007), the association with ICH was accounted for ( P trend <0.0001) by disabling/fatal events (≥5 microbleeds

Effect of an obesogenic diet on circadian activity and serum hormones in old monkeys

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Henryk F Urbanski

2017-07-01

Full Text Available Like women, old female rhesus macaques undergo menopause and show many of the same age-associated changes, including perturbed activity/rest cycles and altered circulating levels of many hormones. Previous studies showed that administration of an estrogen agonist increased activity in female monkeys, that hormone therapy (HT increased activity in postmenopausal women and that obesity decreased activity in women. The present study sought to determine if postmenopausal activity and circulating hormone levels also respond to HT when monkeys are fed a high-fat, high-sugar Western style diet (WSD. Old female rhesus macaques were ovo-hysterectomized (OvH to induce surgical menopause and fed a WSD for 2 years. Half of the animals received estradiol-17β (E, beginning immediately after OvH, while the other half received placebo. Animals in both groups showed an increase in body weight and a decrease in overall activity levels. These changes were associated with a rise in both daytime and nocturnal serum leptin concentrations, but there was no change in serum concentrations of either cortisol or dehydroepiandrosterone sulfate (DHEAS. These data suggest that 2 years of HT has little or no effect on locomotor activity or circadian hormone patterns in menopausal macaques fed an obesogenic diet.

Correlation of serum paraoxonase activities in known cases of 130 elderly hypertensive South Asian aged 56-64 years - a hospital based study

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Arun Kumar

2014-02-01

Full Text Available Objective: To evaluate paraoxonase activity, antioxidant status and lipid peroxidation in hypertensive participants and to address the hypothesis that oxidative modifications of lipids due to hypertension can cause changes in serum paraoxonase activities. Methods: The serum paraoxonase activities, antioxidants and lipid peroxidation were determined in 130 hypertensive participants and 130 age-sexes matched normotensive healthy volunteers served as control. Serum paraoxonase activities were measured by enzymatic kit. The glutathione peroxidase, superoxide dismutase and catalase activity were determined by standard methods. Malondialdehyde was measured by thiobarbituric acid reaction. Conjugated diene level was measured by Recknagel and Glende method. Serum uric acid, total bilirubin, serum albumin, serum ascorbic acid and lipid profile were analyzed by standard methods. Results: Total cholesterol, triglycerides, low-density lipoprotein cholesterol were significantly higher and high-density lipoprotein cholesterol were significantly lower in hypertensive patients when compared to normotensive healthy controls. The superoxide dismutase, glutathione peroxidase and catalase were significantly lower in hypertensive when compared with normotensive. Similar findings were observed in the levels of albumin, uric acid, bilirubin and ascorbic acid when hypertensives were compared with normotensive. The oxidative stress indicators namely malondialdehyde and conjugated diene were significantly higher and paraoxonase activity were significantly lower in hypertensive. Conclusions: Our study concludes that paraoxonase activities are bound to alter in hypertension which is caused due to interplay of several confounding factors namely oxidative stress, increased oxidized low-density lipoprotein and depletion of antioxidants.

Stimulation of LDL receptor activity in Hep-G2 cells by a serum factor(s)

International Nuclear Information System (INIS)

Ellsworth, J.L.; Brown, C.; Cooper, A.D.

1988-01-01

The regulation of low-density lipoprotein (LDL) receptor activity in the human hepatoma cell line Hep-G2 by serum components was examined. Incubation of dense monolayers of Hep-G2 cells with fresh medium containing 10% fetal calf serum (FM) produced a time-dependent increase in LDL receptor activity. Uptake and degradation of 125I-LDL was stimulated two- to four-fold, as compared with that of Hep-G2 cells cultured in the same media in which they had been grown to confluence (CM); the maximal 125I-LDL uptake plus degradation increased from 0.2 microgram/mg cell protein/4 h to 0.8 microgram/mg cell protein/4 h. In addition, a two-fold increase in cell surface binding of 125I-LDL to Hep-G2 cells was observed when binding was measured at 4 degrees C. There was no change in the apparent Kd. The stimulation of LDL receptor activity was suppressed in a concentration-dependent manner by the addition of cholesterol, as LDL, to the cell medium. In contrast to the stimulation of LDL receptor activity, FM did not affect the uptake or degradation of 125I-asialoorosomucoid. Addition of FM increased the protein content per dish, and DNA synthesis was stimulated approximately five-fold, as measured by [3H]thymidine incorporation into DNA; however, the cell number did not change. Cellular cholesterol biosynthesis was also stimulated by FM; [14C]acetate incorporation into unesterified and esterified cholesterol was increased approximately five-fold. Incubation of Hep-G2 cells with high-density lipoproteins (200 micrograms protein/ml) or albumin (8.0 mg/ml) in the absence of the serum factor did not significantly increase the total processed 125I-LDL. Stimulation of LDL receptor activity was dependent on a heat-stable, nondialyzable serum component that eluted in the inclusion volume of a Sephadex G-75 column

Dual antiplatelet therapy reduces stroke but increases bleeding at the time of carotid endarterectomy.

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Jones, Douglas W; Goodney, Philip P; Conrad, Mark F; Nolan, Brian W; Rzucidlo, Eva M; Powell, Richard J; Cronenwett, Jack L; Stone, David H

2016-05-01

Controversy persists regarding the perioperative management of clopidogrel among patients undergoing carotid endarterectomy (CEA). This study examined the effect of preoperative dual antiplatelet therapy (aspirin and clopidogrel) on in-hospital CEA outcomes. Patients undergoing CEA in the Vascular Quality Initiative were analyzed (2003-2014). Patients on clopidogrel and aspirin (dual therapy) were compared with patients taking aspirin alone preoperatively. Study outcomes included reoperation for bleeding and thrombotic complications defined as transient ischemic attack (TIA), stroke, or myocardial infarction. Secondary outcomes were in-hospital death and composite stroke/death. Univariate and multivariable analyses assessed differences in demographics and operative factors. Propensity score-matched cohorts were derived to control for subgroup heterogeneity. Of 28,683 CEAs, 21,624 patients (75%) were on aspirin and 7059 (25%) were on dual therapy. Patients on dual therapy were more likely to have multiple comorbidities, including coronary artery disease (P < .001), congestive heart failure (P < .001), and diabetes (P < .001). Patients on dual therapy were also more likely to have a drain placed (P < .001) and receive protamine during CEA (P < .001). Multivariable analysis showed that dual therapy was independently associated with increased reoperation for bleeding (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.20-2.42; P = .003) but was protective against TIA or stroke (OR, 0.61; 95% CI, 0.43-0.87; P = .007), stroke (OR, 0.63; 95% CI, 0.41-0.97; P = .03), and stroke/death (OR, 0.66; 95% CI, 0.44-0.98; P = .04). Propensity score matching yielded two groups of 4548 patients and showed that patients on dual therapy were more likely to require reoperation for bleeding (1.3% vs 0.7%; P = .004) but less likely to suffer TIA or stroke (0.9% vs 1.6%; P = .002), stroke (0.6% vs 1.0%; P = .04), or stroke/death (0.7% vs 1.2%; P = .03). Within the

Elevated Concentrations of Serum Immunoglobulin Free Light Chains in Systemic Lupus Erythematosus Patients in Relation to Disease Activity, Inflammatory Status, B Cell Activity and Epstein-Barr Virus Antibodies.

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Anette H Draborg

Full Text Available In this study, we examined the concentration of serum immunoglobulin free light chains (FLCs in systemic lupus erythematosus (SLE patients and investigated its association with various disease parameters in order to evaluate the role of FLCs as a potential biomarker in SLE. Furthermore, FLCs' association with Epstein-Barr virus (EBV antibodies was examined.Using a nephelometric assay, κFLC and λFLC concentrations were quantified in sera from 45 SLE patients and 40 healthy controls. SLE patients with renal insufficiency were excluded in order to preclude high concentrations of serum FLCs due to decreased clearance.Serum FLC concentrations were significantly elevated in SLE patients compared to healthy controls (p<0.0001 also after adjusting for Ig levels (p<0.0001. The concentration of serum FLCs correlated with a global disease activity (SLE disease activity index (SLEDAI score of the SLE patients (r = 0.399, p = 0.007. Furthermore, concentrations of FLCs correlated with titers of dsDNA antibodies (r = 0.383, p = 0.009, and FLC levels and SLEDAI scores correlated in the anti-dsDNA-positive SLE patients, but not in anti-dsDNA-negative SLE patients. Total immunoglobulin (IgG and IgA concentrations correlated with FLC concentrations and elevated FLC levels were additionally shown to associate with the inflammatory marker C-reactive protein and also with complement consumption determined by low C4 in SLE patients. Collectively, results indicated that elevated serum FLCs reflects increased B cell activity in relation to inflammation. SLE patients had an increased seropositivity of EBV-directed antibodies that did not associate with elevated FLC concentrations. An explanation for this could be that serum FLC concentrations reflect the current EBV activity (reactivation whereas EBV-directed antibodies reflect the extent of previous infection/reactivations.SLE patients have elevated concentrations of serum FLCs that correlate with global disease

High serum ACE activity predicts severe hypoglycaemia over time in patients with type 1 diabetes

DEFF Research Database (Denmark)

Færch, Louise; Pedersen-Bjergaard, Ulrik; Thorsteinsson, Birger

2011-01-01

High serum angiotensin-converting enzyme (ACE) activity is associated with increased risk of severe hypoglycaemia (SH) within 1 year in type 1 diabetes. We wanted to find out whether ACE activity is stable over time and predicts SH beyond 1 year, and if gender differences exist in the association...

Clinical significance of the changes of serum levels of the rheumatoid activity markers IL-2, sIL-2R, HA and VEGF

International Nuclear Information System (INIS)

Bao Yong; Long Wubin; Yu Ke; Zeng Ying; Liu Deying

2004-01-01

Objective: To explore the relationship between rheumatoid activity and serum levels of the cytokines interleukin-2 (IL-2), soluble interleukin-2 receptor (sIL-2R), hyaluronic acid (HA), vascular endothelial growth factor (VEGF) in patients with rheumatoid arthritis. Methods: Serum IL-2, HA(with RIA) and sIL-2R, VEGF (with ELISA) levels were determined in 30 controls, 30 patients with active rheumatoid arthritis and 30 patients with rheumatoid arthritis in remission. Sensitivity and specificity for each marker were analyzed. Results: In patients with active rheumatoid arthritis, the serum levels of sIL-2R, HA, VEGF were significantly higher and serum levels of IL-2 significantly lower than those in patients in remission and controls (p<0.01). Determination of VEGF levels possessed the highest specificity (93.3%) and also a high sensitivity (93.3% as well). Conclusion: Determination of the serum levels of any of these markers was valuable for monitoring the activity of the rheumatoid process. It is more desirable to take measurements of VEGF levels due to its highest specificity

Regulation of IgE antibody production by serum molecules. II. Strain-specificity of the suppressive activity of serum from complete Freund's adjuvant-immune low responder mouse donors

International Nuclear Information System (INIS)

Katz, D.H.; Tung, A.S.

1978-01-01

IgE antibody production in mice of high and low IgE responder phenotypes, respectively, can be appreciably enhanced in magnitude after low-dose whole-body x irradiation. Such enhanced responses, as well as adoptive secondary IgE responses, can be markedly suppressed by passive transfer of CFA-immune serum in low responder strains, but not in high responder strains. The studies presented here demonstrate that the suppressive activity of CFA-immune serum on IgE antibody production is strain specific. This is true even in reciprocal combinations of low IgE responder SJL and C57BL/6 mice, in which it was shown that serum capable of suppressing mice of the isologous strain was ineffective in diminishing IgE antibody production in the other low responder strain. Absence of suppressive activity in CFA-immune sera obtained from H-2 haplotypes while sharing many similarities in the background genome and, conversely, effective suppressive activity of H-2 congenic donor sera when H-2-identities between donor and recipient mice existed, strongly suggested a role, at least in part, of H-2 genes in dictating the strain specificity of such suppressive activity. Additional experiments provided evidence for a possible role of macrophages in catabolism of the active molecules in CFA-immune sera. These observations, together with those presented in the preceding paper, may provide valuable insight toward successful development of appropriate manipulations that could ultimately convert high IgE responder individuals into low responders

Study on the growth promoting capacity of calf and fetal bovine serum for animal cells "in vitro" II: electrophoretic study and survey on the antiproteolytic activity of pools of calf and fetal bovine serum

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Edda de Rizzo

1984-04-01

Full Text Available Calf serum and fetal bovine serum present great variability as to its growth promoting efficiency (GPE. As supplement of culture media to cultivate cells of animal origin they stimulate the "in vitro" multiplication and maintain cell viability. When fourteen lots of calf sera of variable GPE had the total protein contents as well as the percentages of serum fractions determined, no significant differences that could possibly explain the variability of the GPE were observed. Evaluation of the antiproteolytic activity of nineteen lots of calf serum and eighteen serum lots of younger calves showed that the former exhibited lower antiproteolytic titers (1:40 to 1:80 than the latter (1:80 to 1:160. Twelve lots of fetal bovine serum studied in parallel, showed the highest concentration of antiproteolytic factors, with titers equal to 1:320. Sera of bovine origin, but not fetal sera, are usually heat-inactivated, what was demonstrated to be responsible for the decrease of the antiproteolytic activity of 75% of the lots tested. This could explain the inability of certain heat-inactivated sera in promoting multiplication of some cells "in vitro", as verified with primary monkey kidney cells. The results obtained in this study indicated the convenience of submiting each lot of serum to be introduced in cell culture to previous determination of its characteristics, such as growth promoting efficiency, antiproteolytic activity and also toxicity, absence of extraneous agents, etc., in order to minimize the possibility of using serum lots of questionable quality, thus preventing not only the loss of cell lines, but also undesirable and sometimes expensive delays.

Endoscopy and antiplatelet agents. European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

Science.gov (United States)

Boustière, C; Veitch, A; Vanbiervliet, G; Bulois, P; Deprez, P; Laquiere, A; Laugier, R; Lesur, G; Mosler, P; Nalet, B; Napoleon, B; Rembacken, B; Ajzenberg, N; Collet, J P; Baron, T; Dumonceau, J-M

2011-05-01

With the increasing use of antiplatelet agents (APA), their management during the periendoscopic period has become a more common and more difficult problem. The increase in use is due to the availability of new drugs and the widespread use of drug-eluting coronary stents. Acute coronary syndromes can occur when APA therapy is withheld for noncardiovascular interventions. Guidelines about APA management during the periendoscopic period are traditionally based on assessments of the procedure-related risk of bleeding and the risk of thrombosis if APA are stopped. New data allow better assessment of these risks, of the necessary duration of APA discontinuation before endoscopy, of the use of alternative procedures (mostly for endoscopic retrograde cholangiopancreatography [ERCP]), and of endoscopic methods that can be used to prevent bleeding (following colonic polypectomy). This guideline makes graded, evidence-based, recommendations for the management of APA for all currently performed endoscopic procedures. A short summary and two tables are included for quick reference. © Georg Thieme Verlag KG Stuttgart · New York.

Both antiplatelet and anticoagulant therapy may favorably affect outcome in patients with advanced heart failure. A retrospective analysis of the PRIME-II trial.

NARCIS (Netherlands)

Boer, R.A. de; Hillege, H.L.; Tjeerdsma, G.; Verheugt, F.W.A.; Veldhuisen, D.J. van

2005-01-01

INTRODUCTION: Current guidelines of chronic heart failure (CHF) do not recommend the use of oral anticoagulants (OAC) or antiplatelet therapy (APT). We performed a post-hoc analysis to evaluate the effect of the use of anti-thrombotic therapy with APT and OAC. PATIENTS AND METHODS: We examined 427

Elevated Serum ADA Activity as a Marker for Diagnosis and Prognosis of Visceral Leishmaniasis and Post Kala-Azar Dermal Leishmaniasis in Indian Patients

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Vijayamahantesh; Amit, Ajay; Dikhit, Manas R.; Pandey, Raj K.; Singh, Kuljit; Mishra, Ritesh; Das, V. N. R; Das, Pradeep; Bimal, Sanjiva

2016-01-01

Serum adenosine deaminase (ADA) activity increases in diseases where cellular immunity is involved. Since cell-mediated immune responses play a paramount role in the pathogenesis and healing of the visceral leishmaniasis, therefore, the present study was undertaken to evaluate the serum ADA activity in different pathological conditions. Adenosine deaminase was determined in sera of active visceral leishmaniasis (VL) patients (n = 39), active postkala-azar dermal leishmaniasis (PKDL) cases (n = 34) at the point of diagnosis and after treatment stages along with healthy controls (n = 30), endemic healthy subjects (n = 34) and endemic asymptomatic subjects (n = 34).Our in-vitro result revealed that monocytes secrete significant ADA level in response to Leishmania donovani (L.donovani) stimulation. The serum ADA activity in active VL and PKDL subjects were found to be significantly higher than that of respective treated cases and healthy controls. We also observed a marginal number (17.6%) of endemic asymptomatic subjects showed elevated serum ADA activity. Further, the ADA activity in PKDL was found to be decreased gradually during the different phases of treatment. Interestingly, 2 out of 32 treated VL cases found to have high serum ADA activity during follow up period were relapsed within few days. These results suggest the possibility of ADA as a marker of clinical pathogenesis and can be used as a surrogate marker in the diagnosis and prognosis of VL and PKDL. PMID:27186641

Elevated Serum ADA Activity as a Marker for Diagnosis and Prognosis of Visceral Leishmaniasis and Post Kala-Azar Dermal Leishmaniasis in Indian Patients.

Science.gov (United States)

Vijayamahantesh; Amit, Ajay; Dikhit, Manas R; Pandey, Raj K; Singh, Kuljit; Mishra, Ritesh; Das, V N R; Das, Pradeep; Bimal, Sanjiva

2016-01-01

Serum adenosine deaminase (ADA) activity increases in diseases where cellular immunity is involved. Since cell-mediated immune responses play a paramount role in the pathogenesis and healing of the visceral leishmaniasis, therefore, the present study was undertaken to evaluate the serum ADA activity in different pathological conditions. Adenosine deaminase was determined in sera of active visceral leishmaniasis (VL) patients (n = 39), active postkala-azar dermal leishmaniasis (PKDL) cases (n = 34) at the point of diagnosis and after treatment stages along with healthy controls (n = 30), endemic healthy subjects (n = 34) and endemic asymptomatic subjects (n = 34).Our in-vitro result revealed that monocytes secrete significant ADA level in response to Leishmania donovani (L.donovani) stimulation. The serum ADA activity in active VL and PKDL subjects were found to be significantly higher than that of respective treated cases and healthy controls. We also observed a marginal number (17.6%) of endemic asymptomatic subjects showed elevated serum ADA activity. Further, the ADA activity in PKDL was found to be decreased gradually during the different phases of treatment. Interestingly, 2 out of 32 treated VL cases found to have high serum ADA activity during follow up period were relapsed within few days. These results suggest the possibility of ADA as a marker of clinical pathogenesis and can be used as a surrogate marker in the diagnosis and prognosis of VL and PKDL.

The antiplatelet effects of nitrates: is it of clinical significance in patients with cardiovascular disease?

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Zhou, Rui-Hai; Frishman, William H

2010-01-01

Organic nitrates have been used for over a century in cardiovascular therapy and are still widely used in the treatment of acute coronary syndromes, chronic angina pectoris, and congestive heart failure. Nitrates, together with sodium nitroprusside, generally referred to as nitrovasodilators, exert their biologic effects via the release of nitric oxide. They are also known as nitric oxide donors. The mechanism of action of these drugs is traditionally believed to lie in their arterial vasodilation and venodilation effects, resulting in an improvement of coronary artery blood supply and/or reduction of cardiac workload in the treatment of coronary artery disease and congestive heart failure. Recently it has been recognized that these drugs also have intrinsic antiplatelet and antithrombotic effects, demonstrated both in vitro and in vivo, which would add further rationale for the use of these drugs in atherothrombotic diseases. Research has shown that nitrovasodilators can nonselectively inhibit platelet aggregation induced by multiple stimuli. However, clinical trials have yielded conflicting results regarding clinical outcome, especially with long-term nitrate use. The potentially beneficial effects of nitrates could be negated by the development of tolerance and the generation of deleterious oxidative stress causing endothelial dysfunction during continuous nitrate administration. Much progress has been made in the development of new nitric oxide donors devoid of oxidant-generating properties. Novel combination therapies with nitrovasodilators plus antioxidants or agents with antioxidant properties have shown promise in reducing or reversing tolerance, potentiating antiplatelet effects, and improving clinical outcome. It is expected that clinical introduction of novel nitrovasodilator regimens will provide a new approach to the prevention and treatment of atherothrombotic diseases. Large-scale clinical trials will ultimately provide the evidence-based answers.

Decreased Killing Activity of Micafungin Against Candida guilliermondii, Candida lusitaniae, and Candida kefyr in the Presence of Human Serum.

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Saleh, Qasem; Kovács, Renátó; Kardos, Gábor; Gesztelyi, Rudolf; Kardos, Tamás; Bozó, Aliz; Majoros, László

2017-09-01

Currently, echinocandins are first-line drugs for treatment of invasive candidiasis. However, data on how serum influences killing activity of echinocandins against uncommon Candida species are limited. Therefore, the killing activity of micafungin in RPMI-1640 and in 50% serum was compared against Candida guilliermondii, Candida lusitaniae, and Candida kefyr. Minimum inhibitory concentration (MIC) ranges in RPMI-1640 were 0.5-1, 0.12-0.25, and 0.06-0.12 mg/L, respectively. In 50% serum, MICs increased 32- to 256-fold. In RPMI-1640 ≥ 0.25, ≥4, and 32 mg/L micafungin was fungicidal against all four C. kefyr (≤4.04 hours), two of three C. lusitaniae (≤16.10 hours), and two of three C. guilliermondii (≤12.30 hours), respectively. In 50% serum, all three species grew at ≤4 mg/L. Micafungin at 16-32 mg/L was fungicidal against all C. kefyr isolates (≤3.03 hours) and at 32 mg/L was fungistatic against one of three C. lusitaniae isolates. Two C. lusitaniae isolates and all three C. guilliermondii grew at all tested concentrations. Adding human serum to susceptibility test media drew attention to loss of fungicidal or fungistatic activity of micafungin in the presence of serum proteins, which is not predicted by MICs in case of C. kefyr and C. lusitaniae in RPMI-1640. Our results strongly suggest that micafungin and probably other echinocandins should be used with caution against rare Candida species.

Prevalence of Ex Vivo High On-treatment Platelet Reactivity on Antiplatelet Therapy after Transient Ischemic Attack or Ischemic Stroke on the PFA-100(®) and VerifyNow(®).

LENUS (Irish Health Repository)

Kinsella, Justin A

2012-09-12

BACKGROUND: The prevalence of ex vivo high on-treatment platelet reactivity (HTPR) to commonly prescribed antiplatelet regimens after transient ischemic attack (TIA) or ischemic stroke is uncertain. METHODS: Platelet function inhibition was simultaneously assessed with modified light transmission aggregometry (VerifyNow; Accumetrics Inc, San Diego, CA) and with a moderately high shear stress platelet function analyzer (PFA-100; Siemens Medical Solutions USA, Inc, Malvern, PA) in a pilot, cross-sectional study of TIA or ischemic stroke patients. Patients were assessed on aspirin-dipyridamole combination therapy (n = 51) or clopidogrel monotherapy (n = 25). RESULTS: On the VerifyNow, HTPR on aspirin was identified in 4 of 51 patients (8%) on aspirin-dipyridamole combination therapy (≥550 aspirin reaction units on the aspirin cartridge). Eleven of 25 (44%) patients had HTPR on clopidogrel (≥194 P2Y12 reaction units on the P2Y12 cartridge). On the PFA-100, 21 of 51 patients (41%) on aspirin-dipyridamole combination therapy had HTPR on the collagen-epinephrine (C-EPI) cartridge. Twenty-three of 25 patients (92%) on clopidogrel had HTPR on the collagen-adenosine diphosphate (C-ADP) cartridge. The proportion of patients with antiplatelet HTPR was lower on the VerifyNow than PFA-100 in patients on both regimens (P < .001). CONCLUSIONS: The prevalence of ex vivo antiplatelet HTPR after TIA or ischemic stroke is markedly influenced by the method used to assess platelet reactivity. The PFA-100 C-ADP cartridge is not sensitive at detecting the antiplatelet effects of clopidogrel ex vivo. Larger prospective studies with the VerifyNow and with the PFA-100 C-EPI and recently released Innovance PFA P2Y cartridges (Siemens Medical Solutions USA, Inc) in addition to newer tests of platelet function are warranted to assess whether platelet function monitoring predicts clinical outcome in ischemic cerebrovascular disease.

Biological Activities of Hydrazone Derivatives

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S. Güniz Küçükgüzel

2007-08-01

Full Text Available There has been considerable interest in the development of novel compounds with anticonvulsant, antidepressant, analgesic, antiinflammatory, antiplatelet, antimalarial, antimicrobial, antimycobacterial, antitumoral, vasodilator, antiviral and antischistosomiasis activities. Hydrazones possessing an azometine -NHN=CH- proton constitute an important class of compounds for new drug development. Therefore, many researchers have synthesized these compounds as target structures and evaluated their biological activities. These observations have been guiding for the development of new hydrazones that possess varied biological activities.

New oral anticoagulant and antiplatelet agents for neurosurgeons.

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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.

Molecular spectroscopic and thermodynamic studies on the interaction of anti-platelet drug ticlopidine with calf thymus DNA

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Afrin, Shumaila; Rahman, Yusra; Sarwar, Tarique; Husain, Mohammed Amir; Ali, Abad; Shamsuzzaman; Tabish, Mohammad

2017-11-01

Ticlopidine is an anti-platelet drug which belongs to the thienopyridine structural family and exerts its effect by functioning as an ADP receptor inhibitor. Ticlopidine inhibits the expression of TarO gene in S. aureus and may provide protection against MRSA. Groove binding agents are known to disrupt the transcription factor DNA complex and consequently inhibit gene expression. Understanding the mechanism of interaction of ticlopidine with DNA can prove useful in the development of a rational drug designing system. At present, there is no such study on the interaction of anti-platelet drugs with nucleic acids. A series of biophysical experiments were performed to ascertain the binding mode between ticlopidine and calf thymus DNA. UV-visible and fluorescence spectroscopic experiments confirmed the formation of a complex between ticlopidine and calf thymus DNA. Moreover, the values of binding constant were found to be in the range of 103 M- 1, which is indicative of groove binding between ticlopidine and calf thymus DNA. These results were further confirmed by studying the effect of denaturation on double stranded DNA, iodide quenching, viscometric studies, thermal melting profile as well as CD spectral analysis. The thermodynamic profile of the interaction was also determined using isothermal titration calorimetric studies. The reaction was found to be endothermic and the parameters obtained were found to be consistent with those of known groove binders. In silico molecular docking studies further corroborated well with the experimental results.

Serum activities of liver enzymes in workers exposed to sub-TLV levels of dimethylformamide

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Jinjiang He

2015-04-01

Full Text Available Objectives: The aim of this study has been to investigate serum activities of liver enzymes in workers exposed to sub-TLV levels of dimethylformamide (DMF. Material and Methods: Seventy-two workers and 72 healthy controls participated in the study. All subjects underwent complete physical examinations and abdominal ultrasound examination. Serum aspartate aminotransferase (AST, alanine aminotransferase (ALT, and c-glutamyl transpeptidase (c-GT were determined by an auto-chemistry analyzer. The data of airborne concentrations of DMF was obtained from the local Center of Disease Control and Prevention. The level of urine N-acetyl-S-(N-methylcarbamoylcysteine (AMCC was measured by means of high-performance liquid chromatography. Results: Time weighted average (TWA concentration of the DMF in workplace was 18.6 (range: 9.8–36.2 mg/m3. The concentration of the AMCC in workers’ urine was 28.32 (range: 1.8–58.6 mg/l and 9 workers’ AMCC exceeded the biological exposure index (40 mg/l. Thirty-one workers reported gastrointestinal symptoms (abdominal pain, nausea, anorexia and 10 workers reported headache, dizziness and/or palpitation in the exposed group. Serum analysis revealed that both the mean of serum activities of liver enzymes (ALT, AST and c-GT and the percentage of workers with abnormal liver function were significantly higher in the exposed group as compared to the controls. Conclusions: Dimethylformamide can cause liver damage even if air concentration is in the sub-threshold limit value (sub-TLV level. The protection of skin contact against the exposure to the DMF might be a critical issue as far as the occupational health is concerned.

The effects of Zinc supplementation on serum zinc, alkaline phosphatase activity and fracture healing of bones

International Nuclear Information System (INIS)

Sadighi, A.; Moradi, A.; Roshan, Marjan M.; Ostadrahimi, A.

2009-01-01

Objective was to determine the effect of zinc supplementation on callus information, serum zinc and alkaline phosphatase activity in humans. This randomized, double-blind, placebo controlled clinical trial was conducted on 60 patients with traumatic bone fracture referred to Shohada Hospital of Tabriz, Iran from August to December 2007. Subjects were randomly divided into 2 groups: cases (n=30), receiving one capsule of zinc sulfate consists of 50 mg zinc each day and the controls (n=30), receiving placebo for 60 days. Individual and clinical information was determined by a questionnaire: nutritional intake by 3 days food records at the beginning and the end of trial. Serum zinc and alkaline phosphatase was measured by atomic absorption spectroscopy and by enzymatic method. Callus information during fracture healing was evaluated by radiography of the bone. There was no significant difference in physical activity, gender, age, type of fractures and nutrient intake, between the 2 groups. The administration of zinc caused a significant elevation of serum zinc and alkaline phosphatase activity. Assessment of bone x-rays showed a significant progress in callus formation in cases compared to the controls. This study shows that zinc supplementation can stimulate fracture healing, however, it needs further study. (author)

Serum Inflammatory Mediators as Markers of Human Lyme Disease Activity

Science.gov (United States)

Soloski, Mark J.; Crowder, Lauren A.; Lahey, Lauren J.; Wagner, Catriona A.

2014-01-01

Chemokines and cytokines are key signaling molecules that orchestrate the trafficking of immune cells, direct them to sites of tissue injury and inflammation and modulate their states of activation and effector cell function. We have measured, using a multiplex-based approach, the levels of 58 immune mediators and 7 acute phase markers in sera derived from of a cohort of patients diagnosed with acute Lyme disease and matched controls. This analysis identified a cytokine signature associated with the early stages of infection and allowed us to identify two subsets (mediator-high and mediator-low) of acute Lyme patients with distinct cytokine signatures that also differed significantly (pLyme disease (p = 0.01) and the decrease correlates with chemokine levels (p = 0.0375). The levels of CXCL9/10 did not relate to the size or number of skin lesions but elevated levels of serum CXCL9/CXCL10 were associated with elevated liver enzymes levels. Collectively these results indicate that the levels of serum chemokines and the levels of expression of their respective chemokine receptors on T cell subsets may prove to be informative biomarkers for Lyme disease and related to specific disease manifestations. PMID:24740099

TIMP-1 resistant matrix metalloproteinase-9 is the predominant serum active isoform associated with MRI activity in patients with multiple sclerosis.

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Trentini, Alessandro; Manfrinato, Maria C; Castellazzi, Massimiliano; Tamborino, Carmine; Roversi, Gloria; Volta, Carlo A; Baldi, Eleonora; Tola, Maria R; Granieri, Enrico; Dallocchio, Franco; Bellini, Tiziana; Fainardi, Enrico

2015-08-01

The activity of matrix metalloproteinase-9 (MMP-9) depends on two isoforms, an 82 kDa active MMP-9 modulated by its specific tissue inhibitor (TIMP-1), and a 65 kDa TIMP-1 resistant active MMP-9. The relevance of these two enzymatic isoforms in multiple sclerosis (MS) is still unknown. To investigate the contribution of the TIMP-1 modulated and resistant active MMP-9 isoforms to MS pathogenesis. We measured the serum levels of the 82 kDa and TIMP-1 resistant active MMP-9 isoforms by activity assay systems in 86 relapsing-remitting MS (RRMS) patients, categorized according to clinical and magnetic resonance imaging (MRI) evidence of disease activity, and in 70 inflammatory (OIND) and 69 non-inflammatory (NIND) controls. Serum levels of TIMP-1 resistant MMP-9 were more elevated in MS patients than in OIND and NIND (p < 0.05, p < 0.02, respectively). Conversely, 82 kDa active MMP-9 was higher in NIND than in the OIND and MS patients (p < 0.01 and p < 0.00001, respectively). MRI-active patients had higher levels of TIMP-1 resistant MMP-9 and 82 kDa active MMP-9, than did those with MRI inactive MS (p < 0.01 and p < 0.05, respectively). Our findings suggested that the TIMP-1 resistant MMP-9 seem to be the predominantly active isoform contributing to MS disease activity. © The Author(s), 2015.

Evaluation of Serum Lactate Dehydrogenase Activity in a Virtual Environment

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V.M.T. Trindade

2013-05-01

Full Text Available Introduction: Lactate dehydrogenase is a citosolic enzyme involved in reversible transformation of pyruvate to lactate. It participates in anaerobic glycolysis of skeletal muscle and red blood cells, in liver gluconeogenesis and in aerobic metabolism of heart muscle. The determination of its activity helps in the diagnosis of various diseases, because it is increased in serum of patients suffering from myocardial infarction, acute hepatitis, muscular dystrophy and cancer. This paper presents a learning object, mediated by computer, which contains the simulation of the laboratory determination serum lactate dehydrogenase activity measured by the spectrophotometric method, based in the decrease of absorbance at 340 nm. Materials and Methods: Initially, pictures and videos were obtained recording the procedure of the methodology. The most representative images were selected, edited and inserted into an animation developed with the aid of the tool Adobe ® Flash ® CS3. The validation of the object was performed by the students of Biochemistry I (Pharmacy-UFRGS from the second semester of 2009 and both of 2010. Results and Discussion: The analysis of students' answers revealed that 80% attributed the excellence of the navigation program, the display format and to aid in learning. Conclusion: Therefore, this software can be considered an adequate teaching resource as well as an innovative support in the construction of theoretical and practical knowledge of Biochemistry. Available at: http://www6.ufrgs.br/gcoeb/LDH

The investigation of anti-inflammatory activity of Yi Guanjian decoction by serum metabonomics approach.

Science.gov (United States)

Shui, Sufang; Cai, Xiaorong; Huang, Rongqing; Xiao, Bingkun; Yang, Jianyun

2017-01-30

Yi Guanjian (YGJ), one of the Chinese herbal medicines most commonly used in western countries, reported to possess significant anti-inflammatary effects that inhibit the process of inflammation. However, the mechanisms underlying its anti-inflammation effects remain largely unresolved. This study was aimed to investigate the anti-inflammatory activity of YGJ and to explore its potential anti-inflammatory mechanisms by serum metabonomics approach. An xylene-induced mouse right-ear-edema model was used as an inflammatory response in vivo model. Ear edema, prostaglandin E2 (PGE 2 ) and Tumor-Necrosis-Factor-alpha (TNF-α) were detected. Then, serum metabolic profiling was analyzed and pathway analysis performed on the biomarkers reversed after YGJ administration and further integration of metabolic networks. The results showed that YGJ alleviated ear edema and decreased serum PGE 2 and TNF-α levels. Fourteen biomarkers were screened, and the levels were all reversed to different degrees after YGJ administration. These biomarkers were mainly related to linoleic acid metabolism, taurine and hypotaurine metabolism, glyoxylate and dicarboxylate metabolism, glycine, serine and threonine metabolism and citrate cycle (TCA cycle). In metabolic networks, glycine and pyruvate were node molecules. This indicated that YGJ could significantly inhibit inflammatory response triggered by acute local stimulation and exerted anti-inflammatory activity mainly by regulating node molecules. Copyright © 2016 Elsevier B.V. All rights reserved.

Omega-6 polyunsaturated fatty acids, serum zinc, delta-5- and delta-6-desaturase activities and incident metabolic syndrome.

Science.gov (United States)

Yary, T; Voutilainen, S; Tuomainen, T-P; Ruusunen, A; Nurmi, T; Virtanen, J K

2017-08-01

The associations of n-6 polyunsaturated fatty acids (PUFA) with metabolic syndrome have been poorly explored. We investigated the associations of the serum n-6 PUFA and the activities of enzymes involved in the PUFA metabolism, delta-5-desaturase (D5D) and delta-6-desaturase (D6D) with risk of incident metabolic syndrome. We also investigated whether zinc, a cofactor for these enzymes, modifies these associations. A prospective follow-up study was conducted on 661 men who were aged 42-60 years old at baseline in 1984-1989 and who were re-examined in 1998-2001. Men in the highest versus the lowest serum total omega-6 PUFA tertile had a 70% lower multivariate-adjusted risk of incident metabolic syndrome [odds ratio (OR) = 0.30; 95% confidence interval (CI) = 0.18-0.51, P trend metabolic syndrome components at the re-examinations. Most associations were attenuated after adjustment for body mass index. Finally, the associations of D6D and LA were stronger among those with a higher serum zinc concentration. Higher serum total n-6 PUFA, linoleic acid and arachidonic acid concentrations and D5D activity were associated with a lower risk of developing metabolic syndrome and higher D6D activity was associated with a higher risk. The role of zinc also needs to be investigated in other populations. © 2016 The British Dietetic Association Ltd.

Reduced Antiplatelet Effect of Aspirin Does Not Predict Cardiovascular Events in Patients With Stable Coronary Artery Disease.

Science.gov (United States)

Larsen, Sanne Bøjet; Grove, Erik Lerkevang; Neergaard-Petersen, Søs; Würtz, Morten; Hvas, Anne-Mette; Kristensen, Steen Dalby

2017-08-05

Increased platelet aggregation during antiplatelet therapy may predict cardiovascular events in patients with coronary artery disease. The majority of these patients receive aspirin monotherapy. We aimed to investigate whether high platelet-aggregation levels predict cardiovascular events in stable coronary artery disease patients treated with aspirin. We included 900 stable coronary artery disease patients with either previous myocardial infarction, type 2 diabetes mellitus, or both. All patients received single antithrombotic therapy with 75 mg aspirin daily. Platelet aggregation was evaluated 1 hour after aspirin intake using the VerifyNow Aspirin Assay (Accriva Diagnostics) and Multiplate Analyzer (Roche; agonists: arachidonic acid and collagen). Adherence to aspirin was confirmed by serum thromboxane B 2 . The primary end point was the composite of nonfatal myocardial infarction, ischemic stroke, and cardiovascular death. At 3-year follow-up, 78 primary end points were registered. The primary end point did not occur more frequently in patients with high platelet-aggregation levels (first versus fourth quartile) assessed by VerifyNow (hazard ratio: 0.5 [95% CI, 0.3-1.1], P =0.08) or Multiplate using arachidonic acid (hazard ratio: 1.0 [95% CI, 0.5-2.1], P =0.92) or collagen (hazard ratio: 1.4 [95% CI, 0.7-2.8], P =0.38). Similar results were found for the composite secondary end point (nonfatal myocardial infarction, ischemic stroke, stent thrombosis, and all-cause death) and the single end points. Thromboxane B 2 levels did not predict any end points. Renal insufficiency was the only clinical risk factor predicting the primary and secondary end points. This study is the largest to investigate platelet aggregation in stable coronary artery disease patients receiving aspirin as single antithrombotic therapy. We found that high platelet-aggregation levels did not predict cardiovascular events. © 2017 The Authors. Published on behalf of the American Heart

Multiplex profiling of tumor-associated proteolytic activity in serum of colorectal cancer patients.

Science.gov (United States)

Yepes, Diego; Costina, Victor; Pilz, Lothar R; Hofheinz, Ralf; Neumaier, Michael; Findeisen, Peter

2014-06-01

The monitoring of tumor-associated protease activity in blood specimens has recently been proposed as new diagnostic tool in cancer research. In this paper, we describe the screening of a peptide library for identification of reporter peptides (RPs) that are selectively cleaved in serum specimens from colorectal cancer patients and investigate the benefits of RP multiplexing. A library of 144 RPs was constructed that contained amino acid sequences of abundant plasma proteins. Proteolytic cleavage of RPs was monitored with MS. Five RPs that were selectively cleaved in serum specimens from tumor patients were selected for further validation in serum specimens of colorectal tumor patients (n = 30) and nonmalignant controls (n = 60). RP spiking and subsequent quantification of proteolytic fragments with LC-MS showed good reproducibility with CVs always below 26%. The linear discriminant analysis and PCA revealed that a combination of RPs for diagnostic classification is superior to single markers. Classification accuracy reached 88% (79/90) when all five markers were combined. Functional protease profiling with RPs might improve the laboratory-based diagnosis, monitoring and prognosis of malignant disease, and has to be evaluated thoroughly in future studies. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

STUDY OF SERUM HAPTOGLOBIN LEVEL AND ITS RELATION TO ERYTHROPOIETIC ACTIVITY IN BETA THALASSEMIA CHILDREN .

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Seham Ragab

2015-02-01

Full Text Available Background  :Serum haptoglobin (Hp is a reliable marker for hemolysis regardless the inflammatory state.  Objective: We investigated the possible relation between Hp depletion and hemolysis severity, hepatitis C virus (HCV infection and iron load in β-thalassemia children. Methods: Twenty  two β-thalassemia major (TM ,20 β-thalassemia  intermedia (TI children with 20 age and sex matched healthy controls were involved. Pre-transfusion hemoglobin level was considered . Serum ferritin , Hp  and transferrin receptor  levels (sTfR  (by ELISA , alanine aminotransferase (ALT and  aspartate aminotransferase (AST  (by colorimetric method were assayed. Markers of hepatitis C virus  (HCV  were done by PCR. Results:  The mean Hp levels among the studied groups were as follows; 8.02 ± 0.93 (mg/dl , 8.6 ±0.72 (mg/dl  and 122  ± 18.5(mg/dl   for TM ,TI and the controls respectively . Both patient groups had significantly lower Hp level compared to the controls (P<0.0001  with significant lower level in TM compared to TI  children ( P= 0.034  .Significant inverse correlations were  found between serum Hp and sTfR levels in thalassemia children combined and in each group (TM and TI as well as among HCV infected children. STfR   was the only significant independent predictor for  serum Hp level (t= -5.585 , P<0.0001 . Among  HCV infected patients , no significant correlation was found between serum Hp and serum transaminases  .Conclusion:  Serum Hp depletion in thalassemia had significant relation to disease severity and correlated   well with their erythropoietic activity, as assessed by the measurement of  sTfR without significant relation  HCV infection . Large sample  multicenter studies are  recommended.

Elevated serum cytokines correlated with altered behavior, serum cortisol rhythm, and dampened 24-hour rest-activity patterns in patients with metastatic colorectal cancer.

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Rich, Tyvin; Innominato, Pasquale F; Boerner, Julie; Mormont, M Christine; Iacobelli, Stefano; Baron, Benoit; Jasmin, Claude; Lévi, Francis

2005-03-01

Incapacitating symptom burden in cancer patients contributes to poor quality of life (QOL) and can influence treatment outcomes because of poor tolerance to therapy. In this study, the role of circulating cytokines in the production symptoms in cancer patients is evaluated. Eighty patients with metastatic colorectal cancer with either normal (group I, n = 40) or dampened (group II, n = 40) 24-hour rest/activity patterns measured by actigraphy were identified. Actigraphy patterns were correlated with QOL indices, serum cortisol obtained at 8:00 a.m. and 4:00 p.m. and with serum levels of transforming growth factor-alpha, tumor necrosis factor-alpha, and interleukin 6 (IL-6) obtained at 8:00 a.m. and analyzed in duplicate by ELISA. Cytokine levels and survival were also correlated. Group II patients had significantly higher pre treatment levels of all three cytokines, displayed significantly poorer emotional and social functioning, had higher fatigue, more appetite loss, and poorer performance status compared with group I patients. Transforming growth factor-alpha (TGF-alpha) and IL-6 were significantly increased in the patients with WHO performance status >1 and in those with appetite loss. Fatigue was significantly associated with elevated TGF-alpha only. IL-6 was increased in those patients with extensive liver involvement and multiple organ replacement, and it was significantly correlated with dampened cortisol rhythm. In a multivariate analysis, IL-6 was correlated with poor treatment outcome. Significant correlations were found between serum levels of TGF-alpha and IL-6, circadian patterns in wrist activity and serum cortisol and tumor-related symptoms in patients with metastatic colorectal cancer. These data support the hypothesis that some cancer patient's symptoms of fatigue, poor QOL, and treatment outcome are related to tumor or host generated cytokines and could reflect cytokine effects on the circadian timing system. This interplay between cytokine

Elevated Concentrations of Serum Immunoglobulin Free Light Chains in Systemic Lupus Erythematosus Patients in Relation to Disease Activity, Inflammatory Status, B Cell Activity and Epstein-Barr Virus Antibodies

DEFF Research Database (Denmark)

Draborg, Anette H; Lydolph, Magnus; Westergaard, Marie

2015-01-01

, FLCs' association with Epstein-Barr virus (EBV) antibodies was examined. METHODS: Using a nephelometric assay, κFLC and λFLC concentrations were quantified in sera from 45 SLE patients and 40 healthy controls. SLE patients with renal insufficiency were excluded in order to preclude high concentrations......OBJECTIVE: In this study, we examined the concentration of serum immunoglobulin free light chains (FLCs) in systemic lupus erythematosus (SLE) patients and investigated its association with various disease parameters in order to evaluate the role of FLCs as a potential biomarker in SLE. Furthermore...... of serum FLCs due to decreased clearance. RESULTS: Serum FLC concentrations were significantly elevated in SLE patients compared to healthy controls (pdisease activity (SLE disease activity...

Role of sodium tungstate as a potential antiplatelet agent

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Fernández-Ruiz R

2015-05-01

Full Text Available Rebeca Fernández-Ruiz,1,2 Marc Pino,3 Begoña Hurtado,4 Pablo García de Frutos,4 Carolina Caballo,3 Ginés Escolar,3 Ramón Gomis,1,2,5 Maribel Diaz-Ricart3 1Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS, Rosellón, Barcelona, 2Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Barcelona, 3Hemotherapy–Hemostasis, Hospital Clínic, Universidad de Barcelona, IDIBAPS, Villarroel, Barcelona, 4Institutode Investigaciones Biomédicas de Barcelona, Consejo Superior de Investigaciones Científicas, Institut d’Investigacions Biomediques August Pi i Sunyer, Rosellón, Barcelona, 5Hospital Clinic, Universitat de Barcelona, Villarroel, Barcelona, Spain Purpose: Platelet inhibition is a key strategy in the management of atherothrombosis. However, the large variability in response to current strategies leads to the search for alternative inhibitors. The antiplatelet effect of the inorganic salt sodium tungstate (Na2O4W, a protein tyrosine phosphatase 1B (PTP1B inhibitor, has been investigated in this study.Methods: Wild-type (WT and PTP1B knockout (PTP1B-/- mice were treated for 1 week with Na2O4W to study platelet function with the platelet function analyzer PFA-100, a cone-and-plate analyzer, a flat perfusion chamber, and thrombus formation in vivo. Human blood aliquots were incubated with Na2O4W for 1 hour to measure platelet function using the PFA-100 and the annular perfusion chamber. Aggregometry and thromboelastometry were also performed.Results: In WT mice, Na2O4W treatment prolonged closure times in the PFA-100 and decreased the surface covered (%SC by platelets on collagen. Thrombi formed in a thrombosis mice model were smaller in animals treated with Na2O4W (4.6±0.7 mg vs 8.9±0.7 mg; P<0.001. Results with Na2O4W were similar to those in untreated PTP1B-/- mice (5.0±0.3 mg. Treatment of the PTP1B-/- mice with Na2O4W modified only

Serum inflammatory mediators as markers of human Lyme disease activity.

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Mark J Soloski

Full Text Available Chemokines and cytokines are key signaling molecules that orchestrate the trafficking of immune cells, direct them to sites of tissue injury and inflammation and modulate their states of activation and effector cell function. We have measured, using a multiplex-based approach, the levels of 58 immune mediators and 7 acute phase markers in sera derived from of a cohort of patients diagnosed with acute Lyme disease and matched controls. This analysis identified a cytokine signature associated with the early stages of infection and allowed us to identify two subsets (mediator-high and mediator-low of acute Lyme patients with distinct cytokine signatures that also differed significantly (p<0.0005 in symptom presentation. In particular, the T cell chemokines CXCL9 (MIG, CXCL10 (IP-10 and CCL19 (MIP3B were coordinately increased in the mediator-high group and levels of these chemokines could be associated with seroconversion status and elevated liver function tests (p = 0.027 and p = 0.021 respectively. There was also upregulation of acute phase proteins including CRP and serum amyloid A. Consistent with the role of CXCL9/CXCL10 in attracting immune cells to the site of infection, CXCR3+ CD4 T cells are reduced in the blood of early acute Lyme disease (p = 0.01 and the decrease correlates with chemokine levels (p = 0.0375. The levels of CXCL9/10 did not relate to the size or number of skin lesions but elevated levels of serum CXCL9/CXCL10 were associated with elevated liver enzymes levels. Collectively these results indicate that the levels of serum chemokines and the levels of expression of their respective chemokine receptors on T cell subsets may prove to be informative biomarkers for Lyme disease and related to specific disease manifestations.

Serum Bilirubin Concentrations in Patients With Takayasu Arteritis.

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Peng, You-Fan; Deng, Yi-Bin

2017-06-01

- Bilirubin has strong anti-inflammatory and antioxidative stress action. Progression of inflammation involving arteries is a crucial activator in pathogenesis of Takayasu arteritis (TA). - To investigate the relationship between serum bilirubin and TA. - Our study involved 115 consecutive TA patients. Patients with active-phase disease were followed and received prednisone therapy. - Lower concentrations of serum bilirubin were detected in TA patients compared with healthy subjects (0.6 ± 0.31 versus 0.7 ± 0.22 mg/dL, P = .02). Serum bilirubin concentrations in active TA patients were lower than those in inactive patients (0.5 ± 0.20 versus 0.8 ± 0.32 mg/dL, P bilirubin correlated positively with total protein (r = 0.193, P = .04) and negatively with C-reactive protein and erythrocyte sedimentation rate (r = -0.213, P = .03, and r = -0.532, P bilirubin was associated with a 1.10 times increase in the odds for TA compared with the controls (odds ratio = 0.913, 95% CI, 0.856-0.974; P = .006). Serum bilirubin was correlated with erythrocyte sedimentation rate (β = -0.170, P bilirubin in predicting active TA patients was 0.802. Serum bilirubin levels were found to be significantly increased after prednisone treatment (0.5 ± 0.20 versus 0.7 ± 0.15 mg/dL, P = .002). - Lower serum bilirubin levels are associated with TA, and serum bilirubin may be influenced by prednisone therapy in active TA patients. Serum bilirubin levels in TA patients correlate negatively with erythrocyte sedimentation rate.

Comparison of Deferoxamine, Activated Charcoal, and Vitamin C in Changing the Serum Level of Fe in Iron Overloaded Rats

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Reza Ghafari

2014-02-01

Full Text Available Background: Iron is an essential mineral for normal cellular physiology but its overload can lead to cell injury. For many years, deferoxamine injection has been used as an iron chelator for treatment of iron overload. The aim of this study is to compare oral deferoxamine, activated charcoal, and vitamin C, as an absorbent factor of Fe, in changing the serum level of iron in iron overload rats. Methods: In this experimental study, all groups were administered 150 mg iron dextran orally by gavage. After eight hours, rats in the first group received oral deferoxamine while those in the second and third groups received oral activated charcoal 1 mg/kg and oral vitamin C 150 mg, respectively. Then, serum levels of iron ware measured in all rats. Results: The mean serum level of iron in rats that received oral deferoxamine was 258.11±10.49 µg/dl, whereas mean levels of iron in charcoal and vitamin C groups were 380.88±11.21 µg/dl and 401.22±13.28 µg/dl, respectively. None of the measurements were within safety limits of serum iron. Conclusion: It seems that oral deferoxamine per se may not help physicians in the management of cases presented with iron toxicity. Activated charcoal did not reduce serum iron significantly in this study and further investigations may be warranted to assess the potential clinical utility of its mixture with oral deferoxamine as an adjunct in the clinical management of iron ingestions.

Tailored antiplatelet therapy to improve prognosis in patients exhibiting clopidogrel low-response prior to percutaneous coronary intervention for stable angina or non-ST elevation acute coronary syndrome

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Paarup Dridi, Nadia; Johansson, Pär I; Lønborg, Jacob T

2015-01-01

Abstract Aim: To investigate whether an intensified antiplatelet regimen could improve prognosis in stable or non-ST elevation in acute coronary syndrome (ACS) patients exhibiting high on-treatment platelet reactivity (HTPR) on clopidogrel and treated with percutaneous coronary intervention (PCI...

Testosterone like Activity of Ethanolic and Aqueous Extracts of Mucuna pruriens Seeds and its Effects on Serum Biochemical Metabolites in Immature Male Rats

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Nazir Ahmad*, Zia-ur-Rahman1, Nafees Akhtar and Shujait Ali

2012-01-01

Full Text Available Testosterone like activity of seeds of Mucuna pruriens and its effects on serum biochemical metabolites in immature male rats were investigated. Forty eight immature male rats were divided into four equal groups. Rats of groups A and B were orally given ethanolic and aqueous extracts of Mucuna pruriens seeds daily at the dose rate of 500 mg/kg body weight, respectively, for 14 days. Rats of group C were injected with testosterone at the dose rate of 2.5 mg/kg body weight daily, while rats of group D served as controls. After 7 days, six rats from each group were euthanized, while the remaining six rats from each group were euthanized after 14 days of treatment. Rats given ethanolic extract gained higher weight compared to controls (P<0.05. Testis weight was the highest in rats treated with testosterone. The effect of treatments on the weight of the liver and the kidneys was non significant. Rats given ethanolic or aqueous extract had higher serum testosterone concentration than controls. Similarly, rats given ethanolic or aqueous extract had higher serum total proteins, total cholesterol and HDL cholesterol compared to controls. Moreover, ethanolic extract treated rats also had higher total cholesterol and HDL cholesterol than aqueous extract treated rats. However, differences in serum total proteins, total cholesterol and HDL cholesterol between control and testosterone injected rats were non significant. Serum triglycerides, LDL cholesterol and ALT activity did not differ among rats of four groups. Serum AST activity and urea were lower in rats treated with ethanolic or aqueous extract compared to controls. Thus, seeds of Mucuna pruriens had testosterone like activity and increased serum total proteins, total cholesterol and HDL cholesterol, with no adverse effects on the serum LDL cholesterol, liver or kidney functions.

Serum analysis of coronary heart disease patients by instrumental neutron activation analysis

International Nuclear Information System (INIS)

Jong-Hwa Moon; Yong-Sam Chung; Kwang-Won Park; Okhee Lee

2007-01-01

Due to changes of the dietary pattern and life style, cardiovascular diseases like coronary heart disease (CHD) have been increasing in Korea. In this study, the levels of the serum minerals such as Na, Cl, K, Ca, Fe, Zn and Se for 75 patients with CHD and 25 normal persons, who were older than the age of 40, were investigated by instrumental neutron activation analysis. For analytical quality control, the reference materials, INSPQ and Seronorm, were analyzed simultaneously. The relative errors of the analytical values for the reference materials were within 10% of the certified values. The average concentrations of Na, Cl, K, Ca, Fe, Zn and Se in the serum of the male patients were 2,850±260 mg/l, 3,400±310 mg/l, 160±30 mg/l, 80.9±11.7 mg/l, 1.57±0.73 mg/l, 0.094±0.019 mg/l and 0.795±0.163 mg/l, respectively. The concentrations of Na, Cl, K, Ca, Fe, Zn and Se in the serum of the female patients were 2,890±240 mg/l, 3,430±350 mg/l, 169±27 mg/l, 81.8±13.0 mg/l, 1.26±0.44 mg/l, 0.099±0.015 mg/l and 0.769±0.105 mg/l, respectively. In a comparison between the patients and the normal group for both genders, while the levels of the elemental concentrations such as Na, Cl, K, Ca, Fe and Se were similar, the Zn concentration level of the CHD patients was significantly lower than that of the normal ones. The present study showed that the Zn concentration in the serum could be associated with CHD in Korean adults. (author)

A review exploring biological activities of hydrazones

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Garima Verma

2014-01-01

Full Text Available The development of novel compounds, hydrazones has shown that they possess a wide variety of biological activities viz. antimicrobial, anticonvulsant, antidepressant, anti-inflammatory, analgesic, antiplatelet, antimalarial, anticancer, antifungal, antitubercular, antiviral, cardio protective etc., Hydrazones/azomethines/imines possess-NHN = CH- and constitute an important class of compounds for new drug development. A number of researchers have synthesized and evaluated the biological activities of hydrazones. This review aims at highlighting the diverse biological activities of hydrazones.

Statin Treatment Is Associated with Reduction in Serum Levels of Receptor Activator of NF-κB Ligand and Neutrophil Activation in Patients with Severe Carotid Stenosis

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Sébastien Lenglet

2014-01-01

Full Text Available Systemic and intraplaque biomarkers have been widely investigated in clinical cohorts as promising surrogate parameters of cardiovascular vulnerability. In this pilot study, we investigated if systemic and intraplaque levels of calcification biomarkers were affected by treatment with a statin in a cohort of patients with severe carotid stenosis and being asymptomatic for ischemic stroke. Patients on statin therapy had reduced serum osteopontin (OPN, RANKL/osteoprotegerin (OPG ratio, and MMP-9/pro-MMP-9 activity as compared to untreated patients. Statin-treated patients exhibited increased levels of collagen and reduced neutrophil infiltration in downstream portions of carotid plaques as compared to untreated controls. In upstream plaque portions, OPG content was increased in statin-treated patients as compared to controls. Other histological parameters (such as lipid, macrophage, smooth muscle cell, and MMP-9 content as well as RANKL, RANK, and OPG mRNA levels did not differ between the two patient groups. Serum RANKL/OPG ratio positively correlated with serum levels of neutrophilic products, intraplaque neutrophil, and MMP-9 content within downstream portions of carotid plaques. In conclusion, statin treatment was associated with improvement in serum RANKL levels and reduced neutrophil activity both systemically and in atherosclerotic plaques.

Effects of rosiglitazone on serum paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus

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Atamer, Y. [Department of Medical Biochemistry, Faculty of Medicine, Dicle University, Diyarbakır (Turkey); Atamer, A. [Ministry of Health Haydarpaşa Numune Training and Research Hospital, Division of Gastroenterology, Department of Internal Medicine, Istanbul, Turkey, Division of Gastroenterology, Department of Internal Medicine, Ministry of Health Haydarpaşa Numune Training and Research Hospital, Istanbul (Turkey); Can, A.S. [Termal Professional School, Yalova University, Yalova (Turkey); Hekimoğlu, A. [Dicle University, Department of Pharmacology, Faculty of Medicine, Diyarbakir, Turkey, Department of Pharmacology, Faculty of Medicine, Dicle University, Diyarbakır (Turkey); Ilhan, N. [Firat University, Department of Medical Biochemistry, Faculty of Medicine, Elaziğ, Turkey, Department of Medical Biochemistry, Faculty of Medicine, Fırat University, Elazığ (Turkey); Yenice, N. [Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Harran University, Urfa (Turkey); Koçyiğit, Y. [Dicle University, Department of Physiology, Faculty of Medicine, Diyarbakir, Turkey, Department of Physiology, Faculty of Medicine, Dicle University, Diyarbakır (Turkey)

2013-06-25

Human serum paraoxonase contributes to the anti-atherogenic effect of high-density lipoprotein cholesterol (HDL-C) and has been shown to protect both low-density lipoprotein cholesterol (LDL-C) and HDL-C against lipid peroxidation. We investigated the effects of rosiglitazone on paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus [50 patients (30 males, 20 females); mean±SD age: 58.7±9.2 years, body mass index: 28.2±4.1'kg/m{sup 2}], in whom glucose control could not be achieved despite treatment with metformin, sulphonylurea, and/or insulin. The patients were given 4'mg/day rosiglitazone for 3 months in addition to their usual treatment. Serum paraoxonase activity, malondialdehyde, homocysteine, and lipid profile were measured at the time of initiation and at the end of therapy with rosiglitazone. After rosiglitazone therapy, serum levels of HDL-C, apolipoprotein A-1, and paraoxonase activity increased significantly (P<0.05) and malondialdehyde, homocysteine, lipoprotein(a), and glucose levels decreased significantly (P<0.05), but no significant changes in levels of total cholesterol and apolipoprotein B were observed. Triglyceride levels also increased significantly (P<0.05). Rosiglitazone treatment led to an improvement in glycemic control and to an increase in paraoxonase activity and HDL-C levels. Although rosiglitazone showed favorable effects on oxidant/antioxidant balance and lipid profile, further studies are needed to determine the effect of rosiglitazone on cardiovascular risk factors and cardiovascular morbidity and mortality.

Effects of rosiglitazone on serum paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus

International Nuclear Information System (INIS)

Atamer, Y.; Atamer, A.; Can, A.S.; Hekimoğlu, A.; Ilhan, N.; Yenice, N.; Koçyiğit, Y.

2013-01-01

Human serum paraoxonase contributes to the anti-atherogenic effect of high-density lipoprotein cholesterol (HDL-C) and has been shown to protect both low-density lipoprotein cholesterol (LDL-C) and HDL-C against lipid peroxidation. We investigated the effects of rosiglitazone on paraoxonase activity and metabolic parameters in patients with type 2 diabetes mellitus [50 patients (30 males, 20 females); mean±SD age: 58.7±9.2 years, body mass index: 28.2±4.1'kg/m 2 ], in whom glucose control could not be achieved despite treatment with metformin, sulphonylurea, and/or insulin. The patients were given 4'mg/day rosiglitazone for 3 months in addition to their usual treatment. Serum paraoxonase activity, malondialdehyde, homocysteine, and lipid profile were measured at the time of initiation and at the end of therapy with rosiglitazone. After rosiglitazone therapy, serum levels of HDL-C, apolipoprotein A-1, and paraoxonase activity increased significantly (P<0.05) and malondialdehyde, homocysteine, lipoprotein(a), and glucose levels decreased significantly (P<0.05), but no significant changes in levels of total cholesterol and apolipoprotein B were observed. Triglyceride levels also increased significantly (P<0.05). Rosiglitazone treatment led to an improvement in glycemic control and to an increase in paraoxonase activity and HDL-C levels. Although rosiglitazone showed favorable effects on oxidant/antioxidant balance and lipid profile, further studies are needed to determine the effect of rosiglitazone on cardiovascular risk factors and cardiovascular morbidity and mortality

Quantitative estimation of infarct size by simultaneous dual radionuclide single photon emission computed tomography: comparison with peak serum creatine kinase activity

International Nuclear Information System (INIS)

Kawaguchi, K.; Sone, T.; Tsuboi, H.; Sassa, H.; Okumura, K.; Hashimoto, H.; Ito, T.; Satake, T.

1991-01-01

To test the hypothesis that simultaneous dual energy single photon emission computed tomography (SPECT) with technetium-99m (99mTc) pyrophosphate and thallium-201 (201TI) can provide an accurate estimate of the size of myocardial infarction and to assess the correlation between infarct size and peak serum creatine kinase activity, 165 patients with acute myocardial infarction underwent SPECT 3.2 +/- 1.3 (SD) days after the onset of acute myocardial infarction. In the present study, the difference in the intensity of 99mTc-pyrophosphate accumulation was assumed to be attributable to difference in the volume of infarcted myocardium, and the infarct volume was corrected by the ratio of the myocardial activity to the osseous activity to quantify the intensity of 99mTc-pyrophosphate accumulation. The correlation of measured infarct volume with peak serum creatine kinase activity was significant (r = 0.60, p less than 0.01). There was also a significant linear correlation between the corrected infarct volume and peak serum creatine kinase activity (r = 0.71, p less than 0.01). Subgroup analysis showed a high correlation between corrected volume and peak creatine kinase activity in patients with anterior infarctions (r = 0.75, p less than 0.01) but a poor correlation in patients with inferior or posterior infarctions (r = 0.50, p less than 0.01). In both the early reperfusion and the no reperfusion groups, a good correlation was found between corrected infarct volume and peak serum creatine kinase activity (r = 0.76 and r = 0.76, respectively; p less than 0.01)

Short vs prolonged dual antiplatelet treatment upon endovascular stenting of peripheral arteries

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Kronlage M

2017-10-01

Full Text Available Mariya Kronlage,1 Maximilian Wassmann,1 Britta Vogel,1 Oliver J Müller,1 Erwin Blessing,2 Hugo Katus,1,3 Christian Erbel1 1Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, Heidelberg, 2SRH Klinikum Karlsbad Langensteinbach, Karlsbad, 3DZHK German Center for Cardiovascular Research, Partner Site Heidelberg/Mannheim, Mannheim, Germany Introduction: Peripheral artery disease (PAD is a highly prevalent disorder with a substantial economical burden. Dual antiplatelet treatment (DAPT upon endovascular stenting to prevent acute thrombotic reocclusions is an universally accepted practice for postinterventional management of PAD patients. However, the optimal period of time for DAPT upon endovascular stenting is not known.Methods: In the current nonrandomized, retrospective monocentric study, we evaluated the duration of DAPT upon endovascular stenting. A total of 261 endovascular SFA and iliac stenting procedures were performed on 214 patients and these patients were subdivided into a short (4–6 weeks or a prolonged (8–12 weeks DAPT regime group. More than 65% of the patients included were male, approximately 35% were diabetic, and 61% had a history of smoking. Of all the patients, 90% exhibited a Rutherford stage 2–3, and approximately half of the patients had a moderate-to-severe calcified target lesion with a length of >13 cm. Major safety end points were defined as any bleeding, compartment syndrome, and ischemic events. In addition to this, patency, all-cause mortality, as well as amputation were followed up over a period of 12 months upon intervention.Results: Twelve months after endovascular stenting, primary patency in our cohort was comparable between the groups (83.94% short vs 79.8% long DAPT, P>0.05. Major bleeding occurred in 18 cases without any difference between the groups (P>0.05. In addition, during the 12-month follow-up, 6 (3.4% patients in the short and 3 (3.5% in the prolonged DAPT regime

Mortality in primary angioplasty patients starting antiplatelet therapy with prehospital prasugrel or clopidogrel

DEFF Research Database (Denmark)

Goldstein, Patrick; Grieco, Niccolò; Ince, Hüseyin

2016-01-01

hospitalization, we report here the 1-year follow-up data, including cardiovascular (CV) mortality. METHODS AND RESULTS: MULTIPRAC is a multinational, prospective registry of patients with ST-elevation myocardial infarction (STEMI) from 25 hospitals in nine countries, all of which had an established practice...... of prehospital start of dual antiplatelet therapy in place. The key outcome was CV death at 1 year. Among 2,036 patients followed-up through 1 year, 49 died (2.4%), 10 during the initial hospitalization and 39 within 1 year after hospital discharge. The primary analysis was based on the P2Y12-inhibitor, used...... from prehospital loading dose through hospital discharge. Prasugrel (n=824) was more commonly used than clopidogrel (n=425). The observed 1-year rates for CV death were 0.5% with prasugrel and 2.6% with clopidogrel. After adjustment for differences in baseline characteristics, treatment with prasugrel...

Increased Kappa/Lambda Hybrid Antibody in Serum Is a Novel Biomarker Related to Disease Activity and Inflammation in Rheumatoid Arthritis.

Science.gov (United States)

Yi, Lang; Hao, Mingju; Lu, Tian; Lin, Guigao; Chen, Lida; Gao, Ming; Fan, Gaowei; Zhang, Dong; Wang, Guojing; Yang, Xin; Li, Yulong; Zhang, Kuo; Zhang, Rui; Han, Yanxi; Wang, Lunan; Li, Jinming

2016-01-01

The κ/λ hybrid antibodies in normal human serum were reported recently, but their clinical relevance has not yet been explored. Rheumatoid arthritis (RA) is one of the major joint diseases, and the early diagnosis and treatment of RA remain a challenge. Here, we developed a double-sandwich enzyme-linked immunosorbent assay system to quantify relative serum κ/λ hybrid antibody levels in RA patients, osteoarthritis (OA) patients, and healthy controls (HC) in order to assess their potential use as a serological biomarker of early disease and clinical activity and to preliminarily investigate their immunomodulatory roles in RA. Surprisingly, we found that κ/λ hybrid antibody was markedly increased in both early and established RA. Serum κ/λ hybrid antibody levels were significantly correlated with clinical indexes and inflammatory markers in RA. Further analysis showed a positive correlation between κ/λ hybrid antibody levels and the 28-joint disease activity score (DAS28). In conclusion, serum κ/λ hybrid antibodies in RA were identified for the first time. High levels of κ/λ hybrid antibody may be a useful tool in distinguishing early RA from OA and HC. We suggest κ/λ hybrid antibody as a marker for disease activity. The increased κ/λ hybrid antibodies were associated with inflammatory conditions in RA.

Multiple free-radical scavenging (MULTIS) capacity in cattle serum.

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Sueishi, Yoshimi; Kamogawa, Erisa; Kimura, Anna; Kitahara, Go; Satoh, Hiroyuki; Asanuma, Taketoshi; Oowada, Shigeru

2017-01-01

Multiple free-radical scavenging (MULTIS) activity in cattle and human sera was evaluated with electron spin resonance spectroscopy. Scavenging rates against six active species, namely hydroxyl radical, superoxide anion, alkoxyl radical, alkylperoxyl radical, methyl radical, and singlet oxygen were quantified. The difference in the electron spin resonance signal intensity in the presence and absence of the serum was converted into the scavenging rates. Comparative MULTIS measurements were made in sera from eight beef cattle, three fetal calves and fifteen healthy human volunteers. Further, we determined the MULTIS value of albumin, the most abundant component in serum. MULTIS values in cattle sera indicated higher scavenging activity against most free radical species tested than human sera. In particular, cattle serum scavenging activities against superoxide and methyl radical were higher than human serum by 2.6 and 3.7 fold, respectively. In cattle serum, albumin appears to play a dominant role in MULTIS activity, but in human serum that is not the case. Previous data indicated that the abundance of uric acid in bovine blood is nearly 80% less than humans; however, this difference does not explain the deviation in MULTIS profile.

Patent foramen ovale closure with GORE HELEX or CARDIOFORM Septal Occluder vs. antiplatelet therapy for reduction of recurrent stroke or new brain infarct in patients with prior cryptogenic stroke: Design of the randomized Gore REDUCE Clinical Study.

Science.gov (United States)

Kasner, Scott E; Thomassen, Lars; Søndergaard, Lars; Rhodes, John F; Larsen, Coby C; Jacobson, Joth

2017-12-01

Rationale The utility of patent foramen ovale (PFO) closure for secondary prevention in patients with prior cryptogenic stroke is uncertain despite multiple randomized trials completed to date. Aims The Gore REDUCE Clinical Study (REDUCE) aims to establish superiority of patent foramen ovale closure in conjunction with antiplatelet therapy over antiplatelet therapy alone in reducing the risk of recurrent clinical ischemic stroke or new silent brain infarct in patients who have had a cryptogenic stroke. Methods and design This controlled, open-label trial randomized 664 subjects with cryptogenic stroke at 63 multinational sites in a 2:1 ratio to either antiplatelet therapy plus patent foramen ovale closure (with GORE® HELEX® Septal Occluder or GORE® CARDIOFORM Septal Occluder) or antiplatelet therapy alone. Subjects will be prospectively followed for up to five years. Neuroimaging is required for all subjects at baseline and at two years or study exit. Study outcomes The two co-primary endpoints for the study are freedom from recurrent clinical ischemic stroke through at least 24 months post-randomization and incidence of new brain infarct (defined as clinical ischemic stroke or silent brain infarct) through 24 months. The primary analyses are an unadjusted log-rank test and a binomial test of subject-based proportions, respectively, both on the intent-to-treat population, with adjustment for testing multiplicity. Discussion The REDUCE trial aims to target a patient population with truly cryptogenic strokes. Medical therapy is limited to antiplatelet agents in both arms thereby reducing confounding. The trial should determine whether patent foramen ovale closure with the Gore septal occluders is safe and more effective than medical therapy alone for the prevention of recurrent clinical ischemic stroke or new silent brain infarct; the neuroimaging data will provide an opportunity to further support the proof of concept. The main results are anticipated in 2017

Evaluating Soluble EMMPRIN as a Marker of Disease Activity in Multiple Sclerosis: Studies of Serum and Cerebrospinal Fluid.

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Deepak K Kaushik

Full Text Available Extracellular matrix metalloproteinase inducer (EMMPRIN, CD147 is an inducer of matrix metalloproteinases and has roles in leukocyte activation and migration. We reported previously that in MS and its animal model, experimental autoimmune encephalomyelitis, cell surface-associated EMMPRIN was significantly elevated in leukocytes around inflammatory perivascular cuffs in the CNS. In this study we report that activated T-cells can secrete soluble form of EMMPRIN (sEMMPRIN upon activation. As sEMMPRIN is also present in biological fluids, we determined whether sEMMPRIN is altered in the CSF and sera of MS subjects. Sera from individuals without neurological conditions served as controls, while CSFs collected from subjects undergoing discectomy, and without evidence of CNS pathology, were used as a comparator group. We found that serum levels of sEMMPRIN from clinically stable MS patients or other inflammatory conditions did not differ from control subjects. Paired serum and CSF samples demonstrated poor correlation of sEMMPRIN. Interestingly, sEMMPRIN levels were approximately 60% higher in CSFs compared to sera. sEMMPRIN CSF levels were significantly higher in secondary progressive compared to primary progressive subjects. Thus we conclude that measurement of sEMMPRIN in serum is not informative for disease activity in MS. The differential expression of sEMMPRIN in the CSF of primary and secondary progressive MS invites hypotheses of the still undefined roles of EMMPRIN in the CNS.

Evaluating Soluble EMMPRIN as a Marker of Disease Activity in Multiple Sclerosis: Studies of Serum and Cerebrospinal Fluid.

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Kaushik, Deepak K; Yong, Heather Y F; Hahn, Jennifer N; Silva, Claudia; Casha, Steven; Hurlbert, R John; Jacques, Francois H; Lisak, Robert; Khan, Omar; Ionete, Carolina; Larochelle, Catherine; Prat, Alex; Bar-Or, Amit; Yong, V Wee

2016-01-01

Extracellular matrix metalloproteinase inducer (EMMPRIN, CD147) is an inducer of matrix metalloproteinases and has roles in leukocyte activation and migration. We reported previously that in MS and its animal model, experimental autoimmune encephalomyelitis, cell surface-associated EMMPRIN was significantly elevated in leukocytes around inflammatory perivascular cuffs in the CNS. In this study we report that activated T-cells can secrete soluble form of EMMPRIN (sEMMPRIN) upon activation. As sEMMPRIN is also present in biological fluids, we determined whether sEMMPRIN is altered in the CSF and sera of MS subjects. Sera from individuals without neurological conditions served as controls, while CSFs collected from subjects undergoing discectomy, and without evidence of CNS pathology, were used as a comparator group. We found that serum levels of sEMMPRIN from clinically stable MS patients or other inflammatory conditions did not differ from control subjects. Paired serum and CSF samples demonstrated poor correlation of sEMMPRIN. Interestingly, sEMMPRIN levels were approximately 60% higher in CSFs compared to sera. sEMMPRIN CSF levels were significantly higher in secondary progressive compared to primary progressive subjects. Thus we conclude that measurement of sEMMPRIN in serum is not informative for disease activity in MS. The differential expression of sEMMPRIN in the CSF of primary and secondary progressive MS invites hypotheses of the still undefined roles of EMMPRIN in the CNS.

Serum bilirubin value predicts hospital admission in carbon monoxide-poisoned patients. Active player or simple bystander?

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Gianfranco Cervellin

Full Text Available OBJECTIVES: Although carbon monoxide poisoning is a major medical emergency, the armamentarium of recognized prognostic biomarkers displays unsatisfactory diagnostic performance for predicting cumulative endpoints. METHODS: We performed a retrospective and observational study to identify all patients admitted for carbon monoxide poisoning during a 2-year period. Complete demographical and clinical information, along with the laboratory data regarding arterial carboxyhemoglobin, hemoglobin, blood lactate and total serum bilirubin, was retrieved. RESULTS: The study population consisted of 38 poisoned patients (23 females and 15 males; mean age 39±21 years. Compared with discharged subjects, hospitalized patients displayed significantly higher values for blood lactate and total serum bilirubin, whereas arterial carboxyhemoglobin and hemoglobin did not differ. In a univariate analysis, hospitalization was significantly associated with blood lactate and total serum bilirubin, but not with age, sex, hemoglobin or carboxyhemoglobin. The diagnostic performance obtained after combining the blood lactate and total serum bilirubin results (area under the curve, 0.90; 95% CI, 0.81-0.99; p<0.001 was better than that obtained for either parameter alone. CONCLUSION: Although it remains unclear whether total serum bilirubin acts as an active player or a bystander, we conclude that the systematic assessment of bilirubin may, alongside lactate levels, provide useful information for clinical decision making regarding carbon monoxide poisoning.

Multiplexed activity-based protein profiling of the human pathogen Aspergillus fumigatus reveals large functional changes upon exposure to human serum.

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Wiedner, Susan D; Burnum, Kristin E; Pederson, LeeAnna M; Anderson, Lindsey N; Fortuin, Suereta; Chauvigné-Hines, Lacie M; Shukla, Anil K; Ansong, Charles; Panisko, Ellen A; Smith, Richard D; Wright, Aaron T

2012-09-28

Environmental adaptability is critical for survival of the fungal human pathogen Aspergillus fumigatus in the immunocompromised host lung. We hypothesized that exposure of the fungal pathogen to human serum would lead to significant alterations to the organism's physiology, including metabolic activity and stress response. Shifts in functional pathway and corresponding enzyme reactivity of A. fumigatus upon exposure to the human host may represent much needed prognostic indicators of fungal infection. To address this, we employed a multiplexed activity-based protein profiling (ABPP) approach coupled to quantitative mass spectrometry-based proteomics to measure broad enzyme reactivity of the fungus cultured with and without human serum. ABPP showed a shift from aerobic respiration to ethanol fermentation and utilization over time in the presence of human serum, which was not observed in serum-free culture. Our approach provides direct insight into this pathogen's ability to survive, adapt, and proliferate. Additionally, our multiplexed ABPP approach captured a broad swath of enzyme reactivity and functional pathways and provides a method for rapid assessment of the A. fumigatus response to external stimuli.

Multiplexed Activity-based Protein Profiling of the Human Pathogen Aspergillus fumigatus Reveals Large Functional Changes upon Exposure to Human Serum*

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Wiedner, Susan D.; Burnum, Kristin E.; Pederson, LeeAnna M.; Anderson, Lindsey N.; Fortuin, Suereta; Chauvigné-Hines, Lacie M.; Shukla, Anil K.; Ansong, Charles; Panisko, Ellen A.; Smith, Richard D.; Wright, Aaron T.

2012-01-01

Environmental adaptability is critical for survival of the fungal human pathogen Aspergillus fumigatus in the immunocompromised host lung. We hypothesized that exposure of the fungal pathogen to human serum would lead to significant alterations to the organism's physiology, including metabolic activity and stress response. Shifts in functional pathway and corresponding enzyme reactivity of A. fumigatus upon exposure to the human host may represent much needed prognostic indicators of fungal infection. To address this, we employed a multiplexed activity-based protein profiling (ABPP) approach coupled to quantitative mass spectrometry-based proteomics to measure broad enzyme reactivity of the fungus cultured with and without human serum. ABPP showed a shift from aerobic respiration to ethanol fermentation and utilization over time in the presence of human serum, which was not observed in serum-free culture. Our approach provides direct insight into this pathogen's ability to survive, adapt, and proliferate. Additionally, our multiplexed ABPP approach captured a broad swath of enzyme reactivity and functional pathways and provides a method for rapid assessment of the A. fumigatus response to external stimuli. PMID:22865858

Serum Adenosine Deaminase (ADA) Activity: A Novel Screening Test to Differentiate HIV Monoinfection From HIV-HBV and HIV-HCV Coinfections.

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Abdi, Mohammad; Rahbari, Rizgar; Khatooni, Zahed; Naseri, Nima; Najafi, Adel; Khodadadi, Iraj

2016-05-01

CD4(+) cell count, the common HIV infection screening test, is costly and unable to differentiate HIV monoinfection from its concurrent infection with hepatitis B or C virus. We aimed to ascertain diagnostic value of serum adenosine deaminase (ADA) activity as a useful tool to differentiate HIV mono- and co-infection. Blood samples were collected from 30 HIV-HBV and 30 HIV-HCV coinfected patients, 33 HIV positive subjects, and 72 controls. CD4(+) cell count, serum total ADA (tADA), and ADA1, and ADA2 isoenzyme activities were determined and their sensitivity and specificity were computed. tADA and ADA2 activities were significantly higher and CD4(+) counts were markedly lower in all patients compared with controls. Strong inverse agreements between CD4(+) cell counts and both tADA and ADA2 activities were observed. Serum tADA and ADA1 activities showed the highest specificity and the highest sensitivity, respectively, for differentiating HIV monoinfection from HIV-HBV and HIV-HCV coinfections. We showed strong agreement and correlation between CD4(+) cell count and ADA enzyme activity. Based on high ADA sensitivity and specificity, it is concluded that determination of ADA activity might be a novel diagnostic tool to distinguish of HIV monoinfection from its coinfection with HBV or HCV. © 2015 Wiley Periodicals, Inc.

Platelet activating factor-acylhydrolase (PAF-ase) activity is higher in serum of men than women and is related to levels of low density lipoprotein (LDL)

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Farr, R.S.; Howell, S.E.; Wardlow, M.L.

1986-01-01

PAF-ase is a specific serum enzyme that inactivates PAF by hydrolyzing acetate from the sn-2 position of the glycerol backbone. A reproducible PAF-ase activity assay was developed. A unit is based on the amount of serum required to release 3.61 +/- 0.042 pm 3 H-acetate from 10 pm 3 H-labeled PAF after incubation for 1 hr at 37 0 C. Assays on two single reference serums repeated 7 days were 0.63 +/- 0.013 U and 1.33 +/- 0.031 U. Serum from 20 normal men and 20 normal premenopausal women had significantly different (p = <0.001) levels of 1.32 +/- 0.072 U and 0.97 +/- 0.051 U respectively. They previously reported that PAF-ase is associated with B-lipoprotein. Therefore, total cholesterol (TC), LDL and high density lipoproteins (HDL) were determined on these 40 serums. Regression analysis revealed PAF-ase units were correlated with LDL (r = 0.740; p = < 0.001) and, parenthetically, with the TC (r = 0.620; p = < 0.001) but not with HDL. These correlations were similar for men and women. Thus, serum PAF-ase was partially controlled by serum LDL levels and the higher PAF-ase levels in serum from men were due in part to higher (p = < 0.01) LDL levels in men (147.6 +/- 6.9 mg/dl) as contrasted to women (119.0 +/- 7.6 mg/dl). PAF is a potent inflammatory, bronchoconstrictive and hypotensive agent. These data indicate that sex and serum LDL levels of subjects must be considered during future studies of the role of PAF vs PAF-ase in different disease states

The current state of serum biomarkers of hepatotoxicity.

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Ozer, Josef; Ratner, Marcia; Shaw, Martin; Bailey, Wendy; Schomaker, Shelli

2008-03-20

The level of serum alanine aminotransferase (ALT) activity reflects damage to hepatocytes and is considered to be a highly sensitive and fairly specific preclinical and clinical biomarker of hepatotoxicity. However, an increase in serum ALT activity level has also been associated with other organ toxicities, thus, indicating that the enzyme has specificity beyond liver in the absence of correlative histomorphologic alteration in liver. Thus, unidentified non-hepatic sources of serum ALT activity may inadvertently influence the decision of whether to continue development of a novel pharmaceutical compound. To assess the risk of false positives due to extraneous sources of serum ALT activity, additional biomarkers are sought with improved specificity for liver function compared to serum ALT activity alone. Current published biomarker candidates are reviewed herein and compared with ALT performance in preclinical and on occasion, clinical studies. An examination of the current state of hepatotoxic biomarkers indicates that serum F protein, arginase I, and glutathione-S-transferase alpha (GSTalpha) levels, all measured by ELISA, may show utility, however, antibody availability and high cost per run may present limitations to widespread applicability in preclinical safety studies. In contrast, the enzymatic markers sorbitol dehydrogenase, glutamate dehydrogenase, paraxonase, malate dehydrogenase, and purine nucleoside phosphorylase are all readily measured by photometric methods and use reagents that work across preclinical species and humans and are commercially available. The published literature suggests that these markers, once examined collectively in a large qualification study, could provide additional information relative to serum ALT and aspartate aminotransferase (AST) values. Since these biomarkers are found in the serum/plasma of treated humans and rats, they have potential to be utilized as bridging markers to monitor acute drug-induced liver injury in

The current state of serum biomarkers of hepatotoxicity

International Nuclear Information System (INIS)

Ozer, Josef; Ratner, Marcia; Shaw, Martin; Bailey, Wendy; Schomaker, Shelli

2008-01-01

The level of serum alanine aminotransferase (ALT) activity reflects damage to hepatocytes and is considered to be a highly sensitive and fairly specific preclinical and clinical biomarker of hepatotoxicity. However, an increase in serum ALT activity level has also been associated with other organ toxicities, thus, indicating that the enzyme has specificity beyond liver in the absence of correlative histomorphologic alteration in liver. Thus, unidentified non-hepatic sources of serum ALT activity may inadvertently influence the decision of whether to continue development of a novel pharmaceutical compound. To assess the risk of false positives due to extraneous sources of serum ALT activity, additional biomarkers are sought with improved specificity for liver function compared to serum ALT activity alone. Current published biomarker candidates are reviewed herein and compared with ALT performance in preclinical and on occasion, clinical studies. An examination of the current state of hepatotoxic biomarkers indicates that serum F protein, arginase I, and glutathione-S-transferase alpha (GSTα) levels, all measured by ELISA, may show utility, however, antibody availability and high cost per run may present limitations to widespread applicability in preclinical safety studies. In contrast, the enzymatic markers sorbitol dehydrogenase, glutamate dehydrogenase, paraxonase, malate dehydrogenase, and purine nucleoside phosphorylase are all readily measured by photometric methods and use reagents that work across preclinical species and humans and are commercially available. The published literature suggests that these markers, once examined collectively in a large qualification study, could provide additional information relative to serum ALT and aspartate aminotransferase (AST) values. Since these biomarkers are found in the serum/plasma of treated humans and rats, they have potential to be utilized as bridging markers to monitor acute drug-induced liver injury in early

The effect of Omega-3 fatty acids on serum paraoxonase activity, vitamins A, E, and C in type 2 diabetic patients

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Anis Kouchak

2011-01-01

Full Text Available Background: Diabetes mellitus is a heterogeneous metabolic disorder characterized by hyperglycemia. Studies showed paraoxonase activity, and vitamin C and A levels are decreased in diabetes. The effect of omega-3 fatty acids on serum paraoxonase activity and vitamins A, E, C in patients with type 2 diabetes is not fully understood. This study aimed to determine the effect of omega-3 fatty acids on paraoxonase activity, vitamins C, A and E levels in type 2 diabetic patients. Methods: In a double-blind, placebo controlled trial, 80 type 2 diabetic patients were randomly enrolled into the study. Study subjects received daily 2714 mg of omega-3 fatty acids or placebo for 8 weeks. Ten milliliter fasting blood was collected before and after treatments. Serum paraoxonase activity and vitamin C levels were measured by spectrophotometry. Vitamin A and vitamin E were measured using high performance liquid chromatography. Nutrient intake was estimated using 24-hours dietary recall questionnaire (for 2 days before and after treatments. Dietary data were analyzed using FPII. To compare the means of variables between the two groups, independent t-test was employed. Differences between variables before and after interventions were calculated using paired t-test. Results: Serum levels of paraoxonase activity were significantly increased after omega-3 intake (126.47 IU/ml vs. 180.13 IU/ml. However, omega-3 intake caused no significant change in serum vitamin A, C, and E. Conclusions: Supplementation of omega-3 fatty acids was found to increase paraoxonase activity in diabetic patients.

Effect of early rehabilitation training on the serum NGF, NSE, BDNF, and motor function in patients with acute cerebral infarction

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Zhen-Ping Cui

2017-01-01

Objective:To explore the effect of early rehabilitation training on the serum NGF, NSE, BDNF, and motor function in patients with acute cerebral infarction (ACI).Methods: A total of 150 patients with ACI who were admitted in our hospital from October, 2015 to October, 2016 were included in the study and randomized into the observation group and the control group. The patients in the two groups were given anti-coagulation, anti-platelet aggregation, cerebral circulation improving, and brain cell activators. The patients in the control group were given routine neurological nursing, while the patients in the observation group were given early comprehensive rehabilitation training on the basis of stable vital signs and no disease progression within 48 h. The morning fasting peripheral venous blood before treatment, 2 and 4 weeks after treatment in the two groups was collected. The serum NGF, NSE, BDNF, IL-6, hs-CRP, and TNF-α were detected. The activities of daily living and motor function before treatment, 2 and 4 weeks after treatment in the two groups were evaluated.Results:IL-6, hs-CRP, and TNF-α levels 2 and 4 weeks after treatment in the observation group were significantly lower than those in the control group (P<0.05). NGF and BDNF levels 2 and 4 weeks after treatment in the observation group were significantly higher than those in the control group (P<0.05), while NSE level was significantly lower than that in the control group (P<0.05). MBI and FMA scores 2 and 4 weeks after treatment in the observation group were significantly higher than those in the control group (P<0.05).Conclusions: The early rehabilitation training can effectively reduce the inflammatory reaction of nervous system in patients with ACI, regulate NGF, BDNF, and NSE levels, and play the cerebral function remodeling in order to promote the neural function recovery, and improve the motor function.

The Effects of Physical Activity on Serum Visfatin Level: A Literature Review

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Mohsen Ghanbarzadeh

2017-06-01

Full Text Available Higher concentration of plasma visfatin in obese and diabetic subjects compared with their healthy counterparts shows visfatin relationship to obesity and overweight. This article reviewed the studies on contradictory and different notions regarding the role of physical activity in visfatin response following aerobic and resistance exercises. Recent reports on the impact of physical activity and exercise on visfatin concentration is contradictory. Some studies have identified that exercise can reduce visfatin concentration depending on the duration of physical activity and calorie expenditure, while others have not reported any changes in visfatin concentration. The present review indicated that a balanced diet, low in fat, and physical exercise (aerobic and aerobic-resistance exercises can reduce blood visfatin levels depending on the severity and duration, while resistance training alone exerts no significant effects on serum visfatin level.

Serum Leptin levels do not correlate with disease activity in Rheumatoid Arthritis

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Sibel Yilmaz Oner

2015-01-01

Full Text Available Objectives Leptin, is a fat tissue hormone which effects energy expenditure , food intake , hematopoiesis, osteogenesis, angiogenesis, reproductive and immune systems. We aimed to determine serum leptin levels and investigate the association between disease activity and other parameters in RA patients. Methods Patients with RA (n=106 as the study group, healthy controls (n=52 and osteoarthritis (OA patients (n=37 as a control group were enrolled to the study. RA patients were categorized in four different groups according to DAS28 scores: remission ,low (LDA, moderate (MDA or high (HDA disease activity . Results No differences were present between the body mass indices of the three groups. Mean leptin levels in RA patients, OA group and healthy individuals were 25,60±13,41, 23,03±11,51 and 23,81±12,85 ng/ml, respectively and no significant difference was present between the groups. Nine of (8,5% RA patients were in remission, 16 (15,1% were in LDA, 40 (37,7% in MDA and 41 (38,7% were in HDA. Leptin levels did not correlate with DAS28 scores of RA patients (r=-0,12, p=0,11. Mean leptin levels in RA patients with remission was 32,65±7, 28 in LDA 23,94±10,94 in MDA 26,73±14,92 and in HDA 23,59±13,50 ng/ml (p=NS. No associations were observed between leptin levels and CRP, ESR, RF positivity and disease duration. Conclusions Our study revealed no correlation of disease activity and serum leptin levels. Therefore leptin does not seem to be an appropriate biomarker to monitorize inflammation in RA.

Serum dipeptidyl peptidase-4 activity in insulin resistant patients with non-alcoholic fatty liver disease: a novel liver disease biomarker.

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Gábor Firneisz

Full Text Available BACKGROUND: In a cross-sectional study we studied the fasting serum DPP-4 enzymatic activity (sDPP-4 and the insulin resistance index (HOMA2-IR in gliptin naïve patients with type 2 diabetes and in non-alcoholic fatty liver disease (NAFLD and in healthy controls (CNTRL. METHODS AND FINDINGS: sDPP-4 was measured by kinetic assay in 39 NAFLD (F/M:19/20, mean age: 47.42 yrs and 82 type 2 diabetes (F/M:48/34, 62.8 yrs patients and 26 (F/M:14/12, 35.3 yrs controls. Definition of T2D group as patients with type 2 diabetes but without clinically obvious liver disease created non-overlapping study groups. Diagnosis of NAFLD was based on ultrasonography and the exclusion of other etiololgy. Patients in T2D and NAFLD groups were similarly obese. 75 g CH OGTT in 39 NAFLD patients: 24-NGT, 4-IGT or IFG ("prediabetes", 11-type 2 diabetes. HOMA2-IR: CNTRL: 1.44; T2D-group: 2.62 (p = 0.046 vs CNTRL, parametric tests; NAFLD(NGTonly: 3.23 (p = 0.0013 vs CNTRL; NAFLD(IFG/IGT/type 2 diabetes: 3.82 (p<0.001 vs CNTRL, p = 0.049 vs 2TD group. sDPP-4 activity was higher in NAFLD both with NGT (mean:33.08U/L and abnormal glucose metabolism (30.38U/L than in CNTRL (25.89U/L, p<0.001 and p = 0.013 or in T2D groups (23.97U/L, p<0.001 and p = 0.004. Correlations in NAFLD among sDPP-4 and ALT: r = 0.4637,p = 0.0038 and gammaGT: r = 0.4991,p = 0.0017 and HOMA2-IR: r = 0.5295,p = 0.0026 and among HOMA2-IR and ALT: r = 0.4340,p = 0.0147 and gammaGT: r = 0.4128,p = 0.0210. CONCLUSIONS: The fasting serum DPP-4 activity was not increased in T2D provided that patients with liver disease were intentionally excluded. The high serum DPP-4 activities in NAFLD were correlated with liver tests but not with the fasting plasma glucose or HbA1C supporting that the excess is of hepatic origin and it might contribute to the speedup of metabolic deterioration. The correlation among gammaGT, ALT and serum DPP-4 activity and also between serum DPP-4 activity and HOMA2-IR in NAFLD strongly

Antiplatelet Therapy and Clinical Outcomes Following Myocardial Infarction Among Patients in a U.S. Employer-Based Insurance Database.

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Patel, Mehul D; Wu, David; Chase, Monica Reed; Mavros, Panagiotis; Heithoff, Kim; Hanson, Mary E; Simpson, Ross J

2017-06-01

Estimates of residual cardiovascular risks among patients who have experienced a recent acute myocardial infarction (MI) are predominantly derived from secondary prevention trial populations, patient registries, and population-based cohorts. To generate real-world evidence of antiplatelet treatment and recurrent events following MI in patients on antiplatelet treatment among commercial, employer-based insured patients in a large administrative database. This was a retrospective cohort claims database study using the Truven Health MarketScan Commercial Claims and Encounters and Medicare Supplemental databases between 2007-2011. Patients with an acute MI hospitalization with a discharge date between 2008 and 2010 were included. Excluded were those patients with documentation of stroke, transient ischemic attack (TIA), or severe bleeding at or before index hospitalization and with concomitant use of anticoagulant therapy following index hospitalization. Patients treated with clopidogrel following the index MI hospitalization were followed up to 1 year for repeat MI, stroke, and coronary revascularization. Among 33,943 post-MI continuous clopidogrel users without history of stroke, TIA, or bleeding, 22% had diabetes, whereas angina and renal impairment were less prevalent (5% and 7%, respectively). Over the 1-year follow-up, 2.4% experienced a repeat MI or stroke, and 8.2% underwent coronary revascularization. Angina, diabetes, and renal impairment were associated with elevated 1-year risk of repeat MI or stroke. This study suggests that there is residual cardiovascular risk, although relatively low, in an insured, secondary prevention population on antiplatelet treatment following an MI. In patients with MI, identifying angina, diabetes, and renal impairment may aid risk stratification and guide the effective management of these higher-risk patients. Funding for this research was provided by Merck & Co. Although Merck & Co. formally reviewed a penultimate draft, the

Serum cholinesterase activity in infantile and juvenile spinal muscular atrophy.

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Niebroj-Dobosz, I; Hausmanowa-Petrusewicz, I

1989-09-01

Serum acetylcholinesterase (AChE) and pseudocholinesterase (ChE) activity in infantile and juvenile spinal muscular atrophy (SMA) was determined. The total AChE activity was either normal or decreased in the childhood SMA (Type 1), the other SMA groups and disease controls (ALS, X-linked SMA). In the majority of SMA Type 1 cases (6/7 tested) an absence of the asymmetric A12 form was found. This was accompanied by changes in the other asymmetric and globular forms. The latter was, however, not specific for SMA Type 1 cases. The ChE activity was increased in the majority of SMA cases as well as disease controls. The asymmetric A12 ChE form was increased in all SMA Type 3 cases, the values of this form in SMA Type 1 was variable. A change in the ChE globular forms in SMA Type 1 and SMA Type 2 was a frequent finding. It is suggested that the absence of the asymmetric A12 AChE form in SMA Type 1 arises because of muscle cell immaturity and undeveloped muscle-nerve interactions. The reason of ChE changes is obscure.

Thrombopoietin modulates cardiac contractility in vitro and contributes to myocardial depressing activity of septic shock serum.

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Lupia, Enrico; Spatola, Tiziana; Cuccurullo, Alessandra; Bosco, Ornella; Mariano, Filippo; Pucci, Angela; Ramella, Roberta; Alloatti, Giuseppe; Montrucchio, Giuseppe

2010-09-01

Thrombopoietin (TPO) is a humoral growth factor that has been shown to increase platelet activation in response to several agonists. Patients with sepsis have increased circulating TPO levels, which may enhance platelet activation, potentially participating to the pathogenesis of multi-organ failure. Aim of this study was to investigate whether TPO affects myocardial contractility and participates to depress cardiac function during sepsis. We showed the expression of the TPO receptor c-Mpl on myocardial cells and tissue by RT-PCR, immunofluorescence and western blotting. We then evaluated the effect of TPO on the contractile function of rat papillary muscle and isolated heart. TPO did not change myocardial contractility in basal conditions, but, when followed by epinephrine (EPI) stimulation, it blunted the enhancement of contractile force induced by EPI both in papillary muscle and isolated heart. An inhibitor of TPO prevented TPO effect on cardiac inotropy. Treatment of papillary muscle with pharmacological inhibitors of phosphatidylinositol 3-kinase, NO synthase, and guanilyl cyclase abolished TPO effect, indicating NO as the final mediator. We finally studied the role of TPO in the negative inotropic effect exerted by human septic shock (HSS) serum and TPO cooperation with TNF-alpha and IL-1beta. Pre-treatment with the TPO inhibitor prevented the decrease in contractile force induced by HSS serum. Moreover, TPO significantly amplified the negative inotropic effect induced by TNF-alpha and IL-1beta in papillary muscle. In conclusion, TPO negatively modulates cardiac inotropy in vitro and contributes to the myocardial depressing activity of septic shock serum.

Evaluation of serum prolidase activity and oxidative stress markers in men with BPH and prostate cancer.

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Kucukdurmaz, Faruk; Efe, Erkan; Çelik, Ahmet; Dagli, Hasan; Kılınc, Metin; Resim, Sefa

2017-12-12

Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are diseases of elderly men and are related to increased oxidative stress (OS). Although prolidase has a role in collagen metabolism, it is also used to evaluate OS in many diseases. However, there is a lack of data about serum prolidase activity (SPA) in prostate cancer. The aim of this study was to evaluate and compare SPA levels in males with BPH and PCa. Evaluation was made of a total of 81 men who underwent transrectal ultrasound guided prostate biopsy for a definitive diagnosis due to high PSA levels. Patients were separated into 2 groups as BPH and PCa patients. Pre-biopsy malondialdehyde (MDA), superoxide dismutase (SOD), PSA levels and serum prolidase activities (SPA) were compared between the groups and the correlations of SPA with the other parameters were also investigated in both groups. BPH was diagnosed in 51 patients and PCa in 30. The mean age of patients was similar in both groups as 63.25 ± 5.81 years in the BPH group 65.30 ± 7.35 years in the PCa group(p:0.081). The median MDA and SOD levels were insignificantly increased in the PCa patients. SPA values were similar in BPH and PCa patients. SPA did not correlate with age, PSA, MDA or SOD levels in either group. Our study results revealed that serum prolidase activity is similar in BPH and PCa cases and is not correlated with MDA, SOD or PSA levels.

Increased Kappa/Lambda Hybrid Antibody in Serum Is a Novel Biomarker Related to Disease Activity and Inflammation in Rheumatoid Arthritis

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Lang Yi

2016-01-01

Full Text Available The κ/λ hybrid antibodies in normal human serum were reported recently, but their clinical relevance has not yet been explored. Rheumatoid arthritis (RA is one of the major joint diseases, and the early diagnosis and treatment of RA remain a challenge. Here, we developed a double-sandwich enzyme-linked immunosorbent assay system to quantify relative serum κ/λ hybrid antibody levels in RA patients, osteoarthritis (OA patients, and healthy controls (HC in order to assess their potential use as a serological biomarker of early disease and clinical activity and to preliminarily investigate their immunomodulatory roles in RA. Surprisingly, we found that κ/λ hybrid antibody was markedly increased in both early and established RA. Serum κ/λ hybrid antibody levels were significantly correlated with clinical indexes and inflammatory markers in RA. Further analysis showed a positive correlation between κ/λ hybrid antibody levels and the 28-joint disease activity score (DAS28. In conclusion, serum κ/λ hybrid antibodies in RA were identified for the first time. High levels of κ/λ hybrid antibody may be a useful tool in distinguishing early RA from OA and HC. We suggest κ/λ hybrid antibody as a marker for disease activity. The increased κ/λ hybrid antibodies were associated with inflammatory conditions in RA.

Cutoff Values of Serum Carcinoembryonic Antigen (CEA) in Normal Korean Adults and Factors Influencing Serum CEA Level

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Kim, Jong Soon; Kim, Sun Wook; Chung, June Key; Lee, Dong Soo

1994-01-01

Carcinoembryonic Antigen is one of most frequently checked tumor markers in cancer management. We performed statistical analysis with serum CEA data of 2626 persons who received regular health examination and were thought to be free of active disease to determine the cutoff values of serum CEA level in normal Korean adults and to study the factors influencing serum CEA levels in normal subjects. 1) The cutoff values of serum CEA in normal Korean adults in general were 9.28 ng/ml for men, 5.90 ng/ml for women. 2) Serum CEA level was influenced by age, present smoking history, sex, and abnormal findings in chest X ray. 3) Serum CEA level had no correlation with the history of amount of alcohol consumption or obesity. 4) Cutoff values of serum CEA in normal Korean adults were tabulated according to age, sex, and smoking history. Serum CEA level was influenced by age, sex, present smoking history and abnormal findings in chest X ray and cutoff values of serum CEA were tabulated according to age, sex, and smoking history.

Variation of serum and urine cotinine in passive and active smokers and applicability in preconceptional smoking cessation counseling

International Nuclear Information System (INIS)

Weerd, Sabina de; Thomas, Chris M.G.; Kuster, Josien E.T.G.; Cikot, Rolf J.L.M.; Steegers, Eric A.P.

2002-01-01

This study assessed the applicability of serum and urine cotinine as a biochemical marker of self-reported smoking habits for use in a preconception smoking cessation program. The variation of serum and urine cotinine over the course of the day was investigated in a sample of 21 smokers and 8 passive smokers who reported their smoking habits and exposure to smoke daily in a questionnaire for 10 consecutive days. Blood and urine samples were collected on two sampling days, 1 week apart. Both serum and urine cotinine assay could distinguish between passive and active smokers, but not between higher categories of smokers (1019 and ≥20 cigarettes per ay) due to significant intersubject overlap. In serum, no significant differences were found between morning and afternoon cotinine concentrations in either day, in contrast to urine cotinine (with lower excretions observed n the morning). An overall coefficient of variation of 22- was observed for both specimens in smokers. Because serum cotinine is subject to lower variability over the course of the day, it is more practical for use in a clinical setting where appointments are scheduled throughout the day in order o confirm smoking status

Association of angiotensin-converting enzyme (ACE) gene polymorphism with elevated serum ACE activity and major depression in an Iranian population.

Science.gov (United States)

Firouzabadi, Negar; Shafiei, Massoumeh; Bahramali, Ehsan; Ebrahimi, Soltan Ahmed; Bakhshandeh, Hooman; Tajik, Nader

2012-12-30

Genetic factors contribute substantially to the likelihood of developing major depressive disorder (MDD). The importance of renin-angiotensin system (RAS) elements in cognition and behaviour and their involvement in aetiology and treatment of depression imply that RAS gene polymorphism(s) associated with RAS overactivity might also be associated with depression. In the present study, genotype and allele frequencies of six common polymorphisms of genes encoding for RAS components were determined in DNAs extracted from venous blood of 191 depressed and 104 healthy individuals using polymerase chain reaction (PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and serum angiotensin-converting enzyme (ACE) activity was assayed using a high-performance liquid chromatography (HPLC) method. The results showed, for the first time, that GG genotype of ACE A2350G was significantly associated with MDD among Iranian participants (P=0.001; odds ratio (OR)=6.2; 95% confidence interval (CI)=2.1-18.3). Significant higher serum ACE activity (P=0.0001) as well as higher diastolic blood pressure (P=0.036) were observed in depressed patients compared to the healthy control group. Depressed patients carrying GG genotype of the A2350G polymorphism had a significantly higher serum ACE activity (P=0.02) than individuals with either AA or AG genotype. In conclusion, this study supports the hypothesis of RAS overactivity in depression in that the genotype associated with higher serum ACE activity in an Iranian population was also associated with MDD. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Comparison of bioavailability and antiplatelet action of ticagrelor in patients with ST-elevation myocardial infarction and non-ST-elevation myocardial infarction: A prospective, observational, single-centre study.

Directory of Open Access Journals (Sweden)

Piotr Adamski

Full Text Available Data from available studies suggest that the presence of ST-elevation myocardial infarction (STEMI may be associated with delayed and attenuated ticagrelor bioavailability and effect compared with non-ST-elevation myocardial infarction (NSTEMI.In a single-center, prospective, observational trial 73 patients with myocardial infarction (STEMI n = 49, NSTEMI n = 24 underwent a pharmacokinetic and pharmacodynamic assessment after a 180 mg ticagrelor loading dose (LD. Ticagrelor and its active metabolite (AR-C124910XX plasma concentrations were determined with liquid chromatography tandem mass spectrometry, and their antiplatelet effect was measured with the VASP assay and multiple electrode aggregometry.During the first six hours after ticagrelor LD, STEMI patients had 38% and 34% lower plasma concentration of ticagrelor and AR-C124910XX, respectively, than NSTEMI (ticagrelor AUC(0-6: 2491 [344-5587] vs. 3991 [1406-9284] ng*h/mL; p = 0.038; AR-C124910XX AUC(0-6: 473 [0-924] vs. 712 [346-1616] ng*h/mL; p = 0.027. STEMI patients also required more time to achieve maximal concentration of ticagrelor (tmax: 4.0 [3.0-12.0] vs. 2.5 [2.0-6.0] h; p = 0.012. Impaired bioavailability of ticagrelor and AR-C124910XX seen in STEMI subjects was associated with diminished platelet inhibition in this group, which was most pronounced during the initial hours of treatment.Plasma concentrations of ticagrelor and AR-C124910XX during the first hours after ticagrelor LD were one third lower in STEMI than in NSTEMI patients. This reduced and delayed ticagrelor bioavailability was associated with weaker antiplatelet effect in STEMI.ClinicalTrials.gov identifier: NCT02602444 (November 09, 2015.

Prehospital antiplatelet use and functional status on admission of patients with non-haemorrhagic moyamoya disease: a nationwide retrospective cohort study (J-ASPECT study)

OpenAIRE

Onozuka, Daisuke; Hagihara, Akihito; Nishimura, Kunihiro; Kada, Akiko; Nakagawara, Jyoji; Ogasawara, Kuniaki; Ono, Junichi; Shiokawa, Yoshiaki; Aruga, Toru; Miyachi, Shigeru; Nagata, Izumi; Toyoda, Kazunori; Matsuda, Shinya; Suzuki, Akifumi; Kataoka, Hiroharu

2016-01-01

Objectives To elucidate the association between antiplatelet use in patients with non-haemorrhagic moyamoya disease before hospital admission and good functional status on admission in Japan. Design Retrospective, multicentre, non-randomised, observational study. Setting Nationwide registry data in Japan. Participants A total of 1925 patients with non-haemorrhagic moyamoya disease admitted between 1 April 2012 and 31 March 2014 in Japan. Main outcome measure We performed propensity score-matc...

Correlation between Platelet Gelsolin and Platelet Activation Level in Acute Myocardial Infarction Rats and Intervention Effect of Effective Components of Chuanxiong Rhizome and Red Peony Root

Directory of Open Access Journals (Sweden)

Yue Liu

2013-01-01

Full Text Available The biological role of platelet gelsolin in platelet activation of acute myocardial infarction is not defined. In order to provide a potential new antiplatelet target for Chinese medicine and to elucidate the contribution of Xiongshao capsule, the effective components of Chuanxiong rhizome and red peony root, in this study, we randomly allocated Sprague Dawley rats to left anterior descending coronary artery ligation or sham surgery and different drug prophylaxis as control. We found that gelsolin is highly expressed in platelet rich plasma and lowly expressed in platelet poor plasma, accompanied by the high platelet activation level in model rats; plasma actin filaments and mean fluorescence intensity (MFI of platelet calcium ion increased and plasma vitamin D binding protein decreased in model rats. Xiongshao capsule could inhibit the gelsolin expression in platelet rich plasma and ischemic heart tissue simultaneously and reduce the level of plasma F-actin and MFI of platelet calcium ion. Our study concludes that platelet gelsolin is an important contributor to platelet activation, and platelet gelsolin inhibition may form a novel target for antiplatelet therapy. Xiongshao capsule may be a promising Chinese medicine drug for antiplatelet and aspirin-like cardioprotection effect.

Inhibitor of DNA synthesis is present in normal chicken serum

International Nuclear Information System (INIS)

Franklin, R.A.; Davila, D.R.; Westly, H.J.; Kelley, K.W.

1986-01-01

The authors have found that heat-inactivated serum (57 0 C for 1 hour) from normal chickens reduces the proliferation of mitogen-stimulated chicken and murine splenocytes as well as some transformed mammalian lymphoblastoid cell lines. Greater than a 50% reduction in 3 H-thymidine incorporation was observed when concanavalin A (Con A)-activated chicken splenocytes that were cultured in the presence of 10% autologous or heterologous serum were compared to mitogen-stimulated cells cultured in the absence of serum. Normal chicken serum (10%) also caused greater than 95% suppression of 3 H-thymidine incorporation by bovine (EBL-1 and BL-3) and gibbon ape (MLA 144) transformed lymphoblastoid cell lines. The only cell line tested that was not inhibited by chicken serum was an IL-2-dependent, murine cell line. Chicken serum also inhibited both 3 H-thymidine incorporation and IL-2 synthesis by Con A-activated murine splenocytes. Suppression was caused by actions other than cytotoxicity because viability of chicken splenocytes was unaffected by increasing levels of chicken serum. Furthermore, dialyzed serum retained its activity, which suggested that thymidine in the serum was not inhibiting uptake of radiolabeled thymidine. Suppressive activity was not due to adrenal glucocorticoids circulating in plasma because neither physiologic nor pharmacologic doses of corticosterone had inhibitory effects on mitogen-stimulated chicken splenocytes. These data demonstrate that an endogenous factor that is found in normal chicken serum inhibits proliferation of T-cells from chickens and mice as well as some transformed mammalian lymphoblastoid cell lines

Elevated serum angiotensin-converting enzyme (SACE) activity in acute pulmonary histoplasmosis.

Science.gov (United States)

Davies, S F; Rohrbach, M S; Thelen, V; Kuritsky, J; Gruninger, R; Simpson, M L; DeRemee, R A

1984-03-01

Serum angiotensin-converting enzyme (SACE) levels were measured in 44 subjects six weeks after acute pulmonary histoplasmosis. All patients were infected in a common-source outbreak of histoplasmosis which occurred on one day. All patients had both strictly defined clinical and serologic evidence of infection. The SACE activity was elevated at six weeks compared to normal controls, and seven of the 44 had levels more than 2 SD above the normal mean. SACE levels were also measured at three and 24 weeks after acute infection in a smaller number of the same subjects. Serial observations demonstrated that all subjects (including those with normal and elevated SACE at six weeks) had a rise and fall in SACE activity following symptomatic acute pulmonary histoplasmosis. Our findings suggest that elevated SACE does not reliably separate sarcoidosis from histoplasmosis, although elevations in histoplasmosis are much less common and may occur only briefly following acute pulmonary histoplasmosis. More important, it seems that SACE activity rises acutely in all patients with symptomatic acute histoplasmosis and then falls gradually toward baseline over several months, coinciding temporally with the granulomatous response.

Concentration differences between serum and plasma of the elements cobalt, iron, mercury, rubidium, selenium and zinc determined by neutron activation analysis

International Nuclear Information System (INIS)

Kasperek, K.; Kiem, J.; Iyengar, G.V.; Feinendegen, L.E.

1981-01-01

The differences in concentrations of cesium, cobalt, iron, mercury, rubidium, selenium and zinc between serum and plasma were examined with the aid of instrumental neutron activation analysis. Eighty serum and plasma samples obtained from 13 donors were compared. Serum was prepared in plastic tubes immediately after clotting, and plasma was separated with heparin as anticoagulant. No significant differences in the concentrations of cesium, cobalt, mercury and selenium were observed. However, the concentrations of iron, rubidium and zinc were significantly higher in serum than in plasma. The average differences were 322, 12 and 20 ng/ml for iron, rubidium and zinc, respectively. The average differences found for cesium, rubidium and zinc were far below that which can be expected from a complete, or considerable release of these elements from platelets which aggregate or disintegrate during the clotting process in preparing serum. (orig.)

Serum Epstein-Barr virus DNA, detected by droplet digital PCR, correlates with disease activity in patients with rheumatoid arthritis.

Science.gov (United States)

Kuusela, Elina; Kouri, Vesa-Petteri; Olkkonen, Juri; Koivuniemi, Riitta; Äyräväinen, Leena; Rajamäki, Kristiina; Valleala, Heikki; Nordström, Dan; Leirisalo-Repo, Marjatta; Ainola, Mari; Eklund, Kari K

2018-03-20

To study the prevalence of asymptomatic activation of Epstein-Barr virus (EBV) in patients with rheumatoid arthritis (RA) and to analyse the correlation of serum EBV DNA with the disease activity. The level of EBV DNA was determined by droplet digital PCR assay from the serum of 46 DMARD naive early RA (ERA) and 22 chronic RA (CRA)-patients at study onset. Follow-up samples from 31 ERA and 16 CRA patients were obtained after starting or modifying the anti-rheumatic treatment. EBV DNA was also measured from 33 healthy controls and 9 patients with adult onset Still's disease (AOSD). Disease activity was assessed by the disease activity score (DAS28). At baseline, EBV DNA was detected in the serum of 7 of the 46 ERA patients all of whom had moderate or high disease activity. In the follow-up samples, 11 of 31 patients were EBV DNA positive. At baseline EBV positive patients had significantly higher disease activity (p=0.036) and the concentration of EBV DNA correlated significantly with DAS28 (rs=0.333, p=0.024). EBV DNA was detected in 3 of 22 CRA patients at study onset and in 8 of 16 in the follow-up samples. At follow-up EBV positive patients had significantly higher DAS28 (p=0.027) and the concentration of EBV DNA correlated significantly with DAS28 (rs=0.724, p=0.002). Only one of the healthy controls and none of the AOSD patients were positive for EBV DNA. Active RA is associated with a lytic EBV infection which may have a role in the pathogenesis of RA.

Immobilization of serum albumin and peptide aptamer for EPC on polydopamine coated titanium surface for enhanced in-situ self-endothelialization

International Nuclear Information System (INIS)

Chen, Zhuoyue; Li, Quanli; Chen, Jialong; Luo, Rifang; Maitz, Manfred F.; Huang, Nan

2016-01-01

Restenosis and thrombosis are two major complications associated with vascular stents and grafts. The homing of circulating endothelial progenitor cells (EPCs) onto implant surfaces brings a new strategy to solve these problems by accelerating self -endothelialization in situ. Peptide aptamers with high affinity and specific recognition of EPCs can be immobilized to capture EPCs from the circulating blood. In this study, a biotinylated peptide aptamer (TPSLEQRTVYAK-GGGC-K-Biotin) for EPC, and bovine serum albumin (BSA) were co-immobilized onto titanium surface through avidin–biotin recognition to endow the surface with specific affinity for EPC and anti-platelet adhesion properties. Quartz crystal microbalance with dissipation (QCM-D), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and water contact angle measuring were adopted for coating characterization. EPC affinity and hemocompatibility of the coating were also investigated in vitro. The results demonstrated that aptamer and BSA co-immobilized surface significantly reduced platelet adhesion and fibrinogen adsorption/activation. Besides, such functional surface could remarkably enhance EPC adhesion, without affecting the behavior of endothelial cells (ECs) and smooth muscle cells (SMCs) obviously. The result shows the possibility of utilizing such a multifunctional surface in cardiovascular implants. - Highlights: • We construct a multifunctional surface based on immobilization of BSA and aptamer. • It can significantly reduce platelet adhesion and fibrinogen adsorption/activation. • Such functional surface could remarkably enhance EPC adhesion in vitro. • It can induce rapid self-endothelialization of the implant surface in situ in vivo. • It is possible to use such a multifunctional surface in cardiovascular implants.

Immobilization of serum albumin and peptide aptamer for EPC on polydopamine coated titanium surface for enhanced in-situ self-endothelialization

Energy Technology Data Exchange (ETDEWEB)

Chen, Zhuoyue, E-mail: 362947953@qq.com [Key Lab. of Advanced Technology for Materials of Education Ministry, Southwest Jiaotong University, Chengdu, 610031 (China); RegeMed Lab of Tissue Engineering, Faculty of Life Science, Northwest University, Xi' an, 710069 (China); Li, Quanli [College of Stomology, Anhui Medical University, Hefei, 230032 (China); Chen, Jialong [Key Lab. of Advanced Technology for Materials of Education Ministry, Southwest Jiaotong University, Chengdu, 610031 (China); College of Stomology, Anhui Medical University, Hefei, 230032 (China); Luo, Rifang [Key Lab. of Advanced Technology for Materials of Education Ministry, Southwest Jiaotong University, Chengdu, 610031 (China); Maitz, Manfred F. [Key Lab. of Advanced Technology for Materials of Education Ministry, Southwest Jiaotong University, Chengdu, 610031 (China); Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials, Dresden (Germany); Huang, Nan, E-mail: huangnan1956@163.com [Key Lab. of Advanced Technology for Materials of Education Ministry, Southwest Jiaotong University, Chengdu, 610031 (China)

2016-03-01

Restenosis and thrombosis are two major complications associated with vascular stents and grafts. The homing of circulating endothelial progenitor cells (EPCs) onto implant surfaces brings a new strategy to solve these problems by accelerating self -endothelialization in situ. Peptide aptamers with high affinity and specific recognition of EPCs can be immobilized to capture EPCs from the circulating blood. In this study, a biotinylated peptide aptamer (TPSLEQRTVYAK-GGGC-K-Biotin) for EPC, and bovine serum albumin (BSA) were co-immobilized onto titanium surface through avidin–biotin recognition to endow the surface with specific affinity for EPC and anti-platelet adhesion properties. Quartz crystal microbalance with dissipation (QCM-D), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and water contact angle measuring were adopted for coating characterization. EPC affinity and hemocompatibility of the coating were also investigated in vitro. The results demonstrated that aptamer and BSA co-immobilized surface significantly reduced platelet adhesion and fibrinogen adsorption/activation. Besides, such functional surface could remarkably enhance EPC adhesion, without affecting the behavior of endothelial cells (ECs) and smooth muscle cells (SMCs) obviously. The result shows the possibility of utilizing such a multifunctional surface in cardiovascular implants. - Highlights: • We construct a multifunctional surface based on immobilization of BSA and aptamer. • It can significantly reduce platelet adhesion and fibrinogen adsorption/activation. • Such functional surface could remarkably enhance EPC adhesion in vitro. • It can induce rapid self-endothelialization of the implant surface in situ in vivo. • It is possible to use such a multifunctional surface in cardiovascular implants.

Association between angiotensin II receptor gene polymorphism and serum angiotensin converting enzyme (SACE) activity in patients with sarcoidosis

OpenAIRE

Takemoto, Y.; Sakatani, M.; Takami, S.; Tachibana, T.; Higaki, J.; Ogihara, T.; Miki, T.; Katsuya, T.; Tsuchiyama, T.; Yoshida, A.; Yu, H.; Tanio, Y.; Ueda, E.

1998-01-01

BACKGROUND—Serum angiotensin converting enzyme (SACE) is considered to reflect disease activity in sarcoidosis. SACE activity is increased in many patients with active sarcoid lesions. The mechanism for the increased SACE activity in this disease has not been clarified. ACE insertion/deletion (I/D) gene polymorphism has been reported to have an association with SACE levels in sarcoidosis, but no evidence of an association between angiotensin II receptor gene polymorphism and SA...

Serum lipase activity and concentration during intravenous infusions of GLP-1 and PYY3-36 and after ad libitum meal ingestion in overweight men

DEFF Research Database (Denmark)

Schmidt, Julie Berg; Sjödin, Anders Mikael; Stevner, Lene Susanne

2016-01-01

To examine the effect on serum lipase activity and protein concentration of intravenous infusions of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY3-36) and of an ad libitum meal in healthy overweight men. Twenty-five healthy, male subjects participated in this randomized, double-blinded, pl......To examine the effect on serum lipase activity and protein concentration of intravenous infusions of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY3-36) and of an ad libitum meal in healthy overweight men. Twenty-five healthy, male subjects participated in this randomized, double...... the infusion and after intake of an ad libitum meal for measurement of serum lipase. Serum lipase levels measured by enzyme-linked immunosorbent assay (ELISA) following mono-infusions of GLP-1 and PYY3-36 were comparable to serum lipase levels following placebo (P = 0.054 and P = 0.873, respectively......). Following the co-infusion of GLP-1 and PYY3-36, serum lipase levels measured by ELISA decreased over time compared to placebo (P = 0.012). However, the between-group difference was not consistent when each time point was analyzed separately. On the placebo day, serum lipase levels measured by ELISA after...

Summary of 2017 ESC guidelines on valvular heart disease, peripheral artery disease, STEMI and on dual antiplatelet therapy.

Science.gov (United States)

Van Camp, Guy; De Backer, Tine; Beauloye, Christophe; Desmet, Walter; Claeys, Marc J

2017-12-11

During the ESC congress in September 2017 in Barcelona, the new ESC guidelines were presented and are now available on the ESC website. The new guidelines cover management recommendations on following cardiovascular items: valvular heart disease, peripheral artery disease, ST elevation myocardial infarction (STEMI) and on dual antiplatelet therapy. The present document gives a summary of these guidelines and highlights the most important recommendations and changes in the management of these diseases. It will help to increase awareness about the new guidelines and may stimulate to consult the full document for specific items. Ultimately, the authors hope that this document will enhance implementation of new ESC guidelines in daily clinical practice.

Effect of bilirubin on the spectrophotometric and radionuclide assay for serum angiotensin-converting enzyme

International Nuclear Information System (INIS)

Saxe, A.W.; Hollinger, M.A.; Essam, T.

1986-01-01

The effect of bilirubin on serum angiotensin-converting enzyme (ACE) activity was studied with spectrophotometric and radionuclide assays. In the spectrophotometric assay addition of bilirubin to normal serum from dog, mouse, and human produced a dose-related inhibition of ACE activity. A 50% decrease in human ACE activity was produced by the addition of approximately 250 mg/L in vitro. Serum from icteric patients with elevated bilirubin was also associated with a reduction in ACE activity in the spectrophotometric assay. A 50% decrease in ACE activity in these samples was associated with a serum bilirubin of approximately 220 mg/L. In the radionuclide assay, however, addition of bilirubin to normal human serum failed to reduce measured ACE activity. The use of a radionuclide assay for serum ACE in clinical samples offers the advantage of less interference from serum bilirubin

Viewpoint: "underutilisation of novel antiplatelet agents--myths, generics, and economics".

Science.gov (United States)

Serebruany, V L; Fortmann, S D

2014-07-03

Two oral antiplatelet agents have been recently introduced for acute coronary syndromes indication providing alternatives for dual therapy with aspirin and clopidogrel. In fact, worldwide prasugrel has been on the market for four years, and ticagrelor for over two years. Despite declared benefits over clopidogrel, including hypothetical cost saving advantages, in real life, the clinical utilisation of both agents is small. Generic clopidogrel, and price differences are claimed as major obstacles to prevent broader prasugrel and ticagrelor use. However, these economic difficulties are barely supported by available evidence, and served mostly to protect questionable management spending, as an exuse to explain why in reality cardiologists are so sceptical about both novel agents, and to convince the sharehoders that their money is not wasted, misleading the owners with regard to future success. Importantly, brand Plavix® is used worldwide 5-10 times more often than new agents, despite heavy generic competition. The future of prasugrel outside Japan, where much lower reasonable dose will be used is not impressive due to lack of further outcome studies, negative results of the latest trials, and less than four years left before patent expiration. The fate of ticagrelor will depend on verification of deaths numbers in the ongoing United States Department of Justice PLATO investigation, and confirmation of the mortality benefit in the PEGASUS TIMI-54 trial.

E-ADA activity in serum of lambs experimentally infected with Haemonchus contortus.

Science.gov (United States)

Da Silva, Aleksandro S; Fausto, Guilherme C; Grando, Thirssa H; Cadore, Carlos A; Pimentel, Victor C; Jaques, Jeandre A; Schetinger, Maria R C; Monteiro, Silvia G; Leal, Marta L R

2013-08-01

The aim of this study was to evaluate adenosine deaminase (E-ADA) activity in sera of lambs experimentally infected with Haemonchus contortus. We used 12 lambs divided into 2 groups; Group A had 5 healthy, non-infected animals (control) and Group B had 7 healthy animals infected with H. contortus . Lambs were infected orally with 500 larvae (L3) per animal every 2 days, for a period of 20 days, and later the infection was confirmed by examination of feces (eggs per gram [EPG] via fecal egg count). Blood collection was performed at days 0, 20, 40, 60, and 80 post-infection (PI) for analysis of E-ADA activity. Animals in Group A showed negative EPG throughout the experiment unlike those from Group B that had elevated EPG counts. E-ADA activity was reduced in the serum of animals infected with H. contortus when compared to non-infected controls at days 20, 40, 60, and 80 PI. Therefore, it is concluded that infection with H. contortus influences the E-ADA activity in lambs.

Serum adenosine deaminase activity and its isoenzyme in patients treated for tuberculosis

International Nuclear Information System (INIS)

Rokayan, S.A

2003-01-01

Objective: Increased serum adenosine deaminase (ADA) activity, mainly associated with tuberculosis can also occur in a number of other diseases thus negatively affecting the diagnostic utility of ADA measurements in tuberculosis. The aim of the study was to determine whether or not the combined use of the activity of ADA, its isoenzymes and differential cell counts would provide a more efficient means of diagnosing tuberculosis than the use of ADA levels alone. Results: Data suggested significant (p 0.75) of ADA/sub 2/ADA was found to be better indicator of tuberculosis. Lymphocyte neutrophil ratio (L/N)> 0.69 gave additional benefit to increase the sensitivity and specificity for the use of ADA as marker in diagnosing tuberculosis. Conclusion: The combined use of activity of ADA, its isoenzymes and total and differential cell counts is a better indicator and gives better understanding to diagnose and evaluate tuberculosis and response to therapy. (author)

UP TO DATE ANTIPLATELET THERAPY IN PATIENTS WITH HIGH RISK OF THROMBOTIC EVENTS AND REAL CLINICAL PRACTICE

Directory of Open Access Journals (Sweden)

S. Yu. Martsevich

2012-01-01

Full Text Available Aim. To assess the real rate of dual antiplatelet therapy (DAT, acetylsalicylic acid + clopidogrel use in patients having appropriate indications according to current clinical guidelines and to study the possibility of prescription rate improvement by education activity directed to doctors. Material and methods. The study consisted of 3 parts. Parts I and II present the results of two questionnaire surveys of patients with acute myocardial infarction, or stenting, who needed in DAT according to current clinical guidelines. The real use of the DAT was assessed in part III on the basis of the multicenter study conducted in different regions of Russia (ROMB study in a large sample of patients having DAT indications. Results. Part I - PROGNOZ-IBS study. According to the questionnaire survey only 112 out of 239 patients (47% having an absolute indications, received DOT. Part II - phone survey of patients with acute myocardial infarction in two towns of Lyubertsy and Podolsk. 28 of 71 patients (39% took the DAT (from some days to 6 months and 35 patients (49% — did not take it. Part III - ROMB study. 519 patients did not take DAT, at that 259 (50% in hospital and 260 (50% - in out-patient clinic. 521 patients took DAT according to indications, at that 238 (46% in hospital and 283 (54% - in out-patient clinic. Conclusion. Less than 50% of patients, having direct indications, received DAT in the real clinical practice. The prescription rate can be improved due to education activity directed to doctors and increase in clopidogrel drugs affordability.

Serum protein inhibition of thyrotropin binding to human thyroid tissue

International Nuclear Information System (INIS)

Beall, G.N.; Chopra, I.J.; Solomon, D.H.; Kruger, S.R.

1978-01-01

We used a modificaton of the TSH radioreceptor assay to detect TSH-binding inhibition (TBI) activity in serum and serum fractions from normal subjects and patients with Graves' disease. TBI activity is present in normal IgG prepared by DEAE-Sephadex chromatography and in normal globulins prepared by precipitation at 1.6 M ammonium sulfate. Other normal serum proteins also had TBI activity when large concentrations were tested. Gel filtration chromatography and powder block electrophoresis were used to prepare fractions of normal and Graves' disease sera. In these fractions from normal serum, TBI activity was found in both γ-globulin and α-globulin-albumin fractions electrophoretically and in both 7S and 4S peaks from gel filtration. TBI activity from Graves' disease patients' sera was similarly distributed, but relatively more TBI accompanied the electrophoretic γ-globulins. Sepharose Protein-A and anti-IgG were used as immunoabsorbents to isolate and purify IgG from normal and Graves' disease sera. TBI activity in IgG was proportional to the IgG concentration, indicating that the TBI which migrates as a γ-globulin electrophoretically is an IgG and thus may possibly be an antibody. Inhibitory activity found in normal serum globulins and in the non-IgG fractions of both normal and abnormal sera seriously interferes with attempts to use the TSH radioreceptor assay to study the hypothesized anti-TSH receptor antibody in the serum of patients with Graves' disease

Serum creatine kinase isoenzymes in children with osteogenesis imperfecta.

Science.gov (United States)

D'Eufemia, P; Finocchiaro, R; Zambrano, A; Lodato, V; Celli, L; Finocchiaro, S; Persiani, P; Turchetti, A; Celli, M

2017-01-01

This study evaluates serum creatine kinase isoenzyme activity in children with osteogenesis imperfecta to determine its usefulness as a biochemical marker during treatment with bisphosphonate. The changes of creatine kinase (CK) isoenzyme activity during and after discontinuation therapy were observed. These results could be useful in addressing over-treatment risk prevention. The brain isoenzyme of creatine kinase (CKbb) is highly expressed in mature osteoclasts during osteoclastogenesis, thus plays an important role in bone resorption. We previously identified high serum CKbb levels in 18 children with osteogenesis imperfect (OI) type 1 treated for 1 year with bisphosphonate (neridronate). In the present study, serum CK isoenzymes were evaluated in the same children with continuous versus discontinued neridronate treatment over a further 2-year follow-up period. This study included 18 children with OI type 1, 12 with continued (group A) and 6 with ceased (group B) neridronate treatment. Auxological data, serum biochemical markers of bone metabolism, bone mineral density z-score, and serum total CK and isoenzyme activities were determined in both groups. Serum CKbb was progressively and significantly increased in group A (p < 0.004) but rapidly decreased to undetectable levels in group B. In both groups, the cardiac muscle creatine kinase isoenzyme (CKmb) showed a marked decrease, while serum C-terminal telopeptide (CTx) levels were almost unchanged. This study provides evidence of the cumulative effect of neridronate administration in increasing serum CKbb levels and the reversible effect after its discontinuation. This approach could be employed for verifying the usefulness of serum CKbb as a biochemical marker in patients receiving prolonged bisphosphonate treatment. Moreover, the decreased serum CKmb levels suggest a systemic effect of these drugs.

Concomitant Prevalence of Low Serum Diamine Oxidase Activity and Carbohydrate Malabsorption

Directory of Open Access Journals (Sweden)

Dietmar Enko

2016-01-01

Full Text Available The aim of this retrospective study was to analyze the concomitant prevalence rates for lactose malabsorption (LM, fructose malabsorption (FM, and histamine intolerance (HI in patients with so far unexplained gastrointestinal (GI symptoms. A total of 439 outpatients, who presented unclear abdominal discomfort, underwent lactose (50 g and fructose (25 g hydrogen (H2 breath tests. Additionally, serum diamine oxidase (DAO measurements were performed. Individuals with low serum DAO activity (<10 U/mL, GI symptoms, and response to histamine-free diet were diagnosed with HI. Of all 439 patients, 341 (77.7% were found with 7 various GI conditions. In total, 94 (21.4%, 31 (7.1%, and 100 (22.8% individuals presented LM, FM, or HI only, whereas 116 (26.4% patients showed an overlap of GI entities investigated here. Interestingly, 89 out of 241 (36.9% individuals with carbohydrate malabsorption were also diagnosed with HI (LM + HI: 52 [11.8%], FM + HI: 23 [5.2%], and LM + FM + HI 14 [3.2%] individuals. In conclusion different combinations of LM, FM, and HI are present in individuals with unclear abdominal discomfort/pain. In clinical practice we suggest testing for LM, FM, and additional HI in the diagnostic work-up of these patients. Depending on these various diagnoses possible, patients should get an individualized dietary advice.

Serum lysozyme determinations, April-June 1961

Energy Technology Data Exchange (ETDEWEB)

Finch, S C; Lamphere, J P; Jablon, S

1963-04-18

Serum lysozyme levels were determined on 670 consecutive subjects seen for regularly scheduled clinic examinations of the Adult Health Study in Hiroshima. Serum lysozyme levels were found to vary significantly with the absolute peripheral granulocyte count, age, sex, and month of study. A high level of correlation also was noted between serum lysozyme and diabetes mellitus. This was at least in part attributable to greater average age in patients with diabetes. Suggestive relationship was established between serum lysozyme levels, respiratory diseases, and tuberculosis. These changes are believed to reflect active inflammation with excessive destruction of granulocytes and parenchymal tissues in those patients with the more acute processes. No relationship was found between serum lysozyme and previous exposure to ionizing radiation. These studies indicate that the serum lysozyme level may be useful in the study of the kinetics of leukopoiesis, the aging process, and in the detection of subtle inflammatory processes. 21 references, 5 tables.

Effect of an ionizing radiation on the activity of the components of the system: DNA ase 1-natural DNA ase 1 inhibitor in blood serum of white rats

International Nuclear Information System (INIS)

Ivanova, A.B.; Kerova, N.I.; Pukhova, G.G.; Baraboj, V.A.; AN Ukrainskoj SSR, Kiev. Inst. Problem Onkologii)

1976-01-01

The presence of a natural inhibitor of DNAase 1 of protein nature is responsible for the inhibiting action of blood serum on pancreatic DNAase. Depending on the radiation dose (ranging from 450 to 750 R), the activity of the serum inhibitor of DNAase 1 increases for a short time, then, in the period from 15 minutes to 24 hours, it normalizes (450 R) or drastically decreases on the seventh day (750 R). At the dose of 750 R, the activity of free serum DNAase 1 increases throughout the entire period of the experiment; the activity of bound DNAase 1 gradually decreases and it is not observed on the seventh day. The dose of 450 R does not substantially affect the activity of free DNAase 1. Evidently, at high X-ray doses, formation of the inhibitor-serum DNAase 1 complex is disturbed

Serum levels of tumor necrosis factor-α and soluble adhesion molecules in relation to magnetic resonance imaging results and clinical activity in multiple sclerosis

International Nuclear Information System (INIS)

Millers, A.; Metra, M.; Mastina, M.; Platkajis, A.; Kukaine, R.

2001-01-01

One direction of research in pathogenesis of multiple sclerosis (MS) has been to identify immunological markers associated with disease activity that are capable of predicting subsequent course of disease and are sensitive to intervention by immunomodulatory therapies. Adhesion molecules and tumor necrosis factor-α of the cytokine superfamily are associated with inflammation-mediated blood-brain barrier dysfunction and demyelination in the central nervous system (CNS). This study investigates the relationship between the serum level of soluble vascular adhesion molecule-1 (sVCAM), soluble intercellular adhesion molecule-1 (alCAM), tumor necrosis factor-α (TNF-α) and magnetic resonance imaging (MRI) activity in 18 patients with relapsing-remitting (RR) MS with different clinical activity. Patients with active gadolinium (Gd)-enhanced lesions on MRI showed a higher serum level of TNF-α, sVCA-1, slCAM-1 than RR MS patients without Gd-enhanced lesions. Control individuals (n=10) without MRI abnormalities had significantly lower serum levels of the above immunological parameters. These results suggest that serum levels of TNF-α and adhesion molecules slCAM-1 in RR MS patients are correlated with Gd-enhanced MRI and disease clinical activity and that they can be used as biological markers of disease activity. The soluble form of VCAM levels in peripheral blood did not correlate with disease activity and Gd-enhanced lesions of MRI. sVCAM as an early indicator of blood-brain barrier dysfunction may also serve as marker of beneficial activity in the relapsing phase of MS course. (authors)

The relationship between metabolic presbycusis and serum paraoxonase/arylesterase activity.

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Keleş, Erol; Kapusuz, Zeliha; Gürsu, Mehmet Ferit; Karlıdag, Turgut; Kaygusuz, Irfan; Bulmuş, Funda Gülcü; Yalcın, Sinasi

2014-01-01

To determine the presence of a relationship between metabolic presbycusis and serum paraoxonase/arylesterase activity. A total of 30 patients who had been admitted to the Ear, Nose, and Throat (ENT) Clinic of Fırat University Medical Faculty and diagnosed as metabolic presbycusis were included in the study. The control group was composed of 30 healthy volunteers. Pure tone audiometry and impedencemeter were performed on all subjects included in the study at the audiometry laboratory of the ENT clinic. The presence of a regular hearing curve, a symmetrical sensorineural hearing loss more than 25 dB with preserved speech discrimination were accepted as criteria for metabolic presbycusis. Blood samples were drawn from the patients prior to the hearing tests. The sera were separated for measurements of total cholesterol, triglyceride, high-density lipoprotein, very low-density lipoprotein, low-density lipoprotein, human serum paraoxonase and arylesterase levels, respectively. No statistically significant difference was found between the patient and the control groups in terms of age and gender. Paraoxonase, arylesterase and paraoxonase/arylesterase, high-density lipoprotein levels were found to decrease in the study group and the difference was found to be statistically significant compared to the control group (P presbycusis. Furthermore, the results of this study make us think that there could be a relationship between metabolic presbycusis and cardiovascular diseases. In this case, metabolic presbycusis may be a determining parameter in the early diagnosis of cardiovascular diseases. We consider that this study may be the pioneer for further studies conducted with larger patient numbers.

Radioimmunoassay of haloperidol in human serum: correlation of serum haloperidol with serum prolactin

International Nuclear Information System (INIS)

Poland, R.E.; Rubin, R.T.

1981-01-01

A radioimmunoassay (RIA) for measurement of serum haloperidol is described. Compared to gaschromatography (GC), RIA vaues average 40% higher. However, a simple organic extraction of serum yields statistically equivalent RIA and GC haloperidol determinations. For both men and women combined, there was a positive correlation between dose (mg/kg/day) and steady-state serum haloperidol level (r = +0.86) and between steady-state serum haloperidol and serum prolactin (PRL) concentration

The Process of Separating Bovine Serum Albumin Using Hydroxyapatite and Active Babassu Coal (Orbignya martiana)

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Zuñiga, Abraham Damian Giraldo; Sousa, Rita de Cássia Superbi; Zacchi Scolforo, Carmelita

2016-01-01

Bovine serum albumin is one of the major serum proteins; it plays an important role as a result of its functional and nutritional properties which have bioactive peptides. Adsorption method was used to separate protein, which involves hydroxyapatite, synthetic hydroxyapatite, and active babassu coal. Initially, characterization was carried out using the zeta potential of the adsorbents. Kinetic pseudo-first- and pseudo-second-order models were applied. For isotherms, equilibrium data studies were carried out using the Langmuir and Freundlich models, in addition to determining the efficiency of adsorptive process. The results of the zeta potential showed loads ranging from +6.9 to −42.8 mV. The kinetic data were better represented in the pseudo-second-order model with chemisorption characteristics. The adsorption capacity of the adsorbents decreased as pH increased, indicating that the electrostatic bonds and some functional groups of active babassu coal contributed to the reduction of adsorption, especially oxygen linked to carbon atoms. The value of pH 4.0 showed the best results of adsorption, being obtained as the maximum adsorption capacity (q m) and yield (%) (where q m = 87.95 mg g−1 and 74.2%; 68.26 mg g−1 and 68.6%; and 36.18 mg g−1, 37.4%) of hydroxyapatite, synthetic hydroxyapatite, and active babassu coal, respectively. PMID:27376149

Sex differences in the aging pattern of renin-angiotensin system serum peptidases.

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Fernández-Atucha, A; Izagirre, A; Fraile-Bermúdez, A B; Kortajarena, M; Larrinaga, G; Martinez-Lage, P; Echevarría, E; Gil, J

2017-01-01

Serum peptidases, such as angiotensin-converting enzyme (ACE), angiotensin-converting enzyme-2 (ACE2), neutral endopeptidase (NEP), aminopeptidase N (APN), and aminopeptidase A (APA), are important elements of the renin-angiotensin system (RAS). Dysregulation of these enzymes has been associated with hypertension and cardiovascular risk. In the present study, serum activities of RAS peptidases were analyzed to evaluate the existence of sexual differences, with a possible different pattern in pre- and post-andropausal/post-menopausal participants. One hundred and eighteen healthy men and women between 41 and 70 years of age (58 women and 60 men) were recruited to participate in the study. Serum RAS-regulating enzymes were measured by spectrofluorimetry. Enzymatic activity was recorded as units of enzyme per milliliter of serum (U/mL). Significantly lower serum APA activity was observed in men with respect to women; no sex differences were detected for ACE, ACE2, NEP, or APN. Significantly lower APA and ACE serum activity were observed in older men compared to older women. In contrast, younger (menopausia, on the critical serum enzymatic activities of the RAS, which could correlate with sexual differences in cardiovascular risk.

Calprotectin and TNF trough serum levels identify power Doppler ultrasound synovitis in rheumatoid arthritis and psoriatic arthritis patients in remission or with low disease activity.

Science.gov (United States)

Inciarte-Mundo, José; Ramirez, Julio; Hernández, Maria Victoria; Ruiz-Esquide, Virginia; Cuervo, Andrea; Cabrera-Villalba, Sonia Raquel; Pascal, Mariona; Yagüe, Jordi; Cañete, Juan D; Sanmarti, Raimon

2016-07-08

Serum levels of calprotectin, a major S100 leucocyte protein, are associated with disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients. Higher drug trough serum levels are associated with good response in patients treated with tumour necrosis factor inhibitors (TNFi). Power Doppler ultrasound (PDUS) synovitis is predictive of flare and progression of structural damage in patients in clinical remission. The purpose of this study was to analyse the accuracy of calprotectin and TNFi trough serum levels in detecting PDUS synovitis in RA and PsA patients in clinical remission or with low disease activity who were receiving TNFi. We conducted a cross-sectional study of 92 patients (42 with RA, 50 with PsA) receiving adalimumab (ADA), etanercept (ETN) or infliximab who were in remission or had low disease activity (28-joint Disease Activity Score based on erythrocyte sedimentation rate ultrasound scores (all r coefficients >0.50 in RA). Calprotectin correlated with the PDUS synovitis score in patients treated with ADA and ETN. Using PDUS synovitis (yes or no) as the reference variable, calprotectin had an AUC of 0.826. The best cut-off was ≥1.66 μg/ml, with a likelihood ratio of 2.77. C-reactive protein (AUC 0.673) and erythrocyte sedimentation rate (AUC 0.731) had a lower discriminatory capacity. TNFi trough serum levels were significantly associated with PDUS synovitis (OR 0.67, 95 % CI 0.52-0.85, p < 0.001) but their accuracy (AUC <0.5) was less than that of calprotectin. TNFi trough serum levels were inversely correlated with calprotectin and PDUS synovitis in RA and PsA patients receiving ADA and ETN. Calprotectin and TNFi trough serum levels may help identify PDUS synovitis in RA and PsA patients in clinical remission or with low disease activity.

Clinical outcomes, health resource use, and cost in patients with early versus late dual or triple anti-platelet treatment for acute coronary syndrome.

Science.gov (United States)

Friedman, Howard; Mollon, Patrick; Lian, Jean; Navaratnam, Prakash

2013-08-01

Acute coronary syndrome (ACS) guidelines recommend early dual anti-platelet therapy (thienopyridines + acetylsalicylic acid [aspirin]). However, triple therapy (thienopyridines + aspirin + glycoprotein IIb/IIIa receptor inhibitors [GRIs]) has shown benefit in clinical trials. This study assessed real-world ACS treatment patterns and outcomes in the acute care setting. A retrospective analysis of patients admitted to hospital with ACS (index event) from January 2007 to December 2009 was conducted (Thomson's MarketScan Hospital Drug Database). Eligible patients were ≥18 years of age, of either sex, and had primary admission and discharge diagnoses of ACS. Cohorts were defined by anti-platelet treatment and then by the timing of treatment initiation (early initiation: within ≤2 days of admission; late initiation: ≥2 days post-admission). Patient characteristics, clinical outcomes, resource utilization, and costs were assessed using descriptive statistics. A total of 249,907 eligible patients were placed into four treatment cohorts (aspirin assumed for all patients): aspirin only; clopidogrel only (dual therapy); GRI only (dual therapy); and clopidogrel + GRI (triple therapy). Patients in the 'clopidogrel-only' cohort were more likely to be older, female, and have more co-morbidities than those in other cohorts; stroke (6.2 %) and re-hospitalization (15.4 %) rates were higher than in the 'GRI-only' and 'triple therapy' cohorts. The GRI-only cohort had higher major bleeding rates (3.3 %), mortality (7.6 %), and costs ($US21,975 [year 2010 values]) than the clopidogrel-only and triple-therapy cohorts. Late initiation cohorts were more likely to be older, female, and have more co-morbidities than early initiation cohorts. Major bleeding was more likely with GRI-only patients (regardless of initiation timing) than with other cohorts. Late-treated clopidogrel-only patients had higher rates of stroke (6.9 %), ACS-related re-admissions (6.1 %), and all

Dual Antiplatelet Therapy Does Not Increase the Risk of Bleeding After Carotid Endarterectomy: Results of a Prospective Study.

Science.gov (United States)

Illuminati, Giulio; Schneider, Fabrice; Pizzardi, Giulia; Masci, Federica; Calio', Francesco G; Ricco, Jean-Baptiste

2017-04-01

The purpose of this study was to evaluate the risk of bleeding and other postoperative complications of carotid endarterectomy (CEA) in patients receiving dual antiplatelet therapy (DAPT). From January 2005 to December 2015, 188 consecutive patients undergoing CEA and receiving DAPT (aspirin 100 mg + clopidogrel 75 mg) were enrolled in a prospective study. All of them underwent coronary artery stenting with drug-eluting stents during the 6 months preceding CEA. In the entire series, DAPT was continued until the evening before CEA and resumed on the evening of the operation. All patients received intraoperative heparinization (5,000 IU before carotid clamping), which was reversed in 5 patients. In addition, all of them were given 2,000 units of enoxaparin every 12 hr after the operation, beginning 6 hr after completion of the operation, and until discharge. All the patients presented with carotid artery stenosis >70% (North American Symptomatic Carotid Endarterectomy Trial [NASCET] criteria), which was symptomatic in 42 patients (transient ischemic attack, n = 32; minor stroke, n = 10) and asymptomatic in 146. The CEA technique was standard, with prosthetic patch closure in 109 cases (58%) and eversion in 79 (42%). The primary endpoints of the study were occurrence of a postoperative cervical hematoma requiring surgical hemostasis and occurrence of cranial nerve injuries. The secondary endpoint was the combined rate of postoperative mortality, stroke, and myocardial ischemia. No postoperative cervical hematoma requiring surgical evacuation occurred in this series. One hypoglossal nerve palsy, regressive within 2 weeks, was observed. Postoperative mortality and neurologic and cardiac morbidity were nil. CEA under DAPT yields results comparable with those obtained in patients receiving a single antiplatelet treatment. No hemorrhagic complications were observed in this prospective series. Copyright © 2017 Elsevier Inc. All rights reserved.

Trace element determination in fingernails, hair and blood serum in patients with Crohn's disease using neutron activation analysis

International Nuclear Information System (INIS)

Buschmann, H.

1984-01-01

The determination of trace elements and electrolyte concentrations in blood serum, hair and fingernails of 16 patients with Crohn's disease was carried out by means of instrumental neutron activation analysis. In the serum a significant decline in the zinc content could be registered, while the remaining trace elements remained in the normal range. The parenteral nutrition also showed a zinc deficiency. There was, however, also an iron deficiency. The studies of the hair and fingernails gave the following results: Rubidium and antimony in the normal range; zinc, selenium, iron and cobalt below normal values. (orig./PW) [de

Influence of physical and emotional activity on the metabolic profile of blood serum of race horses

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T. I. Bayeva

2016-09-01

Full Text Available In the article data are presented on dynamics of the level of indicators of metabolic profile of blood serum of race horses of the Ukrainian riding breed in the conditions of physical and emotional loading. Clinically healthy race horses were the object of  research. Blood was taken from the jugular vein to obtain serum and for further biochemical research. For the research 12 race horses from a training group were chosen. From time to time the animals took part in competitions; they were not specially used in races and were mostly used for the training of junior riders and sportsmen of different levels. Blood was taken in conditions of relative rest after ordinary training and after emotional stress during the entertainment performances when a large number of people were present and loud music was played. In the blood serum the following biochemical indicators were defined: whole protein, urea, creatinine, uric acid, total bilirubin and its fractions, glucose, cholestererol, triacylglycerol, calcium, ferrum, lactate, pyruvate, activity of the AlAT, SGOT, GGTP, LDH, an alkaline phosphatase – which makes it possible to determine reasonably accurately the adaptation potential of a horse under various types of loading. We established that during training and psychoemotional loading of racing horses of the training group of the Ukrainian riding breed, multidirectional changes in the level of biochemical indicators of blood serum occurred, which is evidence of stress in the metabolic processes in the animals’ organisms. Concentration of a biomarker of an oxidative stress, uric acid, increased after physical loading by 8.6%, and after emotional loading by 55.1%, which demonstrates that emotional stress had the more negative effect, indicating insufficient adaptation by the horses before demonstration performances. After physical loading, reaction of transamination in the horses’ liver cells intensified, and after emotional loading its intensity

Functional assay of the alternative complement pathway of rat serum

International Nuclear Information System (INIS)

Coonrod, J.D.; Jenkins, S.D.

1979-01-01

Two functional assays of the alternative pathway of complement activation in rat serum were developed. In the first assay, conditions were established for titration of alternative pathway activity by use of the 50% hemolytic end-point of rabbit red blood cells (RaRBC) in serum treated with ethyleneglycol-bis-(beta-aminoethyl ether)-N, N'-tetraacetic acid (EGTA). The second assay of alternative pathway activity was based on the opsonization of heat-killed radiolabeled pneumococci of serotype 25 (Pn25). Opsonization of Pn25 was shown to proceed entirely via the alternative pathway in rat serum. There was excellent correlation between the results obtained with the RaRBC lysis test and those obtained with the opsonization test. Because of its technical simplicity, the RaRBC lysis test appeared to be the single most useful test of alternative pathway activity in rat serum. (Auth.)

Supplementation with mixed tocopherols increases serum and blood cell gamma-tocopherol but does not alter biomarkers of platelet activation in subjects with type 2 diabetes.

Science.gov (United States)

Clarke, Michael W; Ward, Natalie C; Wu, Jason H Y; Hodgson, Jonathan M; Puddey, Ian B; Croft, Kevin D

2006-01-01

Some studies have shown potential benefit of vitamin E on platelet function, but several clinical trials failed to show improved cardiovascular outcome with alpha-tocopherol supplementation. Gamma-tocopherol, a major dietary form of vitamin E, may have protective properties different from those of alpha-tocopherol. We compared the effects of supplementation with alpha-tocopherol (500 mg) and a gamma-tocopherol-rich compound (500 mg, containing 60% gamma-tocopherol) on serum and cellular tocopherol concentrations, urinary tocopherol metabolite excretion, and in vivo platelet activation in subjects with type 2 diabetes. Fifty-eight subjects were randomly assigned to receive either 500 mg alpha-tocopherol/d, 500 mg mixed tocopherols/d, or matching placebo. Serum, erythrocyte, and platelet tocopherol and urinary metabolite concentrations were measured at baseline and after the 6-wk intervention. Soluble CD40 ligand, urinary 11-dehydro-thromboxane B2, serum thromboxane B2, soluble P-selectin, and von Willebrand factor were measured as biomarkers of in vivo platelet activation. Serum alpha-tocopherol increased with both tocopherol treatments. Serum and cellular gamma-tocopherol increased 4-fold (P tocopherol group, whereas red blood cell gamma-tocopherol decreased significantly after alpha-tocopherol supplementation. Excretion of alpha-carboxyethyl-hydroxychroman increased significantly after supplementation with alpha-tocopherol and mixed tocopherols. Excretion of gamma-carboxyethyl-hydroxychroman increased significantly after supplementation with mixed tocopherols and after that with alpha-tocopherol, which may reflect the displacement of gamma-tocopherol by alpha-tocopherol due to incorporation of the latter into lipoproteins in the liver. Neither treatment had any significant effect on markers of platelet activation. Supplementation with alpha-tocopherol decreased red blood cell gamma-tocopherol, whereas mixed tocopherols increased both serum alpha-tocopherol and

Serum Levels of Interleukin 33 and Soluble ST2 Are Associated with the Extent of Disease Activity and Cutaneous Manifestations in Patients with Active Adult-onset Still's Disease.

Science.gov (United States)

Han, Jae Ho; Suh, Chang-Hee; Jung, Ju-Yang; Ahn, Mi-Hyun; Kwon, Ji Eun; Yim, Hyunee; Kim, Hyoun-Ah

2017-06-01

Interleukin 33 (IL-33), a member of the IL-1 family and a ligand of the orphan receptor ST2, plays key roles in innate and adaptive immunity. We examined the associations between IL-33/ST2 levels and clinical manifestations of patients with active adult-onset Still's disease (AOSD). Blood samples were collected from 40 patients with active AOSD, 28 patients with rheumatoid arthritis (RA), and 27 healthy controls (HC). The serum levels of IL-33 and soluble ST2 were determined using ELISA. Expression levels of IL-33 and ST2 in biopsy specimens obtained from 34 AOSD patients with rash were immunohistochemically investigated. IL-33 levels of patients with AOSD were higher than those of patients with RA and HC. Soluble ST2 levels of patients with AOSD were higher than those of HC, but not of patients with RA. Serum IL-33 levels correlated with systemic score, erythrocyte sedimentation rate, ferritin levels, and aspartate transaminase levels. However, serum soluble ST2 levels correlated only with ferritin levels. The numbers of inflammatory cells expressing IL-33 and ST2 were elevated in skin lesions of patients with AOSD compared to HC, but did not differ from those of the skin lesions of eczema or psoriasis. We found significantly higher serum IL-33 and soluble ST2 levels in patients with active AOSD. Results indicate that the IL-33/ST2 signaling pathway may play a role in the pathogenesis of the acute inflammation and skin manifestations associated with AOSD.

Inhibition of platelet aggregation and in vitro free radical scavenging activity of dried fruiting bodies of Pleurotus eous.

Science.gov (United States)

Suseem, S R; Saral, Mary

2015-07-01

To evaluate the ethyl acetate, methanol and aqueous extracts of dried fruiting bodies of Pleurotus eous for its anti-platelet activity on human volunteer's blood. And also to analyze the free radical scavenging property of the extracts of P.eous by using various in vitro models. Anti-platelet activity of dried fruiting bodies of P.eous was evaluated by in vitro model using blood platelets. Inhibition of platelet aggregation was monitored after pre-incubation of platelets with the crude extracts of mushroom P.eous. Antioxidant activities of extracts of P.eous were evaluated by different in vitro experiments, namely, 1, 1-diphenyl-2-picryl hydrazyl (DPPH), superoxide, hydroxyl radical and lipid peroxide radical models. Crude extracts of mushroom P.eous inhibited platelet aggregation dose-dependently which was induced by adenosine diphosphate (ADP). At a maximum concentration of 10 mg/mL, methanol extract effected 64.02% inhibition of lipid per-oxidation and 50.12% scavenging effect on superoxide anion radical. Aqueous extract of P.eous have shown 69.43% chelating ability on ferrous ions, 24.27% scavenging effect on hydroxyl radical and 49.57% scavenging effect on DPPH radical at 10 mg/mL. Increasing concentrations of the extract were found to cause progressively decreasing of the intensity of absorbance. Anti-platelet effects could be related in part to the polyphenolic compounds present in the extracts. Antioxidant activity results indicated the free radical scavenging property of the extracts of P.eous which might be due to the high content of phenolic compounds and flavonoids.

Effect of ionising radiation and salt of cadmium on the activity enzymes in serum of chickens

International Nuclear Information System (INIS)

Kafka, I.; Danova, D.; Kalenicova, Z.; Toropila, M.

2008-01-01

The present study investigated changes of activities alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum of broiler chickens exposed to single of whole-body dose of 3 Gy gamma rays and concentration of cadmium 6 mg · kg -1 live weight. Samples of our experiment was analyse on the 7, 14. and 21 day after irradiation. (authors)

Technetium-99m-ECD SPECT in antiphospholipid antibody syndrome: a drastic improvement in brain perfusion by antiplatelet therapy

Energy Technology Data Exchange (ETDEWEB)

Tokumaru, Sunao; Yoshikai, Tomonori; Uchino, Akira; Kudo, Sho [Dept. of Radiology, Saga Medical School (Japan); Matsui, Makoto; Kuroda, Yasuo [Dept. of Neurology, Saga Medical School (Japan)

2001-12-01

We present a case of antiphospholipid antibody syndrome (APS) with repeated transient ischemic attacks (TIAs). Magnetic resonance imaging showed multiple cerebral infarcts and ischemic changes in the cerebral white matter. Cerebral angiographies showed no abnormalities. Technetium-99m-ethyl cysteinate dimer (Tc-99m-ECD) brain SPECT showed multiple decreased perfusion areas, which were more extensive than the lesions demonstrated on MRI. After treatment with an antiplatelet agent, the patient subsequently recovered from the TIAs. Although no interval changes were observed by MRI after therapy, follow-up Tc-99m-ECD SPECT revealed a marked improvement in brain perfusion. This is the first imaging report of remarkable post-therapy improvement in brain perfusion in APS cases. (orig.)

Technetium-99m-ECD SPECT in antiphospholipid antibody syndrome: a drastic improvement in brain perfusion by antiplatelet therapy

International Nuclear Information System (INIS)

Tokumaru, Sunao; Yoshikai, Tomonori; Uchino, Akira; Kudo, Sho; Matsui, Makoto; Kuroda, Yasuo

2001-01-01

We present a case of antiphospholipid antibody syndrome (APS) with repeated transient ischemic attacks (TIAs). Magnetic resonance imaging showed multiple cerebral infarcts and ischemic changes in the cerebral white matter. Cerebral angiographies showed no abnormalities. Technetium-99m-ethyl cysteinate dimer (Tc-99m-ECD) brain SPECT showed multiple decreased perfusion areas, which were more extensive than the lesions demonstrated on MRI. After treatment with an antiplatelet agent, the patient subsequently recovered from the TIAs. Although no interval changes were observed by MRI after therapy, follow-up Tc-99m-ECD SPECT revealed a marked improvement in brain perfusion. This is the first imaging report of remarkable post-therapy improvement in brain perfusion in APS cases. (orig.)

Interplay between daily rhythmic serum-mediated bacterial killing activity and immune defence factors in rainbow trout (Oncorhynchus mykiss)

DEFF Research Database (Denmark)

Lazado, Carlo Cabacang; Gesto, Manuel; Madsen, Lone

2018-01-01

manifested variations during the LD cycle, where anti-protease (ANTI) and myeloperoxidase (MPO) activities exhibited significant daily oscillation. However, there were no remarkable differences in the daily changes of serum factors amongst emergence fractions. Acrophase analysis revealed that the peaks...

Synovial tissue and serum biomarkers of disease activity, therapeutic response and radiographic progression: analysis of a proof-of-concept randomised clinical trial of cytokine blockade.

LENUS (Irish Health Repository)

Rooney, Terence

2012-02-01

OBJECTIVES: To evaluate synovial tissue and serum biomarkers of disease activity, therapeutic response and radiographic progression during biological therapy for rheumatoid arthritis (RA). METHODS: Patients with active RA entered a randomised study of anakinra 100 mg\\/day, administered as monotherapy or in combination with pegsunercept 800 microg\\/kg twice a week. Arthroscopic synovial tissue biopsies were obtained at baseline and two further time points. Following immunohistochemical staining, selected mediators of RA pathophysiology were quantified using digital image analysis. Selected mediators were also measured in the serum. RESULTS: Twenty-two patients were randomly assigned: 11 received monotherapy and 11 combination therapy. American College of Rheumatology 20, 50 and 70 response rates were 64%, 64% and 46% with combination therapy and 36%, 9% and 0% with monotherapy, respectively. In synovial tissue, T-cell infiltration, vascularity and transforming growth factor beta (TGFbeta) expression demonstrated significant utility as biomarkers of disease activity and therapeutic response. In serum, interleukin 6 (IL-6), matrix metalloproteinase (MMP) 1, MMP-3 and tissue inhibitor of metalloproteinase 1 (TIMP-1) were most useful in this regard. An early decrease in serum levels of TIMP-1 was predictive of the later therapeutic outcome. Pretreatment tissue levels of T-cell infiltration and the growth factors vascular endothelial growth factor\\/TGFbeta, and serum levels of IL-6, IL-8, MMP-1, TIMP-1, soluble tumour necrosis factor receptor types I and II and IL-18 correlated with radiographic progression. CONCLUSIONS: Synovial tissue analysis identified biomarkers of disease activity, therapeutic response and radiographic progression. Biomarker expression in tissue was independent of the levels measured in the serum.

Increased serum ß2-microglobulin is associated with clinical and immunological markers of disease activity in systemic lupus erythematosus patients

DEFF Research Database (Denmark)

Hermansen, M-L F; Hummelshøj, L; Lundsgaard, Dorte

2012-01-01

The objective of this study was to explore the relationship between serum levels of ß2-microglobulin (ß2MG), which some studies suggest reflect disease activity in systemic lupus erythematosus (SLE), and various clinical and immunological markers of disease activity in SLE. Twenty-six SLE patients...

Reassessing the Role of the Active TGF-β1 as a Biomarker in Systemic Sclerosis: Association of Serum Levels with Clinical Manifestations

Directory of Open Access Journals (Sweden)

Andréa Tavares Dantas

2016-01-01

Full Text Available Objective. To determine active TGF-β1 (aTGF-β1 levels in serum, skin, and peripheral blood mononuclear cell (PBMC culture supernatants and to understand their associations with clinical parameters in systemic sclerosis (SSc patients. Methods. We evaluated serum samples from 56 SSc patients and 24 healthy controls (HC. In 20 SSc patients, we quantified spontaneous or anti-CD3/CD28 stimulated production of aTGF-β1 by PBMC. The aTGF-β1 levels were measured by ELISA. Skin biopsies were obtained from 13 SSc patients and six HC, and TGFB1 expression was analyzed by RT-PCR. Results. TGF-β1 serum levels were significantly higher in SSc patients than in HC (p < 0.0001. Patients with increased TGF-β1 serum levels were more likely to have diffuse subset (p = 0.02, digital ulcers (p = 0.02, lung fibrosis (p < 0.0001, positive antitopoisomerase I (p = 0.03, and higher modified Rodnan score (p = 0.046. Most of our culture supernatant samples had undetectable levels of TGF-β1. No significant difference in TGFB1 expression was observed in the SSc skin compared with HC skin. Conclusion. Raised active TGF-β1 serum levels and their association with clinical manifestations in scleroderma patients suggest that this cytokine could be a marker of fibrotic and vascular involvement in SSc.

Glucose-induced serum- and glucocorticoid-regulated kinase activation in oncofetal fibronectin expression

International Nuclear Information System (INIS)

Khan, Zia A.; Barbin, Yousef P.; Farhangkhoee, Hana; Beier, Norbert; Scholz, Wolfgang; Chakrabarti, Subrata

2005-01-01

Preferential expression of oncofetal extra domain-B fibronectin (EDB + FN), a proposed angiogenic marker, has been shown in proliferative diabetic retinopathy. High levels of glucose also increase EDB + FN expression in endothelial cells (ECs) via transforming growth factor-β1 (TGF-β1) and endothelin-1 (ET-1). The present study was aimed at elucidating the role of serum- and glucocorticoid-regulated kinase (SGK-1) in glucose-induced EDB + FN expression. Using human macro- and microvascular ECs, we show that high levels of glucose, TGF-β1, and ET-1 increase the EDB + FN expression via SGK-1 alteration at the mRNA, protein, and activity levels. Inhibition of TGF-β1 and ET-1 prevented glucose-induced SGK-1 activation and the EDB + FN expression. Furthermore, using siRNA-mediated SGK-1 gene silencing, we show that glucose-induced EDB + FN expression can be completely prevented. These findings provide first evidence of glucose-induced SGK-1 activation in altered EDB + FN expression and provide novel avenues for therapeutic modalities

Hepatic copper content, urinary copper excretion, and serum ceruloplasmin in liver disease. [Activation analysis

Energy Technology Data Exchange (ETDEWEB)

Ritland, S; Skrede, S [Rikshospitalet, Oslo (Norway); Steinnes, E [Institutt for Atomenergi, Kjeller (Norway)

1977-01-01

Liver copper content, urinary copper output and plasma ceruloplasmin have been evaluated in a variety of liver disorders. An activation analysis procedure for the determination of liver copper content is described. Dried biopsy samples were irradiated for two days at a thermal neutron flux of 1.5x10/sup 13/ ncm/sup -2/sec/sup -1/. After one day's delay the samples were dissolved in an acid mixture with copper carrier, and separated on an anion exchange column. The /sup 64/Cu activity in the separated fractions was recorded by gamma spectrometry using a Ge(Li) solid detector. The urinary copper excretion and the serum ceruloplasmin were determined by conventional laboratory methods.

Serum and urine metabolomic fingerprinting in diagnostics of inflammatory bowel diseases.

Science.gov (United States)

Dawiskiba, Tomasz; Deja, Stanisław; Mulak, Agata; Ząbek, Adam; Jawień, Ewa; Pawełka, Dorota; Banasik, Mirosław; Mastalerz-Migas, Agnieszka; Balcerzak, Waldemar; Kaliszewski, Krzysztof; Skóra, Jan; Barć, Piotr; Korta, Krzysztof; Pormańczuk, Kornel; Szyber, Przemyslaw; Litarski, Adam; Młynarz, Piotr

2014-01-07

To evaluate the utility of serum and urine metabolomic analysis in diagnosing and monitoring of inflammatory bowel diseases (IBD). Serum and urine samples were collected from 24 patients with ulcerative colitis (UC), 19 patients with the Crohn's disease (CD) and 17 healthy controls. The activity of UC was assessed with the Simple Clinical Colitis Activity Index, while the activity of CD was determined using the Harvey-Bradshaw Index. The analysis of serum and urine samples was performed using proton nuclear magnetic resonance (NMR) spectroscopy. All spectra were exported to Matlab for preprocessing which resulted in two data matrixes for serum and urine. Prior to the chemometric analysis, both data sets were unit variance scaled. The differences in metabolite fingerprints were assessed using partial least-squares-discriminant analysis (PLS-DA). Receiver operating characteristic curves and area under curves were used to evaluate the quality and prediction performance of the obtained PLS-DA models. Metabolites responsible for separation in models were tested using STATISTICA 10 with the Mann-Whitney-Wilcoxon test and the Student's t test (α = 0.05). The comparison between the group of patients with active IBD and the group with IBD in remission provided good PLS-DA models (P value 0.002 for serum and 0.003 for urine). The metabolites that allowed to distinguish these groups were: N-acetylated compounds and phenylalanine (up-regulated in serum), low-density lipoproteins and very low-density lipoproteins (decreased in serum) as well as glycine (increased in urine) and acetoacetate (decreased in urine). The significant differences in metabolomic profiles were also found between the group of patients with active IBD and healthy control subjects providing the PLS-DA models with a very good separation (P value fingerprinting of serum and urine has the potential to be a useful tool in distinguishing patients with active IBD from those in remission.

Age-specific risks, severity, time course, and outcome of bleeding on long-term antiplatelet treatment after vascular events: a population-based cohort study.

Science.gov (United States)

Li, Linxin; Geraghty, Olivia C; Mehta, Ziyah; Rothwell, Peter M

2017-07-29

Lifelong antiplatelet treatment is recommended after ischaemic vascular events, on the basis of trials done mainly in patients younger than 75 years. Upper gastrointestinal bleeding is a serious complication, but had low case fatality in trials of aspirin and is not generally thought to cause long-term disability. Consequently, although co-prescription of proton-pump inhibitors (PPIs) reduces upper gastrointestinal bleeds by 70-90%, uptake is low and guidelines are conflicting. We aimed to assess the risk, time course, and outcomes of bleeding on antiplatelet treatment for secondary prevention in patients of all ages. We did a prospective population-based cohort study in patients with a first transient ischaemic attack, ischaemic stroke, or myocardial infarction treated with antiplatelet drugs (mainly aspirin based, without routine PPI use) after the event in the Oxford Vascular Study from 2002 to 2012, with follow-up until 2013. We determined type, severity, outcome (disability or death), and time course of bleeding requiring medical attention by face-to-face follow-up for 10 years. We estimated age-specific numbers needed to treat (NNT) to prevent upper gastrointestinal bleeding with routine PPI co-prescription on the basis of Kaplan-Meier risk estimates and relative risk reduction estimates from previous trials. 3166 patients (1582 [50%] aged ≥75 years) had 405 first bleeding events (n=218 gastrointestinal, n=45 intracranial, and n=142 other) during 13 509 patient-years of follow-up. Of the 314 patients (78%) with bleeds admitted to hospital, 117 (37%) were missed by administrative coding. Risk of non-major bleeding was unrelated to age, but major bleeding increased steeply with age (≥75 years hazard ratio [HR] 3·10, 95% CI 2·27-4·24; pbleeds (5·53, 2·65-11·54; pbleeds (≥75 years HR 4·13, 2·60-6·57; pbleeds were mostly disabling or fatal (45 [62%] of 73 patients vs 101 [47%] of 213 patients with recurrent ischaemic stroke), and outnumbered

EVALUATION OF IL1-α AND TNF-α SERUM LEVELS IN RHEUMATOID ARTHRITIS PATIONTS WITH ACTIVE AND INACTIVE, WITH OR WITHOUT BONE EROSION

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AR. Rostamian

2007-09-01

Full Text Available Rheumatoid arthritis is the most common inflammatory joint disease with 1 percent prevalence in community which presents with symmetrical polyarthritis of hands with inflammatory behavior. Several studies in recent years were conducted for evaluation of inflammatory cytokines such as IL1-α (Interlukin 1α and TNF- α (Tumor necrosis factor in rheumatologic disorders including rheumatoid arthritis to find new treatment methods base to pathogenesis. In this study different serum levels of IL1-α and TNF- α in 160 rheumatoid arthritis patients with active and inactive disease and also disease with or without bone erosion are assessed. 4% of our patients had rheumatoid nodule and 70% of all patients had positive RF, IL1-α, and TNF- α levels. Active with bone erosion patients had IL1-α and TNF- α serum levels higher than active without bone erosion patients; it was not significant in T-test but it was significant in Mann-Whitney Test. The results was the same as expected; IL1-α, and TNF- α serum levels were higher in active with bone erosion in comparison with inactive without bone erosion patients.

Serum biomarkers for the early diagnosis of TIA: The MIND-TIA study protocol.

Science.gov (United States)

Dolmans, L Servaas; Rutten, Frans H; El Bartelink, Marie-Louise; Seppenwoolde, Gerdien; van Delft, Sanne; Kappelle, L Jaap; Hoes, Arno W

2015-07-28

A Transient Ischaemic Attack (TIA) bears a high risk of a subsequent ischaemic stroke. Adequate diagnosis of a TIA should be followed immediately by the start of appropriate preventive therapy, including antiplatelets. The diagnosis of a TIA based on symptoms and signs only is notoriously difficult and biomarkers of brain ischaemia might improve the recognition, and target management and prognosis of TIA patients. Our aim is to quantify the added diagnostic value of serum biomarkers of brain ischaemia in patients suspected of TIA. a cross-sectional diagnostic accuracy study with an additional six month follow-up period. 350 patients suspected of TIA in the primary care setting. Patients suspected of a TIA will be recruited by at least 200 general practitioners (GPs) in the catchment area of seven TIA outpatient clinics willing to participate in the study. In all patients a blood sample will be drawn as soon as possible after the patient has contacted the GP, but at least within 72 h after onset of symptoms. Participants will be referred by the GP to the regional TIA outpatient clinic for additional investigations, including brain imaging. The 'definite' diagnosis (reference standard) will be made by a panel consisting of three experienced neurologists who will use all available diagnostic information and the clinical information obtained during the outpatient clinic assessment, and a six month follow-up period. The diagnostic accuracy, and value in addition to signs and symptoms of candidate serum biomarkers will be assessed in terms of discrimination with C statistics, and calibration with plots. We aim to include 350 suspected cases, with 250 patients with indeed definite TIA (or minor stroke) according to the panel. We hope to find novel biomarkers that will enable a rapid and accurate diagnosis of TIA. This would largely improve the management and prognosis of such patients. ClinicalTrials.gov Identifier NCT01954329.

[Bactericidal activity of serum and chemotherapy in sensitive and resistant exciter (author's transl)].

Science.gov (United States)

Eyer, H; Metz, H; Preac-Mursic, V

1975-11-21

Comparing examinations with Ampicillin sensitive and resistant bacteria-strains show that the bactericidal activity of serum is dependent on the bacteria-strains, on the Ampicillin sensitivity of the particular exciter and on the number of bacteria/ml (germ count). Bactericide effect could always be obtained with sensitive strains as a result of additional chemotherapy. With several resistant strains a bactericide effect could not be obtained in this case the continuous optimal Ampicillin addition was the decisive factor. Because of the extremely complicated process of the bactericide one should not make general conclusions from the individual experimental results.

Serum γ-Glutamyltransferase, Alanine Aminotransferase and Aspartate Aminotransferase Activity in Healthy Blood Donor of Different Ethnic Groups in Gorgan.

Science.gov (United States)

Marjani, Abdoljalal; Mehrpouya, Masoumeh; Pourhashem, Zeinab

2016-07-01

Measure of liver enzymes may help to increase safety of blood donation for both blood donor and recipient. Determination of liver enzymes may prepare valuable clinical information. To assess serum γ-Glutamyltransferase (GGT), Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) activities in healthy blood donors in different ethnic groups in Gorgan. This study was performed in 450 healthy male blood donors, in three ethnic groups (Fars, Sistanee and Turkman) who attended Gorgan blood transfusion center. Liver enzymes (GGT, ALT and AST) were determined. Serum AST and ALT in three ethnic groups were significant except for serum GGT levels. There was significant correlation between family histories of liver disease and systolic blood pressure and AST in Fars, and GGT in Sistanee ethnic groups. Several factors, such as age, family history of diabetes mellitus, family history of liver disease and smoking habit had no effect on some liver enzymes in different ethnic groups in this area. Variation of AST, ALT, and GGT enzyme activities in healthy subjects was associated with some subjects in our study groups. According to our study, it suggests that screening of AST and GGT enzymes in subjects with family history of liver disease is necessary in different ethnic groups.

Serum Levels of Soluble P-Selectin Are Increased and Associated With Disease Activity in Patients With Behçet's Syndrome

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Yusuf Turkoz

2005-01-01

Full Text Available Behçet's syndrome (BS is a relapsing, chronic, inflammatory disease characterized by endothelial dysfunction, atherothromboembogenesis, and leukocytoclastic vasculitis with complex immunologic molecular interactions. Generalized derangements of the lymphocyte and neutrophil populations, activated monocytes, and increased PMNLs motility with upregulated cell surface molecules such as ICAM-1, VCAM-1, and E-selectin, which are found on the endothelial cells, leukocytes, and platelets, have all been demonstrated during the course of BS. Our aim is to investigate the association of serum concentrations of soluble P-selectin in patients with BS, and to evaluate whether disease activity has an effect on their blood levels. This multicenter study included 31 patients with BS (15 men and 16 women and 20 age- and sex-matched healthy control volunteers (11 men and nine women. Neutrophil count, erythrocyte sedimentation rate, and acute-phase reactants as well as soluble P-selectin levels were determined. The mean age and sex distributions were similar (P>.05 between BS patients (35 years and control volunteers (36 years. Serum levels of soluble P-selectin in patients with BS (399 ± 72 ng/mL were significantly (P<.001 higher when compared with control subjects (164±40   ng/mL. In addition, active BS patients (453±37 ng/mL had significantly (P<.001 elevated levels of soluble P-selectin than those in inactive period (341±52 ng/mL. This study clearly demonstrated that serum soluble P-selectin levels are increased in BS patients when compared with control subjects, suggesting a modulator role for soluble P-selectin during the course of platelet activation and therefore, atherothrombogenesis formation in BS, especially in active disease.

Serum biomarkers for the early diagnosis of TIA : The MIND-TIA study protocol

NARCIS (Netherlands)

Dolmans, LS; Rutten, FH; Bartelink, Marie-Louise; Seppenwoolde, Gerdien; van Delft, Sanne; Kappelle, L Jaap; Hoes, Arno W

2015-01-01

BACKGROUND: A Transient Ischaemic Attack (TIA) bears a high risk of a subsequent ischaemic stroke. Adequate diagnosis of a TIA should be followed immediately by the start of appropriate preventive therapy, including antiplatelets. The diagnosis of a TIA based on symptoms and signs only is

Fatty acyltranferases in serum in cystic fibrosis (CF) patients

International Nuclear Information System (INIS)

Zielenski, J.; Newman, L.J.; Slomiany, B.L.; Slomiany, A.

1987-01-01

Studies on serum and gastrointestinal secretion from CF patient is suggest that defective accumulation of mucus in gastrointestinal tract and excessive amount of a protease resistant peptides in serum are related to the abnormal activity of enzymes responsible for fatty acylation of proteins. Here, the authors investigated the fatty acyltransferase activities in serum of normal and CF patients. A 15μl of serum was mixed with 0.85 nmol [ 14 C]palmitoyl CoA, 200μg of serine and threonine and incubated at 37 0 C for 30 min. The incubates were immediately frozen, dried extracted with C/M and chromatographed in chloroform/methanol/water. The incorporation of [ 14 C]palmitate was determined using linear radioscanner and authoradiography. The results of HPTLC revealed that CF serum in addition of ACAT and LCAT contained enzymes responsible for the transfer of [ 14 C]palmitate to monoacylphosphoglycerides, and serine and threonine. In normal serum the formation of a small amount of palmitoyl serine and palmitoyl threonine was also observed but the acylation of monoacylphosphoglycerides was not detectable. The authors conclude that in cystic fibrosis the abnormal fatty acyltransferases are responsible for the occurrence of protease resistant glycoprotein, unusual peptides in serum and possibly for the modification of membrane proteins and lipids

Role of Serum Iron in the Activation of Lipid Peroxidation in Critical Conditions

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Yu. P. Orlov

2006-01-01

Full Text Available Twenty-four critically ill patients due to generalized purulent peritonitis, pancreatonecrosis, thermal skin injuries, and severe poisoning by acetic acid were examined. The general regularities of the effect of high serum iron concentrations on the health status of patients, on the activity of antioxidative enzymes, and on the initiation of lipid peroxidation (LPO processes, as supported by the values of Fe2+-induced chemiluminescence, were revealed. In critically ill patients, iron metabolism occurs with the overload of a transport protein, such as transferrin, which is caused by intravascular hemolysis and hemoglobin metabolism to ionized iron. The overload of proteins responsible for iron transport leads to the tissue accumulation of free (ferrous and ferric iron that is actively involved in the processes of LPO initiation with excess synthesis of cytotoxic radicals, which in turn accounts for the severity of endotoxicosis.

Drugs elevating extracellular adenosine administered in vivo induce serum colony-stimulating activity and interleukin-6 in mice

Czech Academy of Sciences Publication Activity Database

Weiterová, Lenka; Hofer, Michal; Pospíšil, Milan; Znojil, V.; Štreitová, Denisa

2007-01-01

Roč. 56, č. 4 (2007), s. 463-473 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GP305/03/D050 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : extracellular adenosine * serum colony-stimulating activity * interleukin-6 Subject RIV: BO - Biophysics Impact factor: 1.505, year: 2007

Active Stat3 is required for survival of human squamous cell carcinoma cells in serum-free conditions

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DiGiovanni John

2006-04-01

Full Text Available Abstract Background Squamous cell carcinoma (SCC of the skin is the most aggressive form of non-melanoma skin cancer (NMSC, and is the single most commonly diagnosed cancer in the U.S., with over one million new cases reported each year. Recent studies have revealed an oncogenic role of activated signal transducer and activator of transcription 3 (Stat3 in many human tumors, especially in those of epithelial origin, including skin SCC. Stat3 is a mediator of numerous growth factor and cytokine signaling pathways, all of which activate it through phosphorylation of tyrosine 705. Results To further address the role of Stat3 in skin SCC tumorigenesis, we have analyzed a panel of human skin-derived cell lines ranging from normal human epidermal keratinocytes (NHEK, to non-tumorigenic transformed skin cells (HaCaT, to highly tumorigenic cells (SRB1-m7 and SRB12-p9 and observed a positive correlation between Stat3 phosphorylation and SCC malignancy. We next determined the role of Stat3 activity in cell proliferation and viability under serum-free culture conditions. This was accomplished by suppressing Stat3 activity in the SRB12-p9 cells through stable expression of a dominant negative acting form of Stat3β, which contains a tyrosine 705 to phenylalanine mutation (S3DN. The S3DN cells behaved similar to parental SRB12-p9 cells when cultured in optimal growth conditions, in the presence of 10% fetal calf serum. However, unlike the SRB12-p9 cells, S3DN cells underwent apoptotic cell death when cultured in serum-free medium (SFM. This was evidenced by multiple criteria, including accumulation of sub-G1 particles, induced PARP cleavage, and acquisition of the characteristic morphological changes associated with apoptosis. Conclusion This study provides direct evidence for a role for Stat3 in maintaining cell survival in the conditions of exogenous growth factor deprivation produced by culture in SFM. We also propose that delivery of the S3DN gene or

2.6. Sorption of serum albumin by ethynyl-piperidol hydrogels

International Nuclear Information System (INIS)

Khalikov, D.Kh.

2012-01-01

The sorption of serum albumin by ethynyl-piperidol hydrogels was studied in this article. Albumins adsorption on the surface of solids was considered. The capacity of cross-linked ethynyl piperidol polymers to the serum albumin was considered as well. The kinetic curves of sorption of human serum albumin by triple copolymer of isopropenyl trimethyl ethynyl piperidol were constructed. Sorption activity of ethynyl-piperidol polymers depending on ph of solution of human serum albumin were defined. Influence of solution ionic strength on sorption of human serum albumin was defined as well. The desorption of human serum albumin from the complexes with hydrogels was examined.

Serum prolidase activity and oxidative status in patients with bronchial asthma.

Science.gov (United States)

Cakmak, Alpay; Zeyrek, Dost; Atas, Ali; Celik, Hakim; Aksoy, Nurten; Erel, Ozcan

2009-01-01

Asthma is a disease where there is an accumulation of collagen in the reticular basal membrane of the airway leading to chronic inflammation. The enzyme prolidase plays an important role in the breakdown of collagen and the breakdown of intracellular protein especially in the final stage when peptides and dipeptides contain a high level of proline. To evaluate the relationship between prolidase activity and oxidative status in asthma patients. Comparison was made between 42 patients diagnosed with bronchial asthma and 32 healthy children of similar age and gender. Serum prolidase activity was measured spectrophotometrically. Oxidative status was determined using total antioxidant capacity (TAC) and total oxidant status (TOS) measurement. The prolidase activity of the asthma patient group was statistically significant compared with the control group (P< or =0.001). TAC and TOS levels in the asthma patient group were higher than the control group (P< or =0.001, P< or =0.002, respectively). No correlation was found between the prolidase and oxidative levels of the two groups. A positive correlation was determined between the prolidase activity and TAC in the asthma patient group (P< or =0.001, r=0.501). The prolidase enzyme activity, which plays a role in the collagen turnover, was low in the asthma patients; therefore, their collagen metabolism had undergone a change and this indicates that there may be an effect on the accumulation of collagen in the reticular basal membrane. Moreover, the high level of TOS indicates that these patients were exposed to severe oxidative stress with an increased TAC response. (c) 2009 Wiley-Liss, Inc.

Antiplatelet Effects of Qishen Yiqi Dropping Pill in Platelets Aggregation in Hyperlipidemic Rabbits

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Yi Wang

2012-01-01

Full Text Available We investigated the effects of Qishen Yiqi Dropping Pill (QSYQ on platelets aggregation and its possible mechanisms. Hyperlipidemic model in rabbits was produced by a high fat/cholesterol diet for 6 weeks, the therapeutic effect of QSYQ with 2.0 g/kg, 1.0 g/kg, and 0.5 g/kg was observed. Fourteen days after drug treatment, platelet aggregation induced by adenosine diphosphate (ADP, arachidonic acid (AA, and collagen (COLL was significantly reduced in rabbits of model group. Moreover, β-thromboglobulin (β-TG level decreased obviously but no significant change in P-selectin and platelet factor 4 (PF4 level, while QSYQ significantly decreased the ratio of thromboxane B2 (TXB2 to 6-keto-prostaglandin F1α (6-Keto-PGF1α and increased cyclic adenosine monophosphate (cAMP level in rabbits. In summary, QSYQ can improve platelets aggregation and inhibit the over-release of β-TG in hyperlipidemic rabbits; and the increased cAMP level may be involved in this process. These results suggest that the antiplatelet aggregation effect of QSYQ may be due to its ability to increase cAMP level for improving cAMP metabolism.

Comparative evaluation of direct thrombin and factor Xa inhibitors with antiplatelet agents under flow and static conditions: an in vitro flow chamber model.

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Kazuya Hosokawa

Full Text Available Dabigatran and rivaroxaban are novel oral anticoagulants that specifically inhibit thrombin and factor Xa, respectively. The aim of this study is to elucidate antithrombotic properties of these anticoagulant agents under arterial and venous shear conditions. Whole blood samples treated with dabigatran or rivaroxaban at 250, 500, and 1000 nM, with/without aspirin and AR-C66096, a P2Y12 antagonist, were perfused over a microchip coated with collagen and tissue thromboplastin at shear rates of 240 and 600 s(-1. Fibrin-rich platelet thrombus formation was quantified by monitoring flow pressure changes. Dabigatran at higher concentrations (500 and 1000 nM potently inhibited thrombus formation at both shear rates, whereas 1000 nM of rivaroxaban delayed, but did not completely inhibit, thrombus formation. Dual antiplatelet agents weakly suppressed thrombus formation at both shear rates, but intensified the anticoagulant effects of dabigatran and rivaroxaban. The anticoagulant effects of dabigatran and rivaroxaban were also evaluated under static conditions using thrombin generation (TG assay. In platelet-poor plasma, dabigatran at 250 and 500 nM efficiently prolonged the lag time (LT and moderately reduce peak height (PH of TG, whereas rivaroxaban at 250 nM efficiently prolonged LT and reduced PH of TG. In platelet-rich plasma, however, both anticoagulants efficiently delayed LT and reduced PH of TG. Our results suggest that dabigatran and rivaroxaban may exert distinct antithrombotic effects under flow conditions, particularly in combination with dual antiplatelet therapy.

Measures of anticholinergic drug exposure, serum anticholinergic activity, and all-cause postdischarge mortality in older hospitalized patients with hip fractures

NARCIS (Netherlands)

Mangoni, Arduino A.; van Munster, Barbara C.; Woodman, Richard J.; de Rooij, Sophia E.

Objectives: To assess possible associations between anticholinergic drug exposure and serum anticholinergic activity (SAA) and their capacities to predict all-cause mortality in older hospitalized patients. Setting: Academic medical center. Participants and Measurements: Data on clinical

Changes of serum sex hormones levels in aged patient with peptic ulcer

International Nuclear Information System (INIS)

Huang Xiuhai; Xiao Chuangqing; He Yunnan; Li Xuewen; Bi Chao; Zhang Yifan

2005-01-01

Objective: To investigate the changes of serum contents of testosterone (T), estradiol (E 2 ) and cortisol (Cor) in aged patients with peptic ulcer. Methods: Serum T, E 2 and Cor levels were determined with CLIA in 86 aged patients with peptic ulcer both before treatment (active stage) and after treatment for 6 weeks (healing stage) as well as in 76 controls. Results: Serum contents of T and E 2 in the patients during active stage were significantly lower than those in patients during healing stage and in controls (both P 0.05). Conclusion: A lower serum T and E 2 contents was present in aged patients with peptic ulcer during active stage. (authors)

Analysis of serum adenosine deaminase (ADA) and ADA1 and ADA2 isoenzyme activities in HIV positive and HIV-HBV co-infected patients.

Science.gov (United States)

Khodadadi, Iraj; Abdi, Mohammad; Ahmadi, Abbas; Wahedi, Mohammad Saleh; Menbari, Shahoo; Lahoorpour, Fariba; Rahbari, Rezgar

2011-08-01

To determine adenosine deaminase (ADA) activity as a possible diagnostic marker in HIV and HIV-HBV co-infected patients. Blood samples were collected from 72 healthy, 33 HIV positive and 30 HIV-HBV co-infected subjects. Blood CD4+ cell count was recorded and serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total ADA, and ADA1 and ADA2 isoenzyme activities were determined. Serum ALT, AST, total ADA and ADA2 isoenzyme activities were significantly higher in HIV positive and HIV-HBV co-infected groups compare to the control (pADA activities (R(2)=0.589, pADA was significantly increased in HIV and HIV-HBV co-infections. Therefore, because of its low cost and simplicity to perform, ADA activity might be considered as a useful diagnostic tool among the other markers in these diseases. Copyright © 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Elevation of serum insulin concentration during euglycemic hyperinsulinemic clamp studies leads to similar activation of insulin receptor kinase in skeletal muscle of subjects with and without NIDDM

DEFF Research Database (Denmark)

Klein, H H; Vestergaard, H; Kotzke, G

1995-01-01

The role of skeletal muscle insulin receptor kinase in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM) was investigated. Muscle biopsies from 13 patients with NIDDM and 10 control subjects at fasting serum insulin concentrations and approximately 1,000 pmol/l steady-state serum...... insulin during euglycemic hyperinsulinemic clamps were immediately frozen. The biopsies were then solubilized, and the receptors were immobilized to anti-insulin receptor antibody-coated microwells. Receptor kinase and binding activities were consecutively measured in these wells. The increase in serum...... and control groups, respectively). Moreover, by selecting only the receptors that bound to anti-phosphotyrosine antibody, we found similar hyperinsulinemia-induced increases of this receptor fraction and its kinase activity in both study groups. In vitro activation of the immobilized receptors with 2 mmol...

Effect of Xylitol on Candida albicans resistance in serum (in vitro study

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Ria Puspitawati

2013-07-01

Full Text Available Xylitol is reported to inhibit the growth of C. albicans. Objectives: Investigating serum factor role in inhibiting the growth of C. albicans and the effect of 1%, 5%, 10% xylitol on C. albicans resistance in serum in vitro. Methods: Identification of C. albicans (oral swab of candidiasis patient was conducted using CHROMAgar, confirmed by germ tube test. The cultures were serially diluted, inoculated in Saburoud Dextrose Broth (SDB contained 0% (control, 1%, 5%, or 10% xylitol, and kept for 3 or 7 days. These inoculations were then exposed to either active or inactive serum (Fetal Bovine Serum heated in 65ºC for 30 minutes for 2 hours in 37ºC. The colony forming unit (CFU of C. albicans in Saburoud Dextrose Agar (SDA were counted after 2 days. C. albicans ATCC 10231 strain was used as a comparison. One-way ANOVA with 0.05 was used. Results: After 3 days cultured in media with or without xylitol, the CFU of C. albicans exposed to active serum were significantly lower than those exposed to inactive serum (p=0.032. Although not statistically significant (p=0.689, increased concentration of xylitol lead to increased resistance of C. albicans in active serum. Only 7 day exposure of 10% xylitol resulted in significantly higher growth of C. albicans (p=0.034. No significant difference of C. albicans CFU in active or inactive serum (p=0.404. Conclusion: Serum factor has role in inhibiting C. albicans growth in vitro. Exposure of 1%, 5%, or 10% xylitol for 3 or 7 days has no significant effect on C. albicans resistance in serum.DOI: 10.14693/jdi.v16i2.98

Measures of anticholinergic drug exposure, serum anticholinergic activity, and all-cause postdischarge mortality in older hospitalized patients with hip fractures

NARCIS (Netherlands)

Mangoni, Arduino A.; van Munster, Barbara C.; Woodman, Richard J.; de Rooij, Sophia E.

2013-01-01

To assess possible associations between anticholinergic drug exposure and serum anticholinergic activity (SAA) and their capacities to predict all-cause mortality in older hospitalized patients. Academic medical center. Data on clinical characteristics, full medication exposure, SAA, and 4

Improved activity of immobilized horseradish peroxidase on gold nanoparticles in the presence of bovine serum albumin

International Nuclear Information System (INIS)

Ni, Yuyang; Li, Jun; Huang, Zhenzhen; He, Ke; Zhuang, Jiaqi; Yang, Wensheng

2013-01-01

The using of macromolecular additives is known to be a simple and effective way to improve the activity of immobilized enzymes on solid support, yet the mechanism has not been well understood. Taking horseradish peroxidase (HRP) as an example, only 30 % of its catalytic activity was kept after being immobilized on the surface of 25-nm Au nanoparticles, mainly attributed to the conformational change of the heme-containing active site. The catalytic activity of HRP was significantly improved to 80 % when a certain amount of bovine serum albumin (BSA) was added at the initial stage of the immobilization. Systematic spectral investigation indicated that the addition of BSA inhibited the tertiary structure change around the active site, which was a prerequisite for improved activity of the immobilized HRP. Steady-state kinetic analyses revealed that the introduction of BSA could effectively improve the turnover rate of substrate to product in spite of slight reduced affinity to substrates, which also contributed to the improved catalytic activity

Association between absolute tumor burden and serum bone-specific alkaline phosphatase in canine appendicular osteosarcoma.

Science.gov (United States)

Sternberg, R A; Pondenis, H C; Yang, X; Mitchell, M A; O'Brien, R T; Garrett, L D; Helferich, W G; Hoffmann, W E; Fan, T M

2013-01-01

In dogs with appendicular osteosarcoma (OSA), increased pretreatment serum bone-specific alkaline phosphatase (BALP) activity is a negative prognostic factor, associated with shorter disease-free intervals and survival times, but a biologic basis for observed differential serum BALP activities in canine OSA patients remains incompletely defined. Serum BALP activity will correlate with absolute tumor burden in dogs with OSA. This study included 96 client-owned dogs with appendicular OSA. In canine OSA cell lines, the expression and membranous release of BALP was evaluated in vitro. The correlation between serum BALP activity and radiographic primary tumor size was evaluated in OSA-bearing dogs. In dogs developing visceral OSA metastases, serial changes in serum BALP activities were evaluated in relation to progression of macroscopic metastases, and visceral metastatic OSA cells were evaluated for BALP expression. In vitro, BALP expression was not associated with either tumorigenic or metastatic phenotype, rather the quantity of membranous BALP released was proportional with cell density. In dogs devoid of macroscopic metastases, there was a positive correlation between serum BALP activity and absolute primary tumor size. In dogs with progressive OSA metastases, serum BALP activity increased and coincided with the development of macroscopic metastases. OSA cells derived from visceral metastatic lesions retained BALP expression. Tumor burden is a determinant of serum BALP activity in dogs with appendicular OSA. The association between increased pretreatment BALP activity and negative clinical prognosis may simply be attributed to greater initial tumor burden, and consequently more advanced tumor stage. Copyright © 2013 by the American College of Veterinary Internal Medicine.

Factors Associated with the Serum Myostatin Level in Patients Undergoing Peritoneal Dialysis: Potential Effects of Skeletal Muscle Mass and Vitamin D Receptor Activator Use.

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Yamada, Shunsuke; Tsuruya, Kazuhiko; Yoshida, Hisako; Tokumoto, Masanori; Ueki, Kenji; Ooboshi, Hiroaki; Kitazono, Takanari

2016-07-01

Myostatin is a member of the transforming growth factor-β family, which regulates synthesis and degradation of skeletal muscle proteins and is associated with the development of sarcopenia. It is up-regulated in the skeletal muscle of chronic kidney disease patients and is considered to be involved in the development of uremic sarcopenia. However, serum myostatin levels have rarely been determined, and the relationship between serum myostatin levels with clinical and metabolic factors remains unknown. This cross-sectional study investigated the association between serum myostatin level and clinical factors in 69 outpatients undergoing peritoneal dialysis. Serum myostatin level was determined by commercially available enzyme-linked immunosorbent assay (ELISA). Univariable and multivariable analysis were conducted to determine factors associated with serum myostatin levels. The factors included age, sex, diabetes mellitus, dialysis history, body mass index, residual kidney function, peritoneal dialysate volume, serum biochemistries, and the use of vitamin D receptor activators (VDRAs). Mean serum myostatin level was 7.59 ± 3.37 ng/mL. There was no association between serum myostatin level and residual kidney function. Serum myostatin levels were significantly and positively associated with lean body mass measured by the creatinine kinetic method and negatively associated with the use of VDRAs after adjustment for potential confounding factors. Our study indicated that serum myostatin levels are associated with skeletal muscle mass and are lower in patients treated with VDRAs. Further studies are necessary to determine the significance of measuring serum myostatin level in patients undergoing peritoneal dialysis.

Potential role of peroxisome proliferator activated receptor gamma activation on serum visfatin and trace elements in high fat diet induced type 2 diabetes mellitus.

Science.gov (United States)

Tabassum, Arshia; Zaidi, Syeda Nuzhat Fatima; Yasmeen, Kausar; Mahboob, Tabassum

2018-07-15

Electrolytes and trace elements dysregulation play an important role in the progression of obesity and diabetes complications. The present study was designed to evaluate the insulin sensitizing effects of peroxisomes proliferators activated receptor gamma (PPAR-γ) agonist on trace elements in obesity induced type 2 diabetes mellitus and correlate with serum visfatin. Wistar rats were categorized into five groups. Group I served as control; Group II fed on high fat diet (HFD); Group III fed on HFD and treated with rosiglitazone (3 mg/kg) for 7 days; Group IV were T2DM rats induce by HFD and low dose of streptozotocin (i.p. 35 mg/kg); Group V was T2DM rats treated with rosiglitazone (3 mg/kg) for 7 days. Serum and tissues electrolytes levels and renal, hepatic and cardiac tissues trace elements were estimated by flame photometer and atomic absorption spectroscopy. Serum visfatin was estimated by ELISA. Pearson correlations were analyzed among fasting blood glucose (FBG), serum visfatin and tissues trace elements. Results of the current study showed hyponatremia, hyperkalemia, hypomagnesemia and hypercalcemia in HFD and T2DM groups. HFD and T2DM also showed elevated copper and iron levels; however, zinc and selenium levels were decreased. Rosiglitazone treatment increased the insulin sensitization and altered these changes. A Strong association was observed among FBG, serum visfatin and trace elements levels of HFD and T2DM. Obesity and diabetes mellitus disturbed visfatin, electrolytes and trace elements homeostasis. Rosiglitazone treatment restored these changes. The results of the study could serve as a basis for further studies for the prevention of diabetic complications. Copyright © 2018 Elsevier Inc. All rights reserved.

Antiplatelet drug selection in PCI to vein grafts in patients with acute coronary syndrome and adverse clinical outcomes

DEFF Research Database (Denmark)

Sirker, Alex; Kwok, Chun Shing; Kontopantelis, Evangelos

2018-01-01

OBJECTIVE: This study aims to evaluate outcomes associated with different P2Y12 agents in Saphenous Vein graft (SVG) percutaneous coronary intervention (PCI). BACKGROUND: SVG PCI is associated with greater risks of ischemic complications, compared with native coronary PCI. Outcomes associated...... with the use of potent P2Y12 blocking drugs, Prasugrel and Ticagrelor, in SVG PCI are unknown. METHODS: Patients included in the study underwent SVG PCI in the United Kingdom between 2007 and 2014 for acute coronary syndrome and were grouped by P2Y12 antiplatelet use. In-hospital major adverse cardiac events....... CONCLUSIONS: Our real world national study provides no clear evidence to indicate that use of potent P2Y12 blockers in SVG PCI is associated with improved clinical outcomes....

Serum 25-OH vitamin D level in treatment-naïve systemic lupus erythematosus patients: Relation to disease activity, IL-23 and IL-17.

Science.gov (United States)

Shahin, D; El-Farahaty, R M; Houssen, M E; Machaly, S A; Sallam, M; ElSaid, T O; Neseem, N O

2017-08-01

Objectives The aim of this study was to assess the vitamin D status in treatment-naïve SLE patients and its association with clinical and laboratory markers of disease activity, including serum levels of IL-17 and IL-23. Methods Fifty-seven treatment-naïve SLE patients along with 42 matched controls were included. SLEDAI score was used to estimate disease activity. Serum levels of 25(OH) D, IL-17 and IL-23 were measured. Results The median level of 25(OH) D in SLE patients (40.8; 4-70 ng/ml) was significantly lower than in the controls (47; 25-93 ng/ml) ( P = 0.001). A total of 38.6% of SLE cases had 25 (OH) D levels < 30 ng/ml (hypovitaminosis D) vs. 4.8% of the controls ( P < 0.0001). Apart from thrombocytopenia, vitamin D was not associated with clinical signs of SLE. There were negative correlations between serum 25(OH) D and serum levels of IL-17, IL-23 and ANA (rho = -0.5, -0.8, -0.5, P ≤ 0.05) in SLE patients. Conclusion Hypovitaminosis D is prevalent in treatment naïve SLE patients. It contributes to ANA antibody production and is associated with high serum levels of IL-23 and IL-17; thus they may trigger the inflammatory process in SLE.

Haematological and serum enzymes biomarkers of heavy metals in ...

African Journals Online (AJOL)

Haematological and serum enzymes biomarkers of heavy metals in Chrysichthys Nigrodigitatus and Cynoglossus senegalensis. ... Haematological and serum enzymes activities are predilective biomarkers for the detection and monitoring of aquatic ecosystems pollution. The inclusion of Allium sativum at 1.5g/kg is ...

Blood serum components and serum protein test of Hybro-PG broilers of different ages

Directory of Open Access Journals (Sweden)

PRL Silva

2007-12-01

Full Text Available Blood serum samples of HYBRO PG broilers were analyzed, with 30 samples collected from 21-day-old broilers (G1, 30 from 35-day-old birds (G2, and 30 from 42-day-old birds (G3, with the aim of establishing normal values of some blood serum parameters. The activities of the enzymes gamma-glutamyl-transferase (GGT, aspartate aminotransferase (AST, creatine kinase (CK, alkaline phosphatase (ALP, and lactate dehydrogenase (LDH, serum levels of total calcium, calcium ion, phosphorus, sodium, potassium, magnesium, chlorides, creatinine, uric acid, triglycerides, cholesterol, total protein, albumin, total and indirect and direct bilirubin, and electrophoretic profile of serum proteins in acrylamide (SDS-PAGE and agarose gel were determined. There was no influence of age on total bilirubin and albumin levels. All the other evaluated parameters presented differences in at least one age group. Protein electrophoretic profile also changed as a function of age. The obtained results can be considered as normal for the studied ages, and therefore be used as references for the interpretation of laboratory exams of broilers of this genetic line in the evaluated ages.

A novel protein from the serum of Python sebae, structurally homologous with type-γ phospholipase A(2) inhibitor, displays antitumour activity.

Science.gov (United States)

Donnini, Sandra; Finetti, Federica; Francese, Simona; Boscaro, Francesca; Dani, Francesca R; Maset, Fabio; Frasson, Roberta; Palmieri, Michele; Pazzagli, Mario; De Filippis, Vincenzo; Garaci, Enrico; Ziche, Marina

2011-12-01

Cytotoxic and antitumour factors have been documented in the venom of snakes, although little information is available on the identification of cytotoxic products in snake serum. In the present study, we purified and characterized a new cytotoxic factor from serum of the non-venomous African rock python (Python sebae), endowed with antitumour activity. PSS (P. sebae serum) exerted a cytotoxic activity and reduced dose-dependently the viability of several different tumour cell lines. In a model of human squamous cell carcinoma xenograft (A431), subcutaneous injection of PSS in proximity of the tumour mass reduced the tumour volume by 20%. Fractionation of PSS by ion-exchange chromatography yielded an active protein fraction, F5, which significantly reduced tumour cell viability in vitro and, strikingly, tumour growth in vivo. F5 is composed of P1 (peak 1) and P2 subunits interacting in a 1:1 stoichiometric ratio to form a heterotetramer in equilibrium with a hexameric form, which retained biological activity only when assembled. The two peptides share sequence similarity with PIP {PLI-γ [type-γ PLA(2) (phospholipase A(2)) inhibitor] from Python reticulatus}, existing as a homohexamer. More importantly, although PIP inhibits the hydrolytic activity of PLA(2), the anti-PLA(2) function of F5 is negligible. Using high-resolution MS, we covered 87 and 97% of the sequences of P1 and P2 respectively. In conclusion, in the present study we have identified and thoroughly characterized a novel protein displaying high sequence similarity to PLI-γ and possessing remarkable cytotoxic and antitumour effects that can be exploited for potential pharmacological applications.

The association between serum lipid levels, suicide ideation, and central serotonergic activity in patients with major depressive disorder.

Science.gov (United States)

Park, Young-Min; Lee, Bun-Hee; Lee, Seung-Hwan

2014-04-01

There is some evidence that low lipid levels cause suicide in depressed patients. The purpose of this study was to identify whether low serum lipid levels are associated with suicide ideation or are correlated with central serotonin function. Auditory processing for the loudness dependence of auditory evoked potentials (LDAEP) was measured in 73 outpatients with major depressive disorder. The Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI) were administered on the same day as measurement of the LDAEP. In addition, serum levels of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels were measured. All subjects had received antidepressant monotherapy. The depressed subjects were divided into those with and without suicide ideation according to the score for HAMD item 3 or BDI item 9. TG levels differed significantly between the two groups, whereas body mass index (BMI), total cholesterol, LDL, HDL, and LDAEP did not. The scores for HAMD item 3 and BDI item 9 were negatively correlated with TG levels (p=0.045 and 0.026, respectively). The LDAEP was negatively correlated with TG levels (p=0.012). Although there was tendency toward a negative correlation between the LDAEP and serum LDL, it did not reach statistical significance (p=0.068). The cross-sectional design of this study means that baseline serum lipid levels were not measured. The findings of this study revealed a relationship between TG and suicide ideation that is independent of both BMI and body weight. Furthermore, serum lipid levels were associated with central serotonergic activity, as assessed using the LDAEP. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of breed on plasma endothelin-1 concentration, plasma renin activity, and serum cortisol concentration in healthy dogs

DEFF Research Database (Denmark)

Höglund, K.; Lequarré, A.-S.; Ljungvall, I.

2016-01-01

BACKGROUND: There are breed differences in several blood variables in healthy dogs. OBJECTIVE: Investigate breed variation in plasma endothelin-1 (ET-1) concentration, plasma renin activity, and serum cortisol concentration. ANIMALS: Five-hundred and thirty-one healthy dogs of 9 breeds examined...... at 5 centers (2-4 breeds/center). METHODS: Prospective observational study. Circulating concentrations of ET-1 and cortisol, and renin activity, were measured using commercially available assays. Absence of organ-related or systemic disease was ensured by thorough clinical investigations, including...

Study on the relationship between SLE and the related serum hormone

International Nuclear Information System (INIS)

Lu Yun; Deng Shouzhen; Lin Xiangtong; Feng Shufang; Xu Jinhua; He Wanting; Zhang Guangming; Cheng Wei; Gao Quan

1998-01-01

To explore the relationship between PRL, GH(RIA), GH(RRA) serum levels changes and the onset and development of disease in patients with SLE, and to understand the hormonal changes in active and inactive phase of disease, 28 cases and 20 controls were studied. The results showed that anti-ds-DNA serum level in active and inactive phases was higher than those in controls (P 1 2 <0.05). This study indicated that the higher serum level of PRL, GH(RIA), GH(RRA) is correlated with some autoimmune characteristics of SLE, especially in its active phase. Therefore it gives some help for clinical study of SLE

Preoperative plasma plasminogen activator inhibitor type-1 and serum C-reactive protein levels in patients with colorectal cancer. The RANX05 Colorectal Cancer Study Group

DEFF Research Database (Denmark)

Nielsen, Hans Jørgen; Christensen, Ib Jarle; Sørensen, Steen

2000-01-01

study we analyzed the association between plasma PAI-1 and serum CRP in patients scheduled for elective resection of colorectal cancer. In addition, the prognostic value of PAI-1 and CRP was studied in this patient cohort. METHODS: PAI-1 and CRP were analyzed in citrated plasma and serum, respectively......, excluding patients with Dukes' D disease showed serum CRP to be an independent prognostic variable (P study did not show a strong correlation between plasma PAI-1 and serum CRP in patients with colorectal cancer. Serum CRP was found to be a Dukes......BACKGROUND: Preoperative plasma plasminogen activator inhibitor-1 (PAI-1) is a prognostic variable in patients with colorectal cancer. It has been suggested, however, that plasma PAI-1 is a nonspecific prognostic parameter similar to the acute-phase reactant C-reactive protein (CRP). In the present...

Emergence of anti-red blood cell antibodies triggers red cell phagocytosis by activated macrophages in a rabbit model of Epstein-Barr virus-associated hemophagocytic syndrome.

Science.gov (United States)

Hsieh, Wen-Chuan; Chang, Yao; Hsu, Mei-Chi; Lan, Bau-Shin; Hsiao, Guan-Chung; Chuang, Huai-Chia; Su, Ih-Jen

2007-05-01

Hemophagocytic syndrome (HPS) is a fatal complication frequently associated with viral infections. In childhood HPS, Epstein-Barr virus (EBV) is the major causative agent, and red blood cells (RBCs) are predominantly phagocytosed by macrophages. To investigate the mechanism of RBC phagocytosis triggered by EBV infection, we adopted a rabbit model of EBV-associated HPS previously established by using Herpesvirus papio (HVP). The kinetics of virus-host interaction was studied. Using flow cytometry, we detected the emergence of antibody-coated RBCs, as well as anti-platelet antibodies, at peak virus load period at weeks 3 to 4 after HVP injection, and the titers increased thereafter. The presence of anti-RBCs preceded RBC phagocytosis in tissues and predicted the full-blown development of HPS. The anti-RBC antibodies showed cross-reactivity with Paul-Bunnell heterophile antibodies. Preabsorption of the HVP-infected serum with control RBCs removed the majority of anti-RBC activities and remarkably reduced RBC phagocytosis. The RBC phagocytosis was specifically mediated via an Fc fragment of antibodies in the presence of macrophage activation. Therefore, the emergence of anti-RBC antibodies and the presence of macrophage activation are both essential in the development of HPS. Our observations in this animal model provide a potential mechanism for hemophagocytosis in EBV infection.

Multisite Investigation of Strategies for the Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy.

Science.gov (United States)

Empey, Philip E; Stevenson, James M; Tuteja, Sony; Weitzel, Kristin W; Angiolillo, Dominick J; Beitelshees, Amber L; Coons, James C; Duarte, Julio D; Franchi, Francesco; Jeng, Linda J B; Johnson, Julie A; Kreutz, Rolf P; Limdi, Nita A; Maloney, Kristin A; Owusu Obeng, Aniwaa; Peterson, Josh F; Petry, Natasha; Pratt, Victoria M; Rollini, Fabiana; Scott, Stuart A; Skaar, Todd C; Vesely, Mark R; Stouffer, George A; Wilke, Russell A; Cavallari, Larisa H; Lee, Craig R

2017-12-26

CYP2C19 genotype-guided antiplatelet therapy following percutaneous coronary intervention is increasingly implemented in clinical practice. However, challenges such as selecting a testing platform, communicating test results, building clinical decision support processes, providing patient and provider education, and integrating methods to support the translation of emerging evidence to clinical practice are barriers to broad adoption. In this report, we compare and contrast implementation strategies of 12 early adopters, describing solutions to common problems and initial performance metrics for each program. Key differences between programs included the test result turnaround time and timing of therapy changes, which are both related to the CYP2C19 testing model and platform used. Sites reported the need for new informatics infrastructure, expert clinicians such as pharmacists to interpret results, physician champions, and ongoing education. Consensus lessons learned are presented to provide a path forward for those seeking to implement similar clinical pharmacogenomics programs within their institutions. © 2018, The American Society for Clinical Pharmacology and Therapeutics.

Determination of total creatine kinase activity in blood serum using an amperometric biosensor based on glucose oxidase and hexokinase.

Science.gov (United States)

Kucherenko, I S; Soldatkin, O O; Lagarde, F; Jaffrezic-Renault, N; Dzyadevych, S V; Soldatkin, A P

2015-11-01

Creatine kinase (CK: adenosine-5-triphosphate-creatine phosphotransferase) is an important enzyme of muscle cells; the presence of a large amount of the enzyme in blood serum is a biomarker of muscular injuries, such as acute myocardial infarction. This work describes a bi-enzyme (glucose oxidase and hexokinase based) biosensor for rapid and convenient determination of CK activity by measuring the rate of ATP production by this enzyme. Simultaneously the biosensor determines glucose concentration in the sample. Platinum disk electrodes were used as amperometric transducers. Glucose oxidase and hexokinase were co-immobilized via cross-linking with BSA by glutaraldehyde and served as a biorecognition element of the biosensor. The biosensor work at different concentrations of CK substrates (ADP and creatine phosphate) was investigated; optimal concentration of ADP was 1mM, and creatine phosphate - 10 mM. The reproducibility of the biosensor responses to glucose, ATP and CK during a day was tested (relative standard deviation of 15 responses to glucose was 2%, to ATP - 6%, to CK - 7-18% depending on concentration of the CK). Total time of CK analysis was 10 min. The measurements of creatine kinase in blood serum samples were carried out (at 20-fold sample dilution). Twentyfold dilution of serum samples was chosen as optimal for CK determination. The biosensor could distinguish healthy and ill people and evaluate the level of CK increase. Thus, the biosensor can be used as a test-system for CK analysis in blood serum or serve as a component of multibiosensors for determination of important blood substances. Determination of activity of other kinases by the developed biosensor is also possible for research purposes. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of streptococcal preparation (picibanil) on the postoperative rise in serum alanine aminotransferase activity in patients with urogenital cancer.

OpenAIRE

Taketa, Kazuhisa; Ohmori, Hiroyuki; Matsumura, Yonesuke; Asahi, Toshihiko; Okimune, Masaaki

1980-01-01

The effect of Picibanil, a streptococcal agent, on the development of liver injury after operations for urogenital cancer was studied retrospectively in the light of serum alanine aminotransferase (ALT) activity. The series comprised 32 cases receiving Picibanil and 33 controls with otherwise comparable clinical backgrounds. Picibanil reduced the incidence of postoperative ALT rise over 50 U/l within 6 weeks but increased it thereafter. The increase in ALT activity after 6 weeks was relativel...

Mangifera indica L. (Vimang) protection against serum oxidative stress in elderly humans.

Science.gov (United States)

Pardo-Andreu, Gilberto L; Philip, Sarah J; Riaño, Annia; Sánchez, Carlos; Viada, Carmen; Núñez-Sellés, Alberto J; Delgado, René

2006-01-01

We searched for the protective effect of a natural extract from stem bark of Mangifera indica L. extract (Vimang) on age-related oxidative stress. Healthy subjects were classified in two groups, elderly (>65 years) and young group (Vimang tablets, 300 mg each, before meals) for 60 days. Serum concentration of lipid peroxides, serum peroxidation potential, extracellular superoxide dismutase activity (EC-SOD), glutathione status (GSH, GSSG, GSSG/GSH ratio)) and total antioxidant status (TAS) were determined before (both experimental groups) and 15, 30, and 60 days after treatment (only elderly group). We confirmed the existence of an age-associated oxidative stress in human serum as documented by an age-related increase in serum lipoperoxides and GSSG and a decrease in serum antioxidant capacity and EC-SOD activity. Vimang tablet supplementation increased EC-SOD activity (p Vimang tablets prevent age-associated oxidative stress in elderly humans, which could retard the onset of age-associated disease, improving the quality of life for elderly persons.

Study of the role of serum folic acid in atopic dermatitis: A correlation with serum IgE and disease severity

Directory of Open Access Journals (Sweden)

Maha A Shaheen

2011-01-01

Full Text Available Background : Most atopic dermatitis (AD patients have elevated serum immunoglobulin E (IgE. Impaired folic acid (FA metabolism was found to reduce the intracellular methyl donor pool, associated with a higher prevalence of atopy. Aim : To assess serum IgE and FA in AD patients and to correlate their levels with the disease severity, and with each other. Materials and Methods : Twenty patients with AD were assessed for serum FA and IgE, compared with 20 age- and sex-matched controls. Patients were classified into three groups (mild, moderate, and severe AD based on clinical severity according to Nottingham index. In both patients and controls, serum IgE was measured using Enzyme-linked immunosorbent assay technique and serum FA was measured using Microparticle Enzyme Immunoassay technique. Results : Serum FA levels were lower in AD patients compared with controls, but the difference was not statistically significant. FA levels did not show statistically significant difference among disease severity groups and did not correlate with serum IgE levels. On the other hand, serum IgE levels were significantly elevated in AD patients compared with controls, and among AD patients, its levels were significantly elevated in severe AD compared with mild and moderate disease. Conclusion : Serum IgE is useful in assessment of AD severity and activity. FA contribution to AD needs further investigations.

Association between serum levels of high sensitive C-reactive protein and inflammation activity in chronic gastritis patients.

Science.gov (United States)

Rahmani, Asghar; Moradkhani, Atefeh; Hafezi Ahmadi, Mohammad Reza; Jafari Heirdarlo, Ali; Abangah, Ghobad; Asadollahi, Khairollah; Sayehmiri, Kourosh

2016-01-01

Gastritis is an important premalignant lesion and recent studies suggested a production of inflammatory cytokine-like C-reactive protein during gastritis. This study aimed to determine any relationship between high sensitive C-reactive protein (hs-CRP) and inflammation activity among patients with gastritis. Demographic and clinical variables of participants were collected by a validated questionnaire. Using histology of the gastric mucosa, Helicobacter pylori status was investigated and serum concentrations of hs-CRP were measured among dyspeptic patients. Correlation between hs-CRP serum levels and inflammation activities was evaluated by logistic regression analysis. The relation between active inflammation and other variables was evaluated by logic link function model. Totally 239 patients (56.6% female) were analysed. The prevalence of mild, moderate and severe inflammation activities was 66.5%, 23.8% and 9.6% respectively. Mean ± SD of hs-CRP among men and women were 2.85 ± 2.84 mg/dl and 2.80 ± 4.80 mg/dl (p = 0.047) respectively. Mean ± SD of hs-CRP among patients with H. pylori infection, gland atrophy, metaplasia and dysplasia were 2.83 ± 3.80 mg/dl, 3.52 ± 5.1 mg/dl, 2.22 ± 2.3 mg/dl and 5.3 ± 5.04 mg/dl respectively. Relationship between hs-CRP and inflammation activities (p gastritis, elevated hs-CRP levels may be considered as a predictive marker of changes in gastric mucosa and a promising therapeutic target for patients with gastritis.

Serum levels of soluble urokinase plasminogen activator receptor is associated with parasitemia in children with acute Plasmodium falciparum malaria infection

DEFF Research Database (Denmark)

Perch, M; Kofoed, P; Fischer, TK

2004-01-01

Serum levels of soluble urokinase plasminogen activator receptor (suPAR) are significantly elevated and of prognostic value in patients suffering from serious infectious diseases such as HIV and tuberculosis. Our objective was to investigate suPAR levels during symptomatic malaria infection and 7...

Accuracy of serum luteinizing hormone and serum testosterone measurements to assess the efficacy of medical castration in prostate cancer patients.

Science.gov (United States)

Morote, Juan; Comas, Imma; Ferrer, Roser; Planas, Jacques; Celma, Anna; Regis, Lucas

2017-10-22

Luteinizing hormone-releasing hormone (LH-RH) agonists are the standard for androgen deprivation therapy (ADT) in prostate cancer (PCa) patients. Current guidelines recommend serum testosterone measurement to assess the efficacy of ADT and to define castration resistance. However, serum testosterone does not reflect the exclusive effect of castration due to its extratesticular production. The aim of this study is to analyze if serum LH reflects better than serum testosterone the activity of LH-RH agonists. Serum LH and serum testosterone were measured with chemiluminescent immunoassay (CLIA) in a cohort study of 1091 participants: 488 PCa patients "on LH-RH agonists", 303 "off LH-RH agonist" in whom LH-RH agonists were withdrawn, and 350 men with PCa suspicion "no LH-RH agonist" who never received LH-RH agonists. In a validation cohort of 147 PCa patients, 124 on "LH-RH agonists" and 19 "off LH-RH agonists", serum testosterone was also measured with liquid chromatography and tandem mass spectrometry (LC MSMS). The area under the curve (AUC) to distinguish patients "on versus off LH-RH agonists" was 0.997 for serum LH and 0.740 for serum testosterone, P < 0.001. The 97.5 percentile of serum LH in patients "on LH-RH agonists" was 0.97 U/L, been the most efficient threshold 1.1 U/L. The AUCs for serum LH, testosterone measured with CLIA and with LC MSMS, in the validation cohort, were respectively 1.000, 0.646 and 0.814, P < 0.001. The efficacy to distinguish patients "on versus off LH-RH agonists" was 98.6%, 78.3%, and 89.5% respectively, using 1.1 U/L as threshold for serum LH and 50 ng/dL for serum testosterone regardless the method. Serum LH is more accurate than serum testosterone regardless the method, to distinguish patients "on versus off LH-RH agonists". The castrate level of serum LH is 1.1 U/l. These findings suggest that assessment of LH-RH agonist efficacy and castration resistance definition should be reviewed.