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PrP
Kinds of PrP Terms modified by PrP Selected AbstractsLong-term review of driving potential following bilateral panretinal photocoagulation for proliferative diabetic retinopathyDIABETIC MEDICINE, Issue 1 2009S. A. Vernon Abstract Aim To determine the necessity for repeated Driver and Vehicle Licensing Agency (DVLA) visual field testing in people with diabetes who have had bilateral panretinal photocoagulation (PRP) for proliferative diabetic retinopathy. Methods A questionnaire survey was conducted of driving history in a cohort of people with diabetes who had been treated with bilateral PRP for proliferative retinopathy between 1988 and 1990. In addition, all similarly eligible subjects attending the diabetic retinal review clinic over a 12-month period who had had laser between 1991 and 2000 were questioned as to their driving status. Results Forty-five surviving patients from the 1988,1990 cohort were eligible and 25 returned the questionnaire (55%). Eight had never driven and 15 (13 with Type 1 diabetes) still held a valid licence, having passed the DVLA field test on a number of occasions. Neither of the two patients who had stopped driving reported failing the DVLA field test as the reason for stopping. All 12 of the patients directly questioned in the clinic were still driving and had passed at least one repeat DVLA test. Conclusions People with Type 1 diabetes who have no further laser treatment for proliferative diabetic retinopathy can expect to retain their UK driving licence for at least 15 years following small-burn PRP, provided they maintain sufficient acuity. [source] Chalcones as potent antiplatelet agents and calcium channel blockersDRUG DEVELOPMENT RESEARCH, Issue 1 2001Chun-Nan Lin Abstract In an effort to continually develop potent antiplatelet agents with vasorelaxing and antiinflammatory actions, a novel series of antiinflammatory chalcones was continually screened to evaluate their antiplatelet and vasorelaxing effects. Their structure,activity relationships and mode of action were discussed and characterized. A novel series of antiinflammatory chalcones was studied on antiplatelet effect in rabbit washed platelets and human platelet-rich plasma (PRP) and vasorelaxing effect in rat thoracic aorta. Arachidonic acid-induced platelet aggregation was potently inhibited by almost all the chalcone derivatives and 13,15 also had a potent inhibitory effect on cyclooxygenase. The selective chalcones 12,16 tested in human PRP significantly inhibited secondary aggregation induced by adrenaline. In rat thoracic aorta, most of chalcones at high concentration significantly depressed the contractions induced by Ca2+ (1.9 mM) in high K+ (80 mM) medium and the phasic and tonic contractions caused by norepinephrine (3 ,M). In the rat thoracic aorta, the phenylephrine- and high K+ -induced 45Ca2+ influx were both inhibited by a selective chalcone derivative, 14. These results indicate that the antiplatelet actions of chalcones are mainly mediated through the suppression of cyclooxygenase activity and reduced thromboxane formation and their inhibitory effects on the contractile response caused by high K+ and norepinephrine in rat thoracic aorta are mainly due to inhibition of Ca2+ influx through both voltage-dependent and receptor-operated Ca2+ channels. Drug Dev. Res. 53:9,14, 2001. © 2001 Wiley-Liss, Inc. [source] Evaluation of postoperative drainage with application of platelet-rich and platelet-poor plasma following hemithyroidectomy: A randomized controlled clinical trial,,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 12 2008John Yoo MD Abstract Background. Platelet-rich plasma (PRP) and platelet-poor plasma (PPP) have been used to improve hemostasis and wound healing after surgery; however, randomized controlled trials proving their efficacy are lacking. Methods. Hemithyroidectomy was performed on 52 patients. Autologous PRP and PPP were applied during wound closure in the treatment group, while saline was applied in the controls. Outcome measures were postoperative drainage, pain, analgesic use, and length of hospital stay. Results. The 24-hour cumulative drainage was reduced by 29.3% in the treatment group (44.9 mL vs 63.5 mL, p = .039). The treatment group required less analgesic medication despite similar pain scores; however, the difference was not significant. There was a trend toward decreased length of stay for thePRP/PPP group (p = .059). Conclusions. Hemithyroidectomy served as a stringent test to evaluate the wound-healing capacity of platelet-rich and platelet-poor plasma. This study provides evidence that PRP and PPP reduced postoperative drainage in soft-tissue surgery. © 2008 Wiley Periodicals, Inc. Head Neck, 2008 [source] Haemophilus influenzae type b conjugate vaccinesIMMUNOLOGY, Issue 2 2004Dominic F. Kelly Summary Haemophilus influenzae type b (Hib) is one of the leading causes of invasive bacterial infection in young children worldwide. During childhood, acquisition of antibody directed against the polysaccharide capsule of the organism, presumably as a result of asymptomatic carriage, confers protection and disease is much less common after the age of 4 years. Like other polysaccharides, the polyribosyl ribitol phosphate (PRP) of the Hib capsule is a T-independent antigen and not immunogenic when administered as a vaccine in infancy. Because the highest rates of disease occur in the first 2 years of life, efficacious Hib vaccines have been designed by covalently linking the PRP capsule to a carrier protein that recruits T-cell help for the polysaccharide immune response and induces anti-PRP antibody production even in the first 6 months of life. Introduction of Hib protein,polysaccharide conjugate vaccines into many industrialized countries over the past 15 years has resulted in the virtual elimination of invasive Hib disease. However, despite the success of the vaccine programme several factors may interfere with the effectiveness of the vaccine in the routine programme, as observed in the UK recently. Such factors may include interference with other concomitant vaccines, waning immunity in the absence of booster doses of vaccine, and reduced natural boosting as a result of decreased transmission of the organism. However, the burden of disease remains highest in resource-poor countries and urgent efforts are needed to provide the benefits of this vaccine for children living in regions where it cannot be used for economic and logistical reasons. [source] Platelet-rich plasma may prevent titanium-mesh exposure in alveolar ridge augmentation with anorganic bovine boneJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 10 2010Jesús Torres Torres J, Tamimi F, Alkhraisat MH, Manchón Á, Linares R, Prados-Frutos JC, Hernández G, López Cabarcos E. Platelet-rich plasma may prevent titanium-mesh exposure in alveolar ridge augmentation with anorganic bovine bone. J Clin Periodontol 2010; 37: 943,951. doi: 10.1111/j.1600-051X.2010.01615.x. Abstract Objective: Bone augmentation with the titanium-mesh (Ti-mesh) technique is susceptible to a large rate of complications such as morbidity of bone graft donor site, and mesh exposure to the oral cavity. The purpose of this study was to evaluate the effectiveness of anorganic bovine bone (ABB) in alveolar bone augmentation with the Ti-mesh technique. In addition, we investigated the effect of platelet-rich plasma (PRP) in preventing mesh exposure by using it to cover the Ti-mesh. Patients and Methods: Patients included in the clinical trial were randomly allocated by a blinded assistant into two groups. The 30 patients recruited for this study underwent 43 alveolar bone augmentation with the Ti-mesh technique using ABB as graft material in all of them. In 15 patients, the Ti-meshes were covered with PRP (PRP group) whereas in the other 15 the Ti-meshes were not (control group). After 6 months, patients were called for clinical, radiographic, and histological evaluation, and implant placement surgery. A total of 97 implants were placed in the augmented bone and their evolution was followed up for a period of 24 months. Results: Significant differences were found between the two study groups in terms of complications and bone formation. In the control group, 28.5% of the cases suffered from mesh exposure, while in the PRP group, no exposures were registered. Radiographic analysis revealed that bone augmentation was higher in the PRP group than in the control group. Overall, 97.3% of implants placed in the control group and 100% of those placed in the PRP group were successful during the monitoring period. We suggest that the positive effect of PRP on the Ti-mesh technique is due to its capacity to improve soft tissue healing, thereby protecting the mesh and graft material secured beneath the gingival tissues. Conclusions: Alveolar bone augmentation using ABB alone in the Ti-mesh technique is sufficient for implant rehabilitation. Besides, covering the Ti-meshes with PRP was a determining factor in avoiding mesh exposure. Ti-mesh exposure provoked significant bone loss, but in most cases it did not affect the subsequent placement of implants. [source] Regenerative treatment with platelet-rich plasma combined with a bovine-derived xenograft in smokers and non-smokers: 12-month clinical and radiographic resultsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 1 2010Selcuk Yilmaz Abstract Aim: The purpose of this study was to assess the healing response of intrabony defects following regenerative treatment with platelet-rich plasma (PRP) combined with a bovine-derived xenograft (BDX) in smokers and non-smokers. Materials and Methods: A total of 24 advanced chronic periodontitis patients, 12 smokers and 12 non-smokers, with 113 intrabony defects with an intrabony component of 3 mm were included in this study. Defects were surgically treated with PRP/BDX. At baseline and 12 months after surgery, the following parameters were recorded: plaque and sulcus bleeding indices, probing depth (PD), relative attachment level, marginal recession, probing and radiographic bone levels. Results: Considering the soft tissue measurements, smokers and non-smokers presented a mean PD reduction of 3.97 ± 0.76 and 4.63 ± 0.52 mm, recession of 0.76 ± 0.44 and 0.50 ± 0.12 mm and attachment gain of 3.26 ± 0.42 and 4.06 ± 0.40 mm, respectively. Evaluation of the hard tissue findings revealed that the mean clinical and radiographic bone gains in smokers and non-smokers were 2.83 ± 0.47 and 3.63 ± 0.38 mm, 2.98 ± 0.38 and 3.67 ± 0.48 mm, respectively. Inter-group differences for PD reduction (p<0.05), attachment (p<0.001), clinical (p<0.001) and radiographic bone gains (p<0.001) were found to be significant between smokers and non-smokers. Conclusions: Within the limits of this study, the results indicate that treatment outcome following PRP/BDX application in intrabony defects is impaired with smoking. [source] Effect of partial recording protocols on severity estimates of periodontal diseaseJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 8 2008Albert Kingman Abstract Objectives: The study aim was to assess bias magnitudes of periodontal disease severity estimates for specific partial recording protocols (PRPs) in epidemiological studies. Material and Methods: Estimates of mean clinical attachment loss (MCAL) and mean probing pocket depth (MPPD) were derived for 20 different PRPs using full-mouth periodontal data from 1437 dentate Brazilian subjects 14,103 years old having at least four teeth. Biases, relative biases and intra-class correlations for all PRPs were evaluated. Graphical methods were used to assess how well the PRP-based estimates agreed with full-mouth scores across levels of disease. Results: Slightly higher levels of disease were evidenced on lingual than on buccal sites. Seven multi-site PRPs and the Ramfjörd PRP produced small biases in MPPD (,0.17 to 0.04 mm) and MCAL with relative biases under 8% and 4% in absolute value for MPPD and MCAL, respectively. Biases for full- and random half-mouth-based PRPs were similar. The three-site random half-mouth MB,B,DL and the Ramfjörd PRPs produced the smallest biases, with relative biases <3% in absolute value for MPPD and MCAL. Conclusions: Bias for MPPD or MCAL estimates varies by site type, number of sites per tooth and number of quadrants included in the PRP. [source] Mesenchymal stem cells and platelet-rich plasma enhance bone formation in sinus grafting: a histomorphometric study in minipigsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 6 2008Francesco Pieri Abstract Objectives: Autologous, allogenic, and alloplastic materials for sinus augmentation have specific drawbacks, which has stimulated an ongoing search for new materials and tissue-engineering constructs. We investigated whether mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) seeded on a fluorohydroxyapatite (FH) scaffold can improve bone formation and bone-to-implant contact (BIC) in maxillary sinus grafting. Material and Methods: Bilateral sinus augmentation procedures were performed in eight minipigs. MSCs, PRP, and FH scaffold (test site) or FH alone (control site) were grafted in each maxillary sinus. Distal to the osteotomy, one dental implant per sinus was placed in the grafting material through the facial sinus wall. The animals were killed 3 months after grafting, and block sections of the implant sites were harvested and prepared for histomorphometric analysis. Results: After 12 weeks, a significant increase in bone formation occurred in the test sites compared with the control sites (42.51%versus 18.98%; p=0.001). In addition, BIC was significantly greater in the test sites compared with the control sites in the regenerated area (23.71%versus 6.63%; p=0.028). Conclusions: These findings show that sinus augmentation with MSCs,PRP, combined with FH may enhance bone formation and osseointegration of dental implants compared with FH alone in minipigs. [source] Effectiveness of a combination of platelet-rich plasma, bovine porous bone mineral and guided tissue regeneration in the treatment of mandibular grade II molar furcations in humansJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 8 2003Vojislav Lekovic Abstract Objective: A combination of platelet-rich plasma (PRP), bovine porous bone mineral (BPBM) and guided tissue regeneration (GTR) has been shown to be effective as regenerative treatment for intrabony periodontal defects. The purpose of this study was to evaluate the effectiveness of PRP, BPBM and GTR used in combination as regenerative treatment for grade II molar furcation defects in humans. Material and methods: Using a split-mouth design, a total of 52 grade II mandibular molar furcation defects were treated either with PRP/BPBM/GTR (experimental group, n=26) or with an open flap debridement (control group, n=26). The primary outcomes evaluated in this study included changes in pocket depth, attachment level and re-entry bone levels (horizontal and vertical) between baseline and 6 months postoperatively. Results: The results showed that the experimental group presented with significantly greater pocket reduction (4.07±0.33 mm for experimental and 2.49±0.38 mm for control sites), gain in clinical attachment (3.29 ± 0.42 mm for experimental and 1.68±0.31 mm for control sites), vertical defect fill (2.56± 0.36 mm for experimental and ,0.19±0.02 for control sites) and horizontal defect fill (2.28±0.33 mm for experimental and 0.08±0.02 mm for control sites) than the control group. Conclusions: It was concluded that the PRP/BPBM/GTR combined technique is an effective modality of regenerative treatment for mandibular grade II furcation defects. Further studies are necessary to elucidate the role played by each component of the combined therapy in achieving these results. Zusammenfassung Ziel: Eine Kombination von plättchemreichen Plasma (PRP), bovinem porösem Knochenmineral (BPBM) und gesteuerter Geweberegeneration (GTR) wurde als effektiv bei der regenerativen Behandlung von intraalveolären parodontalen Knochendefekten gezeigt. Der Zweck dieser Studie war die Evaluation der Effektivität von PRP, BPBM und GTR in der Kombination als regenerative Behandlung für Grad II Furkationsdefekte bei menschlichen Molaren. Material und Methoden: Unter Nutzung eines split-mouth Design wurden 52 Grad II Unterkiefermolaren Furkationsdefekte entweder mit PRP/BPBM/GTR (experimentelle Gruppe, n=26) oder mit einer offenen Reinigung (Lappenoperation) (Kontrollgruppe, n=26) behandelt. Die primären Ergebnisse die in dieser Studie evaluiert wurden, bezogen die Veränderung der Sondierungstiefen, des Stützgewebeniveaus und des Knochenniveaus bei reentry-Operationen (horizontal und vertikal) zwischen Basis und 6 Monate post operationem ein. Ergebnisse: Die Ergebnisse zeigten, dass die experimentelle Gruppe eine höhere Reduktion der Sondierungstiefen (4.07±0.33 mm für experimentelle und 2.49±0.38 mm für Kontrollflächen), einen höheren Stützgewebegewinn (3.29±0.42 mm für experimentelle und 1.68± 0.31 mm für Kontrollflächen), eine größere vertikale Defektfüllung (2.56±0.36 mm für experimentelle und ,0.19±0.02 für Kontrollflächen) sowie horizontale Defektfüllung (2.28± 0.33 mm für experimentelle und 0.08±0.02 mm für Kontrollflächen) verglichen mit den Kontrollen zeigte. Schlussfolgerungen: Es wird gefolgert, dass die Kombination von PRB/BPBM/GTR eine effektive Modifikation der regenerativen Behandlung bei Grad II Furkationsdefekten bei unteren Molaren ist. Weitere Studien sind notwendig, um die Rolle jeder Komponente dieser kombinierten Therapie in der Erzielung dieser Ergebnisse zu erfassen. Résumé Objectif: Une combinaison de plasma riche en plaquette (PRP), de minéral d'os bovin poreux (BPBM) et de régénération tissulaire guidée (GTR) a prouvé son efficacité en tant que traitement régénératif pour les lésions intra-osseuses parodontales. Cette étude se propose d'évaluer l'intérêt de l'utilisation en combinaison de PRP, BPBM et GTR comme traitement de régénération des lésions furcatoires molaires de classe II chez l'homme. Matériels et Méthodes: Par une étude conçue en bouche croisée, 52 lésions furcatoires molaires mandibullaires ont été traitées soit avec PRP/BPBM/GTR (groupe expérimental, n=26) ou par simple lambeau d'accès (groupe contrôle, n=26). Les objectifs primaires évalués dans cette étude étaient la modification de la profondeur de poche, le niveau d'attache et les niveaux osseux lors de la réentrée (en horizontal et en vertical) mesurés six mois post-op. Résultats: les résultats montrent que le groupe expérimental présentait significativement une plus importante réduction de poche (4.07±0.33 mm contre 2.49±0.38 mm pour les sites contrôles), un gain d'attache clinique plus important (3.29± 0.42 mm contre 1.68±0.31 mm pour les sites contrôles), un comblement vertical des lésions(2.56±0.36 mm contre ,0.19±0.02 pour les sites contrôles) et un comblement horizontal des lésions (2.28±0.33 mm contre 0.08± 0.02 mm pour les sites contrôles). Conclusions: Nous en concluons que la technique combinant PRP/BPBM/GTR est un traitement régénératif efficace pour les lésions de furcation molaire mandibulaire de classe II. Des études complémentaires sont nécessaires pour élucider le rôle joué par chaque élément de cette combinaison dans l'obtention de ces résultats. [source] Platelet-rich plasma impairs osteoclast generation from human precursors of peripheral bloodJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2010Elisabetta Cenni Abstract Platelet-rich plasma is used to accelerate bone repair for the release of osteogenic growth factors from activated platelets. To date, the effects on osteoclasts have been only scarcely investigated, even though these cells are crucial for bone remodeling. The aim of this research was the evaluation of the effects of thrombin-activated platelets (PRP) on osteoclastogenesis from human blood precursors. We evaluated both the ability to influence osteoclast differentiation induced by the receptor activator of nuclear factor-kappaB ligand (RANKL), and the ability to induce osteoclast differentiation without RANKL. In both assays, the incubation with PRP supernatant at 10% did not significantly affect the formation of tartrate-resistant acid phosphatase (TRACP)-positive multinucleated cells that were able to form the F-actin ring. However, when PRP at 25 and 50% was added to the medium without RANKL, the generation of TRACP-positive multinucleated cells was inhibited. PRP, even at 10%, reduced the osteoclast-mediated bone collagen degradation, suggesting inhibition of osteoclast activation. Similarly, after incubation with PRP supernatant, calcitonin receptor mRNA was lower than the untreated samples. In conclusion, PRP at 10% interfered with the complete differentiation process of human osteoclast precursors. At higher concentration it impaired osteoclast formation also at an early stage of differentiation. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:792,797, 2010 [source] Endothelial cells incubated with platelet-rich plasma express PDGF-B and ICAM-1 and induce bone marrow stromal cell migrationJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 11 2009Elisabetta Cenni Abstract Platelet-rich plasma (PRP) is used to accelerate bone repair through the growth factors released by platelets. The purpose of this study was to evaluate if PRP induce human umbilical vein endothelial cells (HUVEC) to express mRNA for osteogenic growth factors and stimulate the migration of bone marrow stromal cell (BMSC). The effects of PRP were compared to those induced by vascular endothelial growth factor-A (VEGF-A) or, as a negative control, by platelet poor plasma (PPP). After incubation with PRP, but not with PPP, HUVEC showed an increased expression of mRNA for platelet derived growth factor-B (PDGF-B), and this effect was not inhibited by an anti-VEGF-A antibody. The migration of BMSC was more stimulated by HUVEC incubated with PRP than by HUVEC incubated with low serum medium or PPP. Besides, PRP increased the expression of intercellular adhesion molecule-1 (ICAM-1) and osteoprotegerin, but did not affect the expression either of the receptor activator for nuclear factor ,B ligand (RANKL) or of RANK. These findings support the hypothesis that PRP contribute to bone repair by favoring the pro-osteogenic function of endothelial cells, including the recruitment of osteoblast precursors and the expression of adhesion molecules for monocyte/macrophages, while inhibiting their pro-osteolytic properties. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1493,1498, 2009 [source] Antimicrobial activity of platelet-leukocyte gel against Staphylococcus aureusJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2008Dirk Jan F. Moojen Abstract Platelet-leukocyte gel (PLG) contains high concentrations of platelets and leukocytes. As leukocytes play an important role in the innate host-defense, we hypothesized that PLG might have antimicrobial properties. This study investigated the antimicrobial activity of PLG against Staphylococcus aureus and the contribution of myeloperoxidase (MPO), present in leukocytes, in this process. Platelet-rich plasma (PRP) and platelet-poor plasma (PPP) were obtained from whole blood of six donors. PLG was prepared by mixing PRP with autologous (PLG-AT) or bovine thrombin (PLG-BT). Antimicrobial activity of PLG-AT, PLG-BT, PRP, and PPP was determined in a bacterial kill assay. MPO release was measured by ELISA and activity was measured using a MPO activity assay. Cultures showed a rapid decrease in the number of bacteria for both PLG-AT and PLG-BT, which was maximal between 4 and 8 h, to approximately 1% of the bacteria in controls. The effect of PLG-AT was largest and significantly different compared to PRP (p,=,0.004) and PPP (p,<,0.001), however not compared to PLG-BT (p,=,0.093). PLG-AT, PLG-BT, and PRP showed a comparable, gradually increasing MPO release. MPO activity was comparable for all groups and remained stable. No correlation between MPO release, activity, and bacterial kill could be found. PLG appears to have potent antimicrobial capacity, but the role of MPO in this activity is questionable. PLG might represent a useful strategy against postoperative infections. However, additional research should elucidate its exact antimicrobial activity. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:404,410, 2008 [source] In vivo study on the healing of bone defects treated with bone marrow stromal cells, platelet-rich plasma, and freeze-dried bone allografts, alone and in combinationJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2006D. Dallari Abstract The repair of confined trabecular bone defects in rabbits treated by autologous bone marrow stromal cells (BMSC), platelet-rich plasma (PRP), freeze-dried bone allografts (FDBA) alone and in combination (BMSC,+,PRP; FDBA,+,BMSC; FDBA,+,PRP; FDBA,+,PRP,+,BMSC) was compared. A critical size defect was created in the distal part of the femurs of 48 adult rabbits. Histology and histomorphometry were used in the evaluation of healing at 2, 4, and 12 weeks after surgery. The healing rate (%) was calculated by measuring the residual bone defect area. Architecture of the newly formed bone was compared with that of bone at the same distal femur area of healthy rabbits. The defect healing rate was higher in PRP,+,BMSC, FDBA,+,PRP, FDBA,+,BMSC, and FDBA,+,PRP,+,BMSC treatments, while lower values were achieved with PRP treatment at all experimental times. The highest bone-healing rate at 2 weeks was achieved with FDBA,+,PRP,+,BMSC treatment, which resulted significantly different from PRP (p,<,0.05) and BMSC (p,<,0.05) treatments. At 4 weeks, the bone-healing rate increased except for PRP treatment. Finally, the bone-healing rate of FDBA,+,PRP, FDBA,+,BMSC, and FDBA,+,PRP,+,BMSC was significantly higher than that of PRP at 12 weeks (p,<,0.05). At 12 weeks, significant differences still existed between PRP, BMSC, and FDBA groups and normal bone (p,<,0.05). These results showed that the combination of FDBA, BMSC and PRP permitted an acceleration in bone healing and bone remodeling processes. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [source] Epidermal growth factor released from platelet-rich plasma promotes endothelial cell proliferation in vitroJOURNAL OF PERIODONTAL RESEARCH, Issue 1 2010M.-P. Bertrand-Duchesne Bertrand-Duchesne M-P, Grenier D, Gagnon G. Epidermal growth factor released from platelet-rich plasmapromotes endothelial cell proliferation in vitro. J Periodont Res 2009; doi: 10.1111/j.1600-0765.2009.01205.x. © 2009 The Authors. Journal compilation © 2009 Blackwell Munksgaard Background and Objective:, The therapeutic benefits of platelet-rich plasma (PRP) for the promotion of healing and regeneration of periodontal tissues are thought to result from enrichment in growth factors released from platelets. The aim of this study was to evaluate the effects of specific growth factors released from PRP on endothelial cell proliferation. Material and Methods:, The levels of vascular endothelial growth factor (VEGF), platelet-derived growth factor BB (PDGF-BB), basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) in supernatants of calcium- and thrombin-activated PRP samples from five donors were quantified by enzyme-linked immunosorbent assay. Supernatants were treated with neutralizing antibodies specific to each growth factor, and the effects of these treatments on human umbilical vein endothelial cell (HUVEC) proliferation in vitro were determined. The effect of removing EGF from PRP supernatants with antibody-coated beads on HUVEC proliferation was also tested. Results:, Average concentrations of VEGF, PDGF-BB, bFGF and EGF in PRP supernatants were 189, 27,190, 39.5 and 513 pg/mL, respectively. The addition of EGF neutralizing antibodies to the PRP supernatants significantly reduced HUVEC proliferation (up to 40%), while such an inhibition was not observed following neutralization of the other growth factors. Removal of EGF from PRP supernatants by treatment with antibody-coated beads also resulted in a significant decrease in HUVEC proliferation. Recombinant EGF increased HUVEC proliferation in vitro in a dose-dependent manner. Conclusion:, This study showed that PRP supernatants are highly mitogenic for endothelial cells and provided evidence that this effect may be due, at least in part, to the presence of EGF. In vivo experiments are needed to confirm the roles of specific growth factors released from PRP in the healing of oral surgical and/or periodontal wounds. [source] Factor VIIa-mediated tenase function on activated platelets under flowJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2004M. S. Goel Summary.,Background: Tissue factor (TF) and/or active factor (F)VIIa may be stored inside resting platelets. Objectives: The objective of this study was to examine if platelets, following activation of GPVI, could support tenase and prothrombinase activity without any exogenously added tissue factor. Methods: Thrombin (IIa) formation on gel-filtered platelets with added factors or the clotting of platelet-free plasma (PFP) or platelet-rich plasma (PRP) supplemented with corn trypsin inhibitor (CTI) (to inhibit factor XIIa) was studied in well plate assays with a fluorogenic thrombin substrate or in flow assays by fibrin visualization. Results: Pretreatment of convulxin (CVX)-stimulated, fibrinogen-adherent, gel-filtered platelets with anti-TF, anti-FVII/VIIa, or 1 nm PPACK [inhibitor of FVIIa, factor XIa and factor (F)IIa] delayed fibrin deposition on platelets perfused with PFP/CTI at 62.5 s,1. Anti-TF or anti-FVII/VIIa also attenuated thrombin generation in plate assays using recalcified PRP/CTI treated with CVX. Anti-TF or anti-FVII/VIIa (but not inhibited factor IXa) delayed the burst in thrombin production by gel-filtered platelets suspended in prothrombin and CVX by 14 min and 40 min, respectively. Anti-FVII/VIIa completely eliminated thrombin generation on fibrinogen-adherent, gel-filtered platelets pretreated with 10 µm PPACK and 10 µm EGR-CK [inhibitor of factor (F)Xa], rinsed, and then supplemented with CVX, prothrombin, and FX. Addition of anionic phospholipid to PFP/CTI or to a mixture of prothrombin, FX, and recVIIa was not sufficient to generate detectable tenase activity. Lastly, isolated, unactivated neutrophils suspended in FX, FII and recVIIa supported a very low level of thrombin generation sensitive to antagonism of P-selectin, CD18, and TF. Conclusions: Activated platelets supported tenase and prothrombinase activity by elevating the function or level of FVIIa and exposing active FVIIa or FVIIa-cofactor(s), distinct from anionic lipid, that may be, in part, TF. [source] Initiating and potentiating role of platelets in tissue factor-induced thrombin generation in the presence of plasma: subject-dependent variation in thrombogram characteristicsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 3 2004K. Vanschoonbeek Summary., The hemostatic activity of plasma is determined by platelet activation and coagulation, which processes are mutually stimulatory. We studied this interaction by measuring the cleavage of fluorescent thrombin substrate in platelet-rich plasma (PRP), using the calibrated thrombogram method. In freshly isolated human plasma, thrombin formation triggered by tissue factor was fully dependent on the presence of platelets. It was abolished by annexin A5, indicating dependence on phosphatidylserine (PS) exposure at activated platelets. Comparison of plasmas from various subjects showed considerable interindividual variation in total amount of thrombin generation, regardless of whether platelets or PS-containing phospholipids were present. Integrin ,IIb,3 antagonists and ADP receptor blockage, but not aspirin, decreased the rate of thrombin generation (thrombin peak level) and extended the time of onset. Platelet inhibition with cAMP-elevating agents decreased the thrombin-forming rate, but surprisingly shortened the onset time. Stimulation of platelets with agonists of Gi/q-coupled receptors and, to a larger extent, with collagen or Ca2+ -ionophore increased the rate of thrombin generation and shortened its onset. In PRP from donors with low and high generation, platelet inhibitors and activators were similarly effective. Taken together, these results indicate that, in tissue factor-triggered PRP, PS exposure on activated platelets regulates both onset and rate of thrombin generation. However, coagulant activity rather than platelet activation determines the total amount of thrombin formed, i.e. the endogenous thrombin potential. Thus, kinetics of thrombin generation in PRP are controlled by platelet inhibitors and agonists, but the process is restricted in amount by the subject-dependent variation in coagulation. [source] Different effects of abciximab and cytochalasin D on clot strength in thrombelastographyJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2004T. Lang Summary., Maximum amplitude (MA) in thrombelastography (TEG) consists of a plasmatic and a platelet component. To assess the magnitude of the plasmatic component, pharmacological approaches have been proposed to eliminate the platelet component. We evaluated the individual and combined effects of abciximab and cytochalasin D on the MA of TEG. Whole blood, platelet-rich plasma (PRP) and homologous platelet-poor plasma (PPP) from 20 healthy volunteers were spiked with abciximab or cytochalasin D or a combination of both and TEGs performed. Abciximab and cytochalasin D decreased MA in all samples. MA of whole blood (18.6 ± 3.1 mm) and PRP (33.7 ± 3.5 mm) spiked with abciximab or cytochalasin D alone (15.0 ± 2.9 mm and 25.0 ± 4.0 mm) were significantly higher when compared with abciximab and cytochalasin D combined (10.4 ± 3.0 and 20.2 ± 3.5 mm). While MA of PRP and homologous PPP were significantly (P < 0.001) different after individual administration of abciximab and cytochalasin D, combination of both abolished this difference (20.2 ± 3.5 mm and 20.4 ± 3.7 mm, P = 0.372). In whole blood of critically ill patients or patients undergoing major surgery there was also a significant difference of MA between abciximab alone and in combination with cytochalasin D (16.5 ± 11.3 mm and 11.3 ± 7.7 mm, P < 0.001). This indicates that in contrast to individual administration of abciximab or cytochalasin D, a combination of both compounds eliminates the platelet-specific effect on MA of TEG tracings. [source] Cognitive Preference Reversal or Market Price Reversal?KYKLOS INTERNATIONAL REVIEW OF SOCIAL SCIENCES, Issue 2 2005Xiaoyong Chai Summary Preference Reversal Phenomenon (PRP) has been most often scrutinized as a puzzle of ,preferences', while the discovery of the ,endowment effect' explicitly questions the parity between preference and price. The author's experiment (N = 186) connects these two extraordinary findings and illustrates that PRP is only a reversal of price in a ,market.' PRP merely proves that subjects demand to be compensated based on loss under market access deprivation when a ,maximum buying'/,minimum selling' price is elicited, and preference transitivity is restored once the misleading market manipulation is experimentally controlled. By defending preference transitivity, the author asserts that normal access to the bargaining process is indispensable for a competitive market where preference price parity is required. To make valid measurements of preference and price, the sealed envelope method is substituted for the judged-indifferent-point (JIP) method, and the binding statement method is substituted for the Becker-DeGroot-Marschack method. McNemar test scores are calculated to compare the effects of different methods. [source] Acute Juvenile Pityriasis Rubra Pilaris: A Superantigen Mediated Disease?PEDIATRIC DERMATOLOGY, Issue 5 2001Isabel Betlloch M.D. Juvenile acute pityriasis rubra pilaris (JAPRP) is a form of pityriasis rubra pilaris (PRP) with particular clinical characteristics and course. It is usually preceded by an infectious condition. We report a boy, initially thought to have Kawasaki disease, and subsequently diagnosed as having JAPRP, who made a satisfactory recovery. In this case, prior antibiotic treatment made it impossible to show the presence of any microorganism. However, the clinical characteristics of these patients and the similarities with other disorders involving the skin that are mediated by superantigens led us to think that these antigens may be involved in the development of this disease. Also, in view of the obvious differences between JAPRP and the other PRP, we suggest that, in the future this disorder may be considered a separate entity as a reactive exanthem. [source] Pressure-rate product and phase angle as measures of acute inspiratory upper airway obstruction in rhesus monkeysPEDIATRIC PULMONOLOGY, Issue 7 2010FAAP, Patrick A. Ross MD Abstract Rationale There are limited validated, objective, and minimally invasive techniques for the bedside evaluation of upper airway obstruction (UAO) in sick infants, despite its frequency in pediatric medicine. Prior techniques include pressure-rate product (PRP), a product of esophageal pressure and respiratory rate and phase angles (PAs), a measure of asynchrony between ribcage and abdominal respiratory movements in infants with UAO. The purpose of this study is to validate the PRP and compare it to a previously validated PA in rhesus monkeys. Methods Calibrated resistors were applied to the inspiratory limb of 10 anesthetized, intubated, and spontaneously breathing rhesus monkeys (weight 8.7,±,2.5,kg). Airway pressure, respiratory rate, PAs, heart rate, and oxygen saturation were recorded. Obstruction was applied in random order as 0, 5, 20, 200, 500, and 1,000,cmH2O/L/sec for 2-min periods, the last 15,sec (10,20 breaths) were analyzed for each timeframe. Results PA increased significantly at the 200,cmH2O/L/sec level but it reached a plateau above 500,cmH2O/L/sec. PRP rose progressively and was significantly different at all levels of obstruction. Esophageal pressure change was progressively and statistically significantly different from baseline and each other at 200, 500, and 1,000,cmH2O/L/sec (P,<,0.001). Conclusions In this model of UAO, PRP tracks increasing inspiratory load better than PA. PRP continued to be linear up through the highest inspiratory resistance where the change in PA reached a plateau before the highest load. The assessment of esophageal pressure changes may offer the simplest objective measure of UAO. Pediatr Pulmonol. 2010; 45:639,644. © 2010 Wiley-Liss, Inc. [source] Effect of aluminum adjuvants on safety and immunogenicity of Haemophilus influenzae type b-CRM197 conjugate vaccinePEDIATRICS INTERNATIONAL, Issue 3 2003Güler Kanra AbstractObjective:,The present study was carried out to evaluate the safety and immunogenicity of the Haemophilus influenzae type b-CRM197 (Hib-CRM197) conjugate vaccine in relation to the change of adjuvant from aluminum hydroxide to aluminum phosphate (AlPO4). Methods:,The present study was a clinical phase II, observer-blind, randomized, multicenter, controlled study. Subjects were healthy infants aged 6,12 weeks, eligible for expanded program of immunization (EPI) routine vaccination and admitted to Hacettepe University Department of Social Pediatrics and Gülveren Health Center, Ankara. A total of 520 healthy infants were randomized in a 2:2:1 ratio to receive at either Chiron Hib/AlPO4 vaccine or VaxemHib (aluminum hydroxide adjuvant) vaccine or HibTiter (no adjuvant). Vaccines were administered simultaneously with routine diphtheria, tetanus and pertussis (DTaP) and oral polio vaccine (OPV) vaccines at 2, 4 and 6 months of age. Blood samples for anti-plain polysaccharide (PRP) antibody measurement were collected before the first vaccination and 1 month after the last vaccination. After each vaccination parents filled out a diary for 7 days. Results:,Out of 520 subjects enrolled, 514 received three doses and were included for safety analysis. Local and systemic reactions occurred with low and similar frequencies in all groups. Only erythema was more common in Chiron Hib/AlPO4 vaccine (19, 10, 11% in Chiron Hib/AlPO4, VaxemHib and HibTiter, respectively, P < 0.05). Nine serious adverse events were reported in seven cases of which none were related to vaccines. A total of 504 subjects were included in the immunogenicity analysis. The three vaccines were highly immunogenic and equivalent in terms of percentage of acquisition of long-term protective levels. The anti-PRP geometric mean titers were 9.9, 8.3 and 5.14 µg/mL, respectively (P < 0.05). Conclusions:,The use of aluminum compounds adjuvants in Hib-CRM197 conjugate vaccines does not impact the safety profile, while it does increase the magnitude of anti-PRP antibody titers. [source] Effects of ,-endorphin and met-enkephalin on platelet activityAMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2001Angelo Tirelli Abstract In the present study, ,-endorphin and met-enkephalin were tested for their antiplatelet activity in human platelet-rich plasma (PRP). Blood samples were obtained from 15 healthy subjects. The results of the study show that these two endogenous opioids (200 pg/ml final concentration) reduce platelet aggregation when it is induced by ADP at low dose (0.5 ,M). It is likely due to conformational changes on the platelet membrane that cause a non-specific decreased susceptibility to platelet-aggregating agonists. Am. J. Hematol. 68:1,3, 2001. © 2001 Wiley-Liss, Inc. [source] Spirituality in Alcoholics during TreatmentTHE AMERICAN JOURNAL ON ADDICTIONS, Issue 3 2007Katherine M. Piderman PhD The purpose of this study was to measure spiritual well-being (SWB), private religious practices (PRP), positive religious coping, abstinence self-efficacy (AASE), affiliation with AA (AAA), and their associations with alcoholics in treatment. Seventy-four adults in a three-week outpatient addiction treatment program were assessed at admission and discharge. Wilcoxon signed rank and t tests demonstrated significant increases in all variables. Spearman correlation coefficients detected significant associations between the spiritual variables, SWB and AASE, as well as PRP and AAA. Findings suggest that spiritual variables can change during treatment and that there may be connections between spiritual variables and variables associated with longer-term recovery. [source] Activated platelets contribute to stimulation of cardiac afferents during ischaemia in cats: role of 5-HT3 receptorsTHE JOURNAL OF PHYSIOLOGY, Issue 3 2002Liang-Wu Fu Myocardial ischaemia activates blood platelets and cardiac sympathetic afferents, which mediate chest pain and cardiovascular reflex responses. We have demonstrated that activated platelets stimulate ischaemically sensitive cardiac sympathetic afferents. Platelets absorb and release 5-hydroxytryptamine (5-HT) when they are activated. In the present study we hypothesized that, by releasing 5-HT, activated platelets stimulate cardiac afferents during ischaemia through a 5-HT3 receptor mechanism. Platelet-rich plasma (PRP) and platelet-poor plasma (PPP) were obtained from cats. Activation of platelets in PRP was induced by thrombin (5 units ml,1) or collagen (2 mg kg,1). Using high-performance liquid chromatography, we observed that the concentration of 5-HT was increased significantly in suspensions of platelets activated with thrombin (PRP+thrombin, 28 ± 1.7 ,m) or collagen (PRP+collagen, 27 ± 2.5 ,m) compared with suspensions of unactivated platelets (PRP+saline, 2.3 ± 0.8 ,m) and PPP. During myocardial ischaemia and reperfusion, tirofiban, a specific inhibitor of platelet glycoprotein (GP) IIb-IIIa receptors (100 ,g kg,1, I.V., followed by 5 ,g kg,1 min,1), significantly reduced the increase in the concentration of 5-HT in cardiac venous plasma from ischaemic region. Nerve activity of single-unit cardiac afferents was recorded from the left sympathetic chain (T2-T5) in anaesthetized cats. Eighty ischaemically sensitive and seven ischaemically insensitive cardiac afferents were identified. Tirofiban reduced the ischaemia-related increase in activity of seven cardiac sympathetic afferents by 50 %. Injection of 1.5 ml of PRP+collagen or PRP+thrombin into the left atrium (LA) increased activity of 16 cardiac afferents. Tropisetron (300 ,g kg,1, I.V.), a selective 5-HT3 receptor antagonist, eliminated the afferent's responses to platelets activated with collagen or thrombin. Moreover, LA injection of 5-HT (20-40 ,g kg,1) and PBG (100 ,g kg,1), a 5-HT3 receptor agonist, stimulated nine ischaemically sensitive cardiac sympathetic afferents, significantly increasing the activity of these afferents. However, injection of ,-M-5-HT (100 ,g kg,1, LA), a 5-HT2 receptor agonist, stimulated only two of the nine ischaemically sensitive cardiac afferents, and thus did not significantly alter impulse activity of this group of afferents. Both the 5-HT1 (5-CT, 100 ,g kg,1, LA) and 5-HT4 receptor agonists (SC53116, 100 ,g kg,1, LA) did not stimulate any of the nine afferents tested. Tropisetron (300 ,g kg,1, I.V.) also eliminated the response of seven ischaemically sensitive cardiac afferents to exogenous 5-HT and attenuated the ischaemia-related increase in activity of nine cardiac sympathetic afferents by 41 %. Conversely, LA injection of 5-HT (40 ,g kg,1) did not stimulate any of seven ischaemically insensitive cardiac afferents, although this group of afferents consistently responded to bradykinin (3 ,g, LA). These data indicate that during myocardial ischaemia the activated platelets stimulate cardiac sympathetic afferents, at least in part, through a 5-HT3 receptor mechanism. [source] Identification of regulatory pathways involved in the reacquisition of root growth after salt stress in Medicago truncatulaTHE PLANT JOURNAL, Issue 1 2007Francisco Merchan Summary Root growth and function are determined by the action of environmental stresses through specific genes that adapt root development to these restrictive conditions. We have defined in vitro conditions affecting the growth and recovery of Medicago truncatula roots after a salt stress. A dedicated macroarray containing 384 genes, based on a large-scale subtractive hybridization approach, was constructed and used to analyze gene expression during salt stress and recovery of root growth from this stress. Several potential regulatory genes were identified as being linked to this recovery process: a novel RNA-binding protein, a small G-protein homologous to ROP9, a receptor-like kinase, two TF IIIA-like and an AP2-like transcription factors (TF), MtZpt2-1, MtZpt2-2 and MtAp2, and a histidine kinase associated with cytokinin transduction pathways. The two ZPT2-type TFs were also rapidly induced by cold stress in roots. By analyzing transgenic M. truncatula plants showing reduced expression levels of both TFs and affected in their capacity to recover root growth after a salt stress, we identified potential target genes that were either activated or repressed in these plants. Overexpression of MtZpt2-1 in roots conferred salt tolerance and affected the expression of three putative targets in the predicted manner: a cold-regulated A (CORA) homolog, a flower-promoting factor (FPF1) homolog and an auxin-induced proline-rich protein (PRP) gene. Hence, regulatory networks depending on TFIIIA-like transcription factors are involved in the control of root adaptation to salt stress. [source] Synthesis, Antiplatelet and Vasorelaxing Activities of Xanthone DerivativesARCHIV DER PHARMAZIE, Issue 1 2009Kai-Wei Lin Abstract A series of ,-aminoalkoxylxanthones was synthesized and tested in vitro for their ability to inhibit platelet aggregation and cause vasorelaxing action. Compounds 4, 5, 12, 17, and 18 showed significant antiplatelet effects on thrombin-, arachidonic acid (AA)-, collagen-, and platelet activating factor (PAF)-induced washed rabbit platelet aggregation and exhibited inhibition of primary and secondary aggregation induced by adenosine-5'-diphosphate (ADP) in human platelet-rich-plasma (PRP). Compounds 4, 17, and 18 revealed vasorelaxing activities in rat thoracic aorta. We concluded that these compounds may be developed as new antithrombotic agents. [source] In Vitro and In Vivo Study of Ion-Implanted Collagen for the Substrate of Small Diameter Artificial GraftsARTIFICIAL ORGANS, Issue 6 2003Kimi Kurotobi Abstract: Ion implantation into the collagen-coated inner surface of the grafts was performed and evaluated in vitro and in vivo to develop small diameter artificial vascular grafts. He+ ion implanted collagen-coated grafts with a fluence of 1 × 1014 ions/cm2 inhibited platelet adhesion and demonstrated patency for 240 days in an animal study. The platelet adhesion test using platelet rich plasma (PRP) showed antithrombogenicity at the fluence of 1 × 1014 ions/cm2. Washed platelet adhesion test showed thrombus formation at the fluence of 1 × 1014 ions/cm2. The results suggested that plasma protein adsorption onto the ion-implanted collagen significantly improved performance of these synthetic grafts. [source] Participation in research programBIOCHEMISTRY AND MOLECULAR BIOLOGY EDUCATION, Issue 5 2007A Novel Course in Undergraduate Education of Life Science Abstract A novel course, "Participation in Research Program (PRP)" in life sciences is open for 1st to 3rd year undergraduates. PRP introduces the principles of a variety of biological methods and techniques and also offers an opportunity to explore some specific knowledge in more detail prior to thesis research. In addition, the PRP introduces some methodologies that have been proven to be successful at each institution to participants. Through disciplines crossing, students were trained theoretically and practically about modern techniques, facilitating the efficient commutation of general laboratory skills and modern laboratory skills, and the possession of higher research ability. Therefore, during some basic training (e.g., usage and maintenance of equipments, designing and completing experiments, analyzing data and reporting results, etc.), a series of capabilities are strengthened, such as basic experimental skills, searching appropriate methods, explaining unknown biological phenomena, and the capacity of solving problems. To determine the efficiency of these strategies, we carefully examined students' performance and demonstrated the progress in students' basic abilities of scientific research in their training. [source] Impact of a novel, extended approach of perineal radical prostatectomy on surgical margins in localized prostate cancerBJU INTERNATIONAL, Issue 1 2010Shogo Inoue Study Type , Therapy (case series) Level of Evidence 4 OBJECTIVE To validate the rationale of extended perineal radical prostatectomy (ePRP) for treating localized prostate cancer. PATIENTS AND METHODS Between December 2000 and May 2007, 196 patients with localized prostate cancer underwent PRP, among which 91 and 105 patients were treated with conventional PRP (cPRP) and ePRP, respectively. The apex, middle, base, and anterior regions of the prostate were separately analysed, and the focus of analysis was on the distribution, size, Gleason score, and positive surgical margins (PSMs) of prostate cancer foci. RESULTS The operation time was significantly shorter in ePRP compared with cPRP (161 min vs 188 min; P= 0.001), while there was no significant difference in estimated blood loss between cPRP and ePRP (550 mL vs 500 mL). At the apex and base, there was no significant difference in the PSM rate between cPRP and ePRP. In the middle, there was a lower incidence of PSMs in ePRP (2.4%) than in cPRP (10.9%; P= 0.009). On the anterior side, PSMs were more frequent in cPRP (21.6%) than in ePRP (7.1%; P= 0.029). Logistic regression analysis adjusted by PSA level showed that PSM rate was the most significantly affected by the surgical approach. CONCLUSION We think that ePRP provides an effective treatment strategy for localized prostate cancer in light of excellent cancer control and minimum potential of surgical invasiveness. [source] Inhibition of human platelet aggregation by a novel S-nitrosothiol is abolished by haemoglobin and red blood cells in vitro: implications for anti-thrombotic therapyBRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2000Ian L Megson S-Nitrosothiols are nitric oxide (NO) donor drugs that have been shown to inhibit platelet aggregation in platelet rich plasma (PRP) in vitro and to inhibit platelet activation in vivo. The aim of this study was to compare the platelet effects of a novel S-nitrosated glyco-amino acid, RIG200, with an established S-nitrosothiol, S-nitrosoglutathione (GSNO) in PRP, and to investigate the effects of cell-free haemoglobin and red blood cells on S-nitrosothiol-mediated inhibition of platelet aggregation. The effects of GSNO and RIG200 in collagen (2.5 ,g ml,1)-induced platelet aggregation in PRP and whole blood were investigated in vitro. Both compounds were found to be powerful inhibitors of aggregation in PRP, and RIG200 was significantly more potent (IC50=2.0 ,M for GSNO and 0.8 ,M for RIG200; P=0.04). Neither compound inhibited aggregation in whole blood, even at concentrations of 100 ,M. Red blood cell concentrations as low as 1% of the haematocrit, and cell-free haemoglobin (2.5 ,M), significantly reduced their inhibitory effects on platelets. Experiments involving measurement of cyclic GMP levels, electrochemical detection of NO and electron paramagnetic resonance of haemoglobin in red blood cells, indicated that scavenging of NO generated from S-nitrosothiols by haemoglobin was responsible for the lack of effect of S-nitrosothiols on platelets in whole blood. These studies suggest that scavenging of NO by haemoglobin in blood might limit the therapeutic application of S-nitrosothiols as anti-platelet agents. British Journal of Pharmacology (2000) 131, 1391,1398; doi:10.1038/sj.bjp.0703731 [source] | ||||||||||||||||||||||||||||||||||||||||