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Aims: The aim of this study was to evaluate the effects of yoga-based cardiac rehabilitation (Yoga-CaRe) on the endothelial system, oxidative stress, and inflammatory markers in patients with acute myocardial infarction (MI). Methods: A sub-study was conducted in two clinical sites of the Yoga-CaRe trial (a multicenter randomized controlled trial). Participants with acute MI were randomized and allocated to either the Yoga-CaRe program (13 sessions with encouragement to home practice) or enhanced standard care (three educational sessions). Endothelial function, oxidative stress, and inflammatory biomarkers were assessed using biomarkers such as asymmetric dimethylarginine (ADMA), endothelial nitric oxide synthase (eNOS), endothelin-1 (ET-1), E-selectin, P-selectin, vascular cell adhesion molecule (VCAM), intercellular cell-adhesion molecule-1, total nitric oxide concentration (NOx), oxidized low-density lipoprotein (Oxd-LDL), superoxide dismutase, total antioxidant capacity (TAOC), tumor necrosis factor-alpha (TNFα), and C-reactive protein (CRP) at baseline and 12 weeks. Laboratory and statistical analysis were done by staff blinded to group allocation. Results: Eighty-two patients (of the 110 patients recruited) completed the study. The mean age was 53.1 ± 10.6 and 51.9 ± 10.7 years in enhanced standard care and Yoga-CaRe group, respectively. At 12 weeks, Yoga-CaRe significantly reduced ADMA, ET-1, and ICMA-1 than the enhanced standard care group. Although E-selectin and VCAM at 12 weeks were reduced in both groups, enhanced standard care had a significantly higher reduction than the Yoga-CaRe group. Among markers of oxidative stress, TAOC increased in the Yoga-CaRe group. We found no difference in eNOS, NOx, P-selectin, TNFα, CRP, and Oxd-LDL between the two groups. Conclusion: Yoga-CaRe improved the endothelial function (through a reduction in ET-1 and modulating adhesion molecules) and enhanced antioxidant capacity.
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OBJECTIVE: To investigate the oral psychosomatic disorders (PSDs) in family caregivers (FCs) of oral cancer (OC) patients and to evaluate the correlation between these oral PSDs to severity of depression anxiety and stress. METHODS: A total of 50 participants were included each in first degree relative (FDR), second degree relative (SDR) and control group. All the participants completed DASS-21 questionnaire and were subjected to thorough clinical history and oral examination. RESULTS: All the FCs reported statistically significant higher mean levels of depression, anxiety and stress compared to controls (pË0.001). A significantly greater number of FCs (40.00%) reported oral PSDs than control group (12.00%). Most prevalent oral PSD in FCs was aphthous stomatitis followed by oral lichen planus, bruxism, burning mouth syndrome and myofascial pain dysfunction syndrome. Moreover, there was a preponderance of these diseases in FDR (60.86%) compared to SDR (26.08%). FCs with moderate to very severe depression, anxiety and stress showed higher prevalence of these oral PSDs compared to the ones with mild depression, anxiety and stress. CONCLUSION: The observations of higher prevalence of oral PSDs in FCs with psychological alterations can enhance healthcare professionals' awareness to better understand FCs' oral healthcare needs.
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Subject(s)
Carcinoma, Squamous Cell/psychology , Caregivers/psychology , Family/psychology , Mouth Neoplasms/psychology , Psychophysiologic Disorders/epidemiology , Adult , Anxiety/epidemiology , Carcinoma, Squamous Cell/therapy , Case-Control Studies , Cross-Sectional Studies , Depression/epidemiology , Female , Humans , Male , Middle Aged , Mouth Neoplasms/therapy , Prevalence , Psychophysiologic Disorders/diagnosis , Severity of Illness Index , Socioeconomic Factors , Stress, Psychological/epidemiology , Surveys and QuestionnairesABSTRACT
We observed enhanced field emission (FE) behavior for spitzer shaped ZnO nanowires synthesized via a hydrothermal approach. The spitzer shaped and pointed tipped 1D ZnO nanowires of average diameter 120 nm and length â¼5-6 µm were randomly grown over an ITO coated glass substrate. The turn-on field (E on) of 1.56 V µm-1 required to draw a current density of 10 µA cm-2 from these spitzer shaped ZnO nanowires is significantly lower than that of pristine and doped ZnO nanostructures, and MoS2@TiO2 heterostructure based FE devices. The orthodoxy test that was performed confirms the feasibility of a field enhancement factor (ß FE) of 3924 for ZnO/ITO emitters. The enhancement in FE behavior can be attributed to the spitzer shaped nanotips, sharply pointed nanotips and individual dispersion of the ZnO nanowires. The ZnO/ITO emitters exhibited very stable electron emission with average current fluctuations of ±5%. Our investigations suggest that the spitzer shaped ZnO nanowires have potential for further improving in electron emission and other functionalities after forming tunable nano-hetero-architectures with metal or conducting materials.
ABSTRACT
Size confinement for tailoring of electronic structures can in principle be explored for enhancement of photocatalytic properties. In the present work, vanadium-doped bismuth oxide nanoparticles, with an average particle size of 36 nm, are synthesized for the first time, using the thermal plasma method, in large scale with high yield to explore for photocatalytic applications. The electronic and crystallographic structures of the sample are studied experimentally and theoretically. Systematic investigations of the electronic structure of the fluorite type cubic phase of Bi11VO19 nanoparticles are reported for the first time. Enhancement is observed in the photocatalytic activity as compared to other delta phases of bismuth vanadate. The valence band is found to comprise mainly of O 2p states, whereas the conduction band arises from V 3d states giving rise to a band gap value of 2.26 eV. Absence of excess O in δ-Bi2O3 results in shrinking of the band gap because of O 2p, Bi 6s and 6p states from the surrounding atoms at doping sites. Bi11VO19 nanoparticles show an efficient visible light absorption and exhibit excellent photodegradation properties of methylene blue solution under visible light irradiation.
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AIM: The aim of the present study was to investigate the relationship of central giant cell granuloma (CGCG) and giant cell tumor of long bones (GCT) with respect to cannibalistic giant cells (GCs). METHOD: Sixteen cases each of CGCG and GCT were histopathologically analyzed for cannibalistic GCs. One hundred GCs were examined in each section, and the number of cannibalistic GCs was expressed in percentage. RESULTS: Cannibalistic GCs were seen in all cases of CGCG and GCT (100%). GCT showed significantly higher mean cannibalistic GC frequency (44.81 ± 1.013) than CGCG (32.06 ± 1.398), aggressive CGCG (38.17 ± 1.579), non-aggressive CGCG (28.40 ± 0.6360), non-recurrent CGCG (30.42 ± 1.417), and recurrent CGCG (37.00 ± 2.483). In aggressive CGCG, the mean cannibalistic GC frequency was significantly higher (38.17 ± 1.579) than the non-aggressive variant (28.40 ± 0.6360). Recurrent CGCG cases showed significantly higher mean cannibalistic GC frequency (37.00 ± 2.483) than non-recurrent cases (30.42 ± 1.417). Similarly, recurrent GCT showed significantly higher mean cannibalistic GC frequency (47.4 ± 4.97) than non-recurrent GCT (43.63 ± 3.1). CONCLUSION: The distinctness of CGCG and GCT was observed in terms of mean cannibalistic GC count. The assessment of cannibalistic GC in CGCG and GCT could help in predicting the biological behavior and grading of the tumor.
Subject(s)
Giant Cell Tumor of Bone/physiopathology , Giant Cells/physiology , Granuloma, Giant Cell/physiopathology , Adolescent , Adult , Aged , Extremities , Giant Cell Tumor of Bone/pathology , Granuloma, Giant Cell/pathology , Humans , Middle Aged , Photomicrography , Young AdultABSTRACT
We report comparative field electron emission (FE) studies on a large-area array of two-dimensional MoS2-coated @ one-dimensional (1D) brookite (ß) TiO2 nanorods synthesized on Si substrate utilizing hot-filament metal vapor deposition technique and pulsed laser deposition method, independently. The 10 nm wide and 760 nm long 1D ß-TiO2 nanorods were coated with MoS2 layers of thickness â¼4 (±2), 20 (±3), and 40 (±3) nm. The turn-on field (E on) of 2.5 V/µm required to a draw current density of 10 µA/cm2 observed for MoS2-coated 1D ß-TiO2 nanorods emitters is significantly lower than that of doped/undoped 1D TiO2 nanostructures, pristine MoS2 sheets, MoS2@SnO2, and TiO2@MoS2 heterostructure-based field emitters. The orthodoxy test confirms the viability of the field emission measurements, specifically field enhancement factor (ßFE) of the MoS2@TiO2/Si emitters. The enhanced FE behavior of the MoS2@TiO2/Si emitter can be attributed to the modulation of the electronic properties due to heterostructure and interface effects, in addition to the high aspect ratio of the vertically aligned TiO2 nanorods. Furthermore, these MoS2@TiO2/Si emitters exhibit better emission stability. The results obtained herein suggest that the heteroarchitecture of MoS2@ß-TiO2 nanorods holds the potential for their applications in FE-based nanoelectronic devices such as displays and electron sources. Moreover, the strategy employed here to enhance the FE behavior via rational design of heteroarchitecture structure can be further extended to improve other functionalities of various nanomaterials.
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In the recent past, numerous inflammation-mediated molecular pathways have been explored and studied as important events in carcinogenesis with respect to oral squamous cell carcinoma (OSCC). These pathways are engaged in numerous stages during tumorigenesis; which includes processes, like initiation, promotion, malignant conversion, invasion and metastasis. The inflammation-mediated/related carcinogenesis pathways reported in OSCC involves COX-2, epidermal growth factor receptor (EGFR), p38a MAP kinase, NF-kB, STAT, RhoC, PPARy, etc. Many researchers are trying to target these pathways to explore more effective therapeutic interventions in OSCC. The aim of the present paper is to briefly discuss these pathways, with special emphasis on the therapeutic utilities. The therapeutic targets for the aforementioned pathways were searched in databases pubmed and scopus with no restriction to date of publication. Articles published in English medical literature on OSCC were selected for discussion. The recent combinations, modifications in dosage and frequency, or the use of new anti-inflammatory compounds, may exemplify the next generation care for OSCC.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Molecular Targeted Therapy/methods , Mouth Neoplasms/drug therapy , Carcinogenesis , Humans , Inflammation/physiopathology , Signal Transduction/drug effectsABSTRACT
CONTEXT: Inducible nitric oxide synthase (iNOS) is a cytoplasmic enzyme which plays a crucial role in the pathogenesis of oral carcinomas and sarcomas. AIMS: The objective of this study was to analyze the immunohistochemical expression of iNOS in carcinomas and sarcomas affecting the oral cavity in order to understand the possible role of iNOS in their biologic behavior and to correlate iNOS expression with lymph node metastasis in carcinomas and sarcomas. SETTINGS AND DESIGN: Patients, who attended the oral diagnosis department of Vinayaka Missions Sankarachariyar Dental College, were screened, for the purpose of the study. Besides these, paraffin-embedded tissue blocks were also retrieved from archives of the Oral and Maxillofacial Pathology Department. A total of 40 cases (20 carcinomas and 20 sarcomas) were selected for the study. SUBJECTS AND METHODS: A total of 40 cases (20 carcinomas and 20 sarcomas) were selected for the study. Five apparently normal tissues were obtained from the tumor adjacent normal tissue to be used as a control. These were subjected to immunohistochemical staining using antibody to iNOS and evaluated. STATISTICAL ANALYSIS USED: The results were analyzed using the Chi-square test. RESULTS: Among the 20 carcinomas 19 showed a positive immunoreactivity for iNOS and 1 case was negative. Among the 19 immunopositive iNOS cases of carcinomas, 15 cases showed positive lymph node metastasis. Among the sarcomas, positive immunoreactivity for iNOS was seen in 10 hard tissue sarcomas, while the remaining 10 soft tissue sarcomas were negative for iNOS expression. The results were analyzed using the Chi-square test. CONCLUSIONS: iNOS is a reliable marker for lymph node metastasis in carcinomas irrespective of the histologic grade. The high expression in carcinomas shows that the carcinomas elaborate more angiogenesis for growth compared with the sarcomas with the exception of hard tissue sarcomas.
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Plummer-Vinson syndrome (PVS) is a triad of microcytic hypochromic anemia, atrophic glossitis, and esophageal webs or strictures. It is one of the syndromes associated with iron deficiency anemia. Symptoms resulting from anemia predominates the clinical picture, apart from the additional features such as glossitis, angular cheilitis, and dysphagia. Dysphagia is main clinical feature of PVS. PVS carries an increased risk of development of squamous cell carcinoma of esophagus and pharynx. A classic case report of PVS with clinical features, oral manifestations, malignant potential, differential diagnosis, investigation, dental implication, and treatment is discussed here with the literature review from the dentist's point of view. The article carries a message that dental surgeons have to be familiar with the oral manifestations of anemia and be able to suspect PVS to aid in early diagnosis and prompt treatment.
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CONTEXT: Non-Hodgkin's lymphoma (NHL) is a group of highly diverse malignancies whose prognosis depends on the histologic type and associated factors like HIV positivity. AIMS: The aim of this study was to evaluate eight cases of NHL for their histologic type and HIV positivity, since both are major prognostic factors for NHL. SETTINGS AND DESIGN: Eight cases of primary NHL of the oral cavity were evaluated for age, sex, clinical presentation, and the histologic type, along with immunohistochemistry. These cases were also evaluated for HIV positivity. MATERIALS AND METHODS: NHL cases which were diagnosed through the dental OPD and subsequent biopsy procedure were chosen. The patient data, including age, sex, location, clinical presentation, radiographic presentation, metastasis, and histologic subtype, according to the World Health Organization (WHO) classification were tabulated. Immunohistochemical markers were used to confirm the cell type. CD20 and CD3 were used for B cell and T cell, respectively. Subsequent western blot analysis was carried out for HIV detection. RESULTS: 75% of the NHL was of B-cell type; of this, 83% was found to be diffuse large B-cell lymphoma, which is an aggressive variant. 62.5% of cases were found to be HIV positive. CONCLUSIONS: This study emphasizes the need for HIV investigation in NHL cases and the need to determine the histologic type, both of which significantly affect the treatment outcome and prognosis.
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Graphene quantum dots (GQDs) are synthesized from bio-waste and are further modified to produce amine-terminated GQDs (Am-GQDs) which have higher dispersibility and photoluminescence intensity than those of GQDs. A strong fluorescence quenching of Am-GQDs (switch-off) is observed for a number of metal ions, but only for the Ag(+) ions is the original fluorescence regenerated (switch-on) upon addition of L-cysteine.
Subject(s)
Gold/chemistry , Graphite/chemistry , Photochemistry , Quantum Dots , Spectrometry, Fluorescence , Biomass , Carbon/chemistry , Cysteine/chemistry , Fluorescent Dyes/chemistry , Hydrogen Bonding , Ions , Luminescence , Metals/chemistry , Microscopy, Atomic Force , Microscopy, Electron, Transmission , Nanostructures/chemistry , Plant Leaves , Porosity , Spectrophotometry, UltravioletABSTRACT
AIM: This study was undertaken to investigate and analyze the significance of dermatoglyphics in predicting the susceptibility of individuals to develop dental caries. MATERIALS AND METHODS: This case-control study was conducted on 1250 children in the age group of 5 to 12 years from Chennai Corporation School, Vadapalani, Chennai. Out of 1250 subjects, 625 subjects were in the study group and the remaining 625 subjects were the control group. The study group included children with dental caries in 5 or more teeth based on the DMFT index performed and control group consisted of normal, healthy children without any dental caries. The finger and palmar prints of both hands were taken using a stamp pad. The fingertip patterns were analyzed according to the classical method and configurational types were classified according to the topological method. Statistical analysis was performed using nonparametric tests and t-test to compare the dermatoglyphic pattern changes between the study group and the control group and was applied for each variable, to compare the proportions, and p-value. RESULTS: (1) Dental caries susceptibility of an individual increases with an increase in the incidence of whorl pattern (83% correlation). (2) All the variables show statistically significant value, with a degree of divergence of specific dermatoglyphic patterns among study and control group. (3) The dermatoglyphic patterns are efficient and can predict in assessing the risk of susceptibility to dental caries in study group. CONCLUSION: The dental caries susceptibility of an individual increased with incidence of whorl pattern and it decreased with incidence of loop pattern. CLINICAL SIGNIFICANCE: The dermatoglyphic patterns may be utilized effectively to study the genetic basis of dental caries. In a developing country like India, it might prove to be a noninvasive, inexpensive and effective tool for screening.
Subject(s)
Dental Caries Susceptibility/genetics , Dental Caries/genetics , Dermatoglyphics , Case-Control Studies , Child , Child, Preschool , DMF Index , Female , Humans , India , Male , Statistics, NonparametricABSTRACT
OBJECTIVE: Our goal was to study the effects of ticagrelor on murine platelet function and thrombosis and characterize the time course of P2Y(12) inhibition required to inhibit neointima formation following vascular injury. METHODS AND RESULTS: Mice were treated with ticagrelor or vehicle. Platelet aggregation and P-selectin expression were assessed over time, and thrombus formation was assessed in laser-injured cremasteric arterioles of P2Y(12)+/+ and P2Y(12)-/- mice. Neointima formation in FeCl(3)-injured carotid artery was assessed in C57BL/6 mice treated with different regimens of ticagrelor. Ticagrelor inhibited platelet aggregation and P-selectin expression in a dose-dependent, reversible manner. Ticagrelor inhibited thrombus formation to the same extent as seen in P2Y(12)-/- mice. Neointima formation was markedly reduced in mice treated with ticagrelor before and 4 hours after injury (neointima area: control, 39 921±22 749 µm(2), versus ticagrelor, 3705±2600 µm(2); P<0.01), whereas administration of ticagrelor either before injury only or from 4 hours postinjury was ineffective. CONCLUSIONS: Ticagrelor effectively and reversibly inhibits P2Y(12)-mediated platelet function and thrombosis in mice. P2Y(12) inhibition is required both at the time of and after injury to effectively inhibit neointima formation. Additional studies are warranted to evaluate the role of P2Y(12) inhibition in preventing restenosis.
Subject(s)
Adenosine/analogs & derivatives , Blood Platelets/drug effects , Carotid Artery Injuries/prevention & control , Carotid Stenosis/prevention & control , Fibrinolytic Agents/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Purinergic P2Y Receptor Antagonists/pharmacology , Receptors, Purinergic P2Y12/metabolism , Thrombosis/prevention & control , Adenosine/pharmacokinetics , Adenosine/pharmacology , Animals , Bleeding Time , Blood Coagulation/drug effects , Blood Platelets/metabolism , Carotid Artery Injuries/metabolism , Carotid Artery Injuries/pathology , Carotid Artery, Common/drug effects , Carotid Artery, Common/pathology , Carotid Stenosis/metabolism , Carotid Stenosis/pathology , Cell Proliferation/drug effects , Disease Models, Animal , Dose-Response Relationship, Drug , Fibrinolytic Agents/pharmacokinetics , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , P-Selectin/blood , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/pharmacokinetics , Purinergic P2Y Receptor Antagonists/pharmacokinetics , Receptors, Purinergic P2Y12/deficiency , Receptors, Purinergic P2Y12/drug effects , Receptors, Purinergic P2Y12/genetics , Thrombosis/blood , Ticagrelor , Tunica Intima/drug effects , Tunica Intima/pathologyABSTRACT
OBJECTIVES: The PLATO (PLATelet inhibition and patient Outcomes) PLATELET substudy aimed to compare the antiplatelet effects of clopidogrel and ticagrelor in patients with acute coronary syndromes. BACKGROUND: The PLATO study demonstrated superiority of ticagrelor over clopidogrel in the prevention of ischemic events in patients with acute coronary syndromes. METHODS: Patients were randomized to receive either clopidogrel (300- to 600-mg loading dose [LD], 75 mg/day) or ticagrelor (180-mg LD, 90 mg twice daily). The effects of maintenance therapy were studied in 69 patients pre- and 2 to 4 h post-dose after at least 28 days. The LD effect was studied in 24 clopidogrel-naive patients. Light transmittance aggregometry (adenosine diphosphate 5 to 20 µM), VerifyNow P2Y12, and VASP phosphorylation assays were performed. RESULTS: During maintenance therapy, ticagrelor achieved greater suppression of platelet reactivity compared with clopidogrel. The mean maximum light transmittance aggregometry responses (adenosine diphosphate 20 µM) post-maintenance dose were 44±15% for clopidogrel and 28±10% for ticagrelor (p<0.001). High platelet reactivity was seen more frequently in the clopidogrel group. Proton pump inhibitor use was associated with higher platelet reactivity with clopidogrel but not ticagrelor. The ticagrelor LD also achieved greater inhibition of platelet aggregation compared with the clopidogrel LD. CONCLUSIONS: Ticagrelor achieves greater antiplatelet effect than clopidogrel in patients with acute coronary syndromes, both in the first hours of treatment and during maintenance therapy.
Subject(s)
Acute Coronary Syndrome/drug therapy , Adenosine/analogs & derivatives , Blood Platelets/drug effects , Blood Platelets/physiology , Platelet Aggregation Inhibitors/therapeutic use , Ticlopidine/analogs & derivatives , Acute Coronary Syndrome/physiopathology , Adenosine/pharmacology , Adenosine/therapeutic use , Aged , Clopidogrel , Cohort Studies , Female , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/pharmacology , Ticagrelor , Ticlopidine/pharmacology , Ticlopidine/therapeutic use , Treatment OutcomeABSTRACT
OBJECTIVES: We prospectively assessed cardiac and pulmonary function in patients with stable coronary artery disease (CAD) treated with ticagrelor, clopidogrel, or placebo in the ONSET/OFFSET (A Multi-Centre Randomised, Double-Blind, Double-Dummy Parallel Group Study of the Onset and Offset of Antiplatelet Effects of AZD6140 Compared With Clopidogrel and Placebo With Aspirin as Background Therapy in Patients With Stable Coronary Artery Disease) study. BACKGROUND: Ticagrelor reduces cardiovascular events more effectively than clopidogrel in patients with acute coronary syndromes. Dyspnea develops in some patients treated with ticagrelor, and it is not known whether this is associated with changes in cardiac or pulmonary function. METHODS: In all, 123 stable aspirin-treated CAD patients randomly received either ticagrelor (180 mg load, then 90 mg twice daily; n=57), clopidogrel (600 mg load, then 75 mg daily; n=54), or placebo (n=12) for 6 weeks in a double-blind, double-dummy design. Electrocardiography, echocardiography, serum N-terminal pro-brain natriuretic peptide, and pulmonary function tests were performed before (baseline) and 6 weeks after drug administration and/or after development of dyspnea. RESULTS: After drug administration, dyspnea was reported by 38.6%, 9.3%, and 8.3% of patients in the ticagrelor, clopidogrel, and placebo groups, respectively (p<0.001). Most instances were mild and/or lasted<24 h, although 3 patients discontinued ticagrelor because of dyspnea. Eight of 22 and 17 of 22 ticagrelor-treated patients experiencing dyspnea did so within 24 h and 1 week, respectively, after drug administration. In all treatment groups, and in ticagrelor-treated patients with dyspnea, there were no significant changes between baseline and 6 weeks in any of the cardiac or pulmonary function parameters. CONCLUSIONS: Dyspnea is commonly associated with ticagrelor therapy, but was not associated in this study with any adverse change in cardiac or pulmonary function. (A Multi-Centre Randomised, Double-Blind, Double-Dummy Parallel Group Study of the Onset and Offset of Antiplatelet Effects of AZD6140 Compared With Clopidogrel and Placebo With Aspirin as Background Therapy in Patients With Stable Coronary Artery Disease [ONSET/OFFSET]; NCT00528411).
Subject(s)
Adenosine/analogs & derivatives , Coronary Disease/drug therapy , Dyspnea/chemically induced , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/therapeutic use , Ticlopidine/analogs & derivatives , Adenosine/adverse effects , Aged , Aspirin/therapeutic use , Clopidogrel , Coronary Disease/physiopathology , Double-Blind Method , Female , Heart/drug effects , Humans , Lung/drug effects , Male , Middle Aged , Prospective Studies , Ticagrelor , Ticlopidine/therapeutic useABSTRACT
BACKGROUND: Ticagrelor is the first reversibly binding oral P2Y(12) receptor antagonist. This is the first study to compare the onset and offset of platelet inhibition (IPA) with ticagrelor using the PLATO (PLATelet inhibition and patient Outcomes) trial loading dose (180 mg) with a high loading dose (600 mg) of clopidogrel. METHODS AND RESULTS: In a multicenter, randomized, double-blind study, 123 patients with stable coronary artery disease who were taking aspirin therapy (75 to 100 mg/d) received ticagrelor (180-mg load, 90-mg BID maintenance dose [n=57]), clopidogrel (600-mg load, 75-mg/d maintenance dose [n=54]), or placebo (n=12) for 6 weeks. Greater IPA (20 micromol/L ADP, final extent) occurred with ticagrelor than with clopidogrel at 0.5, 1, 2, 4, 8, and 24 hours after loading and at 6 weeks (P<0.0001 for all); by 2 hours after loading, a greater proportion of patients achieved >50% IPA (98% versus 31%, P<0.0001) and >70% IPA (90% versus 16%, P<0.0001) in the ticagrelor group than in the clopidogrel group, respectively. A faster offset occurred with ticagrelor than with clopidogrel (4-to-72-hour slope [% IPA/h] -1.04 versus -0.48, P<0.0001). At 24 hours after the last dose, mean IPA was 58% for ticagrelor versus 52% for clopidogrel (P=NS). IPA for ticagrelor on day 3 after the last dose was comparable to clopidogrel at day 5; IPA on day 5 for ticagrelor was similar to clopidogrel on day 7 and did not differ from placebo (P=NS). CONCLUSIONS: Ticagrelor achieved more rapid and greater platelet inhibition than high-loading-dose clopidogrel; this was sustained during the maintenance phase and was faster in offset after drug discontinuation.