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Sample records for rabbit platelets studies

  1. Influence of platelet-rich plasma on bone regeneration: a histomorphometric study in rabbit calvaria.

    PubMed

    Torres, Jesús; Tresguerres, Isabel; Tamimi, Faleh; Clemente, Celia; Niembro, Enrique; Blanco, Luis

    2007-01-01

    The aim of this study was to evaluate whether local application of platelet-rich plasma (PRP) would induce bone regeneration in cranial defects on rabbits. Twelve female New Zealand rabbits were used for this study. Two identical 10-mm-diameter bicortical cranial defects were created in each animal. One of the defects was grafted with PRP, while the contralateral was left unfilled as a negative control. Animals were sacrificed at 2, 4, 6, and 8 weeks after surgery, and biopsy specimens were evaluated histologically and histomorphometrically under light microscopy. Analysis of variance was used for statistical analysis. The histomorphometric evaluation showed more regenerated bone after local administration of PRP at 2 weeks (P > .05), 4 weeks (P < .05), and 6 weeks (P > .05). At week 8, new bone formation was comparable in both groups. In this animal model, local application of PRP in bone defects enhances healing significantly at 4 weeks.

  2. Effectiveness of Two Methods for Preparation of Autologous Platelet-Rich Plasma: An Experimental Study in Rabbits

    PubMed Central

    Nagata, Maria J. H.; Messora, Michel R.; Furlaneto, Flávia A. C.; Fucini, Stephen E.; Bosco, Alvaro F.; Garcia, Valdir G.; Deliberador, Tatiana M.; de Melo, Luiz G. N.

    2010-01-01

    Objectives: The purpose of this study was to compare the quantity and quality of platelets in platelet-rich plasma (PRP) samples prepared using either the single- or the double-centrifugation protocol. Methods: Ten adult white New Zealand rabbits were used. Ten ml of blood were drawn from each animal via cardiac puncture. Each blood sample was divided into two equal parts for PRP preparation: 5 ml of blood were centrifuged according to a single-centrifugation protocol (Group I), and 5 ml were centrifuged according to a double-centrifugation protocol (Group II). Manual platelet counts were performed on the whole blood and PRP samples of each group. Smears were also done on all samples in order to see the morphology of the platelets. The data obtained in the manual platelet count were submitted to statistical analysis (repeated measures ANOVA, Tukey, P<.05). Results: The average whole blood platelet count was 446,389/μl. The PRP samples in Group II presented an average platelet amount significantly higher than that of Group I (1,986,875 ± 685,020/μl and 781,875 ± 217,693/μl, respectively). The PRP smears from Group II were the only one to present platelets with altered morphology (75% of the smears). A few lymphocytes with increased cytoplasm were observed in the PRP smears of both Groups I (25% of the smears) and II (62.5% of the smears). Conclusions: Within the limits of this study, it can be concluded that the double-centrifugation protocol resulted in higher platelet concentrations than did the single-centrifugation protocol. However, the double-centrifugation protocol caused alterations in platelet morphology and was more sensitive to small processing errors. PMID:20922159

  3. An immunohistochemical study of human platelets using a rabbit antibody against H18-K24 of apolipoprotein CIII (HATKTAK).

    PubMed

    Yamanaka, Takao; Sakamoto, Haruhiko; Nakagawa, Toshitaka; Tanaka, Sumiko; Matsumoto, Kouichi; Ueno, Masaki

    2013-08-01

    H18-K24 of human apolipopotein CIII (Apo CIII) (HATKTAK) is an activator of the macromolecular activators of phagocytosis from platelets (MAPPs). Using a rabbit antibody against HATKTAK, we performed an immunohistochemical study of human platelets. Indirect ELISA showed that this antibody reacts with Apo CIII-derived peptides with a C-terminal of HATKTAK, but not with Apo CIII. Immunoelectron microscopy revealed that reaction of anti-HATKTAK antibody occurred in the pseudopods of activated platelets. In blood coagula produced from the peripheral blood and formalin-fixed after various incubation periods, reaction of this antibody with platelets appeared rapidly with a peak at 3 to 6 h of incubation, and then diminished gradually. Leukocytes in the blood coagula were stained strongly positive. In tissue sections, fresh thrombi and hemorrhages with slight fibrin formation revealed a positive response of platelets to anti-HATKTAK antibody, whereas older ones with leukocytic infiltration, fibrin formation and organization did not. In addition to platelets, endothelial cells and leukocytes were stained positive by anti-HATKTAK antibody. All of the positive reactions by anti-HATKTAK antibody disappeared or diminished by co-incubation with HATKTAK. In conclusion, the anti-HATKTAK antibody reveals platelets during the early phase of activation.

  4. Inhibitory Effects of Platelet-Rich Plasma on Intervertebral Disc Degeneration: A Preclinical Study in a Rabbit Model

    PubMed Central

    Gui, Keke; Ren, Weimin; Yu, Yonglin; Li, Xin; Dong, Jiachun; Yin, Wangping

    2015-01-01

    Background Platelet-rich plasma (PRP) contains multiple growth hormones that may stimulate tissue repair. This study aimed to assess the effects of PRP in a rabbit model of IDD (annulus fibrosus puncture). Material/Methods Thirty-six adult New Zealand white rabbits were randomly divided into 3 groups: 0.1 mL PRP (group A), 0.1 mL phosphate-buffered saline (group B), and control (group C) (n=12/group). Annulus fibrosus puncture was performed to establish L4/5 and L5/6 IDD models. Two and 4 weeks later, 6 rabbits from each group were given an IVD injection at L4/5 and L5/6. Two or 4 weeks after injection, rabbits were scanned with X-ray and MRI before being sacrificed. IVDs were collected for hematoxylin and eosin, Masson’s trichrome, and Safranin O staining, and type II collagen immunohistochemistry. Results Over time, IVD height and disc imaging signal intensity decreased gradually in groups B and C, but only slightly in group A (baseline: 100% for all groups; A: 95.9±4.2% at 4 weeks, 90.1±8.4 at 6 weeks; B: 75.3±5.7% at 4 weeks, 70.8±6.4% at 6 weeks; C: 74.7±5.5% at 4 weeks, 69.9±6.2% at 6 weeks; all P<0.001, P<0.01 between A vs. B and C). Degenerative histological changes in IVDs in groups B and C were more severe compared with group A. Conclusions Platelet-rich plasma interventions can effectively attenuate the IDD process in rabbits. PMID:25965093

  5. EFFECTS OF BACTERIAL ENDOTOXIN ON RABBIT PLATELETS

    PubMed Central

    Des Prez, Roger M.; Bryant, Richard E.

    1966-01-01

    The divalent ion requirements of rabbit platelet injury by endotoxin have been defined by the use of various anticoagulant solutions and have been compared to the divalent ion requirements of platelet injury produced by addition of antigen to immune platelet-rich plasma. The endotoxin-platelet interaction takes place in citrated blood. Platelet damage by antigen is inhibited by citrate, but preincubation of antigen and immune platelet-poor plasma in the absence of citrate results in a substance, presumably antigen-antibody complement complex, which then does injure platelets in the presence of citrate. Neither endotoxin nor preincubated antigen injures platelets in the presence of sodium EDTA in concentrations sufficient to interact with all divalent cations present in plasma. These observations have been interpreted by viewing the platelet-endotoxin interaction as a consequence of platelet phagocytosis of endotoxin, a reaction not requiring complement but requiring definite small concentrations of divalent cations. The interaction of antigen and platelets is regarded as a two phase reaction, the first requiring the participation of complement and concentrations of divalent cation larger than those provided in citrated plasma, the second requiring smaller concentrations of divalent cation, no further participation of complement, and active in citrated plasma. This second phase is regarded as representing platelet phagocytosis of immune complexes. PMID:5951281

  6. Biochemical and functional abnormalities in hypercholesterolemic rabbit platelets

    SciTech Connect

    Dalal, K.B.; Ebbe, S.; Mazoyer, E.; Carpenter, D.; Yee, T. )

    1990-02-01

    This study was designed to elucidate changes in rabbit platelet lipids induced by a cholesterol rich diet and to explore the possible correlation of these lipid changes with platelet abnormalities. Pronounced biochemical alterations were observed when serum cholesterol levels of 700-1000 mg% were reached. Hypercholesterolemic (HC) platelets contained 37% more neutral lipids and 16% less phospholipids than the controls. Lysolecithin, cholesterol esters and phosphatidylinositol (PI) levels were increased in HC platelets, and the levels of phosphatidylcholine (PC) were decreased. The cholesterol/phospholipid molar ratio of lipidemic platelets increased from 0.55 +/- 0.011 to 0.89 +/- 0.016 (P less than 0.01) in eight weeks. HC platelets had 90% more arachidonic acid (AA) in the PI than normal platelets. No significant changes in AA of PC were observed. Platelet function was monitored by the uptake and release of (14C)serotonin in platelet rich plasma (PRP), using varying concentrations of collagen as an aggregating agent. The uptake of (14C)serotonin in HC and normal platelets ranged from 78-94%. The percent of (14C)serotonin released from normal and HC platelets was proportional to the concentration of collagen. However, lipidemic platelets were hyperreactive to low concentrations of collagen. Incorporation of 50 microM acetylsalicylic acid into the aggregating medium suppressed the release of (14C)serotonin in normal PRP by more than 90%, but had only a partial effect on lipidemic PRP.

  7. Effect of leukocyte- and platelet-rich fibrin (L-PRF) on bone regeneration: a study in rabbits.

    PubMed

    Knapen, Michel; Gheldof, Damien; Drion, Pierre; Layrolle, Pierre; Rompen, Eric; Lambert, France

    2015-01-01

    The positive effect of leukocyte- and platelet-rich fibrin (L-PRF) on osteogenesis has been widely described in vitro. However, clinical and preclinical studies are very little and controversial in demonstrating a significant beneficial effect of L-PRF in bone regeneration. The goal of the present study was to compare the potential effect of L-PRF in a standardized model. A total of 72 hemispheres were implanted on the calvaria of 18 rabbits and filled with three different space fillers: L-PRF, bovine hydroxyapatite (BHA), BHA + L-PRF, and an empty hemisphere was used as control. Six rabbits were sacrificed at three distinct time points: 1 week, 5 weeks, and 12 weeks. Histological and histomorphometrical analyses were carried out. At the early phase of bone regeneration (1 week), from a descriptive analysis, a higher proportion of connective tissue colonized the regeneration chamber in the two groups containing BHA particles. Nevertheless, no statistical differences were found within the four groups in terms of bone quantity and quality at each timepoint (p = .3623). According to the present study, L-PRF does not seem to provide any additional effect on the kinetics, quality, and quantity of bone in the present model of guided bone regeneration. © 2013 Wiley Periodicals, Inc.

  8. Use of platelet-rich plasma solution applied with composite chondrocutaneous graft technique: an experimental study in rabbit model.

    PubMed

    Sevim, Kamuran Zeynep; Yazar, Memet; Irmak, Fatih; Tekkeşin, Merva Soluk; Yildiz, Kemalettin; Sirvan, Selami Serhat

    2014-07-01

    Composite chondrocutaneous grafts have been used widely for patients with cleft lip nasal deformity, alar defects, and septal perforations; however, the graft viability can be easily compromised. The aim of the present study was to extend the safe length of the composite chondrocutaneous grafts by enhancement of angiogenesis and re-epithelialization through platelet-rich plasma (PRP) and to investigate the changes that occur when PRP is administered to the graft and the recipient site. Composite grafts of critical sizes (1.5, 2.0, and 2.5 cm) were planned on the rabbit ears on 1 side. Group A consisted of grafts pretreated with PRP, group B consisted of recipient beds pretreated with PRP, and group C was the control group in which defects 1.5, 2.0, and 2.5 cm in size were formed on the right ears of the rabbits. On postoperative day 7, matching size chondrocutaneous grafts were adapted to the defect areas without PRP. In all groups, graft viability was evaluated 7 days after graft adaptation in group C and 14 days after PRP administration in groups A and B. Wound healing was scored histopathologically and immunohistologically using hematoxylin and eosin, CD34, and smooth muscle actin staining. The terminal transferase fluorescein-dUTP nick end labeling assay was performed to quantitatively demonstrate the apoptosis ratio among the groups. In groups A, B, and C, the mean graft survival of the 2.0-cm equilateral triangle-shaped composite grafts was 65.43% ± 15.7%, 78.12% ± 12.8%, and 41.31% ± 37.4%, respectively (P = .0364). PRP pretreatment accelerated composite graft survival in the 2.0-cm equilateral triangle grafts by increasing epithelial regeneration and fibrosis, inducing neovascularization, and ameliorating apoptosis rates. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  9. Serotonergic agonists stimulate inositol lipid metabolism in rabbit platelets

    SciTech Connect

    Schaechter, M.; Godfrey, P.P.; Minchin, M.C.W.; McClue, S.J.; Young, M.M.

    1985-10-28

    The metabolism of inositol phospholipids in response to serotonergic agonists was investigated in rabbit platelets. In platelets prelabelled with (/sup 3/H)-inositol, in a medium containing 10 mM LiCl which blocks the enzyme inositol-1-phosphatase, 5-hydroxytryptamine (5-HT) caused a dose-dependent accumulation of inositol phosphates (IP). This suggests a phospholipase-C-mediated breakdown of phosphoinositides. Ketanserin, a selective 5-HT/sub 2/ antagonist, was a potent inhibitor of the 5-HT response, with a Ki of 28 nM, indicating that 5-HT is activating receptors of the 5-HT/sub 2/ type in the platelet. Lysergic acid diethylamide (LSD) and quipazine also caused dose-related increases in inositol phosphate levels, though these were considerably less than those produced by 5-HT. These results show that relatively small changes in phosphoinositide metabolism induced by serotonergic agonists can be investigated in the rabbit platelet, and this cell may therefore be a useful model for the study of some 5-HT receptors. 30 references, 4 figures.

  10. Platelet-activating factor stimulation of tyrosine kinase and its relationship to phospholipase C in rabbit platelets: Studies with genistein and monoclonal antibody to phosphotyrosine

    SciTech Connect

    Dhar, A.; Paul, A.K.; Shukla, S.D. )

    1990-04-01

    Platelet-activating factor (PAF) is a proinflammatory lipid that has platelet-stimulating property. PAF receptor-coupled activation of phosphoinositide-specific phospholipase C (PLC) and phosphorylation of several proteins has already been established in our laboratory. To investigate further the molecular mechanism and relationship between activation of PLC and protein phosphorylation, we have used Genistein (a putative inhibitor of tyrosine-specific protein kinases), phosphotyrosine antibody, and phosphoamino acid analysis to probe the involvement of tyrosine kinase in this process. Washed rabbit platelets were loaded with myo-(2-3H)inositol and challenged with PAF (100 nM) after pretreatment with Genistein. PLC-mediated production of radioactive inositol monophosphate, inositol diphosphate, and inositol triphosphate was monitored. PAF alone caused stimulation of PLC activity (( 3H)inositol triphosphate production), whereas pretreatment with Genistein (0.5 mM) diminished PAF-stimulated PLC activity to basal level. Genistein also blocked PAF-stimulated platelet aggregation at this dose. In contrast to Genistein, staurosporine which inhibits protein kinase C, potentiated PAF-stimulated (3H)inositol triphosphate production. Genistein substantially inhibited the combined effects of staurosporine and PAF on inositol triphosphate production. Genistein also reduced PAF-induced phosphorylation of Mr 20,000 and 50,000 proteins. Phorbol 12-myristate 13-acetate-induced Mr 40,000 protein phosphorylation was also affected by Genistein. The above results suggested that Genistein inhibited tyrosine kinase at an early stage of signal transduction by inhibiting PLC. This, in turn, decreased the activation of protein kinase C and, therefore, caused a reduction in Mr 40,000 protein phosphorylation.

  11. Effect of solely applied platelet-rich plasma on osseous regeneration compared to Bio-Oss: a morphometric and densitometric study on rabbit calvaria.

    PubMed

    Torres, Jesús; Tamimi, Faleh M; Tresguerres, Isabel F; Alkhraisat, Mohammad H; Khraisat, Ameen; Lopez-Cabarcos, Enrique; Blanco, Luis

    2008-05-01

    The use of platelet-rich plasma (PRP) in bone augmentation procedures is well documented; however, the exact benefit of this material is not yet established. This study aimed to evaluate the benefits of using PRP, when only used, and compare it to Bio-Oss (Geistlich Biomaterials, Wolhusen, Switzerland) in vertical bone augmentation capacity. The study was performed in calvaria of eight adult female New Zealand rabbits using titanium bone conduction cylinder. Two titanium cylinders were fixed into perforated slits made on the parietal bone of each rabbit. On each rabbit, one chamber was grafted with Bio-Oss, and the contralateral was filled with PRP. Animals were sacrificed 4 weeks after intervention and biopsies were taken. Densitometric, histological, and histomorphometric analyses were performed to evaluate bone mineral density, vertical bone augmentation, and remaining graft volume, respectively. Statistical analyses were performed with Mann-Whitney test, using a significance level of p < .05. Densitometric and histomorphometric data analysis revealed that mean bone mineral densities and bone augmentation were significantly lower in the cylinders treated with PRP (p < .0001) 4 weeks after implantation. This study showed no beneficial effect of using PRP on osseous regeneration. In addition, it was emphasized that Bio-Oss presents good osteoconductive properties by achieving suitable bone volume values.

  12. Preparation of platelet-rich plasma as a tissue adhesive for experimental transplantation in rabbits

    PubMed Central

    Luengo Gimeno, Federico; Gatto, Silvia; Ferro, José; Croxatto, Juan Oscar; Gallo, Juan Eduardo

    2006-01-01

    Purpose Platelet-rich plasma (PRP) is an autologous substance with adhesive properties. We aimed at developing and testing the efficacy of a method for PRP preparation in rabbits. Materials and methods An in vitro study was carried out to obtain PRP from forty rabbits and to analyze the number of platelets and type of substance needed to trigger platelet activation. To induce platelet activation, 5%, 10%, 25% and 50% CaCl solutions were used. Then, an in vivo study was performed in twelve rabbits to test PRP adhesiveness in lamellar corneal graft. A control group made up of six rabbits underwent corneal transplantation without using PRP. Results 5% CaCl was the most effective concentration in activating PRP, with a mean time of 19 minutes. An attached corneal flap was seen 3 months after surgery. A detached corneal button was seen in all controls. Conclusion Our method was able to produce rabbit-derived PRP with suitable properties for soft tissue adhesion. These results could be useful for researchers of the growing fields of tissue repair and experimental transplantation. PMID:17005053

  13. Experimental acute pancreatitis induced by platelet activating factor in rabbits.

    PubMed Central

    Emanuelli, G.; Montrucchio, G.; Gaia, E.; Dughera, L.; Corvetti, G.; Gubetta, L.

    1989-01-01

    This study indicates that a single injection of platelet activating factor (PAF, 50-500 ng) into the superior pancreaticoduodenal artery of rabbits induces dose-dependent morphologic alterations of pancreatic tissue and increases serum amylase levels, both consistent with the development of an acute pancreatitis. The main histologic findings observed by light microscopy 24-72 hours after the injection of PAF were edema, polymorphonuclear neutrophil infiltration, cell vacuolization, and acinar cell necrosis. Fat cell necrosis was present in 30% of animals. By electron microscopy an increase of the number of zymogen granules in the apical region of acinar cells was observed 3 hours after PAF challenge. At 24-72 hours, many acinar cells showed vacuoles containing myelinlike figures, zymogen granules, and cellular debris. Pancreatic lesions developed in the area supplied by the artery injected with PAF and they were completely antagonized by the pretreatment of rabbits with CV 3988, a specific antagonist of PAF. In addition, the significant protective effect of atropine suggests a potential role for cholinergic mechanisms in the pancreatic alterations induced by PAF. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:2464939

  14. pA2 values for antagonists of platelet activating factor on aggregation of rabbit platelets.

    PubMed Central

    O'Donnell, S. R.; Barnett, C. J.

    1988-01-01

    1. The relative potencies, and equilibrium dissociation constants, for nine antagonists of platelet activating factor (Paf) have been determined on rabbit platelets (in diluted platelet-rich plasma (PRP)) in experiments in which the aggregatory response to Paf was measured. 2. Log concentration-response (% maximum) curves to Paf were obtained in the absence (controls) and presence of different concentrations of each Paf antagonist drug. The antagonists shifted the Paf curves to a higher concentration range and the slopes of the Schild plots, constructed from these data, suggested that the drugs were competitive antagonists of Paf. The slopes of the Schild plots for CV-3988 and SRI 63-119 were greater than 1. 3. The pA2 values (pKB values in parentheses) were: WEB 2086 7.31 (7.63); SRI 63-119 6.95; L-652,731 6.71 (6.73); BN 52021 6.38 (6.47); SRI 63-072 6.36 (6.43); CV-3988 5.87; 48740 RP 4.97 (5.07); ketotifen 4.94 (4.95); thiazinamium 4.73 (4.76). 4. This study provides, for the first time, some functional response data for Paf antagonists (pKB values) which are in an appropriate form for use in classifying putative Paf receptors. The study also provides the comparative potencies of these Paf antagonists in inhibiting Paf-induced platelet aggregation. WEB 2086 was the most potent of the drugs examined. PMID:3293683

  15. Effect of hyperbaric oxygen therapy combined with autologous platelet concentrate applied in rabbit fibula fraction healing

    PubMed Central

    Neves, Paulo César Fagundes; de Campos Vieira Abib, Simone; Neves, Rogério Fagundes; Pircchio, Oronzo; Saad, Karen Ruggeri; Saad, Paulo Fernandes; Simões, Ricardo Santos; Moreira, Marcia Bento; de Souza Laurino, Cristiano Frota

    2013-01-01

    OBJECTIVES: The purpose is to study the effects of hyperbaric oxygen therapy and autologous platelet concentrates in healing the fibula bone of rabbits after induced fractures. METHODS: A total of 128 male New Zealand albino rabbits, between 6–8 months old, were subjected to a total osteotomy of the proximal portion of the right fibula. After surgery, the animals were divided into four groups (n = 32 each): control group, in which animals were subjected to osteotomy; autologous platelet concentrate group, in which animals were subjected to osteotomy and autologous platelet concentrate applied at the fracture site; hyperbaric oxygen group, in which animals were subjected to osteotomy and 9 consecutive daily hyperbaric oxygen therapy sessions; and autologous platelet concentrate and hyperbaric oxygen group, in which animals were subjected to osteotomy, autologous platelet concentrate applied at the fracture site, and 9 consecutive daily hyperbaric oxygen therapy sessions. Each group was divided into 4 subgroups according to a pre-determined euthanasia time points: 2, 4, 6, and 8 weeks postoperative. After euthanasia at a specific time point, the fibula containing the osseous callus was prepared histologically and stained with hematoxylin and eosin or picrosirius red. RESULTS: Autologous platelet concentrates and hyperbaric oxygen therapy, applied together or separately, increased the rate of bone healing compared with the control group. CONCLUSION: Hyperbaric oxygen therapy and autologous platelet concentrate combined increased the rate of bone healing in this experimental model. PMID:24141841

  16. Ultrastructural changes to rabbit fibrin and platelets due to aspartame.

    PubMed

    Pretorius, E; Humphries, P

    2007-01-01

    The coagulation process, including thrombin, fibrin, as well as platelets, plays an important role in hemostasis, contributing to the general well-being of humans. Fibrin formation and platelet activation are delicate processes that are under the control of many small physiological events. Any one of these many processes may be influenced or changed by external factors, including pharmaceutical or nutritional products, e.g., the sweetener aspartame (L-aspartyl-L-phenylalanine methyl ester). It is known that phenylalanine is present at position P(9) and aspartate at position P(10) of the alpha-chain of human fibrinogen, and plays an important role in the conversion of fibrinogen to fibrin by the catalyst alpha-thrombin. The authors investigate the effect of aspartame on platelet and fibrin ultrastructure, by using the rabbit animal model and the scanning electron microscope. Animals were exposed to 34 mg/kg of aspartame 26x during a 2-month period. Aspartame-exposed fibrin networks appeared denser, with a thick matted fine fiber network covering thick major fibers. Also, the platelet aggregates appeared more granular than the globular control platelet aggregates. The authors conclude by suggesting that aspartame usage may interfere with the coagulation process and might cause delayed fibrin breakup after clot formation. They suggest this, as the fibrin networks from aspartame-exposed rabbits are more complex and dense, due to the netlike appearance of the minor, thin fibers. Aspartame usage should possibly be limited by people on anti-clotting medicine or those with prone to clot formation.

  17. gamma. -hexachlorocyclohexane (. gamma. -HCH) activates washed rabbit platelets

    SciTech Connect

    Lalau-Keraly, C.; Delautier, D.; Benveniste, J.; Puiseux-Dao, S.

    1986-03-01

    In guinea-pig macrophages, ..gamma..-HCH triggers activation of the phosphatidylinositol cycle and Ca/sup 2 +/ mobilization. Since these two biochemical events are also involved in platelet activation, the authors examined the effects of ..gamma..-HCH on washed rabbit platelets. Release of /sup 14/C-serotonin (/sup 14/C-5HT) and ATP from platelets prelabelled with /sup 14/C-5HT was measured simultaneously with aggregation. ..gamma..-HCH induced shape-change, aggregation and release reaction of platelets. Maximal aggregation (89 arbitrary units, AU), was observed using 170 ..mu..M ..gamma..-HCH, and was associated with 38.1 +/- 6.9% and 161 +/- 48 nM for /sup 14/C-5HT and ATP release respectively (mean +/- 1 SD, n=3). Using 80 ..mu..M ..gamma..-HCH yielded 18 AU, 12.8 +/- 1.0% and 27 +/- 14 nM for aggregation, C-5HT and ATP release respectively (n=3). No effect was observed with 40 ..mu.. M ..gamma..-HCH. Aspirin (ASA), a cyclooxygenase blocker, did not affect ..gamma..-HCH-induced platelet activation. Apyrase (APY), an ADP scavenger, inhibited by 90% aggregation induced by 170 ..mu..M ..gamma..-HCH and slightly inhibited (15%) the /sup 14/C-5HT release. In the presence of both ASA and APY, 96% inhibition of aggregation and 48% inhibition of /sup 14/C-5HT release were observed. Thus, ..gamma..-HCH induced platelet activation in a dose-dependent manner ADP, but not cyclooxygenase-dependent arachidonate metabolites, is involved in ..gamma..-HCH-induced aggregation, whereas, both appear to play a role in ..gamma..-HCH-induced release reaction.

  18. Young steady-state rabbit platelets do not have an enhanced capacity to expose procoagulant phosphatidylserine.

    PubMed

    Reddy, Emily C; Wang, Hong; Bang, K W Annie; Packham, Marian A; Rand, Margaret L

    2017-04-13

    Platelets are recognized to be physiologically and functionally heterogeneous. An example of the diversity in reactivity is the formation of a distinct subpopulation of procoagulant phosphatidylserine (PS)-exposing platelets upon activation. Platelet age has been proposed as a determinant of platelet function, and it has been reported that young platelets are more reactive in exposing PS; using the same methodology of thiazole orange (TO) staining to distinguish young and old platelets, the percentages of procoagulant platelets produced by thrombin plus collagen activation of platelets from healthy controls were examined by flow cytometry. The procoagulant subpopulation formed by TO-positive platelets (with high TO fluorescence), purported to be young reticulated platelets, was observed to be significantly larger than that formed by TO-negative platelets (with low TO fluorescence), purported to be older platelets. However, it was noted that TO fluorescence in the total platelet population was unimodal and increased with platelet size, assessed by forward scatter. This observation raised the concern that TO-positive platelets are not necessarily the youngest platelets in the condition of steady-state platelet production. Thus, to unequivocally determine whether platelet age is a factor in procoagulant platelet formation, a different approach to identify young, steady-state platelets was employed. Rabbits were injected with biotin to label >95% of circulating platelets in vivo; 24 hours post-biotinylation, the non-biotinylated platelets in the circulation, detected flow cytometrically, are the youngest, newly-formed platelets. It was demonstrated that these youngest platelets were not larger in size than older, biotinylated platelets, and that they did not have an enhanced capacity to expose PS.

  19. Effect of evening primrose oil on platelet aggregation in rabbits fed an atherogenic diet.

    PubMed

    De La Cruz, J P; Martín-Romero, M; Carmona, J A; Villalobos, M A; Sánchez de la Cuesta, F

    1997-07-01

    Evening primrose oil (Oenothera biennis) is a rich source of omega-6 series fatty acids. We report here the effects of dietary supplementation with evening primrose oil (EPO) on platelet aggregation as the main factor in arterial thrombus formation in an experimental model of atherogenesis in rabbits. A total of 40 male white New Zealand rabbits were divided into four groups (n = 10 animals/group): 1: normal diet, 2: atherogenic diet (ATD), 3: normal diet enriched with 15% EPO, 4: ATD + EPO. Each group was kept on the diet for 6 weeks. We determined serum lipid profile, platelet aggregation in whole blood, platelet thromboxane B2 production and platelet lipid peroxides. The atherogenic diet increased platelet aggregation (135% when ADP was used, and 185% when collagen was used as the inducer). Evening primrose oil reduced hyperaggregation to the values obtained in rabbits fed with the normal diet. Thromboxane synthesis was increased from 0.18 to 2.28 nmol/10(9) platelets); EPO reduced this value to 1.38 nmol/10(9) platelets. Lipid peroxides were increased by ATD from 0.27 to 0.81 nmol/10(8) platelets; EPO prevented this increase (0.35 nmol/10(8) platelets). In conclusion, EPO reduced platelet hyperaggregability in rabbits fed an atherogenic diet.

  20. Treatment of dilated cardiomyopathy in rabbits with mesenchymal stem cell transplantation and platelet-rich plasma.

    PubMed

    Mörschbächer, P D; Alves Garcez, T N; Paz, A H; Magrisso, A B; Mello, H F; Rolim, V M; Neuwald, E B; Driemeier, D; Contesini, E A; Cirne-Lima, E

    2016-03-01

    Dilated cardiomyopathy (DCM) is a major cause of cardiovascular mortality and morbidity, and there is evidence to suggest that stem cell transplantation may be a viable treatment option for this condition. Therefore, the goal of the present study was to assess myocardial regeneration in rabbits with doxorubicin-induced DCM treated with adipose mesenchymal stem cells (MSC) alone or in combination with platelet-rich plasma (PRP). Twenty New Zealand rabbits received doxorubicin for the induction of DCM and were divided into four groups according to treatment: saline, MSC, PRP and MSC + RP. Treatment agents were injected directly into the left ventricular myocardium following a thoracoscopy. Rabbits were assessed through echocardiographic and electrocardiographic examinations, as well as serum cardiac troponin I measurements at baseline, after the induction of DCM and 15 days after treatment. Animals were euthanased following the last assessment, and hearts were collected for histopathological analyses. The MSC group showed improvements in all parameters assessed, while the PRP group showed significantly impaired heart function. Histopathology of the heart revealed that the MSC group displayed the lowest number of lesions, while rabbits in the MSC + PRP, saline and PRP groups had steadily advancing lesions. These results suggest that MSC transplantation can improve heart function in rabbits with DCM, and underscore the need for further studies of the effects of PRP on the myocardium. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Cilostazol Inhibits Accumulation of Triglyceride in Aorta and Platelet Aggregation in Cholesterol-Fed Rabbits

    PubMed Central

    Ito, Hideki; Uehara, Kenji; Matsumoto, Yutaka; Hashimoto, Ayako; Nagano, Chifumi; Niimi, Manabu; Miyakoda, Goro; Nagano, Keisuke

    2012-01-01

    Cilostazol is clinically used for the treatment of ischemic symptoms in patients with chronic peripheral arterial obstruction and for the secondary prevention of brain infarction. Recently, it has been reported that cilostazol has preventive effects on atherogenesis and decreased serum triglyceride in rodent models. There are, however, few reports on the evaluation of cilostazol using atherosclerotic rabbits, which have similar lipid metabolism to humans, and are used for investigating the lipid content in aorta and platelet aggregation under conditions of hyperlipidemia. Therefore, we evaluated the effect of cilostazol on the atherosclerosis and platelet aggregation in rabbits fed a normal diet or a cholesterol-containing diet supplemented with or without cilostazol. We evaluated the effects of cilostazol on the atherogenesis by measuring serum and aortic lipid content, and the lesion area after a 10-week treatment and the effect on platelet aggregation after 1- and 10-week treatment. From the lipid analyses, cilostazol significantly reduced the total cholesterol, triglyceride and phospholipids in serum, and moreover, the triglyceride content in the atherosclerotic aorta. Cilostazol significantly reduced the intimal atherosclerotic area. Platelet aggregation was enhanced in cholesterol-fed rabbits. Cilostazol significantly inhibited the platelet aggregation in rabbits fed both a normal diet and a high cholesterol diet. Cilostazol showed anti-atherosclerotic and anti-platelet effects in cholesterol-fed rabbits possibly due to the improvement of lipid metabolism and the attenuation of platelet activation. The results suggest that cilostazol is useful for prevention and treatment of atherothrombotic diseases with the lipid abnormalities. PMID:22761774

  2. Evaluation of the bone healing process utilizing platelet-rich plasma activated by thrombin and calcium chloride: a histologic study in rabbit calvaria.

    PubMed

    Betoni-Junior, Walter; Dechichi, Paula; Esteves, Jônatas Caldeira; Zanetta-Barbosa, Darceny; Magalhães, Aparecido Eurípedes Onório

    2013-02-01

    To evaluate the bone healing of defects filled with particulate bone graft in combination with platelet-rich plasma (PRP), added with a mixture of calcium chloride and thrombin or just calcium chloride. Two 5-mm bone defects were created in the calvaria of 24 rabbits. Each defect was filled with particulate bone graft and PRP. In one defect the PRP was activated by a mixture of calcium chloride and thrombin; in the other, PRP was activated by calcium chloride only. The animals were euthanized 1, 2, 4, and 8 weeks after the surgeries, and the calvaria was submitted to histologic processing for histomorphometric analysis. The qualitative analysis has shown that both defects presented the same histologic characteristics so that a better organized, more mature, and well-vascularized bone tissue was noticed in the eighth week. A good bone repair was achieved using either the mixture of calcium chloride and thrombin or the calcium chloride alone as a restarting agent of the coagulation process.

  3. Implications of anticoagulants and gender on cell counts and growth factor concentration in platelet-rich plasma and platelet-rich gel supernatants from rabbits.

    PubMed

    González, Juan C; López, Catalina; Carmona, Jorge U

    2016-01-01

    Our objectives were as follows: 1) to validate a protocol for producing rabbit platelet-rich plasma (PRP); 2) to determine the influence of two anticoagulants, sodium citrate and acid-citrate-dextrose solution A, and gender on cell count in PRP and growth factor concentration in pure platelet-rich gel supernatants; 3) to correlate the variables evaluated. Whole blood from 18 New Zealand rabbits (9 males and 9 females) was obtained with sodium citrate and acid-citrate-dextrose solution A for processing PRP fractions (A and B), which were evaluated for haematology. The PRP fractions were either activated with calcium gluconate or lysated with a detergent. The concentrations of transforming growth factor beta 1 and platelet-derived growth factor BB were assayed by ELISA. The sodium citrate PRP-B had significantly higher counts of platelets in comparison to PRP-A and whole blood obtained with the same anticoagulant and the homologous acid-citrate-dextrose solution A PRP fraction. The sodium citrate PRP-A had a significantly higher count of leukocytes compared to the homologous acid-citrate-dextrose solution A fraction. All the PRP fractions had a significant leuko-reduction when compared to whole blood. The sodium citrate PRP-A fraction from female rabbits had significantly lower platelet counts and significantly higher leukocyte counts than the same acid-citrate-dextrose solution A fraction. Growth factor concentration was not affected by the type of anticoagulant or gender. The type of anticoagulant and gender affected the cell counts in PRP, but they did not influence the growth factor concentration. More complete rabbit PRP studies should be performed before evaluating this type of substance in models of disease.

  4. Role of platelet-activating factor in polymorphonuclear neutrophil recruitment in reperfused ischemic rabbit heart.

    PubMed Central

    Montrucchio, G.; Alloatti, G.; Mariano, F.; Comino, A.; Cacace, G.; Polloni, R.; De Filippi, P. G.; Emanuelli, G.; Camussi, G.

    1993-01-01

    This study investigated the role of platelet-activating factor in the recruitment of polymorphonuclear neutrophils (PMN) in a rabbit model of cardiac ischemia and reperfusion. The accumulation of PMN was evaluated 2 and 24 hours after removal of 40 minutes of coronary occlusion by morphometric analysis and 111In-labeled PMN infiltration. The administration of two structurally unrelated platelet-activating factor-receptor antagonists (SDZ 63-675, 5 mg/kg body weight, and WEB 2170, 5 mg/kg body weight) before reperfusion significantly reduced the accumulation of PMN, as well as the hemodynamic alterations and the size of necrotic area. Two hours after reperfusion, the percentage of increase of 111In-labeled PMN in transmural central ischemic zone was significantly reduced in rabbits pretreated with SDZ 63-675 (51.4 +/- 7.9) or WEB 2170 (32.4 +/- 8.8) with respect to untreated rabbits (107.6 +/- 13.5). The morphometric analysis of myocardial sections confirmed the reduction of PMN infiltration at 2 hours and demonstrated that at 24 hours the phenomenon was even more significant. In addition, SDZ 63-675 and WEB 2170 prevented early transient bradycardia and hypotension and reduced the infarct size, judged by staining with tetrazolium at 2 and 24 hours after reperfusion, and by histological examination at 24 hours. These results suggest that platelet-activating factor is involved in the accumulation of PMN in the reperfused ischemic myocardium and contributes to the evolution of myocardial injury. Images Figure 5 Figure 6 PMID:8434642

  5. Role of platelet-activating factor in the reperfusion injury of rabbit ischemic heart.

    PubMed Central

    Montrucchio, G.; Alloatti, G.; Mariano, F.; de Paulis, R.; Comino, A.; Emanuelli, G.; Camussi, G.

    1990-01-01

    This study shows that the administration of the PAF receptor antagonist SDZ 63.675 (5 mg/kg body weight) before reperfusion significantly reduced the hematologic and hemodynamic alterations, as well as the size of necrotic area in rabbits subjected to 40 minutes of coronary occlusion and reperfusion. Pretreatment with SDZ 63.675 prevented the reduction of platelet counts in the blood obtained from the right ventricle (86.6 +/- 2.8% of the control preischemia value) and the transient bradycardia (85.0 +/- 2.8%), the systemic hypotension (58.0 +/- 2.8%), and the increase in right ventricular pressure (125.0 +/- 3.6%) that were evident in the first minutes of reperfusion in untreated control rabbits. Two as well as 24 hours after reperfusion, the infarct size, judged by staining with tetrazolium, was significantly reduced in rabbits treated with SDZ 63.675 (infarct size in control animals, 66.0 +/- 2.9% and 63.46 +/- 2.09% of the risk region at 2 or 24 hours, respectively, compared with 38.9 +/- 5.2% and 37.11 +/- 2.44% of the risk region at 2 and 24 hours in rabbits treated with SDZ 63.675). This result was confirmed by histologic examination of cardiac tissue 24 hours after reperfusion. In addition, SDZ 63.675 markedly reduced the accumulation of 111In-oxine-labeled platelets that occurs 15 minutes after reperfusion in the central ischemic area of the heart and in the lungs. These results suggest that PAF plays a role in the evolution of myocardial injury observed during reperfusion. Images Figure 8 PMID:2372044

  6. Streptococcus sanguis-Induced Platelet Clotting in Rabbits and Hemodynamic and Cardiopulmonary Consequences

    PubMed Central

    Meyer, Maurice W.; Gong, Ke; Herzberg, Mark C.

    1998-01-01

    By mimicking hemostatic structural domains of collagen, Streptococcus sanguis (aggregation-positive phenotype; Agg+) induces platelets to aggregate in vitro. To test the hypothesis that aggregation occurs in vivo, S. sanguis (Agg+ or Agg− suspension) was infused intravenously into rabbits. The extent of hemodynamic and cardiopulmonary changes and the fate of circulating platelets were Agg+ strain dose dependent. Within 45 to 50 s of the start of infusion, 40 × 108 CFU of the Agg+ strain caused increased blood pressure. Thirty seconds after infusion, other changes occurred. Intermittent electrocardiographic abnormalities (13 of 15 rabbits), ST-segment depression (10 of 15 rabbits), and preventricular contractions (7 of 15 rabbits) manifested at 3 to 7 min, with frequencies dose dependent. Respiratory rate and cardiac contractility increased during this phase. Blood catecholamine concentration, thrombocytopenia, accumulation of 111Indium-labeled platelets in the lungs, and ventricular axis deviation also showed dose dependency. Rabbits were unaffected by inoculation of an Agg− strain. Therefore, Agg+ S. sanguis induced platelet aggregation in vitro. Platelet clots caused hemodynamic changes, acute pulmonary hypertension, and cardiac abnormalities, including ischemia. PMID:9826372

  7. A Novel Technique for Conjunctivoplasty in a Rabbit Model: Platelet-Rich Fibrin Membrane Grafting

    PubMed Central

    Çakmak, Hasan Basri; Dereli Can, Gamze; Ünverdi, Hatice; Toklu, Yasin; Hücemenoğlu, Sema

    2016-01-01

    Purpose. To investigate the effect of platelet-rich fibrin (PRF) membrane on wound healing. Methods. Twenty-four right eyes of 24 New Zealand rabbits equally divided into 2 groups for the study design. After the creation of 5 × 5 mm conjunctival damage, it was secured with PRF membrane, which was generated from the rabbit's whole blood samples in PRF membrane group, whereas damage was left unsutured in the control group. Three animals were sacrificed in each group on the 1st, 3rd, 7th, and 28th postoperative days. Immunohistochemical (IHC) stainings and biomicroscopic evaluation were performed and compared between groups. Results. PRF membrane generated significant expressions of vascular endothelial growth factor (VEGF), transforming growth factor-beta (TGF-β), and platelet-derived growth factor (PDGF) in the early postoperative period. However, the IHC evaluation allowed showing the excessive staining at day 28, in control group. Biomicroscopic evaluation revealed complete epithelialization in PRF membrane group, but none of the cases showed complete healing in the control group. Conclusions. This experimental study showed us the beneficial effects of the PRF membrane on conjunctival healing. Besides its chemical effects, it provides mechanical support as a scaffold for the migrating cells that are important for ocular surface regeneration. These overall results encourage us to apply autologous PRF membrane as a growth factor-enriched endogenous scaffold for ocular surface reconstruction. PMID:27747098

  8. Platelet-Rich Plasma May Improve Osteochondral Donor Site Healing in a Rabbit Model

    PubMed Central

    Smyth, Niall A.; Haleem, Amgad M.; Ross, Keir A.; Hannon, Charles P.; Murawski, Christopher D.; Do, Huong T.; Kennedy, John G.

    2016-01-01

    Purpose The purpose of this study was to assess the effect(s) of platelet-rich plasma (PRP) on osteochondral donor site healing in a rabbit model. Methods Osteochondral donor sites 3 mm in diameter and 5 mm in depth were created bilaterally on the femoral condyles of 12 New Zealand White rabbits. Knees were randomized such that one knee in each rabbit received an intra-articular injection of PRP and the other received saline (placebo). Rabbits were euthanized at 3, 6, and 12 weeks following surgery. Repair tissue was evaluated using the International Cartilage Repair Society (ICRS) macroscopic and histological scores. Results No complications occurred as a result of the interventions. There was no significant difference in macroscopic scores between the 2 groups (5.5 ± 3.8 vs. 3.8 ± 3.5; P = 0.13). Subjective macroscopic assessment determined greater tissue infill with fewer fissures and a more cartilage-like appearance in PRP-treated knees. Overall ICRS histological scores were better in the PRP group compared with the placebo (9.8 ± 2.0 vs. 7.8 ± 1.8; P = 0.04). Histological scores were also higher in the PRP group compared with the placebo group at each time point. Greater glycosaminoglycan and type II collagen content were noted in the repair tissue of the PRP group compared with the placebo group. Conclusion The results of this study indicate that PRP used as an intra-articular injection may improve osteochondral healing in a rabbit model. PMID:26958322

  9. Advantages of Pure Platelet-Rich Plasma Compared with Leukocyte- and Platelet-Rich Plasma in Treating Rabbit Knee Osteoarthritis.

    PubMed

    Yin, Wen-Jing; Xu, Hai-Tao; Sheng, Jia-Gen; An, Zhi-Quan; Guo, Shang-Chun; Xie, Xue-Tao; Zhang, Chang-Qing

    2016-04-17

    BACKGROUND Concentrated leukocytes in leukocyte- and platelet-rich plasma (L-PRP) may deliver increased levels of pro-inflammatory cytokines to activate the NF-κB signaling pathway, to counter the beneficial effects of growth factors on osteoarthritic cartilage. However, to date no relevant studies have substantiated that in vivo. MATERIAL AND METHODS Autologous L-PRP and pure platelet-rich plasma (P-PRP) were prepared, measured for componential composition, and injected intra-articularly after 4, 5, and 6 weeks post-anterior cruciate ligament transection. Caffeic acid phenethyl ester (CAPE) was injected intraperitoneally to inhibit NF-κB activation. All rabbits were sacrificed after 8 weeks postoperative. Enzyme-linked immunosorbent assays were performed to determine interleukin 1β (IL-1β) and prostaglandin E2 (PGE2) concentrations in the synovial fluid, Indian ink staining was performed for gross morphological assessment, and hematoxylin and eosin staining and toluidine blue staining were performed for histological assessment. RESULTS Compared with L-PRP, P-PRP injections achieved better outcomes regarding the prevention of cartilage destruction, preservation of cartilaginous matrix, and reduction of IL-1β and PGE2 concentrations. CAPE injections reversed the increased IL-1β and PGE2 concentrations in the synovial fluid after L-PRP injections and improved the outcome of L-PRP injections to a level similar to P-PRP injections, while they had no influence on the therapeutic efficacy of P-PRP injections. CONCLUSIONS Concentrated leukocytes in L-PRP may release increased levels of pro-inflammatory cytokines to activate the NF-κB signaling pathway, to counter the beneficial effects of growth factors on osteoarthritic cartilage, and finally, result in a inferior efficacy of L-PRP to P-PRP for the treatment of osteoarthritis.

  10. Liberation of serotonin from rabbit blood platelets by bacterial cell walls and related compounds.

    PubMed Central

    Harada, K; Kotani, S; Takada, H; Tsujimoto, M; Hirachi, Y; Kusumoto, S; Shiba, T; Kawata, S; Yokogawa, K; Nishimura, H; Kitaura, T; Nakajima, T

    1982-01-01

    A study was made on the activity of various bacterial cell walls and peptidoglycans to liberate serotonin from rabbit blood platelets. All of the test cell walls or peptidoglycans prepared from 27 strains of 21 bacterial species were shown to cause a marked release of serotonin, regardless of differences in types of peptidoglycan and non-peptidoglycan moieties and in some biological properties. The assay made with the water-soluble "digests" of Staphylococcus epidermidis cell wall peptidoglycans, which were prepared by use of appropriate enzymes, revealed that a polymer of peptidoglycan subunits (a disaccharide-stempeptide) was definitely active in the release of serotonin, but a structural unit monomer was inactive. Among a variety of synthetic muramylpeptides and their 6-O-acyl derivatives, only 6-O-(3-hydroxy-2-docosylhexacosanoyl)-N-acetylmuramyl-L-alanyl-D-isoglutaminyl- L-lysyl-D-alanine was found to hold a strong serotonin-liberating activity. Images PMID:7129634

  11. Conversion of 1-alkyl-2-acetyl-sn-glycerols to platelet activating factor and related phospholipids by rabbit platelets

    SciTech Connect

    Blank, M.L.; Lee, T.; Cress, E.A.; Malone, B.; Fitzgerald, V.; Snyder, F.

    1984-10-15

    The metabolic pathway for 1-alkyl-2-acetyl-sn-glycerols, a recently discovered biologically active neutral lipid class, was elucidated in experiments conducted with rabbit platelets. The total lipid extract obtained from platelets incubated with 1-(1-,2-/sup 3/H)alkyl-2-acetyl-sn-glycerols or 1-alkyl-2-(/sup 3/H)acetyl-sn-glycerols contained at least six metabolic products. The six metabolites, identified on the basis of chemical and enzymatic reactions combined with thin-layer or high-performance liquid chromatographic analyses, corresponded to 1-alkyl-sn-glycerols, 1-alkyl-2-acetyl-sn-glycero-3-phosphates, 1-alkyl-2-acyl(long-chain)-sn-glycero-3-phosphoethanolamines, 1-alkyl-2-acetyl-sn-glycero-3-phosphoethanolamines, 1-alkyl-2-acyl(long-chain)-sn-glycero-3-phosphocholines, and 1-alkyl-2-actyl-sn-glycero-3-phosphocholines (platelet activating factor). These results indicate that the metabolic pathway for alkylacetylglycerols involves reaction steps catalyzed by the following enzymatic activities: choline- and ethanolamine- phosphotransferases, acetyl-hydrolase, an acyltransferase, and a phosphotransferase. The step responsible for the biosynthesis of platelet activating factor would appear to be the most important reaction in this pathway and this product could explain the hypotensive activities previously described for alkylacetyl-(or propionyl)-glycerols. Of particular interest was the preference exhibited for the utilization of the 1-hexadecyl-2-acetyl-sn-glycerol species in the formation of platelet activating factor.

  12. Studies on Human Platelet Gangliosides

    PubMed Central

    Marcus, Aaron J.; Ullman, Harris L.; Safier, Lenore B.

    1972-01-01

    Gangliosides, glycosphingolipids which contain sialic acid, were studied in human platelets. They represented 0.5% of the platelet lipids and accounted for 6% of the total neuraminic acid content of platelets. Three major ganglioside fractions were identified and characterized. Ganglioside I was hematoside (G6) and comprised 92% of the platelet gangliosides. It contained glucose, galactose, and sialic acid in molar ratios of 1:1:1 and no hexosamine. The major fatty acid was behenate (22:0). Ganglioside I was also identified in isolated platelet granules and membranes. Ganglioside II (5%) contained glucose, galactose, sialic acid, and hexosamines (molar ratios 1:2:1:1). The hexosamines were glucosamine (72%) and galactosamine (28%). It was therefore designated as ganglioside lacto-N-neotetraose. Ganglioside III (2%) contained disialosyllactosyl ceramide (G3A) as well as two other gangliosides which could not be precisely characterized. Gangliosides I, II, and III were susceptible to the action of Clostridium perfringens neuraminidase as evidenced by full recovery of sialic acid in its free form after incubation. Neutral platelet glycolipids were qualitatively examined by thin-layer chromatography. The major component was lactosyl ceramide. Interactions of gangliosides I and III and serotonin-14C were examined in an equilibrium dialysis system at 4°C. The gangliosides bound serotonin-14C in relatively small quantities, whereas control lipids were negative. The binding was essentially unchanged by reverse dialysis, ultracentrifugation and subsequent thin-layer chromatography. The results are comparable to the previously observed nonmetabolic interactions between whole platelets and serotonin in the cold. It is suggested that the orientation and specific distribution of platelet membrane glycolipids may be important determinants of the unique surface properties of platelets. Images PMID:4341436

  13. Platelet involvement in the nephritis of acute serum sickness in rabbits: protection by dipyridamole and FUT-175.

    PubMed Central

    Koyama, A; Inage, H; Sano, M; Narita, M; Tojo, S; Neild, G H; Cameron, J S

    1985-01-01

    In the acute serum sickness model in rabbits, we investigated platelet release of 5-HT, platelet surface immunoglobulins, and platelet aggregation in response to ADP, together with the effect of dipyridamole and the Clr antagonist FUT-175. The immune release of 5-HT from platelets occurred between 4 and 6 days after injection of bovine serum albumin (BSA), before immune elimination and proteinuria, but coincident with the appearance of immune complexed BSA in the circulation. Nevertheless, platelet turnovers were not detectably accelerated. Treatment with dipyridamole 50 mg/kg/24 h prevented the release of 5-HT and inhibited proteinuria, glomerular hypercellularity and immune complexes in the glomeruli. Using the Clr antagonist FUT-175, similar abrogation of the disease was obtained. We conclude that in the nephritis of acute serum sickness in rabbits, some of the immune release from platelets may be the result of immune complex binding to the platelet, perhaps through the receptor for C3b. PMID:4042428

  14. The effect of platelet-rich plasma on Achilles tendon healing in a rabbit model.

    PubMed

    Takamura, Masaki; Yasuda, Toshito; Nakano, Atsushi; Shima, Hiroaki; Neo, Masashi

    2017-01-01

    The aim of the present study was to evaluate the effects of PRP on Achilles tendon healing in rabbits during the inflammatory, proliferative, and remodeling phases by histological examination and quantitative assessments. Fifty mature male Japanese albino rabbits with severed Achilles tendons were divided into two equal groups and treated with platelet-rich plasma (PRP) or left untreated. Tendon tissue was harvested at 1, 2, 3, 4, and 6 weeks after treatment, and sections were stained with hematoxylin-eosin and monoclonal antibodies against CD31 and type I collagen. Collagen fibers proliferated more densely early after severance, and subsequent remodeling of the collagen fibers and approximation of normal tendinous tissue occurred earlier in the PRP group than in the control group. The fibroblast number was significantly higher in the PRP group than in the control group at 1 and 2 weeks. Similarly, the area ratio of CD31-positive cells was significantly higher in the PRP group than in the control group at 1 and 2 weeks. Positive staining for type I collagen was more intense in the PRP group than in the control group after 3 weeks, indicating tendon maturation. Administration of PRP shortened the inflammatory phase and promoted tendon healing during the proliferative phase. Copyright © 2016 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.

  15. Effect of platelet activating factor (PAF) on pulmonary circulation in isolated rabbit lung.

    PubMed

    Comellas, A; Tristano, S; Pesce, L; Friedman, E; Marcano, H; Sánchez de León, R

    1999-03-01

    Platelet activating factor (PAF) has been implicated in the pathophysiology of acute lung injury. The aim of this work is to study the effect of PAF on isolated and perfused rabbit lungs with blood and with a blood-free solution. 24 isolated and perfused rabbit lungs have been used: 8 control preparations (CP), 4 vehicles preparations (VP), 8 PAF preparations (PP) to which we administered PAF (1 microg/Kg of rabbit weight) and 4 acellular preparations (AP) with the same dose of PAF as in PP but dissolved in BSA-Krebs buffer solution. In the preparations pulmonary artery pressure (Ppa), airway pressure (Paw), left atria pressure (Pla) and fluid filtration rate (FFR) were registered. Ppa resulted in a significant difference in AP vs PP, with a value of 21 cm of water (CI 95%: 12-26) vs 205.1 cm of water (CI 95%: 141.3 - 271) respectively. A increase in FFR was observed in PP but it did not occur in AP, the difference being statistically significant: 5.515 g/min (CI 95 %: 2.425 - 8.865) vs 0.049 g/min (CI 95%: 0.008 - 0.32) respectively. Paw was statistically different in PP vs AP, with a value of 14.3 cm of water (CI 95%: 11.57 - 16.7) vs 8.5 cm of water (CI 95%: 8-9) respectively. These results suggest that PAF does not have a direct effect on the endothelium or smooth muscle in the production of lung edema.

  16. Human Platelet Senescence Study.

    DTIC Science & Technology

    1980-03-01

    ability to measure certain enzymes to their oxidation-reduc other enzymes which can be measured by o phosphatase , acid phosphatase , chymotryp...alkaline sin, trypsin, esterases (17)); M use of n A or wheat germ agglutinin in the second etect specific carbohydrate constituents. We have...Von Willebrand factor. Nurden and Caen also demonstrated that GPI was rich in sialic acid (5) and probably responsible for the platelets’ surface

  17. Metabolism of platelet activating factor (PAF) by rabbit renal homogenates

    SciTech Connect

    Cagen, L.M.; Yeh, Y.M.; Baer, P.G.

    1986-05-01

    Rabbit renal cortical slices convert added (alkyl-/sup 3/H)-PAF to metabolites that cochromatograph with lyso-PAF and alkyl-acyl glycerophosphocholine (AAGPC) and to a tritiated nonpolar metabolite that is the principal product recovered from the tissues. Rabbit renal cortical homogenates convert mixtures of (alkyl-/sup 3/H)-PAF and (choline-/sup 14/C)-PAF to products that cochromatograph with lyso-PAF and with AAGPC and to a tritiated nonpolar and a /sup 14/C-labeled polar metabolite. Formation of the latter products follow parallel time courses; they are the principal species present after extended incubation (30 min). Enzymatic capacity for formation of these metabolites is concentrated in the microsomal fraction (100,000 x g pellet). Their formation by washed microsomes does not require the addition of cofactors, but their rate of formation is enhanced in the presence of high concentrations of Ca/sup + +/ (1mM) and abolished by EDTA (1.25mM) or EGTA (1.25mM). Formation of the polar metabolite does not appear to be due to phospholipase C or D activity. Its formation is not enhanced by addition of glutathione or 2-amino-6,7-dimethyl-tetrahydropteridine, cofactors that support oxidative dealkylation of alkyl ether phospholipids in other tissues. Conversion of PAF to final products other than AAGPC appears to be a significant pathway for disposition of this substance in rabbit kidney.

  18. Platelet-Rich Fibrin Facilitates Rabbit Meniscal Repair by Promoting Meniscocytes Proliferation, Migration, and Extracellular Matrix Synthesis

    PubMed Central

    Wong, Chin-Chean; Kuo, Tzong-Fu; Yang, Tsung-Lin; Tsuang, Yang-Hwei; Lin, Ming-Fang; Chang, Chung-Hsun; Lin, Yun-Ho

    2017-01-01

    Although platelet-rich fibrin (PRF) has been used in clinical practice for some time, to date, few studies reveal its role as a bioactive scaffold in facilitating meniscal repair. Here, the positive anabolic effects of PRF on meniscocytes harvested from the primary culture of a rabbit meniscus were revealed. The rabbit meniscocytes were cultured with different concentrations of PRF-conditioned medium, and were evaluated for their ability to stimulate cell migration, proliferation, and extracellular matrix formation. In vivo, meniscal defects were created via an established rabbit animal model and were evaluated by a histology-based four-stage scoring system to validate the treatment outcome three months postoperatively. The in vitro results showed that PRF could induce cellular migration and promote proliferation and meniscocyte extracellular matrix (ECM) synthesis of cultured meniscocytes. In addition, PRF increased the formation and deposition of cartilaginous matrix produced by cultured meniscocytes. Morphological and histological evaluations demonstrated that PRF could facilitate rabbit meniscal repair. The data highlight the potential utility of using PRF in augmenting the healing of meniscal injuries. These advantages would benefit clinical translation, and are a potential new treatment strategy for meniscal repair. PMID:28783120

  19. Platelet P2Y12 Blockers Confer Direct Postconditioning-like Protection in Reperfused Rabbit Hearts

    PubMed Central

    Yang, Xi-Ming; Liu, Yanping; Cui, Lin; Yang, Xiulan; Liu, Yongge; Tandon, Narendra; Kambayashi, Junichi; Downey, James M.; Cohen, Michael V.

    2012-01-01

    Background Blockade of platelet activation during primary percutaneous intervention for acute myocardial infarction is standard care to minimize stent thrombosis. To determine whether antiplatelet agents offer any direct cardioprotective effect, we tested whether they could modify infarction in a rabbit model of ischemia/reperfusion caused by reversible ligation of a coronary artery. Methods and Results The P2Y12 (adenosine diphosphate) receptor blocker cangrelor administered shortly before reperfusion in rabbits undergoing 30-minute regional ischemia/3-hour reperfusion reduced infarction from 38% of ischemic zone in control hearts to only 19%. Protection was dose dependent and correlated with the degree of inhibition of platelet aggregation. Protection was comparable to that seen with ischemic postconditioning (IPOC). Cangrelor protection, but not its inhibition of platelet aggregation, was abolished by the same signaling inhibitors that block protection from IPOC suggesting protection resulted from protective signaling rather than anticoagulation. As with IPOC, protection was lost when cangrelor administration was delayed until 10 minutes after reperfusion and no added protection was seen when cangrelor and IPOC were combined. These findings suggest both IPOC and cangrelor may protect by the same mechanism. No protection was seen when cangrelor was used in crystalloid-perfused isolated hearts indicating some component in whole blood is required for protection. Clopidogrel had a very slow onset of action requiring 2 days of treatment before platelets were inhibited, and only then the hearts were protected. Signaling inhibitors given just prior to reperfusion blocked clopidogrel’s protection. Neither aspirin nor heparin was protective. Conclusions Clopidogrel and cangrelor protected rabbit hearts against infarction. The mechanism appears to involve signal transduction during reperfusion rather than inhibition of intravascular coagulation. We hypothesize that both

  20. Histological Evaluation of Hydroxyapatite Granules with and without Platelet-Rich Plasma versus an Autologous Bone Graft: Comparative study of biomaterials used for spinal fusion in a New Zealand white rabbit model.

    PubMed

    Zakaria, Zamzuri; Seman, Che N Z C; Buyong, Zunariah; Sharifudin, Mohd A; Zulkifly, Ahmad H; Khalid, Kamarul A

    2016-11-01

    Hydroxyapatite (HA) has osteoconductive properties and is widely used as a bone graft substitute. Platelet-rich plasma (PRP) is an autologous product with osteoinductive effects. Hypothetically, a combination of both would augment the bone formation effect of HA and widen its application in spinal fusion surgeries. This study aimed to compare new bone formation with HA granules alone and in combination with PRP versus an autologous bone graft during a lumbar intertransverse process spinal fusion. A total of 16 adult New Zealand white rabbits underwent single-level bilateral intertransverse process fusion at the L5-L6 vertebrae. One side of the spine received either HA granules alone or a combination of HA granules and PRP, while the contralateral side received an autologous bone graft. Four animals each from the HA group and the HA plus PRP group versus the autograft group were assessed either at six or 16 weeks by undecalcified histology and histomorphometry. The mean percentage of new bone areas over the corresponding fusion masses were compared between groups. No significant difference in new bone formation was observed between the HA and HA plus PRP groups at six or 16 weeks. The autograft group had significantly more new bone formation at six and 16 weeks (P = 0.004 and <0.001, respectively). An autologous bone graft remains superior to HA granules, with or without PRP. HA granules demonstrated an excellent osteoconductive scaffold but had poor biodegradability. While PRP enhances the properties of HA granules, these biomaterials do not have a synergistic effect.

  1. Evaluation of bioactive glass and platelet-rich plasma for bone healing in rabbit calvarial defects.

    PubMed

    Penteado, Luiz A M; Colombo, Carlos E D; Penteado, Roberta A P M; Assis, Angélica O; Gurgel, Bruno C V

    2013-09-01

    Bone regeneration is an important objective in clinical dental practice and has been used for different applications. The aim of this study was to evaluate the effectiveness of platelet-rich plasma (PRP) and bioactive glass (BG) for bone healing of surgical calvarial defects in rabbits. Two 8-mm defects were prepared in the parietal bones of ten animals, and the animals were randomly assigned to two groups. In each group, two subgroups were created with five defects each: BC - blood clot, BG, PRP and PRP + BG. Thus, four treatments were performed with five specimens each. The animals were sacrificed after 12 weeks and the specimens were analyzed radiographically, histologically and histomorphometrically. Data were subjected to ANOVA and Tukey's tests (α = 0.05). Outcomes demonstrated that the PRP group had higher bone density (%) values than the groups not treated with PRP (P < 0.05). Histometrically, both groups treated with PRP (PRP: 25.6 ± 9.9; PRP+BG: 25.8 ± 12.4) demonstrated higher percentages of new bone formation than the groups not treated with PRP (BG: 6.1 ± 4.3; BC: 7.8 ± 5.6) (P < 0.05). The results suggested that PRP improved bone repair and that bioactive glass alone, or in association with PRP, did not improve bone healing.

  2. Inhibitory effects of Atractylodis lanceae rhizoma and Poria on collagen- or thromboxane A2-induced aggregation in rabbit platelets.

    PubMed

    Nasu, Yuiko; Iwashita, Masaya; Saito, Masaki; Fushiya, Shinji; Nakahata, Norimichi

    2009-05-01

    Kami-shoyo-san (Jia-Wei-Xiao-Yao-San), Toki-shakuyaku-san (Dang-Gui-Shao-Yao-San) and Toki-shigyaku-ka-goshuyu-shokyo-to (Dang-Gui-Si-Ni-Jia-Wu-Zhu-Yu-Sheng-Jiang-Tang) are Kampo (traditional Chinese) medicines which are traditionally and effectively used for the treatment of chilly sensation (Hiesho) in Japan, but the active components and their detailed mechanisms have not yet been clarified. Etiologies of Hiesho include poor peripheral blood circulation and platelet aggregability contributes to peripheral blood circulation; therefore, we investigated the effect of Kampo medicines on platelet aggregation using rabbit platelets in vitro. Collagen and U46619, a thromboxane A(2) receptor agonist, caused rabbit platelet aggregation, which was potently inhibited by pretreatment of platelets with Kami-shoyo-san and Toki-shakuyaku-san in vitro. Toki-shigyaku-ka-goshuyu-shokyo-to, however, did not significantly inhibit collagen- or U46619-induced platelet aggregation. Therefore, we examined the effect on platelet aggregation of two herbal medicines, Atractylodis Lanceae Rhizoma and Poria, both of which are contained in Kami-shoyo-san and Toki-shakuyaku-san but not in Toki-shigyaku-ka-goshuyu-shokyo-to. As the results indicate, Atractylodis Lanceae Rhizoma inhibited platelet aggregation induced by collagen but not by U46619. Poria effectively inhibited U46619-induced platelet aggregation and it partially inhibited collagen-induced platelet aggregation. On the other hand, Atractylodis Lanceae Rhizoma and Poria did not inhibit adrenaline/adenosine diphosphate- or adrenaline/serotonin-induced platelet aggregation. These results suggest the possibility that the inhibition of platelet aggregation by two Kampo medicines, Kami-shoyo-san and Toki-shakuyaku-san, is one of the mechanisms underlying the improvement of Hiesho. Furthermore, Atractylodis Lanceae Rhizoma and Poria are possible herbal medicines for the inhibition of platelet aggregation.

  3. Shape changes induced by biologically active peptides and nerve growth factor in blood platelets of rabbits.

    PubMed

    Gudat, F; Laubscher, A; Otten, U; Pletscher, A

    1981-11-01

    1 Nerve growth factor (NGF), substance P (SP) and thymopoietin all caused shape change reactions of rapid onset in rabbit platelets. NGF had the highest maximal effect, and SP the lowest EC50 (concentration causing half maximal shape change). The action of SP was reversible within 5 min, whereas that of NGF lasted for at least 1 h. A series of other peptides were inactive. 2 After preincubation of platelets with SP, a second application of SP no longer caused a shape change reaction, whereas the effect of NGF was not influenced. 3 An oxidized NGF-derivative without biological activity did not cause a shape change reaction, neither did epidermal growth factor. 4 Prostaglandin E1 (PGE1) and pretreatment of the platelets with 3% butanol, which counteract the shape changes caused by 5-hydroxytryptamine (5-HT) and adenosine 3',5'-diphosphate, also antagonized those induced by NGF and SP. Neither heparin nor methysergide, an antagonist of 5-HT-receptors, influenced the shape change induced by NGF or SP. The action of NGF was also antagonized by a specific antibody to NGF. 5 Thymopoietin, like the basic polypeptide polyornithine (mol. wt. 40,000) was not antagonized by PGE1 and butanol. Heparin, which counteracted the effect of polyornithine, did not influence that of thymopoietin. 6 In conclusion, different modes of action are involved in the shape change of blood platelets induced by polypeptides and proteins. SP and NGF may act by stimulating specific membrane receptors.

  4. Effect of platelet-rich plasma combined with demineralised bone matrix on bone healing in rabbit ulnar defects.

    PubMed

    Galanis, Vasilios; Fiska, Alice; Kapetanakis, Stylianos; Kazakos, Konstantinos; Demetriou, Thespis

    2017-09-01

    This study evaluates the effect of autologous platelet-rich plasma (PRP) combined with xenogeneic demineralised bone matrix (DBM) on bone healing of critical-size ulnar defects (2-2.5 times the ulnar diameter) in New Zealand White rabbits. Critical-size defects were created unilaterally in the ulna of 36 rabbits, while keeping the contralateral limb intact. They were divided into three groups. In Group A, the defect was filled with autologous PRP and in Group B, with autologous PRP combined with DBM; in Group C, the defect remained empty. The rabbits were euthanised 12 weeks postoperatively. Radiological, biomechanical and histological assessments were carried out and statistical analysis of the results was performed. Group B had significantly higher radiological and histological scores than Groups A and C. Defects in Group B showed significant new bone formation, whereas there was minimal or no new bone formation in Groups A and C. Only specimens in Group B showed macroscopic bone union. Biomechanical evaluation of the treated and intact contralateral limbs in Group B showed significant differences. In this study, statistically significant enhancement of bone healing was found in critical-size defects treated with PRP and DBM, as shown by radiological findings, gross assessment, and biomechanical and histopathological results. Defects in the two other groups remained unbridged. Therefore, PRP was effective only when it was used in combination with a bone graft.

  5. Comparison between the effects of platelet-rich plasma and bone marrow concentrate on defect consolidation in the rabbit tibia

    PubMed Central

    Batista, Marco Antonio; Leivas, Tomaz Puga; Rodrigues, Consuelo Junqueira; Arenas, Géssica Cantadori Funes; Belitardo, Donizeti Rodrigues; Guarniero, Roberto

    2011-01-01

    OBJECTIVE: To perform a comparative analysis of the effects of platelet-rich plasma and centrifuged bone marrow aspirate on the induction of bone healing in rabbits. METHOD: Twenty adult, male New Zealand rabbits were randomly separated into two equal groups, and surgery was performed to create a bone defect (a cortical orifice 3.3 mm in diameter) in the proximal metaphysis of each rabbit's right tibia. In the first group, platelet-rich plasma was implanted in combination with β-tricalcium phosphate (platelet-rich plasma group), and in the second group, centrifuged bone marrow in combination with β-tricalcium phosphate (centrifuged bone marrow group) was implanted. After a period of four weeks, the animals were euthanized, and the tibias were evaluated using digital radiography, computed tomography, and histomorphometry. RESULTS: Seven samples from each group were evaluated. The radiographic evaluation confirmed the absence of fractures in the postoperative limb and identified whether bone consolidation had occurred. The tomographic evaluation revealed a greater amount of consolidation and the formation of a greater cortical bone thickness in the platelet-rich plasma group. The histomorphometry revealed a greater bone density in the platelet-rich plasma group compared with the centrifuged bone marrow group. CONCLUSION: After four weeks, the platelet-rich plasma promoted a greater amount of bone consolidation than the bone marrow aspirate concentrate. PMID:22012052

  6. Comparison of platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and concentrated growth factor (CGF) in rabbit-skull defect healing.

    PubMed

    Kim, Tae-Hoon; Kim, Sung-Hee; Sándor, George K; Kim, Yong-Deok

    2014-05-01

    The objective of this study was to evaluate the effect of platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and concentrated growth factor (CGF) on bone healing. Twelve rabbits were included in this randomized, blinded, prospective study. 15-mm×10-mm-sized defects were created in the parietal bone, filled with PRP, PRF, CGF, and void. The bone mineral density and bone volume were analyzed with microscopic computed tomography (micro-CT) and histomorphometrics at the 6th and 12th week. In micro-CT analysis, bone mineral density and bone volume were greater in the experimental group than in controls at both 6th and 12th week, but not among the experimental groups. Similarly, histomorphometric examination revealed that more bone formation was seen in the experimental group. The addition of PRP, PRF, and CGF had significantly increased bone formation at the 6th week. The effect of PRP, PRF, and CGF was similar and may be useful in the future to increase the success rate of bone grafting. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Interaction of D-LSD with blood platelets of rabbits: shape change and specific binding.

    PubMed

    Laubscher, A; Pletscher, A; Noll, H

    1981-02-01

    In blood platelets of rabbits, the shape change-inducing effect of D-lysergic acid diethylamide (D-LSD) has been compared with the D-LSD-binding. D-LSD, but not L-LSD, caused a shape change reaction (EC50 1.3 x 10(-9) M) which was inhibited by various 5-HT antagonists (methergoline and neuroleptic drugs), butaclamol showing marked stereospecificity. Strong inhibitors of 5 HT uptake were only weak in counteracting the D-LSD-induced shape change. Furthermore, D-[3H]LSD bound to platelets at a single saturable, high affinity, stereoselective site [Kd = (31.1 +/- 3.3) x 10(-9) M; Bmax = 28.9 +/- 2.7 fmols per 10(8) platelets]. This binding was strongly antagonized by D-LSD and methergoline and less by the hallucinogenic drugs, psilocin, bufotenin and N'N'-dimethyltryptamine. L-LSD an 5 HT, inhibitors of 5 HT uptake and neuroleptics, especially spiroperidol and butaclamol, had only a weak antagonistic effect. The latter showed stereospecificity. It is concluded that 1) the shape change reaction caused by D-LSD in platelets is mediated by the specific 5 HT-receptor, 2) the sites mediating the D-LSD-induced shape change reaction are not identical with those responsible for D-[3H]LSD-binding and both these sites are different from the 5 HT-transport sites and 3) with respect to D-LSD-binding sites, platelets and neurons are not exactly identical.

  8. Effects of Platelet-Rich Plasma on Tissue Expansion in Rabbits.

    PubMed

    Jinming, Wang; Caiyue, Liu; Baojin, Wu; Antang, Liu; Yingfan, Zhang; Hui, Wang; Lie, Zhu; Hua, Jiang

    2017-04-01

    Tissue expansion has been widely applied in clinic practice. However, the expanded skin is always insufficient for clinical use and how to promote tissue expansion is still a challenge. Platelet-rich plasma (PRP) contains multiple tissue growth factors and has been widely utilized in hard- and soft-tissue augmentation. However, its feasibility to promote tissue expansion has not been explored. The purpose of this study was to evaluate the possible effect of PRP in tissue expansion. Tissue expanders were implanted in the dorsal sides of rabbit ears, and the left and right side were for the PRP group and the control group randomly. The PRP group was injected with 1.0 mL of autologous PRP in the expansion skin and the control group with the same volume of saline solution. The expanders were inflated regularly by injecting saline solution under the same pressure. After the inflation phase, the expansion skin was harvested and the inflation volume, gross specimen, and histological characteristics were assayed and evaluated. The mean inflation volume of the PRP group was significantly higher than that of the control (p < 0.05). H&E staining of expanded skin sections showed more epidermal cell layers and thicker skin in the PRP group than that in the control group. There were significantly more capillaries in the expanded skin in the PRP group than those from the control group by IHC staining with its marker anti-CD31. A higher level of mRNA expression of VEGF was observed in the PRP group by real-time PCR. The present study suggests that PRP plays a pivotal role in tissue expansion and skin proliferation. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors. www.springer.com/00266 .

  9. Platelet-rich plasma reduces skin flap inflammatory cells infiltration and improves survival rates through induction of angiogenesis: An experiment in rabbits.

    PubMed

    Wang, Biao; Geng, Qiuhua; Hu, Junling; Shao, Jianchuan; Ruan, Jing; Zheng, Jiansheng

    2016-08-01

    This study was conducted to evaluate the effects of platelet-rich plasma (PRP) on flap survival in an experimental rabbit model. Symmetrical rectangular dorsal cutaneous flaps (8 × 2 cm) were elevated in 15 rabbits. The rabbits were randomly divided into a 3-day group (n = 5), a 7-day group (n = 5), and a 14-day group (n = 5). Either side of the dorsum was selected for injection of PRP into the flap basal surface, while the other side received an equal volume of saline as a control. The flaps were immediately sutured back, after which the flap survival was measured and histology specimens were collected at 3, 7, and 14 days. Platelet-rich plasma significantly improved flap survival rates of the PRP side flaps relative to the control in the 3-day (74.4% ± 4.7% vs 65.8% ± 6.8%; p < 0.05), 7-day (72.4% ± 7.5% vs 58.5% ± 7.0%; p < 0.05), and 14-day (74.5% ± 5.0% vs 65.0% ± 5.4%; p < 0.05) groups. Histological analysis revealed significantly fewer inflammatory cells and an increased blood vessel density in the platelet-rich plasma side flap vs the blank control side flap. Platelet-rich plasma (PRP) promotes the survival of random rabbit flaps and, therefore, represents a promising treatment to prevent skin flap necrosis in reconstructive and plastic surgery.

  10. Platelet satellitism: an ultrastructural study.

    PubMed Central

    Payne, C. M.

    1981-01-01

    The ultrastructural morphology of platelet-polymorph (platelet-polymorphonuclear leukocyte) rosettes was investigated in EDTA-anticoagulated blood obtained from two patients who exhibited the phenomenon of platelet satellitism. Most of the platelet profiles were attached to the polymorph surface by broad areas of contact. Examination of these broad areas of contact at high magnification revealed an intercellular material of low electron density. This material appeared to form strands, which bridged the intercellular space and spanned the entire area formed by the apposing plasma membranes. Phagocytosis of entire platelets was only observed in 1 case. The platelet profiles that participated in rosette formation revealed a large number of glycogen particles, compared with unattached platelets. Ultrastructural examination of "stress" platelets obtained from five normal subjects treated with steroids similarly showed a large number of glycogen particles, although no rosette formation or phagocytosis of platelets was observed. The etiology of platelet satellitism is discussed. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:7223859

  11. Effects of intra-articular injection of mesenchymal stem cells associated with platelet-rich plasma in a rabbit model of osteoarthritis.

    PubMed

    Hermeto, L C; DeRossi, R; Oliveira, R J; Pesarini, J R; Antoniolli-Silva, A C M B; Jardim, P H A; Santana, A E; Deffune, E; Rinaldi, J C; Justulin, L A

    2016-09-02

    The current study aims to evaluate the macroscopic and histological effects of autologous mesenchymal stem cells (MSC) and platelet-rich plasma on knee articular cartilage regeneration in an experimental model of osteoarthritis. Twenty-four rabbits were randomly divided into four groups: control group, platelet-rich plasma group, autologous MSC undifferentiated group, and autologous MSC differentiated into chondrocyte group. Collagenase solution was used to induce osteoarthritis, and treatments were applied to each group at 6 weeks following osteoarthritis induction. After 60 days of therapy, the animals were euthanized and the articular surfaces were subjected to macroscopic and histological evaluations. The adipogenic, chondrogenic, and osteogenic differentiation potentials of MSCs were evaluated. Macroscopic and histological examinations revealed improved tissue repair in the MSC-treated groups. However, no difference was found between MSC-differentiated and undifferentiated chondrocytes. We found that MSCs derived from adipose tissue and platelet-rich plasma were associated with beneficial effects in articular cartilage regeneration during experimental osteoarthritis.

  12. The inhibitory effects of cannabinoids, the active constituents of Cannabis sativa L. on human and rabbit platelet aggregation.

    PubMed

    Formukong, E A; Evans, A T; Evans, F J

    1989-10-01

    Olivetol, cannabigerol (CBG), cannabidiol (CBD), cannabinol (CBN) and tetrahydrocannabinol (delta 1-THC) were assessed for their ability to inhibit agonist-induced platelet aggregation and [14C]5-HT release. With the exception of olivetol, (40% maximal effectiveness), none of the compounds inhibited tetradecanoylphorbolacetate (TPA)-induced aggregation of human or rabbit platelets. All of these cannabinoids partially inhibited primary aggregation and totally inhibited secondary aggregation of human platelets when adrenaline was used as the agonist. Inhibition was dose-dependent over the range 10(-3)-10(-5) M. Both rabbit and human platelet aggregation induced by adenosine diphosphate was inhibited in a dose-dependent manner and the order of potency was CBG greater than CBD greater than olivetol greater than THC greater than CBN, the IC50 of CBG being 2.7 x 10(-4) M. PAF-induced aggregation of rabbit platelets was also inhibited by these compounds in a dose-dependent manner over the concentration range 10(-3) to 10(-4) M, however [14C]5-HT release was only partially prevented by the cannabinoids in a manner which did not correlate with inhibition of aggregation.

  13. Effects of Calcium Sulfate Combined with Platelet-rich Plasma on Restoration of Long Bone Defect in Rabbits.

    PubMed

    Chen, Hua; Ji, Xin-Ran; Zhang, Qun; Tian, Xue-Zhong; Zhang, Bo-Xun; Tang, Pei-Fu

    2016-03-05

    The treatment for long bone defects has been a hot topic in the field of regenerative medicine. This study aimed to evaluate the therapeutic effects of calcium sulfate (CS) combined with platelet-rich plasma (PRP) on long bone defect restoration. A radial bone defect model was constructed through an osteotomy using New Zealand rabbits. The rabbits were randomly divided into four groups (n = 10 in each group): a CS combined with PRP (CS-PRP) group, a CS group, a PRP group, and a positive (recombinant human bone morphogenetic protein-2) control group. PRP was prepared from autologous blood using a two-step centrifugation process. CS-PRP was obtained by mixing hemihydrate CS with PRP. Radiographs and histologic micrographs were generated. The percentage of bone regenerated bone area in each rabbit was calculated at 10 weeks. One-way analysis of variance was performed in this study. The radiographs and histologic micrographs showed bone restoration in the CS-PRP and positive control groups, while nonunion was observed in the CS and PRP groups. The percentages of bone regenerated bone area in the CS-PRP (84.60 ± 2.87%) and positive control (52.21 ± 4.53%) groups were significantly greater than those in the CS group (12.34 ± 2.17%) and PRP group (16.52 ± 4.22%) (P < 0.001). In addition, the bone strength of CS-PRP group (43.10 ± 4.10%) was significantly greater than that of the CS group (20.10 ± 3.70%) or PRP group (25.10 ± 2.10%) (P < 0.001). CS-PRP functions as an effective treatment for long bone defects through stimulating bone regeneration and enhancing new bone strength.

  14. Effects of Calcium Sulfate Combined with Platelet-rich Plasma on Restoration of Long Bone Defect in Rabbits

    PubMed Central

    Chen, Hua; Ji, Xin-Ran; Zhang, Qun; Tian, Xue-Zhong; Zhang, Bo-Xun; Tang, Pei-Fu

    2016-01-01

    Background: The treatment for long bone defects has been a hot topic in the field of regenerative medicine. This study aimed to evaluate the therapeutic effects of calcium sulfate (CS) combined with platelet-rich plasma (PRP) on long bone defect restoration. Methods: A radial bone defect model was constructed through an osteotomy using New Zealand rabbits. The rabbits were randomly divided into four groups (n = 10 in each group): a CS combined with PRP (CS-PRP) group, a CS group, a PRP group, and a positive (recombinant human bone morphogenetic protein-2) control group. PRP was prepared from autologous blood using a two-step centrifugation process. CS-PRP was obtained by mixing hemihydrate CS with PRP. Radiographs and histologic micrographs were generated. The percentage of bone regenerated bone area in each rabbit was calculated at 10 weeks. One-way analysis of variance was performed in this study. Results: The radiographs and histologic micrographs showed bone restoration in the CS-PRP and positive control groups, while nonunion was observed in the CS and PRP groups. The percentages of bone regenerated bone area in the CS-PRP (84.60 ± 2.87%) and positive control (52.21 ± 4.53%) groups were significantly greater than those in the CS group (12.34 ± 2.17%) and PRP group (16.52 ± 4.22%) (P < 0.001). In addition, the bone strength of CS-PRP group (43.10 ± 4.10%) was significantly greater than that of the CS group (20.10 ± 3.70%) or PRP group (25.10 ± 2.10%) (P < 0.001). Conclusion: CS-PRP functions as an effective treatment for long bone defects through stimulating bone regeneration and enhancing new bone strength. PMID:26904990

  15. The relationship between platelet endothelial cell adhesion molecule-1 and paraquat-induced lung injury in rabbits

    PubMed Central

    Shi, Jing; Hu, Chun-lin; Gao, Yu-feng; Liao, Xiao-xing; Xu, Hope

    2012-01-01

    BACKGROUND: Platelet endothelial cell adhesion molecule-1 (PECAM-1), also known as CD31, is mainly distributed in vascular endothelial cells. Studies have shown that PECAM-1 is a very significant indicator of angiogenesis, and has been used as an indicator for vascular endothelial cells. The present study aimed to explore the relationship between the expression of PECAM-1 and the degree of acute lung injury (ALI) and fibrosis in paraquat (PQ) induced lung injury in rabbits. METHODS: Thirty-six adult New Zealand rabbits were randomly divided into three groups (12 rabbits in each group) according to PQ dosage: 8 mg/kg (group A), 16 mg/kg (group B), and 32 mg/kg (group C). After PQ infusion, the rabbits were monitored for 7 days and then euthanized. The lungs were removed for histological evaluation. Masson staining was used to determine the degree of lung fibrosis (LF), and semi-quantitative immune-histochemistry analysis to determine the expression of PECAM-1. Pearson’s product-moment correlation analysis was performed to evaluate the relationship between the expression of PECAM-1 and the extent of lung injuries expressed by ALI score and degree of LF. RESULTS: Rabbits in the three groups showed apparent poisoning. The rabbits survived longer in group A than in groups B and C (6.47±0.99 days vs. 6.09±1.04 days vs. 4.77±2.04 days) (P<0.05). ALI score was lower in group A than in groups B and C (8.33±1.03 vs. 9.83±1.17 vs. 11.50±1.38) (P<0.05), and there was statistically significant difference between group B and group C (P=0.03). LF was slighter in group A than in groups B and C (31.09%±2.05 % vs. 34.37%±1.62 % vs. 36.54%±0.44%) (P<0.05), and there was statistically significant difference between group B and group C (P=0.026). The PEACAM-1 expression was higher in group A than in groups B and C (20.31%±0.70% vs. 19.34%±0.68% vs. 18.37%±0.46%) (P<0.05), and there was statistically significant difference between group B and group C (P=0.017). Pearson

  16. Histological response to platelet-rich plasma added to polypropylene mesh implemented in rabbits

    PubMed Central

    Ávila, Oscar Rubini; Parizzi, Natália Gomes; Souza, Ana Paula Mayumi; Botini, Dayane Silvestre; Alves, João Ytimura; Almeida, Silvio Henrique Maia

    2016-01-01

    ABSTRACT Introduction: The platelet-rich plasma (PRP) is part of a set of biotechnologies, providing some growth factors that promote repair of different tissues. The polypropylene meshes (PPM) are applied in the correction of abdominal defects, pelvic floor and urinary incontinence, however, they induce many significant complications, as a result of an inappropriate inflammatory response. Purpose: To investigate the changes caused by PRP associated with the implantation of PPM in the abdomen of female rabbits, in the production of collagen I and III and the inflammatory infiltrate (ININ). Materials and Methods: We performed implant meshes with and without PRP in adult rabbits (n=30) and euthanasia at 7, 30 and 90 days. Two plates were prepared from each animal and analyzed in five different fields. The ININ was evaluated by quantification of inflammatory cells using hematoxylin-eosin and the collagen by Sirius red method. The results were analyzed applying the Wilcoxon, Kruskal-Wallis, Junckheere and Friedmann tests. Results: There was a significant difference in the number of inflammatory cells between the groups with and without PRP (p=0.01) at 90 days. There was increased production of collagen I, III and total with the use of PRP, at seven days. Conclusion: The PPM coating with PRP was associated with increased ININ at the implant area, and an increasing trend during the process of tissue repair. The PPM coated with PRP was related to increased concentration of collagen I, collagen III and the concentration of total collagen increased after seven days of implantation. PMID:27583354

  17. Histological response to platelet-rich plasma added to polypropylene mesh implemented in rabbits.

    PubMed

    Ávila, Oscar Rubini; Parizzi, Natália Gomes; Souza, Ana Paula Mayumi; Botini, Dayane Silvestre; Alves, João Ytimura; Almeida, Silvio Henrique Maia

    2016-01-01

    The platelet-rich plasma (PRP) is part of a set of biotechnologies, providing some growth factors that promote repair of different tissues. The polypropylene meshes (PPM) are applied in the correction of abdominal defects, pelvic floor and urinary incontinence, however, they induce many significant complications, as a result of an inappropriate inflammatory response. To investigate the changes caused by PRP associated with the implantation of PPM in the abdomen of female rabbits, in the production of collagen I and III and the inflammatory infiltrate (ININ). We performed implant meshes with and without PRP in adult rabbits (n=30) and euthanasia at 7, 30 and 90 days. Two plates were prepared from each animal and analyzed in five different fields. The ININ was evaluated by quantification of inflammatory cells using hematoxylin-eosin and the collagen by Sirius red method. The results were analyzed applying the Wilcoxon, Kruskal-Wallis, Junckheere and Friedmann tests. There was a significant difference in the number of inflammatory cells between the groups with and without PRP (p=0.01) at 90 days. There was increased production of collagen I, III and total with the use of PRP, at seven days. The PPM coating with PRP was associated with increased ININ at the implant area, and an increasing trend during the process of tissue repair. The PPM coated with PRP was related to increased concentration of collagen I, collagen III and the concentration of total collagen increased after seven days of implantation. Copyright® by the International Brazilian Journal of Urology.

  18. Effect of combining platelet-rich plasma with anorganic bovine bone on vertical bone regeneration: early healing assessment in rabbit calvariae.

    PubMed

    Torres, Jesus; Tamimi, Faleh; Tresguerres, Isabel F; Alkhraisat, Mohammad H; Khraisat, Ameen; Blanco, Luis; Lopez-Cabarcos, Enrique

    2010-01-01

    The purpose of this study was to evaluate the combination of anorganic bovine bone allograft (ABB) with platelet-rich plasma (PRP) when used in vertical bone augmentation. Sixteen healthy 6-month-old female New Zealand rabbits were used in this study. Rabbits were randomly divided into two groups of eight animals each. Created calvarial defects were grafted with ABB or PRP in the first group whereas, in the second group, one cylinder was filled with PRP+ABB and the contralateral cylinder was left ungrafted to be filled by autologous blood (control cylinder). Six weeks after intervention, animals were sacrificed and biopsies were taken. Densitometric, histologic, and histomorphometric analyses were performed to evaluate bone mineral density, vertical bone augmentation, and remaining graft volume, respectively. Statistical analyses were performed with the Mann-Whitney test, using a significance level of P < .05. Six weeks after rabbit calvariae were augmented, data analysis revealed that the mixture of PRP and ABB produced twice the vertical bone volume of ABB alone (P < .0001). Based upon this study of 16 rabbits, it appears that the combination of ABB with PRP resulted in increased vertical bone augmentation when compared with autologous blood in similarly sized created defects.

  19. Effect of Leukocyte-Rich and Platelet-Rich Plasma on Healing of a Horizontal Medial Meniscus Tear in a Rabbit Model.

    PubMed

    Shin, Kyun Ho; Lee, Haseok; Kang, Seonghyun; Ko, You-Jin; Lee, Seung-Yup; Park, Jung-Ho; Bae, Ji-Hoon

    2015-01-01

    There are limited reports on the effect of platelet-rich plasma (PRP) on meniscus healing. The purpose of this study was to investigate the effect of leukocyte-rich PRP (L-PRP) on potential healing of the horizontal medial meniscus tears in a rabbit model. A horizontal medial meniscus tear was created in both knees of nine skeletally mature adult rabbits. Left or right knees were randomly assigned to a L-PRP group, or a control group. 0.5 mL of L-PRP from 10 mL of each rabbit's whole blood was prepared and injected into the horizontal tears in a L-PRP group. None was applied to the horizontal tears in a control group. The histological assessment of meniscus healing was performed at two, four, and six weeks after surgery. We found that there were no significant differences of quantitative histologic scoring between two groups at 2, 4, and 6 weeks after surgery (p > 0.05). This study failed to show the positive effect of single injection of L-PRP on enhancing healing of the horizontal medial meniscus tears in a rabbit model. Single injection of L-PRP into horizontal meniscus tears may not effectively enhance healing of horizontal medial meniscus tears.

  20. Platelets

    MedlinePlus

    ... common disorder of platelet function is caused by aspirin. Aspirin blocks one of the steps required for platelets to stick together. This effect of aspirin is what makes it an effective treatment for ...

  1. A combination graft of low-molecular-weight silk fibroin with Choukroun platelet-rich fibrin for rabbit calvarial defect.

    PubMed

    Lee, Eui-Hee; Kim, Jwa-Young; Kweon, Hae Yong; Jo, You-Young; Min, Soo-Kee; Park, Young-Wook; Choi, Je-Yong; Kim, Seong-Gon

    2010-05-01

    The objective of this study was to determine the capabilities of silk fibroin as a biomaterial template for bone formation when mixed with Choukroun platelet-rich fibrin (PRF) in vivo. Ten New Zealand white rabbits were used for this study and bilateral round shaped defects were formed in the parietal bone (diameter 9.0 mm). The silk fibroin was digested by acid and made into powder (molecular weight <1.0 kDa). The right side (experimental group) received the silk fibroin plus platelet-rich fibroin and the left side (control group) did not receive a graft. Animals were killed at 6 weeks and 12 weeks. The specimens were examined by microscopic computerized tomography (micro-CT). Subsequently, they underwent decalcification and were stained for histologic analysis. There was no significant difference between groups at 6 weeks after operation. In the micro-CT results, however, tissue mineral content in the experimental group at 12 weeks after operation was 132.09 +/- 4.41 and that in the control group was 126.42 +/- 6.62 (P = .011). Tissue mineral density in the experimental group was 2,088.88 +/- 648.34, and that in the control group was 2,029.72 +/- 668.22 (P = .013). The results of the histomorphometric analysis were in accordance with the micro-CT results. The total new bone was 49.86 +/- 7.49% in the control group at 12 weeks after the operation and 59.83 +/- 10.92% in the experimental group (P = .021). A combined application of Choukroun PRF with acid-digested silk fibroin showed more rapid bone healing than unfilled control. Copyright (c) 2010 Mosby, Inc. All rights reserved.

  2. Platelet-Rich Plasma Increases the Levels of Catabolic Molecules and Cellular Dedifferentiation in the Meniscus of a Rabbit Model.

    PubMed

    Lee, Hye-Rim; Shon, Oog-Jin; Park, Se-Il; Kim, Han-Jun; Kim, Sukyoung; Ahn, Myun-Whan; Do, Sun Hee

    2016-01-16

    Despite the susceptibility to frequent intrinsic and extrinsic injuries, especially in the inner zone, the meniscus does not heal spontaneously owing to its poor vascularity. In this study, the effect of platelet-rich plasma (PRP), containing various growth factors, on meniscal mechanisms was examined under normal and post-traumatic inflammatory conditions. Isolated primary meniscal cells of New Zealand white (NZW) rabbits were incubated for 3, 10, 14 and 21 days with PRP(-), 10% PRP (PRP(+)), IL(+) or IL(+)PRP(+). The meniscal cells were collected and examined using reverse-transcription polymerase chain reaction (RT-PCR). Culture media were examined by immunoblot analyses for matrix metalloproteinases (MMP) catabolic molecules. PRP containing growth factors improved the cellular viability of meniscal cells in a concentration-dependent manner at Days 1, 4 and 7. However, based on RT-PCR, meniscal cells demonstrated dedifferentiation, along with an increase in type I collagen in the PRP(+) and in IL(+)PRP(+). In PRP(+), the aggrecan expression levels were lower than in the PRP(-) until Day 21. The protein levels of MMP-1 and MMP-3 were higher in each PRP group, i.e., PRP(+) and IL(+)PRP(+), at each culture time. A reproducible 2-mm circular defect on the meniscus of NZW rabbit was used to implant fibrin glue (control) or PRP in vivo. After eight weeks, the lesions in the control and PRP groups were occupied with fibrous tissue, but not with meniscal cells. This study shows that PRP treatment of the meniscus results in an increase of catabolic molecules, especially those related to IL-1α-induced inflammation, and that PRP treatment for an in vivo meniscus injury accelerates fibrosis, instead of meniscal cartilage.

  3. Platelet interaction with polymerizing fibrin.

    PubMed

    Niewiarowski, S; Regoeczi, E; Stewart, G J; Senyl, A F; Mustard, J F

    1972-03-01

    Interaction of washed pig, rabbit, or human platelets with fibrinogen was studied during its transition to fibrin using photometric, isotopic, and electron microscopic techniques. Untreated fibrinogen and fully polymerized fibrin had no detectable effect on platelets. Fibrinogen, incubated with low concentrations of reptilase or thrombin, formed intermediate products which readily became associated with platelets and caused their aggregation. Neutralization of the thrombin did not prevent this interaction. In the absence of fibrinogen, reptilase did not affect platelets. The interaction of polymerizing fibrin with platelets was accompanied by small losses of platelet constituents (serotonin, adenine nucleotides, platelet factor 4, and lactic dehydrogenase). This loss did not appear to be the result of the platelet release reaction. Inhibitors of the release reaction or of adenosine diphosphate (ADP)-induced aggregation did not prevent the interaction of platelets with polymerizing fibrin. Apyrase or prostaglandin E(1) (PGE(1)) reduced the extent of platelet aggregation by polymerizing fibrin, but the amount of protein associated with platelets was slightly increased. The interaction of polymerizing fibrin with platelets was completely inhibited by ethylenediaminetetraacetate (EDTA) or ethylene glycol bis (beta-aminoethyl ether) N, N,N',N'-tetraacetic acid (EGTA).Fibers formed in solutions of polymerizing fibrin were larger in the presence than in the absence of washed platelets, suggesting that platelets affect fibrin polymerization. The adherence of platelets to polymerizing fibrin may be responsible for the establishment of links between platelets and fibrin in hemostatic plugs and thrombi.

  4. Rabbit Models for Studying Human Infectious Diseases

    PubMed Central

    Peng, Xuwen; Knouse, John A; Hernon, Krista M

    2015-01-01

    Using an appropriate animal model is crucial for mimicking human disease conditions, and various facets including genetics, anatomy, and pathophysiology should be considered before selecting a model. Rabbits (Oryctolagus cuniculus) are well known for their wide use in production of antibodies, eye research, atherosclerosis and other cardiovascular diseases. However, a systematic description of the rabbit as primary experimental models for the study of various human infectious diseases is unavailable. This review focuses on the human infectious diseases for which rabbits are considered a classic or highly appropriate model, including AIDS (caused by HIV1), adult T-cell leukemia–lymphoma (human T-lymphotropic virus type 1), papilloma or carcinoma (human papillomavirus) , herpetic stromal keratitis (herpes simplex virus type 1), tuberculosis (Mycobacterium tuberculosis), and syphilis (Treponema pallidum). In addition, particular aspects of the husbandry and care of rabbits used in studies of human infectious diseases are described. PMID:26678367

  5. Review of in vivo studies of dimethyl sulfoxide cryopreserved platelets.

    PubMed

    Slichter, Sherrill J; Jones, Melinh; Ransom, Janet; Gettinger, Irena; Jones, Mary Kay; Christoffel, Todd; Pellham, Esther; Bailey, S Lawrence; Corson, Jill; Bolgiano, Doug

    2014-10-01

    A literature review was conducted to assess the efficacy and safety of dimethyl sulfoxide (DMSO) cryopreserved platelets for potential military use. In vivo DMSO cryopreserved platelet studies published between 1972 and June of 2013 were reviewed. Assessed were the methods of cryopreservation, posttransfusion platelet responses, prevention or control of bleeding, and adverse events. Using the Department of Defense's preferred 6% DMSO cryopreservation method with centrifugation to remove the DMSO plasma before freezing at -65°C and no postthaw wash, mean radiolabeled platelet recoveries in 32 normal subjects were 33% ± 10% (52% ± 12% of the same subject's fresh platelet recoveries), and survivals were 7.5 ± 1.2 days (89% ± 15% of fresh platelet survivals). Using a variety of methods to freeze autologous platelets from 178 normal subjects, mean radiolabeled platelet recoveries were consistently 39% ± 9%, and survivals, 7.4 ± 1.4 days. More than 3000 cryopreserved platelet transfusions were given to 1334 patients. There were 19 hematology/oncology patient studies, and, in 9, mean 1-hour corrected count increments were 11 100 ± 3600 (range, 5700-15 800) after cryopreserved autologous platelet transfusions. In 5 studies, bleeding times improved after transfusion; in 3, there was either no improvement or a variable response. In 4 studies, there was immediate cessation of bleeding after transfusion; in 3 studies, patients being supported only with cryopreserved platelets had no bleeding. In 1 cardiopulmonary bypass study, cryopreserved platelets resulted in significantly less bleeding vs standard platelets. In 3 trauma studies, cryopreserved platelets were hemostatically effective. No significant adverse events were reported in any study. In summary, cryopreserved platelets have platelet recoveries that are about half of fresh platelets, but survivals are only minimally reduced. The platelets appear hemostatically effective and have no significant adverse events.

  6. Platelet-rich plasma limits the nerve injury caused by 10% dextrose in the rabbit median nerve.

    PubMed

    Park, Gi-Young; Kwon, Dong Rak

    2014-01-01

    We evaluated the effect of platelet-rich plasma (PRP) injection in a rabbit model of dextrose-induced median nerve injury. New Zealand white rabbits (n = 15) were divided randomly into 3 groups. Three different regimens (group 1: 0.1 ml saline; group 2: 10% dextrose with PRP; group 3: 10% dextrose with saline) were injected within the carpal tunnel. Electrophysiological and histological findings were evaluated 12 weeks after the injection. The mean median motor latency in group 3 was significantly longer than that in groups 1 and 2. The cross-sectional area of the median nerve and subsynovial connective tissue thickness in group 3 were significantly larger than those in groups 1 and 2. PRP injection may be effective in controlling median nerve injury, as demonstrated by improvement in electrophysiological and histological findings 12 weeks after dextrose injection. Copyright © 2013 Wiley Periodicals, Inc.

  7. Effects of Platelet-Rich Plasma & Platelet-Rich Fibrin with and without Stromal Cell-Derived Factor-1 on Repairing Full-Thickness Cartilage Defects in Knees of Rabbits

    PubMed Central

    Bahmanpour, Soghra; Ghasemi, Maryam; Sadeghi-Naini, Mohsen; Kashani, Iraj Ragerdi

    2016-01-01

    Background: The purpose of this study was to create biomaterial scaffolds like platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) containing stromal cell-derived factor-1 (SDF1) as a chemokine to induce hyaline cartilage regeneration of rabbit knee in a full thickness defect. Methods: We created a full thickness defect in the trochlear groove of thirty-six bilateral knees of eighteen mature male rabbits. The knees were randomly divided into six groups (group I: untreated control, group II: PRP, group III: PRF, group IV: Gelatin+SDF1, group V: PRP+SDF1, and group VI: PRF+SDF1). After four weeks, the tissue specimens were evaluated by macroscopic examination and histological grading, immunofluorescent staining for collagen type II, and analyzed for cartilage marker genes by real-time PCR. The data were compared using statistical methods (SPSS 20, Kruskal-Wallis test, Bonferroni post hoc test and P<0.05). Results: Macroscopic evaluations revealed that international cartilage repair society (ICRS) scores of the PRF+SDF1 group were higher than other groups. Microscopic analysis showed that the ICRS score of the PRP group was significantly lower than other groups. Immunofluorescent staining for collagen II demonstrated a remarkable distribution of type II collagen in the Gel+SDF1, PRP+SDF1 and PRF+SDF1 groups compared with other groups. Real-time PCR analysis revealed that mRNA expression of SOX9 and aggrecan were significantly greater in the PRF+SDF1, PRP+SDF1, Gel+SDF1 and PRF groups than the control group (P<0.05). Conclusion: Our results indicate that implantation of PRF scaffold containing SDF1 led to the greatest evaluation scores of full-thickness lesions in rabbits. PMID:27853331

  8. Autologous leukocyte-reduced platelet-rich plasma therapy for Achilles tendinopathy induced by collagenase in a rabbit model.

    PubMed

    González, Juan C; López, Catalina; Álvarez, María E; Pérez, Jorge E; Carmona, Jorge U

    2016-01-19

    Leukocyte-reduced platelet-rich plasma (LR-PRP) is a therapy for tendinopathy of the Achilles tendon (TAT); however, there is scarce information regarding LR-PRP effects in rabbit models of TAT. We compared, at 4 and 12 weeks (w), the LR-PRP and placebo (PBS) effects on ultrasonography, histology and relative gene expression of collagen types I (COL1A1) and III (COL3A1) and vascular endothelial growth factor (VEGF) in 24 rabbits with TAT induced by collagenase. The rabbits (treated with both treatments) were euthanatised after either 4 or 12 w. A healthy group (HG (n = 6)) was included. At 4 and 12 w, the LR-PRP group had a no statistically different histology score to the HG. At w 4, the COL1A1 expression was significantly higher in the LR-PRP group when compared to HG, and the expression of COL3A1 from both LR-PRP and PBS-treated tendons was significantly higher when compared to the HG. At w 12, the expression of COL3A1 remained significantly higher in the PBS group in comparison to the LR-PRP group and the HG. At w 4, the LR-PRP group presented a significantly higher expression of VEGF when compared to the PBS group and the HG. In conclusion, LR-PRP treatment showed regenerative properties in rabbits with TAT.

  9. Autologous leukocyte-reduced platelet-rich plasma therapy for Achilles tendinopathy induced by collagenase in a rabbit model

    PubMed Central

    González, Juan C.; López, Catalina; Álvarez, María E.; Pérez, Jorge E.; Carmona, Jorge U.

    2016-01-01

    Leukocyte-reduced platelet-rich plasma (LR-PRP) is a therapy for tendinopathy of the Achilles tendon (TAT); however, there is scarce information regarding LR-PRP effects in rabbit models of TAT. We compared, at 4 and 12 weeks (w), the LR-PRP and placebo (PBS) effects on ultrasonography, histology and relative gene expression of collagen types I (COL1A1) and III (COL3A1) and vascular endothelial growth factor (VEGF) in 24 rabbits with TAT induced by collagenase. The rabbits (treated with both treatments) were euthanatised after either 4 or 12 w. A healthy group (HG (n = 6)) was included. At 4 and 12 w, the LR-PRP group had a no statistically different histology score to the HG. At w 4, the COL1A1 expression was significantly higher in the LR-PRP group when compared to HG, and the expression of COL3A1from both LR-PRP and PBS-treated tendons was significantly higher when compared to the HG. At w 12, the expression of COL3A1 remained significantly higher in the PBS group in comparison to the LR-PRP group and the HG. At w 4, the LR-PRP group presented a significantly higher expression of VEGF when compared to the PBS group and the HG. In conclusion, LR-PRP treatment showed regenerative properties in rabbits with TAT. PMID:26781753

  10. Acetylglyceryl ether phosphorylcholine (AGEPC; platelet-activating factor)-induced stimulation of rabbit platelets: correlation between phosphatidic acid level, 45Ca2+ uptake, and (3H)serotonin secretion

    SciTech Connect

    Shukla, S.D.; Hanahan, D.J.

    1984-08-01

    When 32P-labeled rabbits platelet were incubated with 5 X 10(-10) M 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (AGEPC), either in the presence or absence (0.1 mM EGTA) of added Ca2+, there was a three- to five-fold increase in the (32P)phosphatidic acid (PA) pool within 15 to 20 s. This event was followed by a gradual decrease in the (32P)PA level to near basal level in 5 min. AGEPC effected this change in (32P)PA in a characteristic dose- and time-dependent manner. Polar head group analogs of AGEPC, such as AGEDME and AGEMME, also effected an increase in PA labeling at levels comparable to those previously reported for their activity toward rabbit platelets. Other analogs, i.e., lysoGEPC and the enantiomer, sn-1-AGEPC, which are inactive toward rabbit platelets, also showed no effect on the level of (32P)PA. The finding that the PA level in rabbit platelets could be manipulated by the addition of AGEPC, without any added Ca2+, provided an excellent model system for establishing a correlation between the uptake of Ca2+, serotonin release, and PA level. Thus, PA must be regarded as a sensitive indicator of a reaction mechanism important to the platelet response to AGEPC, and could be the focal point in promoting calcium uptake during the stimulation process.

  11. Effects of scorpion venom bioactive polypolypeptides on platelet aggregation and thrombosis and plasma 6-keto-PG F1alpha and TXB2 in rabbits and rats.

    PubMed

    Song, Yi-Min; Tang, Xue-Xi; Chen, Xi-Guang; Gao, Ben-Bo; Gao, Er; Bai, Lin; Lv, Xin-Ran

    2005-08-01

    Effects of scorpion venom active polypeptide (SVAP) from scorpion venom of Buthus Martensii Karsch of Chinese on platelet aggregation in ex vivo and vitro in rabbits, thrombosis in carotid artery of rats and plasma 6-keto-PG F1alpha and TXB2 in rats were studied by the turbidimetry, the duplicated thrombosis model by electrostimulation and RIA, respectively. The results showed that SVAP 0.125, 0.25, 0.5 mg/ml inhibited significantly the rabbit platelet aggregation triggered by 0.3 U/ml thrombin, 10 microM ADP in vitro (P<0.05 or 0.01) and SVAP at the dose of 0.32, 0.64 mg/kg iv prolonged distinctively the occlusion time of thrombosis that were induced by electrical stimulation. Increased% of 0.16, 0.32 and 0.64 mg/kg were 30.16, 71.74, 98.27%, respectively, which showed a good dose-effect relationship. SVAP 0.22 mg/ml (in vitro) or 0.2, 0.4 mg/kg (in ex vivo) could obviously increase the plasma concentration of 6-keto-PG F1alpha, but slightly effect rats plasma concentration of TXB2 in vitro and in ex vivo and significantly increase of value of PG I2/TXA2, which suggested that the mechanism of the antithrombotic action of SVAP is related to the resistance against platelet aggregation, increase of the concentration of PG I2 in plasma.

  12. Ultrastructural studies of the gray platelet syndrome.

    PubMed Central

    White, J. G.

    1979-01-01

    The gray platelet syndrome (GPS) is a rare inherited disorder in which peripheral blood platelets are relatively large, vacuolated, and almost devoid of cytoplasmic granulation. In the present study we have evaluated the ultrastructure and cytochemistry of platelets from 2 patients with the GPS to determine precisely which organelles are missing from their cells. The findings indicate that gray platelets contain normal numbers of mitochondria, dense bodies, peroxisomes, and lysosomes but specifically lack alpha-granules. Preliminary studies of megakaryocytes from 1 of the 2 patients suggest that the defect in granule formation may lie at the level of the Golgi zone. Images Figure 15 Figure 16 Figures 17 and 18 Figures 19 and 20 Figure 3 Figure 4 Figures 5 and 6 Figures 7 and 8 Figure 27 Figure 28 Figure 29 Figure 30 Figure 31 Figure 32 Figure 9 Figure 10 Figure 11 Figure 12 Figures 13 and 14 Figures 21 and 22 Figures 23 through 26 Figure 1 Figure 2 PMID:453324

  13. Platelet profile in patients with gestational diabetes: a retrospective study

    PubMed Central

    Sak, Muhammet Erdal; Soydinç, Hatice Ender; Özler, Ali; Evsen, Mehmet Sıddık; Turgut, Abdülkadir; Sak, Sibel; Gül, Talip

    2012-01-01

    Objective: To assess and compare alterations in the morphology and function of platelets occurring in gestational diabetes and healthy pregnancies. Material and Methods: A retrospective study was performed of 77 pregnant women: 42 cases with gestational diabetes and 35 healthy controls. The two groups were compared in terms of demographics and platelet parameters derived from complete blood counts. Results: The mean platelet volume (p=0.001) and HbA1c (p<0.001) were significantly increased in the patients with gestational diabetes. The mean platelet volume was well correlated with the platelet distribution width (rs=0.404, p<0.001) and the platelet count (rs=0.355, p=0.002) Conclusion: The mean platelet volume and other platelet parameters may significantly aid the identification of diabetic pregnants at risk for vascular complications. The role and possible clinical relevance of these changes during diabetic pregnancy need to be investigated in further studies. PMID:24592046

  14. Differences in the acyl composition of the platelet-activating factor (PAF) precursor and other choline phosphoglycerides of the rabbit retinal rod outer segments and neural retina.

    PubMed

    Bazan, H E; Hurst, J S; Bazan, N G

    1994-01-01

    Choline phosphoglycerides comprise almost half of vertebrate retinal phospholipids. This lipid pool contains the precursor of the potent lipid mediator, platelet-activating factor. The acyl composition and distribution of the different subclasses of the choline phosphoglycerides (alkylacyl-[or the precursor of platelet-activating factor], alkenylacyl-[or choline plasmalogen] and diacyl-glycero-3-phosphocholine) were studied in intact rabbit retina, neural retina and rod outer segments. Choline phosphoglycerides were isolated by high performance liquid chromatography and derivatized by acetylation after phospholipase C treatment. The derivatives were purified by high performance liquid chromatography and subjected to methanolysis. Fatty acids were analyzed by capillary gas liquid chromatography. In the intact retina and in the neural retina, the alkylacyl-glycero-3-phosphocholine and alkenylacyl-glycero-3-phosphocholine comprise 1.2% and 1.5%, respectively, of the total choline phosphoglycerides, whereas the rod outer segments contain twice the proportion of the precursor of platelet-activating factor and no detectable plasmalogens. On a mole percent basis, arachidonic acid was highest in the neural retinal alkenylacyl-glycero-3-phosphocholine (27%), 18% in the alkylacyl-glycero-3-phosphocholine and only 5% in the diacyl-glycero-3-phosphocholine. However, alkylacyl-glycero-3-phosphocholine from rod outer segments was enriched in docosapentaenoic acid (18%) while arachidonic acid was in the 3-4% range. Our results suggest that, in the neural retina, alkyl-arachidonoyl-glycero-3-phosphocholine is a source of both platelet-activating factor and of arachidonic acid which may be a substrate for both prostaglandins and lipoxygenase metabolites during an inflammatory episode and may contribute to the retinal pathology.

  15. Pharmacological studies on the antispasmodic, bronchodilator and anti-platelet activities of Abies webbiana.

    PubMed

    Yasin, Mamoona; Hussain Janbaz, Khalid; Imran, Imran; Gilani, Anwar-ul-Hassan; Bashir, Samra

    2014-08-01

    This study evaluated the antispasmodic, bronchodilator and anti-platelet activities of Abies webbiana to rationalize some of its folk uses in gut and airways disorders and inflammation. The crude extract of A. webbiana (Aw.Cr) caused a complete relaxation of both spontaneous and K(+) (80 mM)-induced contractions in isolated rabbit jejunum in a concentration-dependent manner. Aw.Cr shifted the Ca(++) concentration-response curves (CRCs) to the right, in a fashion similar to verapamil, confirming its Ca(++) channel blocking (CCB) effect. In isolated rabbit tracheal preparations, it caused relaxation of carbachol (1 μM) and K(+) (80 mM)-induced contractions comparable to verapamil suggesting that the bronchodilatory effect may possibly be mediated through CCB activity. Aw.Cr was found to be the inhibitor of both ADP- and epinephrine-induced aggregation of human platelets thereby suggesting therapeutic potential in this plant against thrombo-embolic conditions. The exhibited anti-platelet effect was observed at low doses against epinephrine as compared to ADP. This study confirmed the presence of spasmolytic activity in Abies webbiana through possible blockade of Ca(++) channels providing evidence for its folkloric use in gut and respiratory disorders in addition to anti-platelet activity. Copyright © 2014 John Wiley & Sons, Ltd.

  16. Characterization of a tubular flow chamber for studying platelet interaction with biologic and prosthetic materials: deposition of indium 111-labeled platelets on collagen, subendothelium, and expanded polytetrafluoroethylene

    SciTech Connect

    Badimon, L.; Turitto, V.; Rosemark, J.A.; Badimon, J.J.; Fuster, V.

    1987-12-01

    A plastic (Plexiglas) chamber for evaluating platelet deposition under controlled hemodynamic conditions has been developed. The perfusion chamber has been designed to retain the cylindrical shape typical of the vasculature, to be flexible enough to accept a variety of biologic and prosthetic materials, and to simulate a broad range of physiologic flow conditions in either an ex vivo or in vitro perfusion system. Three type of surfaces were exposed to blood flowing directly from the carotid artery of a heparinized pig through the perfusion chamber: de-endothelialized pig aorta, collagen strips from rabbit Achilles tendon, and an expanded polytetrafluoroethylene material (Gore-Tex). Platelets, previously radiolabeled with indium 111 and injected into the animal, were quantified on the material surface, and the total number of deposited platelets determined for a range of blood flow rates (5 to 40 ml/min) and exposure times (0.5 to 20 minutes). The deposition rates were correlated with theory for describing the mass transport of platelets to the test surface. At the wall shear rates investigated (105 to 850 sec-1), the deposition of platelets on subendothelium was strongly dependent on the local flow conditions. Values of deposition on Gore-Tex obtained at similar flow conditions (105 to 425 sec-1) were reduced compared with that observed on subendothelium and showed a markedly weaker dependence on the shear rate. In contrast, deposition of platelets on collagen was more than an order of magnitude greater than on subendothelium and showed a dependence on flow only at the lowest flow rate studied (10 ml/min). The results indicate that collagen is much more reactive than subendothelium and Gore-Tex with respect to the growth and stability of platelet aggregates and moreover suggest that flow mechanisms for depositing platelets on various surface may be substantially different.

  17. Honokiol as a specific collagen receptor glycoprotein VI antagonist on human platelets: Functional ex vivo and in vivo studies

    PubMed Central

    Lee, Tzu-Yin; Chang, Chao-Chien; Lu, Wan-Jung; Yen, Ting-Lin; Lin, Kuan-Hung; Geraldine, Pitchairaj; Li, Jiun-Yi; Sheu, Joen-Rong

    2017-01-01

    Honokiol, derived from Magnolia officinalis, has various pharmacological properties. Platelet activation plays a critical role in cardiovascular diseases. Honokiol has been reported to inhibit collagen-stimulated rabbit platelet aggregation. However, detailed further studies on the characteristics and functional activity of honokiol in platelet activation are relatively lacking. In the present study, honokiol specifically inhibited platelet aggregation and Ca+2 ion mobilization stimulated with collagen or convulxin, an agonist of glycoprotein (GP) VI, but not with aggretin, an agonist of integrin α2β1. Honokiol also attenuated the phosphorylation of Lyn, PLCγ2, PKC, MAPKs, and Akt after convulxin stimulation. Honokiol have no cytotoxicity in zebrafish embryos. Honokiol diminished the binding of anti-GP VI (FITC-JAQ1) mAb to human platelets, and it also reduced the coimmunoprecipitation of GP VI-bound Lyn after convulxin stimulation. The surface plasmon resonance results revealed that honokiol binds directly to GP VI, with a KD of 289 μM. Platelet function analysis revealed that honokiol substantially prolonged the closure time in human whole blood and increased the occlusion time of thrombotic platelet plug formation in mice. In conclusion, honokiol acts as a potent antagonist of collagen GP VI in human platelets, and it has therapeutic potential in the prevention of the pathological thrombosis. PMID:28054640

  18. Honokiol as a specific collagen receptor glycoprotein VI antagonist on human platelets: Functional ex vivo and in vivo studies.

    PubMed

    Lee, Tzu-Yin; Chang, Chao-Chien; Lu, Wan-Jung; Yen, Ting-Lin; Lin, Kuan-Hung; Geraldine, Pitchairaj; Li, Jiun-Yi; Sheu, Joen-Rong

    2017-01-05

    Honokiol, derived from Magnolia officinalis, has various pharmacological properties. Platelet activation plays a critical role in cardiovascular diseases. Honokiol has been reported to inhibit collagen-stimulated rabbit platelet aggregation. However, detailed further studies on the characteristics and functional activity of honokiol in platelet activation are relatively lacking. In the present study, honokiol specifically inhibited platelet aggregation and Ca(+2) ion mobilization stimulated with collagen or convulxin, an agonist of glycoprotein (GP) VI, but not with aggretin, an agonist of integrin α2β1. Honokiol also attenuated the phosphorylation of Lyn, PLCγ2, PKC, MAPKs, and Akt after convulxin stimulation. Honokiol have no cytotoxicity in zebrafish embryos. Honokiol diminished the binding of anti-GP VI (FITC-JAQ1) mAb to human platelets, and it also reduced the coimmunoprecipitation of GP VI-bound Lyn after convulxin stimulation. The surface plasmon resonance results revealed that honokiol binds directly to GP VI, with a KD of 289 μM. Platelet function analysis revealed that honokiol substantially prolonged the closure time in human whole blood and increased the occlusion time of thrombotic platelet plug formation in mice. In conclusion, honokiol acts as a potent antagonist of collagen GP VI in human platelets, and it has therapeutic potential in the prevention of the pathological thrombosis.

  19. Photoaffinity labeling of human platelet and rabbit kidney. cap alpha. -adrenoceptors with (/sup 3/H)SKF 102229

    SciTech Connect

    Regan, J.W.; Raymond, J.R.; Lefkowitz, R.J.; DeMarinis, R.M.

    1986-06-13

    A newly developed ..cap alpha../sub 2/-adrenergic photoaffinity ligand, 3-methyl-6-chloro-9-azido-1H-2,3,4,5-tetrahydro-3-benzazepine (SKF 102229), has been radiolabeled with tritium to a specific activity of approx. 80 Ci/mmol. Using membranes prepared from human platelets and from rabbit kidney, ..cap alpha../sub 2/-adrenoceptors have been covalently labeled following photolysis in the presence of (/sup 3/H)SKF 102229. As determined by SDS-PAGE, the apparent molecular weight of ..cap alpha../sub 2/-adrenoceptors from both of these tissues was 64,000. The yield of covalent insertion of (/sup 3/H)SKF 102229 into the ..cap alpha../sub 2/-adrenoceptor was very good. Thus, following photolysis up to 90% of the ..cap alpha../sub 2/-adrenoceptors could be irreversibly labeled with (/sup 3/H)SKF 102229.

  20. A novel platelet-rich arterial thrombosis model in rabbits. Simple, reproducible, and dynamic real-time measurement by using double-opposing inverted-sutures model.

    PubMed

    Shieh, S J; Chiu, H Y; Shi, G Y; Wu, C M; Wang, J C; Chen, C H; Wu, H L

    2001-09-01

    Though numerous animal thrombosis models have been introduced, an easy, reliable, and reproducible arterial thrombosis model remains a continuing challenge prior to a thrombolytic study. In an effort to evaluate the efficiency of various recombinant thrombolytic agents with specific affinity to activated platelets in vivo, we developed a novel double-opposing inverted-sutures model to create a platelet-rich thrombus in the femoral artery of rabbits. The arteriotomy was done semicircumferentially, and variously sized microsurgical sutures were introduced intraluminally in a double-opposing inverted manner. The animals were divided into three groups according to the double-opposing inverted-sutures used: Group 1 with 10-0 nylon (n=6), Group 2 with 9-0 nylon (n=6), and Group 3 with 8-0 nylon (n=22). The superficial epigastric branch was cannulated with a thin polyethylene (PE) tube for intraarterial administration of the studied thrombolytic agent. The blood flow was continuously measured with a real-time ultrasonic flow meter. Within 2 h of installation of the sutures, there was no thrombus formation in either Group 1 or 2. In Group 3, the thrombosis rate was 91% (20 of 22) under a steady baseline flow (with an average of 12.23+/-2.40 ml/min). It was highly statistically significant with a P-value of .0000743 using Fisher's Exact Test. The averaged time to thrombosis was 21.8+/-9.8 min. The ultrasonic flow meter to record the dynamic real-time measurement of blood flow was a guideline for thrombus formation or dissolution, which was correlated with the morphological findings of stenotic status of the vessel detected by the Doppler sonography. The components of the thrombus were proven to be platelet-rich predominant by histological examination via hematoxylin and eosin (H&E) stain and transmission electron microscopy (TEM). To confirm that the double-opposing inverted-sutures model would be useful for a study of thrombolytic agents, we evaluated the effects of

  1. A comparison of bone generation capability in rabbits using tooth ash and plaster of Paris with platelet-rich plasma or fibrin sealant.

    PubMed

    Kim, Bong-Kyun; Kim, Su-Gwan; Kim, Seo-Yoon; Lim, Sung-Chul; Kim, Young-Kyun

    2010-09-01

    Increased attention has been focused on determining the most efficacious materials for generalized bone grafts. This article presents the results of a histomorphometric analysis of bone healing in the calvaria of rabbits. The study compared the use of a tooth ash and plaster of Paris mixture alone, in association with platelet-rich plasma (PRP), and in association with fibrin sealant. Twelve rabbits were divided into control (group 1) and experimental groups (groups 2, 3, and 4). Group 1 was maintained as an unfilled control, and tooth ash and plaster of Paris were used in group 2, tooth ash and plaster of Paris with PRP were used in group 3, and tooth ash and plaster of Paris with fibrin sealant (Tissucol Duo Quick) were used in group 4. One-half of the animals were killed after 4 weeks, and the rest were killed after 8 weeks. Bone samples were taken from the defect areas, and newly formed bone was analyzed histomorphometrically. The rate of new bone formation in groups 2, 3, and 4 was significantly higher than the rate in the control group. The rate of new bone formation in groups 3 and 4 was higher than the rate in group 2, but the difference was not statistically significant. The concomitant use of PRP or fibrin sealant with tooth ash and plaster of Paris graft materials may have a positive effect on bone healing. Copyright (c) 2010 Mosby, Inc. All rights reserved.

  2. The significance of platelet counts in coagulation studies.

    PubMed

    Carroll, W E; Wollitzer, A O; Harris, L; Ling, M C; Whitaker, W L; Jackson, R D

    2001-01-01

    Traditionally, the platelet count recommended for coagulation studies has been less than 10 x 10(9)/L, but the documentation for this is obscure. In the present study, platelet rich plasma (PRPs) and platelet poor plasmas (PPPs) were prepared from the same blood specimen to determine prothrombin times (PTs), International Normalized Ratios (INRs), partial thromboplastin times (PTTs), and their results compared. The measurements of all three of these parameters are not statistically or clinically significant in 100 paired comparisons. Incremented platelet count studies, selected by the number of platelets in the PRPs, showed that platelet counts of at least 199 x 10(9)/L, or perhaps even higher, did not compromise the results of PTs, INRs or PTTs. Such increased platelet counts, however, cannot be tolerated in the various studies for antiphospholipid antibodies, the Lupus Anticoagulant (LAC), or when monitoring heparin therapy with PTTs. Here, the < 10 x 10(9)/L platelet levels must be respected; otherwise the tests would be compromised by platelet-liberated phospholipid (Triplett, Brand et al., 1983) or by Platelet Factor 4, respectively.

  3. Quality assessment of platelets stored in a modified platelet additive solution with trehalose at low temperature (10 °C) and in vivo effects on rabbit model of thrombocytopenia.

    PubMed

    Wang, Xin; Fan, Yahan; Shi, Ronghua; Li, Jing; Zhao, Shuming

    2015-01-01

    Trehalose is widely used as a cryoprotective reagent to preserve various cells. Platelet additive solution-III (PAS) has been used to maintain platelet function, benefit the virus inactivation, and extend the storage period. PAS with trehalose (PAS-III M + T) may effectively protect platelets (PLTs) at a relatively low temperature (10 °C). The apheresis PLTs from six donors were divided into two groups. Group A was stored in PAS-III M + T at 10 °C as experimental group and group B in plasma at 22 °C as control group. The samples were collected on different storage dates, and multiple parameters were determined or investigated for in vitro studies. The in vivo recovery and survival of rabbit PLTs stored in the same conditions, and then labeled with (51)Cr were measured and evaluated using a rabbit model of thrombocytopenia. Over 9 days, P-selectin expression increased significantly in a time-dependent manner in both groups (n = 6). The levels of the hypotonic shock reaction and PLT aggregation rate decreased in both groups and were significantly higher in group A than B after 1 day of storage. The lactate dehydrogenase (LDH) release and glucose (GLU) consumption increased similarly, but the levels were significantly lower in group A than B. The pH decreased significantly after 5 days of storage in group B but did not change in group A. After 5 days, the morphology of the PLTs in group B maintained a more normal shape than that of group A. The recovery and survival of PLTs stored in both groups were not significantly different (p > 0.05). The bacteria growth was not examined out in both groups for up to 5 (group A) and 9 (group B) days. Storage of PLTs in the modified PAS at low temperature was more effective in protecting PLT functions than that of standard storage method and may have the potential to decrease the risk of PLT activation and bacterial contamination.

  4. [Pharmacological studies of FUT-175, nafamstat mesilate. IV. Effects on coagulation, platelets and fibrinolysis].

    PubMed

    Koshiyama, Y; Ozeki, M; Motoyoshi, A; Fujita, M; Iwaki, M; Aoyama, T

    1984-11-01

    Inhibitory effects of FUT-175 (nafamstat mesilate) on coagulation, platelets and fibrinolysis were examined. FUT-175 prolonged activated partial thromboplastin time, thrombin time and prothrombin time in rabbit plasma. FUT-175 prolonged these coagulation times in human plasma at lower concentration than in rabbit plasma. FUT-175 inhibited platelet aggregation induced by a variety of aggregation agents in rabbit platelet-rich plasma (PRP). In human PRP, FUT-175 inhibited platelet aggregation induced by a variety of aggregation agents at lower concentration than in rabbit PRP. Lipopolysaccharide induced a dose-dependent platelet aggregation in dog PRP. FUT-175 showed an inhibitory effect on this aggregation. FUT-175 inhibited clot retraction in rabbit plasma. The fibrinolysis activity was measured on fibrinolysis of rabbit plasma activated by urokinase. FUT-175 prolonged this fibrinolysis time. Inhibitory effects on coagulation and fibrinolysis were also found ex vivo. FUT-175 prolonged bleeding time in mice. These results indicate that FUT-175 has potent inhibitory effects on coagulation, platelets and fibrinolysis.

  5. Simple platelet markers: Mean platelet volume and congestive heart failure coexistent with periodontal disease. Pilot studies.

    PubMed

    Czerniuk, Maciej R; Bartoszewicz, Zbigniew; Dudzik-Niewiadomska, Iwona; Pilecki, Tomasz; Górska, Renata; Filipiak, Krzysztof J

    2017-07-17

    Conducted pilot study concerning mean platelet volume parameter among patients suffering from congestive heart failure and periodontal disease. Examination of dynamic changes of platelet and periodontal markers in group of 50 patients before and an average of 6 months subsequent to professional periodontal treatment. Both platelet and periodontal parameters decreased after periodontal treatment, what is more, the decrease of mean platelet volume (MPV) value due to periodontal disease/mm improvement was shown to be statistically significant (p = 0.05). Improvement of periodontal status may influence decrease of MPV value andincrease of congestive heart failure treatment efficacy and effect patient comfort. It is a new, not frequently used pattern of chronic disease treatment optimalization.

  6. Release of platelet activating factor in rabbits with antibody-mediated injury of the lung: the role of leukocytes and of pulmonary endothelial cells.

    PubMed

    Camussi, G; Pawlowski, I; Bussolino, F; Caldwell, P R; Brentjens, J; Andres, G

    1983-10-01

    This paper describes the release of platelet-activating factor (PAF) into the circulation of rabbits with acute pulmonary injury induced by antibody reacting with pulmonary endothelium. Eight rabbits were injected i.v. with 2 mg/kg of body weight of goat anti-rabbit lung angiotensin-converting enzyme gamma-globulin (GtARbACE). All animals developed acute pneumonitis, characterized by severe endothelial damage, accumulation of polymorphonuclear leukocytes (PMN) and platelets (Plt) in the lumina of alveolar capillaries, and deposits of goat IgG and rabbit C3 along alveolar capillary walls. Six of the rabbits died from acute pulmonary edema. PAF was detected in the plasma of all animals within 5 min after injection of GtARbACE. Five other rabbits were depleted of leukocytes by nitrogen mustard and then injected with 2 mg/kg of body weight of GtARbACE. In three of these rabbits release of PAF was demonstrated, though in amounts smaller than in non-leukocyte-depleted rabbits; all three animals died from pulmonary edema. After injection of 0.03 mg/kg of body weight of GtARbACE in six additional rabbits, three of them leukocyte-depleted, small amounts of PAF were detected in the circulation. None of these six rabbits died of pulmonary edema. PAF release was not observed in ten rabbits injected i.v. with 2 or 0.03 mg/kg of body weight of normal goat gamma-globulin. In separate experiments in vitro, incubation of isolated lung or thoracic aorta with GtARbACE resulted in deposits of goat IgG along endothelia and significant release of PAF. PAF was also released from endothelial cells removed from thoracic aorta by cellulose acetate paper and then incubated with GtARbACE. When segments of thoracic aorta were stripped of endothelium and then incubated with GtARbACE, PAF release could not be shown. The data obtained are consistent with the interpretation that PAF released into the circulation after binding of GtARbACE to the endothelia of lung and aorta originates from

  7. Survival and function of transfused platelets. Studies in two patients with congenital deficiencies of platelet membrane glycoproteins.

    PubMed

    Cesar, Jesus M; Vecino, Ana M

    2009-05-01

    Platelets of patients suffering from Glanzmann's thrombasthenia (GT) and Bernard Soulier Syndrome (BSS) are defective in different membrane glycoproteins. Since these integrins can be identified by monoclonal antibodies, normal infused platelets could be distinguished from defective platelets and followed by using flow cytometry (FC). We studied this aspect in two recipients suffering, one from GT and the other one, who underwent splenectomy, from BSS. One hour after transfusion, normal platelets comprised 17% of the total platelet population in the patient with GT. Aggregation tests detected a measurable response to collagen (increase of 15% of transmittance). The presence of transfused platelets decreased progressively to 0.8% on day 4, which corresponded with a half-life of 2.6 days. Studies performed in the patient suffering from BSS found that 1 hour after transfusion, 53% of the platelet population corresponded to normal platelets. There was a progressive decay until day 6, which corresponded to a half-life of 4.6 days. Aggregation tests also detected a platelet response to ristocetin from 1 hour after transfusion (47% increase of transmittance) to day 3. FC is useful to measure platelet lifespan in these kinds of patients. We also report the first studies of platelet aggregation after platelet transfusion.

  8. Effect of platelet-derived growth factor on voltage-operated calcium channels in rabbit isolated ear artery cells.

    PubMed Central

    Wijetunge, S.; Hughes, A. D.

    1995-01-01

    1. Platelet derived growth factor (PDGF), AB and BB isoforms (100 pM) increased calcium channel currents measured by whole cell voltage clamp technique in single vascular smooth muscle cells isolated from rabbit ear arteries. 2. Tyrphostin-23 (100 microM) a selective inhibitor of protein tyrosine kinases, reduced calcium channel currents. Pre-incubation with tyrphostin-23 prevented PDGF-AB induced increase in calcium channel currents. However, in these same cells 10 nM (+)-202791, a dihydropyridine calcium channel agonist, did increase calcium channel currents. 3. Bistyrphostin (10 microM), a selective inhibitor of epidermal growth factor (EGF)-kinase also reduced calcium channel currents and inhibited PDGF-AB-induced increases in calcium channel currents. 4. Genistein (100 microM) a selective inhibitor of tyrosine kinases, structurally unrelated to the tryphostins, also inhibited calcium channel currents and pre-incubation with genistein prevented the PDGF-AB-induced rise in calcium channel currents. 5. These results indicate that PDGF increases calcium channel currents in vascular smooth muscle. This action of PDGF probably involves a tyrosine kinase. PMID:7582469

  9. Effectiveness of xenogenous-based bovine-derived platelet gel embedded within a three-dimensional collagen implant on the healing and regeneration of the Achilles tendon defect in rabbits

    PubMed Central

    Moshiri, Ali; Oryan, Ahmad; Meimandi-Parizi, Abdolhamid; Koohi-Hosseinabadi, Omid

    2014-01-01

    Background and objective: Tissue engineering is an option in reconstructing large tendon defects and managing their healing and regeneration. We designed and produced a novel xenogeneic-based bovine platelet, embedded it within a tissue-engineered collagen implant (CI) and applied it in an experimentally induced large tendon defect model in rabbits to test whether bovine platelets could stimulate tendon healing and regeneration in vivo. Methods: One hundred twenty rabbits were randomly divided into two experimental and pilot groups. In all the animals, the left Achilles tendon was surgically excised and the tendon edges were aligned by Kessler suture. Each group was then divided into three groups of control (no implant), treated with CI and treated with collagen-platelet implant. The pilot groups were euthanized at 10, 15, 30 and 40 days post-injury (DPI), and their gross and histologic characteristics were evaluated to study host–graft interaction mechanism. To study the tendon healing and its outcome, the experimental animals were tested during the experiment using hematologic, ultrasonographic and various methods of clinical examinations and then euthanized at 60 DPI and their tendons were evaluated by gross pathologic, histopathologic, scanning electron microscopic, biophysical and biochemical methods. Results: Bovine platelets embedded within a CI increased inflammation at short term while it increased the rate of implant absorption and matrix replacement compared with the controls and CI alone. Treatment also significantly increased diameter, density, amount, alignment and differentiation of the collagen fibrils and fibers and approximated the water uptake and delivery behavior of the healing tendons to normal contralaterals (p < 0.05). Treatment also improved echogenicity and homogenicity of the tendons and reduced peritendinous adhesion, muscle fibrosis and atrophy, and therefore, it improved the clinical scores and physical activity related to the

  10. The Influence of Reserpine and Ethylenediaminetetraacetic Acid (EDTA) on Serotonin Storage Organelles of Blood Platelets

    PubMed Central

    Gerrard, Jonathan M.; Rao, Gundu H. R.; White, James G.

    1977-01-01

    The present investigation has evaluated the influence of reserpine on the serotonin-rich organelles bodies) in platelets from dogs, rabbits, and humans. Reserpine markedly depresses the levels of stored serotonin in human and animal platelets, accompanied by a small decrease in platelet ATP but no change in platelet ADP content. Thin sections of human platelets showed no change in the number or morphology of serotonin storage organelles during reserpine therapy, whereas a profound decrease in the size and number of dense bodies occurred in platelets from rabbits treated with reserpine. Dog platelets also showed a decrease in the number and density of serotonin storage organelles after reserpine therapy. The basis for the difference between rabbit and human platelets was explored by fixing platelets in glutaraldehyde and osmium in the presence or absence of the chelating agent ethylenediaminetetraacetic acid (EDTA). Most of the dense bodies in fixed human platelets were removed by EDTA while rabbit platelet dense bodies remained essentially intact. The results suggested that the opacity of rabbit platelet dense bodies following fixation with glutaraldehyde and osmium relate primarily to their serotonin content, while the electron density of human serotonin storage organelles in fixed cells is due primarily to their calcium content. Further confirmation of this concept came from studies of platelets using the whole mount technique. Rabbit platelet serotonin storage organelles were found to lack the inherent opacity of the human dense bodies, a finding consistent with the lower concentration of calcium in the rabbit organelles. ImagesFigures 1A-DFigure 2Figure 3Figure 4Figures 5 and 6Figure 7Figure 8 PMID:405872

  11. Homogenous demineralized dentin matrix and platelet-rich plasma for bone tissue engineering in cranioplasty of diabetic rabbits: biochemical, radiographic, and histological analysis.

    PubMed

    Gomes, M F; Valva, V N; Vieira, E M M; Giannasi, L C; Salgado, M A C; Vilela-Goulart, M G

    2016-02-01

    This study evaluated the effects of homogenous demineralized dentin matrix (HDDM) slices and platelet-rich plasma (PRP) in surgical defects created in the parietal bones of alloxan-induced diabetic rabbits, treated with a guided bone regeneration technique. Biochemical, radiographic, and histological analyses were performed. Sixty adult New Zealand rabbits were divided into five groups of 12: normoglycaemic (control, C), diabetic (D), diabetic with a PTFE membrane (DM), diabetic with a PTFE membrane and HDDM slices (DM-HDDM), and diabetic with PTFE membrane and PRP (DM-PRP). The quantity and quality of bone mass was greatest in the DM-HDDM group (respective radiographic and histological analyses: at 15 days, 71.70 ± 16.50 and 50.80 ± 1.52; 30 days, 62.73 ± 16.51 and 54.20 ± 1.23; 60 days, 63.03 ± 11.04 and 59.91 ± 3.32; 90 days, 103.60 ± 24.86 and 78.99 ± 1.34), followed by the DM-PRP group (respective radiographic and histological analyses: at 15 days 23.00 ± 2.74 and 20.66 ± 7.45; 30 days 31.92 ± 6.06 and 25.31 ± 5.59; 60 days 25.29 ± 16.30 and 46.73 ± 2.07; 90 days 38.10 ± 14.04 and 53.38 ± 9.20). PRP greatly enhanced vascularization during the bone repair process. Abnormal calcium metabolism was statistically significant in the DM-PRP group (P<0.001) for all four time intervals studied, especially when compared to the DM-HDDM group. Alkaline phosphatase activity was significantly higher in the DM-HDDM group (P<0.001) in comparison to the C, D, and DM-PRP groups, confirming the findings of intense osteoblastic activity and increased bone mineralization. Thus, HDDM promoted superior bone architectural microstructure in bone defects in diabetic rabbits due to its effective osteoinductive and osteoconductive activity, whereas PRP stimulated angiogenesis and red bone marrow formation.

  12. Platelet-rich plasma increases transforming growth factor-beta1 expression at graft-host interface following autologous osteochondral transplantation in a rabbit model

    PubMed Central

    Boakye, Lorraine A; Ross, Keir A; Pinski, John M; Smyth, Niall A; Haleem, Amgad M; Hannon, Charles P; Fortier, Lisa A; Kennedy, John G

    2015-01-01

    AIM: To explore the effect of platelet-rich plasma on protein expression patterns of transforming growth factor-beta1 (TGF-β1) in cartilage following autologous osteochondral transplantation (AOT) in a rabbit knee cartilage defect model. METHODS: Twelve New Zealand white rabbits received bilateral AOT. In each rabbit, one knee was randomized to receive an autologous platelet rich plasma (PRP) injection and the contralateral knee received saline injection. Rabbits were euthanized at 3, 6 and 12 wk post-operatively. Articular cartilage sections were stained with TGF-β1 antibody. Histological regions of interest (ROI) (left, right and center of the autologous grafts interfaces) were evaluated using MetaMorph. Percentage of chondrocytes positive for TGF-β1 was then assessed. RESULTS: Percentage of chondrocytes positive for TGF-β1 was higher in PRP treated knees for selected ROIs (left; P = 0.03, center; P = 0.05) compared to control and was also higher in the PRP group at each post-operative time point (P = 6.6 × 10-4, 3.1 × 10-4 and 7.3 × 10-3 for 3, 6 and 12 wk, respectively). TGF-β1 expression was higher in chondrocytes of PRP-treated knees (36% ± 29% vs 15% ± 18%) (P = 1.8 × 10-6) overall for each post-operative time point and ROI. CONCLUSION: Articular cartilage of rabbits treated with AOT and PRP exhibit increased TGF-β1 expression compared to those treated with AOT and saline. Our findings suggest that adjunctive PRP may increase TGF-β1 expression, which may play a role in the chondrogenic effect of PRP in vivo. PMID:26716092

  13. The Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study: Variation in Platelet Response to Clopidogrel and Aspirin.

    PubMed

    Bozzi, Laura M; Mitchell, Braxton D; Lewis, Joshua P; Ryan, Kathy A; Herzog, William R; O'Connell, Jeffrey R; Horenstein, Richard B; Shuldiner, Alan R; Yerges-Armstrong, Laura M

    2016-01-01

    Clopidogrel and aspirin are commonly prescribed anti-platelet medications indicated for patients who have experienced, or are at risk for, ischemic cardiovascular events. The Pharmacogenomics of Anti-Platelet Intervention (PAPI) Study was designed to characterize determinants of clopidogrel and dual anti-platelet therapy (DAPT) response in a healthy cohort of Old Order Amish from Lancaster, PA. Following a loading dose, clopidogrel was taken once a day for 7 days. One hour after the last dose of clopidogrel, 325 mg of aspirin was given. Ex vivo platelet aggregometry was performed at baseline, post-clopidogrel, and post-DAPT. Platelet aggregation measurements were significantly lower after both interventions for all agonists tested (p <0.05), although there was large inter-individual variation in the magnitude of anti-platelet response. Female sex and older age were associated with higher platelet aggregation at all three time-points. Change in aggregation was correlated among the various agonists at each time point. Heritability (h2) of change in platelet aggregation was significant for most traits at all time-points (range h2=0.14-0.57). Utilization of a standardized, short-term intervention provided a powerful approach to investigate sources of variation in platelet aggregation response due to drug therapy. Further, this short-term intervention approach may provide a useful paradigm for pharmacogenomics studies.

  14. Pilot study of homologous platelet gel in venous ulcers*

    PubMed Central

    de Oliveira, Mariele Gobo; Abbade, Luciana Patricia Fernandes; Miot, Hélio Amante; Ferreira, Rosana Rossi; Deffune, Elenice

    2017-01-01

    Background Venous ulcers represent 70% of the lower limb ulcers. They are difficult to heal, requiring a correct diagnostic and therapeutic approach. Many products have been developed to healing, such as homologous platelet gel obtained from the platelet concentrate exceeding from blood transfusion. Objective To evaluate the safety and efficacy of homologous platelet gel in venous ulcers compared with hydrocolloid dressing. Method A pilot randomized clinical trial in patients with venous ulcers. Randomized groups (homologous platelet gel and hydrocolloid groups) were followed for 90 days and were assessed through the evolution of ulcerated area, qualitative analysis of vascularization and adverse events. Both groups used elastic compression. Results We included 16 participants, with a total of 21 venous ulcers. Both treatments promoted a reduction of the areas of the ulcers in 90 days (mean 69%), there was significant difference between the groups concerning the gradual reduction of the ulcers areas, favorably to the hydrocolloid (70% vs 64%; p <0.01). There were some mild adverse events in both groups. Study limitations Single-center study with a small number of patients, preventing more accurate assessment of the effects of platelet gel. Conclusion The homologous platelet gel associated with the elastic compression can be an alternative to the venous ulcer treatment and is safe due to the occurrence of a few mild local adverse events and no serious adverse events. Clinical trials with larger numbers of patients must be performed to maintain the indication of this treatment for venous ulcer. PMID:28954098

  15. Exploratory studies of extended storage of apheresis platelets in a platelet additive solution (PAS).

    PubMed

    Slichter, Sherrill J; Corson, Jill; Jones, Mary Kay; Christoffel, Todd; Pellham, Esther; Bailey, S Lawrence; Bolgiano, Doug

    2014-01-09

    To evaluate the poststorage viability of apheresis platelets stored for up to 18 days in 80% platelet additive solution (PAS)/20% plasma, 117 healthy subjects donated platelets using the Haemonetics MCS+, COBE Spectra (Spectra), or Trima Accel (Trima) systems. Control platelets from the same subjects were compared with their stored test PAS platelets by radiolabeling their stored and control platelets with either (51)chromium or (111)indium. Trima platelets met Food and Drug Administration poststorage platelet viability criteria for only 7 days vs almost 13 days for Haemonetics platelets; ie, platelet recoveries after these storage times averaged 44 ± 3% vs 49 ± 3% and survivals were 5.4 ± 0.3 vs 4.6 ± 0.3 days, respectively. The differences in storage duration are likely related to both the collection system and the storage bag. The Spectra and Trima platelets were hyperconcentrated during collection, and PAS was added, whereas the Haemonetics platelets were elutriated with PAS, which may have resulted in less collection injury. When Spectra and Trima platelets were stored in Haemonetics' bags, poststorage viability was significantly improved. Platelet viability is better maintained in vitro than in vivo, allowing substantial increases in platelet storage times. However, implementation will require resolution of potential bacterial overgrowth during storage.

  16. Exploratory studies of extended storage of apheresis platelets in a platelet additive solution (PAS)

    PubMed Central

    Corson, Jill; Jones, Mary Kay; Christoffel, Todd; Pellham, Esther; Bailey, S. Lawrence; Bolgiano, Doug

    2014-01-01

    To evaluate the poststorage viability of apheresis platelets stored for up to 18 days in 80% platelet additive solution (PAS)/20% plasma, 117 healthy subjects donated platelets using the Haemonetics MCS+, COBE Spectra (Spectra), or Trima Accel (Trima) systems. Control platelets from the same subjects were compared with their stored test PAS platelets by radiolabeling their stored and control platelets with either 51chromium or 111indium. Trima platelets met Food and Drug Administration poststorage platelet viability criteria for only 7 days vs almost 13 days for Haemonetics platelets; ie, platelet recoveries after these storage times averaged 44 ± 3% vs 49 ± 3% and survivals were 5.4 ± 0.3 vs 4.6 ± 0.3 days, respectively. The differences in storage duration are likely related to both the collection system and the storage bag. The Spectra and Trima platelets were hyperconcentrated during collection, and PAS was added, whereas the Haemonetics platelets were elutriated with PAS, which may have resulted in less collection injury. When Spectra and Trima platelets were stored in Haemonetics’ bags, poststorage viability was significantly improved. Platelet viability is better maintained in vitro than in vivo, allowing substantial increases in platelet storage times. However, implementation will require resolution of potential bacterial overgrowth during storage. PMID:24258816

  17. A rabbit model for study of Mycobacterium paratuberculosis infection.

    PubMed Central

    Mokresh, A H; Czuprynski, C J; Butler, D G

    1989-01-01

    Of 21 newborn rabbits inoculated orally with Mycobacterium paratuberculosis ATCC 19698, 13 (62%) became infected, as determined by histopathology and culture. Of the 21 inoculated rabbits, 14 (67%) experienced episodes of intermittent diarrhea, sometimes as early as 5 months after inoculation. Feces varied in consistency from soft-semisolid to watery. The organism was isolated from the sacculus rotundus, vermiform appendix of the cecum, ileum, mesenteric lymph node, and feces of 9 of 21 (43%) M. paratuberculosis-inoculated rabbits 8 to 10 months after inoculation. One infected rabbit gradually became severely emaciated; advanced paratuberculosis was confirmed by culture and histopathology. Of 21 rabbits, 9 (43%) developed multifocal, well-demarcated granulomatous enteritis in the sacculus rotundus and the vermiform appendix of the cecum. There was no significant difference in the rate of infection when the organisms were administered daily for 5 or 10 days in cow milk or broth. There was no discernible effect of pregnancy, parturition, or lactation on the severity of intestinal lesions, clinical signs, or the number of rabbits infected. Complement fixation and delayed-type hypersensitivity skin tests failed to detect infection. The results of this study suggest that newborn rabbits inoculated orally with M. paratuberculosis constitute a useful animal model for the study of paratuberculosis infection. Images PMID:2807547

  18. Platelets for neonatal transfusion - study 2: a randomised controlled trial to compare two different platelet count thresholds for prophylactic platelet transfusion to preterm neonates.

    PubMed

    Curley, Anna; Venkatesh, Vidheya; Stanworth, Simon; Clarke, Paul; Watts, Timothy; New, Helen; Willoughby, Karen; Khan, Rizwan; Muthukumar, Priya; Deary, Alison

    2014-01-01

    Neonatal thrombocytopenia is a common and important clinical problem in preterm neonates. A trial assessing clinically relevant outcomes in relation to the different platelet count thresholds used to trigger transfusion has never been undertaken in preterm neonates with severe thrombocytopenia. Platelets for Neonatal Transfusion - Study 2 (PlaNeT-2) aims to assess whether a higher prophylactic platelet transfusion threshold is superior to the lower thresholds in current standard practice in reducing the proportion of patients who have a major bleed or die up to study day 28. PlaNeT-2 is a two-stage, randomised, parallel-group, superiority trial. PlaNet-2 compares clinical outcomes in preterm neonates (<34 weeks' gestation at birth) randomised to receive prophylactic platelet transfusions to maintain platelet counts at or above either 25 × 10(9)/l or 50 × 10(9)/l. The primary outcome measure is the proportion of patients who either die or experience a major bleed up to and including study day 28. A total of 660 infants will be randomised. This trial will help define optimal platelet transfusion support for severely thrombocytopenic preterm neonates by evaluating the risks and benefits of two different prophylactic neonatal platelet transfusion thresholds. © 2014 S. Karger AG, Basel.

  19. Ristocetin-Induced Platelet Aggregation (RIPA) and RIPA Mixing Studies.

    PubMed

    Frontroth, Juan Pablo; Favaloro, Emmanuel J

    2017-01-01

    Ristocetin-induced platelet aggregation (RIPA) is used as an in vitro test to determine the presence and integrity of the platelet glycoprotein (GP) Ibα-V-IX complex and von Willebrand factor (VWF) interaction and is usually performed using platelet-rich plasma (PRP). Impairment in the response of VWF/GPIbα-V-IX is measured with reference to several established concentrations of ristocetin and may indicate defects in VWF or in GPIbα-V-IX function. RIPA-based mixing studies comprise an additional approach to testing this interaction to help define whether defects identified by RIPA lie in VWF or in GPIbα-V-IX. For example, the correction of an abnormal RIPA trace after mixing PRP with normal plasma and rechallenging with ristocetin at 1.0 mg/mL suggests VWF function/quantity defect. RIPA mixing studies at lower doses of ristocetin (0.5 mg/mL) are recommended for discrimination of von Willebrand disease type 2B (VWD2B) from the rarer platelet-type (PT) VWD and for the phenotypic laboratory diagnosis of VWD2B. The demonstration of a plasma factor capable of inducing platelet aggregation at such low doses of ristocetin represents the hallmark for the phenotypic laboratory diagnosis of VWD2B. Moreover, since both VWD2B and PT-VWD may present with thrombocytopenia, RIPA-based mixing studies are also useful in thrombocytopenic patients in whom RIPA testing is difficult to assess.

  20. Indium 111-labeled platelet kinetic studies and platelet-associated IgG in hairy cell leukemia

    SciTech Connect

    Panzer, S.; Lechner, K.; Neumann, E.; Meryn, S.; Haubenstock, A.

    1986-07-15

    In order to study the pathogenesis of thrombocytopenia in patients with hairy cell leukemia (HCL), levels of platelet-associated IgG (PAIgG), platelet life span (MLS), and the sequestration site of autologous /sup 111/In-labeled platelets were measured in nine patients with HCL. Splenectomized patients (n = 4) had a higher platelet count (x = 122.5 X 10(9)/l; range, 80-190 X 10(9)/l) as well as higher levels of PAIgG (x = 10.7%; range, 5.8-16.9%), than nonsplenectomized patients (platelets x = 76 X 10(9)/l, range 40-100 X 10(9)/l; PAIgG x = 3.2%, range 2.2-4.2%). A normal recovery of /sup 111/In-labeled platelets was found in splenectomized patients, whereas a very low recovery was observed in the nonsplenectomized group (x = 70.2%, range, 50-82.5%, versus x = 22.4%, range, 15-28.2%). The MLS was borderline normal in all patients. The site of sequestration was the spleen in nonsplenectomized patients. The low recovery of /sup 111/In-labeled platelets in nonsplenectomized patients suggests hypersplenism with pooling as a major cause of thrombocytopenia, in addition to impaired thrombocytopoiesis and possible immune-mediated platelet destruction.

  1. Platelet function in baboons and humans - A comparative study of whole blood using impedance platelet aggregometry (Multiplate®).

    PubMed

    Ponschab, Martin; van Griensven, Martijn; Heitmeier, Stefan; Laux, Volker; Schlimp, Christoph J; Calatzis, Andreas; Bahrami, Soheyl; Redl, Heinz; Schöchl, Herbert

    2016-11-01

    Platelets play a pivotal role in coagulation, inflammation and wound healing. Suitable animal models that have the potential to mimic human platelet function are limited. The objective of the current study was to compare platelet aggregation response in the whole blood of baboons and humans using impedance aggregometry. Blood was drawn from 24 anesthetised male baboons and 25 healthy volunteers. The platelet aggregation response was determined by impedance aggregometry (Multiplate®). Platelets in the hirudinised whole blood samples were stimulated with four different activators: adenosine diphosphate (ADP), collagen (COL), thrombin receptor activating peptide-6 (TR1AP), and activation of PAR-4 thrombin receptor subtype (TR4AP) at standard concentrations. Higher than standard concentrations were tested in a subgroup of the animals. The cell counts showed no differences between baboons and humans. The platelet aggregation response was significantly lower in baboons compared to humans when stimulated with the platelet agonists ADP (p<0.0001), COL (p=0.021) and TR4AP (p<0.0001). TR1AP did not stimulate platelet aggregation in the baboon blood. Doubling the concentration of ADP and of TR4AP significantly increased the AUC compared to the standard concentration. In contrast, increased COL levels did not further increase the AUC. The current study revealed that testing the platelet function in baboon blood by impedance aggregometry is feasible with ADP, COL and TR4AP, but not with TR1AP. Compared to humans, the aggregation response is lower in baboons. Considering the limitations in accordance to these results, baboons might represent a potential species for further platelet research. Copyright © 2016. Published by Elsevier Ltd.

  2. A Meta-Analysis and Genome-Wide Association Study of Platelet Count and Mean Platelet Volume in African Americans

    PubMed Central

    Qayyum, Rehan; Snively, Beverly M.; Ziv, Elad; Nalls, Michael A.; Liu, Yongmei; Tang, Weihong; Yanek, Lisa R.; Lange, Leslie; Evans, Michele K.; Ganesh, Santhi; Austin, Melissa A.; Lettre, Guillaume; Becker, Diane M.; Zonderman, Alan B.; Singleton, Andrew B.; Harris, Tamara B.; Mohler, Emile R.; Logsdon, Benjamin A.; Kooperberg, Charles; Folsom, Aaron R.; Wilson, James G.

    2012-01-01

    Several genetic variants associated with platelet count and mean platelet volume (MPV) were recently reported in people of European ancestry. In this meta-analysis of 7 genome-wide association studies (GWAS) enrolling African Americans, our aim was to identify novel genetic variants associated with platelet count and MPV. For all cohorts, GWAS analysis was performed using additive models after adjusting for age, sex, and population stratification. For both platelet phenotypes, meta-analyses were conducted using inverse-variance weighted fixed-effect models. Platelet aggregation assays in whole blood were performed in the participants of the GeneSTAR cohort. Genetic variants in ten independent regions were associated with platelet count (N = 16,388) with p<5×10−8 of which 5 have not been associated with platelet count in previous GWAS. The novel genetic variants associated with platelet count were in the following regions (the most significant SNP, closest gene, and p-value): 6p22 (rs12526480, LRRC16A, p = 9.1×10−9), 7q11 (rs13236689, CD36, p = 2.8×10−9), 10q21 (rs7896518, JMJD1C, p = 2.3×10−12), 11q13 (rs477895, BAD, p = 4.9×10−8), and 20q13 (rs151361, SLMO2, p = 9.4×10−9). Three of these loci (10q21, 11q13, and 20q13) were replicated in European Americans (N = 14,909) and one (11q13) in Hispanic Americans (N = 3,462). For MPV (N = 4,531), genetic variants in 3 regions were significant at p<5×10−8, two of which were also associated with platelet count. Previously reported regions that were also significant in this study were 6p21, 6q23, 7q22, 12q24, and 19p13 for platelet count and 7q22, 17q11, and 19p13 for MPV. The most significant SNP in 1 region was also associated with ADP-induced maximal platelet aggregation in whole blood (12q24). Thus through a meta-analysis of GWAS enrolling African Americans, we have identified 5 novel regions associated with platelet count of which 3 were replicated in other ethnic

  3. [Mechanism of cooked blanched garlic leaves against platelet aggregation].

    PubMed

    Wang, Xin-Hua; Di, Yan-Hui

    2014-06-01

    This study was purposed to explore the mechanism of cooked blanched garlic leave juice against platelet aggregation. The juice of blanched garlic leaves was mixed with platelet rich plasma (PRP), the human platelet aggregation, the activation of human platelets induced by adenosine diphosphate (ADP) and collagen were observed; the expression levels of the activated platelets (Fib-R) and P-selectin (CD62P), and the amount of platelet fibrinogen binding were detected by flow cytometry; 10 rabbits were randomly divided into two groups, in addition to the normal diet, they were fed with physiologic saline and cooked blanched garlic leave juice respectively. After 1, 3, 5 , 8 weeks, the maximum ratio of rabbit platelet aggregation induced by ADP and collagen were observed . The results showed that the cooked blanched garlic leave juice could significantly inhibit human platelet aggregation induced by ADP and collagen (P < 0.05), the inhibitory ratio were 87.37% and 86.24% respectively; the juice could not inhibit activated platelets Fib-R and CD62P expression levels (P > 0.05), but was able to inhibit platelet fibrinogen binding capacity (P < 0.05); the rabbit platelet aggregation rate in the group given cooked blanched garlic leave juice was significantly lower than that in control group (P < 0.05). It is concluded that the cooked blanched garlic leave juice can inhibit platelet aggregation in vitro and in vivo, the inhibition of aggregation pathway mainly is blocking the combination of fibrinogen with Fib-R, which finally results in the inhibition of platelet aggregation. Therefore, regular consumption of cooked blanched garlic leaves may prevent cardiovascular thrombotic diseases.

  4. BIORESORBABLE POLYMERIC MENISCAL PROSTHESIS: STUDY IN RABBITS

    PubMed Central

    Cardoso, Tulio Pereira; de Rezende Duek, Eliana Aparecida; Amatuzzi, Marco Martins; Caetano, Edie Benedito

    2015-01-01

    Objective: To induce growth of a neomeniscus into the pores of a prosthesis in order to protect the knee joint cartilage. Methods: 70 knees of 35 New Zealand rabbits were operated. The rabbits were five to seven months old, weighed 2 to 3.8 kilograms, and 22 were male and 13 were female. Each animal underwent medial meniscectomy in both knees during a single operation. A bioabsorbable polymeric meniscal prosthesis composed of 70% polydioxanone and 30% L-lactic acid polymer was implanted in one side. The animals were sacrificed after different postoperative time intervals. The femoral condyles and neomeniscus were subjected to histological analysis. Histograms were used to measure the degradation and absorption of the prosthesis, the growth of meniscal tissue in the prosthesis and the degree of degradation of the femoral condyle joint cartilage. Results: The data obtained showed that tissue growth histologically resembling a normal meniscus occurred, with gradual absorption of the prosthesis, and the percentages of chondrocytes on the control side and prosthesis side. Conclusion: Tissue growth into the prosthesis pores that histologically resembled the normal rabbit meniscus was observed. The joint cartilage of the femoral condyles on the prosthesis side presented greater numbers of chondrocytes in all its layers. PMID:27022549

  5. Effects of platelet-rich plasma-containing fragmin/protamine microparticles in enhancing endothelial and smooth muscle cell growth and inducing collateral vessels in a rabbit model of hindlimb ischemia.

    PubMed

    Fujita, Masanori; Horio, Takuya; Kishimoto, Satoko; Nakamura, Shingo; Takikawa, Megumi; Nakayama, Takefumi; Yamamoto, Yoritsuna; Shimizu, Masafumi; Hattori, Hidemi; Tachibana, Shoichi; Ishihara, Masayuki

    2013-01-01

    The purpose of the study was to evaluate the effects of isogenous platelet-rich plasma (PRP)-containing fragmin/protamine microparticles (F/P MPs) as a delivery system for proteins in PRP on growth of endothelial and smooth muscle cells (SMCs) in vitro and as an alternative treatment for peripheral arterial disease (PAD) and critical limb ischemia. Frozen and thawed PRP contains high concentrations of growth factors that are adsorbed by F/P MPs. Human aorta endothelial cells (AECs) and SMCs were grown in a medium with PRP. Addition of F/P MPs significantly enhanced the proliferative effects of PRP on AECs and SMCs at 37 °C for >10 days. Intramuscular administration of phosphate-buffered saline (PBS; 2 mL, control), F/P MPs (12 mg in 2 mL PBS), PRP (2 mL), or PRP (2 mL) containing F/P MPs (12 mg) was then performed in a rabbit model of hindlimb ischemia prepared by resection of the left femoral artery. Blood flow and pressure were measured on days 0, 14, and 28, and angiography to assess arteriogenesis was performed on day 28. PRP-containing F/P MPs strongly induced functional collateral vessels in the rabbit model of hindlimb ischemia, indicating possible use of these microparticles in therapy for PAD. Copyright © 2012 Wiley Periodicals, Inc.

  6. Platelet rich plasma enhances osteoconductive properties of a hydroxyapatite-β-tricalcium phosphate scaffold (Skelite) for late healing of critical size rabbit calvarial defects.

    PubMed

    El Backly, Rania M; Zaky, Samer H; Canciani, Barbara; Saad, Manal M; Eweida, Ahmed M; Brun, Francesco; Tromba, Giuliana; Komlev, Vladimir S; Mastrogiacomo, Maddalena; Marei, Mona K; Cancedda, Ranieri

    2014-07-01

    The use of platelet rich plasma (PRP) in bone repair remains highly controversial. In this work, we evaluated the effect of lyophilized PRP on bone regeneration when associated with a silicon stabilized hydroxyapatite tricalcium phosphate scaffold in a rabbit calvarial defect (Skelite). Critical defects were created in the calvaria of twenty-four rabbits. The periosteum was removed and the defects were either left empty or filled with allogeneic PRP gel; Skelite particles; Skelite and PRP gel. Four animals were killed after 4 weeks, 10 animals after 8 and 10 after 16 weeks. Specimens were processed for X-ray microtomography (μCT) and for resin embedded histology. μCT analysis revealed significant osteoid-like matrix and new bone deposition in PRP + Skelite group at both 8 and 16 weeks in respect to Skelite alone. Histologically, PRP + Skelite defects were highly cellular with more abundant osteoid deposition and more regular collagen fibres. Moreover, in vitro migration assays confirmed the chemotactic effect of PRP to endothelial and osteoprogenitor cells. We conclude that the addition of PRP influenced the local tissue microenvironment by providing key cryptic factors for regeneration, thereby enhancing progenitor cell recruitment, collagen and bone matrix deposition, and by creating a bridging interface between the scaffold and bone.

  7. Bone Augmentation in Rabbit Tibia Using Microfixed Cobalt-Chromium Membranes with Whole Blood and Platelet-Rich Plasma

    PubMed Central

    Decco, Oscar A.; Beltrán, Víctor; Zuchuat, Jésica I.; Cura, Andrea C.; Lezcano, María F.; Engelke, Wilfried

    2015-01-01

    Background: Bone augmentation is a subject of intensive investigation in regenerative bone medicine and constitutes a clinical situation in which autogenous bone grafts or synthetic materials are used to aid new bone formation. Method: Based on a non-critical defect, Co-Cr barrier membranes were placed on six adult Fauve de Bourgogne rabbits, divided into two groups: whole blood and PRP. Three densitometric controls were performed during the experiment. The animals were euthanized at 30, 45, 60, and 110 days. The presence of newly formed bone was observed. Samples for histological studies were taken from the augmentation center. Results: External and internal bone tissue augmentation was observed in almost all cases. Significant differences between PRP- and whole blood–stimulated bone augmentation were not observed. At 60 days, bones with PRP presented higher angiogenesis, which may indicate more proliferation and cellular activity. Conclusion: PRP activates the bone regeneration process under optimized conditions by stimulation of osteoblast proliferation after six weeks, when a significant difference in cellular activity was observed. Membranes could stimulate bone augmentation at the site of placement and in the surrounding areas. PMID:28793476

  8. Back to the Future: Studying Cholera Pathogenesis Using Infant Rabbits

    PubMed Central

    Ritchie, Jennifer M.; Rui, Haopeng; Bronson, Roderick T.; Waldor, Matthew K.

    2010-01-01

    ABSTRACT Cholera is a severe diarrheal disease, caused by Vibrio cholerae, for which there has been no reproducible, nonsurgical animal model. Here, we report that orogastric inoculation of V. cholerae into 3-day-old rabbits pretreated with cimetidine led to lethal, watery diarrhea in virtually all rabbits. The appearance and chemical composition of the rabbit diarrheal fluid were comparable to those of the “rice-water stool” produced by cholera patients. As in humans, V. cholerae mutants that do not produce cholera toxin (CT) and toxin-coregulated pilus (TCP) did not induce cholera-like disease in rabbits. CT induced extensive exocytosis of mucin from intestinal goblet cells, and wild-type V. cholerae was predominantly found in close association with mucin. Large aggregates of mucin-embedded V. cholerae were observed, both attached to the epithelium and floating within the diarrheal fluid. These findings suggest that CT-dependent mucin secretion significantly influences V. cholerae’s association with the host intestine and its exit from the intestinal tract. Our model should facilitate identification and analyses of factors that may govern V. cholerae infection, survival, and transmission, such as mucin. In addition, our results using nontoxigenic V. cholerae suggest that infant rabbits will be useful for study of the reactogenicity of live attenuated-V. cholerae vaccines. PMID:20689747

  9. Rabbit care unit for intravenous feeding and metabolic studies.

    PubMed

    Haukipuro, K; Harju, E

    1986-01-01

    A simple rabbit care unit for peripheral intravenous feeding and metabolic studies was developed. The unit consists of six aluminum boxes with a common cover. Inverted T-shaped mobile supports hanging from the upper horizontal part of a frame hold the infusion lines. The side walls of the box prevent the rabbit from turning around, but other movements are possible. After initial training with 21 surgically treated animals, there was only one early anesthetic death among the subsequent 21 rabbits (4.8%). There was one late death (4.8%), and one animal was slightly, and two animals clearly, deteriorated. The ear vein cannula had to be changed in one-third of the animals not more than 3 days from the outset. Problems associated with the infusion systems or urinary bladder catheterization were minor. The results showed that it is practical to infuse rabbits via a peripheral intravenous route in a semi-restraining metabolic unit. The cases of late death and deterioration can be explained in part by the stress of experimental conditions with starvation and surgery, rather than by the effect of the metabolic unit alone. With previous experience in treating rabbits, we find the period required to learn this technique is short.

  10. Connective tissue growth factor differentially binds to members of the cystine knot superfamily and potentiates platelet-derived growth factor-B signaling in rabbit corneal fibroblast cells.

    PubMed

    Pi, Liya; Chung, Pei-Yu; Sriram, Sriniwas; Rahman, Masmudur M; Song, Wen-Yuan; Scott, Edward W; Petersen, Bryon E; Schultz, Gregory S

    2015-11-26

    To study the binding of connective tissue growth factor (CTGF) to cystine knot-containing ligands and how this impacts platelet-derived growth factor (PDGF)-B signaling. The binding strengths of CTGF to cystine knot-containing growth factors including vascular endothelial growth factor (VEGF)-A, PDGF-B, bone morphogenetic protein (BMP)-4, and transforming growth factor (TGF)-β1 were compared using the LexA-based yeast two-hybrid system. EYG48 reporter strain that carried a wild-type LEU2 gene under the control of LexA operators and a lacZ reporter plasmid (p80p-lacZ) containing eight high affinity LexA binding sites were used in the yeast two-hybrid analysis. Interactions between CTGF and the tested growth factors were evaluated based on growth of transformed yeast cells on selective media and colorimetric detection in a liquid β-galactosidase activity assay. Dissociation constants of CTGF to VEGF-A isoform 165 or PDGF-BB homo-dimer were measured in surface plasma resonance (SPR) analysis. CTGF regulation in PDGF-B presentation to the PDGF receptor β (PDGFRβ) was also quantitatively assessed by the SPR analysis. Combinational effects of CTGF protein and PDGF-BB on activation of PDGFRβ and downstream signaling molecules ERK1/2 and AKT were assessed in rabbit corneal fibroblast cells by Western analysis. In the LexA-based yeast two-hybrid system, cystine knot motifs of tested growth factors were fused to the activation domain of the transcriptional factor GAL4 while CTGF was fused to the DNA binding domain of the bacterial repressor protein LexA. Yeast co-transformants containing corresponding fusion proteins for CTGF and all four tested cystine knot motifs survived on selective medium containing galactose and raffinose but lacking histidine, tryptophan, and uracil. In liquid β-galactosidase assays, CTGF expressing cells that were co-transformed with the cystine knot of VEGF-A had the highest activity, at 29.88 ± 0.91 fold above controls (P < 0.01). Cells

  11. [Dose-effect relationship of traditional Chinese medicine formula for promoting blood circulation to remove stasis on ADP-induced platelet aggregation and rabbit plasma thrombin time].

    PubMed

    Zhang, Yanhua; Tang, Yuping; Guo, Jianming; Ding, Anwei; Duan, Jinao

    2009-11-01

    To investigate the effect of five traditional Chinese medicine formula for promoting blood circulation to remove stasis (Xuefuzhuyu Tang, Shaofuzhuyu Tang, Gexiazhuyu Tang, ShentongZhuyu Tang, Tongqiaohuoxue Tang) on platelet aggregation and clotting time in a dose-response relationship. The platelet aggregation was tested with Born's method and thrombin time (TT) method was established to determine the clotting time. The formula for promoting blood circulation to remove stasis showed significant inhibitory effects on the platelet aggregation and prolonged clotting time, the supernate of 80% alcohol solution showed the most potent inhibitory activity among the three kinds of samples from one formula (P < 0.01), especially the supernate of Shaofuzhuyu Tang and Gexiazhuyu Tang were better than other formula on platelet aggregation. About the anticoagulant, the whole formula showed the evidently prolonging the clotting time than other two fractions (P < 0.01) and the precipitation were the worst. The formula for promoting blood circulation to remove stasis showed significant effect on platelet aggregation and clotting time, and different samples of the formula had different efficacy. The study established a foundation for further bio-activity evaluation of these formulae and provided evidence for the treatment of cardiovascular and cerebrovascular diseases.

  12. Comparison of different procedures to prepare platelet-rich plasma for studies of platelet aggregation by light transmission aggregometry.

    PubMed

    Femia, Eti Alessandra; Pugliano, Mariateresa; Podda, Gianmarco; Cattaneo, Marco

    2012-01-01

    Light transmission aggregometry (LTA), the gold standard for the study of patients with defects of platelet function, is a poorly standardized technique. The guidelines that have been produced so far are largely based on consensus of experts, due to the absence of studies directly comparing different procedures. Therefore, ad hoc studies are needed to gather scientific evidence on how to choose the most appropriate procedures for LTA measurement. In this study, we aimed at evaluating the most appropriate conditions for preparing samples of platelet-rich plasma (PRP) for studies of platelet aggregation by LTA. Citrate-anticoagulated blood from 32 individuals was centrifuged at 150, 200, 250 or 300×g at room temperature for 10 min. Red blood cells contamination was highest in PRP prepared at 150×g; mean platelet volume (MPV) was lowest in PRP prepared at 300×g. The extent of platelet aggregation measured by LTA was lower and more variable in PRP prepared at 300×g. Therefore, centrifugation of blood at 200×g or 250×g for 10 min appears to be the best condition for preparing PRP for LTA studies.

  13. Formation of a highly stable complex between BN 50730 [tetrahydro-4,7,8,10 methyl-1(chloro-2 phenyl)-6 (methoxy-4 phenyl-carbamoyl)-9 pyrido [4',3'-4,5] thieno [3,2-f] triazolo-1,2,4 [4,3-a] diazepine-1,4] and the platelet-activating factor receptor in rabbit platelet membranes.

    PubMed

    Silva, C L; Cruz, H N; Violante, F A; Cordeiro, R S; Martins, M A; Noël, F

    1996-01-26

    BN 50730 [tetrahydro-4,7,8,10 methyl-1(chloro-2 phenyl)-6 (methoxy-4 phenyl-carbamoyl)-9 pyrido [4',3'-4,5] thieno [3,2-f] triazolo-1,2,4 [4,3-alpha] diazepine-1,4], a novel platelet-activating factor (PAF) receptor antagonist with a hetrazepine structure, decreased the maximal number of binding sites (Bmax) of [3H]PAF in rabbit platelet membranes without altering its dissociation constant. Platelet aggregation induced by 1 microM PAF was prevented by preincubation with 1 microM BN 50730. The washing of the platelets preincubated with BN 50730 failed to revert its inhibitory effects. We conclude that BN 50730 acts as a non-competitive antagonist of the PAF receptor, due to the formation of a highly stable drug-receptor complex.

  14. ApoE knockout rabbits: A novel model for the study of human hyperlipidemia.

    PubMed

    Niimi, Manabu; Yang, Dongshan; Kitajima, Shuji; Ning, Bo; Wang, Chuan; Li, Shen; Liu, Enqi; Zhang, Jifeng; Eugene Chen, Y; Fan, Jianglin

    2016-02-01

    Rabbits are one of the best animal models for the study of hyperlipidemia and atherosclerosis. Although many transgenic rabbits have been created, the development of gene knockout (KO) rabbits has been impossible due to the lack of rabbit embryonic stem cells. We along with others recently generated KO rabbits using genome editing techniques. In the current study, we characterized the lipoprotein profiles of apoE KO rabbits on both chow and cholesterol diets and investigated their susceptibility to a diet-induced atherosclerosis. We analyzed plasma lipids and lipoproteins of apoE KO rabbits and compared them with those of wild-type rabbits. On a chow diet, homozygous (but not heterozygous) apoE KO rabbits showed mild hyperlipidemia and, when challenged with a cholesterol diet, they showed greater susceptibility to diet-induced hyperlipidemia than did the wild-type rabbits and their plasma total cholesterol levels were remarkably increased (1070 ± 61 mg/dL in apoE KO vs. 169 ± 79 mg/dL in the wild type, p < 0.001). Hyperlipidemia in apoE KO rabbits was caused by elevated remnant lipoproteins. Interestingly, increased remnant lipoproteins in apoE KO rabbits were predominated by apoB-48 and rich in both apoA-I and apoA-IV contents. Furthermore, apoE KO rabbits developed greater aortic atherosclerosis than wild-type rabbits when fed with a cholesterol diet for 10 weeks. To our knowledge, this is the first report of generating KO rabbits for the study of lipid and lipoprotein metabolism. ApoE KO rabbits should be a useful model for the study of human hyperlipidemia and atherosclerosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Platelet interaction with modified articular cartilage. Its possible relevance to joint repair.

    PubMed Central

    Zucker-Franklin, D; Drosenberg, L

    1977-01-01

    During studies concerned with the platelet-collagen interaction, it was observed that platelets did not adhere to bovine or human articular cartilage and that cartilage did not induce platelet aggregation in vivo or in vitro. To study the mechanism responsible for this observation, the role of proteoglycans was examined. Purified cartilage collagen proved to be fully active as a platelet aggregant. Addition of small amounts of proteoglycan subunit (PGS) blocked platelet aggregation, whereas chondroitin sulfate, a major glycosaminoglycan component of cartilage matrix, impaired platelet aggregation only at concentrations which resulted in a marked increase in viscosity. Moreover, PGS abolished aggregation of platelets by polylysine but did not prevent aggregation by ADP, suggesting that PGS may block strategically placed lysine sites on the collagen molecule. Treatment of fresh articular cartilage with proteolytic enzymes rendered the tissue active as a platelet aggregant. In vivo experiments demonstrated that surgical scarification of rabbit articular cartilage does not result in adhesion of autologous platelets. Treatment of rabbit knee joints with intraarticular trypsin 1 wk before the injection of blood resulted in adhesion and aggregation of platelets on the surface of the lesions. Since there is evidence from other studies that some degree of cartilage healing may take place after initiation of an inflammatory response, it is postulated that induction of platelet-cartilage interaction may eventuate in cartilage repair. Images PMID:557500

  16. A prospective cohort study of light transmission platelet aggregometry for bleeding disorders: is testing native platelet-rich plasma non-inferior to testing platelet count adjusted samples?

    PubMed

    Castilloux, Jean Francois; Moffat, Karen A; Liu, Yang; Seecharan, Jodi; Pai, Menaka; Hayward, Catherine P M

    2011-10-01

    Light transmission platelet aggregometry (LTA) is important to diagnose bleeding disorders. Experts recommend testing LTA with native (N) rather than platelet count adjusted (A) platelet-rich plasma (PRP), although it is unclear if this provides non-inferior, or superior, detection of bleeding disorders. Our goal was to determine if LTA with NPRP is non-inferior to LTA with APRP for bleeding disorder assessments. A prospective cohort of patients, referred for bleeding disorder testing, and healthy controls, were evaluated by LTA using common agonists, NPRP and APRP (adjusted to 250 x 10⁹ platelets/l). Recruitment continued until 40 controls and 40 patients with definite bleeding disorders were tested. Maximal aggregation (MA) data were assessed for the detection of abnormalities from bleeding disorders (all causes combined to limit bias), using sample-type specific reference intervals. Areas under receiver-operator curves (AUROC) were evaluated using pre-defined criteria (area differences: < 0.15 for non-inferiority, > 0 for superiority). Forty-four controls and 209 patients were evaluated. Chart reviews for 169 patients indicated 67 had bleeding disorders, 28 from inherited platelet secretion defects. Mean MA differences between NPRP and APRP were small for most agonists (ranges, controls: -3.3 to 5.8; patients: -3.0 to 13.7). With both samples, reduced MA with two or more agonists was associated with a bleeding disorder. AUROC differences between NPRP and APRP were small and indicated that NPRP were non-inferior to APRP for detecting bleeding disorders by LTA, whereas APRP met superiority criteria. Our study validates using either NPRP or APRP for LTA assessments of bleeding disorders.

  17. Counting platelets in platelet concentrates on hematology analyzers: a multicenter comparative study.

    PubMed

    van der Meer, Pieter F; Dijkstra-Tiekstra, Margriet J; Mahon, Anne; de Wildt-Eggen, Janny

    2009-01-01

    Hematology analyzers are designed to count whole blood samples, but are also used by blood centers to perform quality control on blood components. In platelet (PLT) concentrates, the number of PLTs is approximately fivefold higher and red blood cells are absent, causing variable PLT counting results. It was our aim to compare currently used hematology analyzers for counting PLTs in PLT concentrates using fixed human PLTs. PLT samples were fixed, diluted into seven concentration levels (plus one blank), aliquoted, and shipped to 68 centers. Evaluable data were obtained for 89 hematology analyzers. All samples were counted six times, and results were reported to the coordinating center. The overall group mean was calculated, and the percentage deviation from this mean was calculated for each analyzer. At PLT levels relevant for blood centers, 750 x 10(9) to 2000 x 10(9) per L, analyzers gave results that were between 35 percent lower and 16 percent higher than the overall group mean. Within a group of analyzers, results were comparable with coefficient of variations usually below 10 percent, indicating that the observed differences were caused by instrument characteristics. A smaller study with fresh, unfixed PLT samples showed that analyzers behaved similarly for fixed and fresh PLTs. With a wide array of currently used hematology analyzers, a marked difference was determined for the PLT counts of fixed human-based identical samples provided to 68 laboratories by a centralized facility. A gold standard method is needed to allow for more valid interlaboratory comparisons between hematology analyzers.

  18. Role of Platelet Parameters on Sudden Sensorineural Hearing Loss: A Case-Control Study in Iran

    PubMed Central

    2016-01-01

    Sudden sensorineural hearing loss (SSNHL) is a common otological disorder characterized by a hearing loss greater than 30 dB over three consecutive frequencies, in less than 72 hours. It has been established that platelet parameters, such as mean platelet volume, are associated with ischemic heart events, whose clinical manifestations are similar to those of SSNHL. Hence, we aimed to determine if the platelet count, mean platelet volume and platelet distribution width are related to the occurrence and severity of sudden sensorineural hearing loss. A case-control prospective study was conducted in a teaching hospital in Iran. One hundred-eight patients with SSNHL and an equal number of healthy, age- and sex-matched controls were enrolled in the study. Peripheral venous blood samples were collected from the subjects, and the platelet count, mean platelet volume and platelet distribution width were measured with an automated blood cell counter. Analysis of the audiometry and hematological test results using SPSS22 software showed no statistical correlation between the platelet parameters and the occurrence of SSNHL, but correlation coefficients showed a significant correlation between PDW and hearing loss severity in patients group. However, further investigation is required to unequivocally establish the absence of correlation between the platelet parameters and occurrence of SSNHL. PMID:26829393

  19. Development of a Zealand white rabbit deposition model to study inhalation anthrax

    SciTech Connect

    Asgharian, Bahman; Price, Owen; Kabilan, Senthil; Jacob, Richard E.; Einstein, Daniel R.; Kuprat, Andrew P.; Corley, Richard A.

    2016-01-28

    Despite using rabbits in several inhalation exposure experiments to study diseases such as anthrax, there is a lack of understanding regarding deposition characteristics and fate of inhaled particles (bio-aerosols and viruses) in the respiratory tracts of rabbits. Such information allows dosimetric extrapolation to humans to inform human outcomes. The lung geometry of the New Zealand white rabbit (referred to simply as rabbits throughout the article) was constructed using recently acquired scanned images of the conducting airways of rabbits and available information on its acinar region. In addition, functional relationships were developed for the lung and breathing parameters of rabbits as a function of body weight. The lung geometry and breathing parameters were used to extend the existing deposition model for humans and several other species to rabbits. Evaluation of the deposition model for rabbits was made by comparing predictions with available measurements in the literature. Deposition predictions in the lungs of rabbits indicated smaller deposition fractions compared to those found in humans across various particle diameter ranges. The application of the deposition model for rabbits was demonstrated by extrapolating deposition predictions in rabbits to find equivalent human exposure concentrations assuming the same dose-response relationship between the two species. Human equivalent exposure concentration levels were found to be much smaller than those for rabbits.

  20. Development of a Zealand white rabbit deposition model to study inhalation anthrax.

    PubMed

    Asgharian, Bahman; Price, Owen; Kabilan, Senthil; Jacob, Richard E; Einstein, Daniel R; Kuprat, Andrew P; Corley, Richard A

    2016-01-01

    Despite using rabbits in several inhalation exposure experiments to study diseases such as anthrax, there is a lack of understanding regarding deposition characteristics and fate of inhaled particles (bio-aerosols and viruses) in the respiratory tracts of rabbits. Such information allows dosimetric extrapolation to humans to inform human outcomes. The lung geometry of the New Zealand white rabbit (referred to simply as rabbits throughout the article) was constructed using recently acquired scanned images of the conducting airways of rabbits and available information on its acinar region. In addition, functional relationships were developed for the lung and breathing parameters of rabbits as a function of body weight. The lung geometry and breathing parameters were used to extend the existing deposition model for humans and several other species to rabbits. Evaluation of the deposition model for rabbits was made by comparing predictions with available measurements in the literature. Deposition predictions in the lungs of rabbits indicated smaller deposition fractions compared to those found in humans across various particle diameter ranges. The application of the deposition model for rabbits was demonstrated by extrapolating deposition predictions in rabbits to find equivalent human exposure concentrations assuming the same dose-response relationship between the two species. Human equivalent exposure concentration levels were found to be much smaller than those for rabbits.

  1. [Applications of platelets in studies on traditional Chinese medicines promoting blood circulation to remove blood stasis].

    PubMed

    Wang, Feng-Qin; Chen, Cen; Xia, Zhi-Ning; Yang, Feng-Qing

    2014-08-01

    Thrombotic diseases in different forms become a great threat to human health. Such anti-platelet aggregation drugs as aspirin and clopidogrel are common drugs in clinic. However, along with the appearance of resistance and side effects of western anti-platelet aggregation drugs, anti-platelet aggregation traditional Chinese medicines promoting blood circulation to remove blood stasis have gradually become an important study orientation. Platelet is one of major participant in thrombosis, and plays an important role as a bioactive material in studies on traditional Chinese medicines promoting blood circulation to remove blood stasis, mainly involving two aspects--the evaluation for the anti-platelet aggregation activity of traditional Chinese medicines and the screening of their active components. This paper summarized the applications of platelets in studies on traditional Chinese medicines promoting blood circulation to remove blood stasis, so as to provide basis for further studies.

  2. Platelet function in reconstituted whole blood variants: An observational study over 5 days of storage time.

    PubMed

    Ponschab, Martin; Schlimp, Christoph J; Zipperle, Johannes; Gabriel, Christian; Süssner, Susanne; Cadamuro, Janne; Gratz, Johannes; Redl, Heinz; Schöchl, Herbert

    2015-11-01

    Platelet concentrates (PCs) are usually stored at room temperature under constant gentle agitation. Risk of bacterial contamination limits maximum storage time to 5 days. The objective of the study was to investigate platelet function with regard to storage time in different reconstituted whole blood (RWB) variants. Donated apheresis PCs were stored at 22°C over 5 days. To obtain RWB, apheresis PCs were mixed with plasma-free packed red blood cells (RBCs) and either prethawed fresh frozen plasma (PT) or solvent-detergent plasma (SD) [1:1:1 ratio], or with leukocyte- and platelet-depleted whole blood (LD-WB) as control. Platelet function in RWB variants was assessed by impedance aggregometry (Multiplate) on Days 0, 1, 3, and 5 following platelet donation. Platelet aggregometry did not reach the lower limits determined from healthy volunteers in any of the RWB variants. Platelet aggregability measured by ASPI test, ADP test, and COL test declined over storage time in all RWB variants. No differences were observed in the TRAP test. At most measurement time points, LD-RWB provided significantly higher platelet aggregability compared with SD-RWB and PT-RWB (p < 0.01). SD-RWB demonstrated higher platelet aggregability on Day 0 in the ASPI test, ADP test, and TRAP test compared with PT-RWB. Apheresis PCs stored for 5 days at 22°C demonstrated reduced platelet aggregability, as measured by multiple electrode aggregometry when mixed with RBCs and plasma. As platelet aggregation in LD-RWB was superior compared with SD-RWB and PT-RWB variants, it might be possible that additives in RBCs or plasma are responsible for the observed depressed platelet function. Critical evaluation of current massive transfusion recommendations proposing early platelet transfusion is indicated.

  3. Rabbit models for the study of human atherosclerosis: from pathophysiological mechanisms to translational medicine

    PubMed Central

    Fan, Jianglin; Kitajima, Shuji; Watanabe, Teruo; Xu, Jie; Zhang, Jifeng; Liu, Enqi; Chen, Y. Eugene

    2014-01-01

    Laboratory animal models play an important role in the study of human diseases. Using appropriate animals is critical not only for basic research but also for the development of therapeutics and diagnostic tools. Rabbits are widely used for the study of human atherosclerosis. Because rabbits have a unique feature of lipoprotein metabolism (like humans but unlike rodents) and are sensitive to a cholesterol diet, rabbit models have not only provided many insights into the pathogenesis and development of human atherosclerosis but also made a great contribution to translational research. In fact, rabbit was the first animal model used for studying human atherosclerosis, more than a century ago. Currently, three types of rabbit model are commonly used for the study of human atherosclerosis and lipid metabolism: (1) cholesterol-fed rabbits, (2) Watanabe heritable hyperlipidemic rabbits, analogous to human familial hypercholesterolemia due to genetic deficiency of LDL receptors, and (3) genetically modified (transgenic and knock-out) rabbits. Despite their importance, compared with the mouse, the most widely used laboratory animal model nowadays, the use of rabbit models is still limited. In this review, we focus on the features of rabbit lipoprotein metabolism and pathology of atherosclerotic lesions that make it the optimal model for human atherosclerotic disease, especially for the translational medicine. For the sake of clarity, the review is not an attempt to be completely inclusive, but instead attempts to summarize substantial information concisely and provide a guideline for experiments using rabbits. PMID:25277507

  4. Rabbit models for the study of human atherosclerosis: from pathophysiological mechanisms to translational medicine.

    PubMed

    Fan, Jianglin; Kitajima, Shuji; Watanabe, Teruo; Xu, Jie; Zhang, Jifeng; Liu, Enqi; Chen, Y Eugene

    2015-02-01

    Laboratory animal models play an important role in the study of human diseases. Using appropriate animals is critical not only for basic research but also for the development of therapeutics and diagnostic tools. Rabbits are widely used for the study of human atherosclerosis. Because rabbits have a unique feature of lipoprotein metabolism (like humans but unlike rodents) and are sensitive to a cholesterol diet, rabbit models have not only provided many insights into the pathogenesis and development of human atherosclerosis but also made a great contribution to translational research. In fact, rabbit was the first animal model used for studying human atherosclerosis, more than a century ago. Currently, three types of rabbit model are commonly used for the study of human atherosclerosis and lipid metabolism: (1) cholesterol-fed rabbits, (2) Watanabe heritable hyperlipidemic rabbits, analogous to human familial hypercholesterolemia due to genetic deficiency of LDL receptors, and (3) genetically modified (transgenic and knock-out) rabbits. Despite their importance, compared with the mouse, the most widely used laboratory animal model nowadays, the use of rabbit models is still limited. In this review, we focus on the features of rabbit lipoprotein metabolism and pathology of atherosclerotic lesions that make it the optimal model for human atherosclerotic disease, especially for the translational medicine. For the sake of clarity, the review is not an attempt to be completely inclusive, but instead attempts to summarize substantial information concisely and provide a guideline for experiments using rabbits.

  5. Developmental toxicity study of pentachlorophenol in the rabbit.

    PubMed

    Bernard, B K; Ranpuria, A K; Hoberman, A M

    2001-01-01

    The potential for developmental toxicity of pentachlorophenol (penta) was studied in New Zealand white rabbits at doses of 0 (corn oil), 7.5, 15, and 30 mg/kg/day administered by gavage on days 6 to 18 of gestation. The rabbits were sacrificed on day 29 of presumed gestation and necropsied. Measurements included number of corpora lutea, pregnancy, number and distribution of implantations, early and late resorptions, live and dead fetuses, fetal weight, gender, and gross external, soft tissue, and skeletal alterations. The mid and high doses reduced maternal body weight gain; the high dose caused transient weight loss and reduced feed consumption. There were no effects on embryofetal development at any of the doses evaluated. Based on these data, the maternal no-observable-adverse-effect level (NOAEL) is 7.5 mg/kg/day, while the developmental NOAEL is 30 mg/kg/day. Penta is not a developmental toxicant in a nonrodent animal model.

  6. [Experimental study regarding the ureteral cicatrization pattern in rabbit].

    PubMed

    Pintilie, R A; Grigorovici, Mirela

    2008-01-01

    This study aimed to elaborate an experimental model for ureteral cicatrization following surgical lesion, with direct involvement in urological therapy. The study was realized on a group of 9 female rabbits on which we have performed ureteral surgery. First surgical event consisted in partial cut of the left ureter following transperitoneal approach, ureteral stent insertion and the suture of the ureteral wound. The second surgical event has accomplished the harvesting of the ureteral fragment during cicatrisation process and was performed at various times from the first surgical event, accordingly at 1, 2, 3...6 days--on different rabbits. 3 rabbits composed the witness group. Fragments were fixed in formol 4%, and histologically stained with hematoxilin-eosin and van Gieson. In the first two days we have observed an obvious inflammatory process on the postoperative ureteral scar. In days 3 and 4, the limited fibrosis appeared in the 2nd day engaged a peak in the 4th day when appeared a sketch of ureteral lumen constriction. In the 5th and 6th day the fibrosis process underwent a moderate resolution, simultaneously with a local diffuse congestion, marker for the remodeling processes of the connective matrix. Animal cicatrisation model follows the same pattern as in human but at different timing so as extrapolation requires considering these facts.

  7. Cardiovascular correlates of platelet count and volume in the Framingham Heart Study

    PubMed Central

    Sloan, Arielle; Gona, Philimon; Johnson, Andrew

    2015-01-01

    Purpose Platelet count and volume are inexpensive, routinely-assayed biomarkers associated with cardiovascular health, but specific relationships among platelet indices, cardiovascular risk factors, and disease warrant further investigation. The purpose of this study was to understand associations among platelet count, volume, and 20 cardiovascular health-related variables in the Framingham Heart Study. Methods Cross-sectional analyses were performed on platelet count and volume associations with cardiovascular health indicators in three Framingham Heart Study cohorts (Original n=964, Offspring n=2,699, and Third Generation n=2,419) using multivariable linear regression analysis. Time-to-event analysis was employed for cardiovascular disease-related event incidences using Kaplan-Meier plots and Cox proportional hazards regression adjusted for age and gender. Results Results were concordant with the hypothesis that higher platelet counts are associated with less favorable cardiovascular risk profiles, although mean platelet volume associations were weaker. In our analysis, increased platelet count across FHS cohorts was consistently associated with smoking, triglycerides, LDL and total cholesterol levels. Some associations with platelet count appeared gender-dependent. Conclusions Significant associations of common blood platelet measurements are observed with gender and cardiovascular risk factors, namely smoking and lipids. Research is warranted to confirm these relationships in other cohorts, evaluate differences by ethnicity and examine longitudinal effects on disease risk. PMID:25771288

  8. Electric impedance platelet aggregometry in cardiac surgery patients: A comparative study of two technologies.

    PubMed

    Ranucci, Marco; Baryshnikova, Ekaterina; Crapelli, Giulia Beatrice; Ranucci, Matteo; Meloni, Silvia; Pistuddi, Valeria

    2016-01-01

    Platelet function tests are suggested to assess platelet reactivity before cardiac and major non-cardiac surgery. Different point-of-care platelet function tests are available. Among these, electric impedance platelet aggregometry (EIPA) (Multiplate®, MP) is one of the most widely used techniques. Recently, a new EIPA system (Rotem Platelet®, RP) was released. This is a comparative study of platelet function measured with MP and RP. Fifty cardiac surgery patients were admitted to this study. All the patients received a preoperative platelet function test with both the MP and the RP; for each technology, two tests were performed: the ADPtest (investigating P2Y12 receptor platelet reactivity) and the TRAPtest (investigating the thrombin-dependent platelet reactivity). ADP-based platelet reactivity values demonstrated a significant (p = 0.019) correlation between the MP and the RP; and a marginally significant (p = 0.042) correlation for TRAP-based tests. The Bland-Altman analysis of the ADPtest demonstrated a positive bias of 5.94 units (MP > RP) and a percentage error of 88%. For the TRAPtest, there was a positive bias of 12 units (MP > RP) and a percentage error of 89%. In patients who were preoperatively treated with P2Y12 receptor inhibitors, only the MP ADPtest was positively associated with the days from drug discontinuation (p = 0.003). Platelet function assessment with RP greatly differs from the equivalent MP measure, and no correction value can be applied due to the low level of precision. This applies both to ADPtest and TRAPtest. The MP ADPtest is more reliable for platelet reactivity after discontinuation of P2Y12 receptor inhibitors.

  9. Radioimmunoassay of platelet factor 4 and beta-thromboglobulin: development and application to studies of platelet release in relation to fibrinopeptide A generation.

    PubMed

    Kaplan, K L; Nossel, H L; Drillings, M; Lesznik, G

    1978-05-01

    Platelet and fibrinogen survival and turnover studies have shown that platelet activation and fibrin formation may occur to different degrees in different thrombotic disorders. More direct evidence of differential involvement of platelet activation and fibrin formation should be provided by specifically measuring the products of these reactions, i.e. released platelet proteins and fibrinopeptide A. Two platelet proteins, platelet factor 4 (PF4) and beta-thromboglobulin (betaTG), were isolated and characterized, and sensitive and specific radioimmunoassays were developed to measure them. These assays were employed, along with the radioimmunoassay for fibrinopeptide A (FPA), to study the release of PF4 and betaTG in relation to FPA cleavage. PF4 and betaTG were released by ADP and collagen with time course and concentration dependence similar to that of [14C]serotonin release. FPA was not cleaved from fibrinogen during ADP or collagen-induced platelet release. Thrombin caused release of PF4 and betaTG as well as cleavage of FPA. Cleavage of FPA occurred with concentrations of thrombin about 100 times less than did release of PF4 and betaTG, and release of [14C]serotinin required still higher thrombin concentrations. Release of [14C]serotonin and platelet proteins was similar as a function of time. Sodium citrate was found to inhibit platelet release induced by thrombin.

  10. A structure-activity relationship study of platelet-activating factor

    SciTech Connect

    Surles, J.R.

    1987-01-01

    Several analogues of platelet-activating factor (1-0-alkyl-2-0-acetyl-sn-glycero-3-phosphocholine, PAF), an alkylglycerophospholipid that was found to be a mediator in Type I immediate hypersensitivity and also possessed potent hypotensive properties, were synthesized. These PAF analogues were evaluated in a qualitative structure-activity relationship study for their rabbit neutrophil degranulation properties and their antihypertensive properties in rats. Variations were made in each of the moieties attached to the three glycerol backbone carbons. Variation in sn-1-0-alkyl chain length from fourteen to nineteen carbons and introduction of one or two double bonds revealed that the 1-0-hexadecyl species of PAF was the most active analogue in this series in our assay systems. Substitution of various deoxyalkyl groups for the 2-0-acetyl moiety resulted in severely diminished bioactivities and no inhibition of rat plasma acetylhydrolase activity. Substitution of bulky trialkylammonium moieties for the trimethylammonium portion of the phosphocholine moiety resulted in an analogue (triethylammonium, 41) with reduced immediate hypersensitivity properties and 560% relative antihypertensive potency.

  11. Anti-platelet effects of olive oil extract: in vitro functional and proteomic studies.

    PubMed

    de Roos, Baukje; Zhang, Xuguang; Rodriguez Gutierrez, Guillermo; Wood, Sharon; Rucklidge, Garry J; Reid, Martin D; Duncan, Gary J; Cantlay, Louise L; Duthie, Garry G; O'Kennedy, Niamh

    2011-10-01

    Platelets play a key role in haemostasis and wound healing, contributing to formation of vascular plugs. They are also involved in formation of atherosclerosic plaques. Some traditional diets, like the Mediterranean diet, are associated with a lower risk of cardiovascular disease. Components in these diets may have anti-platelet functions contributing to their health benefits. We studied the effects of alperujo extract, an olive oil production waste product containing the majority of polyphenols found in olive fruits, through measurement of effects on platelet aggregation and activation in isolated human platelets, and through identification of changes in the platelet proteome. Alperujo extract (40 mg/L) significantly decreased in vitro ADP- (p = 0.002) and TRAP- (p = 0.02) induced platelet activation as measured by the flow cytometry using the antibody for p-selectin (CD62p), but it did not affect the conformation of the fibrinogen receptor as measured by flow cytometry using the antibodies for anti-fibrinogen, CD42a and CD42b. Alperujo extract (100 mg/L) inhibited both collagen- and TRAP-induced platelet aggregation by 5% (p < 0.05), and a combination of hydroxytyrosol and 3,4-dihydroxyphenylglycol were, at least partly, responsible for this effect. Proteomic analysis identified nine proteins that were differentially regulated by the alperujo extract upon ADP-induced platelet aggregation. These proteins represent important mechanisms that may underlie the anti-platelet effects of this extract: regulation of platelet structure and aggregation, coagulation and apoptosis, and signalling by integrin αIIb/β3. Alperujo extract may protect against platelet activation, platelet adhesion and possibly have anti-inflammatory properties.

  12. Platelet fibrinogen

    PubMed Central

    Castaldi, P. A.; Caen, J.

    1965-01-01

    Platelet fibrinogen has been studied in normal, thrombasthenic, and hypofibrinogenaemic subjects. It has been differentiated into adsorbed (plasma) and extractable (intraplatelet) fractions. Isotopic studies suggest that exchange does not occur between intraplatelet and plasma fibrinogen and it appears possible that the intra-platelet fraction may be derived from the megakaryocyte. Six of nine thrombasthenic patients were found to have a severe deficiency of both adsorbed and extractable fibrinogen. Since the remaining three had near-normal platelet fibrinogen and all nine failed to aggregate it is improbable that the failure to adsorb fibrinogen is responsible for the defect in aggregation. Magnesium partially corrects adhesion to fibrin and clot retraction by these platelets, but has not been found to influence their fibrinogen adsorption. It is considered that the basic platelet surface defect, of varying severity, is responsible for the abnormalities of adsorption, aggregation, and adhesion in thrombasthenia. In the case of congenital hypofibrinogenaemia, fibrinogen transfusion corrects the long bleeding time, platelet-adsorbed fibrinogen, and the ability of platelets to spread on glass. It is possible that fibrinogen influences the surface properties of human platelets, although the final mechanism is not determined. Images PMID:5835438

  13. Experimental study of pathogenicity of Pasteurella multocida serogroup F in rabbits.

    PubMed

    Jaglic, Zoran; Jeklova, Edita; Leva, Lenka; Kummer, Vladimir; Kucerova, Zdenka; Faldyna, Martin; Maskova, Jarmila; Nedbalcova, Katerina; Alexa, Pavel

    2008-01-01

    The role of Pasteurella multocida serogroup F in inducing disease in rabbits was investigated in this study. Three groups of 12 Pasteurella-free rabbits each were intranasally (i.n.), subcutaneously (s.c.), and perorally (p.o.) challenged, respectively. Six rabbits of each group were immunosuppressed using dexamethasone. Eight rabbits (four of them immunosuppressed) inoculated i.n. showed symptoms of respiratory distress resulting in respiratory failure and died or were euthanized in the terminal stage of the disease 3-6 days post-infection (p.i.). The main pathological findings were fibrinopurulent pleuropneumonia (immunocompetent rabbits) or diffuse haemorrhagic pneumonia (immunosuppressed rabbits). Septicemic syndrome ending with shock occurred in 11 rabbits (6 of them immunosuppressed) inoculated s.c., which died or were euthanized in the terminal stage of the disease 2-3 days p.i. The most significant pathological findings were extensive cutaneous and subcutaneous lesions. All of the p.o. inoculated rabbits survived the challenge showing no clinical signs of the disease and no macroscopic lesions. The observations in this study indicate that in addition to serogroups A and D of P. multocida, serogroup F also can be highly pathogenic for rabbits and therefore might be a cause of considerable economic loss in commercial rabbit production.

  14. Transfusion related adverse events in the Platelet Dose study

    PubMed Central

    Kaufman, Richard M.; Assmann, Susan F.; Triulzi, Darrell J.; Strauss, Ronald G.; Ness, Paul; Granger, Suzanne; Slichter, Sherrill J.

    2014-01-01

    BACKGROUND How platelet (PLT) product characteristics such as dose, source (whole blood-derived (WBD) vs. apheresis), storage duration, and ABO matching status affect the risks of transfusion-related adverse events (TRAEs) is unclear. Similarly, more information is needed to define how recipient characteristics affect the frequency of TRAEs following PLT transfusion. STUDY DESIGN AND METHODS In the multicenter Platelet Dose (“PLADO”) study, pediatric and adult hematology-oncology patients with hypoproliferative thrombocytopenia were randomized to receive low-dose (LD), medium-dose (MD), or high-dose (HD) PLT prophylaxis for a pre-transfusion PLT count ≤10,000/μL. All PLT units (apheresis or WBD) were leukoreduced. Post hoc analyses of PLADO data were performed using multi-predictor models. RESULTS 5034 PLT transfusions to 1102 patients were analyzed. A TRAE occurred with 501 PLT transfusions (10.0%). The most common TRAEs were fever (6.6% of transfusions), allergic/hypersensitivity reactions (1.9%), and sinus tachycardia (1.8%). Patients assigned HD PLTs were more likely than LD or MD patients to experience any TRAE (OR for HD vs. MD 1.50, 95% CI (1.10, 2.05), three-group comparison p=0.02). PLT source and ABO matching status were not significantly related to overall TRAE risk. Compared to a patient’s first PLT transfusion, subsequent PLT transfusions were less likely to have a TRAE reported, primarily due to a lower risk of allergic/hypersensitivity reactions. CONCLUSION The most important PLT unit characteristic associated with TRAEs was PLT dose per transfusion. HD PLTs may increase the risk of TRAEs, and LD PLTs may reduce the risk. PMID:25065959

  15. Prevalence and pathological study on rabbit hepatic coccidiosis in Taiwan.

    PubMed

    Wang, J S; Tsai, S F

    1991-10-01

    Five breeds of rabbits, which included the New Zealand, Californian, Spot, Rex and Angora rabbit, were found from a survey of 1,152 rabbits in Taiwan. The prevalence of coccidia in young rabbits (weaning-2 months old) was 95% to 100%. Adult female rabbits usually acted as carriers within the farm and transmitted the parasite to young rabbits, which caused severe infection with clinical signs and even death. Parasitism of hepatic coccidia (Eimeria stiedai) in the rabbit led to severe mortality. Numerous and scattered white nodules about 0.1 to 0.5 cm in diameter were seen on the liver surface and dark greenish mucoid exudate was found in intestinal lumen. Histopathologic lesions included hyperplasia of the bile duct epithelium with different developmental stages of coccidia within. Oocysts could be seen in the lumen, and granuloma tissues encircle the bile duct with infiltration of inflammatory cells. The other organs were not infected.

  16. A kinetic study of rabbit muscle pyruvate kinase

    PubMed Central

    Ainsworth, Stanley; Macfarlane, Neil

    1973-01-01

    The paper reports a study of the kinetics of the reaction between phosphoenolpyruvate, ADP and Mg2+ catalysed by rabbit muscle pyruvate kinase. The experimental results indicate that the reaction mechanism is equilibrium random-order in type, that the substrates and products are phosphoenolpyruvate, ADP, Mg2+, pyruvate and MgATP, and that dead-end complexes, between pyruvate, ADP and Mg2+, form randomly and exist in equilibrium with themselves and other substrate complexes. Values were determined for the Michaelis, dissociation and inhibition constants of the reaction and are compared with values ascertained by previous workers. PMID:4737316

  17. Mathematical model and numerical method for studying platelet adhesion and aggregation during blood clotting

    SciTech Connect

    Fogelson, A.L.

    1984-10-01

    The repair of small blood vessels and the pathological growth of internal blood clots involve the formation of platelet aggregates adhering to portions of the vessel wall. Our microscopic model represents blood by a suspension of discrete massless platelets in a viscous incompressible fluid. Platelets are initially noncohesive; however, if stimulated by an above-threshold concentration of the chemical ADP or by contact with the adhesive injured region of the vessel wall, they become cohesive and secrete more ADP into the fluid. Cohesion between platelets and adhesion of a platelet to the injured wall are modeled by creating elastic links. Repulsive forces prevent a platelet from coming too close to another platelet or to the wall. The forces affect the fluid motion in the neighborhood of an aggregate. The platelets and secreted ADP both move by fluid advection and diffusion. The equations of the model are studied numerically in two dimensions. The platelet forces are calculated implicitly by minimizing a nonlinear energy function. Our minimization scheme merges Gill and Murray's (Math. Programming 7 (1974), 311) modified Newton's method with elements of the Yale sparse matix package. The stream-function formulation of the Stokes' equations for the fluid motion under the influence of platelet forces is solved using Bjorstad's biharmonic solver (''Numerical Solution of the Biharmonic Equation,'' Ph.D. Thesis, Stanford University, 1980). The ADP transport equation is solved with an alternating-direction implicit scheme. A linked-list data structure is introduced to keep track of changing platelet states and changing configurations of interplatelet links.

  18. Embryotoxicity and teratogenicity study with gamma-cyclodextrin in rabbits.

    PubMed

    Waalkens-Berendsen, D H; Smits van Prooije, A E; Bär, A

    1998-04-01

    In a standard embryotoxicity/teratogenicity study, gamma-cyclodextrin (gamma-CD) was administered to groups of 16, artificially inseminated New Zealand White rabbits at dietary concentrations of 0, 5, 10, or 20%. A comparison group received a diet containing 20% lactose. Treatment started on day 0 of gestation and ended on day 29 when the animals were killed. Except for the occurrence of transient diarrhea in 2 and 3 rabbits of the 10 and 20% gamma-CD groups, respectively, in the first few days, the treatment was well tolerated. A reduced food intake in the 20% gamma-CD group during the first week of treatment resulted in a reduced weight gain during this period. However, after week 1 there were no differences in weight gains between the groups, and at termination of the study body weights were similar in all groups. Even at the highest dose level, which corresponds to an intake of 5-7 g/kg body wt/day, no signs of maternal toxicity were observed. Reproductive performance was not affected by the treatment. Uterine weight, placental weight, fetal weight, number of fetuses, sex ratio, number of implantation sites, resorptions, and corpora lutea did not differ among the groups. Visceral and skeletal examinations of the fetuses did not reveal any malformations, anomalies, or variations that could be attributed to treatment. It was concluded that dietary gamma-CD is well tolerated by pregnant rabbits, has no adverse effect on reproductive performance, and is not embryotoxic, fetotoxic, or teratogenic at dietary concentrations of up to 20%.

  19. Effect of intravascular neutrophil chemotactic factors on blood neutrophil and platelet kinetics

    SciTech Connect

    Issekutz, A.C.; Ripley, M.

    1986-02-01

    Intravenous infusion of an analogue (f-met-leu-phe (FMLP)) of a bacterial-derived polymorphonuclear leukocyte (PMNL) chemotactic factor, or of the complement-derived chemotactic stimulus, zymosan-activated plasma (ZAP, containing C5ades Arg) into rabbits induces acute PMNL margination in the pulmonary vasculature. The pulmonary PMNL sequestration is accompanied by thrombocytopenia. Because of the role platelets and PMNLs play in hemostasis and defense against infection, we studied the fate of these blood elements following sequestration induced by chemotactic factors. By employing 111In-labelled platelets and external radioisotope scanning, platelets were found to sequester in the pulmonary vasculature during FMLP infusion. Simultaneous 51Cr PMNL and 111In-platelet studies showed that following sequestration, PMNLs returned to the circulation and disappeared with a normal half-life (T1/2) whereas the T1/2 of the platelets was markedly shortened (T1/2 of control = 49 +/- 3.0 hr; FMLP or ZAP infused T1/2 = 27 +/- 2.7 hr). Infusion of platelet-activating factor (PAF) induced PMN and platelet sequestration with similar abnormalities in platelet kinetics. Studies with 51Cr- and 14C-serotonin-labelled platelets showed that platelets did not release serotonin during FMLP, ZAP, or low dose PAF-induced sequestration. In contrast to platelet survival, platelet size, platelet aggregation responses, and platelet glycoproteins were not affected by transient sequestration. These results indicate that during PMNL margination induced by relatively pure PMNL stimuli such as FMLP, platelets may reversibly marginate and subsequently be cleared at an accelerated rate. The reason for accelerated platelet clearance is not a result of circulating platelet aggregates or detectable proteolytic modification of membrane glycoproteins.

  20. The rabbit as a model for reproductive and developmental toxicity studies.

    PubMed

    Foote, R H; Carney, E W

    2000-01-01

    The rabbit has many advantages as a nonrodent and second model for assessing the effects of toxic agents on semen quality, fertility, developmental toxicity, and teratology. The male and female reproductive systems of the rabbit are described, and data on growth, sexual development and reproduction are compared with mice, rats, and humans. Techniques for semen collection and evaluation in the male, and artificial insemination, superovulation, embryo culture, and embryo transfer in the female are included as useful procedures in toxicity testing. Examples of the use of rabbits and experimental replication for toxicity testing are given. Special features of the visceral yolk sac and development of the chorioallantoic placenta of the rabbit are compared with rodents. The rabbit extraembryonic membranes more closely resemble the human than do the rodents, in some respects. The use of the rabbit in developmental toxicity and teratology studies is discussed.

  1. Bacterial contamination of platelet concentrates: results of a prospective multicenter study comparing pooled whole blood-derived platelets and apheresis platelets.

    PubMed

    Schrezenmeier, Hubert; Walther-Wenke, Gabriele; Müller, Thomas H; Weinauer, Franz; Younis, Adelheid; Holland-Letz, Tim; Geis, Gabriele; Asmus, Jens; Bauerfeind, Ursula; Burkhart, Jürgen; Deitenbeck, Robert; Förstemann, Elisabeth; Gebauer, Wolfgang; Höchsmann, Britta; Karakassopoulos, Apostolos; Liebscher, Ute-Maja; Sänger, Werner; Schmidt, Michael; Schunter, Friedrich; Sireis, Walid; Seifried, Erhard

    2007-04-01

    The GERMS Group initiated a prospective multicenter study to assess prevalence and nature of bacterial contamination of pooled buffy-coat platelet concentrates (PPCs) and apheresis platelet concentrates (APCs) by routine screening with a bacterial culture system. In nine centers overall, 52,243 platelet (PLT) concentrates (15,198 APCs, 37,045 PPCs) were analyzed by aerobic and anaerobic cultures (BacT/ALERT, bioMérieux). In 135 PLT concentrates (PCs; 0.26%), bacteria could be identified in the first culture (0.4% for APCs vs. 0.2% for PPCs; p < 0.001). In 37 (0.07%) of these PC units, the same bacteria strain could be identified in a second culture from the sample bag and/or the PC unit. The rate of confirmed-positive units did not differ significantly between APC (0.09%; 1/1169) and PPC units (0.06%; 1/1544). Bacteria from skin flora (Propionibacterium acnes, Staphylococcus epidermidis) were the most prevalent contaminants. Median times to first positive culture from start of incubation were 0.7 and 3.7 days in aerobic and anaerobic cultures for confirmed-positive units. With a "negative-to-date" issue strategy, most PC units (55%) had already been issued by time of the first positive culture. The rate of confirmed bacterial contamination of PC units was low. Nevertheless, clinicians must be aware of this risk. The risk of bacterial contamination does not warrant universal preference of APCs. It must be questioned whether routine bacterial screening by a culture method can sufficiently prevent contaminated products from being transfused due to the delay until a positive signal in the culture system and due to false-negative results.

  2. Shear-mediated platelet activation in patients implanted with continuous flow LVADs: A preliminary study utilizing the platelet activity state (PAS) assay.

    PubMed

    Valerio, Lorenzo; Consolo, Filippo; Bluestein, Danny; Tran, Phat; Slepian, Marvin; Redaelli, Alberto; Pappalardo, Federico

    2015-08-01

    Left ventricular assist devices (LVADs) have emerged as vital life-saving therapeutic systems for patients with advanced and end-stage heart failure (HF). Despite their efficacy, VAD systems remain limited by post-implantation thrombotic complications. Shear-mediated platelet activation is the major driver of such complications in these devices. Nowadays few platelet function assays are routinely utilized in assessing the degree of platelet activation in VAD implanted patients. No assays exist that specifically target shear-mediated platelet activation. The platelet activity state (PAS) is a novel assay that has been well validated in vitro, measuring thrombin release as a surrogate for shear-mediated platelet activation. To date limited data exist as to the utility of this assay in the clinical setting. In the present study we evaluated eight LVAD patients' platelet activation level using the PAS assay. Simultaneous measurements of conventional prothrombotic and hemolysis markers, - i.e. fibrinogen and lactate dehydrogenase (LDH) - were also performed. Trends as to alteration from baseline were studied. We observed that the PAS assay allowed detection of an abnormal level of platelet activation in one patient in our series who suffered from an overt thrombosis. Interestingly in the same patient no signal of major abnormality in fibrinogen or LDH was detected. Further for 7/8 patients who were free of thrombosis, no significant level of platelet activation was detected via PAS assay, while elevation in fibrinogen and LDH were observed. As such, from our observational series it appears that the PAS assay is a sensitive and specific indicator of shear-mediated platelet activation. Further patients' experience will help elucidate the role of this promising assay in the management of LVAD implanted patients.

  3. Low platelet counts alone do not cause bleeding in an experimental immune thrombocytopenic purpura in mice.

    PubMed

    Domínguez, Victoria; Govezensky, Tzipe; Gevorkian, Goar; Larralde, Carlos

    2003-06-01

    The physiopathogenesis of hemorrhagic phenomena in patients with autoimmune thrombocytopenic purpura is associated with low platelet levels. In the present work the relation between thrombocytopenia and bleeding was examined. The possible participation of endothelial cells in bleeding was also investigated. Immune thrombocytopenia and bleeding were studied in mice injected with anti-mouse and anti-human platelet polyclonal rabbit IgG. Platelet levels were measured at different times and bleeding signs were systematically recorded. ANOVA tests were used to compare platelet levels. Binding of anti-platelet antibodies to vascular endothelial cells was analyzed by immunohistochemistry. Three different doses of anti-platelet IgG caused the same low platelet levels, but bleeding occurred only with high doses of anti-platelet IgG irrespective of the platelet levels. No inflammation around blood vessels was observed in paraffin-embedded tissue sections of organs. Immunohistochemistry demonstrated anti-platelet antibodies bound to vascular endothelium. We showed lack of correlation between platelet counts and bleeding in a murine model. The binding of anti-platelet IgG to endothelial cells of small vessels is an indication that antibody-mediated endothelial activation, in addition to thrombocytopenia, could be participating in bleeding.

  4. Differential inhibitory action of apixaban on platelet and fibrin components of forming thrombi: Studies with circulating blood and in a platelet-based model of thrombin generation

    PubMed Central

    Arellano-Rodrigo, Eduardo; Reverter, Joan Carles; Lopez-Farre, Antonio; Diaz-Ricart, Maribel; Badimon, Juan Jose; Escolar, Gines

    2017-01-01

    Introduction Mechanisms of action of direct oral anticoagulants (DOAC) suggest a potential therapeutic use in the prevention of thrombotic complications in arterial territories. However, effects of DOACs on platelet activation and aggregation have not been explored in detail. We have investigated the effects of apixaban on platelet and fibrin components of thrombus formation under static and flow conditions. Methods We assessed the effects of apixaban (10, 40 and 160 ng/mL) on: 1) platelet deposition and fibrin formation onto a thrombogenic surface, with blood circulating at arterial shear-rates; 2) viscoelastic properties of forming clots, and 3) thrombin generation in a cell-model of coagulation primed by platelets. Results In studies with flowing blood, only the highest concentration of apixaban, equivalent to the therapeutic Cmax, was capable to significantly reduce thrombus formation, fibrin association and platelet-aggregate formation. Apixaban significantly prolonged thromboelastometry parameters, but did not affect clot firmness. Interestingly, results in a platelet-based model of thrombin generation under more static conditions, revealed a dose dependent persistent inhibitory action by apixaban, with concentrations 4 to 16 times below the therapeutic Cmax significantly prolonging kinetic parameters and reducing the total amount of thrombin generated. Conclusions Our studies demonstrate the critical impact of rheological conditions on the antithrombotic effects of apixaban. Studies under flow conditions combined with modified thrombin generation assays could help discriminating concentrations of apixaban that prevent excessive platelet accumulation, from those that deeply impair fibrin formation and may unnecessarily compromise hemostasis. PMID:28192448

  5. Differential inhibitory action of apixaban on platelet and fibrin components of forming thrombi: Studies with circulating blood and in a platelet-based model of thrombin generation.

    PubMed

    Pujadas-Mestres, Lluis; Lopez-Vilchez, Irene; Arellano-Rodrigo, Eduardo; Reverter, Joan Carles; Lopez-Farre, Antonio; Diaz-Ricart, Maribel; Badimon, Juan Jose; Escolar, Gines

    2017-01-01

    Mechanisms of action of direct oral anticoagulants (DOAC) suggest a potential therapeutic use in the prevention of thrombotic complications in arterial territories. However, effects of DOACs on platelet activation and aggregation have not been explored in detail. We have investigated the effects of apixaban on platelet and fibrin components of thrombus formation under static and flow conditions. We assessed the effects of apixaban (10, 40 and 160 ng/mL) on: 1) platelet deposition and fibrin formation onto a thrombogenic surface, with blood circulating at arterial shear-rates; 2) viscoelastic properties of forming clots, and 3) thrombin generation in a cell-model of coagulation primed by platelets. In studies with flowing blood, only the highest concentration of apixaban, equivalent to the therapeutic Cmax, was capable to significantly reduce thrombus formation, fibrin association and platelet-aggregate formation. Apixaban significantly prolonged thromboelastometry parameters, but did not affect clot firmness. Interestingly, results in a platelet-based model of thrombin generation under more static conditions, revealed a dose dependent persistent inhibitory action by apixaban, with concentrations 4 to 16 times below the therapeutic Cmax significantly prolonging kinetic parameters and reducing the total amount of thrombin generated. Our studies demonstrate the critical impact of rheological conditions on the antithrombotic effects of apixaban. Studies under flow conditions combined with modified thrombin generation assays could help discriminating concentrations of apixaban that prevent excessive platelet accumulation, from those that deeply impair fibrin formation and may unnecessarily compromise hemostasis.

  6. Mediterranean wild plants reduce postprandial platelet aggregation in patients with metabolic syndrome.

    PubMed

    Fragopoulou, Elizabeth; Detopoulou, Paraskevi; Nomikos, Tzortzis; Pliakis, Emmanuel; Panagiotakos, Demosthenes B; Antonopoulou, Smaragdi

    2012-03-01

    Postprandial platelet hyperactivity and aggregation play a crucial role in the pathogenesis of metabolic syndrome. The purpose of the present study was to evaluate the effect of boiled wild plants consumption on the postprandial platelet aggregation in metabolic syndrome patients. Patients consumed 5 meals in a random order (ie, 4 wild plant meals, namely, Reichardia picroides [RP], Cynara cardunculus, Urospermum picroides [UP], and Chrysanthemum coronarium, and a control meal, which contained no wild plants). Several biochemical indices as well as platelet activating factor (PAF)- and adenosine diphosphate-induced ex vivo platelet aggregation were measured postprandially. Moreover, the ability of plants extract to inhibit rabbit platelet aggregation was tested in vitro. The consumption of RP and UP meals significantly reduced ex vivo adenosine diphosphate-induced postprandial platelet aggregation compared with the control meal. The consumption of UP meals significantly reduced the ex vivo PAF-induced platelet aggregation postprandially. Both UP and RP extracts significantly inhibited PAF-induced rabbit platelet aggregation in vitro. Wild plants consumption reduced postprandial platelet hyperaggregability of metabolic syndrome patients, which may account for their healthy effects. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Low incidence of anti-D alloimmunization following D+ platelet transfusion: The Anti-D Alloimmunization after D-incompatible Platelet Transfusions (ADAPT) study

    PubMed Central

    Cid, Joan; Lozano, Miguel; Ziman, Alyssa; West, Kamille A.; O'Brien, Kerry L.; Murphy, Michael F.; Wendel, Silvano; Vázquez, Alejandro; Ortín, Xavier; Hervig, Tor A.; Delaney, Meghan; Flegel, Willy A.; Yazer, Mark H.

    2014-01-01

    Summary The reported frequency of D alloimmunization in D- recipients after transfusion of D+ platelets varies. This study was designed to determine the frequency of D alloimmunization, previously reported to be an average of 5%±2%. A primary anti-D immune response was defined as the detection of anti-D ≥28 days following the first D+ platelet transfusion. Data were collected on 485 D- recipients of D+ platelets in 11 centres between 2010-2012. Their median age was 60 (range 2-100) years. Diagnoses included: haematological (203/485, 42%), oncological (64/485, 13%) and other diseases (218/485, 45%). Only 7/485 (1.44%; 95%CI 0.58-2.97%) recipients had a primary anti-D response after a median serological follow-up of 77 days (range: 28-2111). There were no statistically significant differences between the primary anti-D formers and the other patients, in terms of gender, age, receipt of immunosuppressive therapy, proportion of patients with haematological/oncological diseases, transfusion of whole blood-derived or apheresis platelets or both, and total number of transfused platelet products. This is the largest study with the longest follow-up of D alloimmunization following D+ platelet transfusion. The low frequency of D alloimmunization should be considered when deciding whether to administer Rh Immune Globulin to D- males and D- females without childbearing potential after transfusion of D+ platelets. PMID:25283094

  8. Genome-wide association study of platelet aggregation in African Americans.

    PubMed

    Qayyum, Rehan; Becker, Lewis C; Becker, Diane M; Faraday, Nauder; Yanek, Lisa R; Leal, Suzanne M; Shaw, Chad; Mathias, Rasika; Suktitipat, Bhoom; Bray, Paul F

    2015-05-30

    We have previously shown that platelet aggregation has higher heritability in African Americans than European Americans. However, a genome-wide association study (GWAS) of platelet aggregation in African Americans has not been reported. We measured platelet aggregation in response to arachidonic acid, ADP, collagen, or epinephrine by optical aggregometry. The discovery cohort was 825 African Americans from the GeneSTAR study. Two replication cohorts were used: 119 African Americans from the Platelet Genes and Physiology Study and 1221 European Americans from GeneSTAR. Genotyping was conducted with Illumina 1 M arrays. For each cohort, age- and sex-adjusted linear mixed models were used to test for association between each SNP and each phenotype under an additive model. Six SNPs were significantly associated with platelet aggregation (P<5×10(-8)) in the discovery sample. Of these, three SNPs in three different loci were confirmed: 1) rs12041331, in PEAR1 (platelet endothelial aggregation receptor 1), replicated in both African and European Americans for collagen- and epinephrine-induced aggregation, and in European Americans for ADP-induced aggregation; 2) rs11202221, in BMPR1A (bone morphogenetic protein receptor type1A), replicated in African Americans for ADP-induced aggregation; and 3) rs6566765 replicated in European Americans for ADP-induced aggregation. The rs11202221 and rs6566765 associations with agonist-induced platelet aggregation are novel. In this first GWAS of agonist-induced platelet aggregation in African Americans, we discovered and replicated, novel associations of two variants with ADP-induced aggregation, and confirmed the association of a PEAR1 variant with multi-agonist-induced aggregation. Further study of these genes may provide novel insights into platelet biology.

  9. A comparative study of 2 methods for obtaining platelet-rich plasma.

    PubMed

    Tamimi, Faleh M; Montalvo, Santiago; Tresguerres, Isabel; Blanco Jerez, Luis

    2007-06-01

    Double and single centrifugation are the most commonly used techniques for obtaining platelet-rich plasma (PRP) in dentistry. In this study, we used and compared 2 methods for obtaining PRP: double centrifugation (ACE system; Surgical Supply and Surgical Science Systems, Brockton, MA) and single centrifugation (Nahita system; Nahita, Navarra, Spain). Blood samples were obtained from 30 random patients. Each blood sample was treated using the ACE system and Nahita system methods, after which the obtained material was analyzed by flow cytometry for platelet counts and by transmission electron microscopy (TEM) for ultrastructural analysis of the PRP gel. Platelet count analysis of the PRP obtained from both methods revealed that the ACE and Nahita systems accomplished platelet concentrations of (336%) and (227%), respectively. The platelet counting results obtained from the ACE system samples were more dispersed than their Nahita system counterpart. The ultrastructural (ie, TEM) study showed considerable alterations of the platelet aggregates in the ACE's PRP, especially when the samples were not mixed in the final stage of the procedure, whereas the Nahita aggregates always had a normal physiological appearance. The ACE double-centrifugation method is able to achieve higher platelet concentrations than the single-centrifugation Nahita system, although the results obtained by ACE were more dispersed. Nevertheless, the ACE system provoked alterations in the PRP ultrastructure, and it was more sensitive to small errors during preparation.

  10. A note on the use of Quin2 in studying shear-induced platelet aggregation.

    PubMed

    Giorgio, T D; Hellums, J D

    1986-02-01

    Quin2, a calcium ion chelator which can penetrate plasma membranes, was used to study the role of intracellular calcium ion concentration in mediating shear-induced platelet activation. Washed platelet suspensions were subjected to various levels of uniform, known shear stress in a cone and plate viscometer in the absence of added agonists. Additional samples were aggregated in response to chemical platelet agonists in a conventional aggregometer. The aggregometer response of Quin2-containing platelets to collagen, thrombin and ADP exhibited increased lag time and reduced maximum rate of aggregation in comparison to controls. However, the extent of aggregation of the Quin2-containing platelets eventually reached the same level as that of the controls. Very different results were obtained for aggregation by shear stress in the viscometer. Shear-induced aggregation was significantly suppressed by Quin2 treatment at both short (30 seconds) and long (300 seconds) times of exposure to the shear field. Shear-induced dense granular release and cellular lysis were unaltered by Quin2 treatment at 30 second exposure times, but both were significantly increased by Quin2 treatment at 300 second exposure times. These results suggest that intracellular calcium ion mobilization is an important early step in shear-induced platelet activation. Additionally, Quin2 appears to have effects resulting in increased platelet fragility. Thus, the findings raise questions on the suitability of Quin2 as an intracellular calcium ion probe in studies in shear fields.

  11. Hepatoprotective and toxicological studies of Salvia bucharica methanolic extract in rabbits.

    PubMed

    Ahmad, Mansoor; Muhammed, Shafi; Mehjabeen, -; Jahan, Noor

    2014-11-01

    Most of the species of genus Salvia are famous for having medicinal properties due to their chemical constituents. Salvia bucharica (Lamiacea) is found in Balochistan near Quetta in Hannaurak and Kalat. It is used in traditional system of medicine and claims to cure liver ailments. In current study crude methanolic extract (CME) of Salvia bucharica was obtained from the leaves and tested for hepatoprotective activity and possible toxicity in rabbits. Liver toxicity was induced in rabbits by administration of carbon tetra chloride (CCl4) and evaluated by biochemical tests and histopathology of tissues. In this study rabbits were divided in to 3 groups (5 rabbit in each group). Rabbits of group I (control) were administered only vehicle (0.9% sodium chloride) orally. Rabbits of group II were given CCl4 and group III were treated with CCl4 and S. bucharica CME orally. For hepatoprotective effect serum enzyme level and total protein level were calculated. Histopathology of liver sections of rabbits was also carried out to observe protective effect. Biochemical, hematological and histoptahological parameters were studied on rabbits for toxicological studies. S. bucharica CME showed significant liver protection with reduction in total bilirubin, direct bilirubin, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), gamma glutamyl transpeptidase (γ-GT). And decrease in Albumin and globulin. In toxicological studies, biochemical and histoptahological parameters showed no significant toxicity in liver, heart and kidneys. It is concluded that S. bucharica CME showed hepatoprotective effects with nontoxic profile.

  12. Effect of platelet-rich plasma and bioactive glass powder for the improvement of rotator cuff tendon-to-bone healing in a rabbit model.

    PubMed

    Wu, Yang; Dong, Yu; Chen, Shiyi; Li, Yunxia

    2014-11-28

    To test the hypothesis that a platelet-rich plasma (PRP) plus bioactive glass (BG) mixture could shorten the tendon-bone healing process in rotator cuff tendon repair, thirty mature male New Zealand white rabbits were randomly divided into three groups, Control, PRP, and PRP + BG. All groups underwent a surgical procedure to establish a rotator cuff tendon healing model. Mechanical examinations and histological assays were taken to verify the adhesion of the tendon-bone. Real-time PCR was adopted to analyze Bone Morphogenetic Protein-2 (BMP-2). The maximum load-to-failure value in mechanical examinations was significantly higher in the PRP + BG group than that in the control group after six weeks (Control 38.73 ± 8.58, PRP 54.49 ± 8.72, PRP + BG 79.15 ± 7.62, p < 0.001), but it was not significantly different at 12 weeks (PRP 74.27 ± 7.74, PRP + BG 82.57 ± 6.63, p = 0.145). In histological assays, H&E (hematoxylin-eosin) staining showed that the interface between the tendon-bone integration was much sturdier in the PRP + BG group compared to the other two groups at each time point, and more ordered arranged tendon fibers can be seen at 12 weeks. At six weeks, the mRNA expression levels of BMP-2 in the PRP + BG group were higher than those in the other groups (PRP + BG 0.65 ± 0.11, PRP 2.284 ± 0.07, Control 0.12 ± 0.05, p < 0.05). However, there was no significant difference in the mRNA expression levels of BMP-2 among the three groups at 12 weeks (p = 0.922, 0.067, 0.056). BMP-2 levels in PRP and PRP+BG groups were significantly lower at 12 weeks compared to six weeks (p = 0.006, <0.001).We found that the PRP + BG mixture could enhance tendon-bone healing in rotator cuff tendon repair.

  13. Methods for studying the platelet-derived growth factor receptor

    SciTech Connect

    Bowen-Pope, D.F.; Ross, R.

    1985-01-01

    Platelet-derived growth factor (PDGF) is a basic 30,000-dalton protein circulating in normal blood sequestered within the platelet alpha granule. Radioiodinated PDGF shows saturable (e.g., 60,000-120,000 receptors per diploid human fibroblast) high affinity binding to culture PDGF-responsive cells. The apparent dissociation constant reported for this binding interaction has varied widely. This paper focuses on factors which affect (/sup 125/I)PGDF binding and on the development of a radioreceptor assay for PDGF.

  14. Rationale and design of platelet transfusions in haematopoietic stem cell transplantation: the PATH pilot study

    PubMed Central

    Tay, Jason; Allan, David; Beattie, Sara; Bredeson, Christopher; Fergusson, Dean; Maze, Dawn; Sabloff, Mitchell; Thavorn, Kednapa; Tinmouth, Alan

    2016-01-01

    Introduction In patients with transient thrombocytopenia being treated with high-dose chemotherapy followed by stem cell rescue—haematopoietic stem cell transplantation (HSCT), prophylactic transfusions are standard therapy to prevent bleeding. However, a recent multicentre trial suggests that prophylactic platelet transfusions in HSCT may not be necessary. Additionally, the potential overuse of platelet products places a burden on a scarce healthcare resource. Moreover, the benefit of prophylactic platelet transfusions to prevent clinically relevant haemorrhage is debatable. Current randomised data compare different thresholds for administering prophylactic platelets or prophylactic versus therapeutic platelet transfusions. An alternative strategy involves prescribing prophylactic antifibrinolytic agents such as tranexamic acid to prevent bleeding. Methods and analysis This report describes the design of an open-labelled randomised pilot study comparing the prophylactic use of oral tranexamic acid with platelet transfusions in the setting of autologous HSCT. In 3–5 centres, 100 patients undergoing autologous HSCT will be randomly assigned to either a prophylactic tranexamic acid or prophylactic platelets bleeding prevention strategy-based daily platelet values up to 30 days post-transplant. The study will be stratified by centre and type of transplant. The primary goal is to demonstrate study feasibility while collecting clinical outcomes on (1) WHO and Bleeding Severity Measurement Scale (BSMS), (2) transplant-related mortality, (3) quality of life, (4) length of hospital stay, (5) intensive care unit admission rates, (6) Bearman toxicity scores, (7) incidence of infections, (8) transfusion requirements, (9) adverse reactions and (10) economic analyses. Ethics and dissemination This study is funded by a peer-reviewed grant from the Canadian Institutes of Health Research (201 503) and is registered on Clinicaltrials.gov NCT02650791. It has been approved by

  15. Platelet adhesion changes during storage studied with a novel method using flow cytometry and protein-coated beads.

    PubMed

    Tynngård, Nahreen; Wallstedt, Maria; Södergren, Anna L; Faxälv, Lars; Ramström, Sofia

    2015-01-01

    The aim of the present study was to set up and evaluate a novel method for studies of platelet adhesion and activation in blood and platelet suspensions such as platelet concentrate (PC) samples using protein-coated polystyrene beads and flow cytometry. To demonstrate its usefulness, we studied PCs during storage. PCs were prepared by aphaeresis technique (n = 7). Metabolic variables and platelet function was measured on day 1, 5, 7 and 12 of storage. Spontaneous and TRAP-6-induced adhesion to fibrinogen- and collagen-coated beads was analyzed by flow cytometry. P-selectin and phosphatidyl serine (PS) expression was assessed on platelets bound to beads as well as on non-adherent platelets. Platelet adhesion to fibrinogen beads had increased by day 12 and adhesion to collagen beads at day 7 of storage (p < 0.05). TRAP-6 stimulation significantly increased the platelet adhesion to fibrinogen beads (p < 0.05) as well as the P-selectin and PS exposure on platelets bound to beads (p < 0.01) during the first 7 days of storage, but by day 12, significant changes were no longer induced by TRAP-6 stimulation. We demonstrate that our adhesion assay using protein-coated polystyrene beads can be used to assess the adhesion properties of platelets during storage without the addition of red blood cells. Therefore it may offer a useful tool for future studies of platelet adhesive capacity in transfusion medicine and other settings.

  16. A novel property of an aqueous guaraná extract (Paullinia cupana): inhibition of platelet aggregation in vitro and in vivo.

    PubMed

    Bydlowski, S P; Yunker, R L; Subbiah, M T

    1988-01-01

    Aqueous extracts of guaraná were studied in terms of effects on the aggregation of human and rabbit platelets. Guaraná extracts have anti-aggregatory and de-aggregatory actions on platelet aggregation induced by ADP or arachidonate but not by collagen. The active material was shown to be water soluble and heat resistant and appeared to be different from salicylates, nicotinic acid or known xanthines. Guaraná extracts inhibited platelet aggregation in rabbits following either intravenous or oral administration.

  17. Radionuclide study of platelets and prosthetic interactions: External versus specimen quantitation

    SciTech Connect

    Nordestgaard, A.G.; Marcus, C.S.; Wilson, S.E. )

    1988-01-01

    Twenty-nine New Zealand white rabbits were allocated to undergo insertion of either polytetrafluoroethylene (PTFE) (n = 22) or microporous silicone rubber (SR) (n = 7), 3-mm diameter, 10-mm long aortic grafts. Animals with PTFE grafts received aspirin (ASA) 10 mg/kg/d and dipyridamole (DPM) 10 mg/kg/d (n = 11) or placebo (n = 11). Autologous In-111-oxine-labeled platelets were reinfused on reestablishment of blood flow through the graft. Using gamma camera images, an external graft platelet accumulation index (E-GPAI) was calculated as the In-111 activity in the graft area to the reference aorta at 24, 48, and 72 hours post implantation. Mean E-GPAI +/- SEM values for the ASA/DPM (n = 4) and control groups (n = 7) were 1.13 +/- 0.16 and 1.34 +/- 0.05 (NS) at 24 hours, 1.20 +/- 0.16 and 1.33 +/- 0.07 (NS) at 48 hours, and 1.38 +/- 0.07 and 1.35 +/- 0.10 (NS) at 72 hours, respectively. A similar internal graft platelet accumulation index (I-GPAI) was constructed based on In-111 activity in excised grafts and reference aorta measured in a scintillation counter. Mean I-GPAI +/- SEM values for the PTFE ASA/DPM (n = 9) and control groups (n = 8) at 48 hours post implantation were 43.1 +/- 2.7 and 216.8 +/- 73.9 (P = 0.05), respectively. I-GPAI values for the SR grafts were 192.5 +/- 43.1. The E-GPAI was not sensitive enough to demonstrate the effect of antiplatelet medication on platelet accumulation on the PTFE grafts.

  18. The Inflammatory Role of Platelets: Translational Insights from Experimental Studies of Autoimmune Disorders

    PubMed Central

    Pankratz, Susann; Bittner, Stefan; Kehrel, Beate E.; Langer, Harald F.; Kleinschnitz, Christoph; Meuth, Sven G.; Göbel, Kerstin

    2016-01-01

    Beyond their indispensable role in hemostasis, platelets have shown to affect the development of inflammatory disorders, as they have been epidemiologically and mechanistically linked to diseases featuring an inflammatory reaction in inflammatory diseases like multiple sclerosis, rheumatoid arthritis and inflammatory bowel disorders. The identification of novel molecular mechanisms linking inflammation and to platelets has highlighted them as new targets for therapeutic interventions. In particular, genetic and pharmacological studies have identified an important role for platelets in neuroinflammation. This review summarizes the main molecular links between platelets and inflammation, focusing on immune regulatory factors, receptors, cellular targets and signaling pathways by which they can amplify inflammatory reactions and that make them potential therapeutic targets. PMID:27754414

  19. Low-level HLA antibodies do not predict platelet transfusion failure in TRAP study participants

    PubMed Central

    Deng, Xutao; Bolgiano, Douglas; Lebedeva, Mila; Heitman, John W.; Busch, Michael P.; Slichter, Sherrill J.; Norris, Philip J.

    2013-01-01

    In the Trial to Reduce Alloimmunization to Platelets (TRAP) study, 101 of 530 participants became refractory to platelet transfusions without evidence of HLA or human platelet antigen (HPA) antibodies. We used a more sensitive bead-based assay to detect and quantify HLA antibodies and a qualitative solid-phase enzyme-linked immunosorbet assay for HPA to determine whether low-level antibodies could predict refractoriness in longitudinal panels from 170 lymphocytotoxicity assay (LCA)− and 20 LCA+ TRAP participants. All TRAP recipients who previously tested LCA+ were HLA antibody+, using the bead-based system. Levels of HLA or HPA antibodies did not predict refractoriness among LCA− recipients, although higher levels of HLA antibodies were associated with refractoriness among LCA+ recipients. These data demonstrate that weak to moderate HLA antibody levels detectable by modern binding assays are not associated with platelet refractoriness. PMID:23393051

  20. Study on impression smears of hepatic coccidiosis in rabbits.

    PubMed

    Sivajothi, S; Reddy, B Sudhakara; Rayulu, V C

    2016-09-01

    Hepatic coccidiosis is a contagious and lethal disease condition in rabbits. The disease was recorded in six rabbits suffering with watery diarrhoea. Clinically, affected rabbits showed decreased growth rate, anorexia, debilitation, diarrhea and rough hair coat. Examination of the faecal samples revealed the presence of unsporulated oocysts of Eimeria spp. After sporulation Eimeria stiedae oocysts were identified. Postmortem examination revealed hepatomegaly with presence of discrete yellowish-white nodules on the surface of the liver. Impression smears from the liver revealed the presence of numerous developmental stages of E. stiedae corresponding with the stage of the liver lesion and also represent the histological changes of the liver. Rabbits were treated with a combination of sulphaquinoxaline and diaveridine for five days.

  1. EPIDEMIOLOGICAL STUDIES ON RESPIRATORY INFECTIONS OF THE RABBIT

    PubMed Central

    Webster, Leslie T.

    1926-01-01

    Rabbits with no previous exposure to Bact. lepisepticum were given, intranasally, a known dose of one strain or another of this organism, or of B. bronchisepticus. The results give grounds for the following conclusions. PMID:19869145

  2. Comparative toxicology studies in Sprague-Dawley rats, rhesus monkeys, and New Zealand White rabbits to determine a no observed adverse effect level for 1,1'-methylenebis[4-[(hydroxyimino)methyl]-pyridinium] dimethanesulfonate.

    PubMed

    Osheroff, Merrill R; Kobs, Dean J; Buccellato, Matthew; Croutch, Claire R; Elcock, Laura E; Burback, Brian L; Johnson, Jerry D

    2013-01-01

    Studies were conducted in Sprague-Dawley rats, New Zealand White (NZW) rabbits, and rhesus monkeys to characterize the toxicity of 1,1'-methylenebis[4-[(hydroxyimino)methyl]-pyridinium] dimethanesulfonate (MMB4 DMS) following intramuscular administration. Rats received MMB4 DMS once daily for 7 days at 100, 200, 400, and 800 mg/kg/d; rabbits received a range of dose levels in 3 separate 7-day studies from 3 to 800 mg/kg/d and in a single-dose study from 50 to 200 mg/kg; and monkeys received MMB4 DMS at 150 to 600 mg/kg/d. Mortality was noted in rats and rabbits administered ≥ 200 mg/kg. All monkeys survived until scheduled termination. Adverse clinical observations were noted in the rats at ≥ 400 mg/kg/d and in rabbits administered ≥ 200 mg/kg; no adverse findings were noted in the monkeys. Clinical pathology changes were noted in the rabbit related to cardiac and renal function. In the rabbit and monkey, elevations in myoglobin, alanine aminotransferase/aspartate aminotransferase, platelets, creatine kinase, and coagulation factors were related to local inflammation at the intramuscular administration site. Light microscopic examination at the injection sites revealed acute skeletal muscle necrosis in vehicle control and treated groups. Target tissues in the rabbit studies were identified as kidney, heart, and lungs at ≥ 100 mg/kg/d. All changes noted in all the species demonstrated partial to complete recovery comparable to control values or to a clinically irrelevant level of effect. The NZW rabbit was the most sensitive species, and the no observed adverse effect level (NOAEL) was determined as 50 mg/kg/d; the NOAEL in the rat was 100 mg/kg/d; and the NOAEL in rhesus monkeys was >600 mg/kg/d.

  3. Platelet Aggregation and Mental Stress Induced Myocardial Ischemia: Results from the REMIT Study

    PubMed Central

    Jiang, Wei; Boyle, Stephen H.; Ortel, Thomas L.; Samad, Zainab; Velazquez, Eric J.; Harrison, Robert W.; Wilson, Jennifer; Kuhn, Cynthia; Williams, Redford B.; O’Connor, Christopher M.; Becker, Richard C.

    2015-01-01

    BACKGROUND Mental stress-induced myocardial ischemia (MSIMI) is common in patients with ischemic heart disease (IHD) and associated with a poorer cardiovascular prognosis. Platelet hyperactivity is an important factor in acute coronary syndrome. This study examined associations between MSIMI and resting and mental stress-induced platelet activity. METHODS Eligible patients with clinically stable IHD underwent a battery of 3 mental stress tests during the recruitment phase of REMIT (Responses of Myocardial Ischemia to Escitalopram Treatment) study. MSIMI was assessed by echocardiography and electrocardiography. Ex vivo platelet aggregation in response to ADP, epinephrine, collagen, serotonin, and combinations of serotonin plus ADP, epinephrine, and collagen were evaluated as was platelet serotonin transporter expression. RESULTS Of the 270 participants who completed mental stress testing, and had both resting and post-stress platelet aggregation evaluation, 43.33% (N=117) met criteria for MSIMI and 18.15% (N=49) had normal left ventricular response to stress (NLVR). The MSIMI group, relative to the NLVR groups, demonstrated heightened mental stress-induced aggregation responses, as measured by area under the curve, to collagen 10 μM (6.95[5.54] vs. −14.23[8.75].; p=0.045), epinephrine 10 μM (12.84[4.84] vs. −6.40[7.61].; p=0.037) and to serotonin 10 μM plus ADP 1 μM (6.64[5.29] vs. −27.34[8.34]; p < .001). The resting platelet aggregation and serotonin transporter expression, however, were not different between the two groups. CONCLUSIONS These findings suggest that the dynamic change of platelet aggregation caused by mental stress may underlie MSIMI. While the importance of these findings requires additional investigation, they raise concern given the recognized relationship between mental stress-induced platelet hyperactivity and cardiovascular events in patients with IHD. PMID:25819856

  4. Microparticle detection to guide platelet management for the reduction of platelet refractoriness in children - A study proposal.

    PubMed

    Kanzler, Peter; Mahoney, Andrew; Leitner, Gerda; Witt, Volker; Maurer-Spurej, Elisabeth

    2016-12-29

    Microparticles have been shown to shed from a variety of viable cells as a consequence of inflammatory processes, activation or physical stress. Seventy to 90% of circulating microparticles are thought to be platelet-derived. The content of microparticles in blood collected from normal blood donors is highly variable and transfers into the final blood component. Elevated microparticle content (MPC) in donor blood might indicate an asymptomatic clinical condition of the donor which might affect the transfusion recipient, particularly pediatric patients. ThromboLUX is a new technology designed to routinely test biological samples for microparticle content. We compared MPC in platelet-rich plasma (PRP) of apheresis donors and the corresponding INTERCEPT-treated apheresis products (N=24). The MPCs in donor and product samples were correlated (r=0.74, P<0.001). Microparticles were significantly reduced after plasma replacement and INTERCEPT treatment. These findings are supported by phase contrast microscopy. Platelet transfusions given to patients with fever or systemic inflammation are less efficacious. In addition, transfusing heterogeneous platelets - concentrates with high MPC and activated platelets - to patients whose immune systems are activated might tip them over a threshold and cause platelet refractoriness. Restricting prophylactic platelet transfusions to homogeneous products - concentrates with resting platelets and therefore low MPC - may reduce the risk of refractoriness in cancer patients, especially children with immature immunity. To test this hypothesis we introduce an evaluation protocol for platelet management, i.e., keeping a split inventory of homogeneous and heterogeneous platelets, and using only homogeneous platelets for prophylaxis as a strategy to reduce refractoriness.

  5. Immunochemical studies with a specific antiserum to rabbit fibroblast collagenase.

    PubMed Central

    Werb, Z; Reynolds, J J

    1975-01-01

    1. Antisera were raised against the collagenase from rabbit synovial fibroblasts and characterized by immunoprecipitation and immunoinhibition reactions. 2. Immunoglobulins from the antisera were potent inhibitors of the action of rabbit collagenase on both reconstituted collagen fibrils and collagen in solution. 3. The antibody-binding fragment, Fab', produced by digesting the IgG (immunoglobulin G) with pepsin, inhibited collagenase activity just as well as whole IgG. 4. A specific antiserum to the rabbit collagenase was raised by a multi-step procedure. An initial antiserum was made by injecting partially purified collagenase as a complex with sheep alpha2-macroglobulin into a sheep. The non-specific antiserum so obtained was used to produce precipitin lines with the purified enzyme, and these lines were used as antigen for the production of the specific antiserum. 5. An IgG preparation from the specific antiserum was a specific and potent inhibitor of the rabbit synovial fibroblast collagenase. Neutral metallo-proteinase activity secreted by the rabbit fibroblasts was not inhibited by the antibody to the rabbit collagenase. 6. Criteria for determination of the specificity of antisera are discussed. Images PLATE 1 PLATE 2 PMID:175786

  6. STUDIES ON THE ETIOLOGY OF SPONTANEOUS CONJUNCTIVAL FOLLICULOSIS OF RABBITS

    PubMed Central

    Olitsky, Peter K.; Syverton, Jerome T.; Tyler, Joseph R.

    1934-01-01

    Spontaneous conjunctival folliculosis is widespread among various species of rabbits. It exists in two forms: Type I, in which the lesions are localized and the disease is relatively inactive, and Type II, in which the follicles are closely distributed over the entire surface of the conjunctivae and the affection is more active and characterized by extensive inflammatory reactions. One type can be converted into the other either by experimental methods or by natural processes. The disease can be transmitted from rabbit to rabbit by means of subconjunctival inoculation of suspensions of the affected tissues or by instillation of such material into the conjunctival sac, or even by mere contact of folliculosis animals with rabbits having smooth conjunctivae. It is plain that the disease is an infection. The causal agent of the infection is not filtrable through Seitz discs that retain Serratia marcescens nor through Berkefeld V candles that permit the passage of this organism. Furthermore, the lesions of the spontaneous or of the experimental disease do not exhibit the cytotropic effects or the inclusion bodies suggestive of the action of an ultramicroscopic virus. They are characterized, on the other hand, by a persistent and progressive chronicity and show certain resemblances to the granulomata. The evidence suggests that the spontaneous conjunctival folliculosis of rabbits is due to a microorganism—one having a low grade pathogenic action. In a paper shortly to be published, a bacterium capable of reproducing folliculosis in normal rabbits will be described. PMID:19870281

  7. Effect of adjunctive dipyridamole to DAPT on platelet function profiles in stented patients with high platelet reactivity. The result of the ACCEL-DIP Study.

    PubMed

    Park, Y; Jeong, Y-H; Tantry, U S; Ahn, J H; Kim, K H; Koh, J-S; Park, J-R; Hwang, S-J; Kwak, C H; Hwang, J-Y; Gurbel, P A

    2014-12-01

    Adjunctive use of phosphodiesterase (PDE) inhibitor can enhance antiplatelet and vasoprotective properties in patients with cardiovascular disease. The aim of this study was to evaluate the impact of PDE5 inhibitor dipyridamole on platelet function in stented patients with high platelet reactivity (HPR) during dual antiplatelet therapy (DAPT) with aspirin and clopidogrel. Patients with HPR after 600-mg clopidogrel loading were randomly assigned to adjunctive dipyridamole 75 mg twice daily to standard DAPT (DIP group; n = 45) or double-dose clopidogrel of 150 mg daily (DOUBLE group; n = 46) for 30 days. Platelet function was assessed at baseline and 30-day follow-up with platelet reactivity index (PRI) by vasodilator-stimulated phosphoprotein-phosphorylation (VASP-P) assay and platelet aggregation (PA) by light transmittance aggregometry (LTA). Primary endpoint was PRI at 30-day follow-up. HPR was defined as PRI > 50%. Baseline platelet function did not differ between the groups. Following 30-day therapy, platelet function was significantly reduced in the DIP and DOUBLE groups (all p-values ≤ 0.004 and ≤ 0.068, respectively). PRI values were not significantly different between the two groups (mean difference: 3.1%; 95% confidence interval: -2.8% to 9.0%: p = 0.295). PA values and prevalence of HPR were similar between the groups. However, a significant number of patients still exhibited HPR in the DIP (75.6%) and DOUBLE (67.4%) groups. In conclusion, among stented HPR patients, adding dipyridamole to DAPT does not reduce platelet reactivity and prevalence of HPR compared with double-dose clopidogrel therapy, and therefore both strategies are inadequate to overcome HPR.

  8. Freezing of Apheresis Platelet Concentrates in 6% Dimethyl Sulfoxide: The First Preliminary Study in Turkey

    PubMed Central

    Yılmaz, Soner; Çetinkaya, Rıza Aytaç; Eker, İbrahim; Ünlü, Aytekin; Uyanık, Metin; Tapan, Serkan; Pekoğlu, Ahmet; Pekel, Aysel; Erkmen, Birgül; Muşabak, Uğur; Yılmaz, Sebahattin; Avcı, İsmail Yaşar; Avcu, Ferit; Kürekçi, Emin; Eyigün, Can Polat

    2016-01-01

    Objective: Transfusion of platelet suspensions is an essential part of patient care for certain clinical indications. In this pioneering study in Turkey, we aimed to assess the in vitro hemostatic functions of platelets after cryopreservation. Materials and Methods: Seven units of platelet concentrates were obtained by apheresis. Each apheresis platelet concentrate (APC) was divided into 2 equal volumes and frozen with 6% dimethyl sulfoxide (DMSO). The 14 frozen units of APCs were kept at -80 °C for 1 day. APCs were thawed at 37 °C and diluted either with autologous plasma or 0.9% NaCl. The volume and residual numbers of leukocytes and platelets were tested in both before-freezing and post-thawing periods. Aggregation and thrombin generation tests were used to analyze the in vitro hemostatic functions of platelets. Flow-cytometric analysis was used to assess the presence of frozen treated platelets and their viability. Results: The residual number of leukocytes in both dilution groups was <1x106. The mean platelet recovery rate in the plasma-diluted group (88.1±9.5%) was higher than that in the 0.9% NaCl-diluted group (63±10%). These results were compatible with the European Directorate for the Quality of Medicines quality criteria. Expectedly, there was no aggregation response to platelet aggregation test. The mean thrombin generation potential of post-thaw APCs was higher in the plasma-diluted group (2411 nmol/L per minute) when compared to both the 0.9% NaCl-diluted group (1913 nmol/L per minute) and the before-freezing period (1681 nmol/L per minute). The flow-cytometric analysis results for the viability of APCs after cryopreservation were 94.9% and 96.6% in the plasma and 0.9% NaCl groups, respectively. Conclusion: Cryopreservation of platelets with 6% DMSO and storage at -80 °C increases their shelf life from 7 days to 2 years. Besides the increase in hemostatic functions of platelets, the cryopreservation process also does not affect their viability

  9. Freezing of Apheresis Platelet Concentrates in 6% Dimethyl Sulfoxide: The First Preliminary Study in Turkey.

    PubMed

    Yılmaz, Soner; Çetinkaya, Rıza Aytaç; Eker, İbrahim; Ünlü, Aytekin; Uyanık, Metin; Tapan, Serkan; Pekoğlu, Ahmet; Pekel, Aysel; Erkmen, Birgül; Muşabak, Uğur; Yılmaz, Sebahattin; Avcı, İsmail Yaşar; Avcu, Ferit; Kürekçi, Emin; Eyigün, Can Polat

    2016-03-05

    Transfusion of platelet suspensions is an essential part of patient care for certain clinical indications. In this pioneering study in Turkey, we aimed to assess the in vitro hemostatic functions of platelets after cryopreservation. Seven units of platelet concentrates were obtained by apheresis. Each apheresis platelet concentrate (APC) was divided into 2 equal volumes and frozen with 6% dimethyl sulfoxide (DMSO). The 14 frozen units of APCs were kept at -80 °C for 1 day. APCs were thawed at 37 °C and diluted either with autologous plasma or 0.9% NaCl. The volume and residual numbers of leukocytes and platelets were tested in both before-freezing and post-thawing periods. Aggregation and thrombin generation tests were used to analyze the in vitro hemostatic functions of platelets. Flow-cytometric analysis was used to assess the presence of frozen treated platelets and their viability. The residual number of leukocytes in both dilution groups was <1x106. The mean platelet recovery rate in the plasma-diluted group (88.1±9.5%) was higher than that in the 0.9% NaCl-diluted group (63±10%). These results were compatible with the European Directorate for the Quality of Medicines quality criteria. Expectedly, there was no aggregation response to platelet aggregation test. The mean thrombin generation potential of post-thaw APCs was higher in the plasma-diluted group (2411 nmol/L per minute) when compared to both the 0.9% NaCl-diluted group (1913 nmol/L per minute) and the before-freezing period (1681 nmol/L per minute). The flow-cytometric analysis results for the viability of APCs after cryopreservation were 94.9% and 96.6% in the plasma and 0.9% NaCl groups, respectively. Cryopreservation of platelets with 6% DMSO and storage at -80 °C increases their shelf life from 7 days to 2 years. Besides the increase in hemostatic functions of platelets, the cryopreservation process also does not affect their viability rates.

  10. Intravenous immunoglobulins induce CD32-mediated platelet aggregation in vitro.

    PubMed

    Pollreisz, A; Assinger, A; Hacker, S; Hoetzenecker, K; Schmid, W; Lang, G; Wolfsberger, M; Steinlechner, B; Bielek, E; Lalla, E; Klepetko, W; Volf, I; Ankersmit, H J

    2008-09-01

    Intravenous immunoglobulins (IVIg) and cytomegalovirus immunoglobulins (CMVIg) are currently finding increased acceptance in clinical states of high immune activity and in transplant recipients. A rare side-effect of their application is intravascular thrombosis, which is thought to be related to pre-existing hyperviscosity. In a previous study we have shown that rabbit antithymocyte globulin causes platelet aggregation in vitro via the Fc IgG receptor (CD32). To investigate if IVIg and CMVIg have the potential to cause CD32-dependent platelet aggregation. The influence of CMVIg or IVIg on platelets pre-incubated with or without monoclonal antibody AT10 was studied in an aggregometer. Expression of platelet surface activation marker CD62P was determined by fluorescence-activated cell sorting analysis and presence of soluble CD40L (sCD40L) was evaluated by enzyme-linked immunosorbent assay. All in vitro experiments were performed using platelet concentrates from the blood bank, at therapeutic concentrations of immunoglobulins. Results Incubation of platelets with CMVIg and IVIg markedly induced platelet aggregation, and increased expression of CD62P and secretion of sCD40L. The capacity of CMVIg and IVIg to induce platelet aggregation was completely abrogated by adding the blocking antibody AT10 directed against the low-affinity Fc IgG receptor (CD32). Our results suggest that CMVIg and IVIg solutions with activating Fc domains are able to bind CD32 on platelets and cause platelet aggregation in vitro. These results indicate a mechanism by which in vivo intravascular thrombosis may be explained and suggest caution with concomitant use of packed platelets and IVIg in autoimmune diseases in the clinical setting.

  11. [Comparative study of five techniques of preparation of platelet-rich plasma].

    PubMed

    Kaux, J-F; Le Goff, C; Seidel, L; Péters, P; Gothot, A; Albert, A; Crielaard, J-M

    2011-06-01

    Injections of platelet-rich plasma (PRP) constitute a new therapeutic for treating chronic tendinopathies. The injection being carried out in the tendon, the volume of PRP should thus be minimal (to decrease the intratendinous pressure and to minimize pain). This PRP should also have a raised platelet count. The quantity of released growth factors could be related to the system of preparation employed. We thus carried out a comparative study of five techniques of preparation of PRP described in the literature. Samples of venous blood were taken among five patients in order to compare five techniques of preparation of PRP: University Hospital of Liège technique, Curasan(®) PRP Kit, Plateltex(®), GPS(®)II and RegenLab(®). The various techniques make it possible to obtain more important platelet concentration than in blood, with variable volumes (0,3 to 6ml). The number of platelets per microlitre appears higher with Plateltex(®) and obtains smallest volume of PRP. The other techniques also give small volumes except for the GPS(®)II. The number of collected platelets with this technique appears thus higher. The best collect efficiency is obtained with RegenLab(®). The technique Plateltex(®) makes it possible to collect the highest concentration of platelets in the smallest volume available. Copyright © 2009 Elsevier Masson SAS. All rights reserved.

  12. Modulation of P-selection and platelet aggregation in chronic periodontitis: A clinical study

    PubMed Central

    Perumal, Ramesh; Rajendran, Maheashwari; Krishnamurthy, Malathi; Ganji, Kiran Kumar; Pendor, Sunil Dattuji

    2014-01-01

    Background: The primary etiologic factor of periodontitis is the subgingival infection with a group of Gram negative pathogens. Transient bacteremia in periodontitis patients underlie chronic production and systemic increases of various proinflammatory mediators, including Interleukin (IL)-1α, IL-6, C-reactive protein and Tumor necrosis factor (TNF)-α. P- selectin is a member of selectin family of cell surface receptor which is located in the membrane of the secretory granules (alpha granules) of platelets and in the membrane of the Weibel-Palade bodies of the vascular endothelial cells. P selectin redistributes from the membrane of the granules to the plasma membrane when platelets and endothelial cells are activated and thus degranulated. Aim: To compare the level of platelet activation, soluble P Selectin level and morphological changes and aggregation of platelets in patients in periodontitis patients compared to healthy controls. Materials and Methods: 80 patients were included in the study with the age group of 35-60. The patients were divided into 2 groups, 40 subjects with generalized chronic periodontitis and 40 healthy subjects taken as control. Periodontal Examination using clinical parameters namely, Bleeding Index, Plaque Index, Probing Pocket Depth and Clinical Attachment Level were recorded. Collection of blood samples for estimation of serum soluble P- selectin level by ELISA method. Evaluation of Platelet morphology and grading the platelet aggregation. Results: P-selectin expression shows that the mean value for control group is 4.97 ± 16.56 ng/mL and study group 13.05 ± 29.94 ng/mL which was significantly higher than control group with P value 0.001. Platelet morphological changes shows small form – mean value for control group is 75.83% ± 14.24% while for study group is 39.08%. ± 21.59; Big form – mean value for control group 0.80% ± 0.35% while for study group 0.48% ± 1.3%and Spider form- mean value for control group 23.88% ± 14

  13. Dynamic redistribution of major platelet surface receptors after contact-induced platelet activation and spreading. An immunoelectron microscopy study.

    PubMed Central

    Kieffer, N.; Guichard, J.; Breton-Gorius, J.

    1992-01-01

    The authors used an immunogold labeling procedure to investigate the redistribution of platelet receptors and their ligands on the surface of contact-activated adherent platelets before and after thrombin stimulation. During the initial stage of platelet adhesion, a typical segregation of receptors occurred. Gold particles identifying glycoprotein (GP) Ib (CD42b) and GPIIb-IIIa (CD41a) remained distributed over the entire platelet surface, whereas gold particles identifying GPIa-IIa (CDw 49b) and GPIV (CD36) were found essentially overlying the granulomere; p24 (CD9) was present at the peripheral platelet rim and over the cell body. An increased labeling of GPIIb-IIIa, GPIV and p24 was also observed on pseudopods, with GPIIb-IIIa and GPIV concentrated at the enlarged extremities and at sites of contact between two platelets, whereas GPIb was absent from pseudopods. After thrombin stimulation of adherent platelets, GPIb underwent a relocation to the cell center, in contrast to GPIIb-IIIa which still remained randomly distributed over the cell body. To investigate whether ligand distribution paralleled this receptor segregation, platelet released von Willebrand factor (vWF), fibrinogen (Fg) and thrombospondin (TSP) were visualized. During the early stages of platelet activation, surface labeling for all three adhesive proteins was minimal and almost undetectable. Occasionally, intragranular Fg and vWF was accessible to gold-coupled antibodies, with vWF exhibiting the typical eccentric alpha-granular localization. At later stages of activation and especially after thrombin stimulation, no surface labeling for vWF was observed, whereas immunogold particles identifying vWF were still present inside enlarged clear vacuoles. In contrast, labeling of Fg and TSP was increased over the granulomere and extended to the cell periphery and the pseudopods, but was absent from the hyalomere, despite the presence of GPIIb-IIIa molecules. Double labeling experiments showed

  14. Study on prevalence and genotype of hepatitis E virus isolated from Rex Rabbits in Beijing, China.

    PubMed

    Geng, J; Wang, L; Wang, X; Fu, H; Bu, Q; Zhu, Y; Zhuang, H

    2011-09-01

    A novel genotype of hepatitis E virus (HEV) isolated from rabbits is reported. The aim of this study was to confirm and further investigate the prevalence of the novel HEV genotype in rabbits in China. Sera and faecal samples were collected from farmed rex rabbits in Beijing, China. All serum samples were tested for anti-HEV antibody by EIA. Both the serum and the faecal samples were evaluated for detection of HEV RNA using a nested RT-PCR assay. The nucleotide sequences of rabbit HEV were then analysed, and sequence homology of rabbit HEV compared against human HEV genotypes 1-4, and avian HEV. The prevalence of positive serum anti-HEV from rex rabbits was 54.62% (65/119). The detection rate of HEV RNA using ORF2 primers was 6.96% (8/115) amongst rabbit faecal samples. All eight amplicons shared 98.3-100% nucleotide homology with each other and had identities of 75.8-78.6%, 73.9-75.0%, 77.5-81.0%, 74.2-78.6% and 54.8-57.6% with the corresponding regions of genotypes 1-4 and avian HEV, respectively. Phylogenetic analysis showed that the eight sequences formed one individual branch and were on the same branch with GDC9 and GDC46, both of which were reported to be a novel genotype of HEV isolated from rabbits. The conclusion is that this study provides further information about HEV infecting rabbits, which may be a new animal host of HEV, as well as genetical evidence of a new mammalian genotype of HEV. © 2010 Blackwell Publishing Ltd.

  15. Correlation study in skin and eye irritation between rabbits and humans based on published literatures.

    PubMed

    Ishii, Satoko; Ishii, Kaori; Nakadate, Masahiro; Yamasaki, Kanji

    2013-05-01

    The purpose of this study was to investigate the correlations in skin and eye irritations between rabbits and humans using published international databases. We selected 60 and 56 compounds for skin and eye irritation, respectively. When the reactions were divided into irritation-negative or irritation-positive, including corrosion, similar reactions between rabbits and humans were detected for 53 compounds in skin irritation and 54 compounds in eye irritation, showing rates of agreement in skin and eye as 88% and 96%, respectively. These findings revealed that correlation in skin and eye irritations between rabbits and humans were high. However, corrosion was observed in rabbit skin treated with 14 compounds, 4 of which showed similar changes in humans, and in rabbit eyes treated with 9 compounds, 1 of which revealed similar changes in humans. These findings indicated that the incidence of corrosion was higher in rabbits than in humans. Our results showed that the data on rabbit irritations in the skin and eye were useful for identifying risk of irritation in human. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. A rabbit jejunal isolated enterocyte preparation suitable for transport studies.

    PubMed Central

    Brown, P D; Sepúlveda, F V

    1985-01-01

    A method is described for isolating viable enterocytes from rabbit jejunum. Estimates of sucrase and gamma-glutamyl transferase activities in cells isolated by this method suggest that they originate from the upper villus only. Isolated cells accumulate both alpha-methyl-D-glucoside and alanine, maintaining high intracellular concentrations for at least 60 and 40 min respectively. Accumulation of alpha-methyl-D-glucoside is inhibited by the presence of phloridzin. The cells accumulate 42K and 86Rb in an identical manner. This uptake, which is maintained for at least 60 min, is inhibited in the presence of ouabain. Passive efflux of 42K and 86Rb occurs with rate constants which are virtually identical. The efflux follows a single exponential suggesting that it originates from only one intracellular compartment. It is suggested that the preparation can be used to study the effect of sugars and amino acids on K efflux. The advantages of using such a preparation are discussed. PMID:2862277

  17. Technical considerations in the study of /sup 111/In-oxine labelled platelet survival patterns in dogs

    SciTech Connect

    Sharefkin, J.; Rich, N.M.

    1982-04-01

    A detailed technique for labelling canine platelets with /sup 111/In-oxine for the study of platelet survival patterns in four to six dogs at a time was developed. Useful modifications of earlier methods included splitting of the platelet rich plasma into multiple aliquots to improve pelleting efficiency at low gravity forces, use of saved platelet poor plasma to flush out injection syringes, and prompt use of commercial /sup 111/In-oxine sources 3 to 5 minutes after mixing with Ringer's Citrate Dextrose. Avoidable pitfalls of the method included excessive lengths of incubation time in plasma free medium and loss of labelling efficacy by exposure of the chelate to iron or other metal contaminants in glassware. The method was used to study changes in platelet survival time in dogs with large synthetic arterial prostheses, and gave results in good agreement with earlier studies using /sup 51/Cr labelled platelets.

  18. Evaluation of platelets prepared by apheresis and stored for 5 days. In vitro and in vivo studies

    SciTech Connect

    Shanwell, A.; Gulliksson, H.; Berg, B.K.; Jansson, B.A.; Svensson, L.A.

    1989-11-01

    To evaluate the effect of storage on apheresis platelets collected with a closed-system blood cell separator, an in vitro investigation was performed, with measurements of pH, lactate, ATP, the ratio of ATP to the total adenine nucleotide content, and adenylate kinase. Unmodified apheresis platelets and apheresis platelets with plasma added were compared with conventional platelets stored in PL-1240 or PL-732 plastic containers. During 6 days of storage, there were similar changes in all variables with one exception: the extracellular activity of adenylate kinase was lower in apheresis platelets with plasma than in the other three groups (p less than 0.01). In vivo studies were carried out with 111Indium-labeled autologous platelets in eight volunteers. Apheresis platelets with 100 mL of plasma added were stored in two 1000-mL containers (PL-732) at 22 degrees C during agitation. Platelets from one of the containers were labeled with 111Indium and transfused into the volunteer within 24 hours. Platelets from the other container were labeled after 5 days of storage and transfused into the same donor. There were no significant differences between apheresis platelets stored for 1 day and those stored for 5 days: the mean percentage of recovery was 58.4 and 57.6 percent, t1/2 was 69 and 67 hours, and the survival time was 5.5 and 5.6 days, respectively.

  19. Iodine-125 metaraminol: A new platelet specific labeling agent

    SciTech Connect

    Ohmomo, Y.; Yokoyama, A.; Kawaii, K.; Horiuchi, K.; Saji, H.; Torizuka, K.

    1984-01-01

    In the search for a platelet specific labeling agent, Metaraminol (MA), which is a sympatomimetic amine used for the treatment of hypotension, cardiogenic shock and well recognized as a drug actively incorporated and accumulated in platelet, attracted the authors' attention. Using the classical chloramine-T iodination method, a high labeling efficiency near 98%, reaching a specific activity up to about 1000 Ci/mmole was obtained. Upon the harvest of platelet, only as platelet rich plasma (PRP), the labeling with this radiopharmaceutical was easily performed by incubation at 37/sup 0/C for 10 min. Labeling efficiency as high as 63.0 +- 3.1% at 24 x 10/sup 8/ cells/ml was obtained. In in-vitro studies, the unaltered state of I-125 MA labeled platelet, with their cellular functions fully retained was demonstrated. Pharmacological study indicated a specific incorporation of I-125 MA by active transport system similar to that of 5-HT, along with passive diffusion. Then the in-vivo study carried out in rabbits with induced thrombi on the femoral artery, showed rather rapid disappearance of the I-125 MA labeled autologous platelet radioactivity, from circulating blood reaching as high thrombus-to-blood activity ratio as 19.8+-4.3 within 30 min post-administration. This new platelet labeling agent, I-125 MA, has many advantages over the use of IN-111 oxine and holds considerable promise for thrombus imaging with single photon emission CT upon the availability of I-123 MA.

  20. Comparing different preparation methods to study human fibrin fibers and platelets using TEM.

    PubMed

    Buys, Antoinette V; Pretorius, Etheresia

    2012-06-01

    For the study of cellular ultrastructure, the sample needs to be stabilized by fixation, with the ultimate aim to preserve the native tissue organization and to protect the tissue against later stages of preparation. Chemical and freezing fixation are most used, and chemical fixation employs agents that permeate tissues and cells by diffusion and covalently bind with their major biochemical constituents to fix them. Most widely used chemical fixatives are aldehydes, e.g., formaldehyde and glutaraldehyde, which are noncoagulating, crosslinking agents. Cryofixation methods for ultrastructural studies are also popular, and high-pressure freezing immobilizes all cell constituents and arrests biological activity by removing the thermal energy from the system. In the current research, we used platelet-rich plasma (PRP) to study expansive fibrin fibers and platelet ultrastructure to compare the two fixation techniques. We also used thrombin and calcium chloride as a clotting agent to determine the technique most suitable for the formation of extensive fibrin networks. Chemically fixated fibrin fibers were more compact and condensed and also showed a banding pattern on longitudinal sections. High-pressure frozen samples were more dispersed while platelets fixated showed better preserved cellular membranes and organelle structure. PRP coagulated by addition of CaCl(2) showed blood platelets that are noticeably more activated compared with PRP; however, with thrombin, a sharp ultrastructure was seen. We conclude that PRP mixed with thrombin, and freeze substituted, is the most suitable method for the study of extensive fibrin fibers as well as platelets.

  1. A platelet alpha granule membrane protein that is associated with the plasma membrane after activation. Characterization and subcellular localization of platelet activation-dependent granule-external membrane protein.

    PubMed Central

    Berman, C L; Yeo, E L; Wencel-Drake, J D; Furie, B C; Ginsberg, M H; Furie, B

    1986-01-01

    We have identified and purified a platelet integral membrane protein (140,000 mol wt), using the KC4 monoclonal antibody specific for activated platelets, that is internal in resting platelets but exposed on activated platelets (Hsu-Lin S.-C., C.L. Berman, B.C. Furie, D. August, and B. Furie, 1984, J. Biol. Chem. 259: 9121-9126.). The expression of the protein on the platelet surface is secretion-dependent. This protein has been named platelet activation-dependent granule-external membrane (PADGEM) protein. PADGEM protein is distinct from the surface glycoproteins of resting platelets, but identical to the S12 antigen, GMP-140. Using immunofluorescent staining, resting platelets failed to stain for PADGEM protein with the KC4 antibody, but after permeabilization showed a punctate staining of the cell interior. Thrombin-stimulated intact platelets stained with a peripheral rim pattern thus demonstrating the translocation of PADGEM protein from an internal location to the cell surface. PADGEM protein expression on the platelet surface at varying thrombin concentrations correlated with alpha granule release, as measured by the secretion of platelet factor 4. Further evidence for an alpha granule localization of PADGEM protein was provided by nitrogen cavitation of resting platelets followed by metrizamide density gradient centrifugation; PADGEM protein codistributed with platelet factor 4. Using immunoelectron microscopy, the protein was localized to the alpha granule in frozen ultrathin sections of resting platelets labeled using rabbit anti-PADGEM protein antibodies, whereas in thrombin-activated platelets, the plasma membrane was labeled. These studies indicate that PADGEM protein is a component of the alpha granule membrane of resting platelets and is incorporated into the plasma membrane upon activation and secretion. Images PMID:2941452

  2. Inhibition of Platelet Aggregation by the Leaf Extract of Carica papaya During Dengue Infection: An In Vitro Study.

    PubMed

    Chinnappan, Shobia; Ramachandrappa, Vijayakumar Shettikothanuru; Tamilarasu, Kadhiravan; Krishnan, Uma Maheswari; Pillai, Agiesh Kumar Balakrishna; Rajendiran, Soundravally

    2016-04-01

    Dengue cases were reported to undergo platelet activation and thrombocytopenia by a poorly understood mechanism. Recent studies suggested that Carica papaya leaf extract could recover the platelet count in dengue cases. However, no studies have attempted to unravel the mechanism of the plant extract in platelet recovery. Since there are no available drugs to treat dengue and considering the significance of C. papaya in dengue treatment, the current study aimed to evaluate two research questions: First one is to study if the C. papaya leaf extract exerts its action directly on platelets and second one is to understand if the extract can specifically inhibit the platelet aggregation during dengue viral infection. Sixty subjects with dengue positive and 60 healthy subjects were recruited in the study. Platelet-rich plasma (PRP) and platelet-poor plasma were prepared from both the dengue-infected and healthy control blood samples. Effect of the leaf extract obtained from C. papaya leaves was assessed on plasma obtained as well as platelets collected from both healthy and dengue-infected individuals. Platelet aggregation was significantly reduced when leaf extract preincubated with dengue plasma was added into control PRP, whereas no change in aggregation when leaf extract incubated-control plasma was added into control PRP. Upon direct addition of C. papaya leaf extract, both dengue PRP and control PRP showed a significant reduction in platelet aggregation. Within the dengue group, PRP from severe and nonsevere cases showed a significant decrease in aggregation without any difference between them. From the study, it is evident that C. papaya leaf extract can directly act on platelet. The present study, the first of its kind, found that the leaf extract possesses a dengue-specific neutralizing effect on dengue viral-infected plasma that may exert a protective role on platelets.

  3. Primary arrest of circulating platelets on collagen involves phosphorylation of Syk, cortactin and focal adhesion kinase: studies under flow conditions.

    PubMed Central

    Arderiu, Gemma; Díaz-Ricart, Maribel; Buckley, Byron; Escolar, Ginés; Ordinas, Antonio

    2002-01-01

    After a vessel wall injury, platelets adhere to the subendothelium following a sequence of events: arrest of single platelets on the surface, progression to platelet spreading and final aggregation. Primary arrest of circulating platelets on subendothelial components occurs through platelet glycoprotein (GP) Ib and collagen receptors; then platelets spread and aggregate through a GPIIb-IIIa-dependent mechanism. A series of strategies were applied to analyse the tyrosine-phosphorylation mechanisms occurring at the different stages of platelet adhesion on subendothelial components under flow conditions, with special attention to primary arrest. To evaluate spread platelets, samples were exposed to acetylsalicylic acid, which blocks aggregate formation. To study single platelets in contact, a monoclonal antibody specific for GPIIb-IIIa was used to prevent platelet spreading and further aggregation. This experimental situation was also investigated using blood from two patients with Glanzmann's thrombasthenia (i.e. lacking GPIIb-IIIa). Results demonstrated that blockade of both spreading and aggregation results in significant changes in the tyrosine-phosphorylation patterns. Arrest of single platelets on collagen-rich surfaces resulted in phosphorylation of p125, identified as focal adhesion kinase (FAK), the 80/85 kDa doublet (cortactin), and p72, identified as Syk. Arrest of single platelets on von Willebrand factor as adhesive substrate showed that interaction through GPIb induces Syk phosphorylation, but not that of cortactin and FAK. Our data indicate that the initial arrest of platelets on subendothelial components involves Syk phosphorylation, which seems to be GPIb-dependent, and this is followed by activation and phosphorylation of cortactin and FAK. These processes seem to occur before GPIIb-IIIa becomes activated. PMID:11988077

  4. Radioimmune assay of human platelet prostaglandin synthetase

    SciTech Connect

    Roth, G.J.; Machuga, E.T.

    1982-02-01

    Normal platelet function depends, in part, on platelet PG synthesis. PG synthetase (cyclo-oxygenase) catalyzes the first step in PG synthesis, the formation of PGH/sub 2/ from arachidonic acid. Inhibition of the enzyme by ASA results in an abnormality in the platelet release reaction. Patients with pparent congenital abnormalities in the enzyme have been described, and the effects have been referred to as ''aspirin-like'' defects of the platelet function. These patients lack platelet PG synthetase activity, but the actual content of PG synthetase protein in these individuals' platelets is unknown. Therefore an RIA for human platelet PG synthetase would provide new information, useful in assessing the aspirin-like defects of platelet function. An RIA for human platelet PG synthetase is described. The assay utilizes a rabbit antibody directed against the enzyme and (/sup 125/I)-labelled sheep PG synthetase as antigen. The human platelet enzyme is assayed by its ability to inhibit precipitation of the (/sup 125/I)antigen. The assay is sensitive to 1 ng of enzyme. By the immune assay, human platelets contain approximately 1200 ng of PG synethetase protein per 1.5 mg of platelet protein (approximately 10/sup 9/ platelets). This content corresponds to 10,000 enzyme molecules per platelet. The assay provides a rapid and convenient assay for the human platelet enzyme, and it can be applied to the assessment of patients with apparent platelet PG synthetase (cyclo-oxygenase) deficiency.

  5. GNAS defects identified by stimulatory G protein alpha-subunit signalling studies in platelets.

    PubMed

    Freson, Kathleen; Izzi, Benedetta; Labarque, Veerle; Van Helvoirt, Monique; Thys, Chantal; Wittevrongel, Christine; Bex, Marie; Bouillon, Roger; Godefroid, Nathalie; Proesmans, Willem; de Zegher, Francis; Jaeken, Jaak; Van Geet, Chris

    2008-12-01

    GNAS is an imprinted region that gives rise to several transcripts, antisense transcripts, and noncoding RNAs, including transcription of RNA encoding the alpha-subunit of the stimulatory G protein (Gsalpha). The complexity of the GNAS cluster results in ubiquitous genomic imprints, tissue-specific Gsalpha expression, and multiple genotype-phenotype relationships. Phenotypes resulting from genetic and epigenetic abnormalities of the GNAS region include Albright's hereditary osteodystrophy, pseudohypoparathyroidism types Ia (PHPIa) and Ib (PHPIb), and pseudopseudohypoparathyroidism (PPHP). The aim was to study the complex GNAS pathology by a functional test as an alternative to the generally used but labor-intensive erythrocyte complementation assay. We report the first platelet-based diagnostic test for Gsalpha hypofunction, supported by clinical, biochemical, and molecular data for six patients with PHPIa or PPHP and nine patients with PHPIb. The platelet test is based on the inhibition of platelet aggregation by cAMP, produced after Gsalpha stimulation. Platelets are easily accessible, and platelet aggregation responses were found to reflect Gsalpha signaling defects in patients, in concordance with the patient's phenotype and genotype. Gsalpha hypofunction in PHPIa and PPHP patients with GNAS mutations was clearly detected by this method. Mildly decreased or normal Gsalpha function was detected in patients with PHPIb with either an overall or exon 1A-only epigenetic defect, respectively. Platelet Gsalpha expression was reduced in both PHPIb patient groups, whereas XLalphas was up-regulated only in PHPIb patients with the broad epigenetic defect. The platelet-based test is a novel tool for establishing the diagnosis of Gsalpha defects, which may otherwise be quite challenging.

  6. A study of platelets in the armadillo chaetophractus villosus (xenarthra, dasypodidae).

    PubMed

    Bermúdez, Paula Mariela; Polini, Nélida Nora; Casanave, Emma Beatriz

    2004-08-01

    Nothing is known about haemostasis in Xenarthra, a widely distributed Order of American mammalians. Chaetophractus villosus, a member of the Dasypodidae family of this group, which is easily adapted to captivity, is of growing interest for biomedical research. In this work, we studied platelet number, MPV, ultrastructure of the platelets by SEM and TEM, and aggregation responses to ADP and ristocetin in this species. Blood samples were obtained by cardiac puncture in 20 anaesthetised animals. Platelet count and MPV were evaluated at the beginning and at the end of a 3-year experimental period, to detect possible variations related to time of captivity. SEM and TEM were done by routine methods adapted to the material, and aggregation response to ADP and ristocetin were evaluated by the Born method. The parameters studied did not show any sex-related differences, nor did the platelet count change during captivity. Nevertheless, MPV decreased during this period. Platelets were ultrastructurally similar to those of other mammals and human beings and responded to proven agonists. Data provided in this study will contribute to the understanding of the haemostatic process in this species.

  7. The use of indium-111 oxine platelet scintigraphy and survival studies in pediatric patients with thrombocytopenia

    SciTech Connect

    Castle, V.P.; Shulkin, B.L.; Coates, G.; Andrew, M. )

    1989-11-01

    We have utilized {sup 111}In-labeled heterologous platelets to investigate the mechanism of thrombocytopenia in ten children. From the scintigraphic findings, platelet survival times, and clinical information, thrombocytopenia was ascribed to decreased production or to increased destruction. Two patients were found to have bone marrow production defects. Two patients with hemangiomas were studied. In one, the hemangioma was shown not to be the cause of thrombocytopenia. In the second, the hemangioma was proven the source of platelet destruction, but was much more extensive than clinically evident. In both, surgical manipulation of the hemangioma was avoided. Six additional patients had thrombocytopenia due to accelerated destruction. In four, the spleen was shown responsible. In two, however, the spleen was shown not to be responsible for the low platelet counts, and splenectomy was avoided. Thus, {sup 111}In-platelet scintigraphy and survival studies are valuable in the classification and management of childhood thrombocytopenia. We believe that this study should be performed, when possible, in any child with thrombocytopenia where the mechanism is unclear or the therapeutic intervention involves splenectomy or resection of a hemangioma.

  8. Immunoreactions involving platelets. III. Quantitative aspects of platelet agglutination, inhibition of clot retraction, and other reactions caused by the antibody of quinidine purpura.

    PubMed

    SHULMAN, N R

    1958-05-01

    Quantitative aspects of platelet agglutination and inhibition of clot retraction by the antibody of quinidine purpura were described. The reactions appeared to depend on formation of types of antibody-quinidine-platelet complexes which could fix complement but complement was not necessary for these reactions. Complement fixation was at least 10 times more sensitive than platelet agglutination or inhibition of clot retraction for measurement and detection of antibody activity. Although it has been considered that antibodies of drug purpura act as platelet lysins in the presence of complement and that direct lysis of platelets accounts for development of thrombocytopenia in drug purpura, the present study suggests that attachment of antibody produces a change in platelets which is manifested in vitro only by increased susceptibility to non-specific factors which can alter the stability of platelets in the absence of antibody. The attachment of antibody to platelets in vivo may only indirectly affect platelet survival. In contrast to human platelets, dog, rabbit, and guinea pig platelets, and normal or trypsin-treated human red cells did not agglutinate, fix complement, or adsorb antibody; and intact human endothelial cells did not fix complement or adsorb antibody. Rhesus monkey platelets were not agglutinated by the antibody but did adsorb antibody and fix complement although their activity in these reactions differed quantitatively from that of human platelets. Cinchonine could be substituted for quinidine in agglutination and inhibition of clot retraction reactions but quinine and cinchonidine could not. Attempts to cause passive anaphylaxis in guinea pigs with the antibody of quinidine purpura were not successful.

  9. PATCH: platelet transfusion in cerebral haemorrhage: study protocol for a multicentre, randomised, controlled trial.

    PubMed

    de Gans, Koen; de Haan, Rob J; Majoie, Charles B; Koopman, Maria M; Brand, Anneke; Dijkgraaf, Marcel G; Vermeulen, Marinus; Roos, Yvo B

    2010-03-18

    Patients suffering from intracerebral haemorrhage have a poor prognosis, especially if they are using antiplatelet therapy. Currently, no effective acute treatment option for intracerebral haemorrhage exists. Limiting the early growth of intracerebral haemorrhage volume which continues the first hours after admission seems a promising strategy. Because intracerebral haemorrhage patients who are on antiplatelet therapy have been shown to be particularly at risk of early haematoma growth, platelet transfusion may have a beneficial effect. The primary objective is to investigate whether platelet transfusion improves outcome in intracerebral haemorrhage patients who are on antiplatelet treatment. The PATCH study is a prospective, randomised, multi-centre study with open treatment and blind endpoint evaluation. Patients will be randomised to receive platelet transfusion within six hours or standard care. The primary endpoint is functional health after three months. The main secondary endpoints are safety of platelet transfusion and the occurrence of haematoma growth. To detect an absolute poor outcome reduction of 20%, a total of 190 patients will be included. To our knowledge this is the first randomised controlled trial of platelet transfusion for an acute haemorrhagic disease.

  10. Distinguishing postganglionic from preganglionic lesions. Studies in rabbits with surgically produced Horner's syndrome.

    PubMed

    Skarf, B; Czarnecki, J S

    1982-08-01

    It has been suggested that the pupillary response to hydroxyamphetamine hydrobromide eyedrops will separate distal from proximal lesions of the sympathetic pathway from the brain to the eye (the pupil fails to dilate in postganglionic lesions). We studied the pupillary response to hydroxyamphetamine in two groups of rabbits with surgically produced Horner's syndrome. Rabbits in one group had postganglionic lesions. In all animals, a miotic pupil developed ipsilateral to the surgical lesion, and oculosympathetic paresis was confirmed in each by testing pupillary response to topically applied cocaine. In rabbits with postganglionic lesions, hydroxyamphetamine failed to dilate the miotic (Horner's) pupils as well as it dilated the normal pupils, while in rabbits with preganglionic lesions both miotic and normal pupils dilated equally. Hydroxyamphetamine appears to be a diagnostically useful drug in Horner's syndrome.

  11. Physical inactivity and platelet function in humans and brown bears: A comparative study.

    PubMed

    Arinell, K; Blanc, S; Welinder, K G; Støen, O-G; Evans, A L; Fröbert, O

    2017-07-31

    Physical inactivity increases the risk of thromboembolism. However, good standardized human models on inactivity are in short supply and experimental models are few. Our objective was to investigate how standardized bed rest affects platelet aggregation in humans and to investigate if aggregation is altered in a translational model system - the hibernating brown bear (Ursus arctos). We collected blood from (1) healthy male volunteers participating in a 21-day bed rest study in head-down tilt position (-6°) 24 h a day; (2) free-ranging brown bears captured during winter hibernation and again during active state in summer. We analyzed platelet function using multiple electrode platelet aggregometry. In total, 9 healthy male volunteers (age 31.0 ± 6.4 years) and 13 brown bears (7 females and 6 males, age 2.8 ± 0.6 years) were included. In hibernating bears adenosine diphosphate, arachidonic acid, thrombin receptor activating peptide, and collagen impedance aggregometry tests were all halved compared to summer active state. In human volunteers no statistically significant changes were found between baseline and the end of bed rest. In human male volunteers 3 weeks of bed rest did not affect platelet function. In hibernating brown bears platelet aggregation was halved compared to summer and we hypothesize that this is a protective measure to avoid formation of thrombi under periods of low blood flow.

  12. Surface wettability and platelet adhesion studies on Langmuir Blodgett films

    NASA Astrophysics Data System (ADS)

    Lee, Yuh-Lang; Chen, Chi-Yun

    2003-02-01

    Because Langmuir-Blodgett (LB) deposition technique is known to be capable of preparing highly ordered monomolecular films with densely packed structure, LB technique is used to prepare films of DPPC, DMPC, cholesterol, octadecylamine (ODA), and stearic acid, with thickness of one molecular layer. The film surfaces were characterized by dynamic contact angle measurement and the interaction between blood and these materials were investigated. The properties of LB films were also compared with the results obtained on continuous films prepared by solution dipping. The results show that the contact angles of water on LB films of the five compounds decreases as the following order: ODA> DMPC≈ DPPC> stearic acid > cholesterol. The hydrophobic property reflects the highest organization of ODA molecules on the substrate, which is related to its interaction between the molecule and substrate. The advancing contact angle of ODA is equivalent to that of a methyl-terminated SAM, but its receding contact angle is smaller which implies the exposing of hydrophilic pole or glass substrate on LB film. The irregular orientation of molecules on LB film increases with decreasing of contact angle and is especially significant on LB film of cholesterol which has highest hydrophilic property. The plate adhesion experiments on the continuous films show that the hemocompatibility of the five materials decreases as the order: DPPC≈ DMPC> ODA> cholesterol> stearic acid ≈ glass. This result implies that the lipid has highest blood compatibility, and then -NH 2, and then -OH functionality. On the contrary, the glass surface, -COOH and -CH 3 functionalities have high reactivity to platelet. Due to the possibility of glass exposure on LB films, as estimated from the surface wettability, the LB films have higher platelet reactivity, especially for the cholesterol, compared with the continuous films. Because the interaction of the LB film to the substrate is physical force, the deposited

  13. Experimental study and micromechanical modeling of MMT platelet-reinforced PP nanocomposites

    NASA Astrophysics Data System (ADS)

    Cauvin, Ludovic; Bhatnagar, Naresh; Brieu, Mathias; Kondo, Djimédo

    2007-11-01

    Nanocomposites with platelets reinforcements are emerging materials with strong potential for future engineering applications. The present study is a first step to characterize and predict the elastic behavior of Montmorillonite (MMT) clay reinforced Polypropylene (PP) nanocomposites. The pellets of nanoclay composites were made by first uniformly mixing the MMT platelets in a twin-screw extruder by the melt intercalation route. These pellets were then converted into tensile specimens as per ASTM 638 by injection molding process. From tensile tests it is shown that there is a significant increase of the Young modulus with the mass fraction (2-7%) of clay platelets. A first approach of homogenization allows to conclude that the Ponte Castañeda and Willis (1995) bound predicts the measured moduli provided that a suitable aspect ratio of the reinforcement is considered. To cite this article: L. Cauvin et al., C. R. Mecanique 335 (2007).

  14. Study on the relationship between mean platelet volume and platelet distribution width with coronary artery lesion in children with Kawasaki disease.

    PubMed

    Liu, Ruixi; Gao, Fang; Huo, Junming; Yi, Qijian

    2012-01-01

    Mean platelet volume (MPV) and platelet distribution width (PDW) are correlated with platelet function and may be a more sensitive index than platelet number as a marker of clinical interest in various disorders. Therefore, this study was designed to answer the following questions: do MPV and PDW levels change in Kawasaki disease (KD), is there any relation between CAL in children with MPV and PDW and whether MPV and PDW might support a diagnosis of incomplete KD. A total of 309 KD patients and 160 sex-age matched healthy subjects were enrolled into the study. For all subjects following tests were performed: MPV, PDW, platelet count, white blood cells counts (WBC), C reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Patients with CALs were assigned to three groups depending on the extent of CALs which were visualized by echocardiography: dilatation and/or ectasia, aneurysm and giant aneurysms. We compared patients with fever and four or five of the principal criteria (complete KD, cKD) to the other patients (iKD). Compared with healthy controls a significant decrease in MPV and PDW (p < 0.001 and p < 0.05, respectively) and increase in WBC, platelet count, CRP and ESR (p all < 0.001) was noted in children with KD. There were no statistically differences in MPV and PDW between KD with CALs and KD without CALs (p > 0.05). However, MPV and PDW were significantly lower in patients with iKD than in group with cKD (p = 0.003, p = 0.014, respectively). It was first shown that patients with KD have lower MPV and PDW than control subjects. The diagnosis of iKD is challenging but can be supported by the presence of lower MPV and PDW.

  15. Histopathological Studies on Rabbits Infected by Bacteria Causing Infectious Keratitis in Human through Eye Inoculation

    PubMed Central

    Aldebasi, Yousef H.; Mohamed, Hala A.; Aly, Salah M.

    2014-01-01

    Aim This study aimed to investigate the pathogenic effect of bacteria causing infectious keratitis among patients through experimental study conducted on rabbits’ eyes with the aid of histopathology as eye infection is a common disease in developing countries that may complicate to loss of vision. Methodology 100 swab samples were collected from human infected eyes, at Qassim region during 2012, for the isolation of Pseudomonas aeruginosa and Staphylococcus aureus. The isolated pathogenic bacteria were tested to various antibiotics using some selected antibiotics discs through agar-well diffusion method. Then, experimental study conducted on 27 rabbits. The rabbits were divided randomly into three equal groups, each containing 9 rabbits. Rabbits of group (1) served as control group (Negative Control) and their eyes were inoculated with the buffer only. Rabbits of group (2) were inoculated through eyes with the isolated Pseudomonas aeruginosa. Rabbits of group (3) were inoculated through eyes with the isolated Staphylococcus aureus. Results Out of 100 collected swab samples from human infected eyes, Pseudomonas aeruginosa and Staphylococcus aureus were isolated with a total percentage of 25.21% and 15.65%; respectively and used in this study. Both bacterial isolates were sensitive to Gentamicin and Cefuroxime. Clinically, experimentally infected rabbits by Pseudomonas aeruginosa, revealed varying degree corneal abrasions, corneal abscess and dense corneal opacity. Histopathologically, at 3rd day post-infection (PI), the cornea revealed polymorpho-nuclear cells infiltration with loss of the outer epithelial lining. At 7th day PI, neutrophils were seen in the stroma. At 15th day PI, proliferation of fibroblasts and new vascularisation were seen in the stroma. Clinically, rabbits experimentally infected with Staphylococcus aureus, revealed corneal ulcers and focal abscesses. Histopathologically, at 3rd and 7th day PI, the cornea revealed edema and infiltration of

  16. Clopidogrel pretreatment of patients with ST-elevation myocardial infarction does not affect platelet reactivity after subsequent prasugrel-loading: platelet reactivity in an observational study.

    PubMed

    Nührenberg, Thomas G; Trenk, Dietmar; Leggewie, Stefan; Ristau, Inga; Amann, Michael; Stratz, Christian; Hochholzer, Willibald; Valina, Christian M; Neumann, Franz-Josef

    2013-01-01

    Current guidelines recommend prasugrel or ticagrelor for patients undergoing percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI). Whereas available data support ticagrelor independent of pretreatment with clopidogrel, corresponding data for prasugrel are missing. Here, we investigated platelet reactivity after loading with prasugrel in clopidogrel-naïve vs. clopidogrel-pretreated patients. Forty-seven consecutive patients with STEMI referred for primary PCI were enrolled. Use of GPIIb/IIIa inhibitors and known contraindications to prasugrel served as exclusion criteria. A total of 31 patients were already treated with a loading dose of clopidogrel 600 mg by the emergency medical system before admission, while 16 patients were P2Y12 antagonist naïve. All patients received a loading dose of prasugrel 60 mg immediately before PCI. Adenosine diphosphate (ADP) induced platelet reactivity was determined by VerifyNow™ P2Y12 assay, by light transmission aggregometry (LTA) and by multiple electrode impedance aggregometry (MEIA; Multiplate™ analyser). No differences in platelet reactivity were observed at day 1 after PCI between the bolus-on-bolus treatment regimen and single prasugrel loading. Platelet reactivity was profoundly decreased to 10 [8-31] platelet reactivity unit (PRU; median [interquartile range]) in patients on clopidogrel + prasugrel vs. 9 [6-60] PRU in patients on prasugrel only (p = 0.916). Consistent results were obtained by LTA and MEIA. The proportion of patients reaching a MEIA associated with increased risk bleeding (<188 AU*min) was also similar between the two study groups. The level of platelet reactivity at day 1 after the 60 mg loading dose of prasugrel was independent of pretreatment with clopidogrel. Our results do not support withholding prasugrel in patients pretreated with clopidogrel who undergo PCI for STEMI.

  17. Regulation of platelet activating factor receptor coupled phosphoinositide-specific phospholipase C activity

    SciTech Connect

    Morrison, W.J.

    1988-01-01

    The major objectives of this study were two-fold. The first was to establish whether binding of platelet activating factor (PAF) to its receptor was integral to the stimulation of polyphosphoinositide-specific phospholipase C (PLC) in rabbit platelets. The second was to determine regulatory features of this receptor-coupled mechanism. ({sup 3}H)PAF binding demonstrated two binding sites, a high affinity site with a inhibitory constant (Ki) of 2.65 nM and a low affinity site with a Ki of 0.80 {mu}M. PAF receptor coupled activation of phosphoinositide-specific PLC was studied in platelets which were made refractory, by short term pretreatments, to either PAF or thrombin. Saponin-permeabilized rabbit platelets continue to regulate the mechanism(s) coupling PAF receptors to PLC stimulation. However, TRP{gamma}S and GDP{beta}S, which affect guanine nucleotide regulatory protein functions, were unable to modulate the PLC activity to any appreciable extent as compared to PAF. The possible involvement of protein kinase C (PKC) activation in regulating PAF-stimulated PLC activity was studied in rabbit platelets pretreated with staurosporine followed by pretreatments with PAF or phorbol 12-myristate 13-acetate (PMA).

  18. Developmental Toxicity Studies with Atrazine and its Major Metabolites in Rats and Rabbits

    PubMed Central

    Scialli, Anthony R; DeSesso, John M; Breckenridge, Charles B

    2014-01-01

    Atrazine (ATR), hydroxyatrazine (OH-ATR), and the three chloro metabolites of ATR (deethylatrazine [DEA], deisopropylatrazine [DIA], diaminochlorotriazine [DACT]) were evaluated for developmental effects in rats and rabbits. Three developmental toxicity studies were conducted on ATR in rats (two studies) and rabbits and a developmental toxicity study was conducted in rats for each of the four ATR metabolites DEA, DIA, DACT, and OH-ATZ. ATR administration by gavage to pregnant rats and rabbits from implantation (gestation day [GD] 6 in rat, GD 7 in rabbit) through closure of the palate (GD 15 in rat and GD 19 in rabbit) did not statistically significantly alter the incidence of developmental abnormalities or malformations at dose levels up to 100 (rat) or 75 (rabbit) mg/kg bw/day. There were no effects on developmental toxicity parameters for DEA, DIA, DACT, or OH-ATR at oral dose levels up to 100, 100, 150, or 125 mg/kg bw/day, respectively, with the exception of reductions in fetal body weight by DACT and OH-ATR in the presence of decreased maternal body weight gain. ATR did not adversely affect developmental end points in a two-generation study conducted in rats exposed to dose levels up to 500 ppm (38.7 mg/kg/day) in the diet. The 500-ppm dose level resulted in significantly reduced maternal body weight gain. Overall, data show that neither ATR nor its metabolites statistically significantly affected rat or rabbit embryo-fetal development even at dose levels producing maternal toxicity. PMID:24797531

  19. Effect of levofloxacin on lithium - a pharmacokinetic study in rabbits.

    PubMed

    Rajagopalan, Sujit; Shafiq, Nusrat; Pandhi, Promila; Malhotra, Samir

    2013-04-01

    The aim of this study was to evaluate potential drug-drug interaction between lithium and levofloxacin. The study was conducted on New Zealand white rabbits with three groups having two subgroups each (n = 12). The first group compared the pharmacokinetic (Pk) parameters of lithium when lithium was given as a single dose (56 mg/kg) and when lithium was co-administered with levofloxacin (35 mg/kg). The second group compared the Pk parameters of lithium when lithium was given for 6 days alone and when levofloxacin was given on the sixth day after lithium steady-state levels were achieved. The third group compared the Pk parameters of lithium when lithium was given alone for 8 days and levofloxacin was given on days 6, 7, and 8 along with lithium. Apart from this, creatinine levels were also measured to detect nephrotoxicity effects because of this co-administration. It was found that there was increase in lithium levels in all three groups. The increase was significant when a single dose of levofloxacin was administered with steady-state level of lithium (C(max) of lithium: 2.54 ± 0.15 vs 2.79 ± 0.12 mm, P < 0.001 and AUC(0-α) of lithium: 24.36 ± 3.68 vs 31.88 ± 4.83 mmol/mL h, P < 0.001). The increase in lithium levels was also significant when levofloxacin was coprescribed for 3 days after lithium steady-state levels were achieved (C(max) increased from 2.72 ± 0.29 to 3.96 ± 0.29 mm, P < 0.001 and AUC(0-α) increased from 27.1 ± 4.96 to 42.64 ± 4.94 mmol/mL h). Levofloxacin increases lithium levels when they are co-administered, and this interaction might be clinically significant as they may be coprescribed.

  20. Hydroxyethyl starch increases patency and reduces thrombus formation following arteriotomy/intimectomy in small arteries: An experimental study in the rabbit

    SciTech Connect

    Wieslander, J.B.; Salemark, L.; Dougan, P. )

    1990-10-01

    Twenty-four arteries of rabbit ears, divided into two groups of 12 vessels each, were prepared and {sup 32}P-labelled platelets were infused. Arteriotomy/intimectomy was performed after 1 hr and in vivo platelet accumulation recorded for 2 hr. Group A comprised untreated control animals and group B was treated with 1 g hydroxyethyl starch (HES), MW 450,000 in 17 ml saline/kg b.w. (Plasma-steril). Vessel bleeding-times were normal, patency was improved, and intraluminal thrombotic material was reduced after HES treatment. Initial in vivo platelet accumulation was rapid and reached similar levels in both groups. However, the platelet accumulation curves decreased more frequently following HES than in the control group. HES does not prevent platelet accumulation at trauma sites, but reduces the sizes of the thrombi formed and may enhance disaggregation/fibrinolysis.

  1. MRI study of atherosclerotic plaque progression using ultrasmall superparamagnetic iron oxide in Watanabe heritable hyperlipidemic rabbits.

    PubMed

    Kaneko, C; Nitta, N; Tsuchiya, K; Watanabe, S; Nitta-Seko, A; Ohta, S; Otani, H; Sonoda, A; Murata, K; Shiomi, M

    2015-09-01

    The purpose of this study was to evaluate plaque progression by using MRI with ultrasmall superparamagnetic iron oxide (USPIO) and by histopathological studies. We divided 12 Watanabe heritable hyperlipidemic (WHHL) rabbits into 4 groups based on their age (3, 9, 14 and 26 months) and injected them intravenously with 0.8 mmol (Fe) kg(-1) of USPIO (size, 32 nm; concentration, 15 mg dl(-1)). On the fifth post-injection day, they were again given an intravenous injection with 40 μmol kg(-1) of the same USPIO, and MR angiography (MRA) was performed. The signal-to-noise ratio (SNR) in regions of interest in the wall of the upper abdominal aorta was calculated on coronal images. Specimens from the same level of the aorta were subjected to iron staining and RAM-11 immunostaining and used for histopathological study. For statistical analysis of the MRA and histopathological findings, we used analysis of variance [Tukey's honest significant difference (HSD) test]. In 9-month-old rabbits, the SNR was significantly lower than in rabbits of the other ages (p < 0.01), and the area of RAM-11 (DAKO Corporation, Glostrup, Denmark) and iron uptake in the aortic wall was significantly larger (RAM-11, p < 0.01; iron, p < 0.05). These areas were the smallest in 3-month-old rabbits. Histopathologically, the number of macrophages was the greatest in 9-month-old rabbits. Our findings indicate that the SNR on MRI scans reflects the number of macrophages in the aortic wall of WHHL rabbits. USPIO-enhanced MRI visualized the accumulation of macrophages in early atherosclerotic plaques of WHHL rabbits in the course of natural progression.

  2. Releasing growth factors from activated human platelets after chitosan stimulation: a possible bio-material for platelet-rich plasma preparation.

    PubMed

    Shen, E-Chin; Chou, Tz-Chong; Gau, Ching-Hwa; Tu, Hsiao-Pei; Chen, Yen-Teen; Fu, Earl

    2006-10-01

    Thrombin is commonly used for activating the platelets and releasing the growth factors on the application of platelet-rich plasma (PRP). We have previously reported that chitosan can enhance rabbit platelet aggregation. In this study, the effects of chitosan on the subsequent growth factors release after human platelets activation were examined to evaluate the possibility of chitosan being used as a substitute for thrombin during PRP preparation. Human platelet activation was determined by aggregation, adhesion and alpha-granule membrane glycoprotein expression. Platelet aggregation was measured by the turbidimetric method, the adhesion was directly examined on chitosan-coated glass plates under light microscope and scanning electron microscope (SEM), and the alpha-granule membrane glycoprotein was detected by fluorescent isothiocyanate (FITC)-conjugated anti-CD61 antibody through flow cytometry. The subsequent epidermal growth factor (EGF), platelet-derived growth factor (PDGF)-AB and transforming growth factor (TGF)-beta1 release from platelets were assayed by ELISA after mixing with chitosan. The enhancing effects on the platelet adhesion and the aggregation from chitosan were observed. Under both microscopes, the adhesive platelets on the chitosan-coated plates were not only greater in number but also earlier in activation than those on the control plates. With flow cytometry, increased glycoprotein IIIa expression in platelets was detected after chitosan treatment. Greater concentrations of growth factors were measured from PRP after chitosan treatment than after the solvent treatment. Because of the observations of growth factors releasing from activated human platelets after chitosan stimulation, we suggest that chitosan may be an appropriate substitute for thrombin in PRP preparation.

  3. Viral infections of rabbits.

    PubMed

    Kerr, Peter J; Donnelly, Thomas M

    2013-05-01

    Viral diseases of rabbits have been used historically to study oncogenesis (e.g. rabbit fibroma virus, cottontail rabbit papillomavirus) and biologically to control feral rabbit populations (e.g. myxoma virus). However, clinicians seeing pet rabbits in North America infrequently encounter viral diseases although myxomatosis may be seen occasionally. The situation is different in Europe and Australia, where myxomatosis and rabbit hemorrhagic disease are endemic. Advances in epidemiology and virology have led to detection of other lapine viruses that are now recognized as agents of emerging infectious diseases. Rabbit caliciviruses, related to rabbit hemorrhagic disease, are generally avirulent, but lethal variants are being identified in Europe and North America. Enteric viruses including lapine rotavirus, rabbit enteric coronavirus and rabbit astrovirus are being acknowledged as contributors to the multifactorial enteritis complex of juvenile rabbits. Three avirulent leporid herpesviruses are found in domestic rabbits. A fourth highly pathogenic virus designated leporid herpesvirus 4 has been described in Canada and Alaska. This review considers viruses affecting rabbits by their clinical significance. Viruses of major and minor clinical significance are described, and viruses of laboratory significance are mentioned. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Treatment of rabbit cheyletiellosis with selamectin or ivermectin: a retrospective case study

    PubMed Central

    Mellgren, Marianne; Bergvall, Kerstin

    2008-01-01

    Background A retrospective study of rabbits treated against cheyletiellosis was performed to evaluate the efficacy and safety of selamectin or ivermectin in clinical practice. Methods Medical records from 53 rabbits with microscopically confirmed Cheyletiella infestation were collected from two small animal clinics. The rabbits were divided into three groups, based on treatment protocols. Group 1 included 11 rabbits treated with ivermectin injections at 200–476 μg kg-1 subcutaneously 2–3 times, with a mean interval of 11 days. In Group 2, 27 rabbits were treated with a combination of subcutaneous ivermectin injections (range 618–2185 μgkg-1) and oral ivermectin (range 616–2732 μgkg-1) administered by the owners, 3–6 times at 10 days interval. The last group (Group 3) included 15 rabbits treated with selamectin spot-on applications of 6.2–20,0 mgkg-1, 1–3 times with an interval of 2–4 weeks. Follow-up time was 4 months–4.5 years. Results Rabbits in remission were 9/11 (81,8%), 14/27 (51,9%) and 12/15 (80,8%) in groups 1, 2 and 3, respectively. Conclusion All treatment protocols seemed to be sufficiently effective and safe for practice use. Though very high doses were used in Group 2 (ivermectin injections followed by oral administration), the protocol seemed less efficacious compared to ivermectin injections (Group 1) and selamectin spot on (Group 3), respectively, although not statistically significant. Controlled prospective studies including larger groups are needed to further evaluate efficacy of the treatment protocols. PMID:18171479

  5. Licochalcones extracted from Glycyrrhiza inflata inhibit platelet aggregation accompanied by inhibition of COX-1 activity.

    PubMed

    Okuda-Tanino, Asa; Sugawara, Daiki; Tashiro, Takumi; Iwashita, Masaya; Obara, Yutaro; Moriya, Takahiro; Tsushima, Chisato; Saigusa, Daisuke; Tomioka, Yoshihisa; Ishii, Kuniaki; Nakahata, Norimichi

    2017-01-01

    Licochalcones extracted from Glycyrrhiza inflata are known to have a variety of biological properties such as anti-inflammatory, anti-bacterial, and anti-tumor activities, but their action on platelet aggregation has not yet been reported. Therefore, in this study we investigated the effects of licochalcones on platelet aggregation. Collagen and U46619, a thromboxane A2 receptor agonist, caused rabbit platelet aggregation, which was reversed by pretreatment with licochalcones A, C and D in concentration-dependent manners. Among these compounds, licochalcone A caused the most potent inhibitory effect on collagen-induced platelet aggregation. However, the licochalcones showed marginal inhibitory effects on thrombin or ADP-induced platelet aggregation. In addition to rabbit platelets, licochalcone A attenuated collagen-induced aggregation in human platelets. Because licochalcone A also inhibited arachidonic acid-induced platelet aggregation and production of thromboxane A2 induced by collagen in intact platelets, we further examined the direct interaction of licochalcone A with cyclooxygenase (COX)-1. As expected, licochalcone A caused an inhibitory effect on both COX-1 and COX-2 in vitro. Regarding the effect of licochalcone A on COX-1 enzyme reaction kinetics, although licochalcone A showed a stronger inhibition of prostaglandin E2 synthesis induced by lower concentrations of arachidonic acid, Vmax values in the presence or absence of licochalcone A were comparable, suggesting that it competes with arachidonic acid at the same binding site on COX-1. These results suggest that licochalcones inhibit collagen-induced platelet aggregation accompanied by inhibition of COX-1 activity.

  6. Licochalcones extracted from Glycyrrhiza inflata inhibit platelet aggregation accompanied by inhibition of COX-1 activity

    PubMed Central

    Okuda-Tanino, Asa; Sugawara, Daiki; Tashiro, Takumi; Iwashita, Masaya; Obara, Yutaro; Moriya, Takahiro; Tsushima, Chisato; Saigusa, Daisuke; Tomioka, Yoshihisa; Ishii, Kuniaki; Nakahata, Norimichi

    2017-01-01

    Licochalcones extracted from Glycyrrhiza inflata are known to have a variety of biological properties such as anti-inflammatory, anti-bacterial, and anti-tumor activities, but their action on platelet aggregation has not yet been reported. Therefore, in this study we investigated the effects of licochalcones on platelet aggregation. Collagen and U46619, a thromboxane A2 receptor agonist, caused rabbit platelet aggregation, which was reversed by pretreatment with licochalcones A, C and D in concentration-dependent manners. Among these compounds, licochalcone A caused the most potent inhibitory effect on collagen-induced platelet aggregation. However, the licochalcones showed marginal inhibitory effects on thrombin or ADP-induced platelet aggregation. In addition to rabbit platelets, licochalcone A attenuated collagen-induced aggregation in human platelets. Because licochalcone A also inhibited arachidonic acid-induced platelet aggregation and production of thromboxane A2 induced by collagen in intact platelets, we further examined the direct interaction of licochalcone A with cyclooxygenase (COX)-1. As expected, licochalcone A caused an inhibitory effect on both COX-1 and COX-2 in vitro. Regarding the effect of licochalcone A on COX-1 enzyme reaction kinetics, although licochalcone A showed a stronger inhibition of prostaglandin E2 synthesis induced by lower concentrations of arachidonic acid, Vmax values in the presence or absence of licochalcone A were comparable, suggesting that it competes with arachidonic acid at the same binding site on COX-1. These results suggest that licochalcones inhibit collagen-induced platelet aggregation accompanied by inhibition of COX-1 activity. PMID:28282426

  7. Status of Neutrophils, Lymphocytes and Platelets in Patients with Recurrent Aphthous Stomatitis: A Retrospective Study

    PubMed Central

    Terzi, Suat; Dursun, Engin; Özgür, Abdulkadir; Yiğit, Enes; Özergin-Coşkun, Zerrin; Çelebi-Erdivanl, Özlem; Demirci, Münir; Çeliker, Metin

    2016-01-01

    Introduction: The aim of this study was to evaluate the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV) in patients with recurrent aphthous stomatitis (RAS). Materials and Methods: Eighty patients who were diagnosed with RAS between January 2014 and January 2016 were included in this study. Eighty age- and gender-matched healthy subjects were also enrolled as a control group. Neutrophil, lymphocyte, and platelet counts were compared between groups, in addition to NLR, PLR, and MPV values. Results: There was no significant difference in terms of lymphocyte count, platelet count, PLR, or MPV values between the two groups (P>0.05). However, white blood count, neutrophil count, and NLR were significantly higher in patients with RAS compared with the control group (P<0.05). Conclusion: The present study revealed an increased NLR among RAS patients compared with healthy controls. This suggests that development of RAS involves an inflammatory process. We believe that NLR could be used as a cheap and simple marker of inflammation. PMID:28008393

  8. Intrastromal Injection of China Painting Ink in Corneas of Male Rabbits: Clinical and Histological Study

    PubMed Central

    Alsmman Hassan, Alahmady Hamad; Abd Elhaliem Soliman, Nesreen Gamal-Eldeen

    2016-01-01

    Background. Many patients with corneal opacity or complicated cataract in blind eye ask for cosmoses. In this study we tried to investigate the staining of corneas of male rabbits by Rotring China painting ink and to study the histological changes. Method. 10 eyes of 10 male Baladi Egyptian rabbits were injected (0.1 mL) intrastromally in the cornea by the use of China painting ink (Rotring Tinta China) through insulin syringe (27-gauge needle) by single injection; clinical follow-up is for 6 months and lastly the rabbits were scarified and the stained eyes were enucleated for histological analysis. Results. Clinically the stain was stable in color and distribution in corneas with no major complications. Histological results of the stained rabbit corneas showed blackish pigmentation in the corneal stroma without any inflammatory cellular infiltration. Some fibroblast cells had pigment granules in their cytoplasm in the adjacent layers. Conclusion. Corneal staining by China painting ink is effective and safe in staining of male rabbits cornea; however further study in human corneas with longer follow-up period is advisable. PMID:27195146

  9. Quantitative study of starving platelets in a minimal medium: maintenance by acetate or plasma but not by glucose.

    PubMed

    Whisson, M E; Nakhoul, A; Howman, P; Niu, X; Guppy, M

    1993-06-01

    The requirement of donor platelets for fuels, plasma and calcium were studied using platelets washed, filtered to remove leucocytes and resuspended in a new glucose-free minimal platelet storage medium with low citrate (3 mmol/l), low buffer capacity and no calcium. This is the first study of platelets stored without plasma, glucose or calcium and it was shown that platelets continued to aggregate with collagen plus adrenaline for 48 h and showed only a 50% fall in 'swirl index', an objective morphology score, after 3 days, showing that by these criteria human platelets do not require glucose. Sodium acetate extended the storage time by between 2 and 4 days, depending on the index parameter. This is the first evidence showing that failure of platelets in these conditions is at least partly due to exhaustion of fuel, and the first evidence that acetate prolongs in vitro survival. As little as 10% low-glucose plasma extended the storage time, but it was no better than acetate. New observations using this system included a very rapid fall in pH during resuspension of the washed platelet pellet, a rising pH in the absence of added fuel and an increased pH with added acetate.

  10. Platelet dysfunction in cardiopulmonary bypass: an experimental comparative study between a centrifugal and a new pulsatile pump.

    PubMed

    Herreros, J; Berjano, E J; Más, P; Padrós, C; Sales-Nebot, L; Vlaanderen, W; Díaz, P; Páramo, J A; Rábago, G; Mercé, S

    2003-12-01

    The aim of this investigation was to study the effect of a new pulsatile pump for extracorporeal circulation (ECC) on platelet count and platelet function with respect to a Biomedicus centrifugal pump. Thirteen pigs, 8 in the pulsatile group (PG) and 5 in the centrifugal group (CG), underwent a partial extracorporeal circulation lasting 3 h. The animals were sacrificed 3 h post-ECC. The platelet study was both quantitative (platelet count) and qualitative (platelet function analysis) by assessing the closure time (CT) with a PFA-100 system. The decrease in platelet number from basal to 3 h post ECC was only significant in CG (p = 0.009). The platelet function was impaired in both groups, but the value of CT with col/ADP increased significantly only in CG (p < 0.001). The increase of CT with col/EPI was greater in CG (p = 0.07) than in PG (p = 0.2). The results indicated that the new pulsatile pump preserves platelets quantitatively and qualitatively well compared to a Biomedicus pump.

  11. Studies on the structural stability of rabbit prion probed by molecular dynamics simulations of its wild-type and mutants.

    PubMed

    Zhang, Jiapu

    2010-05-07

    Prion diseases are invariably fatal and highly infectious neurodegenerative diseases that affect humans and animals. Rabbits are the only mammalian species reported to be resistant to infection from prion diseases isolated from other species (Vorberg et al., 2003). Fortunately, the NMR structure of rabbit prion (124-228) (PDB entry 2FJ3), the NMR structure of rabbit prion protein mutation S173N (PDB entry 2JOH) and the NMR structure of rabbit prion protein mutation I214V (PDB entry 2JOM) were released recently. This paper studies these NMR structures by molecular dynamics simulations. Simulation results confirm the structural stability of wild-type rabbit prion, and show that the salt bridge between D177 and R163 greatly contributes to the structural stability of rabbit prion protein.

  12. Experiment studies of iodinated oil nanometer ferrofluid retention in rabbit liver.

    PubMed

    Zhang, X; Lin, R; Lin, Y; Wu, R H

    2005-01-01

    To study possibility for iodinated oil nanometer ferrofluid retention in rabbit liver. 131I- iodinated oil nanometer ferrofluid were injected into liver right lobe through portal vein in 5 rabbits... - calibrate meter showed continuous.. counts in the region injected. Then the relative metabolic parameters were calculated. Left lobe livers, right lobe livers and lungs of the rabbits were examined in pathology, and the right lobe livers were examined by electron microscope. Five rabbits injected purely 131Iiodinated oil were designated as control group. Single metabolic mode was found in the rabbits in nanometer ferrofluid group. The biological half-life of 131I- iodinated oil nanometer ferrofluid was not different from control group's slow metabolic portion. But control group's rapid metabolic portion were eliminated in a higher speed, range from 8% to 44%. More damage was found in nanometer ferrofluid group's right lobe livers. 131I- iodinated oil nanometer ferrofluid possess the opportunity of local retention in human body and further study is worthwhile.

  13. Platelet reactivity in thromboelastometry. Revision of the FIBTEM test: a basic study.

    PubMed

    Biolik, Grzegorz; Kokot, Michał; Sznapka, Mariola; Święszek, Agnieszka; Ziaja, Damian; Pawlicki, Krzysztof; Ziaja, Krzysztof

    2017-05-01

    This study aimed to investigate modifications to the FIBTEM test to better assess fibrinogen levels and the quality of fibrin polymerization in citrated blood using Multiplate impedance aggregometry to verify platelet inhibition. Blood samples from 26 healthy volunteers were subjected to thromboelastometry studies (EXTEM/FIBTEM tests) in accordance with the standard study protocol (cytochalasin D) and according to a modified protocol (synthetic IIbIIIa receptor antagonist vs. acetylsalicylic acid [ASA] + synthetic IIbIIIa receptor antagonist instead of cytochalasin D). Independent of thromboelastometry, Multiplate impedance aggregometry was used to assess the degree of restriction by the platelet blocked with the following treatments: (1) cytochalasin D, (2) synthetic IIbIIIa antagonist or (3) ASA + synthetic IIbIIIa antagonist to assess the aggregation response to activation with an agonist (ADP, collagen, thrombin receptor activating peptide-6 [TRAP-6], and arachidonic acid). Via aggregometry, cytochalasin D more weakly inhibited platelet aggregation than simultaneous administration of the -IIbIIIa receptor antagonist with ASA. However, total platelet aggregation inhibition was observed after simultaneous administration of cytochalasin D combined with a synthetic IIbIIIa receptor antagonist. In the thromboelastometry, a significant decrease of the A10, A20 and MCF parameters were observed in the EXTEM/FIBTEM tests after they were modified by the addition of a synthetic IIbIIIa receptor antagonist alone or in combination with ASA. In conclusion, in this Multiplate- and ROTEM-based laboratory approach, a two-way blockade (IIbIIIa-antagonist + cytochalasine D) was sufficient to completely inhibit procoagulant platelet function as observed by aggregometry and thromboelastometry.

  14. Abnormal VWF modifies megakaryocytopoiesis: studies of platelets and megakaryocyte cultures from patients with von Willebrand disease type 2B.

    PubMed

    Nurden, Paquita; Gobbi, Giuliana; Nurden, Alan; Enouf, Jocelyne; Youlyouz-Marfak, Ibtissam; Carubbi, Cecilia; La Marca, Silvia; Punzo, Margherita; Baronciani, Luciano; De Marco, Luigi; Vitale, Marco; Federici, Augusto B

    2010-04-01

    von Willebrand factor (VWF) is an essential mediator of platelet adhesion to the vessel wall, but little is known about its role in megakaryocytopoiesis. VWF and its platelet receptor, glycoprotein Ibalpha (GPIbalpha), are both expressed during megakaryocyte (MK) maturation. This study was designed to evaluate whether the enhanced VWF-GPIbalpha interactions typical of patients with von Willebrand disease type 2B (VWD2B) modify platelet production. Platelets from 9 patients with VWD2B with 7 different gain-of-function mutations were examined by electron microscopy (EM) and immunofluorescence labeling. For the patients with VWD2B, EM characteristically showed variable numbers of structurally abnormal giant platelets, sometimes in agglutinates. Cultures of MKs from controls performed with or without purified VWF confirmed a positive influence of VWF on platelet production with specific inhibition by an antibody blocking VWF binding to GPIbalpha. VWD2B MK cultures examined by EM showed a disorganized demarcation membrane system and abnormal granule distribution. They produced platelets with structural abnormalities typical of VWD2B. Confocal examination of MK revealed limited extension of pseudopods with few large proplatelets. These results confirm that megakaryocytopoiesis is modified by the enhanced VWF-GPIbalpha interactions. These data obtained for controls and patients with VWD2B suggest a novel regulatory role of VWF-GPIbalpha interactions in platelet production.

  15. Evolution of the degradation mechanism of pure zinc stent in the one-year study of rabbit abdominal aorta model.

    PubMed

    Yang, Hongtao; Wang, Cong; Liu, Chaoqiang; Chen, Houwen; Wu, Yifan; Han, Jintao; Jia, Zichang; Lin, Wenjiao; Zhang, Deyuan; Li, Wenting; Yuan, Wei; Guo, Hui; Li, Huafang; Yang, Guangxin; Kong, Deling; Zhu, Donghui; Takashima, Kazuki; Ruan, Liqun; Nie, Jianfeng; Li, Xuan; Zheng, Yufeng

    2017-11-01

    In the present study, pure zinc stents were implanted into the abdominal aorta of rabbits for 12 months. Multiscale analysis including micro-CT, scanning electron microscopy (SEM), scanning transmission electron microscopy (STEM) and histological stainings was performed to reveal the fundamental degradation mechanism of the pure zinc stent and its biocompatibility. The pure zinc stent was able to maintain mechanical integrity for 6 months and degraded 41.75 ± 29.72% of stent volume after 12 months implantation. No severe inflammation, platelet aggregation, thrombosis formation or obvious intimal hyperplasia was observed at all time points after implantation. The degradation of the zinc stent played a beneficial role in the artery remodeling and healing process. The evolution of the degradation mechanism of pure zinc stents with time was revealed as follows: Before endothelialization, dynamic blood flow dominated the degradation of pure zinc stent, creating a uniform corrosion mode; After endothelialization, the degradation of pure zinc stent depended on the diffusion of water molecules, hydrophilic solutes and ions which led to localized corrosion. Zinc phosphate generated in blood flow transformed into zinc oxide and small amounts of calcium phosphate during the conversion of degradation microenvironment. The favorable physiological degradation behavior makes zinc a promising candidate for future stent applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Significance of Platelet Volume Indices in STEMI Patients: A Case-Control Study

    PubMed Central

    Shetty, Ranjan; Marupuru, Srujitha; Yedavalli, Nishanth; Shetty, Kiran

    2017-01-01

    Introduction Platelets have been well known contributors in the pathogenesis of cardiovascular disorders such as atherosclerosis and its complications such as acute Myocardial Infarction (MI). Aim To study the changes in platelet volume indices and platelet count in ST-Elevated Myocardial Infarction (STEMI) and assess their usefulness in predicting coronary events. Materials and Methods A case-control observational study was carried out on 173 cases diagnosed with STEMI and 191 controls from January 2015 to December 2015, considering the inclusion and exclusion criteria. In total, 364 patients were included, 173 patients with STEMI, from those patients admitted to the intensive care unit and the emergency ward. In addition, 191 healthy non diabetic non hypertensive age-matched controls were enrolled. Results The mean age of cases was 59.4±11.9 years and of controls were 55.25±8.5 years. Males (74.6%) had higher incidence of STEMI then females (25.4%). The Mean Platelet Volume (MPV) was significantly higher in patients with STEMI (10.2±2.8) as compared to controls (8.5±6.9). The Platelet Distribution Width (PDW) was also significantly higher in cases compared to controls (p<0.05). According to Pearson correlation analysis, the positive relationship determined between MPV and Gensini score was statistically significant (p < 0.001, r = 0.132). Conclusion High MPV and PDW seem to be an independent risk factor for STEMI and correlated with the severity of the STEMI. They can be used as a simple, reliable, and economical method for predicting an impending acute coronary event. PMID:28571169

  17. Relationship between mean platelet volume and recurrent miscarriage: a preliminary study.

    PubMed

    Yilmaz, Mehmet; Delibas, Ilhan Bahri; Isaoglu, Unal; Ingec, Metin; Borekci, Bunyamin; Ulug, Pasa

    2015-10-12

    The aim of the study was to examine the relationship between mean platelet volume (MPV) and recurrent miscarriage in order to illuminate the etiopathogenesis of recurrent miscarriage. We retrospectively investigated the data of 120 patients with unexplained recurrent miscarriage (group 1), and compared them with the data of 120 match-paired patients in the control group (group 2). The definition of recurrent miscarriage was accepted as two or more failed clinical pregnancies which were documented by ultrasonography or histopathologic examination. All patients in the recurrent miscarriage group were evaluated with diagnostic tests for the etiology of recurrent miscarriage. Total blood count parameters, including hemoglobin, mean corpuscular volume, red cell distribution width, white blood cells, platelets, and mean platelet volume, were compared. The average patient age at the time of examination was 29.07 ±2.81 years in group I and 28.53 ±3.5 years in group II (p > 0.05). Mean body mass index (BMI) was similar between group 1 and group 2, 22.54 ±3.17 and 22.99 ±2.38, respectively (p > 0.05). Mean hemoglobin, mean corpuscular volume, red cell distribution width, and white blood cell and platelet levels were similar in both groups (p > 0.05). Mean platelet volume levels were significantly higher in group I (9.45 ±1.09 fl) than in group II (7.63 ±0.52 fl) (p = 0.001). Higher MPV values in the study group suggest and support the importance of thromboembolic events in the etiology of recurrent miscarriage.

  18. Relationship between mean platelet volume and recurrent miscarriage: a preliminary study

    PubMed Central

    Delibas, Ilhan Bahri; Isaoglu, Unal; Ingec, Metin; Borekci, Bunyamin; Ulug, Pasa

    2015-01-01

    Introduction The aim of the study was to examine the relationship between mean platelet volume (MPV) and recurrent miscarriage in order to illuminate the etiopathogenesis of recurrent miscarriage. Material and methods We retrospectively investigated the data of 120 patients with unexplained recurrent miscarriage (group 1), and compared them with the data of 120 match-paired patients in the control group (group 2). The definition of recurrent miscarriage was accepted as two or more failed clinical pregnancies which were documented by ultrasonography or histopathologic examination. All patients in the recurrent miscarriage group were evaluated with diagnostic tests for the etiology of recurrent miscarriage. Total blood count parameters, including hemoglobin, mean corpuscular volume, red cell distribution width, white blood cells, platelets, and mean platelet volume, were compared. Results The average patient age at the time of examination was 29.07 ±2.81 years in group I and 28.53 ±3.5 years in group II (p > 0.05). Mean body mass index (BMI) was similar between group 1 and group 2, 22.54 ±3.17 and 22.99 ±2.38, respectively (p > 0.05). Mean hemoglobin, mean corpuscular volume, red cell distribution width, and white blood cell and platelet levels were similar in both groups (p > 0.05). Mean platelet volume levels were significantly higher in group I (9.45 ±1.09 fl) than in group II (7.63 ±0.52 fl) (p = 0.001). Conclusions Higher MPV values in the study group suggest and support the importance of thromboembolic events in the etiology of recurrent miscarriage. PMID:26528341

  19. Repair of bone defects with absorbable membranes. A study on rabbits.

    PubMed

    Ashammakhi, N; Mäkelä, E A; Vihtonen, K; Rokkanen, P; Törmälä, P

    1995-01-01

    Self-reinforced polyglycolic acid (SR-PGA) devices were developed in the mid-eighties, applied for fixation purposes and proved to be biocompatible. In this study SR-PGA membranes (10 x 10 mm) were used to augment defects on the medial aspect of distal femoral metaphysis in 31 New Zealand rabbits. Defects of 3.5 mm were either filled with autografts or left non-grafted. In a control group, no membranes were used. The rabbits were followed up for six, 12 and 24 weeks. Radiography, histology, oxytetracycline (OTC) fluorescence labelling and microradiography were used. Defects where membranes were used, healed by new bone formation. In some cases where polyglycolic acid (PGA) membranes were not used, defects were invaded by fibrous tissue. Membranes sometimes slipped away from their positions opposite to grafted defects. This study proved that the advantage of the use of PGA membranes could be taken in augmentation of cancellous bone defects in rabbits.

  20. Technical advances in studying cardiac electrophysiology - Role of rabbit models.

    PubMed

    Kang, C; Brennan, J A; Kuzmiak-Glancy, S; Garrott, K E; Kay, M W; Efimov, I R

    2016-07-01

    Cardiovascular research has made a major contribution to an unprecedented 10 year increase in life expectancy during the last 50 years: most of this increase due to a decline in mortality from heart disease and stroke. The majority of the basic cardiovascular science discoveries, which have led to this impressive extension of human life, came from investigations conducted in various small and large animal models, ranging from mouse to pig. The small animal models are currently popular because they are amenable to genetic engineering and are relatively inexpensive. The large animal models are favored at the translational stage of the investigation, as they are anatomically and physiologically more proximal to humans, and can be implanted with various devices; however, they are expensive and less amenable to genetic manipulations. With the advent of CRISPR genetic engineering technology and the advances in implantable bioelectronics, the large animal models will continue to advance. The rabbit model is particularly poised to become one of the most popular among the animal models that recapitulate human heart diseases. Here we review an array of the rabbit models of atrial and ventricular arrhythmias, as well as a range of the imaging and device technologies enabling these investigations. Copyright © 2016. Published by Elsevier Ltd.

  1. Lipid metabolism abnormalities in alcohol-treated rabbits: a morphometric and haematologic study comparing high and low alcohol doses

    PubMed Central

    Ikemura, Satoshi; Yamamoto, Takuaki; Motomura, Goro; Iwasaki, Kenyu; Yamaguchi, Ryosuke; Zhao, Garida; Iwamoto, Yukihide

    2011-01-01

    The pathogenesis of alcohol-induced osteonecrosis remains unclear. The purpose of the present study was to evaluate the morphological changes in bone marrow fat cells and the changes in the serum lipid levels in alcohol-treated rabbits. Fifteen rabbits were randomly assigned into three groups: Four rabbits intragastrically received low-dose alcohol (LDA) (15 ml/kg per day) containing 15% ethanol for 4 weeks, five rabbits received high-dose alcohol (HDA) (30 ml/kg per day) for 4 weeks and six rabbits received physiologic saline for 4 weeks as a control group. Six weeks after the initial alcohol administration, all rabbits were sacrificed. The mean size of the bone marrow fat cells in rabbits treated with HDA was significantly larger than that in the control group (P = 0.0001). Haematologically, the levels of triglycerides and free fatty acids in the rabbits treated with both low-dose and HDA were significantly higher than those in the control group (P = 0.001 for both comparisons). The results of this study are that there are lipid metabolism abnormalities, both morphologically and haematologically, after alcohol administration. Also these findings were more apparent in rabbits treated with HDA than those treated with LDA. PMID:21645143

  2. Physiopathology of blood platelets: a model system for studies of cell-to-cell interaction. Progress report, November 1, 1979-October 31, 1980

    SciTech Connect

    1980-01-01

    This report covers the studies on basic mechanisms of cellular interactions, utilizing platelets as a model system and, when possible, concentrating on the influence that environmental factors (nutritional, metabolic, cellular, immunologic and others) have on them. The four major sections include: platelet interaction with tumor cells; a model for the study of cell-to-cell interaction; interaction of platelets with vessel walls; and platelet interactions with immune proteins.

  3. In vivo studies to highlight possible illegal treatments of rabbits with carbadox and olaquindox.

    PubMed

    Segato, Giulia; Biancotto, Giancarlo; Agnoletti, Fabrizio; Berto, Giacomo; Montesissa, Clara; Benetti, Cristiana

    2015-01-01

    For the treatment of rabbit dysentery and bacterial enteritis, veterinary practitioners often adopt veterinary medicinal products authorised for other food-producing species, but in some cases non-authorised drugs frequently used in the past, such as carbadox and olaquindox, might be illegally adopted. To verify the carbadox and olaquindox distribution and persistence in rabbit tissues, two independent in vivo studies were carried out. In the first study, 24 healthy rabbits received water medicated with carbadox at 100 mg l(-1) over a period 28 days, whereas in the second one, 24 healthy rabbits were administered water containing olaquindox at 100 mg l(-1). In each study rabbits were randomly assigned to four groups to be sacrificed respectively at 0, 5, 10 and 20 days from treatment withdrawal, for depletion studies. A control group of six animals was adopted for control and as a reservoir of blank tissues. Muscle and liver samples collected from each treated animal were stored at -20°C pending the analysis. Sensitive and robust liquid chromatography-tandem mass spectrometry analytical methods were set up for the parent compounds and their main metabolites quinoxaline-2-carboxylic acid, desoxycarbadox and 3-methylquinoxaline-2-carboxylic acid to verify their residual. Data collected demonstrate that the combination of liver as target matrix, quinoxaline-2-carboxylic acid and 3-methylquinoxaline-2-carboxylic acid as marker residue and enzymatic digestion is strategic to evidence carbadox and/or olaquindox illegal treatments in rabbits, even 20 days after treatment withdrawal at concentration levels higher than 0.5 µg kg(-1). This findings suggests that liver should be proposed as target matrix for official control in national monitoring plan.

  4. Prevalence, serologic and genetic studies of high expressers of the blood group A antigen on platelets*.

    PubMed

    Sant'Anna Gomes, B M; Estalote, A C; Palatnik, M; Pimenta, G; Pereira, B de B; Do Nascimento, E M

    2010-10-01

    The aim of this study is to describe the distribution of the platelet blood group A antigenicity in Euro-Brazilians (EUBs) and Afro-Brazilians (AFBs). A small but significant proportion of individuals express high levels of A or B antigen on their platelets corresponding to the erythrocyte ABO group. The mechanism of increased antigen expression has not been elucidated. A cohort of 241 blood group A donors was analysed by flow cytometry. Although mean fluorescence intensity (MFI) is a typical continuous variable, platelets were screened and divided into two categories: low expressers (LEs) and high expressers (HEs). A three-generation family was investigated looking for an inheritance mechanism. The prevalence of the HE platelet phenotype among group A(1) donors was 2%. The mean of MFI on platelets of A(1) subgroup of EUBs differs from that of AFBs (P = 0·0115), whereas the frequency of the HE phenotype was similar between them (P = 0·5251). A significant difference was found between sexes (P = 0·0039). Whereas the serum glycosyltransferase from HE family members converted significantly more H antigen on group O erythrocytes into A antigens compared with that in LE serum, their ABO, FUT1 and FUT2 genes were consensus. The theoretically favourable, transcriptionally four-repeat ABO enhancer was not observed. The occurrence of HE in several members suggests familial aggregation. Indeed, in repeated measures, stability of the MFI values is suggesting an inherited condition. Factors outside the ABO locus might be responsible for the HE phenotype. Whether the real mechanism of inheritance is either of a polygenic or of a discrete Mendelian nature remains to be elucidated. © 2010 The Authors. Transfusion Medicine © 2010 British Blood Transfusion Society.

  5. An ultrastructural study, effects of Proteus vulgaris OX19 on the rabbit spleen cells.

    PubMed

    Gul, Nursel; Ozkorkmaz, Ebru Gokalp; Kelesoglu, Ilknur; Ozluk, Aydin

    2013-01-01

    Effects of Proteus vulgaris OX19 on the spleen cells of rabbits were investigated. Control group (n=5) and Proteus treated group (n=5) of New Zealand male rabbits were used in this study. Bacteria were injected to the rabbits in five days periods with increasing dosages for one month. Thin sections were examined by transmission electron microscope (Jeol 100CXII). Ultrastructural changes were defined in spleen tissue cells due to the antigenic stimulation of bacteria. Spleen cells observed in control group were in normal structure and cells were in close contact with each other. However, spleen cells of Proteus treated group displayed structural changes with regard to the control group in electron microscopic examinations. Chemotaxis of macrophages, forming of pseudopodia and presence of phagocytic vacuoles were observed. Lymphocytes, the major cells of spleen revealed mitotic activity. In addition, chromatin condensation in nucleus and dilatations in perinuclear space were significant. Interactions of lymphocytes and macrophages were noteworthy.

  6. Pesticide deposition in hair: preliminary results of a model study of methomyl incorporation into rabbit hair.

    PubMed

    Tsatsakis, A M; Tutudaki, M I; Tzatzarakis, M N; Psaroudakis, K; Dolapsakis, G P; Michalodimitrakis, M N

    1998-08-01

    This work studied the incorporation of methomyl, a carbamate insecticide, into the hair of New Zealand white rabbits. A total of 600 mg methomyl was administered by drinking water over 4 mo, and acetylcholinesterase activity in serum was monitored. At the end of the dosing period, hair from the back of the rabbits was cut off, and the methomyl concentration was measured using ELISA and HPLC. A decrease of serum acetylcholinesterase occurred. The top cm of hair contained no methomyl, the second cm contained 0.9 ng/mg and the 3rd cm of hair contained 3 ng methomyl/mg. Methomyl was incorporated into the rabbit hair in a process independent of gender but dependent on the hair growth rate.

  7. In vivo evaluation of titanium-prepared platelet-rich fibrin (T-PRF): a new platelet concentrate.

    PubMed

    Tunalı, Mustafa; Özdemir, Hakan; Küçükodacı, Zafer; Akman, Serhan; Fıratlı, Erhan

    2013-07-01

    We have developed a new, titanium-prepared, platelet-rich fibrin (T-PRF) together with the protocol for forming it, which is based on the hypothesis that titanium tubes may be more effective at activating platelets than the glass tubes used by Chouckroun in his platelet-rich fibrin (PRF) method. The aim of this study was to find a suitable animal model in which to evaluate the method and to investigate the efficacy of T-PRF for wound healing. Blood samples from 6 rabbits were used to confirm the protocol for formation of T-PRF. We evaluated T-PRF or T-PRF-like clots morphologically using scanning electron microscopy (EM). Blood samples from 5 rabbits were used to develop an experiment in which to evaluate the effects of T-PRF on wound healing. The mucoperiosteal flaps were filled with autologous T-PRF membranes from the vestibule in the anterior mandibular regions. Samples collected from the surgical sites were stained with haematoxylin and eosin. We found a mature fibrin network in T-PRF clots that had been centrifuged for 15 min at 3500 rpm and, 15 days after placement of the membrane, we found newly-forming connective tissue and islets of bony tissue in the T-PRF membrane. These results show that T-PRF could induce the formation of new bone with new connective tissue in a rabbit model of wound healing within 30 days of treatment. Published by Elsevier Ltd.

  8. Role of xenogenous bovine platelet gel embedded within collagen implant on tendon healing: an in vitro and in vivo study

    PubMed Central

    Oryan, Ahmad; Meimandi-Parizi, Abdolhamid; Maffulli, Nicola

    2015-01-01

    Surgical reconstruction of large Achilles tendon defects is demanding. Platelet concentrates may be useful to favor healing in such conditions. The characteristics of bovine platelet-gel embedded within a collagen-implant were determined in vitro, and its healing efficacy was examined in a large Achilles tendon defect in rabbits. Two cm of the left Achilles tendon of 60 rabbits were excised, and the animals were randomly assigned to control (no implant), collagen-implant, or bovine-platelet-gel-collagen-implant groups. The tendon edges were maintained aligned using a Kessler suture. No implant was inserted in the control group. In the two other groups, a collagen-implant or bovine-platelet-gel-collagen-implant was inserted in the defect. The bioelectricity and serum platelet-derived growth factor levels were measured weekly and at 60 days post injury, respectively. After euthanasia at 60 days post injury, the tendons were tested at macroscopic, microscopic, and ultrastructural levels, and their dry matter and biomechanical performances were also assessed. Another 60 rabbits were assigned to receive no implant, a collagen-implant, or a bovine-platelet-gel-collagen-implant, euthanized at 10, 20, 30, and 40 days post injury, and their tendons were evaluated grossly and histologically to determine host-graft interactions. Compared to the control and collagen-implant, treatment with bovine-platelet-gel-collagen-implant improved tissue bioelectricity and serum platelet-derived growth factor levels, and increased cell proliferation, differentiation, and maturation. It also increased number, diameter, and density of the collagen fibrils, alignment and maturation of the collagen fibrils and fibers, biomechanical properties and dry matter content of the injured tendons at 60 days post injury. The bovine-platelet-gel-collagen-implant also increased biodegradability, biocompatibility, and tissue incorporation behavior of the implant compared to the collagen-implant alone

  9. Developmental toxicity studies of lumefantrine and artemether in rats and rabbits.

    PubMed

    Clark, Robert L; Youreneff, Maureen; DeLise, Anthony M

    2016-12-01

    The combination of artemether plus lumefantrine is a type of artemisinin-based combination therapy (ACT) recommended by the World Health Organization for uncomplicated falciparum malaria except in the first trimester of pregnancy. The first trimester restriction was based on the marked embryotoxicity in animals (including embryo death and cardiac and skeletal malformations) of artemisinins such as artesunate, dihydroartemisinin, and artemether. Before recommending ACTs for use in the first trimester, the World Health Organization has requested that all information relevant to the assessment of risk of ACTs to the embryo be made available to the public. This report describes the results of embryo-fetal development studies of artemether alone, lumefantrine alone, and the combination in rats and rabbits as well as toxicokinetic studies of lumefantrine in pregnant rabbits. The developmental no-effect levels for lumefantrine were 300 mg/kg/day in rats (based on a 25% decrease in litter size at 1000 mg/kg/day) and 1000 mg/kg/day in rabbits. The calculated safety margins based on human equivalent dose and plasma Cmax and AUC values were in the range of 2.5- to 17-fold. The developmental no-effect levels for artemether were 3 mg/kg/day in rats and 25 mg/kg/day in rabbits. Lumefantrine caused no teratogenicity and was not a potent embryotoxin in rats and rabbits. Expected artemisinin-like findings were seen with artemether alone and with artemether/lumefantrine combined except that no malformations were observed. There were no findings in pregnant rats and rabbits that would cause increased concern for the use of artemether-lumefantrine in the first trimester compared to other ACTs.

  10. Effects of etamsylate on equine platelets: in vitro and in vivo studies.

    PubMed

    Segura, Dídac; Monreal, Luis; Pérez-Pujol, Sílvia; Alonso, Antonio; Díaz-Ricart, Maribel; Brugués, Rosa; Ordinas, Antonio; Escolar, Ginés

    2007-09-01

    The aim of this study was to investigate whether etamsylate produces equine platelet activation. In vitro and in vivo studies were designed in which seven and eight adult healthy horses were included, respectively. In the in vitro study, citrated blood was incubated with different concentrations of etamsylate, and P-selectin expression and annexin V binding were determined by flow cytometry. In the in vivo study, blood was collected before and 1 and 2h after IV administration of etamsylate, and P-selectin expression was evaluated. In the in vitro study, a significant increase in P-selectin expression, leukocyte-platelet aggregate formation and annexin V binding were observed. In the in vivo study, a marked increase in P-selectin expression and heterotypic aggregate formation was seen in two and five horses, respectively, although no significant differences were detected when analyzing results from all the animals together. The results of the in vitro study indicate that etamsylate produces a pre-activation state in equine platelets, but this fact could be confirmed by the in vivo study.

  11. [Autologous grafting of extraocular muscles: experimental study in rabbits].

    PubMed

    Meireles-Teixeira, Jorge; Bicas, Harley E A

    2005-01-01

    To evaluate the feasibility of autologous extraocular muscle grafting as a type of muscle expansion surgery. The left superior rectus muscle of twenty-nine rabbits was resected and this fragment was attached to the endpoint of the respective right superior rectus (test group). Thereafter, the superior rectus of the left eye was reattached to the sclera (control group). Both groups were examined during different postoperative periods in order to assess their outcomes. The presence of hyperemia was slightly more frequent in the grafted group. Secretion and muscle atrophy were negligible in both groups. Fibrosis was greater in grafted animals. These muscles were weaker than the control muscles, although the force required to split muscular parts was always greater than the physiological one. This surgical technique was reliable and useful if one intends to achieve muscle expansion without the intrinsic risks of dealing with heterologous/artificial materials.

  12. Mechanism study of endothelial protection and inhibits platelet activation of low molecular weight fucoidan from Laminaria japonica

    NASA Astrophysics Data System (ADS)

    Chen, Anjin; Zhang, Fang; Shi, Jie; Zhao, Xue; Yan, Meixing

    2016-10-01

    Several studies have indicated that fucoidan fractions with low molecular weight and different sulfate content from Laminaria japonica could inhibit the activation of platelets directly by reducing the platelet aggregation. To explore the direct effect of LMW fucoidan on the platelet system furthermore and examine the possible mechanism, the endothelial protection and inhibits platelet activation effects of two LMW fucoidan were investigated. In the present study, Endothelial injury model of rats was made by injection of adrenaline (0.4 mg kg-1) and human umbilical vein endothelial cells were cultured. vWF level was be investigated in vivo and in vitro as an important index of endothelial injury. LMW fucoidan could significantly reduce vWF level in vascular endothelial injury rats and also significantly reduce vWF level in vitro. The number of EMPs was be detected as another important index of endothelial injury. The results showed that LMW fucoidan reduced EMPs stimulated by tumor necrosis factor. In this study, it was found that by inhibiting platelet adhesion, LMW fucoidan played a role in anti-thrombosis and the specific mechanism of action is to inhibit the flow of extracellular Ca2+. All in a word, LMW fucoidan could inhibit the activation of platelets indirectly by reducing the concentration of EMPs and vWF, at the same time; LMW fucoidan inhibited the activation of platelets directly by inhibiting the flow of extracellular Ca2+.

  13. Embryo-Fetal Developmental Toxicity Studies with Pregabalin in Mice and Rabbits.

    PubMed

    Morse, Dennis C

    2016-04-01

    Pregabalin was evaluated for potential developmental toxicity in mice and rabbits. Pregabalin was administered once daily by oral gavage to female albino mice (500, 1250, or 2500 mg/kg) and New Zealand White rabbits (250, 500, or 1250 mg/kg) during organogenesis (gestation day 6 through 15 [mice] or 6 through 20 [rabbits]). Fetuses were evaluated for viability, growth, and morphological development. Pregabalin administration to mice did not induce maternal or developmental toxicity at doses up to 2500 mg/kg, which was associated with a maternal plasma exposure (AUC0-24 ) of 3790 μg•hr/ml, ≥30 times the expected human exposure at the maximum recommended daily dose (MRD; 600 mg/day). In rabbits, treatment-related clinical signs occurred at all doses (AUC0-24 of 1397, 2023, and 4803 μg•hr/ml at 250, 500, and 1250 mg/kg, respectively). Maternal toxicity was evident at all doses and included ataxia, hypoactivity, and cool to touch. In addition, abortion and females euthanized moribund with total resorption occurred at 1250 mg/kg. There were no treatment-related malformations at any dose. At 1250 mg/kg, compared with study and historical controls, the percentage of fetuses with retarded ossification was significantly increased and the mean number of ossification sites was decreased, which correlated with decreased fetal and placental weights, consistent with in utero growth retardation. Therefore, the no-effect dose for developmental toxicity in rabbits was 500 mg/kg, which produced systemic exposure approximately 16-times human exposure at the MRD. These findings indicate that pregabalin, at the highest dose tested, was not teratogenic in mice or rabbits. © 2016 Wiley Periodicals, Inc.

  14. The effects of low-dose radiotherapy on fresh osteochondral allografts: An experimental study in rabbits.

    PubMed

    Gönç, Uğur; Çetinkaya, Mehmet; Atabek, Mesut

    2016-10-01

    The aim of this study was to investigate the effects of low-dose fractionated radiotherapy on cartilage degeneration after distal femoral fresh massive osteochondral allograft transplantation. Twenty-four New Zealand White rabbits were divided into three groups of 8 rabbits each. All rabbits underwent distal femoral medial condyle fresh massive osteochondral allograft transplantation from California rabbits. The group 1 underwent transplantation without any preliminary process. The group 2 underwent fractionated local radiotherapy of 100 cGy for five days starting on the transplantation day. The group 3 included the rabbits to which the grafts transplanted after radiating in vitro by a single dose radiation of 1500 cGy. The hosts were sacrificed twelve weeks later. Anteroposterior and lateral radiographs were taken. Synovial tissue, cartilaginous tissue, and subchondral bone were assessed histopathologically. Nonunion was present in three cases of group 2 and one of group 3 in which cartilage degeneration was more severe. Synovial hypertrophy and pannus formation were more obvious in non-radiated rabbits. Hypocellularity and necrosis of the subchondral bone were rare in group 2. More cartilage tissue impairment was present in group 3 compared to group 1. In osteochondral massive allograft transplantations, the immune reaction of the host could be precluded with radiotherapy, and the side-effects can be prevented by low-dose fractionated regimen. The total dose of fractionated radiotherapy for an immune suppression should be adjusted not to damage the cartilage tissue, but to avoid articular degeneration in the long term. Copyright © 2016 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.

  15. Indium-111 labeled platelet survival time studies in patients with prosthetic heart valves

    SciTech Connect

    Martinovitch, U.; Carrick, P.; Lieberman, L.M.

    1985-05-01

    Platelet survival time (PST) studies are useful to demonstrate whether or not patients with prosthetic heart valves have normal or shortened PST. During treatment for recurrent TIAs the PST will signal whether the patient is returning towards a normal PST. Using Indium-111 labeled platelets (ILP) the authors studied 10 patients suffering recurrent TIAs after prosthetic valve surgery to determine whether low dose aspirin increased their PST toward normal and whether the treatment had a beneficial effect on their TIA episodes. The authors conclude that low dose aspirin therapy as studied by ILP has no beneficial effect on PST or in preventing recurrent TIA. ILP is an important technique that allows the physician to identify those patients with shortened PST and to determine response to therapy.

  16. Binding studies of platelet alpha 2- and lymphocyte beta 2-adrenoceptors in patients with cirrhosis.

    PubMed Central

    MacGilchrist, A J; Deighton, N M; Hamilton, C A; Reid, J L

    1990-01-01

    Radioligand binding studies were performed on 10 patients with cirrhosis and 10 healthy subjects. Bmax and KD of platelet alpha 2-adrenoceptors, studied using [3H]-yohimbine, were similar in both groups (Bmax 24.9 vs 22.1 fmol/10(9) platelets, P = 0.47; KD 4.6 vs 5.5 nmol 1-1, P = 0.56). Bmax and KD of lymphocyte beta 2-adrenoceptors, studied using [125I]-iodocyanopindolol, were also similar in both groups (Bmax 24.0 vs 27.2 fmol mg-1 protein, P = 0.55; KD 49.6 vs 55.3 pmol 1-1, P = 0.65). In this model there is no evidence of adrenoceptor down-regulation in cirrhosis despite the increased sympathetic activity in this condition. PMID:1963313

  17. [The rabbit ear model as comedogenic test. 3. Histologic and enzyme histochemical studies of the follicle and sebaceous gland epithelium].

    PubMed

    Zimmermann, R

    1990-01-01

    A strongly comedogenic mineral oil induced histologically and enzyme-histochemically detectable changes in the follicles and sebaceous gland ducts in the skin of rabbit ears. These correlate to findings concerning acne vulgaris in humans. The rabbit ear model thus appears to be suitable for experimental studies into acne vulgaris.

  18. Interactions of gallic acid, resveratrol, quercetin and aspirin at the platelet cyclooxygenase-1 level. Functional and modelling studies.

    PubMed

    Crescente, Marilena; Jessen, Gisela; Momi, Stefania; Höltje, Hans-Dieter; Gresele, Paolo; Cerletti, Chiara; de Gaetano, Giovanni

    2009-08-01

    While resveratrol and quercetin possess antiplatelet activity, little is known on the effect of gallic acid on platelets. We studied the interactions of these three different polyphenols among themselves and with aspirin, at the level of platelet cyclooxygenase-1 (COX-1). Both functional (in vitro and in vivo) and molecular modelling approaches were used. All three polyphenols showed comparable antioxidant activity (arachidonic acid [AA]-induced intraplatelet ROS production); however, resveratrol and quercetin, but not gallic acid, inhibited AA-induced platelet aggregation. Gallic acid, similarly to salicylic acid, the major aspirin metabolite, prevented inhibition of AA-induced platelet function by aspirin but, at variance with salicylic acid, also prevented inhibition by the other two polyphenols. Molecular modelling studies, performed by in silico docking the polyphenols into the crystal structure of COX-1, suggested that all compounds form stable complexes into the COX-1 channel, with slightly different but functionally relevant interaction geometries. Experiments in mice showed that gallic acid administered before aspirin, resveratrol or quercetin fully prevented their inhibitory effect on serum TxB(2). Finally, a mixture of resveratrol, quercetin and gallic acid, at relative concentrations similar to those contained in most red wines, did not inhibit platelet aggregation, but potentiated sub-inhibitory concentrations of aspirin. Gallic acid interactions with other polyphenols or aspirin at the level of platelet COX-1 might partly explain the complex, and possibly contrasting, effects of wine and other components of the Mediterranean diet on platelets and on the pharmacologic effect of low-dose aspirin.

  19. The effect of clopidogrel on platelet activity in patients with and without type-2 diabetes mellitus: a comparative study.

    PubMed

    Schuette, Claudia; Steffens, Daniel; Witkowski, Marco; Stellbaum, Caroline; Bobbert, Peter; Schultheiss, Heinz-Peter; Rauch, Ursula

    2015-02-03

    Although antiplatelet therapy involving clopidogrel is a standard treatment for preventing cardiovascular events after coronary stent implantation, patients can display differential responses. Here, we assessed the effectiveness of clopidogrel on platelet function inhibition in subjects with and without type-2 diabetes and stable coronary artery disease. In addition, we investigated the correlation between platelet function and routine clinical parameters. A total of 64 patients with stable coronary heart disease were enrolled in the study. Among these, 32 had known type-2 diabetes, whereas the remaining 32 subjects were non-diabetics (control group). A loading dose of 300 mg clopidogrel was given to clopidogrel-naïve patients (13 patients in the diabetes group and 14 control patients). All patients were given a daily maintenance dose of 75 mg clopidogrel. In addition, all patients received 100 mg ASA per day. Agonist-induced platelet aggregation measurements were performed on hirudin-anticoagulated blood using an impedance aggregometer (Multiple Platelet Function Analyzer, Dynabyte, Munich, Germany). Blood samples were drawn from the antecubital vein 24 h after coronary angiography with percutaneous coronary intervention. The platelets were then stimulated with ADP alone or ADP and prostaglandin-E (ADP and ADP-PGE tests, respectively) in order to evaluate clopidogrel-mediated inhibition of platelet function. The effectiveness of ASA was measured by stimulation with arachidonic acid (ASPI test). In addition, maximal platelet aggregation was assessed via stimulation with thrombin receptor-activating peptide (TRAP test). Patients with diabetes exhibited significantly less inhibition of platelet function than patients without diabetes (ADP-PGE test p = 0.003; ASPI test p = 0.022). Administering a clopidogrel loading dose of 300 mg did not result in a lower level of ADP-PGE-induced platelet reactivity in comparison to the use of a 75 mg maintenance dose

  20. A uniform-shear rate microfluidic bioreactor for real-time study of proplatelet formation and rapidly-released platelets.

    PubMed

    Martinez, Andres F; McMahon, Richard D; Horner, Marc; Miller, William M

    2017-09-27

    Platelet transfusions, with profound clinical importance in blood clotting and wound healing, are entirely derived from human volunteer donors. Hospitals rely on a steady supply of donations, but these methods are limited by a 5-day shelf life, the potential risk of contamination, and differences in donor/recipient histocompatibility. These challenges invite the opportunity to generate platelets ex vivo. Although much progress has been made in generating large numbers of culture-derived megakaryocytes (Mks, the precursor cells to platelets), stimulating a high percentage of Mks to undergo platelet release remains a major challenge. Recent studies have demonstrated the utility of shear forces to enhance platelet release from cultured Mks. In this study, we performed a computational fluid dynamics (CFD) analysis of several published platelet microbioreactor systems, and used the results to develop a new 7-µm slit bioreactor - with well-defined flow patterns and uniform shear profiles. This uniform-shear-rate bioreactor (USRB-7µm) permits real-time visualization of the proplatelet (proPLT) formation process and the rapid-release of individual platelet-like-particles (PLPs), which has been observed in vivo, but not previously reported for platelet bioreactors. We showed that modulating shear forces and flow patterns had an immediate and significant impact on PLP generation. Surprisingly, using a single flow instead of dual flows led to an unexpected 6-fold increase in PLP production. By identifying particularly effective operating conditions within a physiologically relevant environment, this USRB-7µm will be a useful tool for the study and analysis of proPLT/PLP formation that will further understanding of how to increase ex vivo platelet release. This article is protected by copyright. All rights reserved. © 2017 American Institute of Chemical Engineers.

  1. A microangiographic study of the effect of hyperthermia on the rabbit bladder

    NASA Technical Reports Server (NTRS)

    Hietala, S. O.; Howells, R.; Hazra, I. A.

    1978-01-01

    A model was used to study the effect of hyperthermia on a normal tissue. The model selected was the rabbit bladder and the end point measured was the changes in the micro-vasculature of the bladder wall. It was already demonstrated clinically that hot water bladder infusions produce regression in bladder tumors.

  2. In vivo imaging in the rabbit as a model for the study of ovulation-inducing factors.

    PubMed

    Cervantes, M P; Palomino, J M; Adams, G P

    2015-01-01

    The study of factors responsible for eliciting ovulation in rabbits has been hampered by the lack of a suitable method of monitoring the ovaries in vivo. Ovarian imaging by ultrasound biomicroscopy was used in two experiments designed to determine the effects of seminal plasma on the ovulatory response in rabbits. In Experiment 1, female rabbits were group-housed and treated intramuscularly with saline, gonadotropin releasing hormone (GnRH), or seminal plasma of llamas or rabbits (n = 4 to 6 per group). Rabbits were euthanized eight days later to evaluate the ovarian response by ultrasound biomicroscopy ex situ. No differences among groups were detected in the proportion of rabbits that ovulated or in the number and size of corpora lutea. The high incidence of ovulation in the negative control group was unexpected, and confounded determination of an ovulation-inducing effect of seminal plasma. In Experiment 2, female rabbits were caged individually, and treated as in Experiment 1 (n = 5 to 7 per group). The ovarian response was evaluated in vivo by transcutaneous ultrasound biomicroscopy. Ovulation and formation of corpora lutea were detected only in rabbits given GnRH. A preovulatory surge in plasma luteinizing hormone concentration and a post-ovulatory rise in plasma progesterone concentration were detected only in rabbits treated with GnRH. Surgical translocation of the ovaries to a subcutaneous position enabled longitudinal assessment of the ovulatory response by ultrasound biomicroscopy. Results clearly documented the effect of physical/social interaction on ovulation in rabbits, and did not support the hypothesis that seminal plasma elicits ovulation in rabbits. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  3. A retrospective analysis of developmental toxicity studies in rat and rabbit: what is the added value of the rabbit as an additional test species?

    PubMed

    Janer, Gemma; Slob, Wout; Hakkert, Betty C; Vermeire, Theo; Piersma, Aldert H

    2008-03-01

    In contrast to most toxicological tests, developmental studies are usually required in both a rodent and a non-rodent species. This study retrospectively assessed the added value of the rabbit developmental test when a rat developmental test is available. In contrast with previous reviews, we looked at developmental toxicity instead of teratogenicity, and took into account maternal toxicity in the evaluation of developmental toxicity. We analyzed data for 54 substances classified for developmental toxicity and 73 substances considered to be teratogenic in the rabbit and not in the rat in two previous reviews. On average, the rat and the rabbit developmental toxicity studies were similarly sensitive: the average ratio of the NOAELs between the two species was about one, and for most compounds there were no differences between rat and rabbit studies in terms of classification for developmental toxicity. For certain substances the developmental study in either one of the two species appeared to be more sensitive than in the other species. However, these differences are partly due to differences between studies other than the test species used. Overall, our analysis does not clearly indicate that the evaluation of developmental toxicity, as opposed to other types of toxicity, would specifically require the rabbit as an additional test species. The discrimination between direct and indirect (i.e., as a consequence of maternal toxicity) developmental effects was often doubtful, and is one of the factors that could explain the apparent differences between the two species. A more accurate assessment of maternal toxicity might improve the reliability of the results from a single developmental toxicity study. More knowledge about the interaction between maternal and developmental effects is required before decisions on omitting the requirement for the developmental toxicity testing in a second species can be considered.

  4. Use of indium-111 oxine to study the effects of terbutaline on pulmonary and hepatic platelet sequestration in endotoxin shock

    SciTech Connect

    Christenson, J.T.; Sigurdsson, G.H.; Mousawi, M.; Owunwanne, A.

    1987-01-01

    This study describes the effects of the beta 2 receptor agonist terbutaline on platelet sequestration in sheep exposed to endotoxin shock. The in vivo behavior of Indium-111-labeled platelets was followed simultaneously in the lungs, liver, spleen, and kidneys. The effects on the respiratory function and the central hemodynamics were also followed. Twelve adult sheep were given endotoxin (10 micrograms/kg bw), and six of those received a continuous intravenous infusion of terbutaline (20 micrograms/kg/hr) during 4 hr, starting 30 min after injection of endotoxin. The other six acted as controls. It was found that a marked pulmonary and hepatic platelet sequestration occurred during and just after the endotoxin infusion and was followed by a marked platelet disaggregation within 30 min in both groups. Three hours after the endotoxin a second wave of platelet trapping occurred in the control animals in both the lungs and the liver, while no such increase was seen in the terbutaline-treated animals. In the spleen, however, there was a decrease in platelet sequestration after endotoxin in both groups, and in the kidneys only minor changes occurred. Furthermore, less marked hemodynamic and respiratory alterations occurred in the terbutaline group compared with the controls. It was concluded that terbutaline decreased sequestration of platelets in the lungs and in the liver of sheep in endotoxin shock, which may be of importance in the development of multiple organ failure.

  5. Biologic nanoparticles and platelet reactivity

    PubMed Central

    Miller, Virginia M; Hunter, Larry W; Chu, Kevin; Kaul, Vivasvat; Squillace, Phillip D; Lieske, John C; Jayachandran, Muthuvel

    2009-01-01

    Aim Nanosized particles (NPs) enriched in hydroxyapatite and protein isolated from calcified human tissue accelerate occlusion of endothelium-denuded arteries when injected intravenously into rabbits. Since platelet aggregation and secretory processes participate in normal hemostasis, thrombosis and vascular remodeling, experiments were designed to determine if these biologic NPs alter specific platelet functions in vitro. Methods Platelet-rich plasma was prepared from citrate anticoagulated human blood. Platelet aggregation and ATP secretion were monitored in response to thrombin receptor agonists peptide (10 μM) or convulxin (50 μg/ml) prior to and following 15 min incubation with either control solution, human-derived NPs, bovine-derived NPs or crystals of hydroxyapatite at concentrations of 50 and 150 nephelometric turbidity units. Results Incubation of platelets for 15 min with either human- or bovine-derived NPs reduced aggregation induced by thrombin receptor activator peptide and convulxin in a concentration-dependent manner. Hydroxyapatite caused a greater inhibition than either of the biologically derived NPs. Human-derived NPs increased ATP secretion by unstimulated platelets during the 15 min incubation period. Conclusion Effects of bovine-derived and hydroxyapatite NPs on basal release of ATP were both time and concentration dependent. These results suggest that biologic NPs modulate both platelet aggregation and secretion. Biologically derived NPs could modify platelet responses within the vasculature, thereby reducing blood coagulability and the vascular response to injury. PMID:19839809

  6. Preliminary study: fibre content in pet rabbit diets, crude fibre versus total dietary fibre.

    PubMed

    Molina, J; Martorell, J; Hervera, M; Pérez-Accino, J; Fragua, V; Villaverde, C

    2015-04-01

    Fibre is an important nutrient for rabbit health, and, on commercial pet rabbit packaging, it is labelled as crude fibre (CF). In several species, it is considered that CF is not an accurate representation of the fibre content in feedstuffs. The objective of this study was to compare the CF stated on the label (CFL) with laboratory analysis of CF (CFA) and the analysed content of total dietary fibre (TDF) in different commercial pet rabbit feeds. We selected 15 commercial diets and analysed CF and TDF. A mixed model was used to evaluate differences between CFL, CFA and TDF, and linear regression was performed to study the correlation between CFL and CFA with TDF. CFA and CFL were not significantly different (p = 0.836) in the feeds studied, and both were lower than TDF (p < 0.001). The correlations between TDF and both CFA and CFL were significant (p < 0.001 and p = 0.02, respectively), but the correlation was better with CFA (R = 0.86) than with CFL (R = 0.53). As expected, TDF content was higher than CF content, an average of two times. These results suggest that the CF content in rabbit diets reported on the label is not an appropriate indicator of their total fibre content, although further work with a larger sample size is required to confirm these results.

  7. Nitric oxide released from activated platelets inhibits platelet recruitment.

    PubMed Central

    Freedman, J E; Loscalzo, J; Barnard, M R; Alpert, C; Keaney, J F; Michelson, A D

    1997-01-01

    Vessel injury and thrombus formation are the cause of most ischemic coronary syndromes and, in this setting, activated platelets stimulate platelet recruitment to the growing thrombus. Recently, a constitutive nitric oxide synthase (NOS) has been identified in human platelets. To further define the capacity of platelets to produce nitric oxide (NO), as well as to study the role of this NO in platelet recruitment, we adapted a NO-selective microelectrode for use in a standard platelet aggregometer, thereby permitting simultaneous measurement of platelet aggregation and NO production. Treatment of platelets with the NO synthase inhibitor -NG-nitroarginine methyl ester (L-NAME), reduced NO production by 92+/-8% in response to 5 microM ADP compared to control but increased aggregation by only 15+/-2%. In contrast, L-NAME had a more pronounced effect on platelet recruitment as evidenced by a 35+/-5% increase in the extent of aggregation, a 33+/-3% decrease in cyclic GMP content, and a 31+/-5% increase in serotonin release from a second recruitable population of platelets added to stimulated platelets at the peak of NO production. To study platelet recruitment accurately, we developed an assay that monitors two platelet populations simultaneously. Nonbiotinylated platelets were incubated with L-NAME or vehicle and activated with ADP. At peak NO production, biotinylated platelets were added. As measured by three-color flow cytometry, there was a 56+/-11% increase in the number of P selectin- positive platelets in the nonbiotinylated population treated with L-NAME as compared to control. When biotinylated platelets were added to the L-NAME-treated nonbiotinylated population, the number of P selectin positive biotinylated plate-lets increased by 180+/-32% as compared to biotinylated platelets added to the control. In summary, stimulated platelets produce NO that modestly inhibits platelet activation but markedly inhibits additional platelet recruitment. These data suggest

  8. Anatomic and histological study of the rabbit mandible as an experimental model for wound healing and surgical therapies.

    PubMed

    Campillo, V-E; Langonnet, S; Pierrefeu, A; Chaux-Bodard, A-G

    2014-10-01

    The rabbit is one of the most widely used models for studying bone remodeling or dental implant osseointegration but very few data are available about the rabbit's mandible. The aim of this work was to describe the anatomy of the rabbit mandible and to estimate the available bone volume for experimental studies. First, with a dissection, the morphology of the mandible was described and the mental foramen, the position of the main salivary glands and muscular insertions were located. Then, by X-ray imaging, the position of the inferior alveolar canal, the dental root courses and volume and bone density were described. Finally, with frontal sections of the mandible body, the rabbit's dental and alveolar bone histological structure were assessed. Thus, the relevance of the rabbit mandible as an experimental model for wound healing or surgical therapies was discussed.

  9. Clinical uses of radiolabeled platelets

    SciTech Connect

    Datz, F.L.; Christian, P.E.; Baker, W.J.

    1985-12-01

    Platelets were first successfully radiolabeled in 1953. At that time, investigators were primarily interested in developing a technique to accurately measure platelet life span in both normal and thrombocytopenic patients. Studies using platelets labeled with /sup 51/Cr have shown shortened platelet survival times in a number of diseases including idiopathic thrombocytopenic purpura, coronary artery disease, and diabetes mellitus. More recently, labels such as /sup 111/In have been developed that allow in vivo imaging of platelets. Indium-111 platelets are being used to better understand the pathophysiology of atherosclerosis, thrombophlebitis, pulmonary embolism and clotting disorders, and to improve the clinical diagnosis of these diseases.

  10. Effect of Deviated Nasal Septum on Mean Platelet Volume: A Prospective Study.

    PubMed

    Poorey, Vijay Kumar; Thakur, Pooja

    2014-12-01

    In E.N.T clinical practice, patients with nasal obstruction due to deviated nasal septum is a common presentation. Nasal airway obstruction is a common cause of upper airway obstruction further leading to obstructive and hypoxic manifestations. Mean platelet volume (MPV) levels increase in hypoxic conditions. MPV is one of the platelet activation index which reflects the platelet production rate. Present prospective study conducted in the department of Otorhinolaryngology and Head and Neck surgery, Gandhi Medical College and Hamidia Hospital, Bhopal, on 63 patients with the clinical evidence of DNS and 63 healthy age matched subjects as control group, aimed to evaluate the relationship between MPV levels and nasal obstruction due to deviated nasal septum (DNS). The diagnosis of patients with DNS was based on anterior rhinoscopy and endoscopic nasal examination. Blood samples were collected before surgical correction. In present study, the authors found that there is preponderance of DNS in the age group of 25-45 years being the most active age group, males having the higher incidence. Majority of cases of DNS being left sided and of obstructed type. MPV were significantly higher in patients with DNS than the control group. Among the cases MPV being higher in females and in the impacted type of DNS. Present study reemphasized the concept that MPV is increased in chronic nasal obstruction due to DNS and this increase is in accordance with the severity of DNS.

  11. The association between placenta previa and leukocyte and platelet indices - a case control study.

    PubMed

    Ersoy, Ali O; Ozler, Sibel; Oztas, Efser; Ersoy, Ebru; Kirbas, Ayse; Danisman, Nuri

    2016-01-01

    Despite medical advances, rising awareness, and satisfactory care facilities, placenta previa (PP) remains a challenging clinical entity due to the risk of excessive obstetric hemorrhage. Etiological concerns gave way to life-saving concerns about the prediction of maternal outcomes due to hemorrhage. Our study aimed to detect an early predictive marker of placenta previa. Ninety-three pregnant patients diagnosed with PP and 247 controls were recruited for this retro-spective study. Platelet and leukocyte indices were compared between the two groups. The groups were similar with regard to age distribution (31.2 ± 5.1 years [mean ± SD] in the PP group and 31.7 ± 4.2 years in controls), body mass index (BMI) (27.7 ± 3.6 kg/m2 in the PP group and 27.4 ± 4.6 kg/m2 in controls), and most characteristics of the obstetric history. Total leukocyte count, neutrophil count, and neutrophil-to-lymphocyte ratio were significantly higher in the PP group. Mean platelet volume (MPV) and large platelet cell ratio (P-LCR) values were significantly lower in the PP group as compared to controls, with regard to third trimester values. However, patients who were diagnosed postnatally with placenta percreta had lower MPV and P-LCR values than other patients with PP. There were no statistically significant differences between the two groups as far as first trimester values were concerned. Platelet and leukocyte indices in the third trimester of pregnancy may be valuable predictors of placenta previa and placenta percreta. More comprehensive studies are needed to address this issue.

  12. Emulsified halothane produces long-term epidural anesthetic effect: a study in rabbits.

    PubMed

    Li, Fengshan; Liao, Daqing; Liu, Jin; Xiao, Lin; Guo, Jiao; Yi, Mingliang; Zhou, Cheng

    2015-01-01

    Previous studies have demonstrated that volatile anesthetics could produce local anesthesia. Emulsified isoflurane at 8% has been reported to produce epidural anesthetic effect in rabbits. This study was designed to investigate the long-term epidural anesthetic effect of emulsified halothane in rabbits. In this study, 40 healthy adult rabbits (weighting 2.0-2.5 kg) with an epidural catheter were randomly divided into 4 groups (n=10/group), receiving epidural administration of 1% lidocaine (lido group), 8% emulsified isoflurane 1ml (8% E-iso group), 8% emulsified halothane (8% E-Halo group) and 12% emulsified halothane (12% E-Halo group). After administration, sensory and motor functions as well as consciousness state were assessed until 60 minutes after sensory and motor function returned to its baseline or at least for 180 min. After epidural anesthesia, all the rabbits were continuously observed for 7 days and sacrificed for pathological evaluations. As a result, all the four study solutions produced typical epidural anesthesia. Onset times of sensory and motor function blockade were similar among the four groups (P>0.05). Duration of sensory blockade in 12% E-Halo group (83±13 min) was significantly longer than other groups: 51±12 min in 8% E-Halo group (P<0.01), 57±8 min in 8% E-iso group (P<0.01) and 47±9 min in lido group (P<0.01). Duration of sensory blockade in 8% E-iso group is longer than lido group (P<0.05). Duration of motor blockade in 12% E-Halo group (81±12 min) was also significantly longer than other groups: 40±8 min in 8% E-Halo group (P<0.01), 37±3 min in 8% E-iso group (P<0.01), 37±6 min in lido group (P<0.01). Normal consciousness was found in the rabbits from 8% E-Halo, 8% E-iso and lido groups while there were four rabbits in 12% E-Halo group (4/10) showed a light sedation. For all the rabbits, no pathological injury was found. The present study demonstrates that emulsified halothane produces reversible concentration

  13. [Mechanism of action of biogenic chloramines and hypochlorite on initial aggregation of blood platelets].

    PubMed

    Murina, M A; Savel'eva, E L; Roshchupkin, D I

    2006-01-01

    The antiaggregant action of two reactive oxidants N,N-dichlorotaurine (chloramine of biogenic type) and sodium hypochlorite on the initial ADP-induced aggregation of rabbit blood platelets has been studied. Platelet aggregation in the reconstructed platelet-rich plasma (PRP) was measured by the nephelometric method, and the aggregation index was an increase in the intensity of small-angle light scattering. The introduction of chloramine at comparatively small concentrations (no greater than 1 mM active chlorine) directly into the reconstructed platelet-rich plasma induces the suppression of the initial aggregation (formation of small aggregates) several times stronger than in the case of its preliminary incubation with plasma alone. This suggests that N,N-dichlorotaurine exerts its antiaggeregant action on the platelet-rich plasma by direct interaction with cells. The effects of the inhibition of platelet aggregation in two variants of introduction of high concentrations of N,N-dichlorotaurine do not significantly differ. In this case a great amount of residual chloramine remains in the plasma, which just induces the suppression of platelet aggregation during subsequent reconstruction of the platelet-rich plasma. Similar data have been obtained in the study of the antiaggregant action of hypochlorite. N,N-Dichlorotaurine and hypochlorite at final concentrations of 0.2-0.3 and 0.15 mM, respectively, inhibit strongly the initial aggregation of isolated platelets (approximately 2 x 10(8) cells in 1 ml) preliminarily activated for 1.5 min by the addition of 100-500 nM ADP. However, the antiaggregants show a more profound suppression of aggregation of unstimulated platelets. The antiaggregant effects of N,N-dichlorotaurine and hypochlorite are probably due to the oxidative modification of sulfur-containing groups in platelet plasmatic membrane.

  14. Correlation study between platelet count, leukocyte count, nonhemorrhagic complications, and duration of hospital stay in dengue fever with thrombocytopenia

    PubMed Central

    Jayanthi, Hari Kishan; Tulasi, Sai Krishna

    2016-01-01

    Introduction: Dengue is one of the common diseases presenting as fever with thrombocytopenia, also causing significant morbidity and complications. Objectives: Though the correlation between platelet count, bleeding manifestations and hemorrhagic complications has been extensively studied, less is known about the correlation between platelet count and non hemorrhagic complications. This study was done to see the correlation between platelet count and non hemorrhagic complications, duration of hospital stay and additive effect of leucopenia with thrombocytopenia on complications. Methods: Our study is prospective observational study done on 99 patients who had dengue fever with thrombocytopenia. Correlations were obtained using scatter plot and SPSS software trail version. Results: Transaminitis (12.12%) was the most common complication followed by acute renal injury (2%). In our study we found that, as the platelet count decreased the complication rate increased (P = 0.0006). In our study duration of hospital increased (P is 0.00597) with decreasing platelet count when compared to other study where there was no correlation between the two. There was no correlation between thrombocytopenia with leucopenia and complications (P is 0.292), similar to other study. Conclusion: Platelet count can be used to predict the complication and duration of hospital stay and hence better use of resources. PMID:27453855

  15. Using a new plateau hyperbaric chamber to alleviate high altitude hypoxia: Rabbit and human studies.

    PubMed

    Sun, Liang; Ding, Meng-Jiang; Cai, Tian-Cai; Fan, Hao-Jun; Gao, Hong-Mei; Zhang, Jian-Peng

    2017-04-19

    To validate the effects of the new plateau hyperbaric chamber on alleviating high altitude hypoxia on Mount Kun Lun. A prospective, controlled study of rabbits and adult volunteers was conducted at altitudes of 355, 2880 and 4532m. We obtained arterial blood samples from rabbits and volunteers before and after hyperbaric treatment. The respiratory rate, heart rate, and blood pressure (BP) of adult volunteers were monitored during hyperbaric treatment. The mean PaO2 levels of experimental group rabbits and volunteers increased significantly after 60min of hyperbaric treatment at 350, 2880 and 4532m. The mean PaCO2 and pH levels of rabbits were not significant different before and after hyperbaric treatment at each altitude. The mean PaCO2 and pH levels were not significant different at 355m in the human study. However, at 2880 and 4532m, pH fell with increasing PaCO2 levels in humans before and after hyperbaric treatment. The new multiplace plateau hyperbaric chamber may be used to alleviate plateau hypoxia by increasing patient PaO2. However, its value in treating AMS must be confirmed in field conditions. Copyright © 2017. Published by Elsevier Inc.

  16. Sodium iodoacetate induced osteoarthrosis model in rabbit temporomandibular joint: CT and histological study (part I).

    PubMed

    Güler, N; Kürkçü, M; Duygu, G; Cam, B

    2011-11-01

    Studies to elucidate the pathophysiology of osteoarthrosis have been hampered by the lack of a rapid, reproducible animal model that mimics the histopathology and symptoms associated with the disease. The aim of this study is to evaluate the radiological, histological and histomorphometrical findings of four different concentrations of sodium iodoacetate (MIA) to create osteoarthrosis by using an arthrocentesis technique on rabbit temporomandibular joint (TMJ). 12 New Zealand white male rabbits received an injection of MIA (50 μl dose of 1.5, 2, 2.5, 3mg/ml concentrations) to a single joint of each group by arthrocentesis. Computed tomography (CT) images were obtained pre- and post-injections at 2, 4 and 6 weeks. Early osteoarthritic changes in the rabbit TMJ were found histologically at 4 weeks and with a 3mg/ml concentration of MIA. The mean subchondral bone volume depended on the concentration of MIA and was 62±2.6%, 63±4.1%, 42±3.6% and 38±3.8%, respectively. A minor abnormality was found on CT in six joints at the 4-week follow up. MIA injection and arthrocentesis offer a rapid and minimally invasive method of reproducing histologically osteoarthrotic lesions in the rabbit TMJ.

  17. Platelet Donation

    MedlinePlus

    ... donating platelets, can I still donate blood? What blood types should donate platelets? Can I donate plasma at ... Community Learn About Blood Blood Facts and Statistics Blood Types Blood Components What Happens to Donated Blood Blood ...

  18. Effects of autologous platelet-rich plasma on implantation and pregnancy in repeated implantation failure: A pilot study

    PubMed Central

    Nazari, Leila; Salehpour, Saghar; Hoseini, Sedighe; Zadehmodarres, Shahrzad; Ajori, Ladan

    2016-01-01

    Background: Repeated implantation failure (RIF) is a major challenge in reproductive medicine and despite several methods that have been described for management, there is little consensus on the most effective one. Objective: This study was conducted to evaluate the effectiveness of platelet-rich plasma in improvement of pregnancy rate in RIF patients. Materials and Methods: Twenty women with a history of RIF who were candidates for frozen-thawed embryo transfer were recruited in this study. Intrauterine infusion of 0.5 ml of platelet-rich plasma that contained platelet 4-5 times more than peripheral blood sample was performed 48 hrs before blastocyst transfer. Results: Eighteen participants were pregnant with one early miscarriage and one molar pregnancy. Sixteen clinical pregnancies were recorded and their pregnancies are ongoing. Conclusion: According to this study, it seems that platelet-rich plasma is effective in improvement of pregnancy outcome in RIF patients. PMID:27921085

  19. Functional fractionation of platelets.

    PubMed

    Haver, V M; Gear, A R

    1981-02-01

    Studies of platelet populations suggest that they are heterogeneous in size, age, and metabolic parameters. In an attempt to correlate these parameters with efficiency of aggregation, a new technique, functional fractionation, was developed. Platelet populations are separated by their differential reactivity to aggregating agents. For example, low doses of ADP (0.1 to 0.7 microM) are added to stirred PRP, after which gentle centrifugation is used to remove aggregates from single unreacted platelets. The loose aggregates can be readily dispersed for comparison of the physical or biochemical properties of the reacted versus unreacted platelets. It was found that reactive platelets were larger (6.5 micrometer3) than unreacted platelets (5.51 micrometer3). No significant difference in density existed between the two populations, and no release of [14C]serotonin from prelabeled platelets occurred during functional fractionation. Scanning and transmission electron microscopy confirmed the size difference and revealed that in both populations platelets were structurally intact with a normal discoid shape and no significant difference in organelle content. Human platelets most reactive to ADP were also enriched in glycogen (3.6-fold), ATP (1.6-fold), and ADP (twofold), compared with less reactive cells. These "reactive" cells took up more 51[Cr] and contained 1.9 times more surface sialic acid. In an in vivo aging experiment, rats were injected with 75[Se]methionine. Shortly after labeling (1 day), the most reactive platelets possessed the highest amount of 75[Se]. These results reveal that functionally active platelets, which are also larger, are more active metabolically than less reactive platelets, possess a higher negative surface charge, and may be a younger population.

  20. Subpopulations in purified platelets adhering on glass.

    PubMed

    Donati, Alessia; Gupta, Swati; Reviakine, Ilya

    2016-06-22

    Understanding how platelet activation is regulated is important in the context of cardiovascular disorders and their management with antiplatelet therapy. Recent evidence points to different platelet subpopulations performing different functions. In particular, procoagulant and aggregating subpopulations have been reported in the literature in platelets treated with the GPVI agonists. How the formation of platelet subpopulations upon activation is regulated remains unclear. Here, it is shown that procoagulant and aggregating platelet subpopulations arise spontaneously upon adhesion of purified platelets on clean glass surfaces. Calcium ionophore treatment of the adhering platelets resulted in one platelet population expressing both the procoagulant and the adherent population markers phosphatidylserine and the activated form of GPIIb/IIIa, while all of the platelets expressed CD62P independently of the ionophore treatment. Therefore, all platelets have the capacity to express all three activation markers. It is concluded that platelet subpopulations observed in various studies reflect the dynamics of the platelet activation process.

  1. Platelet size in man.

    PubMed

    Paulus, J M

    1975-09-01

    The shape and parameters of platelet size distributions were studied in 50 normal persons and 97 patients in order to test the proposed thesis that platelet size heterogeneity results mainly from aging in the circulation. This thesis was contradicted (1) by size distributions of age-homogeneous, newly-born cell populations which were lognormal with increased (instead of decreased) dispersion of volumes and (2) by the macrothrombocytosis found in some populations with normal age distribution. For these reasons, thrombocytopoiesis appeared to play the major role in determining platelet size. A model was built in which the volume variation of platelet territories due to megakaryocyte growth and membrane demarcation at each step of maturation was a random proportion of the previous value of the volume. This model explains the lognormal shape of both newborn and circulating platelet size distributions. It also implies that (1) the mean and standard deviation of platelet logvolumes depend on the rates of volume change of the individual platelet territories (growth rate minus demarcation rate) as well as on megakaryocyte maturation time; (2) platelet hyperdestruction causes an increase in the mean and dispersion of the rates of territory volume change; (3) Mediterranean macrothrombocytosis and some hereditary macrothrombocytotic thrombocytopenias or dysthrombocytopoieses reflect a diminished rate of territory demarcation, and (4) platelet size heterogeneity is caused mainly by the variations in territory growth and demarcation and not by aging in the circulation.

  2. Growth factor expression after lesion creation in the avascular zone of the meniscus: a quantitative PCR study in rabbits.

    PubMed

    Ruiz Ibán, Miguel Ángel; Comellas Melero, Nerea; Martinez-Botas, Javier; Ortiz, Ana; Diaz Heredia, Jorge

    2014-09-01

    To define the variations in the expression of 5 growth factor genes in meniscal tissue after a lesion is created in the avascular zone of the medial meniscus of the rabbit. A longitudinal lesion was created in the avascular zone of the anterior horn of the medial meniscus in 42 rabbits. Six animals were killed at 0, 1, 3, 7, 14, 21, and 120 days after lesion creation. Meniscal tissue from the avascular and vascular zones was harvested. A quantitative polymerase chain reaction analysis was performed to evaluate the expression levels of 5 different growth factors: vascular endothelial growth factor A (VEGF-A), insulin-like growth factor 1 (IGF-1), transforming growth factor β1 (TGF-β1), platelet-derived growth factor β (PDGF-β), and interleukin 1β. The basal expression levels of all the growth factors studied were similar in the avascular and vascular zones. There was an increase in VEGF-A expression in the avascular zone on the 14th day, an increase in IGF-1 expression in the vascular zone on the 14th day, a decrease in PDGF-β expression in both zones in the first week, an increase in interleukin 1β expression in both zones on the first day, and a decrease in TGF-β1 expression in the vascular zone in the first week. At 120 days, the expression levels of all 5 growth factors returned to basal levels. There are significant variations in the expression of the growth factors studied during the first weeks after meniscal lesion creation. The preinjury expression levels are similar in the avascular and vascular zones and are not significantly different from the basal levels 4 months after injury. This study identifies potential therapeutic molecular targets (VEGF-A, IGF-1, TGF-β1, and PDGF-β) that can be used in the treatment of meniscal tears. Copyright © 2014 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  3. Prenatal developmental toxicity study of ethyl tertiary-butyl ether in rabbits.

    PubMed

    Asano, Yuzo; Ishikura, Toshikazu; Kudoh, Kayoko; Haneda, Ryo; Endoh, Takako

    2011-07-01

    Ethyl tertiary-butyl ether (ETBE) is commonly used as an oxygenated gasoline additive. In this study, the prenatal developmental toxicity of ETBE was determined in rabbits. New Zealand white rabbits were given ETBE by gavage at 100, 300, or 1,000 mg/kg/day on gestational days (GDs) 6-27, and the pregnancy outcome was determined on GD 28. Neither death nor abortion occurred in the pregnant rabbits at any dose. Slightly and significantly suppressed maternal body-weight gain and transiently decreased maternal food consumption were found at 1,000 mg/kg/day during the administration period. At this dose, no changes in clinical or macroscopic finding were noted in dams. No treatment-related changes were observed in any dam treated at 300 mg/kg/day or less. There was no significant effect of ETBE on the numbers of corpora lutea, implantations, live fetuses, resorptions and dead fetuses, incidences of pre- and postimplantation loss, viability of fetuses, fetal body weight, sex ratio of fetuses, or weights of gravid uteri. No significant difference was detected in the incidences of fetuses with malformations or variations between the ETBE-treated and control groups. Also, no adverse effects on the progress of ossification were noted in fetuses of dams given ETBE. Based on these findings, it is concluded that the no observed adverse effect levels of ETBE were 300 mg/kg/day for dams and 1,000 mg/kg/day for fetuses in rabbits.

  4. Molecular dynamics studies on the NMR and X-ray structures of rabbit prion proteins.

    PubMed

    Zhang, Jiapu; Zhang, Yuanli

    2014-02-07

    Prion diseases, traditionally referred to as transmissible spongiform encephalopathies (TSEs), are invariably fatal and highly infectious neurodegenerative diseases that affect a wide variety of mammalian species, manifesting as scrapie in sheep and goats, bovine spongiform encephalopathy (BSE or mad-cow disease) in cattle, chronic wasting disease in deer and elk, and Creutzfeldt-Jakob diseases, Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia, and kulu in humans, etc. These neurodegenerative diseases are caused by the conversion from a soluble normal cellular prion protein (PrP(C)) into insoluble abnormally folded infectious prions (PrP(Sc)), and the conversion of PrP(C) to PrP(Sc) is believed to involve conformational change from a predominantly α-helical protein to one rich in β-sheet structure. Such a conformational change may be amenable to study by molecular dynamics (MD) techniques. For rabbits, classical studies show that they have a low susceptibility to be infected by PrP(Sc), but recently it was reported that rabbit prions can be generated through saPMCA (serial automated Protein Misfolding Cyclic Amplification) in vitro and the rabbit prion is infectious and transmissible. In this paper, we first do a detailed survey on the research advances of rabbit prion protein (RaPrP) and then we perform MD simulations on the NMR and X-ray molecular structures of rabbit prion protein wild-type and mutants. The survey shows to us that rabbits were not challenged directly in vivo with other known prion strains and the saPMCA result did not pass the test of the known BSE strain of cattle. Thus, we might still look rabbits as a prion resistant species. MD results indicate that the three α-helices of the wild-type are stable under the neutral pH environment (but under low pH environment the three α-helices have been unfolded into β-sheets), and the three α-helices of the mutants (I214V and S173N) are unfolded into rich β-sheet structures under

  5. A comprehensive study on different modelling approaches to predict platelet deposition rates in a perfusion chamber

    PubMed Central

    Pallarès, Jordi; Senan, Oriol; Guimerà, Roger; Vernet, Anton; Aguilar-Mogas, Antoni; Vilahur, Gemma; Badimon, Lina; Sales-Pardo, Marta; Cito, Salvatore

    2015-01-01

    Thrombus formation is a multiscale phenomenon triggered by platelet deposition over a protrombotic surface (eg. a ruptured atherosclerotic plaque). Despite the medical urgency for computational tools that aid in the early diagnosis of thrombotic events, the integration of computational models of thrombus formation at different scales requires a comprehensive understanding of the role and limitation of each modelling approach. We propose three different modelling approaches to predict platelet deposition. Specifically, we consider measurements of platelet deposition under blood flow conditions in a perfusion chamber for different time periods (3, 5, 10, 20 and 30 minutes) at shear rates of 212 s−1, 1390 s−1 and 1690 s−1. Our modelling approaches are: i) a model based on the mass-transfer boundary layer theory; ii) a machine-learning approach; and iii) a phenomenological model. The results indicate that the three approaches on average have median errors of 21%, 20.7% and 14.2%, respectively. Our study demonstrates the feasibility of using an empirical data set as a proxy for a real-patient scenario in which practitioners have accumulated data on a given number of patients and want to obtain a diagnosis for a new patient about whom they only have the current observation of a certain number of variables. PMID:26391513

  6. Effect of platelet concentrate on quality of life after periradicular surgery: a randomized clinical study.

    PubMed

    Del Fabbro, Massimo; Ceresoli, Valentina; Lolato, Alessandra; Taschieri, Silvio

    2012-06-01

    Control of postoperative discomfort might enhance the patient's quality of life and treatment acceptance. The aim of the present randomized single-blind study was to evaluate whether the use of platelet concentrate during endodontic surgery might have a favorable impact on pain and other factors related to patient's quality of life during the first week after surgery. Eighteen patients with periapical lesion were treated with modern endodontic surgical procedure (control group). In another 18 patients, in adjunct to surgical procedure, platelet concentrate was applied on the root end in liquid form, within the bone defect in clot form, and over the suture in liquid form (test group). All patients completed a questionnaire for evaluation of main symptoms and daily activities during the first week after surgery. The outcomes of the questionnaires of the 2 groups were statistically compared. The test group showed significantly less pain and swelling, fewer analgesics taken, and improved functional activities as compared with the control group. The adjunct of platelet concentrate to the endodontic surgical procedure produced significant beneficial effect to patients' quality of life during the early postoperative stage. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  7. Giant Platelets in Platelet Donors – A Blessing in Disguise?

    PubMed Central

    Choudhury, Nabajyoti; Ray, Deepanjan

    2015-01-01

    Introduction Inherited thrombocytopenias, including inherited giant platelet disorders (IGPD) are relatively rare, but their prevalence is probably underestimated. Harris platelet syndrome, the most common IGPD reported from Indian subcontinent, mostly from eastern part, is characterised by a low platelet count, high mean platelet volume (MPV) and absence of bleeding. Aim A short study was conducted to assess the prevalence of giant platelets in voluntary donors of single donor platelets (SDP) and analyse the effect of transfusion of such SDPs in patients. Materials and Methods Voluntary donors of SDPs were screened as per standard guidelines prior to the procedure. A complete blood count (including MPV) along with a peripheral smear was done. A total of 45 donors were screened for plateletpheresis. Following plateletpheresis from these donors, a platelet count from the collection bag was done after one hour. The SDP was transfused as a single unit or divided into two and transfused to the same patient at two different occasions, as per clinical need. Platelet counts on pateints were done after one hour and the platelet recovery was noted. Results Out of the 45 donors who were screened, 30 (66.67%) were found to have giant platelets. It was observed that the pre procedure platelet counts in donors having giant platelets were relatively low (1.5 -1.7 lacs) and so also the platelet yield (2.7-3x1011) compared to donors who did not, but the post transfusion platelet recovery was greater. Conclusion Since presence of giant platelets has been seen to be common in the Eastern part of India, a peripheral smear examination should always be considered during screening of plateletpheresis donors to avoid rejecting donors with giant platelets whose platelet counts are given falsely low by autoanalysers. PMID:26266124

  8. Effect of alendronate on endosseous implant integration: an in vivo study in rabbits.

    PubMed

    Chacon, Guillermo E; Stine, Eric A; Larsen, Peter E; Beck, F Michael; McGlumphy, Edwin A

    2006-07-01

    Alendronate sodium (Fosamax; Merck, Whitehouse Station, NJ) is a second-generation bisphosphonate used widely in osteopenic individuals for decreasing bone resorption and increasing bone density. The ability of alendronate to affect systemic bone remodeling raises natural questions about the drug's influence on dental implant osseointegration. Current knowledge regarding the effect of systemic bisphosphonates, specifically alendronate, on all 3 phrases of osseointegration is incomplete and only a few studies have started to investigate peri-implant bone responses to alendronate-coated implants. The purpose of this study was to determine the effect of systemic alendronate therapy on osseointegration of dental implants based on torque-removal values in rabbits. Identical titanium dental implants were placed using a standardized surgical protocol in the bilateral distal femur and proximal tibia of 20 New Zealand white rabbits (79 implants total). One week before implant placement, 10 rabbits were given doses of alendronate and continued on weekly dosing for 5 weeks until euthanized. The other 10 rabbits were untreated controls. Torque-removal values were determined using a Tohinichi 15-BTG torque wrench (Tohinichi Mfg Co, Ltd, Tokyo, Japan) for all implants. Analysis of torque data showed no statistical differences between the alendronate and control groups in both femur and tibia sites. A statistically significant difference, however, was noted in torque removal values between femur and tibia sites regardless of drug or non-drug groups. In summary, orally dosed alendronate administration in rabbits had no significant effect on dental implant torque-removal values 6 weeks after endosseous placement in femur and tibia.

  9. Platelet interactions with Candida albicans.

    PubMed Central

    Skerl, K G; Calderone, R A; Sreevalsan, T

    1981-01-01

    The interaction of human platelets and Candida albicans was studied. Platelet-rich plasma was obtained from freshly drawn blood or outdated platelet concentrates. From the platelet-rich plasma, a platelet extract was derived which stimulated germ tube formation by C. albicans when incubated with yeast cells at 37 degrees C. The active component(s) was heat stable, trypsin sensitive, and ribonuclease and deoxyribonuclease insensitive, and possessed cationic properties since it readily attached to carboxymethyl-Sephadex. The active component(s) seemed to bind to heparin also, since germ tube-promoting activity was eluted from a heparin-cyanogen bromide-activated Sepharose 4B column. In addition, platelet-derived growth factor (Collaborative Research, Inc.) stimulated germination when incubated with low amounts (0.4% final concentration) of bovine calf serum. The aggregation of platelets, prepared as platelet-rich plasma by C. albicans cell wall or alkali-extracted cell wall fractions, was also studied. Aggregation of platelets was observed when cell wall or cell wall fractions were incubated with platelet-poor plasma at 37 degrees C for 20 min and then added to platelet-rich plasma. The component of platelet-poor plasma which promoted aggregation of platelets by C. albicans cell wall or alkali-extracted fractions was inactivated at 56 degrees C (30 min) and by cobra venom factor, indicating a role for the alternate complement pathway in the aggregation response. PMID:7037646

  10. Effects of combination treatment with policosanol and omega-3 fatty acids on platelet aggregation: A randomized, double-blind clinical study

    PubMed Central

    Castaño, Gladys; Arruzazabala, Maria L.; Fernández, Lilia; Mas, Rosa; Carbajal, Daisy; Molina, Vivian; Illnait, José; Mendoza, Sarahí; Gámez, Rafael; Mesa, Melbis; Fernández, Julio

    2006-01-01

    Background: Policosanol is a mixture of long-chain primary aliphatic alcoholspurified from sugar cane wax that has cholesterol lowering and antiplatelet effects. Omega-3 fatty acids (FA) have triglyceride lowering and antiplatelet effects. Combination treatment with policosanol and omega-3 FA (Ω23FA) has been associated with significant inhibition of platelet aggregation in rabbits compared with either drug alone. Objective: The aim of this study was to investigate the effects of combination treatment with Ω3FA (1 g/d) and policosanol (Ω3FA+Poli) compared with Ω3FA (1 g/d) plus placebo (Ω3FA+Pla) on platelet aggregation in human patients with hypercholesterolemia. Methods: This randomized, double-blind, clinical study at the Surgical Medical Research Center (Havana City, Cuba) recruited outpatients from lipid clinics, with some atherosclerotic risk factors. Outpatients of both sexes aged 20 to 75 years with serum total cholesterol (TC) levels ≥5 and <6 mmol/L were eligible to enroll. They were included in the study at the end of a 4-week diet stabilization period if their platelet aggregation to arachidonic acid (AA) was ≥50% and serum TC level remained ≥5 mmol/L. Patients were then evenly randomized to receive Ω3FA (1 g/d) + placebo or Ω3FA (1 g/d) + policosanol (10 mg/d) to be taken PO with the evening meal for 21 days. Treatment was assigned according to a randomization code using balanced blocks and a 1:1 allocation ratio. Inhibition of platelet aggregation to AA was the primary efficacy variable, while effects on platelet aggregation to collagen and epinephrine and on lipid profile were secondary variables. Drug compliance and adverse events (AEs) were monitored. Tolerability was assessed using physical examinations and laboratory test results. Results: Sixty-four subjects were initially enrolled. Fifty-four patients (30 women, 24 men; mean [SD] age, 58.4 [12] years, [range, 40–70 years]) met the inclusion criteria and were randomized to

  11. An association of platelet indices with blood pressure in Beijing adults: Applying quadratic inference function for a longitudinal study.

    PubMed

    Yang, Kun; Tao, Lixin; Mahara, Gehendra; Yan, Yan; Cao, Kai; Liu, Xiangtong; Chen, Sipeng; Xu, Qin; Liu, Long; Wang, Chao; Huang, Fangfang; Zhang, Jie; Yan, Aoshuang; Ping, Zhao; Guo, Xiuhua

    2016-09-01

    The quadratic inference function (QIF) method becomes more acceptable for correlated data because of its advantages over generalized estimating equations (GEE). This study aimed to evaluate the relationship between platelet indices and blood pressure using QIF method, which has not been studied extensively in real data settings.A population-based longitudinal study was conducted in Beijing from 2007 to 2012, and the median of follow-up was 6 years. A total of 6515 cases, who were aged between 20 and 65 years at baseline and underwent routine physical examinations every year from 3 Beijing hospitals were enrolled to explore the association between platelet indices and blood pressure by QIF method. The original continuous platelet indices were categorized into 4 levels (Q1-Q4) using the 3 quartiles of P25, P50, and P75 as a critical value. GEE was performed to make a comparison with QIF.After adjusting for age, usage of drugs, and other confounding factors, mean platelet volume was negatively associated with diastolic blood pressure (DBP) (Equation is included in full-text article.)in males and positively linked with systolic blood pressure (SBP) (Equation is included in full-text article.). Platelet distribution width was negatively associated with SBP (Equation is included in full-text article.). Blood platelet count was associated with DBP (Equation is included in full-text article.)in males.Adults in Beijing with prolonged exposure to extreme value of platelet indices have elevated risk for future hypertension and evidence suggesting using some platelet indices for early diagnosis of high blood pressure was provided.

  12. Mean platelet volume is a risk factor for venous thromboembolism: the Tromsø Study, Tromsø, Norway.

    PubMed

    Braekkan, S K; Mathiesen, E B; Njølstad, I; Wilsgaard, T; Størmer, J; Hansen, J B

    2010-01-01

    Platelet size, measured as mean platelet volume (MPV), is associated with platelet reactivity. MPV is increased in acute myocardial infarction, and has been identified as an independent risk factor for future myocardial infarction and stroke. The purpose of the study was to determine the impact of platelet count and MPV on the incidence of venous thromboembolism (VTE) in a prospective, population-based study. Platelet count, MPV and baseline characteristics were registered in 25 923 subjects aged 25-96 years who participated in the Tromsø Study in 1994-1995. Incident VTE events were registered to the end of follow-up (1 September 2007). There were 445 validated incident VTE events (1.6 per 1000 person-years), of which 186 (42%) were unprovoked, during a mean of 10.8 years of follow-up. Subjects with MPV >or= 9.5 fL had a 1.3-fold [95% confidence interval (CI) 1.0-1.7] higher risk of total VTE and a 1.5-fold (95% CI 1.1-2.3) higher risk of unprovoked VTE than subjects with MPV < 8.5 fL in analyses adjusted for age, sex, smoking, body mass index, and platelet count. Increasing MPV was associated with increased risk of total VTE (P for trend = 0.09) and unprovoked VTE (P for trend = 0.03) in analyses adjusted for age and sex. There was no significant association between increasing platelet count and risk of VTE. An increasing MPV was identified as a predictor for VTE, in particular VTE of unprovoked origin. The present findings support the concept that platelet reactivity is important in the pathogenesis of VTE.

  13. Low toxicity of diphenyl diselenide in rabbits: a long-term study.

    PubMed

    de Bem, Andreza Fabro; de Lima Portella, Rafael; Farina, Marcelo; Perottoni, Juliano; Paixão, Márcio Weber; Nogueira, Cristina Wayne; Teixeira Rocha, João Batista

    2007-07-01

    Selenium compounds, like diphenyl diselenide (Ph(2)Se(2)), possess glutathione peroxidase (GSHPx)-like activities and other antioxidant properties. The aim of this study was to evaluate the effects of a long-term oral supplementation with Ph(2)Se(2) on various toxicological parameters in rabbits. Adult New Zealand male rabbits were divided into four groups: Group I served as control; Groups II, III and IV received 0.3, 3.0 and 30 p.p.m. of Ph(2)Se(2) pulverized in the chow for 8 months. A number of toxicological parameters were examined in liver, kidney, cerebral cortex and hippocampus, such as delta-aminolaevulinic acid dehydratase (delta-ALA-D), catalase (CAT), GSHPx activities, non-protein thiol (-SH), lipid peroxidation and ascorbic acid levels. The results indicated that supplementation 30 p.p.m. Ph(2)Se(2 )significantly increased delta-ALA-D activity in liver and in cerebral cortex. Non-protein -SH levels were significantly increased in liver but not in kidney, cerebral cortex and hippocampus of rabbits. Ascorbic acid content was significantly lower in the liver and cerebral cortex after supplementation with 30 p.p.m. Ph(2)Se(2). Conversely, no alterations in GSHPx and CAT activities, nor in thiobarbituric acid reactive substances levels were observed in rabbit tissues. These results indicate that oral supplementation with Ph(2)Se(2) is relatively secure in rabbits after 8 months of exposure. The findings encourage further experiments on the potential therapeutic effects of such compound.

  14. [Reproductive and developmental toxicity studies of landiolol hydrochloride (ONO-1101) (3). Teratogenicity study in rabbits].

    PubMed

    Nishimura, T; Chihara, N; Sakamoto, T; Nakagawa, Y; Aze, Y; Tanaka, M; Shimouchi, K; Ozeki, Y; Fujita, T

    1997-12-01

    A teratogenicity study of landiolol hydrochloride (ONO-1101), a novel ultra short acting beta-blocker, was conducted in KAR:NZW rabbits. ONO-1101 was administered intravenously at a dose level of 0 (control), 25, 50 or 100 mg/kg/day to pregnant rabbit from day 6 to 18 of gestation to examine the effects on dams and fetuses. Death occurred on 3 animals in the 100 mg/kg/day group and one animal in the 50 mg/kg/day group during the treatment period. Hypoactivity, bradypnea/apnea and clonic convulsion after administration was observed in animal dosed 100 mg/kg/day. No maternal effects were seen on body weight, food consumption, necropsy findings or organ weights. External, skeletal and visceral findings revealed no adverse effects of ONO-1101 on fetuses. From the above results, it is estimated that the no-toxic dose level of ONO-1101 under these experimental conditions is 25 mg/kg/day for dams and 100 mg/kg for fetuses.

  15. The platelet fibrinogen receptor: an immunogold-surface replica study of agonist-induced ligand binding and receptor clustering

    PubMed Central

    1987-01-01

    Platelet aggregation requires the binding of fibrinogen to its receptor, a heterodimer consisting of the plasma-membrane glycoproteins (GP) IIb and IIIa. Although the GPIIb-IIIa complex is present on the surface of unstimulated platelets, it binds fibrinogen only after platelet activation. We have used an immunogold-surface replica technique to study the distribution of GPIIb-IIIa and bound fibrinogen over broad areas of surface membranes in unstimulated, as well as thrombin-activated and ADP-activated human platelets. We found that the immunogold-labeled GPIIb-IIIa was monodispersed over the surface of unstimulated platelets, although the cell surface lacked immunoreactive fibrinogen. On thrombin-stimulated platelets, approximately 65% of the GPIIb-IIIa molecules were in clusters within the plane of the membrane. Fibrinogen, which had been released from the alpha-granules of these cells, bound to GPIIb-IIIa on the cell surface and was similarly clustered. To determine whether the receptors clustered before ligand binding, or as a consequence thereof, we studied the surface distribution of GPIIb-IIIa after stimulation with ADP, which causes activation of the fibrinogen receptor function of GPIIb-IIIa without inducing the release of fibrinogen. In the absence of added fibrinogen, the unoccupied, yet binding-competent receptors on ADP-stimulated platelets were monodispersed. The addition of fibrinogen caused the GPIIb-IIIa molecules to cluster on the cell surface. Clustering was also induced by the addition of the GPIIb-IIIa-binding domains of fibrinogen, namely the tetrapeptide Arg-Gly-Asp-Ser on the alpha-chain or the gamma-chain decapeptide gamma 402-411. These results show that receptor occupancy causes clustering of GPIIb-IIIa in activated platelets. PMID:3584243

  16. Which platelet function test best reflects the in vivo plasma concentrations of ticagrelor and its active metabolite? The HARMONIC study.

    PubMed

    Koziński, Marek; Ostrowska, Małgorzata; Adamski, Piotr; Sikora, Joanna; Sikora, Adam; Karczmarska-Wódzka, Aleksandra; Marszałł, Michał Piotr; Boinska, Joanna; Laskowska, Ewa; Obońska, Ewa; Fabiszak, Tomasz; Kubica, Jacek

    2016-11-30

    Aim of this study was assessment of the relationship between concentrations of ticagrelor and its active metabolite (AR-C124910XX) and results of selected platelet function tests. In a single-centre, cohort study, patients with myocardial infarction underwent blood sampling following a 180 mg ticagrelor loading dose intake (predose, 1, 2, 3, 4, 6, 12, 24 hours postdose) to perform pharmacokinetic and pharmacodynamic assessments. Platelet reactivity was evaluated using the VASP-assay, the VerifyNow device and the Multiplate analyzer. Analysis of 36 patients revealed high negative correlations between ticagrelor concentrations and platelet reactivity evaluated with all three platelet function tests (the VASP-assay: RS=-0.722; p<0.0001; the VerifyNow device: RS=-0.715; p<0.0001; the Multiplate analyzer: RS=-0.722; p<0.0001), with no significant differences between correlation coefficients. Similar results were found for AR-C124910XX. Platelet reactivity values assessed with all three methods generally correlated well with each other; however, a significantly higher correlation (p<0.02) was demonstrated between the VerifyNow and Multiplate tests (RS=0.707; p<0.0001) than in other assay combinations (the VASP-assay and the VerifyNow device: RS=0.595; p<0.0001; the VASP-assay and the Multiplate analyzer: RS=0.588; p<0.0001). With respect to the recognition of high platelet reactivity, we found higher measurement concordance between the VerifyNow and Multiplate tests compared with other assay combinations, while for low platelet reactivity, only results of the VerifyNow and Multiplate assay were related to each other. Platelet reactivity measurements performed with the VASP, VerifyNow and Multiplate tests show comparably strong negative correlations with ticagrelor and AR-C124910XX concentrations.

  17. Pet rabbits.

    PubMed

    Hillyer, E V

    1994-01-01

    Pet rabbits are becoming more common, and rabbit owners are demanding quality veterinary care. This article provides a broad overview of pet rabbit medicine, which is a relatively new field compared to laboratory and farm rabbit medicine. The most common differential diagnoses for presenting complaints are summarized in table form. Disease conditions are reviewed individually in the text. Sources of further information on veterinary care of rabbits are listed throughout the text, in an appendix, and in the references.

  18. Surface modifications in the platelets of a patient with alpha-N-acetyl-D-galactosamine residues, the Tn-syndrome.

    PubMed Central

    Nurden, A T; Dupuis, D; Pidard, D; Kieffer, N; Kunicki, T J; Cartron, J P

    1982-01-01

    The Tn-syndrome is an acquired disorder characterized by the polyagglutination of blood cells and the pathological exposure of alpha-N-acetyl-D-galactosamine residues (Tn-antigen) at the cell surface. We now report studies on the platelet of a patient (Ba.) of which 81% reacted positively with a fluorescein conjugate of Helix pomatia agglutinin (HPA). The surface proteins of Ba. platelets were labeled with 125I by the lactoperoxidase-catalyzed procedure; single and two-dimensional electrophoresis on sodium dodecyl sulfate (SDS)-polyacrylamide gels was followed by autoradiography that revealed normal 125I-labeling of the major membrane glycoproteins (GP) but that GP Ib had a faster than normal migration. the abnormal GP Ib of Ba. platelets was strongly labeled when platelet suspensions were treated sequentially with neuraminidase, galactose oxidase, and sodium [3H]borohydride. Unlike the GP Ib of normal human platelets, it was also strongly labeled when Ba. platelets were treated with galactose oxidase and sodium [3H]borohydride alone. Both the alloantigen, PlA1, and quinidine-dependent antibody receptor activity were normally expressed by Ba. platelets, which also bound a monoclonal antibody (AN51) to GP Ib. Analysis of Ba. platelets by crossed immunoelectrophoresis using a rabbit anti-human platelet antibody preparation revealed the presence of an immunoprecipitate in the GP Ib position that had an abnormal appearance and migration in the second dimension. An altered position of the precipitate given by Factor VIIIR:Ag was also noted. Incorporation of HPA into the agarose gel during the first dimension electrophoresis resulted in the specific precipitation of the abnormal GP Ib of Ba. platelets. Our studies show that circulating Tn-platelets contain GP Ib with a modified oligosaccharide chain structure responsible for the platelet expression of Tn-antigen activity. Images PMID:7174794

  19. Studies on antioxidant properties of polyphenol-rich extract from berries of Aronia melanocarpa in blood platelets.

    PubMed

    Olas, B; Wachowicz, B; Nowak, P; Kedzierska, M; Tomczak, A; Stochmal, A; Oleszek, W; Jeziorski, A; Piekarski, J

    2008-12-01

    The antioxidant properties of extract from berries of Aronia melanocarpa (chokeberry) containing: anthocyanidines, phenolic acids and quercetine glycosides on oxidative/nitrative stress induced by peroxynitrite (ONOO(-), a powerful physiological oxidant, nitrating species and inflammatory mediator) in human blood platelets were studied in vitro. The extract from A. melanocarpa (5 - 50 microg/mL) significantly inhibited platelet protein carbonylation (measured by ELISA method) and thiol oxidation estimated with 5,5'-dithio-bis(2-nitro-benzoic acid) (DTNB) induced by peroxynitrite (0.1 mM) (IC(50)--35 microg/mL for protein carbonylation, and IC(50)--33 microg/mL for protein thiol oxidation). The tested extract only slightly reduced platelet protein nitration (measured by C- ELISA method). The extract also caused a distinct reduction of platelet lipid peroxidation induced by peroxynitrite. Moreover, in our preliminary experiments we observed that the extract (50 microg/mL) reduced oxidative/nitrative stress in blood platelets from patients with breast cancer. The obtained results indicate that in vitro the extract from A. melanocarpa has the protective effects against peroxynitrite-induced oxidative/nitrative damage to the human platelet proteins and lipids. The extract from A. melanocarpa seems to be also useful as an antioxidant in patients with breast cancer.

  20. Levels of platelet-derived microparticles and soluble p-selectin in patients of acute myocardial infarction (case control study).

    PubMed

    Hameed, Aisha; Rubab, Zille; Abbas Rizvi, Syed Khizar; Hussain, Shabbir; Latif, Waqas; Mohsin, Shahida

    2017-07-01

    TTo measure levels of platelet-derived microparticles and soluble P-selectin in patients of acute myocardial infarction and their comparison with healthy controls. This case-control study was conducted in Department of Haematology, University of Health Sciences Lahore from April to September 2013, and comprised patients of acute myocardial infarction in group 1 and healthy controls in group 2. Platelet-derived microparticles and soluble P-selectin were measured by enzyme-linked immunosorbent assay. SPSS21 was used for data analysis. Of the 80 participants, 50(62.5%) were patients and 30(37.5%) were controls. The mean levels of platelet-derived microparticles and soluble P-selectin were significantly higher in group 1 compared to group 2 (45.70±10.30 vs 10.60±0.96, and 51.46±9.30 vs 9.16±1.04, respectively) (p<0.001). There was no significant difference in levels of platelet-derived microparticles and soluble P-selectin in three intervals after acute myocardial infarction (p>0.05). Although levels of platelet-derived microparticles and soluble P-selectin did not correlate to creatinekinase-myocardial band levels (p>0.05), but there was a trend of significant correlation with cardiac troponin T (p<0.05). Levels of platelet-derived microparticles and soluble P-selectin can be used as novel early diagnostic marker of acute myocardial infarction.

  1. An in vitro study of hematopoietic progenitor cells from peripheral blood of rabbits

    PubMed Central

    2005-01-01

    Abstract The purpose of this study was to isolate and cultivate a subpopulation of pluripotent stem cells (PSCs) from the peripheral blood of rabbits, which are frequently used in veterinary research as an animal model. Pluripotent stem cells, as described in human beings, are fibroblast-like cells that exhibit a CD34 marker, specific from other hematopoietic stem cells. Commonly used human commercial media has been researched for culturing rabbit PSCs. These findings allow us to contemplate the direct application of this simple and standardized methodology in several areas of study, such as of the pharmacological effect of many drugs on hematopoietic cells, veterinary practice, and even the study of new strategies in cellular therapy for some human diseases. PMID:16479731

  2. Current radiological techniques used to evaluate unilateral partial ureteral obstruction: an experimental rabbit study.

    PubMed

    Yazıcı, Mehmet; Celebi, Suleyman; Kuzdan, Özgür; Koçan, Hüseyin; Ayyıldız, Halil Suat; Bayrak, İlkay Koray; Bilgici, Meltem Ceyhan; Yapıcı, Oktay; Kefeli, Mehmet; Arıtürk, Ender

    2015-07-01

    The aim of this study was to evaluate functional and prognostic benefits of Doppler ultrasonography (DU), diuretic renal scintigraphy (DRS), and magnetic resonance urography (MRU) during diagnosis and follow-up of ureteropelvic junction obstruction (UPJO) and to examine apoptosis rates caused by UPJO in an experimental rabbit model. Twenty-four rabbits were divided randomly into two groups. The left kidneys of 15 rabbits from the first group underwent Ulm-Miller surgery to create UPJO, whereas the left kidneys of nine rabbits from the second group underwent sham surgery. A pressure flow study (Whitaker's test) was done during postoperative week 6. Based on the Whitaker test, the DU, DRS, and MRU findings were compared. The number of apoptotic renal cells was counted after death. The Whitaker test run during postoperative week 6 revealed obstructions in 15 rabbits from group 1; the nine rabbits of the sham group had no obstructions. Sensitivity and specificity of DRS were 93.3 and 88.8 %, respectively, and those of MRU were 93.3 and 88.8 %, respectively. The postoperative mean RI values were significantly higher than the preoperative values, associated with sensitivity of 86.6 % and specificity of 77.5 % for detecting UPJO. DRS, MRU, and RI could not predict UPJO in one (8 %), one (8 %), and two (16 %) kidneys, respectively. Likelihood ratio (LR) was 8.4 for MRU and scintigraphy, while for RI, LR was 3.9. Pathology specimens revealed that all kidneys with UPJO underwent apoptosis, and the number of apoptotic cells was significantly higher on the UPJO-created side than on the contralateral and in the sham group (p < 0.05). No test predicted all apoptosis related to UPJO. The RI, DRS, and DMRU results correlated with the pressure flow results for detecting UPJO. No single radiological technique predicted all initial UPJO-created kidneys that concluded with apoptosis. Further studies are required to seek with better methods for diagnosing an obstruction or to define a

  3. Rabbit hematology.

    PubMed

    Marshall, Kemba L

    2008-09-01

    Using laboratory animal medicine as an established resource, companion animal veterinarians have access to many physiologic and basic science studies that we can now merge with our clinical impressions. By working with reference laboratories, companion animal veterinarians are poised to accelerate our knowledge of the normal rabbit rapidly. The aim of this article is to discuss normal hematopoiesis and infectious and metabolic diseases that specifically target the hemolymphatic system. Additionally, photographic representation of cell types is provided.

  4. STUDIES IN THE BLOOD CYTOLOGY OF THE RABBIT : IV. CONSECUTIVE NEUTROPHILE, BASOPHILE, AND EOSINOPHILE OBSERVATIONS ON GROUPS OF NORMAL RABBITS.

    PubMed

    Pearce, L; Casey, A E

    1930-07-31

    Consecutive weekly observations on the neutrophile, the basophile, and the eosinophile counts of the peripheral blood were made on 5 groups of normal rabbits, a total of 45 animals, during a period of 20 months from October, 1927 to July, 1929. Individual groups were examined 8 to 35 weeks. In the case of the 4 groups followed 13 to 35 weeks, the general trend of the neutrophile cells was towards increased mean values; with the group followed 8 weeks, decreasing values were found. An increase in the mean values of the basophile cells was observed in the two groups of rabbits followed in 1927-28; in the groups of 1928-29, the mean values decreased. The mean values of the eosinophile cells showed no definite trends but the findings were characterized by abrupt and marked fluctuations. The periods of greatest irregularity in mean neutrophile and eosinophile values occurred in the fall and the late winter and spring months of both years, but in the case of the basophiles, the irregularities were distributed throughout the first year and occurred chiefly in the winter months of the second year. The major trends and many of the minor fluctuations as well which were observed in the mean cell values of one group of rabbits were also generally seen in another group examined during the same months. The general levels of the neutrophile, the basophile, and the eosinophile mean values in the groups examined during 1927-28 were higher than in the groups of 1928-29.

  5. The effects of intellan and cytacon on hematological and biochemical parameter in rabbits: a comparative study.

    PubMed

    Anser, Humera; Najam, Raheela; Khan, Saira Saeed; Riaz, Bushra; Sarfaraz, Sana

    2014-09-01

    Several plants have been selected based on their use in traditional systems of medicine, and research has identified a number of natural compounds that could act as Nootropicagents. In this study a herbal product Intellan containing Centella asiatica, Bacopa monniera, Coriandum sativum, Amomum subulatum, Emblica officinalis and another product Cytacon (Cyanocobalamine) were selected The study was designed on animal models to explore the effects on different parameters. For this the animals were given chronic dosing for 6-8 weeks during and after which the parameters were observed to determine their effects. The purpose of focusing on such formulations is to do hematological screening in long-term use. The hematological parameter included hemoglobin/HCT, total leucocyte count, platelets. The lymphocytes and the monocytes counts were increased significantly by intellan, while cyanocobalamine increases RBC counts, platelet counts, monocyte counts, hematocrit etc significantly. The SGPT, SGOT were found increased in both of these drugs.

  6. Platelet interaction with bacteria. V. Ultrastructure of congenital afibrinogenemic platelets.

    PubMed Central

    Clawson, C. C.; White, J. G.

    1980-01-01

    Platelets from a patient with congenital afibrinogenemia (CA) were tested in their native plasma for reactivity in vitro to Staphylococcus aureus 502A. Previous studies of the interactions between normal human platelets and this organism have shown rapid irreversible aggregation responses in which the bacteria were regularly trapped between aggregating platelets. Engulfment of microbes by single normal platelets in a process akin to phagocytosis was a very rare occurrence. In contrast, CA platelets showed a delayed aggregation response to contact with this microorganism. The CA platelets were also much more sensitive to the concentration of bacteria than were normal platelets. Electron microscopy showed that individual CA platelets often engulfed the stimulatory organism rather than participating in aggregation. Postfixation staining with a colloidal tracer, lanthanum nitrate, indicated that the bacteria were sequestered in the open canalicular system of the CA platelets in a manner analogous to that previously observed with latex particles. Restoration of normal levels of human fibrinogen to the CA platelet-rich plasma corrected the delay in aggregation but did not eliminate the frequent engulfment of bacteria by the CA platelets. These findings indicate that fibrinogen is an important, although not essential, cofactor in the response of human platelets to contact with this common bacterial pathogen. Images p[209]-a Figures 6 and 7 Figures 8 and 9 Figures 10 and 11 Figures 12 and 13 Figure 1 Figure 2 Figure 3 PMID:7350814

  7. EFFECT OF USE OF BONE-MARROW CENTRIFUGATE ON MUSCLE INJURY TREATMENT: EXPERIMENTAL STUDY ON RABBITS

    PubMed Central

    Vieira, Daniel Ferreira Fernandes; Guarniero, Roberto; Vaz, Carlos Eduardo Sanches; de Santana, Paulo José

    2015-01-01

    Objective: The objective of this study was to evaluate the effect of bone-marrow centrifugate on the healing of muscle injuries in rabbits. Methods: This experimental study involved use of fifteen adult male New Zealand White rabbits. Each animal received a transverse lesion in the middle of the right tibialis anterior muscle, to which an absorbable collagen sponge, soaked in a centrifugate of bone marrow aspirate from the ipsilateral iliac bone, was added. The left hind limb was used as a control and underwent the same injury, but in this case only the absorbable collagen sponge. Thirty days later, the animals were sacrificed to study the muscle healing. These muscle areas were subjected to histological analysis with histomorphometry, with the aim of measuring the number of muscle cells per square micrometer undergoing regeneration and the proportion of resultant fibrosis. Results: The centrifugation method used in this study resulted in an average concentration of nucleated cells greater than the number of these cells in original aspirates, without causing significant cell destruction. Addition of the bone marrow centrifugate did not result in any significant increase in the number of muscle cells undergoing regeneration, in relation to the control group. There was also no significant difference in the proportion of resultant fibrosis, compared with the control group. Conclusion: Administration of the bone marrow centrifugate used in this study did not favor healing of muscle injuries in rabbits. PMID:27047832

  8. Studies on the antigenicity of bone. I. Freeze-dried and deep-frozen bone allografts in rabbits.

    PubMed

    Friedlaender, G E; Strong, D M; Sell, K W

    1976-09-01

    The antigenicity of deep-frozen and freeze-dried cortical and corticocancellous bone allografts placed orthotopically in rabbits was studied using a sensitive microcytotoxicity assay. Target cells were phytohemagglutinin-P-stimulated, 51chromium-labeled peripheral blood lymphocytes from the bone donors (Dutch belted rabbits), and sera or peripheral blood lymphocytes from the graft recipients (New Zealand white rabbits) were used as effectors of cytotoxicity. Fresh allografts and deep-frozen corticocancellous bone evoked detectable humoral and cell-mediated immunity,, whereas freeze-dried cortical bone allografts failed to sensitize the recipients and were the least antigenic of the allografts examined.

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

    PubMed Central

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

    2016-01-01

    Introduction: 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. Materials and Methods: Platelets were harvested; platelet count of platelet-rich plasma adjusted to 2.5 Χ 105/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 Results: All the concentrations of lycopene (4–12 μmol/L) exhibited reduction in maximum platelet aggregation induced by aggregating agents ADP and collagen (P < 0.01 vs. vehicle) and were comparable with aspirin. 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. Conclusion: 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. PMID:26997718

  10. Clodronate combined with a surfactant (Tween 20) does not improve osseointegration: a rabbit immunohistomorphometric study.

    PubMed

    Berardi, D; Raffaelli, L; Perfetti, G; Paolantonio, M; Trisi, P

    2009-01-01

    Biphosphonates are compounds that inhibit bone reabsorption mediated by osteoclasts or the progression of periodontal disease independent on the host response to pathogenic bacteria that colonize the tooth surface. The use of biphosphonates in oral implantology is still in the experimental stage. The aim of this study is to evaluate the efficacy of a non-aminobiphosphonate combined with a surfactant to increase the ability of the drug to link to the implant and bone surfaces in the development of osseointegration in rabbits. Smooth titanium implants were devised to be used on rabbit femurs. A topical administration of clodronate combined with the surfactant (Tween 20) at different concentrations was made on the implant surface and in the implant site to increase the bone and implant adhesiveness. Placebo was given to the control group. New Zealand rabbits were used and sacrificed by CO2 after 8 weeks from the implantations. A histologic and histomorphometric analysis was carried out. Results did not show significant difference between the tests and the placebo groups. Our data are different from other similar studies obtaining statistically significant differences. These differences could depend on the efficacy of the drug used and on the procedure of application of the drug on the implant. This study demonstrates poor efficacy of clodronate applied topically to the implant and implant site during surgery to increase the percentage of osseointegration in the implant. Further studies using different fixation techniques of the drug may be necessary to confirm the present data.

  11. Inhalation developmental toxicology studies: Developmental toxicity of chloroprene vapors in New Zealand white rabbits. Final report

    SciTech Connect

    Mast, T.J.; Evanoff, J.J.; Westerberg, R.B.; Rommereim, R.L.; Weigel, R.J.

    1994-04-01

    Chloroprene, 2-chloro-1,3-butadiene, is a colorless liquid with a pungent ethereal odor that is primarily used as an intermediate in the manufacture of neoprene rubber, and has been used as such since about 1930. This study addressed the potential for chloroprene to cause developmental toxicity in New Zealand white rabbits following gestational exposure to 0, 10, 40, or 175 ppm chloroprene vapors, 6h/dy, 7dy/wk. Each treatment group consisted of 15 artificially inseminated females exposed on 6 through 28 days of gestation (dg). Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice on 29 dg. Implants were enumerated and their status recorded and live fetuses were examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. There were no overt signs of maternal toxicity and the change in maternal body weight over the course of the study was not affected. Exposure of pregnant rabbits to chloroprene vapors on 6-28 dg had no effect on the number of implantation, the mean percent of live pups per litter, or on the incidence of resorptions per litter. The incidence of fetal malformations was not increased by exposure to chloroprene. Results of this study indicate that gestational exposure of New Zealand white rabbits to 10, 40, or 175 ppm chloroprene did not result in observable toxicity to either the dam or the offspring.

  12. Primary and secondary patient data in contrast: the use of observational studies like RABBIT.

    PubMed

    Richter, Adrian; Meißner, Yvette; Strangfeld, Anja; Zink, Angela

    2016-01-01

    The study of secondary patient data, particularly represented by claims data, has increased in recent years. The strength of this approach involves easy access to data that have been generated for administrative purposes. By contrast, collection of primary data for research is time-consuming and may therefore appear outdated. Both administrative data and data collected prospectively in clinical care can address similar research questions concerning effectiveness and safety of treatments. Therefore, why should we invest the precious time of rheumatologists to generate primary patient data? This article will outline some features of primary patient data collection illustrated by the German biologics register RABBIT (Rheumatoid arthritis: observation of biologic therapy). RABBIT is a long-term observational cohort study that was initiated more than 15 years ago. We will discuss as quality indicators: (i) study design, (ii) type of documentation, standardisation of (iii) clinical and (iv) safety data, (v) monitoring of the longitudinal follow-up, (vi) losses to follow-up as well as (vii) the possibilities to link the data base. The impact of these features on interpretation and validity of results is illustrated using recent publications. We conclude that high quality and completeness of data prospectively-collected offers many advantages over large quantities of non-standardised data collected in an unsupervised manner. We expect the enthusiasm about the use of secondary patient data to decline with more awareness of their methodological limitations while studies with primary patient data like RABBIT will maintain and broaden their impact on daily clinical practice.

  13. Oral (drinking water) developmental toxicity study of ammonium perchlorate in New Zealand White rabbits.

    PubMed

    York, R G; Brown, W R; Girard, M F; Dollarhide, J S

    2001-01-01

    This developmental toxicity study was conducted to evaluate the embryo-fetal toxicity and teratogenic potential of ammonium perchlorate in New Zealand White [Hra:(NZW)SPF] rabbits. Pregnant rabbits were given continual access to ammonium perchlorate in drinking water at target doses of 0, 0.1, 1.0, 10.0, 30.0, and 100.0 mg/kg-day on gestation days 6 through 28. The actual consumed doses in the study were 0, 0.1, 0.9, 10.4, 30.3, and 102.3 mg/kg-day. The rabbits were sacrificed on gestation day 29, and fetuses were examined for developmental alterations. In addition, blood was collected from does for determination of serum thyroid stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) levels and the thyroid was subjected to histopathologic examination. No maternal deaths were attributed to perchlorate exposure. Ammonium perchlorate as high as 100.0 mg/kg-day did not affect caesarean sectioning or litter parameters studied, and all values were found to be within the historical ranges of the laboratory. The litter averages for corpora lutea, implantations, litter sizes, live and dead fetuses, percent dead or resorbed conceptuses, and fetal body weights were comparable and also did not differ significantly in the six dose groups. All placentae appeared normal and no dam had a litter consisting of only resorbed conceptuses. The maternal thyroid was the target organ for ammonium perchlorate in this study. Increased incidence of thyroid follicular hypertrophy was observed in does treated with > or =10 mg/kg-day perchlorate and significantly decreased T4 was observed in does treated with > or =30 mg/kg-day. Based on these data, the maternal no-observable-adverse-effect level (NOAEL) for ammonium perchlorate was 1.0 mg/kg-day. The developmental NOAEL for ammonium perchlorate was found to be 100.0 mg/kg-day for rabbits.

  14. Teratology Studies of Lewisite and Sulfur Mustard Agents: Effects of Lewisite in Rats and Rabbits

    DTIC Science & Technology

    1987-12-31

    semen donors were trained to service an AV during a 2- to 3-week period (Gregoire et al., 1958). On the day of AI, semen samples from at least 3... Semen samples of satisfactory quality were pooled and diluted with buffered citrate/egg-yolk extender to a concentration of 21 to 30 million sperm/ml...V) ,NI REPORT NO. PNL-6408 00 TERATOLOGY STUDIES OF LEWISITE AND SULFUR MUSTARD AGENTS: EFFECTS OF LEWISITE IN RATS AND RABBITS FINAL REPORT P. L

  15. The impact of electromagnetic radiation of different parameters on platelet oxygen metabolism - in vitro studies.

    PubMed

    Lewicka, Małgorzata; Henrykowska, Gabriela A; Pacholski, Krzysztof; Szczęsny, Artur; Dziedziczak-Buczyńska, Maria; Buczyński, Andrzej

    2015-01-01

    Electromagnetic radiation emitted by a variety of devices, e.g. cell phones, computers and microwaves, interacts with the human body in many ways. Research studies carried out in the last few decades have not yet resolved the issue of the effect of this factor on the human body and many questions are left without an unequivocal answer. Various biological and health-related effects have not been fully recognized. Thus further studies in this area are justified. A comparison of changes within catalase enzymatic activity and malondialdehyde concentration arising under the influence of the electromagnetic radiation emitted by car electronics, equipment used in physiotherapy and LCD monitors. The suspension of human blood platelets at a concentration of 1 × 109/0.001 dm 3, obtained from whole blood by manual apheresis, was the study material. Blood platelets were exposed to an electromagnetic field for 30 min in a laboratory stand designed for the reconstruction of the electromagnetic radiation generated by car electronics, physiotherapy equipment and LCD monitors. The changes in catalase activity and malondialdehyde concentration were investigated after the exposure and compared to the control values (unexposed material). An increase in catalase activity and malondialdehyde concentration was observed after 30 min exposure of platelets to EMF regardless of the radiation source. The most significant changes determining the degree of oxidative stress were observed after exposure to the EMF generated by car electronics. The low frequency electromagnetic fields generated by car electronics, physiotherapy equipment and LCD monitors may be a cause of oxidative stress in the human body and may lead to free radical diseases.

  16. A comparative evaluation of the blood clot, platelet-rich plasma, and platelet-rich fibrin in regeneration of necrotic immature permanent teeth: A clinical study

    PubMed Central

    Narang, Isha; Mittal, Neelam; Mishra, Navin

    2015-01-01

    Introduction: This study was designed as a clinical trial to evaluate and compare the regenerative potential of platelet-rich fibrin (PRF), platelet-rich plasma (PRP), and blood clot in immature necrotic permanent teeth with or without associated apical periodontitis. Methods: Access preparation was done under rubber dam isolation. Copious irrigation was done with 2.5% NaOCl and triple antibiotic paste was placed as an intracanal medicament. After 4 weeks, the cases were divided into four groups with five patients in each group. The study design had three test arms and one control arm. Group I in which mineral trioxide aggregate apexification was carried out and it was kept as control group to evaluate the regenerative potential of blood clot and platelet concentrates, Group II in which blood clot was used as scaffold in the canal, Group III in PRF was used as scaffold, and Group IV in which PRP carried on collagen was used as a scaffold. Results: The clinical and radiographic evaluation after 6 and 18 months was done by two independent observers who were blinded from the groups. The scoring was done as: None score was denoted by, Fair by 1, Good by 2, and Excellent by 3. The data were then analyzed statistically by Fisher's exact test using Statistics and Data 11.1(PRP Using harvest Smart PReP2) which showed statistically significant values in Group III as compared to other Groups. Conclusion: PRF has huge potential to accelerate the growth characteristics in immature necrotic permanent teeth as compared to PRP and blood clot. PMID:25684914

  17. Protective effect of policosanol on endothelium and intimal thickness induced by forceps in rabbits.

    PubMed

    Noa, Miríam; Más, Rosa; Lariot, Carlos

    2007-09-01

    Policosanol is a cholesterol-lowering drug isolated from sugar cane wax with concomitant antiplatelet effects that prevents lipofundin-induced atherosclerotic lesions in rabbits and rats, including foam cell formation, and also reduces foam cell formation in carrageenan-induced granulomas in rats, while it inhibits proliferation of smooth muscle cells induced in rabbit cuffed artery. This study was undertaken to determine whether policosanol prevents endothelium damage and increase in arterial wall thickness in rabbits with arterial walls damaged with a forceps. Artery forceps were placed over the central artery of the right ear of all rabbits, and each artery was injured eight times. Animals were randomly distributed into four groups: a positive control group treated with Tween 20/H2O vehicle, two groups treated with policosanol (5 and 25 mg/kg, respectively), and a group treated with aspirin (8 mg/kg). Treatments were given for 30 days. Damaged arteries were examined by light and electron (transmission and scanning) microscopy. To evaluate intimal thickening, areas of intima were measured, and a significant reduction in policosanol-treated animals was observed. The endothelial surface, studied with scanning electron microscopy, revealed several types of damage. In control group, the endothelial surface was severely damaged. De-endothelialized areas were reduced in policosanol-treated animals. Platelet adhesion to subendothelium was seen in all animals of the control group, whereas policosanol-treated groups exhibited significantly reduced platelet adhesion. Policosanol also reduced, dose-dependently, the platelet sequestration induced in the damaged vessel wall, partially preventing the reduction in platelet count. It is concluded that policosanol prevents endothelium injury and reduces significantly intimal thickness of rabbit arteries damaged with forceps.

  18. Three-dimensional structure and cytokine distribution of platelet-rich fibrin

    PubMed Central

    Bai, Meng-Yi; Wang, Ching-Wei; Wang, Jyun-Yi; Lin, Ming-Fang; Chan, Wing P

    2017-01-01

    OBJECTIVES: Previous reports have revealed that several cytokines (including platelet-derived growth factor-BB, transforming growth factors-β1 and insulin-like growth factor-1) can enhance the rate of bone formation and synthesis of extracellular matrix in orthopaedics or periodontology. This study aimed to determine the concentration of cytokines within platelet-rich fibrin microstructures and investigate whether there are differences in the different portions of platelet-rich fibrin, which has implications for proper clinical use of platelet-rich fibrin gel. METHODS: Whole blood was obtained from six New Zealand rabbits (male, 7 to 39 weeks old, weight 2.7-4 kg); it was then centrifuged for preparation of platelet-rich fibrin gels and harvest of plasma. The resultant platelet-rich fibrin gels were used for cytokine determination, histological analyses and scanning electron microscopy. All plasmas obtained were subject to the same cytokine determination assays for the purpose of comparison. RESULTS: Cytokines platelet-derived growth factor-BB and transforming growth factor-β1 formed concentration gradients from high at the red blood cell end of the platelet-rich fibrin gel (p=1.88×10-5) to low at the plasma end (p=0.19). Insulin-like growth factor-1 concentrations were similar at the red blood cell and plasma ends. The porosities of the platelet-rich fibrin samples taken in sequence from the red blood cell end to the plasma end were 6.5% ± 4.9%, 24.8% ± 7.5%, 30.3% ± 8.5%, 41.4% ± 12.3%, and 40.3% ± 11.7%, respectively, showing a gradual decrease in the compactness of the platelet-rich fibrin network. CONCLUSION: Cytokine concentrations are positively associated with platelet-rich fibrin microstructure and portion in a rabbit model. As platelet-rich fibrin is the main entity currently used in regenerative medicine, assessing cytokine concentration and the most valuable portion of PRF gels is essential and recommended to all physicians. PMID:28273236

  19. Effects of postoperative immobilization on the reconstructed anterior cruciate ligament. An experimental study in rabbits.

    PubMed

    Muneta, T; Yamamoto, H; Takakuda, K; Sakai, H; Furuya, K

    1993-01-01

    To investigate the effects of postoperative immobilization and limited motion on reconstructed anterior cruciate ligaments, 28 rabbits received an anterior cruciate ligament reconstruction using autogenous Achilles tendon and were then divided into three groups: fully immobilized, 4 weeks immobilized, and limited motion. Two rabbits from each group were evaluated macroscopically, histologically and microangiographically at 4-week intervals until 12 weeks postoperatively. An additional six rabbits in the 4 weeks immobilized and limited motion groups were studied biomechanically at 12 weeks postoperatively. Macroscopically, both immobilized groups showed more proliferation of the infrapatellar fat pad, which was adherent to the reconstructed anterior cruciate ligament. Histology revealed more rapid regeneration of reconstructed anterior cruciate ligaments in the limited motion group, with no findings of necrosis in the mid-substance. Microangiography indicated faster normalization of vascularity in the limited motion group. The biomechanical study showed no significant difference in laxity between the 4 weeks immobilized and limited motion groups. The graft stiffness and maximum load to failure were greater for the limited motion group, although the increase was not statistically significant. The histologic and microangiographic results from the limited number of animals in this study support limited postoperative motion in the anterior cruciate ligament reconstructed knee. However, there were no differences in terms of the biomechanical parameters at 12 weeks postoperatively between the immobilized and limited motion treatment modes.

  20. Potential for osseous regeneration of platelet rich plasma: a comparitive study in mandibular third molar sockets.

    PubMed

    Vivek, G K; Sripathi Rao, B H

    2009-12-01

    To evaluate the efficacy of autologous platelet-rich plasma in soft tissue healing & bone regeneration in mandibular third molar extraction socket. The study was conducted in 10 patients visiting the outpatient Department of Oral & Maxillofacial Surgery, requiring extraction of bilateral mandibular third molars. Following extraction, autologous Platelet Rich Plasma (PRP) was placed in one extraction socket, the other socket was studied as the control site with no PRP. The patients were assessed for postoperative pain, soft tissue healing, bone blending and trabecular formation. Radiological assessment of the extraction site was done for a period of 4 months to evaluate the change in bone density. Pain was less in the study site compared to control site, soft tissue healing was better in study site. Evaluation for bone blending and trabecular bone formation started earlier in PRP site compared to control, non PRP site. The evaluation of bone density by radiological assessment showed the grey level values calculated after 4 months at the PRP site were comparatively higher than the average baseline value of bone density at extraction site in control site. The study showed that autologous PRP is biocompatible and has significantly improved soft tissue healing, bone regeneration and increase in bone density in extraction sockets. However a more elaborate study with a larger number of clinical cases is essential to be more conclusive regarding its efficacy.

  1. Influence of olive oil on alveolar bone response during orthodontic retention period: rabbit model study.

    PubMed

    Al-Hamdany, Afrah K; Al-Khatib, Ali R; Al-Sadi, Hafidh I

    2017-08-01

    This study attempted to evaluate clinically and histologically the effects of olive oil (Ol) consumption on orthodontic relapse after the retention period. Thirty apparently healthy female albino rabbits, weight more than 1000 g each was used in this study. The animals were grouped randomly into six groups of five animals each: two control and four experimental groups. In control groups, the relapse was estimated either at zero day, or at the end of the fourth week after orthodontic retention period. In the experimental groups, the animals' groups received Ol, 7.7, or 15.4 ml/kg b.w. per day during the orthodontic retention period. The relapse was estimated either at zero day, or at the end of the fourth week after orthodontic retention period for each concentration. Modified fixed orthodontic appliances were attached to the rabbits' lower central incisors. Each rabbit received orthodontic intervention for one week, followed by six weeks retention period. At the end of the experiments, the clinical and histological investigations were conducted. Data analyses were performed at the level of p < .05 for the statistically significant difference. Clinically, Ol high concentration four weeks group showed a significantly lower relapse tendency than control four weeks group. Histologically, Ol low concentration zero time group showed significantly higher osteoblasts numbers than control zero time group. Olive oil low and high concentrations four weeks group showed significantly lower fibroblasts count. Moreover, Ol high concentration four weeks group revealed significantly higher bone mineralization, osteoblasts and osteocytes counts than control four weeks study group. Supplementation with Ol during an orthodontic retention period, especially at 15.4 ml/kg b.w. per day concentration, clinically reduced orthodontic relapse on rabbit model. Histologically, Ol increased osteoblasts and osteocytes counts and the relative amount of bone mineralization of connective

  2. Recovery of Platelet Count among Apheresis Platelet Donors

    PubMed Central

    Radhakrishnan, Krishnamoorthy; Anandan, Ashwin; Panicker, Vinod Kumar

    2016-01-01

    Introduction Increase in awareness regarding use of single donor platelets and the availability of technology has resulted in increased platelet pheresis procedures. The interval between two succesive plateletpheresis donations is much less compared to whole blood donations. Plateletpheresis procedures are associated with short term and long term adverse events. The effect of plateletpheresis on haematopoietic system remains significant. Aim To study the recovery of platelet count to baseline in plateletpheresis donors. Materials and Methods Fifty, first time apheresis donors were followed for platelet count recovery. Platelet count was measured before donation and at 30 minutes, 48 hours, 7th day and 14th day post-donation. Donor platelet count recovery to baseline was observed during the two week period. Results were analysed statistically, p<0.05 was considered statistically significant. Results Platelet count recovered to baseline by 7th day post-donation in 50% of donors in groups I (Pre-donation platelet count 1.5 lacs/μl to 2.2 lacs/μl) and II (Donors with platelet count >2.2 lacs/μl to 2.75 lacs/μl), 30% of donors in group III (Donors with platelet count >2.75 lacs/μl to 3.5 lacs/μl) of the donors. Donor’s platelet count recovered to baseline in 85% of donors by day 14 in across the three groups. Recruitment of platelets from spleen was observed in donors with pre-donation platelet count on the lower limit of normal. Conclusion By day 7, donor’s platelet count recovered to baseline in majority of the donors. Allowing enough recovery periods for donor platelet count, the minimum interval between two apheresis donations can be 7 days till more prospective studies conclude on the frequency and minimum interval between plateletpheresis donations. PMID:28208861

  3. Alveolar Ridge Preservation After Tooth Extraction with DFDBA and Platelet Concentrates: A Radiographic Retrospective Study

    PubMed Central

    Baniasadi, Behrang

    2017-01-01

    Objectives: The purpose of this study was to evaluate vertical alveolar bone loss 3 months after tooth extraction when a technique of ridge preservation was applied using a particulate demineralized freeze-dried bone allograft 300 - 500 µm associated with platelet concentrates (platelet-rich-fibrin) in the form of gel and membranes. Material and Methods: A retrospective radiological clinical study was conducted on 56 patients for whom 95 extractions had been performed immediately followed by alveolar filling. Among the patients, 17 were smokers and 16 were provided with an immediate removable temporary prosthesis after extractions. Vertical bone loss was measured radiologically by panoramic X-ray before extractions and by a computed tomography scan 3 months after, at the level of mid-buccal bone wall, by two independent observers. For statistical analysis, Student’s t-test was performed to compare the mean bone loss between mono- and pluri-radicular teeth and to compare the mean bone loss between tobacco users versus non users and finally to compare the mean bone loss between individuals that had provisional removable prosthesis and those that had not. Results: Three months after tooth extraction, the mean of vertical loss of the mid-buccal bone wall was 0.72 (SD 0.71) mm (5.53% SD 5.19). No significant difference between bone loss at mono-radicular and pluri-radicular teeth (P = 0.982) was observed. There was no significant correlation between tobacco habits and bone loss (P = 0.2), nor between provisional removable prosthesis and bone loss (P = 0.786). Conclusion: These results indicate a good potential for the technique using Demineralized Freeze-Dried Bone Allograft 300 - 500 µm and platelet concentrates in alveolar bone preservation. PMID:28357003

  4. Epiphyseal distraction and centrally located bone bar: an experimental study in the rabbit.

    PubMed

    Cottalorda, J; Jouve, J L; Bollini, G; Panuel, M; Guisiano, B; Jimeno, M T

    1996-01-01

    The purpose of this study was to analyze the force required for an epiphysiolysis in vitro in the distal femoral growth plate of rabbits with different sized central physeal bone bars. The bars were operatively induced by drilling through the physis. An epiphyseal distraction was then performed, and the response was evaluated. Forty rabbits (67 femurs) divided into five groups were used for experimentation. Group A had not been operated on and manifested no physeal bone bridge. Groups B, C, D, and E manifested some bone bridges obtained surgically by drills 2, 2.5, 3.5, and 4.5 mm in diameter, respectively. The average force required to obtain an epiphysiolysis is not statistically significant in the different groups. However, we noted that the epiphysiolysis differed depending on the diameter of the surgically performed bridge. Group E was Salter-Harris type II fractures, whereas groups A, B, and C were type I fractures. Group D comprised both types.

  5. Study of fertilising capacity of spermatozoa after heterospermic insemination in rabbit using DNA markers.

    PubMed

    Vicente, José-Salvador; Viudes de Castro, María-Pilar; Lavara, Raquel; Mocé, Eva

    2004-05-01

    The aim of this study was to evaluate the fertilising capacity of males belonging to a rabbit line selected for growth rate using heterospermic insemination and genetic markers. Semen from five males was used to make pools of three of them, and to perform homospermic insemination. Insemination was carried out in receptive multiparous lactating does with 6 million spermatozoa per insemination dose. DNA from 360 young rabbits born from heterospermic insemination, 5 sires and 42 does were amplified to nine microsatellite loci for determination of the offspring rate per male. Although each female was inseminated with the same number of spermatozoa from each male (2 million from a total dose of 6 million), sperm from one male was always dominant, notable differences being observed in the offspring among the males with similar semen quality (83-68% from dominant male versus 31-0% from non-dominant, P<0.05 ).

  6. Role of Platelet Parameters on Neovascular Glaucoma: A Retrospective Case-Control Study in China

    PubMed Central

    Li, Shengjie; Cao, Wenjun; Sun, Xinghuai

    2016-01-01

    Purpose Retinal vein occlusion (RVO) and diabetic retinopathy (DR) are two major sight-threatening diseases which may lead to neovascular glaucoma (NVG). The aim of this study was to explore the association between platelet parameters and NVG. Methods A total of 185 subjects were enrolled for the study from January, 2012 to December, 2015 at the Eye-ENT Hospital of Fudan University. Patients include those with NVG secondary to RVO (RVO group, n = 38), patients with NVG secondary to DR (DR group, n = 47), diabetics mellitus without retinopathy (DM group, n = 52), and healthy individuals (control group, n = 48). A complete ophthalmological examination including visual field examination, A-scan ultrasound, Fundus photography, and measurement of platelet parameters were performed for NVG subjects. Results There was no statistical difference in the mean age and gender among the RVO, DR, and control groups (p>0.05). The mean level of platelet distribution width (PDW) was higher (p<0.001) in the RVO group (15.16±2.13fl) and DR group (16.17±1.66fl) when compared with the control group (13.77±2.99fl). The mean plateletcrit (PCT) value of the RVO group (0.229±0.063%) was also higher (p = 0.049) than the control group (0.199±0.045). In the DR group, mean platelet volume (MPV) value (10.72±1.57fl) was significantly higher (p = 0.002) than the control group (9.75±0.89fl). A similar trend was observed when platelet parameters were compared among the 3 groups with respect to age. The mean level of PDW was significantly higher (p<0.001) in the DR group (16.17±1.66fl) compared with the DM group (13.80±3.32fl). Stepwise multiple logistic regression analysis revealed that PDW (OR = 1.44, 95%CI = 1.149–1.805, p = 0.002) and MPV (OR = 1.503, 95%CI = 1.031–2.192, p = 0.034) were associated with the DR group, PDW (OR = 1.207, 95%CI = 1.010–1.443, p = 0.039) and PCT (OR = 1.663, 95%CI = 1.870–2.654, p = 0.036) were associated with the RVO group. Conclusion Our results

  7. In vitro study of platelet function confirms the contribution of the ultraviolet B (UVB) radiation in the lesions observed in riboflavin/UVB-treated platelet concentrates.

    PubMed

    Abonnenc, Mélanie; Sonego, Giona; Crettaz, David; Aliotta, Alessandro; Prudent, Michel; Tissot, Jean-Daniel; Lion, Niels

    2015-09-01

    Platelet inactivation technologies (PITs) have been shown to increase platelet storage lesions (PSLs). This study investigates amotosalen/ultraviolet (UV)A- and riboflavin/UVB-induced platelet (PLT) lesions in vitro. Particular attention is given to the effect of UVB alone on PLTs. Buffy coat-derived PLT concentrates (PCs) were treated with amotosalen/UVA, riboflavin/UVB, or UVB alone and compared to untreated PCs throughout storage. In vitro PLT function was assessed by blood gas and metabolite analyses, flow cytometry-based assays (CD62P, JC-1, annexin V, PAC-1), hypotonic shock response, and static adhesion to fibrinogen-coated wells. In our experimental conditions, riboflavin/UVB-treated PCs showed the most pronounced differences compared to untreated and amotosalen/UVA-treated PCs. The riboflavin/UVB treatment led to a significant increase of anaerobic glycolysis rate despite functional mitochondria, a significant increase of CD62P on Day 2, and a decrease of JC-1 aggregates and increase of annexin V on Day 7. The expression of active GPIIbIIIa (PAC-1) and the adhesion to fibrinogen was significantly increased from Day 2 of storage in riboflavin/UVB-treated PCs. Importantly, we showed that these lesions were caused by the UVB radiation alone, independently of the presence of riboflavin. The amotosalen/UVA-treated PCs confirmed previously published results with a slight increase of PSLs compared to untreated PCs. Riboflavin/UVB-treated PCs present significant in vitro PSLs compared to untreated PCs. These lesions are caused by the UVB radiation alone and probably involve the generation of reactive oxygen species. The impact of these observations on clinical use must be investigated. © 2015 AABB.

  8. A comparative study of platelet-rich fibrin (PRF) and platelet-rich plasma (PRP) on the effect of proliferation and differentiation of rat osteoblasts in vitro.

    PubMed

    He, Ling; Lin, Ye; Hu, Xiulian; Zhang, Yu; Wu, Hui

    2009-11-01

    The purpose of this study was to evaluate the effect of biologic characteristics of platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) on proliferation and differentiation of rat osteoblasts. Blood samples were collected from 14 healthy volunteers (7 male) with a mean age of 23.2 +/- 2.24 years. PRP and PRF were prepared with standard protocols. The exudates of PRP and PRF were collected at the time points of 1, 7, 14, 21, and 28 days. The levels of platelet-derived growth factor AB (PDGF-AB) and transforming growth factor beta1 (TGF-beta1) were quantified in PRP and PRF. Then the exudates of PRP and PRF were used to culture rat calvaria osteoblasts. The biologic characteristics of osteoblasts were analyzed in vitro for 14 days. PRP released the highest amounts of TGF-beta1 and PDGF-AB at the first day, followed by significantly decreased release at later time points. PRF released the highest amount of TGF-beta1 at day 14 and the highest amount of PDGF-AB at day 7. Exudates of PRP collected at day 1 and exudates of PRF collected at day 14 expressed maximum alkaline phosphatase (ALP) activity, though no significance was shown. Cells treated with exudates of PRF collected at day 14 reached peak mineralization significantly more than both negative control and positive control groups. PRF is superior to PRP, from the aspects of expression of ALP and induction of mineralization. PRF released autologous growth factors gradually and expressed stronger and more durable effect on proliferation and differentiation of rat osteoblasts than PRP in vitro.

  9. Immunoelectrophoretic Studies of Sera from Rabbits Experimentally Infected with Histoplasma capsulatum

    PubMed Central

    Adamson, David M.; Cozad, George C.

    1966-01-01

    Adamson, David M. (University of Oklahoma, Norman), and George C. Cozad. Immunoelectrophoretic studies of sera from rabbits experimentally infected with Histoplasma capsulatum. J. Bacteriol. 92:887–891. 1966.—In a study involving 24 mature Dutch rabbits inoculated intravenously with 2.6 × 108Histoplasma capsulatum yeast cells per kg of body weight, all rabbits were shown to develop precipitins by the end of the 5th week. Precipitins were demonstrated both by the micro-Ouchterlony method and microimmunoelectrophoresis with the use of concentrated histoplasmin as the antigen. The latter technique proved to be the more sensitive. The 10 × concentrate of histoplasmin gave better precipitin patterns than did the 5 × concentrate. Agglutinins were formed by 90% of the rabbits by the end of the 4th week, as shown by the capillary tube agglutination test. Three precipitin bands, arbitrarily designated A, B, and C, were demonstrated by immunoelectrophoresis with use of the sera of the test animals. Band A occurred between the 1st and 2nd weeks after inoculation and was, for a period, present in 100% of the sera of the test animals. Band A occurred separately or in conjunction with band B or B and C, and it persisted longer than these other two bands. Bands B and C appeared between the 3rd and 4th weeks and were found, by the end of the 5th week, in 35 and 15%, respectively, of the sera tested. They were never seen separately or together without the presence of band A. Band C disappeared by the end of the 6th week, and band B, by the 10th week, but band A was still present in 19% of the sera at the end of 10 weeks. PMID:5926755

  10. Experimental study of sutureless vascular anastomosis with use of glued prosthesis in rabbits.

    PubMed

    Vokrri, Lulzim; Qavdarbasha, Arsim; Rudari, Hajriz; Ahmetaj, Halil; Manxhuka-Kërliu, Suzana; Hyseni, Nexhmi; Porcu, Paolo; Cinquin, Philippe; Sessa, Carmine

    2015-01-01

    The objective of this study is to explore the feasibility and efficacy of a new technique for sutureless vascular anastomosis, using glued prosthesis, as a sole anastomosis fixation method in rabbits. Ten rabbits were randomly selected to conduct the experiment. Five rabbits underwent direct anastomosis of infrarenal abdominal aorta, with glued prosthesis. In five other rabbits, reconstruction was done by sutured anastomosis. All animals were immediately examined by echo-Doppler for patency of anastomosis. The burst pressure of the glued anastomosis was measured and compared with that of a sutured artery. The animals were euthanized, and tissue samples were taken for histological examination immediately after the experiment. Compared to conventional anastomoses, sutureless vascular anastomoses required shorter time of creation and significantly reduced blood loss (P<5%). There was no significant difference on the average blood flow through the anastomosis between two groups at the end of surgery. All anastomoses with glued prosthesis, examined by echo-Doppler, were patent at the anastomotic site, except one, which was stenosed immediately after surgery. In the control group, except one with stenosis, all conventional anastomoses were patent. Mean burst pressure at the anastomotic site for sutureless anastomoses was lower than in control group. Macroscopically, the BioGlue did not demonstrate any adhesion to the surrounding tissue as it was covered by the vascular prosthesis. Histological examination showed low-grade inflammatory reaction in glued anastomoses versus no inflammatory reaction at the sutured anastomoses. This technique may provide a feasible and successful alternative in vascular surgery. However, further long-term studies are necessary to elucidate the break pressure and degree of inflammation at the anastomotic site.

  11. Immunoelectrophoretic studies of sera from rabbits exprimentally infected with Histoplasma capsulatum.

    PubMed

    Adamson, D M; Cozad, G C

    1966-10-01

    Adamson, David M. (University of Oklahoma, Norman), and George C. Cozad. Immunoelectrophoretic studies of sera from rabbits experimentally infected with Histoplasma capsulatum. J. Bacteriol. 92:887-891. 1966.-In a study involving 24 mature Dutch rabbits inoculated intravenously with 2.6 x 10(8)Histoplasma capsulatum yeast cells per kg of body weight, all rabbits were shown to develop precipitins by the end of the 5th week. Precipitins were demonstrated both by the micro-Ouchterlony method and microimmunoelectrophoresis with the use of concentrated histoplasmin as the antigen. The latter technique proved to be the more sensitive. The 10 x concentrate of histoplasmin gave better precipitin patterns than did the 5 x concentrate. Agglutinins were formed by 90% of the rabbits by the end of the 4th week, as shown by the capillary tube agglutination test. Three precipitin bands, arbitrarily designated A, B, and C, were demonstrated by immunoelectrophoresis with use of the sera of the test animals. Band A occurred between the 1st and 2nd weeks after inoculation and was, for a period, present in 100% of the sera of the test animals. Band A occurred separately or in conjunction with band B or B and C, and it persisted longer than these other two bands. Bands B and C appeared between the 3rd and 4th weeks and were found, by the end of the 5th week, in 35 and 15%, respectively, of the sera tested. They were never seen separately or together without the presence of band A. Band C disappeared by the end of the 6th week, and band B, by the 10th week, but band A was still present in 19% of the sera at the end of 10 weeks.

  12. Experimental study of sutureless vascular anastomosis with use of glued prosthesis in rabbits

    PubMed Central

    Vokrri, Lulzim; Qavdarbasha, Arsim; Rudari, Hajriz; Ahmetaj, Halil; Manxhuka-Kërliu, Suzana; Hyseni, Nexhmi; Porcu, Paolo; Cinquin, Philippe; Sessa, Carmine

    2015-01-01

    Objective The objective of this study is to explore the feasibility and efficacy of a new technique for sutureless vascular anastomosis, using glued prosthesis, as a sole anastomosis fixation method in rabbits. Methods Ten rabbits were randomly selected to conduct the experiment. Five rabbits underwent direct anastomosis of infrarenal abdominal aorta, with glued prosthesis. In five other rabbits, reconstruction was done by sutured anastomosis. All animals were immediately examined by echo-Doppler for patency of anastomosis. The burst pressure of the glued anastomosis was measured and compared with that of a sutured artery. The animals were euthanized, and tissue samples were taken for histological examination immediately after the experiment. Results Compared to conventional anastomoses, sutureless vascular anastomoses required shorter time of creation and significantly reduced blood loss (P<5%). There was no significant difference on the average blood flow through the anastomosis between two groups at the end of surgery. All anastomoses with glued prosthesis, examined by echo-Doppler, were patent at the anastomotic site, except one, which was stenosed immediately after surgery. In the control group, except one with stenosis, all conventional anastomoses were patent. Mean burst pressure at the anastomotic site for sutureless anastomoses was lower than in control group. Macroscopically, the BioGlue did not demonstrate any adhesion to the surrounding tissue as it was covered by the vascular prosthesis. Histological examination showed low-grade inflammatory reaction in glued anastomoses versus no inflammatory reaction at the sutured anastomoses. Conclusion This technique may provide a feasible and successful alternative in vascular surgery. However, further long-term studies are necessary to elucidate the break pressure and degree of inflammation at the anastomotic site. PMID:25848302

  13. Femoral head blood flow in long-term steroid therapy: study of rabbit model

    SciTech Connect

    Wang, G.J.; Hubbard, S.L.; Reger, S.I.; Miller, E.D.; Stamp, W.G.

    1983-12-01

    Using a rabbit model, previous studies showed steroid-induced hyperlipidemia with subsequent fatty embolization of the subchondral arteries and hypertrophy of the marrow fat cells, followed by elevation of femoral head pressure from the normal level of 25 cm to nearly 60 cm H2O after eight weeks of treatment. This has led us to believe that pressure changes lead to decreased blood flow in the femoral head. In our study of 22 New Zealand white adult rabbits, weighing an average of 4.0 kg, 14 received a weekly dose of 12.45 mg of methylprednisolone (Depo-Medrol), and eight served as control. Femoral head blood flow was established using the radioactive microsphere technique. Control and cortisone-treated rabbits had femoral head blood flow measured 6, 8 and 10 weeks after treatment. The average blood flow in the control femoral heads averaged 0.2039 +/- 0.076 ml/min/gm, with no difference in the left side and the right side. In the treated group, the average blood flow at ten weeks was 0.162 +/- 0.039 ml/min/gm on the right and 0.164 +/- 0.037 ml/min/gm on the left, which was significantly different. This is parallel to unpredictable clinical findings in human beings.

  14. External heating of stents by radio waves: pilot studies in rabbit aorta.

    PubMed

    Levitt, Adam B; Robinson, Keith; Chronos, Nicolas A F; Daum, Wolfgang

    2003-01-01

    This experiment was designed to assess the feasibility of radio frequency energy delivered by a prototype radio frequency generator inductive heating device (REVAX) positioned external to the body, for transient heating of stents after arterial implant. Twenty-one New Zealand White rabbits underwent stenting of their infrarenal aorta. Nine rabbits were stented and immediately placed in the REVAX for external stent heating with internal temperature probes in place. Twelve rabbits were stented and 3 days later either heated or placed in the generator as a sham for 20 min. The animals were terminated 28 days later. The REVAX was able to heat the aortic stents in a controlled fashion; in Phase II experiments, the stent temperature was raised to 42 degrees C for 20 min. In Phase I mild necrosis was noted at the stent struts. In Phase II, necrosis and mineralization of the media was seen at the stent struts, and evidence of neointimal suppression was observed. This study demonstrated that external heating of stents in a blood vessel in a live animal via radio frequency energy is feasible. Further studies will be needed to assess whether any specific heating regimen might inhibit fibrocellular neointimal hyperplasia.

  15. Platelet function in diabetic and non-diabetic patients with chronic obstructive pulmonary disease: A case control study.

    PubMed

    Makhlouf, Hoda Ahmed; Sadek, Samiaa Hamdy; Nafady, Asmaa Abdel Hakim

    2016-03-22

    The effect of association between chronic obstructive pulmonary disease (COPD) and diabetes (DM) on platelet function has not been studied before. To evaluate the effect of the association between COPD and DM on platelet function and C reactive protein (CRP). This case control study was carried out on 110 stable COPD patients who were classified into diabetic and non-diabetic groups. In addition to 40 apparently healthy, age and sex-matched individuals. Chest X-ray, pulmonary function testing and arterial blood gases were done for COPD patients. CRP and complete blood count (CBC) were measured in both patient and control groups. Mean Platelet volume (MPV), Platelet distribution width (PDW), Platelet crit (PCT) and CRP were significantly higher in COPD patients either non-diabetic or diabetic compared to control group. Moreover MPV and CRP markers were significantly higher in COPD diabetic patients compared to non-diabetic. There was no significant difference in various laboratory data among different stages of COPD either diabetic or non-diabetic (P >0.05). In COPD patients, MPV was a significantly positively correlated with CRP and PDW (r= 0.346, P<0.001; r=0.510, P<0.001 respectively) and negatively correlated with PLT count (r= -0.294, P=0.002). MPV. PDW, PCT and CRP were significantly higher in COPD patients either non -diabetic or diabetic. Platelet function may be modified by the systemic inflamattion that associated with COPD. Platelet activation as a prothrombotic sequence of this disease may be used as novel therapeutic target. This article is protected by copyright. All rights reserved. Copyright © 2016 John Wiley & Sons Ltd.

  16. Autologous Platelet Concentrates for Pulp and Dentin Regeneration: A Literature Review of Animal Studies.

    PubMed

    Del Fabbro, Massimo; Lolato, Alessandra; Bucchi, Cristina; Taschieri, Silvio; Weinstein, Roberto L

    2016-02-01

    The purpose of this study was to evaluate the effectiveness of autologous platelet concentrates (APCs) in promoting pulp and dentin regeneration in animal models. An electronic search was performed on MEDLINE, Embase, Scopus, SciELO, LILACS, and CENTRAL. Animal studies using APC as a root filling material after pulpectomy in mature or immature teeth were included. Articles underwent risk of bias assessment. Histologic evaluation of intracanal neoformed tissue was the primary outcome; root development, root wall thickening, apical closure, and periapical healing in apical periodontitis were the secondary outcomes. Seven articles were included. Platelet-rich plasma (PRP) was used as root filling material during regenerative procedures in the experimental group in either mature or immature teeth. After revascularization with PRP alone or in conjunction with stem cells of a different source, the histologic analyses revealed that, in addition to an odontoblastic cell layer or dentinlike structure, the neoformed intracanal tissues were mainly cementumlike, bonelike, and connective tissues. True regeneration of necrotic pulp may not be achieved with current techniques using PRP, all of which stimulated tissue repair. Benefits of PRP adjunct for pulp tissue regeneration in preclinical studies remain unclear. Further studies with standardized protocols are necessary to assess the actual contribution of PRP in endodontic regenerative therapies. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  17. Recombinant activated factor VII does not reduce bleeding in rabbits treated with aspirin and clopidogrel.

    PubMed

    Hindy-François, Clemence; Bachelot-Loza, Christilla; Le Bonniec, Bernard; Grelac, Francoise; Dizier, Blandine; Godier, Anne; Emmerich, Joseph; Gaussem, Pascale; Samama, Charles-Marc

    2010-10-01

    Combined antiplatelet agents (cAPA), aspirin plus clopidogrel, increase the risk of bleeding. We hypothesised that recombinant activated FVIIa (rFVIIa), which normalises thrombin generation in platelet-rich plasma from patients treated with cAPA, could limit this bleeding risk. It was the objective of this study to investigate the efficacy and safety of rFVIIa compared to placebo, in a bleeding and thrombosis model in rabbits treated with aspirin and clopidogrel. New-Zealand rabbits, randomised into two groups (Placebo1, n=36 ; cAPA, n=34), were anaesthetised, ventilated and monitored for blood pressure, temperature and carotid blood flow. The Folts model was applied to a carotid artery. Cyclic flow reductions (CFR) were recorded over a first 20-min period (Obs1). Each rabbit was then randomly assigned into one of three subgroups (Placebo2, 40μg/kg rFVIIa, 160 μg/kg rFVIIa) and CFR were monitored for a second 20-min period (Obs2). Ear bleeding time (BT) was measured at the end of each period. Hepatosplenic (HS) section was performed at the end of the experiment and HS blood loss defines the primary endpoint. Secondary endpoints were thrombosis (CFR), prothrombin time, platelet aggregation, and thrombin generation. Non- parametric statistical tests were used (p<0.05). cAPA significantly increased HS blood loss, BT and suppressed CFR compared to Placebo1 (p<0.05). rFVIIa injection did not modify HS blood loss, BT or CFR rate in Placebo1 rabbits nor in cAPA animals. These effects were unaffected by either rFVIIa dose. rFVIIa accelerated thrombin generation but had no effect on platelet aggregation in citrated platelet-rich plasma. rFVIIa did not modify HS blood loss associated with cAPA in rabbits.

  18. Study on the Efficacy of Platelet-rich Fibrin Matrix in Hair Follicular Unit Transplantation in Androgenetic Alopecia Patients

    PubMed Central

    Mahapatra, Sandeep; Kumar, Dhruva; Subramanian, Vignesh; Chakrabarti, Swarup K.

    2016-01-01

    Objective: Hair loss is a significant problem worldwide. The most common cause of hair loss in men is male androgenetic alopecia, male pattern baldness, which is primarily due to the presence of nonfunctional or dead hair follicles in the scalp. Hair follicular unit transplantation has been a widely used technique to transplant hair follicles into bald areas. Although follicular unit transplantation generally gives satisfactory hair transplantation, efforts have been made to further increase the efficacy of follicular unit transplantation in hair regeneration. The crucial discovery of platelet-derived growth factors has resulted in the development of novel autologous therapeutic methods. Platelet-rich fibrin matrix represents a revolutionary step in the platelet gel therapeutic concept. This technique is fast and involves minimal in vitro manipulations. In this paper, the authors studied the efficacy of platelet-rich fibrin matrix in conjunction with follicular unit transplantation for regeneration of new hair in bald areas in male androgenetic alopecia patients. Design: Ten male subjects between 18 and 50 years of age with Norwood Alopecia from Grade 4 to 6 were chosen for the study. Setting: The study was performed at Derma Solutions clinic, Bengaluru, Karnataka, India. Participants: Patients with thyroid disorders, bleeding disorders, or other co-existing morbidities were excluded. Results: The number of hair follicles began to increase progressively after platelet-rich fibrin matrix treatment was performed on the right side of the scalp and the effect was very distinct after six months of platelet-rich fibrin matrix treatment. Conclusion: This study clearly indicates that platelet-rich fibrin matrix plays a key role in hair regeneration using follicular unit transplantation techniques. Further studies are needed to determine how platelet-rich fibrin matrix helps improve hair retention and regeneration. Additionally, it would be interesting to know how long the

  19. A randomized comparative prospective study of platelet-rich plasma, platelet-rich fibrin, and hydroxyapatite as a graft material for mandibular third molar extraction socket healing.

    PubMed

    Dutta, Shubha Ranjan; Passi, Deepak; Singh, Purnima; Sharma, Sarang; Singh, Mahinder; Srivastava, Dhirendra

    2016-01-01

    The purpose of this study was to compare the efficacy of platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and hydroxyapatite (HA) for reduction of pain and swelling, absence of dry socket, soft tissue healing, and bone regeneration after mandibular third molar extraction in human patients. Forty patients requiring extraction of mandibular third molars were randomly grouped as control, PRP, PRF, and HA-treated. The patients were assessed for postoperative pain, swelling, dry socket, and soft tissue healing on the 3(rd), 7(th), and 14(th) day of postoperative periods depending on the standard methods. Radiological assessment of the extraction site was done at 1, 2, and 6 months interval to compare the change in bone density in the sockets in control and treated patients. Pain and swelling were less on PRP and PRF site when compared to HA and control site. PRP and PRF site showed better soft tissue healing when compared to HA and control site. Radiographic assessment showed comparatively lesser bone density values in PRP, PRF, and control site at 1, 2, and 6 months than HA site. Our study showed that PRP and PRF are better graft materials than HA regarding pain, swelling, dry socket, and soft tissue healing. Bone regeneration is induced promptly by HA as compared to other graft materials. However, a more elaborate study with a larger number of clinical cases is very much essential to be more conclusive regarding the efficacy of the graft materials.

  20. A randomized comparative prospective study of platelet-rich plasma, platelet-rich fibrin, and hydroxyapatite as a graft material for mandibular third molar extraction socket healing

    PubMed Central

    Dutta, Shubha Ranjan; Passi, Deepak; Singh, Purnima; Sharma, Sarang; Singh, Mahinder; Srivastava, Dhirendra

    2016-01-01

    Aim: The purpose of this study was to compare the efficacy of platelet-rich plasma (PRP), platelet-rich fibrin (PRF), and hydroxyapatite (HA) for reduction of pain and swelling, absence of dry socket, soft tissue healing, and bone regeneration after mandibular third molar extraction in human patients. Materials and Methods: Forty patients requiring extraction of mandibular third molars were randomly grouped as control, PRP, PRF, and HA-treated. The patients were assessed for postoperative pain, swelling, dry socket, and soft tissue healing on the 3rd, 7th, and 14th day of postoperative periods depending on the standard methods. Radiological assessment of the extraction site was done at 1, 2, and 6 months interval to compare the change in bone density in the sockets in control and treated patients. Results: Pain and swelling were less on PRP and PRF site when compared to HA and control site. PRP and PRF site showed better soft tissue healing when compared to HA and control site. Radiographic assessment showed comparatively lesser bone density values in PRP, PRF, and control site at 1, 2, and 6 months than HA site. Conclusion: Our study showed that PRP and PRF are better graft materials than HA regarding pain, swelling, dry socket, and soft tissue healing. Bone regeneration is induced promptly by HA as compared to other graft materials. However, a more elaborate study with a larger number of clinical cases is very much essential to be more conclusive regarding the efficacy of the graft materials. PMID:28163478

  1. Combined Therapy of Radiofrequency Ablation and Ethanol Injection of Rabbit Liver: An In Vivo Feasibility Study

    SciTech Connect

    Lee, Jeong Min; Lee, Young Hwan; Kim, Young Kon; Kim, Sang Won; Kim, Chong Soo

    2004-03-15

    Our purpose was to compare the effects of percutaneous radiofrequency ablation (RFA) combined with percutaneous ethanol injection (PEI) on the extent of ablation in in vivo rabbit liver tissue as compared with either therapy alone. Twenty-two New Zealand white rabbits were included in this study and allocated into three groups: group A: conventional RFA (n = 6); group B: PEI (n = 6); group C: combined RFA and PEI (n = 10). For combined RFA and PEI, under ultrasound guidance, 1 mL of absolute ethanol was injected into the target area of the liver parenchyma through a 21-gauge Chiba needle before performing RFA. RFA was performed using a 17- gauge internally cooled electrode with 1-cm active tip, and RF energy (30 W) was applied for 3 minutes, with or without ethanol injection. After RFA or PEI, contrast-enhanced computed tomography and CT-pathologic correlation were performed. The short- axis and long-axis diameters of thermal lesions of each group were compared. All procedures were technically successful and a total of 38 lesions were produced. The mean short-axis and long-axis diameter of the coagulation necrosis in rabbits of group C (combination of RFA and PEI), were significantly larger than those of other groups: group A: 10.3 {+-} 2 mm and 11.4 {+-} 2 mm; group B: 3.1 {+-} 1 mm and 4.3 {+-} 2 mm; group C: 12.8 {+-} 3 mm and 17.8 {+-} 6 mm (p < 0.05). On contrast-enhanced CT scan, the lesions of rabbits of the group C appeared to be more frequently irregular compared to those of group A (20% in group A vs. 67% in group C). There were three complications including two localized hematomas and one cardiopulmonary failure. Combined RFA and PEI could increase the dimension of coagulation necrosis without increasing complications and therefore, may be successfully used for treating larger lesions.

  2. Corneal wound healing after ultraviolet-A/riboflavin collagen cross-linking: a rabbit study.

    PubMed

    Salomão, Marcella Q; Chaurasia, Shyam S; Sinha-Roy, Abhijit; Ambrósio, Renato; Esposito, Andrew; Sepulveda, Ricardo; Agrawal, Vandana; Wilson, Steven E

    2011-06-01

    To investigate corneal wound healing following ultraviolet-A (UVA)/riboflavin corneal collagen cross-linking (CXL) in rabbit corneas. Thirty-six rabbits were enrolled in the study. Animals were divided into three treatment groups and corneas were analyzed at 24 hours and 4 weeks postoperatively. Thus, each group had 6 rabbits at each time point. Treatment groups were: 1) standard UVA+riboflavin CXL, 2) UVA alone, and 3) riboflavin alone. One eye of each rabbit served as an untreated control eye. TUNEL assay was performed to detect stromal cell apoptosis. Immunocytochemistry was performed to detect the inflammatory marker CD11b expressed in monocytes and the alpha-smooth muscle actin (SMA) marker expressed in myofibroblasts. At 24 hours, corneas from the UVA+riboflavin CXL group had significantly more apoptosis than the UVA alone and riboflavin alone groups. Eyes from all three groups had significantly more inflammatory cell influx into the cornea than unwounded controls. Four weeks after the procedure, many corneas in the UVA+riboflavin CXL group had mild haze, but very few SMA-positive myofibroblasts could be detected in the central cornea. Riboflavin+UVA CXL triggers more anterior keratocyte apoptosis than corneal scrape with UVA alone or riboflavin alone. Inflammation monitored by the monocyte marker CD11b was present, but not statistically different among the three groups. Very little myofibroblast generation could be detected after UVA+riboflavin CXL, indicating that the mild stromal haze associated with this procedure is normally related to transient corneal fibroblast generation rather than more persistent haze due to generation of myofibroblasts. Copyright 2011, SLACK Incorporated.

  3. THE EFFECT OF ACETYLSALICYLIC ACID ON PLATELET FUNCTION

    PubMed Central

    Evans, Geoffrey; Packham, Marian A.; Nishizawa, Edward E.; Mustard, James F.; Murphy, Edmund A.

    1968-01-01

    Acetylsalicylic acid (ASA, aspirin) and sodium salicylate inhibit platelet aggregation induced by collagen, antigen-antibody complexes, gamma globulin-coated particles or thrombin. These compounds suppress the release of platelet constituents, such as adenosine diphosphate (ADP) and serotonin, induced by such stimuli. Since ASA and sodium salicylate do not inhibit ADP-induced platelet aggregation, it appears that their effect on the action of the other stimuli is due to a decrease in the amount of ADP released. The administration of ASA to rabbits (in doses which inhibited collagen-induced platelet aggregation) impaired hemostasis, prolonged platelet survival, and diminished the amount of deposit formed in an extracorporeal shunt. PMID:4176225

  4. Blood vessels are concentrated within the implant surface concavities: a histologic study in rabbit tibia.

    PubMed

    Scarano, Antonio; Perrotti, Vittoria; Artese, Luciano; Degidi, Marco; Degidi, Davide; Piattelli, Adriano; Iezzi, Giovanna

    2014-07-01

    Angiogenesis plays a key role in bone formation and maintenance. Bone formation has been reported to initiate in the concavities rather than the convexities in a hydroxyapatite substratum and the implant threads of dental implants. The aim of the present study was to evaluate the number of the blood vessels inside the concavities and around the convexities of the threads of implants in a rabbit tibia model. A total of 32 thread-shaped implants blasted with apatitic calcium phosphate (TCP/HA blend) (Resorbable Blast Texturing, RBT) (Maestro, BioHorizons(®), Birmingham, AL, USA) were inserted in 8 rabbits. Each rabbit received 4 implants, 2 in the right and 2 in left tibia. Implants were retrieved after 1, 2, 4, and 8 weeks and treated to obtain thin ground sections. Statistically significant differences were found in the number of vessels that had formed in the concavities rather than the convexities of the implants after 1 (p = 0.000), and 2 weeks (p = 0.000), whilst no significant differences after 4 (p = 0.546) and 8 weeks (p = 0.275) were detected. The present results supported the hypothesis that blood vessel formation was stimulated by the presence of the concavities, which may provide a suitable environment in which mechanical forces, concentrations and gradients of chemotactic molecules and blood clot retention may all drive vascular and bone cell migration.

  5. Effects of cortical bone perforation on periosteal distraction: an experimental study in the rabbit mandible.

    PubMed

    Oda, Tomoo; Kinoshita, Kazuhiko; Ueda, Minoru

    2009-07-01

    To investigate tissue reactions using periosteal distraction with decorticating holes in a rabbit model. Twenty-five Japanese white rabbits weighing 3.2 to 3.7 kg were used. The periosteum was carefully detached, and the buccal cortical bone was porously perforated by drilling in the decortication group. Titanium mesh was placed between the periosteum and the cortical bone, with or without holes. A distraction screw was placed rigidly under the center of the mesh. After a 7-day latency period, the periosteum was distracted 0.5 mm per day for 8 consecutive days. Rabbits were sacrificed after consolidation periods of 4 and 8 weeks. Cross-sectional radiographs were evaluated with densitometry. Specimens were fixed, decalcified, and stained with hematoxylin and eosin. At 8 weeks after periosteal distraction, the area of new bone formation averaged 25.7 +/- 5.1 mm2 and 12.9 +/- 3.2 mm2 (mean +/- SD) with and without decortication, respectively. In this study, periosteal distraction showed better bone regeneration on the lateral aspect of mandibles with rather than without decorticating holes. Periosteal distraction with decorticating holes can be effective in augmenting atrophic bone.

  6. Potential Role of Local Estrogen in Enhancement of Fracture Healing: Preclinical Study in Rabbits

    PubMed Central

    Tahami, Mohammad; Haddad, Behrooz; Abtahian, Armin; Hashemi, Ali; Aminian, Amir; Konan, Sujith

    2016-01-01

    Background: Effects of estrogen on bone metabolism and its protective role on prevention of osteoporosis are well documented. However, the efficacy of estrogen treatment on bone healing is not well investigated. The drug can be delivered both systemically or locally to the bone with differences in concentrations and side effects. The aim of this study was to investigate the effect of local and systemic administration of estrogen on the fracture healing process. Methods: Standardized tibial fractures with 4 millimeter gaps were created in twenty four adult male Dutch rabbits. Fractures were fixed using intramedullary wires and long leg casts. Rabbits were randomly divided into three groups. Group A was treated with twice a week administration of long acting systemic estrogen; group B was treated with a similar regimen given locally at the fracture gap; and group C received sham normal saline injections (control). Fracture healing was assessed at six weeks post fracture by gross examination, radiographic and histomorphometric analysis. Results: Group B had significantly higher gross stability, radiographic union and gap reduction than the two other groups. Histomorphometric analysis showed higher cartilaginous proportion of periosteal callus area in the control group. Conclusions: Our results showed that estrogen may enhance fracture healing of long bone in rabbits. Furthermore, local estrogen treatment might have better effect than systemic treatment. PMID:27847844

  7. Effects of Hypericum perforatum on the healing of xenografts: a histomorphometric study in rabbits.

    PubMed

    Damlar, I; Arpağ, O F; Tatli, U; Altan, A

    2016-12-19

    The aim of this study was to investigate effects of the Hypericum perforatum (St John's Wort) on bone healing in rabbit calvarium. Ten male New Zealand rabbits each had three bicortical defects made in the calvarial bones, which were filled with xenograft, xenograft+H perforatum oil extract, and autogenous graft. Four weeks postoperatively all rabbits were killed and the bony defects examined histomorphometrically. Tissue compartments including new bone (p<0.001), marrow space (p<0.001), and residual bone grafts (p=0.014) differed significantly among groups (p=0.00?). The volume of residual graft was significantly decreased in the xenograft/H perforatum group compared with those with xenografts alone (p=0.0147). The differences in microarchitectural variables of de novo bone formation were also significant (trabecular thickness (p<0.001), trabecular width (p<0.001), trabecular separation (p=0.001). There were no significant differences in node:terminus ratio between the xenograft/H perforatum group and the other two groups. However, the difference in node:terminus ratio between the autogenous graft and xenograft group was significant (p=0.001) Oil extracts of H perforatum improved bony healing in defects filled with bovine-derived xenografts.

  8. Repeated transchoroidal implantation and explantation of compound subretinal prostheses: an exploratory study in rabbits.

    PubMed

    Gekeler, Florian; Kobuch, Karin; Blatsios, Georgios; Zrenner, Eberhart; Shinoda, Kei

    2010-09-01

    For human trials with retinal prostheses it is mandatory to develop procedures to safely explant and possibly reimplant the devices. This prompted us to investigate in a small exploratory study the safety of repeated transchoroidal implantation and explantation procedures of complex subretinal devices in laboratory animals. Repeated transchoroidal surgery was performed in four rabbits. The rabbits were examined by clinical examination and funduscopy. Function was assessed by electroretinography and cortical recordings following light and subretinal electrical stimulation. Sections of the retina and of the implantation channel were examined by light microscopy. Using the same access route, repeated transchoroidal subretinal implantation surgery was successfully performed in all cases. Fixation of implants was stable for up to 13 months; retinas remained attached at all examination dates. Electroretinograms and visual evoked cortical potential proved retinal and visual pathway integrity. Subretinal electrical stimulation elicited retinal and cortical responses. While retinal morphology at earlier stages was found to be essentially unaltered, atrophic disorganization in the region of the subretinal channel was observed after 10 months and after subretinal electrical stimulation. Repeated transchoroidal surgery can be safely performed for implantation, explantation, and reimplantation of subretinal devices in rabbits. With modifications, we believe the technique can be applied in human surgery.

  9. Histochemical study of Encephalitozoon cuniculi spores in the kidneys of naturally infected New Zealand rabbits.

    PubMed

    Rodríguez-Tovar, Luis E; Villarreal-Marroquín, Alejandra; Nevárez-Garza, Alicia M; Castillo-Velázquez, Uziel; Rodríguez-Ramírez, Heidi G; Navarro-Soto, Magda C; Zárate-Ramos, Juán J; Hernández-Vidal, Gustavo; Trejo-Chávez, Armando

    2017-05-01

    Encephalitozoon cuniculi is an important microsporidian pathogen that is considered an emergent, zoonotic, and opportunistic. It infects both domestic and laboratory rabbits, generating severe chronic interstitial and granulomatous nephritis with fibrosis and granulomatous encephalitis. Encephalitozoonosis is diagnosed in paraffin-embedded sections by examining the spores in the host tissues. The spores are difficult to observe when the samples are stained with hematoxylin and eosin (H&E), particularly when there is an inflammatory reaction and tissue damage. The spores are easily mistaken for other microorganisms, such as fungi (yeasts), protozoa, and bacteria. In our study, we used kidney samples from E. cuniculi-positive rabbits and employed 14 recommended histologic stains for detecting microsporidia spores: alcian blue, calcofluor white, Giemsa, Gram, Grocott, H&E, Luna, Luxol fast blue, Masson trichrome, modified trichrome stain (MTS), periodic acid-Schiff reaction (PAS), Van Gieson, Warthin-Starry (WS), and Ziehl-Neelsen (ZN).We concluded that MTS and Gram stain, detected by light microscopy, and calcofluor white stain, detected by ultraviolet light microscopy, are the best stains for detecting spores of E. cuniculi in paraffin-embedded tissues from infected rabbits. These stains were superior to WS, ZN, Giemsa, and PAS for identifying spores without background "noise" or monochromatic interference. Also, they allow individual spores to be discerned in paraffin-embedded tissues. MTS allows observation of the polar tube, polaroplast, and posterior vacuole, the most distinctive parts of the spore.

  10. [Efficacy of clopidogrel as ADP-dependent platelet aggregation inhibitor. Study on individuals with coronary artery disease].

    PubMed

    Izaguirre Avila, R; de la Peña, A; González Pacheco, H; Ramírez Gutiérrez, A; González Valdez, H; Quiroz, A; Cortina, E; Huerta, M; Lupi, E

    2000-01-01

    Acetyl-salicylic acid inhibits thromboxane A2 production and reduces the risk of vascular occlusive events by 20 to 25%. Ticlopidine inhibits ADP-dependent platelet aggregation and reduces the same risk by 30 to 35%, but produces some adverse effects. Clopidogrel is a ticlopidin-derived antiplatelet-drug, with the same mechanism of action; reduces the expression of the glycoprotein IIb/IIIa, the fibrinogen receptor on the platelet surface. Clopidogrel has the same clinical efficacy of ticlopidin and lowers the incidence of adverse effects. In this study, we evaluated the effects of one daily dosis of 75 mg of clopidogrel on platelet function in 33 subjects with coronary artery disease. Before treatment and after the 6th and 12th week, the following parameters were evaluated: 5 microM-ADP and 20 micrograms/mL collagen-induced platelet aggregation, bleeding time and fibrinogen concentration. In basal and in the 6th and 12th week samples, ADP-induced platelet aggregation was 90.7% +/- 13.2, 54.6% +/- 23.2 and 49.2% +/- 23.7 respectively, that represents a significant reduction of 38.6% and 44.4%. Reduction of collagen-induced platelet aggregation was not significative. Plasmatic fibrinogen did not suffer variation during treatment. Bleeding time was significant prolonged from 4.1 minutes to 15.4 and 14.6 minutes (3.7-3.5 times compared with the test before treatment). There were no haemorrhagic complications, only digestive discomfort in fewer than 3% of patients. We concluded that clopidogrel is a safe and efficacious drug for patients, it efficiently reduces ADP-induced platelet aggregation and prolongs bleeding time.

  11. Thrombospondin-induced adhesion of human platelets.

    PubMed Central

    Tuszynski, G P; Kowalska, M A

    1991-01-01

    Washed human unactivated platelets attached and spread on thrombospondin (TSP)-coated microtiter plates. Platelet adhesion was promoted by divalent cations Mn2+, Mg2+, and Ca2+ as compared to buffer having all divalent cations complexed with EDTA. TSP-dependent adhesion was inhibited by anti-TSP fab fragments, an anti-TSP monoclonal antibody, an RGD-containing peptide, complex-specific anti-glycoprotein (GP)IIb-IIIa monoclonal antibodies (A2A9 or AP-2) and anti-VLA-2 monoclonal antibodies (6F1 and Gi9), but not by rabbit preimmune fab fragments, mouse IgG, an anti-GPIIIa monoclonal antibody, or monoclonal antibodies against either the human vitronectin receptor, glycocalicin, or GPIV. At saturating concentrations, anti-GPIIb-IIIa inhibited adhesion by 40-60%. Glanzman's thrombasthenic platelets, which lack GPIIb-IIIa, adhered to TSP to the same extent as anti-GPIIb-IIIa-treated normal platelets or 40-60% as well as untreated normal platelets. Antibody 6F1 (5-10 micrograms/ml) inhibited platelet adhesion of both normal and thrombasthenic platelets by 84-100%. Both VLA-2 antibodies also inhibited collagen-induced platelet adhesion, but had no effect on fibronectin-induced adhesion of normal platelets. These data indicate that platelets specifically adhere to TSP and that this adhesion is mediated through GPIIb-IIIa and/or VLA-2. Images PMID:2010551

  12. Rabbit medicine.

    PubMed

    Jordan, Dinah G

    2007-01-01

    When filling prescriptions for a rabbit, it is important to know whether the rabbit is a pet or is being raised as a source of food for human consumption. Several drugs widely used for pet rabbits are prohibited from exralabel use in animals raised for food production. The list of banned drugs should always be perused prior to filling a prescription for a rabbit being raised for food production. Since no veterinary-approved products exist for rabbits and most medications must be compounded, pharmacists are likely to encounter prescriptions for rabbits in their practice. A basic understanding of rabbit anatomy, physiolgy and common diseases will assist pharmacists in distinguishing between safe and dangerous drugs for administration to rabbits.

  13. Roles of focal adhesion kinase (FAK) in megakaryopoiesis and platelet function: studies using a megakaryocyte lineage–specific FAK knockout

    PubMed Central

    Hitchcock, Ian S.; Fox, Norma E.; Prévost, Nicolas; Sear, Katherine; Shattil, Sanford J.

    2008-01-01

    Focal adhesion kinase (FAK) plays a key role in mediating signaling downstream of integrins and growth factor receptors. In this study, we determined the roles of FAK in vivo by generating a megakaryocyte lineage–specific FAK-null mouse (Pf4-Cre/FAK-floxed). Megakaryocyte and platelet FAK expression was ablated in Pf4-Cre/FAK-floxed mice without affecting expression of the FAK homologue PYK2, although PYK2 phosphorylation was increased in FAK−/− megakaryocytes in response to fibrinogen. Megakaryopoiesis is greatly enhanced in Pf4-Cre/FAK-floxed mice, with significant increases in megakaryocytic progenitors (CFU-MK), mature megakaryocytes, megakaryocyte ploidy, and moderate increases in resting platelet number and platelet recovery following a thrombocytopenic stress. Thrombopoietin (Tpo)–mediated activation of Lyn kinase, a negative regulator of megakaryopoiesis, is severely attenuated in FAK-null megakaryocytes compared with wild-type controls. In contrast, Tpo-mediated activation of positive megakaryopoiesis regulators such as ERK1/2 and AKT is increased in FAK-null megakaryocytes, providing a plausible explanation for the observed increases in megakaryopoiesis in these mice. In Pf4-Cre/FAK-floxed mice, rebleeding times are significantly increased, and FAK-null platelets exhibit diminished spreading on immobilized fibrinogen. These studies establish clear roles for FAK in megakaryocyte growth and platelet function, setting the stage for manipulation of this component of the Tpo signaling apparatus for therapeutic benefit. PMID:17925492

  14. Effects of tranexamic acid on platelet function and thrombin generation (ETAPlaT): WOMAN trial sub-study

    PubMed Central

    2016-01-01

    Background. Postpartum haemorrhage (PPH) is a leading cause of maternal death. Tranexamic acid (TXA) has the potential to reduce bleeding and a large randomized placebo controlled trial of its effect in women with PPH (The WOMAN trial) is underway. TXA might also affect coagulation factors and platelets.  Objectives. To examine the effect of TXA on thrombin generation, platelet function, fibrinogen, D-dimer and coagulation factors in women with PPH.  Methods. We will conduct a sub-study within the WOMAN trial. Women with clinically diagnosed primary PPH after vaginal or caesarean delivery are eligible for inclusion. Blood samples will be collected at baseline and 30 minutes after the first dose of study treatment. Using platelet poor plasma we will measure thrombin generation, fibrinogen, D-dimer, factor V and VIII, and Von Willebrand factor. Platelet function will be evaluated in whole blood using Multiplate® tests. Outcomes. The primary outcome is the effect of TXA on thrombin generation. Secondary outcomes include the effect of TXA on platelet function, fibrinogen, D-dimer and coagulation factors. PMID:28090594

  15. In vitro study of the specific interaction between poly(2-dimethylamino ethylmethacrylate) based polymers with platelets and red blood cells.

    PubMed

    Flebus, Luca; Lombart, François; Martinez-Jothar, Lucía; Sevrin, Chantal; Delierneux, Céline; Oury, Cécile; Grandfils, Christian

    2015-08-15

    Poly(2-dimethylamino)ethyl methacrylate (PDMAEMA) is an attractive polycation frequently proposed as a non-viral vector for gene therapy. As expected for other cationic carriers, intravenous administration of PDMAEMA can result in its ionic complexation with various negatively charged domains found within the blood. To gain more insight into this polycation hemoreactivity, we followed the binding kinetics of a free form (FF) of fluorescein labelled PDMAEMA (Mn below 15 kDa) in normal human blood using flow cytometry. This in vitro study highlighted that platelets display higher affinity for this polycation compared to red blood cells (RBCs), with an adsorption isotherm characteristics of a specific saturable binding site. PDMAEMA (1-20 μg/mL) exerted a concentration dependent proaggregant effect with a biphasic aggregation of washed platelets. Activation of platelets was also noticed in whole blood with the expression of P-selectin and fibrinogen on platelet surface. Although additional studies would be needed in order to elucidate the mechanism of PDMAEMA mediated activation of platelets, our manuscript provides important information on the hemoreactivity of FF PDMAEMA. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Agents that elevate the concentration of cAMP in platelets inhibits the formation of a NaDodSO/sub 4/-resistant complex between thrombin and a 40-kDa protein

    SciTech Connect

    Lerea, K.M.; Glomset, J.A.

    1987-08-01

    The authors studied the influence of prostaglandin E/sub 1/ and theophylline on the ability of rabbit or human platelets to form NaDodSO/sub 4/-resistant complexes between /sup 125/I-labeled thrombin and a platelet protein of approx. =40 kDa. Control platelets formed two types of these complexes, one that sedimented with the platelets and one that was found in the suspension medium. There were 30-40 sedimentable complexes per platelet and about three times this number of soluble complexes. Pretreatment of rabbit or human platelets with prostaglandin E/sub 1/ and theophylline decreased the formation of both types of complex by as much as 60-80%. The pretreatment was particularly effective when low doses of thrombin were used. When added to control platelets, such doses of thrombin caused the formation of sedimentable complexes and the concomitant formation of inositol trisphosphate. However, when added to platelets that had been pretreated with prostaglandin E/sub 1/ and theophylline, low doses of thrombin had little or no effect on either reaction.

  17. Rho GTPases in platelet function.

    PubMed

    Aslan, J E; McCarty, O J T

    2013-01-01

    The Rho family of GTP binding proteins, also commonly referred to as the Rho GTPases, are master regulators of the platelet cytoskeleton and platelet function. These low-molecular-weight or 'small' GTPases act as signaling switches in the spatial and temporal transduction, and amplification of signals from platelet cell surface receptors to the intracellular signaling pathways that drive platelet function. The Rho GTPase family members RhoA, Cdc42 and Rac1 have emerged as key regulators in the dynamics of the actin cytoskeleton in platelets and play key roles in platelet aggregation, secretion, spreading and thrombus formation. Rho GTPase regulators, including GEFs and GAPs and downstream effectors, such as the WASPs, formins and PAKs, may also regulate platelet activation and function. In this review, we provide an overview of Rho GTPase signaling in platelet physiology. Previous studies of Rho GTPases and platelets have had a shared history, as platelets have served as an ideal, non-transformed cellular model to characterize Rho function. Likewise, recent studies of the cell biology of Rho GTPase family members have helped to build an understanding of the molecular regulation of platelet function and will continue to do so through the further characterization of Rho GTPases as well as Rho GAPs, GEFs, RhoGDIs and Rho effectors in actin reorganization and other Rho-driven cellular processes. © 2012 International Society on Thrombosis and Haemostasis.

  18. Disposable rabbit

    DOEpatents

    Lewis, Leroy C.; Trammell, David R.

    1986-01-01

    A disposable rabbit for transferring radioactive samples in a pneumatic transfer system comprises aerated plastic shaped in such a manner as to hold a radioactive sample and aerated such that dissolution of the rabbit in a solvent followed by evaporation of the solid yields solid waste material having a volume significantly smaller than the original volume of the rabbit.

  19. Disposal rabbit

    DOEpatents

    Lewis, L.C.; Trammell, D.R.

    1983-10-12

    A disposable rabbit for transferring radioactive samples in a pneumatic transfer system comprises aerated plastic shaped in such a manner as to hold a radioactive sample and aerated such that dissolution of the rabbit in a solvent followed by evaporation of the solid yields solid waste material having a volume significantly smaller than the original volume of the rabbit.

  20. A study of different modeling choices for simulating platelets within the immersed boundary method.

    PubMed

    Shankar, Varun; Wright, Grady B; Fogelson, Aaron L; Kirby, Robert M

    2013-01-01

    The Immersed Boundary (IB) method is a widely-used numerical methodology for the simulation of fluid-structure interaction problems. The IB method utilizes an Eulerian discretization for the fluid equations of motion while maintaining a Lagrangian representation of structural objects. Operators are defined for transmitting information (forces and velocities) between these two representations. Most IB simulations represent their structures with piecewise linear approximations and utilize Hookean spring models to approximate structural forces. Our specific motivation is the modeling of platelets in hemodynamic flows. In this paper, we study two alternative representations - radial basis functions (RBFs) and Fourier-based (trigonometric polynomials and spherical harmonics) representations - for the modeling of platelets in two and three dimensions within the IB framework, and compare our results with the traditional piecewise linear approximation methodology. For different representative shapes, we examine the geometric modeling errors (position and normal vectors), force computation errors, and computational cost and provide an engineering trade-off strategy for when and why one might select to employ these different representations.

  1. A study of different modeling choices for simulating platelets within the immersed boundary method

    PubMed Central

    Shankar, Varun; Wright, Grady B.; Fogelson, Aaron L.; Kirby, Robert M.

    2012-01-01

    The Immersed Boundary (IB) method is a widely-used numerical methodology for the simulation of fluid–structure interaction problems. The IB method utilizes an Eulerian discretization for the fluid equations of motion while maintaining a Lagrangian representation of structural objects. Operators are defined for transmitting information (forces and velocities) between these two representations. Most IB simulations represent their structures with piecewise linear approximations and utilize Hookean spring models to approximate structural forces. Our specific motivation is the modeling of platelets in hemodynamic flows. In this paper, we study two alternative representations – radial basis functions (RBFs) and Fourier-based (trigonometric polynomials and spherical harmonics) representations – for the modeling of platelets in two and three dimensions within the IB framework, and compare our results with the traditional piecewise linear approximation methodology. For different representative shapes, we examine the geometric modeling errors (position and normal vectors), force computation errors, and computational cost and provide an engineering trade-off strategy for when and why one might select to employ these different representations. PMID:23585704

  2. Impact of prostaglandin glaucoma drops on platelet-activating factor action: an in vitro study

    PubMed Central

    Moschos, Marilita M; Nitoda, Eirini; Chatziralli, Irini P; Panos, Georgios D; Demopoulos, Constantinos A

    2016-01-01

    Aim The aim of this study was to investigate the effect of different prostaglandin analogs on platelet-activating factor (PAF) levels. Methods Three prostaglandin analogs were selected: bimatoprost 0.3 mg/mL, latanoprost 50 μg/mL, and tafluprost 15 μg/mL. Each drug sample was tested for its ability to cause platelet aggregation, which was measured as PAF-induced aggregation, before and after the addition of various concentrations of the examined sample, creating a linear curve of percentage inhibition (ranging from 0% to 100%) versus different concentrations of the sample. The concentration of the sample that inhibited 50% PAF-induced aggregation was calculated based on this curve, and this value was defined as IC50. In addition, the effect of eye drops on PAF metabolism was examined, through an in vitro analysis on PAF basic metabolic enzymes (PAF-cholinephosphotransferase, PAF-acetyl-CoA:1-O-alkyl-sn-glycero-3-phosphocholine acetyltransferase, and PAF-acetylhydrolase). Results The IC50 values for Lumigan UD® (bimatoprost 0.3 mg/mL), Monoprost® (latanoprost 50 μg/mL), and Saflutan (tafluprost 15 μg/mL) were 8.7, 0.28, and 1.4 μg/mL, respectively. Discussion All three prostaglandin analogs suspended PAF, but bimatoprost induced the most potent inhibition, compared to tafluprost and to the weak effect of latanoprost. PMID:27994439

  3. Shiga toxin binds to activated platelets.

    PubMed

    Ghosh, S A; Polanowska-Grabowska, R K; Fujii, J; Obrig, T; Gear, A R L

    2004-03-01

    Hemolytic uremic syndrome (HUS) is associated with acute renal failure in children and can be caused by Shiga toxin (Stx)-producing Escherichia coli. Thrombocytopenia and formation of renal thrombi are characteristic of HUS, suggesting that platelet activation is involved in its pathogenesis. However, whether Shiga toxin directly activates platelets is controversial. The present study evaluates if potential platelet sensitization during isolation by different procedures influences platelet interaction with Shiga toxin. Platelets isolated from sodium citrate anticoagulated blood were exposed during washing to EDTA and higher g forces than platelets prepared from acid-citrate-dextrose (ACD) plasma. Platelet binding of Stx was significantly higher in EDTA-washed preparations relative to ACD-derived platelets. Binding of Stx was also increased with ACD-derived platelets when activated with thrombin (1 U mL-1) and exposure of the Gb3 Stx receptor was detected only on platelets subjected to EDTA, higher g forces or thrombin. EDTA-exposed platelets lost their normal discoid shape and were larger. P-selectin (CD62P) exposure was significantly increased in EDTA-washed preparations relative to ACD-derived platelets, suggesting platelet activation. Taken together, these results suggest that direct binding of Stx occurs only on 'activated' platelets rather than on resting platelets. The ability of Stx to interact with previously activated platelets may be an important element in understanding the pathogenesis of HUS.

  4. Mechanisms of hemolysis-associated platelet activation

    PubMed Central

    Helms, C. C.; Marvel, M.; Zhao, W.; Stahle, M.; Vest, R.; Kato, G. J.; Lee, J. S.; Christ, G.; Gladwin, M. T.; Hantgan, R. R.; Kim-Shapiro, D. B.

    2013-01-01

    Summary Background Intravascular hemolysis occurs after blood transfusion, in hemolytic anemias and other conditions, and is associated with hypercoagulable states. Hemolysis has been shown to potently activate platelets in vitro and in vivo and several mechanisms have been suggested to account for this including (1) direct activation by hemoglobin, (2) increase in reactive oxygen species (ROS), (3) scavenging of nitric oxide by released hemoglobin, and (4) release of intraerythrocytic ADP. Objective The aim of the current study is to elucidate the mechanism of hemolysis-mediated platelet activation. Methods We used flow cytometry to detect PAC-1 binding to activated platelets for in vitro experiments and a Siemens’ Advia 120 hematology system to assess platelet aggregation using platelet counts from in vivo experiments in a rodent model. Results We show that Hb does not directly activate platelets. However, ADP bound to Hb can cause platelet activation. Furthermore, platelet activation due to shearing of RBCs is reduced in the presence of apyrase which metabolizes ADP to AMP. Use of ROS scavengers did not affect platelet activation. We also show that cell free Hb does enhance platelet activation by abrogating the inhibitory effect of NO on platelet activation. In vivo infusions of ADP and purified (ADP-free) Hb as well as hemolysate result in platelet aggregation as evidenced by decreased platelet counts. Conclusion Two primary mechanisms account for red blood cell hemolysis-associated platelet activation: ADP release which activates platelets and cell-free hemoglobin release which enhances platelet activation by lowering NO bioavailability. PMID:24119131

  5. Nonalcoholic steatohepatitis as a novel player in metabolic syndrome-induced erectile dysfunction: an experimental study in the rabbit.

    PubMed

    Vignozzi, Linda; Filippi, Sandra; Comeglio, Paolo; Cellai, Ilaria; Sarchielli, Erica; Morelli, Annamaria; Rastrelli, Giulia; Maneschi, Elena; Galli, Andrea; Vannelli, Gabriella Barbara; Saad, Farid; Mannucci, Edoardo; Adorini, Luciano; Maggi, Mario

    2014-03-25

    A pathogenic link between erectile dysfunction (ED) and metabolic syndrome (MetS) is now well established. Nonalcoholic steatohepatitis (NASH), the hepatic hallmark of MetS, is regarded as an active player in the pathogenesis of MetS-associated cardiovascular disease (CVD). This study was aimed at evaluating the relationship between MetS-induced NASH and penile dysfunction. We used a non-genomic, high fat diet (HFD)-induced, rabbit model of MetS, and treated HFD rabbits with testosterone (T), with the selective farnesoid X receptor (FXR) agonist obeticholic acid (OCA), or with the anti-TNFα mAb infliximab. Rabbits fed a regular diet were used as controls. Liver histomorphological and gene expression analysis demonstrated NASH in HFD rabbits. Several genes related to inflammation (including TNFα), activation of stellate cells, fibrosis, and lipid metabolism parameters were negatively associated to maximal acetylcholine (Ach)-induced relaxation in penis. When all these putative liver determinants of penile Ach responsiveness were tested as covariates in a multivariate model, only the association between hepatic TNFα expression and Ach response was confirmed. Accordingly, circulating levels of TNFα were increased 15-fold in HFD rabbits. T and OCA dosing in HFD rabbits both reduced TNFα liver expression and plasma levels, with a parallel increase of penile eNOS expression and responsiveness to Ach. Also neutralization of TNFα with infliximab treatment fully normalized HFD-induced hypo-responsiveness to Ach, as well as responsiveness to vardenafil, a phosphodiesterase type 5 inhibitor. Thus, MetS-induced NASH in HFD rabbits plays an active role in the pathogenesis of ED, likely through TNFα, as indicated by treatments reducing liver and circulating TNFα levels (T or OCA), or neutralizing TNFα action (infliximab), which significantly improve penile responsiveness to Ach in HFD rabbits.

  6. MRI and Histopathologic Study of a Novel Cholesterol-Fed Rabbit Model of Xanthogranuloma

    PubMed Central

    Chen, Yuanxin; Hamilton, Amanda M.; Parkins, Katie M.; Wang, Jian-Xiong; Rogers, Kem A.; Zeineh, Michael M.; Rutt, Brian K.; Ronald, John A.

    2016-01-01

    Purpose To develop a rabbit model of xanthogranuloma based on supplementation of dietary cholesterol. The aim of this study was to analyze the xanthogranulomatous lesions using magnetic resonance imaging (MRI) and histological examination. Materials and Methods Rabbits were fed a low-level cholesterol (CH) diet (n = 10) or normal chow (n = 5) for 24 months. In vivo brain imaging was performed on a 3T MR system using fast imaging employing steady state acquisition, susceptibility-weighted imaging, spoiled gradient recalled, T1-weighted inversion recovery imaging and T1 relaxometry, PD-weighted and T2-weighted spin-echo imaging and T2 relaxometry, iterative decomposition of water and fat with echo asymmetry and least-squares estimation, ultrashort TE MRI (UTE-MRI), and T2∗ relaxometry. MR images were evaluated using a Likert scale for lesion presence and quantitative analysis of lesion size, ventricular volume, and T1, T2, and T2∗ values of lesions was performed. After imaging, brain specimens were examined using histological methods. Results In vivo MRI revealed that 6 of 10 CH-fed rabbits developed lesions in the choroid plexus. Region-of-interest analysis showed that for CH-fed rabbits the mean lesion volume was 8.5 ± 2.6mm3 and the volume of the lateral ventricle was significantly increased compared to controls (P < 0.01). The lesions showed significantly shorter mean T2 values (35 ± 12 msec, P < 0.001), longer mean T1 values (1581 ± 146 msec, P < 0.05), and shorter T2∗ values (22 ± 13 msec, P < 0.001) compared to adjacent brain structures. The ultrashort T2∗ components were visible using UTE-MRI. Histopathologic evaluation of lesions demonstrated features of human xanthogranuloma. Conclusion Rabbits fed a low-level CH diet develop sizable intraventricular masses that have similar histopathological features as human xanthogranuloma. Multiparametric MRI techniques were able to provide information about the complex composition of these lesions. PMID

  7. [Experimental study on vascular bundle implantation combined with cellular transplantation in treating rabbit femoral head necrosis].

    PubMed

    Chen, Shuang-Tao; Zhang, Wei-Ping; Liu, Chang-An; Wang, Jun-Jiang; Song, Heng-Yi; Chai, Zhi-wen

    2013-03-01

    To discuss the feasibility of vascular bundle implantation combined with allogeneic bone marrow stromal cells (BMSCs) transplantation in treating rabbit femoral head osteonecrosis and bone defect, in order to explore a new method for the treatment of femoral head necrosis. Thirty-six New Zealand rabbits were randomly divided into three groups,with 12 rabbits in each group. Bilateral femoral heads of the rabbits were studied in the experiment. The models were made by liquid nitrogen frozen, and the femoral heads were drilled to cause bone defect. Group A was the control group,group B was stem cells transplantaion group of allograft marrow stromal,and group C was stem cells transplantation group of allograft marrow stromal combined with vascular bundle implantation. Three rabbits of each group were sacrificed respectively at 2, 4, 8, 12 weeks after operation. All specimens of the femoral heads were sliced for HE staining. Furthermore ,vascular density and the percentage of new bone trabecula of femoral head coronary section in defect area were measured and analyzed statistically. In group C,new bone trabecula and original micrangium formed at the 2nd week after operation; new bone trabecula was lamellar and interlaced with abundant micrangium at the 8th week;at the 12th week,the broadened,coarsened bone trabecula lined up regularly,and the mature bone trabecula and new marrow were visible. At the 2nd week after operation,there was no statistical significance in the percentage of new bone trabecula of femoral head coronary section in defect area between group B and C. While at 4, 8, 12 week after operation, vascular density and the percentage of new bone trabecula of femoral head coronary section in defect area of group C was higher than that of group B. Allogeneic bone marrow stromal cells cultured in vivo can form new bone trabecula, and can be applied to allotransplant. Vascular bundle implanted into the bone defect area of femoral head necrosis could improve blood

  8. Lovastatin induces platelet apoptosis.

    PubMed

    Zhao, Qing; Li, Ming; Chen, Mengxing; Zhou, Ling; Zhao, Lili; Hu, Renping; Yan, Rong; Dai, Kesheng

    2016-03-01

    Statins are widely used in the prevention of atherosclerosis and treatment of coronary artery disease because of pleiotropic effects on thrombosis. Thrombocytopenia and hemorrhage occurred in some statin-treated patients, but the reason remains unclear. In the current study, we show that lovastatin dose-dependently induces depolarization of mitochondrial inner transmembrane potential, leading to up-regulation of Bak, down-regulation of Bcl-XL, and activation of caspase-3/8/9. Lovastatin treatment did not increase the surface expression of P-selectin or PAC-1 binding but led to strongly reduced collagen- and thrombin-induced platelet aggregation. The integrin αIIbβ3 antagonist, RGDS, inhibited lovastatin-induced apoptosis in both human platelets and Chinese hamster ovary (CHO) cells stably expressing integrin αIIbβ3. The number of circulating platelets in mice was significantly reduced after intraperitoneal injections with lovastatin. Taken together, these data indicate that lovastatin induced caspase-dependent platelet apoptosis. Lovastatin does not incur platelet activation, whereas impairs platelet function and reduces circulating platelets in vivo, suggesting the possible pathogenesis of thrombocytopenia and hemorrhage in patients treated with statins. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Myopathy induced by HMG-CoA reductase inhibitors in rabbits: a pathological, electrophysiological, and biochemical study.

    PubMed

    Nakahara, K; Kuriyama, M; Sonoda, Y; Yoshidome, H; Nakagawa, H; Fujiyama, J; Higuchi, I; Osame, M

    1998-09-01

    A combination of electrophysiological, pathological, and biochemical studies were performed in myopathy induced by 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors. Simvastatin (a lipophilic inhibitor) or pravastatin (a hydrophilic inhibitor) were administered by gavage to rabbits. In Group I (simvastatin-treated group, 50 mg/kg/day for 4 weeks), four rabbits showed muscle necrosis and high serum creatine kinase (CK) levels, and all six rabbits showed electrical myotonia. In Group II (pravastatin-treated group, 100 mg/kg/day for 4 weeks), no rabbit showed either condition. In Group III (pravastatin-treated group, 200 mg/kg/day for 3 weeks plus 300 mg/kg/day for 3 weeks), one rabbit showed muscle necrosis and high serum CK level and two rabbits showed electrical myotonia. The pathological findings were muscle fiber necrosis and degeneration with increased acid phosphatase activity by light microscopy, autophagic vacuoles and mitochondrial swelling, and disruption and hypercontraction of myofibrils by electron microscopy. Ubiquinone content decreased in skeletal muscle by 22 to 36% in Group I, by 18 to 52% in Group II, and by 49 to 72% in Group III. However, mitochondrial enzyme activities of respiratory chain were normal in all groups. These results indicate that myopathy was not induced by a secondary dysfunction of mitochondrial respiration due to low ubiquinone levels.

  10. A cellular scale numerical study of the effect of mechanical properties of erythrocytes on the near-wall motion of platelets

    NASA Astrophysics Data System (ADS)

    Xu, Jing; Wang, Xiao-Long; Liu, Yun-Qiao; Gong, Xiao-Bo

    2014-04-01

    The effect of mechanical properties of erythrocytes on the near-wall motion of platelets was numerically studied with the immersed boundary method. Cells were modeled as viscous-fluid-filled capsules surrounded by hyper-elastic membranes with negligible thickness. The numerical results show that with the increase of hematocrit, the near-wall approaching of platelets is enhanced, with which platelets exhibit larger deformation and orientation angle of its near-wall tank-treading motion, and the lateral force pushing platelets to the wall is increased with larger fluctuation amplitude. Meanwhile the near-wall approaching is reduced by increasing the stiffness of erythrocytes. [Figure not available: see fulltext.

  11. Platelets are not critical effector cells for the time course of murine passive crescentic glomerulonephritis.

    PubMed

    Hohenstein, Bernd; Daniel, Christoph; Johnson, Richard J; Amann, Kerstin U; Hugo, Christian P M

    2013-01-01

    Although platelets are well-known effector cells of inflammatory renal disease, clinical studies were not able to establish platelet inhibition as an effective therapy. Our previous studies using Vasodilator stimulated Phosphoprotein- and P2Y1-deficient mice suggested some early, but no long-term effects of platelets in passive crescentic glomerulonephritis. To define the role of platelets for this disease model, passive crescentic glomerulonephritis was induced in 72 C57Bl/6 mice by intraperitoneal injection of sheep anti-rabbit glomerular basement membrane antibody on 2 consecutive days. Platelets were depleted using anti-glycoprotein Ibα antibodies (p0p3/p0p4) every 4th day. Mice treated with equal amounts of sterile Phosphate buffered solution or rat-IgG served as controls. Blood, urine, and tissues were harvested on days 3 and 28. Renal tissue sections were evaluated after immunostaining using (semi)quantitative and computer-assisted image analysis. Compared to controls, efficient depletion was achieved as indicated by a markedly prolonged bleeding time and a more than 90% reduction in platelet counts (800/nl vs. 42/nl; P < 0.001). Functional (creatinine-clearance and proteinuria) parameters demonstrated no significant differences between the groups. Neither parameters of renal injury (glomerulosclerosis and fibrosis) nor glomerular/tubulointerstitial matrix expansion (by collagen IV staining), glomerular capillary rarefaction (lectin staining), and the glomerular/tubulointerstitial proliferative response (proliferating cell nuclear antigen) demonstrated any differences between platelet-depleted mice and PBS- or rat-IgG-treated nephritic mice at any time point. Despite effective platelet inhibition/depletion, neither the short- nor long-term course of passive crescentic nephrotoxic nephritis was affected. These data indicate that platelets play a minor role during the time course of this disease model in the mouse.

  12. Platelet dysfunction associated with Wilms tumor and hyaluronic acid.

    PubMed

    Bracey, A W; Wu, A H; Aceves, J; Chow, T; Carlile, S; Hoots, W K

    1987-03-01

    Acquired von Willebrand disease (AVWD) has been described in two cases of nephroblastoma. We studied a patient with nephroblastoma who presented with a coagulopathy suggestive of AVWD. The subject had undetectable levels of F.VIIIR:Ag, diminished F.VIIIR:WF (16.3%), F.VIII:C activity (37%), and lack of platelet aggregation to ADP, epinephrine, collagen, and arachidonic acid. These results were associated with abnormally high serum levels (850 mg/dl) of hyaluronic acid (HA), which made the patient's serum hyperviscous. Examination of the neoplasm revealed HA in the tumor matrix. All abnormalities of coagulation resolved after chemotherapy and extirpation of the neoplasm, which produced normal serum HA levels. To study the effects of HA on platelet function, we added HA to normal platelet-poor plasma (NPP), which rendered F.VIIIR:Ag undetectable; treatment of HA with hyaluronidase eliminated F.VIIIR:Ag assay interference caused by HA. F.VIII:C activity decreased in vitro when HA was mixed with normal platelet-poor plasma (NPP). HA reduced the initial slope of normal platelet aggregation. Partial correction of platelet aggregation occurred after hyaluronidase treatment of HA-spiked PRP. Experiments in rabbits exposed to HA (serum level 400 mg/dl) demonstrated abnormalities similar to those noted in the patient. Shear rate studies of whole blood containing HA (500 mg/dl) yielded high shear stress, 27-136 dynes/cm2 over shear rates of 10-216 sec-1. We conclude that the coagulopathy demonstrated in this case is secondary to hyperviscosity produced by elevated levels of HA, which interferes with the assay for F.VIIIR:Ag. Thus the acquired coagulopathy associated with other cases of nephroblastoma may present as spurious von Willebrand disease.

  13. A randomized, controlled study on the influence of acetaminophen, diclofenac, or naproxen on aspirin-induced inhibition of platelet aggregation.

    PubMed

    Galliard-Grigioni, Katja S; Reinhart, Walter H

    2009-05-01

    Nonsteroidal anti-inflammatory drugs (NSAID) may interfere with aspirin (acetylsalicylic acid) and increase the risk for cardiovascular events. The clinical relevance is uncertain. The aim of this study was to analyse the influence of a co-administration of aspirin and NSAID on platelet aggregation. In a randomized, placebo controlled trial, eleven healthy volunteers were studied during 4 separate study periods of 4 days each. Individuals were treated on each occasion with 100 mg aspirin daily in combination with either 3 x 1 g acetaminophen, 3 x 50 mg diclofenac, 3 x 250 mg naproxen, or 3 x 1 placebo. Primary hemostasis was assessed with a platelet function analyser (PFA-100), which measures the closure time (CT) of a collagen- and epinephrine-coated pore by aggregating platelets in flowing blood. Naproxen enhanced the anti-aggregatory action of aspirin after 24 h (CT rising from 104+/-16 s at baseline to 212+/-69 s at 24 h, P<0.001), which was not seen with any other drug combination. Diclofenac reduced the anti-aggregatory action of aspirin in the first two days, since the CT did not rise significantly (109+/-19 s, 148+/-56 s, and 168+/-66 s at 0 h, 24 h, 48 h, respectively, P>0.05). Acetaminophen had no effect compared with placebo. After 4 days of treatment platelet aggregation was similarly inhibited by all combinations. We conclude that a co-administration of NSAID and aspirin may interfere with platelet inhibition at the beginning of a treatment with an increase of naproxen and a decrease of diclofenac. This effect is lost after 4 days, suggesting that a regular daily co-administration of NSAID does not have an influence on platelet inhibition by aspirin.

  14. Uranyl nitrate: 91-day exposure and recovery studies in the male New Zealand white rabbit.

    PubMed

    Gilman, A P; Moss, M A; Villeneuve, D C; Secours, V E; Yagminas, A P; Tracy, B L; Quinn, J M; Long, G; Valli, V E

    1998-01-01

    This study was undertaken to examine the reversibility of renal injury in the male New Zealand White rabbit subsequent to a 91-day exposure to uranyl nitrate (UN) in drinking water, followed by various recovery periods. Specific pathogen-free (SPF) animals were exposed for 91 days to UN in their drinking water (24 or 600 mg UN/L). Control groups were given municipal tap water (< 0.001 mg U/L). Regular clinical observations were recorded, and urine was collected periodically. Recovery periods between the last UN exposure and termination were 0, 8, 14, 45, or 91 days. Following the study, all animals were anesthetized and terminated by exsanguination, and multiple hematological and biochemical parameters were determined. Necropsies were conducted, and histopathological examination was performed. Exposure-related histopathological changes were observed only at much higher doses than in our previous male rabbit study where non-SPF-free animals had been used. Minor increases in kidney to body weight ratios were observed in the high-dose groups following exposure and early recovery. Renal tubular injury with degenerative nuclear changes, cytoplasmic vacuolation, and tubular dilation was seen in the high-dose group, without consistent resolution even after 91 days recovery. Animals ingested approximately 33% more uranium per day in this study than did males in a comparable dose group in the previous study, yet their kidney tissue uranium residues were 30% lower. These results suggest that SPF rabbits are less sensitive to uranyl injury than the non-SPF animals. The lowest-observed-adverse-effect level is estimated to lie at or below 24 mg UN/L.

  15. An association between anti-platelet drug use and reduced cancer prevalence in diabetic patients: results from the Vermont Diabetes Information System Study.

    PubMed

    Holmes, Chris E; Ramos-Nino, Maria E; Littenberg, Benjamin

    2010-06-15

    Diabetes is associated with an increased risk of several malignancies. Both diabetic patients and patients with cancer have an increase in platelet reactivity and platelet activation has recently emerged as a potential mediator of cancer progression. Drug therapies, such as aspirin, that reduce platelet reactivity reduce both cardiovascular and cancer risk. We performed a cross-sectional analysis to assess the association between history of cancer and current anti-platelet drug use in a primary care population of adults with diabetes enrolled in the Vermont Diabetes Information System. Self-reported characteristics, medical history, and a complete medication list were recorded on 1007 diabetic adults. Fifty percent of diabetic patients used an anti-platelet drug. In unadjusted analysis, no association was seen between anti-platelet drug use and cancer history (OR = 0.93; P = .70). Platelet inhibitor use was associated with a decreased patient-reported history of malignancy in a multivariate logistic regression adjusted for age, sex, body mass index, comorbidity, and number of medications (OR = 0.66; CI 0.44-0.99; P = .045). Similar odds of association were seen in both males and females, and for aspirin and non-aspirin platelet inhibitor therapy. Our data suggest an association between anti-platelet drug use and reduced cancer prevalence in patients with diabetes. Given the potentially large implications of our observations in the diabetic population, further studies are required to determine if this association is causal.

  16. An association between anti-platelet drug use and reduced cancer prevalence in diabetic patients: results from the Vermont Diabetes Information System Study

    PubMed Central

    2010-01-01

    Background Diabetes is associated with an increased risk of several malignancies. Both diabetic patients and patients with cancer have an increase in platelet reactivity and platelet activation has recently emerged as a potential mediator of cancer progression. Drug therapies, such as aspirin, that reduce platelet reactivity reduce both cardiovascular and cancer risk. Methods We performed a cross-sectional analysis to assess the association between history of cancer and current anti-platelet drug use in a primary care population of adults with diabetes enrolled in the Vermont Diabetes Information System. Results Self-reported characteristics, medical history, and a complete medication list were recorded on 1007 diabetic adults. Fifty percent of diabetic patients used an anti-platelet drug. In unadjusted analysis, no association was seen between anti-platelet drug use and cancer history (OR = 0.93; P = .70). Platelet inhibitor use was associated with a decreased patient-reported history of malignancy in a multivariate logistic regression adjusted for age, sex, body mass index, comorbidity, and number of medications (OR = 0.66; CI 0.44-0.99; P = .045). Similar odds of association were seen in both males and females, and for aspirin and non-aspirin platelet inhibitor therapy. Conclusions Our data suggest an association between anti-platelet drug use and reduced cancer prevalence in patients with diabetes. Given the potentially large implications of our observations in the diabetic population, further studies are required to determine if this association is causal. PMID:20546622

  17. Detection of platelet alloimmunity with a platelet-associated IgG assay

    SciTech Connect

    Myers, T.J.; Kim, B.K.; Steiner, M.; Bishop, J.; Baldini, M.G.

    1981-06-01

    A quantitative immunofluorescence PA-IgG assay was used to detect alloimmunity to platelets. The assay identified serum alloantibodies in 10 out of 14 multitransfused patients and for two of three infants with neonatal thrombocytopenia. The correct separation of all multitransfused patients into alloimmune and nonalloimmune groups by the PA-IgG assay was substantiated with chromium-51-labeled platelet survival studies. The allogeneic nature of the serum antibodies was demonstrated by progressive absorption of the antibody with increasing numbers of allogeneic platelets but not with autologous platelets. The sensitivity of the PA-IgG assay for detection of serum alloantibodies was superior to that of platelet aggregation, platelet serotonin release, and lymphocytotoxicity testing. In dilution experiments with alloimmune serum, elevated levels of serum PA-IgG could still be detected on donor platelets when platelet aggregation and serotonin release tests became negative. Platelet survival studies with selected platelets performed in the 10 alloimmunized, multitransfused patients confirmed the results of the PA-IgG assays, predicting alloimmunity to the donor platelets. In contrast, platelet aggregation, platelet serotonin release, and lymphocytotoxicity testing indicated alloimmunity for 50% or less of the patients. Reduced platelet survival times were also seen with HLA A- and HLA B-matched donor platelets when donor-recipient incompatibility was demonstrated by the PA-IgG assay. Thus the PA-IgG assay provides a sensitive method to detect serum platelet alloantibodies and may offer a technique in platelet crossmatching.

  18. Antioxidant potential of evening primrose oil administration in hyperlipemic rabbits.

    PubMed

    De La Cruz, J P; Quintero, L; Galvez, J; Villalobos, M A; Sánchez de la Cuesta, F

    1999-01-01

    The dietary intake of saturated fatty acids affects arteriosclerosis. We studied the effect of supplementation (15% wt/wt) of a hyperlipemic diet (1.33% cholesterol) with evening primrose oil (EPO) (Oenothera biennis) for 6 weeks in four groups of 10 rabbits each. At the end of this period we determined lipid peroxidation, glutathione content, and glutathione peroxidase, reductase and transferase activities in liver, brain, heart, aorta and platelets. The atherogenic diet increased tissue lipid peroxidation and decreased the protective antioxidant effect of glutathione. Dietary supplementation with EPO reduced tissue lipid peroxidation (61% in liver, 57% in brain, 42% in heart, 24% in aorta, 33% in platelets). Total glutathione was increased, especially in the aorta (90%) and platelets (200%); however, in all tissues the percentage of oxidised glutathione decreased. Evening primrose oil reduced glutathione peroxidase activity and increased the activities of glutathione reductase and transferase. We conclude that in rabbits made hyperlipemic with a diet rich in saturated fatty acids, EPO decreased tissue oxidative stress.

  19. The effects of changes in diet on lipid levels and platelet thrombus formation in living blood vessels.

    PubMed Central

    Honour, A. J.; Carter, R. D.; Mann, J. I.

    1978-01-01

    The work reported here describes an in vivo study over several days in each animal, of the formation and behaviour of platelet thrombi in injured living blood vessels in response to topically applied adenosine diphosphate (ADP) in rabbits fed initially on normal diets, then on experimental "saturated" or "polyunsaturated" diets. The effects of these diets on triglyceride fatty acids and on cholesterol and triglyceride levels are reported. It may be of significance that in each experiment the "polyunsaturated" and "saturated" diets appeared to be associated with an increased sensitivity to ADP greater than observed in rabbits on a normal diet or in normal animals in other studies. PMID:708587

  20. A novel antithrombotic effect of sulforaphane via activation of platelet adenylate cyclase: ex vivo and in vivo studies.

    PubMed

    Jayakumar, Thanasekaran; Chen, Wei-Fan; Lu, Wan-Jung; Chou, Duen-Suey; Hsiao, George; Hsu, Chung-Yi; Sheu, Joen-Rong; Hsieh, Cheng-Ying

    2013-06-01

    Sulforaphane is a naturally occurring isothiocyanate, which can be found in cruciferous vegetables such as broccoli and cabbage. Sulforaphane was found to have very potent inhibitory effects on tumor growth through regulation of diverse mechanisms. However, no data are available concerning the effects of sulforaphane on platelet activation and its relative issues. Activation of platelets caused by arterial thrombosis is relevant to a variety of cardiovascular diseases. Hence, the aim of this study was to examine the in vivo antithrombotic effects of sulforaphane and its possible mechanisms in platelet activation. Sulforaphane (0.125 and 0.25 mg/kg) was effective in reducing the mortality of ADP-induced acute pulmonary thromboembolism in mice. Other in vivo studies also revealed that sulforaphane (0.25 mg/kg) significantly prolonged platelet plug formation in mice. In addition, sulforaphane (15-75 μM) exhibited more-potent activity of inhibiting platelet aggregation stimulated by collagen. Sulforaphane inhibited platelet activation accompanied by inhibiting relative Ca(2+) mobilization; phosphorylation of phospholipase C (PLC)γ2, protein kinase C (PKC), mitogen-activated protein kinases (MAPKs) and Akt; and hydroxyl radical (OH(●)) formation. Sulforaphane markedly increased cyclic (c)AMP, but not cyclic (c)GMP levels, and stimulated vasodilator-stimulated phosphoprotein (VASP) phosphorylation. SQ22536, an inhibitor of adenylate cyclase, but not ODQ (1H-[1,2,4]Oxadiazolo[4,3-a]quinoxal in-1-one), an inhibitor of guanylate cyclase, obviously reversed the sulforaphane-mediated effects on platelet aggregation; PKC activation, p38 MAPK, Akt and VASP phosphorylation; and OH(●) formation. Furthermore, a PI3-kinase inhibitor (LY294002) and a p38 MAPK inhibitor (SB203580) both significantly diminished PKC activation and p38 MAPK and Akt phosphorylation; in contrast, a PKC inhibitor (RO318220) did not diminish p38 MAPK or Akt phosphorylation stimulated by collagen. This

  1. PLATELET FORMATION

    PubMed Central

    Thon, Jonathan N.; Italiano, Joseph E.

    2010-01-01

    Thrombocytopenia is the underlying cause of a number of major clinical conditions and genetic disorders worldwide. While therapeutic agents that bind and stimulate the thrombopoietin receptor are currently available, the development of drugs that directly stimulate megakaryocytes to generate platelets has lagged behind. To improve the management of thrombocytopenia, we will need to define the cell biological pathways that drive the production of platelets from megakaryocytes. This review integrates the latest research of platelet biogenesis and focuses on the molecular pathways that power and regulate proplatelet production. PMID:20620432

  2. An in vitro method for assessing biomaterial-associated platelet activation.

    PubMed

    LaFayette, Nathan G; Skrzypchak, Amy M; Merz, Scott; Bartlett, Robert H; Annich, Gail M

    2007-01-01

    The development of a nonthrombogenic artificial surface for use with indwelling sensors or catheters remains an elusive goal despite decades of ongoing research. In vivo studies are both labor intensive and costly, and are therefore an inefficient way to rapidly screen possible surface materials. The following in vitro model used glass, polyvinyl chloride (PVC), and polypropylene test tubes incubated with 111In-labeled rabbit platelets and illustrated that, despite equivalent platelet count and function, platelet adhesion was greatest on glass (n = 13), with PVC (n = 17) at 67 +/- 8% and polypropylene (n = 13) at 43 +/- 5% when compared with glass. Extrapolating this method by coating test tubes with new, nonthrombogenic materials is a quick and reliable way to screen material before embarking upon more lengthy in vivo animal studies.

  3. Studies on the biological effects of ozone: 10. Release of factors from ozonated human platelets.

    PubMed Central

    Valacchi, G; Bocci, V

    1999-01-01

    In a previous work we have shown that heparin, in the presence of ozone (O3), promotes a dose-dependent platelet aggregation, while after Ca2+ chelation with citrate, platelet aggregation is almost negligible. These results led us to think that aggregation may enhance the release of platelet components. We have here shown that indeed significantly higher amount of platelet-derived growth factor (PDGF), transforming growth factor beta1 (TGF-beta1) and interleukin-8 (IL-8) are released in a dose-dependent manner after ozonation of heparinised platelet-rich plasma samples. These findings may explain the enhanced healing of torpid ulcers in patients with chronic limb ischemia treated with O3 autohaemoteraphy (O3-AHT). PMID:10704074

  4. Studies on the biological effects of ozone: 10. Release of factors from ozonated human platelets.

    PubMed

    Valacchi, G; Bocci, V

    1999-01-01

    In a previous work we have shown that heparin, in the presence of ozone (O3), promotes a dose-dependent platelet aggregation, while after Ca2+ chelation with citrate, platelet aggregation is almost negligible. These results led us to think that aggregation may enhance the release of platelet components. We have here shown that indeed significantly higher amount of platelet-derived growth factor (PDGF), transforming growth factor beta1 (TGF-beta1) and interleukin-8 (IL-8) are released in a dose-dependent manner after ozonation of heparinised platelet-rich plasma samples. These findings may explain the enhanced healing of torpid ulcers in patients with chronic limb ischemia treated with O3 autohaemoteraphy (O3-AHT).

  5. A conscious-rabbit model to study vardenafil hydrochloride and other agents that influence penile erection.

    PubMed

    Bischoff, E; Schneider, K

    2001-08-01

    Experimental models to study the effect of agents on penile erection usually include electrical stimulation of peripheral nerves in anesthetized animals combined with systemic or intracavernous injection of drugs. The objective of this study was to demonstrate that conscious rabbits can be used as a simple and quantitative model for the assessment of compounds that show potential for the treatment of erectile dysfunction. Erection was assessed by measuring the length of uncovered penile mucosa before and after the intravenous (i.v.) administration of agents. Animals did not require anesthesia during the course of the study. The phosphodiesterase 5 (PDE5) inhibitors vardenafil x HCl (hereafter called vardenafil) and sildenafil were given intravenously, and measurements were taken for 0-5 h. The effects of phentolamine and milrinone were also evaluated. Vardenafil (0.1-3 mg/kg) induced dose-dependent penile erections in conscious rabbits following i.v. administration. The efficacy of vardenafil was potentiated, and the minimal effective dose was reduced significantly to 0.01 mg/kg by simultaneous administration of the nitric oxide (NO) donor sodium nitroprusside (SNP). Administration of the NO-synthase inhibitor L-NAME abolished the effect. Sildenafil was effective in this model after i.v. administration. The alpha-adrenergic receptor antagonist phentolamine (0.1, 0.3 and 1 mg/kg i.v.) induced erections with a slower t(max) compared with vardenafil and sildenafil. Intravenous administration of the PDE3 inhibitor milrinone (1 mg/kg i.v.) was less effective than the PDE5 inhibitor vardenafil. The conscious rabbit is a suitable and reliable model for the evaluation of compounds with potential for the treatment of erectile dysfunction. This was demonstrated using compounds that target different signaling pathways that induce smooth muscle relaxation in the penis.

  6. [Treatment of corneal ulcers with platelet rich plasma].

    PubMed

    Acosta, L; Castro, M; Fernandez, M; Oliveres, E; Gomez-Demmel, E; Tartara, L

    2014-02-01

    To assess the efficacy of platelet rich plasma (PRP) in the treatment of extensive corneal ulcers in albino rabbits. New Zealand rabbits, divided in 3 groups, were used for the study. Corneal ulcers of 10mm diameter were made. Rabbits blood was extracted for the preparation of the PRP of the corresponding group. The blood was processed by differential centrifugation. The first group, named control, was treated with sterile saline every 8h. The second group, named gel, was treated with deproteinized extract gel beef fat every 8h, and the third group, named PRP received one PRP drop on the first and third day of monitoring. The rabbits were monitored, by taking photographs, each day for the 7 days that the study lasted. A better outcome was observed in the group with deproteinized extract gel beef fat (GE group), and the PRP group (PL group), in comparison with the control group (CO group) (P<.05). The PRP showed to be just as effective as the commercial product (Solcoseryl®), for the regeneration of the extensive and deep corneal ulcers. Besides, it stands out as a no surgical procedure is required, and there is easy access, low cost and reduced doses. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  7. The clinical efficacy of using autologous platelet rich plasma in hip arthroplasty: A retrospective comparative study

    PubMed Central

    Safdar, Atif; Shaaban, Hamid; Tibayan, Restituto; Miller, Richard; Boairdo, Richard; Guron, Gunwant

    2015-01-01

    Background: Platelet rich plasma (PRP) is a blood derivative concentrate of platelets, fibrin and growth factors obtained through withdrawal and centrifugation of autologous blood and use for its inherent hemostatic and adhesive properties to promote wound healing. Hip arthroplasty is often associated with significant perioperative complications including blood loss necessitating blood transfusions, which can lead to multiple adverse reactions, infection transmission, and longer hospital stay. Materials and Methods: We conducted this retrospective comparative study to determine whether the use of PRP can reduce the bleeding complications in hip replacement surgeries and therefore decrease analgesic requirements and shorten the hospital stay. Results: Sixty patients had consecutive hip replacement surgeries. The study group (n=23) received PRP applications while the control group (n=37) were operated without PRP applications. Postoperative drop of hemoglobin, number of red blood cell (RBC) transfusions, analgesic requirements, and duration of hospital stay were recorded. There was no significant difference in the drop of hemoglobin preoperatively and postoperatively comparing study and control groups (P=0.75). There was no difference in transfusion requirements between the two groups (P=0.16) but there was trend toward less transfusion in the PRP-treated group. There were also no statistical differences in analgesic use (P=0.83) and lengths of hospitalization (P=0.68) between the two groups. Conclusion: We concluded that there is no clinical efficacy in using PRP in hip replacement surgeries. We recommend a larger prospective study be conducted to determine its clinical utility as an optimization strategy to improve outcome after hip arthroplasty PMID:25810634

  8. An artificial nanoemulsion carrying paclitaxel decreases the transplant heart vascular disease: a study in a rabbit graft model.

    PubMed

    Lourenço-Filho, Domingos D; Maranhão, Raul C; Méndez-Contreras, Carlos A; Tavares, Elaine R; Freitas, Fatima R; Stolf, Noedir A

    2011-06-01

    In previous studies cholesterol-rich nanoemulsions (LDE) resembling low-density lipoprotein were shown to concentrate in atherosclerotic lesions of rabbits. Lesions were pronouncedly reduced by treatment with paclitaxel associated with LDE. This study aimed to test the hypothesis of whether LDE-paclitaxel is able to concentrate in grafted hearts of rabbits and to ameliorate coronary allograft vasculopathy after the transplantation procedure. Twenty-one New Zealand rabbits fed 0.5% cholesterol were submitted to heterotopic heart transplantation at the cervical position. All rabbits undergoing transplantation were treated with cyclosporin A (10 mg · kg(-1) · d(-1) by mouth). Eleven rabbits were treated with LDE-paclitaxel (4 mg/kg body weight paclitaxel per week administered intravenously for 6 weeks), and 10 control rabbits were treated with 3 mL/wk intravenous saline. Four control animals were injected with LDE labeled with [(14)C]-cholesteryl oleate ether to determine tissue uptake. Radioactive LDE uptake by grafts was 4-fold that of native hearts. In both groups the coronary arteries of native hearts showed no stenosis, but treatment with LDE-paclitaxel reduced the degree of stenosis in grafted hearts by 50%. The arterial luminal area in grafts of the treated group was 3-fold larger than in control animals. LDE-paclitaxel treatment resulted in a 7-fold reduction of macrophage infiltration. In grafted hearts LDE-paclitaxel treatment reduced the width of the intimal layer and inhibited the destruction of the medial layer. No toxicity was observed in rabbits receiving LDE-paclitaxel treatment. LDE-paclitaxel improved posttransplantation injury to the grafted heart. The novel therapeutic approach for heart transplantation management validated here is thus a promising strategy to be explored in future clinical studies. Copyright © 2011. Published by Mosby, Inc.

  9. Impact of reticulated platelets on antiplatelet response to thienopyridines is independent of platelet turnover.

    PubMed

    Stratz, Christian; Nührenberg, Thomas; Amann, Michael; Cederqvist, Marco; Kleiner, Pascal; Valina, Christian M; Trenk, Dietmar; Neumann, Franz-Josef; Hochholzer, Willibald

    2016-10-28

    Reticulated platelets are associated with impaired antiplatelet response to thienopyridines. It is uncertain whether this interaction is caused by a decreased drug exposure due to high platelet turnover reflected by elevated levels of reticulated platelets or by intrinsic properties of reticulated platelets. This study sought to investigate if the impact of reticulated platelets on early antiplatelet response to thienopyridines is mainly caused by platelet turnover as previously suggested. Elective patients undergoing coronary intervention were randomised to loading with clopidogrel 600 mg or prasugrel 60 mg (n=200). Adenosine diphosphate (ADP)-induced platelet reactivity was determined by impedance aggregometry before, at 30, 60, 90, and 120 minutes and at day 1 after loading. Immature platelet count was assessed as marker of reticulated platelets by flow cytometry. Platelet reactivity increased with rising levels of immature platelet count in both groups. This effect was more distinctive in patients on clopidogrel as compared to patients on prasugrel. Overall, immature platelet count correlated well with on-treatment platelet reactivity at all time-points (p < 0.001). These correlations did not change over time in the entire cohort as well as in patients treated with clopidogrel or prasugrel indicating an effect independent of platelet turnover (comparison of correlations 120 minutes/day 1: p = 0.64). In conclusion, the association of immature platelet count with impaired antiplatelet response to thienopyridines is similar early and late after loading. This finding suggests as main underlying mechanism another effect of reticulated platelets on thienopyridines than platelet turnover.

  10. Platelet proteome reveals novel pathways of platelet activation and platelet-mediated immunoregulation in dengue

    PubMed Central

    Teixeira-Ferreira, André; Carvalho, Paulo Costa; Salazar, Gustavo Adolfo; Zimmerman, Guy A.; Perales, Jonas

    2017-01-01

    Dengue is the most prevalent human arbovirus disease worldwide. Dengue virus (DENV) infection causes syndromes varying from self-limiting febrile illness to severe dengue. Although dengue pathophysiology is not completely understood, it is widely accepted that increased inflammation plays important roles in dengue pathogenesis. Platelets are blood cells classically known as effectors of hemostasis which have been increasingly recognized to have major immune and inflammatory activities. Nevertheless, the phenotype and effector functions of platelets in dengue pathogenesis are not completely understood. Here we used quantitative proteomics to investigate the protein content of platelets in clinical samples from patients with dengue compared to platelets from healthy donors. Our assays revealed a set of 252 differentially abundant proteins. In silico analyses associated these proteins with key molecular events including platelet activation and inflammatory responses, and with events not previously attributed to platelets during dengue infection including antigen processing and presentation, proteasome activity, and expression of histones. From these results, we conducted functional assays using samples from a larger cohort of patients and demonstrated evidence for platelet activation indicated by P-selectin (CD62P) translocation and secretion of granule-stored chemokines by platelets. In addition, we found evidence that DENV infection triggers HLA class I synthesis and surface expression by a mechanism depending on functional proteasome activity. Furthermore, we demonstrate that cell-free histone H2A released during dengue infection binds to platelets, increasing platelet activation. These findings are consistent with functional importance of HLA class I, proteasome subunits, and histones that we found exclusively in proteome analysis of platelets in samples from dengue patients. Our study provides the first in-depth characterization of the platelet proteome in dengue

  11. Platelet proteome reveals novel pathways of platelet activation and platelet-mediated immunoregulation in dengue.

    PubMed

    Trugilho, Monique Ramos de Oliveira; Hottz, Eugenio Damaceno; Brunoro, Giselle Villa Flor; Teixeira-Ferreira, André; Carvalho, Paulo Costa; Salazar, Gustavo Adolfo; Zimmerman, Guy A; Bozza, Fernando A; Bozza, Patrícia T; Perales, Jonas

    2017-05-01

    Dengue is the most prevalent human arbovirus disease worldwide. Dengue virus (DENV) infection causes syndromes varying from self-limiting febrile illness to severe dengue. Although dengue pathophysiology is not completely understood, it is widely accepted that increased inflammation plays important roles in dengue pathogenesis. Platelets are blood cells classically known as effectors of hemostasis which have been increasingly recognized to have major immune and inflammatory activities. Nevertheless, the phenotype and effector functions of platelets in dengue pathogenesis are not completely understood. Here we used quantitative proteomics to investigate the protein content of platelets in clinical samples from patients with dengue compared to platelets from healthy donors. Our assays revealed a set of 252 differentially abundant proteins. In silico analyses associated these proteins with key molecular events including platelet activation and inflammatory responses, and with events not previously attributed to platelets during dengue infection including antigen processing and presentation, proteasome activity, and expression of histones. From these results, we conducted functional assays using samples from a larger cohort of patients and demonstrated evidence for platelet activation indicated by P-selectin (CD62P) translocation and secretion of granule-stored chemokines by platelets. In addition, we found evidence that DENV infection triggers HLA class I synthesis and surface expression by a mechanism depending on functional proteasome activity. Furthermore, we demonstrate that cell-free histone H2A released during dengue infection binds to platelets, increasing platelet activation. These findings are consistent with functional importance of HLA class I, proteasome subunits, and histones that we found exclusively in proteome analysis of platelets in samples from dengue patients. Our study provides the first in-depth characterization of the platelet proteome in dengue

  12. Distribution of bone remodeling units in the otic capsule of the rabbit. A semiquantitative morphometric study.

    PubMed

    Sørensen, M S; Jørgensen, M B; Bretlau, P

    1992-01-01

    Distribution of bone remodeling units (BRU) in relation to the perilymphatic space was studied in undecalcified temporal bones from adult rabbits labeled in vivo with bone-seeking fluorochromes. Based on recordings of focal bone formation, relative densities of BRUs inside concentric tissue zones around the inner ear spaces were estimated. Zonal densities of BRUs were found to decline towards the perilymphatic space, lending further support to the existence of a local inner ear mechanism in control of capsular bone tissue dynamics. The possible nature of this mechanism is considered briefly with special reference to inner ear electromechanic activity.

  13. Aortic endothelium of alloxan diabetic rabbits: a quantitative study using scanning electron microscopy.

    PubMed

    Dolgov, V V; Zaikina, O E; Bondarenko, M F; Repin, V S

    1982-05-01

    Scanning electron microscope studies of the aorta and other major arteries have been performed in alloxan-induced diabetic rabbits. After 5 weeks, a variety of structural abnormalities of the endothelial lining were detected including a significant increase in the number of argyrophilic cells and an increased number of craters or openings in the endothelial junctional region. Evidence of more extensive micro-damage was present after 5 months duration of diabetes. These zones with structural changes in the endothelial lining of major vessels seem to be areas of high predilection to atherosclerosis in diabetes.

  14. Safety Studies for Use of Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells in a Rabbit Model for Osteoarthritis to Support a Phase I Clinical Trial.

    PubMed

    Riester, Scott M; Denbeigh, Janet M; Lin, Yang; Jones, Dakota L; de Mooij, Tristan; Lewallen, Eric A; Nie, Hai; Paradise, Christopher R; Radel, Darcie J; Dudakovic, Amel; Camilleri, Emily T; Larson, Dirk R; Qu, Wenchun; Krych, Aaron J; Frick, Matthew A; Im, Hee-Jeong; Dietz, Allan B; Smith, Jay; van Wijnen, Andre J

    2017-03-01

    Adipose-derived mesenchymal stem cells (AMSCs) offer potential as a therapeutic option for clinical applications in musculoskeletal regenerative medicine because of their immunomodulatory functions and capacity for trilineage differentiation. In preparation for a phase I clinical trial using AMSCs to treat patients with osteoarthritis, we carried out preclinical studies to assess the safety of human AMSCs within the intra-articular joint space. Culture-expanded human AMSCs grown in human platelet-lysate were delivered via intra-articular injections into normal healthy rabbit knees and knees at risk for the development of osteoarthritis after bilateral medial anterior hemimeniscectomy. Treatment outcomes and safety were evaluated by assessing the general health, function, and behavior of the animals. Joint tissues were analyzed by x-ray, magnetic resonance imaging, and histopathology. Intra-articular AMSC therapy was well tolerated in this study. We did not observe adverse systemic reactions, nor did we find evidence of damage to intra-articular joint tissues. Thus, the data generated in this study show a favorable safety profile for AMSCs within the joint space in support of a phase I clinical trial evaluating the clinical utility of AMSCs to treat osteoarthritis. Stem Cells Translational Medicine 2017;6:910-922.

  15. Fecal Nitrogen Concentration as a Nutritional Quality Indicator for European Rabbit Ecological Studies

    PubMed Central

    Gil-Jiménez, Esperanza; Villamuelas, Miriam; Serrano, Emmanuel; Delibes, Miguel; Fernández, Néstor

    2015-01-01

    Measuring the quality of the nutritional resources available to wild herbivores is critical to understanding trophic regulation processes. However, the direct assessment of dietary nutritional characteristics is usually difficult, which hampers monitoring nutritional constraints in natural populations. The feeding ecology of ruminant herbivores has been often assessed by analyzing fecal nitrogen (FN) concentrations, although this method has been less evaluated in other taxa. This study analyzed the suitability of FN as an indicator of ingesta quality in the European rabbit (Oryctolagus cuniculus), which is a keystone lagomorph species in Mediterranean ecosystems and of great conservation interest. Firstly, domestic O. cuniculus were used to evaluate under experimental conditions the accuracy of total FN and the metabolic FN as diet quality indicators of forages with characteristics similar to those available under natural conditions. Secondly, the accuracy of Near-Infrared Spectroscopy (NIRS) to calculate FN was tested using partial least squares regression. Thirdly, a pilot field study was conducted to monitor FN dynamics from wild O. cuniculus in three different habitats during wet and drought periods. A strong association was found between diet type and total FN and metabolic FN (Pseudo-R2 ≥ 0.89). It was also found that NIRS calibrations were accurate for depicting nitrogen concentrations (R2 > 0.98 between NIRS and chemical results). Finally, the seasonal FN dynamics measured in the field were consistent with current knowledge on vegetation dynamics and forage limitations in the three habitats. The results support the use of NIRS methods and FN indices as a reliable and affordable approach to monitoring the nutritional quality of rabbit habitats. Potential applications include the assessment of the mechanistic relationships between resource limitations and population abundance, e.g., in relation to natural drought cycles and to habitat interventions aimed at

  16. Rabbit rectus femoris muscle for ischemia-reperfusion studies: an improved model.

    PubMed

    Hoballah, J J; Mohan, C R; Schipper, P H; Chalmers, R T; Corry, D C; Corson, J D

    1996-11-01

    The rabbit rectus femoris muscle was evaluated as a potential model for skeletal muscle reperfusion injury studies. Six white New Zealand rabbits were used. On one randomly selected hind limb, ischemia was induced by direct clamping of the rectus femoris muscle's vascular pedicle. On the other side, blood flow was interrupted by clamping the femoral artery above and below the origin of the vascular pedicle that supplies the rectus femoris muscle. The duration of normothermic ischemia was 4 hr and was followed by 24 hr of normothermic reperfusion. The interruption and restoration of blood flow was monitored using a laser flow meter. The rectus femoris muscles were weighed on a suspension spring balance prior to ischemia and at the end of reperfusion to estimate edema. The extent of muscle necrosis was determined using planimetry following staining with nitroblue tetrazolium. The muscle necrosis obtained by direct clamping of the vascular pedicle (66.9 +/- 14.3%) was significantly greater than that obtained by indirect clamping (18.6 +/- 11.4%) (P < 0.03 by t test). Unlike the indirect clamping technique, direct clamping achieved a good magnitude of muscle necrosis, thus allowing that specific model to be used in skeletal muscle reperfusion injury studies. The muscle weight gain observed in the direct clamping muscle group was 19.8 +/- 9.0% and was significantly greater than that observed in the opposite group being 6.3 +/- 6.5% (P < 0.05 by t test). The rabbit rectus femoris muscle is a suitable model for evaluating skeletal muscle reperfusion injury provided that direct clamping of the vascular pedicle is utilized.

  17. An experimental model for studies on delayed tooth replantation and ankylosis in rabbits.

    PubMed

    Maslamani, Manal; Almusawi, Ala; Joseph, Bobby; Gabato, Severino; Andersson, Lars

    2016-12-01

    To develop an experimental in vivo model to study dentoalveolar ankylosis and osseous replacement resorption after delayed replantation. The maxillary right incisors of eight rabbits were extracted and replanted, while the maxillary left incisors served as controls. A special technique for extraction was used, luxating the incisor laterally prior to extraction. Extra-oral root canal treatment was performed. In four of the eight replanted teeth, periodontal ligament was removed using gauze. All teeth were replanted after one-hour dry storage. A horizontal line was drilled on the labial enamel surface of the incisors to enable registration of possible subsequent infraposition. The rabbits were sacrificed after 1 week or 4 weeks, respectively. Percussion test of the teeth was carried out and infraposition was registered. Histological processing and evaluation were performed. Percussion sound was normal after 1 week and high in the 4 week group; infraposition was noted in all replanted teeth in the 4-week group. Fusion between the bone and dentin was seen in some areas on the root already after 1 week, but there was little or no osseous replacement. Larger areas of ankylosis were seen in the 4-week group although not significant, but deeper progressive osseous replacement was noted in this group. There was no significant difference in ankylosis with regard to periodontal ligament removal or not. Pulp and periodontal tissues were normal in all control teeth. The rabbit tooth model may be useful for experimental in-vivo studies on delayed replantation, subsequent ankylosis, osseous replacement and infraposition. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Fecal nitrogen concentration as a nutritional quality indicator for European rabbit ecological studies.

    PubMed

    Gil-Jiménez, Esperanza; Villamuelas, Miriam; Serrano, Emmanuel; Delibes, Miguel; Fernández, Néstor

    2015-01-01

    Measuring the quality of the nutritional resources available to wild herbivores is critical to understanding trophic regulation processes. However, the direct assessment of dietary nutritional characteristics is usually difficult, which hampers monitoring nutritional constraints in natural populations. The feeding ecology of ruminant herbivores has been often assessed by analyzing fecal nitrogen (FN) concentrations, although this method has been less evaluated in other taxa. This study analyzed the suitability of FN as an indicator of ingesta quality in the European rabbit (Oryctolagus cuniculus), which is a keystone lagomorph species in Mediterranean ecosystems and of great conservation interest. Firstly, domestic O. cuniculus were used to evaluate under experimental conditions the accuracy of total FN and the metabolic FN as diet quality indicators of forages with characteristics similar to those available under natural conditions. Secondly, the accuracy of Near-Infrared Spectroscopy (NIRS) to calculate FN was tested using partial least squares regression. Thirdly, a pilot field study was conducted to monitor FN dynamics from wild O. cuniculus in three different habitats during wet and drought periods. A strong association was found between diet type and total FN and metabolic FN (Pseudo-R(2) ≥ 0.89). It was also found that NIRS calibrations were accurate for depicting nitrogen concentrations (R(2) > 0.98 between NIRS and chemical results). Finally, the seasonal FN dynamics measured in the field were consistent with current knowledge on vegetation dynamics and forage limitations in the three habitats. The results support the use of NIRS methods and FN indices as a reliable and affordable approach to monitoring the nutritional quality of rabbit habitats. Potential applications include the assessment of the mechanistic relationships between resource limitations and population abundance, e.g., in relation to natural drought cycles and to habitat interventions

  19. EX VIVO STUDY OF QUANTITATIVE ULTRASOUND PARAMETERS IN FATTY RABBIT LIVERS

    PubMed Central

    Ghoshal, Goutam; Lavarello, Roberto J.; Kemmerer, Jeremy P.; Miller, Rita J.; Oelze, Michael L.

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) affects more than 30% of Americans, and with increasing problems of obesity in the United States, NAFLD is poised to become an even more serious medical concern. At present, accurate classification of steatosis (fatty liver) represents a significant challenge. In this study, the use of high-frequency (8 to 25 MHz) quantitative ultrasound (QUS) imaging to quantify fatty liver was explored. QUS is an imaging technique that can be used to quantify properties of tissue giving rise to scattered ultrasound. The changes in the ultrasound properties of livers in rabbits undergoing atherogenic diets of varying durations were investigated using QUS. Rabbits were placed on a special fatty diet for 0, 3, or 6 weeks. The fattiness of the livers was quantified by estimating the total lipid content of the livers. Ultrasonic properties, such as speed of sound, attenuation, and backscatter coefficients, were estimated in ex vivo rabbit liver samples from animals that had been on the diet for varying periods. Two QUS parameters were estimated based on the backscatter coefficient: effective scatterer diameter (ESD) and effective acoustic concentration (EAC), using a spherical Gaussian scattering model. Two parameters were estimated based on the backscattered envelope statistics (the k parameter and the μ parameter) according to the homodyned K distribution. The speed of sound decreased from 1574 to 1565 m/s and the attenuation coefficient increased from 0.71 to 1.27 dB/cm/MHz, respectively, with increasing fat content in the liver. The ESD decreased from 31 to 17 μm and the EAC increased from 38 to 63 dB/cm3 with increasing fat content in the liver. A significant increase in the μ parameter from 0.18 to 0.93 scatterers/mm3 was observed with increasing fat content in the liver samples. The results of this study indicate that QUS parameters are sensitive to fat content in the liver. PMID:23062376

  20. Statistical analysis plan for the WOMAN-ETAPlaT study: Effect of tranexamic acid on platelet function and thrombin generation

    PubMed Central

    Dallaku, Kastriot; Shakur, Haleema; Edwards, Phil; Beaumont, Danielle; Roberts, Ian; Huque, Sumaya; Delius, Maria; Mansmann, Ulrich

    2017-01-01

    Background. Postpartum haemorrhage (PPH) is a potentially life-threatening complication for women, and the leading cause of maternal mortality. Tranexamic acid (TXA) is an antifibrinolytic used worldwide to treat uterine haemorrhage and to reduce blood loss in general surgery. TXA may have effects on thrombin generation, platelet function and coagulation factors as a result of its inhibition on the plasmin. Methods. WOMAN ETAPlaT is a sub-study of the World Maternal Antifibrinolitic trial (WOMAN trial). All adult women clinically diagnosed with PPH after a vaginal delivery or caesarean section, are eligible for inclusion in the study. Blood samples will be collected at the baseline and 30 minutes after the first dose of study treatment is given. Platelet function will be evaluated in whole blood immediately after sampling with Multiplate® tests (ADPtest and TRAPtest). Thrombin generation, fibrinogen, D-dimer, and coagulation factors vW, V and VIII will be analysed using platelet poor plasma. Results. Recruitment to WOMAN ETAPlaT started on 04 November 2013 and closed on 13 January 2015, during this time  188 patients were recruited. The final participant follow-up was completed on 04 March 2015. This article introduces the statistical analysis plan for the study, without reference to unblinded data.   Conclusion. The data from this study will provide evidence for the effect of TXA on thrombin generation, platelet function and coagulation factors in women with PPH. Trial registration: ClinicalTrials.gov Identifier: NCT00872469; ISRCTN76912190 PMID:28413832

  1. Statistical analysis plan for the WOMAN-ETAPlaT study: Effect of tranexamic acid on platelet function and thrombin generation.

    PubMed

    Dallaku, Kastriot; Shakur, Haleema; Edwards, Phil; Beaumont, Danielle; Roberts, Ian; Huque, Sumaya; Delius, Maria; Mansmann, Ulrich

    2016-12-15

    Background. Postpartum haemorrhage (PPH) is a potentially life-threatening complication for women, and the leading cause of maternal mortality. Tranexamic acid (TXA) is an antifibrinolytic used worldwide to treat uterine haemorrhage and to reduce blood loss in general surgery. TXA may have effects on thrombin generation, platelet function and coagulation factors as a result of its inhibition on the plasmin. Methods. WOMAN ETAPlaT is a sub-study of the World Maternal Antifibrinolitic trial (WOMAN trial). All adult women clinically diagnosed with PPH after a vaginal delivery or caesarean section, are eligible for inclusion in the study. Blood samples will be collected at the baseline and 30 minutes after the first dose of study treatment is given. Platelet function will be evaluated in whole blood immediately after sampling with Multiplate® tests (ADPtest and TRAPtest). Thrombin generation, fibrinogen, D-dimer, and coagulation factors vW, V and VIII will be analysed using platelet poor plasma. Results. Recruitment to WOMAN ETAPlaT started on 04 November 2013 and closed on 13 January 2015, during this time  188 patients were recruited. The final participant follow-up was completed on 04 March 2015. This article introduces the statistical analysis plan for the study, without reference to unblinded data.   Conclusion. The data from this study will provide evidence for the effect of TXA on thrombin generation, platelet function and coagulation factors in women with PPH. Trial registration: ClinicalTrials.gov Identifier: NCT00872469; ISRCTN76912190.

  2. Autologous platelet-labeling in thrombocytopenia

    SciTech Connect

    Sinzinger, H.; Virgolini, I.; Vinazzer, H. )

    1990-11-01

    Field studies performed with peripheral platelets obtained from 6 male volunteers aged 23 to 29 years revealed an extraordinary dependence of labeling efficiency on incubation time and platelet concentration after {sup 111}In-oxine platelet labeling. Since the monitoring of in vivo-platelet function in patients with thrombocytopenia may cause problems due to insufficient labeling results and homologous platelets may show a different in vivo behaviour to autologous ones, we have searched for the minimal amount of platelets necessary to allow appropriate labeling and imaging in patients with thrombocytopenia. In 15 patients with untreated thrombocytopenia aged 14 to 79 years demonstrating a mean peripheral platelet count of 2.509 +/- 1.45 x 10(4) cells/microliters autologous {sup 111}In-oxine platelet labeling was performed. The results indicate that approximately 1 x 10(8) (concentrated) platelets/ml are necessary to obtain an adequate labeling efficiency and recovery. This platelet concentration can be easily achieved by drawing one more Monovette of whole blood per each 5 x 10(4) platelets/microliter peripheral platelet count less than 2 x 10(5)/microliter. It is concluded, that calculation of the required number of platelets in advance, variation of the blood volume drawn and the volume of incubation buffer allow informative, qualitative and quantitative results using autologous platelets. The method presented effectively circumvents the requirement of homologous platelets for radiolabeling in thrombocytopenia.

  3. Docetaxel Inhibits Urethral Stricture Formation, an Initial Study in Rabbit Model

    PubMed Central

    Fu, Delai; Chong, Tie; Li, Hecheng; Zhang, Huibo; Wang, Ziming

    2014-01-01

    Introduction Urethral stricture, a frequent source of lower urinary tract disorders in men, is still a difficult problem for urologists. Based the anti-restenosis effect of paclitaxel on coronary artery, the role of docetaxel, a semi-synthetic analogue of paclitaxel, in limiting urethral stricture formation was studied. Methods Forty adult New Zealand male rabbits were involved in this study, which were randomly assigned into 3 groups, namely a high dose docetaxel (DH, 0.1 mg/d), a low dose docetaxel (DL, 0.01 mg/d) and a control (C) group, with 16, 16, 8 rabbits in each group, respectively. All animals underwent a 10 mm-long circumferential electrocoagulation of the bulbar urethra with a 13Fr pediatric resectoscope. Drugs were given by urethral irrigation daily and continuous for 28 days. Stricture formation was assessed by retrograde urethrography and videourethroscopy. Urethra pathology was evaluated by hematoxylin and eosin staining and Sirius red staining. Results At the end of this study, 15, 14 and 7 rabbits remained for evaluation in DH, DL and C group, respectively. Urethral diameters in DH, DL and C group were (7.17±1.63) mm, (6.55±0.62) mm, (3.23±1.36) mm, with a normal urethral diameter of (9.08±1.29) mm. Lumen reduction in DH, DL and C group were (36.93±11.58)%, (48.03±7.89)% and (84.66±14.95)%, respectively. Statistically difference could be found between every two groups (p<0.05) both in urethral diameters and in lumen reduction, except for compare of urethral diameters between DH and DL group. Histological examination confirmed mass fibrous tissue and collagen content at the stricture sit in C group, whereas less in docetaxel treated rabbits. Conclusions Docetaxel could limit urethral stricture formation, which may be due to inhibition of fibrous tissue and collagen expression. Docetaxel may become a new choice in the prevention of urethral stricture formation. PMID:25375859

  4. Platelet-rich plasma versus open surgical release in chronic tennis elbow: A retrospective comparative study.

    PubMed

    Karaduman, Mert; Okkaoglu, Mustafa Caner; Sesen, Hakan; Taskesen, Anil; Ozdemir, Mahmut; Altay, Murat

    2016-03-01

    To compare short and mid-term results in the treatment of chronic elbow tendinosis with platelet-rich plasma (PRP) or Nirschl surgical technique. A retrospective study was conducted on patients with chronic lateral epicondylitis, treated by Nirschl surgical technique (50 elbows) or PRP (60 elbows). Outcome was evaluated with Visual Analog Score (VAS), Mayo Elbow Scores and grip strength measurements. VAS and Mayo Elbow Scores of the PRP group had improved as a mean of 83% (p = 0.0001), 74% (p = 0.0001) over baseline and 34.2 pounds gain of grip strength. The PRP seems to be better for pain relief and functionality in the short and mid-term periods.

  5. Platelet-rich plasma versus open surgical release in chronic tennis elbow: A retrospective comparative study

    PubMed Central

    Karaduman, Mert; Okkaoglu, Mustafa Caner; Sesen, Hakan; Taskesen, Anil; Ozdemir, Mahmut; Altay, Murat

    2016-01-01

    Purpose To compare short and mid-term results in the treatment of chronic elbow tendinosis with platelet-rich plasma (PRP) or Nirschl surgical technique. Method A retrospective study was conducted on patients with chronic lateral epicondylitis, treated by Nirschl surgical technique (50 elbows) or PRP (60 elbows). Outcome was evaluated with Visual Analog Score (VAS), Mayo Elbow Scores and grip strength measurements. Results VAS and Mayo Elbow Scores of the PRP group had improved as a mean of 83% (p = 0.0001), 74% (p = 0.0001) over baseline and 34.2 pounds gain of grip strength. Conclusion The PRP seems to be better for pain relief and functionality in the short and mid-term periods. PMID:26955228

  6. In vitro effects of ethanol on the pathways of platelet aggregation

    SciTech Connect

    Rand, M.L.; Kinlough-Rathbone, R.L.; Packham, M.A.; Mustard, J.F.

    1986-03-01

    Ethanol is reported to inhibit platelet aggregation in vivo and in vitro, but the mechanisms of its action on stimulus-response coupling in platelets is unknown. Platelet aggregation to thrombin occurs through at least three pathways: released ADP; thromboxane A/sub 2/ (TXA/sub 2/); and a third pathway(s). Aggregation of rabbit platelets in citrated platelet-rich plasma (PRP) or washed suspensions to ADP (0.5-10 ..mu..M) was not affected by ethanol, at concentrations up to 5 mg/ml (lethal). Primary ADP-induced (5 ..mu..M) aggregation of human platelets in PRP was also unaffected by ethanol, but secondary aggregation and release of /sup 14/C-serotonin, due to TXA/sub 2/ formation, was inhibited by ethanol (2 and 4 mg/ml). Since arachidonate (AA)-induced (25-250 ..mu..M) aggregation and release by washed rabbit platelets was unaltered by ethanol, it may inhibit mobilization of AA from platelet membrane phospholipids. Ethanol (2-4 mg/ml) inhibited rabbit platelet aggregation and release to low concentrations of thrombin (< 10 mU/ml) or collagen, and also inhibited aggregation and release of aspirin-treated (500 ..mu.. M) rabbit platelets (that cannot form TXA/sub 2/) to low concentrations of thrombin (< 10 mU/ml). Thus, ethanol does not inhibit the mobilization of AA, and partially inhibits the third pathway(s) of platelet aggregation.

  7. Effects of Khaya senegalensis leaves on performance, carcass traits, hemtological and biochemical parameters in rabbits

    PubMed Central

    Abdel-Wareth, A. A. A.; Hammad, Seddik; Ahmed, Hassan

    2014-01-01

    One of the challenges facing farmers today is to ensure adequate integration of natural resources into animal feeds. The aim of the present study is to evaluate the effects of Khaya senegalensis (KS) leaves on the performance of growing male rabbits, carcass traits and biochemical as well as hematological parameters. Thirty New Zealand White male growing rabbits were randomly divided into 3 groups (10 rabbits per group). Group I (control) received standard rabbit diet. Rabbits in group II and group III were fed standard rabbit diet supplemented with 35 % and 65 % KS leaves, respectively. All rabbits were fed daily for 25 days. The performance parameters and carcass criteria, including daily body weight gain, final body weight, and the percentage of dressing, were increased in rabbits fed 35 % KS when compared to the control group. Kidney and liver weight ratios increased significantly in group II but dropped in group III. Furthermore, liver enzymes - alanine aminotransferase and aspartate transaminase and kidney function parameters - urea, and creatinine - increased in both group II (significant P<0.05) and in group III (significant P<0.01) when compared to the control group. Moreover, KS leaves induced a significant increase (P<0.05) in the total white blood cell count, the percentage of granulocytes and the platelet count; whereas, the percentage of lymphocytes, red blood cell count, hemoglobin content, mean corpuscular hemoglobin, mean corpuscular volume and mean corpuscular hemoglobin concentration were not statistically significantly changed. This study demonstrates that the performance parameters and carcass traits are improved by the replacement of rabbit's diet with KS leaves. However, KS leaves may adversely affect liver and kidney function in a dose-dependent manner. Therefore, further studies are required to elucidate the maximum tolerable and toxic, as well as lethal doses, and to isolate the pharmacologically active components from KS leaves. PMID

  8. Drilling k-wires, what about the osteocytes? An experimental study in rabbits

    PubMed Central

    van Diest, Paul J.; Schuurman, Arnold H.; Kon, Moshe

    2007-01-01

    Introduction The function of osteocytes regarding osteonecrosis has been underestimated for a long time. Recently it has been suggested that apoptosis of osteocytes results in strong osteoclastic bone resorption. Death of osteocytes due to drilling may therefore increase the risk of K-wire loosening. The purposes of our in vivo study were to assess the minimal drill time needed to notice disappearance of osteocytes and to measure the distance of the empty osteocyte lacunae surrounding the drill tract in relation with the insertion time, directly and 4 weeks after drilling Kirschner (K-) wires into the femur and tibia of rabbits. Materials and methods Trocar tipped K-wires (70 mm length and 0.6 mm thickness) were drilled into the femur and tibia of 14 New Zealand white rabbits [mean body weight 2.81 kg (2.66–3.09 kg)]. Six rabbits were terminated following surgery (t = 0) and eight rabbits were terminated 4 weeks (t = 4) after surgery. Following termination, hematoxylin and eosin stained sections were cut from femur and tibia until the drill hole was visible. The sections were evaluated under a light microscope for the presence or absence of osteocytes in osteocyte lacunae surrounding the drill holes. Results All osteocyte lacunae were empty around the K-wires in 50 and 87% of the cases, directly and 4 weeks after the surgery, respectively. The osteocytes disappeared especially beyond a drilling time of 37 s (P = 0.011) and 27 s (P = 0.008) at t = 0 and t = 4, respectively. Furthermore, a significantly positive correlation was seen between the distances of the empty osteocyte lacunae surrounding the drill holes in relation with time at t = 0 (P = 0.008) and t = 4 (P = 0.000). Conclusion Although only drilling without cooling was studied, short drilling times may prevent the disappearance of osteocytes in case cooling is not used in clinical practice as is the case in percutaneous K-wire insertion. PMID:17598116

  9. Experimental erbium: YAG laser photoablation of trabecular meshwork in rabbits: an in-vivo study.

    PubMed

    Dietlein, T S; Jacobi, P C; Schröder, R; Krieglstein, G K

    1997-05-01

    Photoablative laser trabecular surgery has been proposed as an outflow-enhancing treatment for open-angle glaucoma. The aim of the study was to investigate the time course of repair response following low-thermal Erbium: YAG laser trabecular ablation. In 20 anaesthetized rabbits gonioscopically controlled ab-interno photoablation of the ligamenta pectinata and underlying trabecular meshwork (TM) was performed with a single-pulsed (200 microseconds) Erbium: YAG (2.94 microns) laser. The right eye received 12-15 single laser pulses (2 mJ) delivered through an articulated zirconium fluoride fiberoptic and a 200 microns (core diameter) quartz fiber tip, the left unoperated eye served as control. At time intervals of 30 minutes, 2, 10, 30, and 60 days after laser treatment, eyes were processed for light- and scanning electron microscopy. The applied energy density of 6-4 J cm-2 resulted in visible dissection of the ligamenta pectinata and reproducible microperforations of the TM exposing scleral tissue accompanied by blood reflux from the aqueous plexus. The initial ablation zones measured 154 +/- 36 microns in depth and 45 +/- 6 microns in width. Collateral thermal damage zones were 22 +/- 8 microns. At two days post-operative, ablation craters were still blood- and fibrin-filled. The inner surface of the craters were covered with granulocytes. No cellular infiltration of the collateral thermal damage zone was observed. At 10 days post-operative, progressive fibroblastic proliferation was observed, resulting in dense scar tissue formation with anterior synechiae, proliferating capillaries and loss of intertrabecular spaces inside the range of former laser treatment at 60 days post-operative. Trabecular microperforations were closed 60 days after laser treatment in all rabbits. IOP in treated and contralateral eyes did not significantly change its level during whole period of observation. Low-thermal infrared laser energy with minimal thermal damage to collateral

  10. Pharmacokinetic study of conventional sorafenib chemoembolization in a rabbit VX2 liver tumor model.

    PubMed

    Parvinian, Ahmad; Casadaban, Leigh C; Hauck, Zane Z; van Breemen, Richard B; Gaba, Ron C

    2015-01-01

    Use of oral sorafenib, an antiangiogenic chemotherapeutic agent for hepatocellular carcinoma (HCC), is limited by an unfavorable side effect profile. Transarterial chemoembolization (TACE) employs targeted intravascular drug administration, and has potential as a novel sorafenib delivery method to increase tumoral concentrations and reduce systemic levels. This study aimed to discern the pharmacokinetics of sorafenib TACE in a rabbit VX2 liver tumor model. A 3 mg/kg dose of sorafenib ethiodized oil emulsion was delivered via an arterial catheter to VX2 liver tumors in seven New Zealand white rabbits. Following TACE, serum sorafenib levels were measured at days 0, 1, 2, 3, 7, 10, and 14 until the time of sacrifice, after which rabbit livers were harvested for analysis of sorafenib concentrations within treated tumors and normal liver. Liquid chromatography tandem mass spectrometry was used for drug quantification. Sorafenib uptake within liver tumor and nontumorous liver tissue peaked at mean 3.53 and 0.75 μg/mL, respectively, immediately post-procedure (5:1 tumor to normal tissue drug uptake ratio), before decreasing with a 10-18 hour half-life. Serum sorafenib levels peaked immediately after TACE at a mean value of 58.58 μg/mL before normalizing with a 5.2-hour half-life, suggesting early drug washout from liver into the systemic circulation. Hepatic lab parameters showed transient increase 24 hours post-TACE with subsequent resolution. While targeted transarterial delivery of sorafenib ethiodized oil emulsion shows preferential tumor uptake compared to normal liver, systemic washout occurs with a short half-life, resulting in high circulating drug levels.

  11. Influence of soft tissue contamination on the integration of titanium implants. An experimental study in rabbits.

    PubMed

    Ivanoff, C J; Sennerby, L; Lekholm, U

    1996-06-01

    In the present study, the influence of peroperative soft tissue contamination on the healing of titanium implants was studied in 9 lop-eared rabbits. Titanium implants (Brånemark System) were inserted in the tibiae, a location with cortical bone only, in such a way that one group was inserted the standard way (control), and another group was contaminated for 30 s in the adjacent soft tissues, prior to insertion. The implants were allowed to heal for 12 weeks and were then retrieved together with surrounding bone, fixed, dehydrated and embedded in plastic resin. About 10 micron thick ground sections were prepared for light microscopic morphometry. The mineralized bone-to-titanium contact, and the amount of bone occupying the threads, were calculated for each implant, and the results of the two groups were compared. All retrieved implants were clinically stable at the end of the experiment. Regarding bone-to-titanium contact and bone area within the threads, a statistically nonsignificant difference was observed between the 2 groups. This study indicated that peroperative soft tissue contamination of c.p. titanium implants does not prevent osseointegration from occurring, when studied in the rabbit tibia.

  12. In vitro function of platelets treated with ultraviolet C light for pathogen inactivation: a comparative study with nonirradiated and gamma-irradiated platelets.

    PubMed

    Tynngård, Nahreen; Trinks, Marie; Berlin, Gösta

    2015-06-01

    During storage of platelet concentrates (PCs) replication of contaminating pathogens might occur, which can be prevented by various pathogen inactivation (PI) methods using photoactive substances in combination with ultraviolet (UV) light. A new method uses only UVC light for PI without photoactive substances. This study evaluates the in vitro function, including hemostatic properties (clot formation and elasticity), of platelets (PLTs) treated with UVC light. A PC with 35% plasma and 65% PLT additive solution (SSP+) was prepared from five buffy coats. Three PCs were pooled and divided into 3 units. One unit was used as a nonirradiated control, the second was a gamma-irradiated control, and the third unit was treated with UVC light. In vitro variables including analysis of coagulation by free oscillation rheometry were analyzed on Days 1, 5, and 7 of storage. Ten units in each group were investigated. Swirling was well preserved, and the pH level was higher than the reference limit (6.4) during storage of PLTs in all groups. Glycolysis and PLT activation were higher for UVC-treated PLTs but the clot-forming capacity was unaffected. However, immediately after UVC treatment, the clot elastic properties were slightly affected. Hypotonic shock response decreased immediately after UVC treatment but recovered partly during the storage period. UVC treatment affected the in vitro properties, but PLT quality and storage stability were well preserved for up to 7 days, and the in vitro hemostatic capacity of UVC-treated PLTs was only minimally altered. The clinical relevance of these changes needs to be evaluated in controlled trials. © 2014 AABB.

  13. Typing for human platelet alloantigens.

    PubMed

    Juji, T; Saji, H; Satake, M; Tokunaga, K

    1999-01-01

    Antibodies to platelet alloantigens, and sometimes to isoantigens, induce severe clinical problems such as neonatal alloimmune thrombocytopenia (NAIT), post-transfusion purpura (PTP) and refractoriness to platelet transfusions (PTR). For example, NAIT affects approximately 1 in 5,000 live births. It is essential, therefore, to screen pregnant women for platelet antibodies in order to save babies' lives. Almost 40 years ago, two platelet alloantigen systems were discovered using relatively simple methods, namely the platelet agglutination test and the complement fixation test. However, these methods were not sensitive enough to identify all antibodies in mothers and patients, even in those with severe clinical problems. Tremendous effort has been devoted to establish more sensitive and reliable methods. In recent years, excellent new serological and immunochemical methods have been established and several new platelet antigen systems have been discovered. Simultaneously, newly developed molecular genetic techniques have been introduced for the typing and analysis of human platelet alloantigen systems. These methods allow DNA typing for cases in which serological typing is not available. In this article, the history of studies on human platelet alloantigen systems and isoantigens, the nomenclature of platelet alloantigen systems and their alleles, the present status of antibody detection and typing techniques and, finally, ethnic variations in platelet antigen profiles are reviewed.

  14. Interaction of inorganic nanoparticles of lunar soil simulant with blood platelets

    NASA Astrophysics Data System (ADS)

    Borisova, Tatiana; Kasatkina, Ludmila; Krisanova, Natalia; Sivko, Roman; Borisov, Arseniy; Slenzka, Klaus

    Blood platelets play a central role in the physiology of primary hemostasis and in the patholog-ical processes of arterial thrombosis. Also, blood platelets contain neuronal high-affinity Na+-dependent glutamate transporters (EAAT 1 -3) and are able to uptake glutamate, thereby playing possible physiological role in extracellular glutamate homeostasis in the mammalian CNS as an additional powerful target for excessive neurotoxic glutamate accumulation and storage. The health effects of lunar soil exposure are almost completely unknown, whereas the observations suggest that it can be deleterious to human physiology. It is important that the components of lunar soil may be internalized with lipid fractions of the lung epithelium, which in turn may help ions to overcome the blood-brain barrier. The study focused on the effects of JSC-1a Lunar Soil Simulant (LSS) (Orbital Technologies Corporation, Madison, USA) on platelets isolated from rabbit blood. We revealed that platelets were not indifferent to the expo-sure to LSS. Flow cytometric analysis showed that the incubation of platelets with LSS resulted in an upper shift of platelet spot in histograms presenting cell size (FS) and granularity (SS) as x and y coordinates, thereby demonstrating apparent increase in platelet granularity. Analysis of control platelet preparation did not reveal the alterations in platelet size and granularity during the same incubation period. LSS scatter per se did not cover area of platelet prepara-tion in histogram. Using Zetasizer Nanosystem (Malvern Instruments) with helium-neon laser for dynamic light scattering (DLS), the platelet size before and after the addition of LSS was measured. We have found the increase in the mean size of the population of platelets from 2.45 ±0.09 µm in control to 3.0 ± 0.25 µm in the presence of LSS. Thus, we report that inorganic nanoparticles of LSS bind to blood platelets and this fact may have considerable harmful conse-quences to human

  15. A simulation study on the phase behavior of hard rhombic platelets

    NASA Astrophysics Data System (ADS)

    Tasios, N.; Dijkstra, M.

    2017-04-01

    Using Monte Carlo simulations, we investigate the phase behavior of hard rhombic platelets as a function of the thickness of the platelets, T. The phase diagram displays a columnar phase and a crystal phase in which the platelets are stacked in columns that are arranged in a two-dimensional lattice. We find that the shape of the platelets determines the symmetry of the two-dimensional lattice, i.e., rhombic platelets form an oblique columnar phase and a simple monoclinic crystal phase. For sufficiently thick platelets, i.e., for a thickness-to-length ratio T / L > 0.17 , we find only an isotropic fluid, an oblique columnar phase, and a monoclinic crystal phase. Surprisingly, for an intermediate plate thickness, 0.083 < T / L < 0.17 , we also find a region in between the isotropic (or nematic) phase and the columnar phase, where the smectic phase is stable. For sufficiently thin platelets, T / L < 0.13 , the phase diagram displays a nematic phase. With the exception of the smectic phase, our results resemble the phase behavior of discotic particles. Our results may guide the synthesis and future experiments on rhombic nanoplatelets.

  16. Selection of donor platelets for alloimmunized patients using a platelet-associated IgG assay

    SciTech Connect

    Myers, T.J.; Kim, B.K.; Steiner, M.; Baldini, M.G.

    1981-09-01

    A quantitative immunofluorescence platelet-associated immunoglobulin-G (PA-IgG) assay was used to detect alloimmunity to platelets in 8/12 multitransfused patients and to perform platelet crossmatching in the 8 alloimmunized patients. The correct separation of multitransfused patients into alloimmune and nonalloimmune groups was substantiated with chromium-51-labeled platelet survival studies. For 5 alloimmunized patients, compatible and incompatible donor platelets were demonstrated by PA-IgG crossmatching and were confirmed by platelet survival studies. With the other 3 alloimmunized patients, only Pa-IgG incompatible donor platelets were found. Survival studies with 5 of these incompatible donor platelets showed markedly reduced survival times on 4 occasions. Pa-IgG compatible donor platelets survived 3.5 to 8.7 days, while Pa-IgG incompatible platelets showed survival times of 0.1 to 2.4 days.

  17. Bioequivalence and tolerability study of two brands of clopidogrel tablets, using inhibition of platelet aggregation and pharmacodynamic measures☆

    PubMed Central

    Rao, Takallapalli Ramesh Kumar; Usha, P.Rani; Naidu, M.U.R; Gogtay, J.A; Meena, Matthew

    2003-01-01

    Background The role of platelets in acute cardiovascular atherothrombotic events has been well established and attention has focused on platelet inhibition therapy. Clopidogrel is a novel thienopyridine inhibitor of adenosine diphosphate–induced platelet activation. Recent studies have shown that in the setting of coronary angioplasty/stenting, a loading dose of 300 mg followed by 75 mg once daily is required for optimum benefit. Objective This study assessed the bioequivalence and tolerability of 2 oral formulations of clopidogrel 75-mg tablets. Methods This 10-day, open-label, randomized, parallel-group, comparative bioequivalence and tolerability study was carried out in the Department of Clinical Pharmacology and Therapeutics, Nizam's Institute of Medical Sciences (Hyderabad, India). Young healthy male volunteers were enrolled. Subjects were randomized to receive one of two 75-mg tablet formulations of clopidogrel (Clopivas® [test formulation] or Plavix® [reference formulation]). Subjects first received a 300-mg loading dose (four 75-mg tablets) on day 1, followed by 75 mg (1 tablet) at 8:00 AM daily for the next 6 days. Inhibition of platelet aggregation, which is the pharmacologic basis for the therapeutic efficacy of antiplatelet agents, and the effect on bleeding time were used as the pharmacodynamic assessment criteria. Pharmacodynamic variables included mean of maximum activity of percentage of inhibition of platelet aggregation (Emax), mean time to reach Emax (tmax), and mean area under the activity–time curve from time 0 to 168 hours (AUC0–168). Tolerability assessments included blood pressure and heart rate measurements before and at regular intervals (every hour for 12 hours and then at 24 hours) over a 24-hour period after drug administration. Clinical tolerability was assessed using adverse effects, platelet count (assessed on days 3, 6, and 10 after first-dose administration), and neutrophil count (assessed on day 10 after first

  18. Protein and glycoprotein abnormalities in platelets from human Chediak-Higashi syndrome: polyacrylamide gel electrophoretic study of platelets from five patients.

    PubMed

    Ledezma, E; Apitz-Castro, R

    1985-10-01

    Polyacrylamide electrophoretic analysis of proteins and Tritium-labelled glycoproteins of the platelets from five patients with Chediak-Higashi Syndrome shows the existence of marked quantitative differences when compared to normal platelets. While the glycoprotein abnormalities are solely related to the plasma membrane, some of the abnormalities detected in the Coomasie blue pattern are probably representative of defects related to the dense bodies and the alpha-granules. Some of the abnormalities found may, in part, explain the variability of aggregatory responses described in these patients, as well as the marked tendency towards desaggregation exhibited by platelets from humans with the Chediak-Higashi Syndrome.

  19. Hypotensive effects of hemopressin and bradykinin in rabbits, rats and mice. A comparative study.

    PubMed

    Blais, Paul-André; Côté, Jérôme; Morin, Josée; Larouche, Annie; Gendron, Gabrielle; Fortier, Audrey; Regoli, Domenico; Neugebauer, Witold; Gobeil, Fernand

    2005-08-01

    Hemopressin is a novel vasoactive nonapeptide derived from hemoglobin's alpha-chain as recently reported by Rioli et al. [Rioli V, Gozzo FC, Heimann AS, Linardi A, Krieger JE, Shida CS, et al. Novel natural peptide substrates for endopeptidase 24.15, neurolysin, and angiotensin-converting enzyme. J Biol Chem 2003;278(10):8547-55]. In anesthetized male Wistar rats, this peptide exhibited hypotensive actions similar to those of bradykinin (BK) when administered intravenously (i.v.), and was found to be metabolized both in vitro and in vivo by several peptidases, including the angiotensin-converting enzyme (ACE). In this study, these findings were expanded upon by examining: (i) the degradation kinetics following incubation with ACE purified from rabbit lung and (ii) the blood pressure lowering effects of HP and BK injected i.v. or intra-arterially (i.a.) in male rabbits, rats, and mice. Our findings demonstrate that, in vitro, HP and BK are both degraded by ACE, but at different velocity rates. Furthermore, both HP and BK induced transient hypotension in all animals tested, although the responses to HP relative to the administration sites were significantly lower (by 10-100-fold) on an equimolar basis compared to those of BK. In rabbits, the decrease of blood pressure induced by HP (10-100 nmol/kg) did not differ whether it was administered i.v. or i.a., suggesting an absence of pulmonary/cardiac inactivation in contrast to BK (0.1-1 nmol/kg). The in vivo effect of HP was significantly potentiated in rabbits immunostimulated with bacterial lipopolysaccharide (LPS), but was unaffected by both the B2 receptor antagonist HOE 140 (0.1 micromol/kg) and captopril (100 microg/kg), contrary to BK. Therefore, HP acts as a weak hypotensive mediator, which does not activate kinin B2 receptors, but uses a functional site and/or signaling paths appearing to be up-regulated by LPS.

  20. Cytoplasmic calcium levels and membrane fluidity of platelets in contact with polyether-polyamide multiblock-copolymer surfaces.

    PubMed

    Yui, N; Okano, T; Sakurai, Y; Kora, S; Ishikawa, K; Hiranuma, T; Yamashita, S

    1996-02-01

    Cytoplasmic calcium levels and the membrane fluidity of rabbit platelets stored in mini blood bags of crystalline-amorphous microstructured polymers (polyether-polyamide multiblock-copolymers) were studied. Fluorescent dye (Fura 2 or 1,6-diphenyl-1,3,5-hexatriene)-loaded platelet suspensions were stored at 37 degrees C for 1 h in the blood bags, and metabolic changes in the platelets during storage were evaluated by the fluorescent spectroscopic technique. The surfaces of poly(vinyl chloride) and polyolefin elastomers, which are used for commercially available blood bags, enhanced the progress of platelet metabolism; i.e., there was a dramatic decrease in membrane fluidity and an increase in [Ca2+]i. Furthermore, the decrease in membrane fluidity was observed prior to the increase in [Ca2+]i. These results suggest that the decrease in membrane fluidity of platelets in contact with polymer surfaces can be the dominant stage in the activation of these platelets. In contrast, the surfaces of polyether-polyamide multiblock-copolymers exhibited few changes in either membrane fluidity or [Ca2+]i levels. These results suggest that the platelets in contact with the crystalline-amorphous microstructured copolymer surfaces can be inert and inactivated in terms of the prevention of a decrease in membrane fluidity.

  1. Platelet-rich fibrin (PRF): a second-generation platelet concentrate. Part II: platelet-related biologic features.

    PubMed

    Dohan, David M; Choukroun, Joseph; Diss, Antoine; Dohan, Steve L; Dohan, Anthony J J; Mouhyi, Jaafar; Gogly, Bruno

    2006-03-01

    Platelet-rich fibrin (PRF) belongs to a new generation of platelet concentrates, with simplified processing and without biochemical blood handling. In this second article, we investigate the platelet-associated features of this biomaterial. During PRF processing by centrifugation, platelets are activated and their massive degranulation implies a very significant cytokine release. Concentrated platelet-rich plasma platelet cytokines have already been quantified in many technologic configurations. To carry out a comparative study, we therefore undertook to quantify PDGF-BB, TGFbeta-1, and IGF-I within PPP (platelet-poor plasma) supernatant and PRF clot exudate serum. These initial analyses revealed that slow fibrin polymerization during PRF processing leads to the intrinsic incorporation of platelet cytokines and glycanic chains in the fibrin meshes. This result would imply that PRF, unlike the other platelet concentrates, would be able to progressively release cytokines during fibrin matrix remodeling; such a mechanism might explain the clinically observed healing properties of PRF.

  2. CD8+ T cells induce platelet clearance in the liver via platelet desialylation in immune thrombocytopenia

    PubMed Central

    Qiu, Jihua; Liu, Xuena; Li, Xiaoqing; Zhang, Xu; Han, Panpan; Zhou, Hai; Shao, Linlin; Hou, Yu; Min, Yanan; Kong, Zhangyuan; Wang, Yawen; Wei, Yu; Liu, Xinguang; Ni, Heyu; Peng, Jun; Hou, Ming

    2016-01-01

    In addition to antiplatelet autoantibodies, CD8+ cytotoxic T lymphocytes (CTLs) play an important role in the increased platelet destruction in immune thrombocytopenia (ITP). Recent studies have highlighted that platelet desialylation leads to platelet clearance via hepatocyte asialoglycoprotein receptors (ASGPRs). Whether CD8+ T cells induce platelet desialylation in ITP remains unclear. Here, we investigated the cytotoxicity of CD8+ T cells towards platelets and platelet desialylation in ITP. We found that the desialylation of fresh platelets was significantly higher in ITP patients with positive cytotoxicity of CD8+ T cells than those without cytotoxicity and controls. In vitro, CD8+ T cells from ITP patients with positive cytotoxicity induced significant platelet desialylation, neuraminidase-1 expression on the platelet surface, and platelet phagocytosis by hepatocytes. To study platelet survival and clearance in vivo, CD61 knockout mice were immunized and their CD8+ splenocytes were used. Platelets co-cultured with these CD8+ splenocytes demonstrated decreased survival in the circulation and increased phagocytosis in the liver. Both neuraminidase inhibitor and ASGPRs competitor significantly improved platelet survival and abrogated platelet clearance caused by CD8+ splenocytes. These findings suggest that CD8+ T cells induce platelet desialylation and platelet clearance in the liver in ITP, which may be a novel mechanism of ITP. PMID:27321376

  3. A Study of Platelet Inhibition, Using a ‘Point of Care’ Platelet Function Test, following Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction [PINPOINT-PPCI

    PubMed Central

    Johnson, Thomas W.; Mumford, Andrew D.; Scott, Lauren J.; Mundell, Stuart; Butler, Mark; Strange, Julian W.; Rogers, Chris A.; Reeves, Barnaby C.; Baumbach, Andreas

    2015-01-01

    Background Rapid coronary recanalization following ST-elevation myocardial infarction (STEMI) requires effective anti-platelet and anti-thrombotic therapies. This study tested the impact of door to end of procedure (‘door-to-end’) time and baseline platelet activity on platelet inhibition within 24hours post-STEMI. Methods and Findings 108 patients, treated with prasugrel and procedural bivalirudin, underwent Multiplate® platelet function testing at baseline, 0, 1, 2 and 24hours post-procedure. Major adverse cardiac events (MACE), bleeding and stent thrombosis (ST) were recorded. Baseline ADP activity was high (88.3U [71.8–109.0]), procedural time and consequently bivalirudin infusion duration were short (median door-to-end time 55minutes [40–70] and infusion duration 30minutes [20–42]). Baseline ADP was observed to influence all subsequent measurements of ADP activity, whereas door-to-end time only influenced ADP immediately post-procedure. High residual platelet reactivity (HRPR ADP>46.8U) was observed in 75% of patients immediately post-procedure and persisted in 24% of patients at 2hours. Five patients suffered in-hospital MACE (4.6%). Acute ST occurred in 4 patients, all were <120mins post-procedure and had HRPR. No significant bleeding was observed. In a post-hoc analysis, pre-procedural morphine use was associated with significantly higher ADP activity following intervention. Conclusions Baseline platelet function, time to STEMI treatment and opiate use all significantly influence immediate post-procedural platelet activity. PMID:26672598

  4. Primary thrombophilia in México X: a prospective study of the treatment of the sticky platelet syndrome.

    PubMed

    Velázquez-Sánchez-de-Cima, Sara; Zamora-Ortiz, Gabriela; Hernández-Reyes, Jesús; Vargas-Espinosa, Jocelyn; García-Chavez, Jessica; Rosales-Padrón, Jaime; Ruiz-Delgado, Guillermo J; Ruiz-Arguelles, Alejandro; Ruiz-Argüelles, Guillermo J

    2015-01-01

    The sticky platelet syndrome (SPS) is a common cause of thrombosis. There are no prospective studies concerning treatment. To analyze changes in platelet hyperaggregability of patients with SPS who were given antiplatelet drugs and to assess its association with rethrombosis. A total of 55 patients with a history of thrombosis and SPS phenotype were prospectively studied before and after treatment with aspirin and/or clopidogrel. Patients were followed for 1 to 129 months, median 13. Of 55 patients, 40 received aspirin, 13 received aspirin + clopidogrel, and 2 received only clopidogrel. The platelet aggregation response to adenosine diphosphate and epinephrine significantly diminished after treatment, and only 2 patients developed rethrombosis 52 and 129 months after starting therapy, with the freedom from rethrombosis rate of the patients being 96.4% at 129 months. Using antiplatelet drugs, the platelet hyperreactivity of patients with the SPS phenotype was reverted; and this translated into a substantial decrease in the rethrombosis rate. © The Author(s) 2013.

  5. Evaluation of Dried Storage of Platelets for Transfusion: Physiologic Integrity and Hemostatic Functionality

    DTIC Science & Technology

    1994-06-17

    ONR Grant No. N00014-92-J-1244 EVALUATION OF DRIED STORAGE OF PLATELETS FOR TRANSFUSION: PHYSIOLOGIC INTEGRITY AND HEMOSTATIC FUNCTIONALITY. Principal...protection for commercialization of the manufacture and use of lyophilized platelets in transfusion medicine is still pending in U.S. Patent Court and... platelets for correction of bleeding times in thrombocytopenic rabbits. Three different preparations, representing the platelets from a total of six units

  6. A Pilot Study on the Effect of Angiotensin Receptor Blockers on Platelet Aggregation in Hypertensive Patients- A Prospective Observational Study

    PubMed Central

    Sanji, Narendranath; Kamath, Pallavi Mahadeva; Devendrappa, Srinivas Lokikere; Hanumanthareddy, Shashikala Gowdara; Maniyar, Imran; Rudrappa, Suresh Surappla

    2016-01-01

    Introduction Thrombosis is an invariable component contributing to cardiovascular events in patients with hypertension. One of the risk factors of cardiovascular disease is increased platelet activity. One among the widely used antihypertensive agents are Angiotensin II type 1 Receptor Blockers (ARBs). Even though there are many studies involving antihypertensive agents, their antithrombotic properties remain elusive and not fully characterized. Aim To evaluate the anti-aggregatory effect of ARBs on platelets in-vivo. Materials and Methods A total of 60 subjects were included in this observational pilot study conducted in the medicine out patient department of JJM Hospital, Davanagere, Karnataka, India. Among them, 30 patients with essential hypertension attending Medicine OPD of a tertiary care hospital, who were on ARB for at least one month, were enrolled into study group. The control group consisted of 30 normotensive subjects who were not on any drug affecting platelet function. The Bleeding Time (BT) was evaluated for both the groups using Duke method of BT estimation. Data was analysed using SPSS software version 20. The test group was compared with control group using student’s unpaired t-test. Results The mean BT of study group was 2.488 minutes ± 0.0361 Standard Error of Mean (SEM) and that of control group was 1.998 minutes ± 0.0362 SEM. The result was statistically significant (p<0.001). The average duration of treatment was 2.933 years. Conclusion ARB have antiplatelet activity. Increase in BT in ARB group when compared with that of control group is a reflection of antiplatelet activity. PMID:28050394

  7. A biochemical and histopathologic study showing protection and treatment of gentamicin-induced nephrotoxicity in rabbits using vitamin C.

    PubMed

    Rehman, K; Akash, M S H; Azhar, S; Khan, S A; Abid, R; Waseem, A; Murtaza, G; Sherazi, T A

    2012-01-01

    Gentamicin and vitamin C have been proposed as nephrotoxic and antioxidant, respectively. This study involved biochemical and histopathologic investigation showing protection and treatment of gentamicin-induced nephrotoxicity in rabbits using vitamin C for 26 days hypothesizing that whether vitamin C would inhibit or decrease the raised serum urea and creatinine levels. This study was conducted on 25 healthy male albino rabbits (average weight 1.5±0.2 kg), classified into 5 groups: group A, B, C, D and E for nephrocurative (study-I) and nephroprotective (study-II) studies. Control group of rabbits (group A) received only the vehicle of gentamicin ampoule. In study-I, gentamicin sulphate (GS 80 mg/kg, i.m.) was administered to group B and C rabbits for ten days, then group C rabbits received vitamin C 250 mg/Kg for remaining 16 days. Group D and E received GS 80 mg/kg and GS 80 mg/kg i.m.-vitamin C 250 mg/kg orally, respectively during whole period (26 days) of study-II. After 26 days, various biochemical parameters, i.e. serum creatinine, blood urea nitrogen (BUN), and serum antioxidant activity, and histopathologic investigations were made. Nephrotoxicity was observed in rabbit groups B, C and D as evident from significant (p<0.05) high levels of serum creatinine and BUN and low serum antioxidant levels as compared to the levels of control group. Decrease in the levels of serum creatinine and BUN along with the increase in serum antioxidant activity was observed after vitamin C treatment in group C. While, renal-protective role of vitamin C was seen in group E as compared to the control. In conclusion, Gentamicin induced nephrotoxicity can be attenuated or treated using vitamin C.

  8. A histomorphometric study of necrotic femoral head in rabbits treated with extracorporeal shock waves

    PubMed Central

    Ma, Huan-Zhi; Zhou, Dong-Sheng; Li, Dong; Zhang, Wei; Zeng, Bing-Fang

    2017-01-01

    [Purpose] This study aimed to determine the effectiveness and mechanisms of extracorporeal shock wave therapy in the treatment of femoral head osteonecrosis. [Subjects and Methods] Histomorphometric analysis of necrotic femoral head in rabbits treated with shock waves was performed. Bilateral osteonecrosis of femoral heads was induced with methylprednisolone and lipopolysaccharide in eight rabbits. The left limb (study side) received shock waves to the femoral head. The right limb (control side) received no shock waves. Biopsies of the femoral heads were performed at 12 weeks after shock wave therapy. [Results] Necrotic femoral heads treated with shock waves, compared with controls, had higher bone volume per tissue volume, trabecular thickness, trabecular number, osteoblast surface/bone surface, osteoid surface/bone surface, osteoid thickness, mineralizing surface/bone surface, mineralizing apposition rate, and bone formation rate. However, trabecular separation was lower in shock wave-treated femoral heads than in controls. Eroded surface/bone surface and osteoclast surface/bone surface did not differ significantly between groups. [Conclusion] The bone mass of necrotic femoral heads treated with shock waves increases. Extracorporeal shock wave may promote bone repair in necrotic femoral heads through the proliferation and activation of osteoblasts. PMID:28210032

  9. Percutaneous cartilage injection: A prospective animal study on a rabbit model

    PubMed Central

    2013-01-01

    Background Cartilage grafting is a useful technique in nasal reconstruction. Implantation of a whole graft is usually done through an incision. Crushed cartilage can also be used. Injection of cartilage could be an alternative to implantation. The objective of this study is to compare the long-term viability of percutaneously injected crushed auricular cartilage to surgically implanted cartilage in the rabbit. Methods Auricular cartilage was harvested bilaterally in 10 New Zealand white rabbits. A 1 cm2 cartilage graft was implanted surgically on the upper nasal dorsum. The remaining cartilage was crushed and percutaneously injected on the lower nasal dorsum. Volume and mass of each graft were compared between pre-implantation and after 3 months of observation. A histological study was conducted to evaluate chondrocyte viability and degree of fibrosis on pre and post-implantation cartilage. Results Mass and volume remained similar for surgically implanted cartilage grafts. Mass and volume diminished by an average of 47% and 40% respectively after 3 months for the injected crushed cartilage grafts. Chondrocyte viability was an average of 25% lower in the injected grafts. Conclusions Cartilage injection is a promising technique that must be refined to increase chondrocyte viability. Developing an appropriate injection apparatus would improve this technique. PMID:23663241

  10. Bone regeneration using porous titanium particles versus bovine hydroxyapatite: a sinus lift study in rabbits.

    PubMed

    Lambert, France; Lecloux, Geoffrey; Léonard, Angelique; Sourice, Sophie; Layrolle, Pierre; Rompen, Eric

    2013-06-01

    The first objective of this study was to qualitatively and quantitatively assess the bone formation process, particularly the long-term behavior and three-dimensional volume stability of subsinusal bone regeneration, using titanium (Ti) or bovine hydroxyapatite (BHA) granules, in a rabbit model. The second objective was to evaluate the effect of the hydration of the BHA particles with a therapeutic concentration of doxycycline solution on the osteogenesis and biomaterial resorption. Rabbits underwent a double sinus lift procedure using one of three materials: grade 1 porous Ti particles, BHA, or BHA hydrated with doxycycline solution (0.1mg/ml) (BHATTC). Animals were sacrificed after 1 week, 5 weeks, or 6 months. Samples were analyzed using µCT and nondecalcified histology. The materials used in each of the three groups allowed an optimal bone formation; bone quantities and densities were not statistically different between the three groups. At 6 months, more stable three-dimensional volume stability was found with Ti and BHATTC (p=.0033). At 5 weeks and 6 months, bone to material contact corroborating osteoconduction was significantly higher with BHA and BHATTC than with Ti (p<.0001). Even though the studied biomaterials displayed different architectures, they are relevant candidates for sinus lift bone augmentation prior to dental implants because they allow adequate three-dimensional stability and osteogenesis. However, to recommend the clinical use of Ti, both an observation on the drilling effects of Ti particles and clinical trials are needed. © 2011 Wiley Periodicals, Inc.

  11. An initial study of insect succession on decomposing rabbit carrions in Harare, Zimbabwe

    PubMed Central

    Mabika, Nyasha; Masendu, Ron; Mawera, Gilbert

    2014-01-01

    Objective To investigate insects visiting sun exposed and shaded decomposing rabbit carcasses and to establish the relationship between insects and carcasses which may be of forensic importance in Harare. Methods Two rabbits weighing 2.3 kg and 2.5 kg were killed by sharp blows on the head. One was exposed to the sun while the other was placed under shade. The carcasses were allowed to decompose and insects were collected twice a day for the first week and thereafter once a day up to the end of the 7 weeks. Maggots were also collected from the decomposing carcasses and reared. Results Five dipteran families (Calliphoridae, Muscidae, Sarcophagidae, Phoridae and Drosophilidae) were identified from the sun-exposed carcass. Species collected included Lucilia cuprina (L. cuprina), Chrysomya albiceps (C. albiceps), Musca domestica, Sarcophaga sp. and Drosophila sp. Four families (Calliphoridae, Muscidae, Phoridae, Anthomyiidae) were identified from the shaded carcass. Representatives of these families included L. cuprina, C. albiceps, Musca domestica, and Hydrotaea sp. Three Coleopteran families (Histeridae, Cleridae and Dermestidae) were identified from both carcasses. The observed species were Saprinus sp., Necrobia rufipes and Dermestes sp. Formicidae (Hymenoptera) was represented by only one species (Pheidole sp.). Flies which emerged from the rearing units were L. cuprina, Lucilia sp., C. albiceps, Sarcophaga sp. and Sepsis sp.). Conclusions Of the dipteran species collected during the study, L. cuprina and C. albiceps could be important for further forensic studies since they were collected from the carcasses and also observed from the rearing units. PMID:25183277

  12. Treatment of endometriosis with local acetylsalicylic acid injection: experimental study in rabbits.

    PubMed

    Siqueira, Juliana Menezes; Barreto, Adriana Beatriz; Saad-Hossne, Rogério

    2011-01-01

    The objective of the present study was to estimate the effects of introduction of acetylsalicylic acid solution into peritoneal implants in autologous endometrium as a method for treating endometriosis. Forty adult female rabbits were subdivided into 4 groups of 10 rabbits each, and endometriosis was induced via autotransplantation of endometrial fragments into the peritoneal cavity. At 30 days after induction of endometriosis, all animals were randomly assigned to 1 of 2 protocols. In protocol 1, animals were evaluated at 24 hours after treatment; group 1 (control) received physiologic solution, and group 2 received acetylsalicylic acid. In protocol 2, animals were evaluated at 10 days after treatment, group 3 (control) and group 4 received acetylsalicylic acid. After measuring the lesion, the endometriotic focus was removed and prepared for mounting on slides for histologic analysis. Imaging software was used for analysis of the total remaining area of endometrial tissue. The affected area in acetylsalicylic acid-treated animals was smaller than that in control animals at 24 hours and 10 days after treatment; a significant difference was found between control and treated groups (p < .001). Statistical analysis comparing protocols 1 and 2 demonstrated no differences between controls groups or acetylsalicylic acid groups (p = .30), and no differences between times (p = .75). Acetylsalicylic acid solution led to less growth (or higher involution) of endometrial implants. Acetylsalicylic acid injected directly into endometriotic foci was effective in their destruction. This presents new perspectives for treatment of endometriosis and for clinical applications based on further clinical studies.

  13. [The study of new soft one-piece PHEMA keratoprosthesis implanted into alkali burned rabbits cornea].

    PubMed

    Bai, Hua; Huang, Yi-fei; Wang, Li-qiang

    2013-10-01

    This study was to evaluate clinical results of two types soft one-piece keratoprosthesis (KPros) made of PHEMA implanted to alkali burned rabbit corneas. Experimental study. Twelve pieces KPros were implanted alkali burned rabbit corneas(type I and II, 6 pieces respectively). The examinations including slit-lamp, fundus photography,B-ultrasound and ultrasound biomicroscopy (UBM) were carried out. All Kpros were stable and no complications happened including conjunctiva flap dehiscence, aqueous leak and infection. IOP were normal by finger touch. B-ultrasound show no retina detachment and UBM show synechia in most animals (10 case). Retroprosthetic membrane happened in type I (3 case) . Visible conjunctiva hyperplasia covering the optical region happened in all KPros. (1) The same material, integrated design, maybe eliminating the material interface problem. (2)Simple surgical skills. (3)IOP measurement is possible because of soft material. (4)KPro I do not need removal of the lens and vitrectomy. The projecting portion of KPro II may reduce the incidence of proliferative membrane. Long term effects need more cases and further observation.

  14. Electrophysiological studies of transgenic long QT type 1 and type 2 rabbits reveal genotype-specific differences in ventricular refractoriness and His conduction

    PubMed Central

    Odening, Katja E.; Kirk, Malcolm; Brunner, Michael; Ziv, Ohad; Lorvidhaya, Peem; Liu, Gong Xin; Schofield, Lorraine; Chaves, Leonard; Peng, Xuwen; Zehender, Manfred; Choi, Bum-Rak

    2010-01-01

    We have generated transgenic rabbits lacking cardiac slow delayed-rectifier K+ current [IKs; long QT syndrome type 1 (LQT1)] or rapidly activating delayed-rectifier K+ current [IKr; long QT syndrome type 2 (LQT2)]. Rabbits with either genotype have prolonged action potential duration and QT intervals; however, only LQT2 rabbits develop atrioventricular (AV) blocks and polymorphic ventricular tachycardia. We therefore sought to characterize the genotype-specific differences in AV conduction and ventricular refractoriness in LQT1 and LQT2 rabbits. We carried out in vivo electrophysiological studies in LQT1, LQT2, and littermate control (LMC) rabbits at baseline, during isoproterenol infusion, and after a bolus of dofetilide and ex vivo optical mapping studies of the AV node/His-region at baseline and during dofetilide perfusion. Under isoflurane anesthesia, LQT2 rabbits developed infra-His blocks, decremental His conduction, and prolongation of the Wenckebach cycle length. In LQT1 rabbits, dofetilide altered the His morphology and slowed His conduction, resulting in intra-His block, and additionally prolonged the ventricular refractoriness, leading to pseudo-AV block. The ventricular effective refractory period (VERP) in right ventricular apex and base was significantly longer in LQT2 than LQT1 (P < 0.05) or LMC (P < 0.01), with a greater VERP dispersion in LQT2 than LQT1 rabbits. Isoproterenol reduced the VERP dispersion in LQT2 rabbits by shortening the VERP in the base more than in the apex but had no effect on VERP in LQT1. EPS and optical mapping experiments demonstrated genotype-specific differences in AV conduction and ventricular refractoriness. The occurrence of infra-His blocks in LQT2 rabbits under isoflurane and intra-His block in LQT1 rabbits after dofetilide suggest differential regional sensitivities of the rabbit His-Purkinje system to drugs blocking IKr and IKs. PMID:20581090

  15. Effect of Atorvastatin-Eluting Stents in a Rabbit Iliac Artery Restenosis Model

    PubMed Central

    Lim, Kyung Seob; Bae, In Ho; Park, Jun-Kyu; Park, Dae Sung; Kim, Jong Min; Kim, Jung Ha; Cho, Dong Lyun; Sim, Doo Sun; Park, Keun-Ho; Hong, Young Joon; Ahn, Youngkeun

    2013-01-01

    Statins have pleiotropic effects, which include the inhibition of neointima hyperplasia, the inhibition of vascular inflammation, and platelet inhibition. The aim of this study was to examine the effect of an atorvastatin-eluting stent (AES) in a rabbit iliac artery overstretch restenosis model. Ten rabbits were used in this study (10 rabbits, 10 iliac arteries for each stent). An AES and paclitaxel-eluting stent (PES) were implanted in the left and right iliac arteries in a rabbit (2 stents in each rabbit). The stents were deployed with oversizing (stent/artery ratio 1.3:1), and histopathologic analysis was assessed at 28 days after stenting. There were no significant differences in the injury score, lumen area, or inflammation score. There were significant differences in the neointimal area (0.7±0.18 mm2 in the AES group vs. 0.4±0.25 mm2 in the PES group, p<0.01), in the percentage stenosis area (14.8±5.06% in the AES group vs. 10.5±6.80% in the PES group, p<0.05), and in the fibrin score (0.4±0.51 in the AES group vs. 2.7±0.48 in the PES group, p<0.001). Although the AES did not suppress neointimal hyperplasia compared with the PES, it showed a superior arterial healing effect in a rabbit iliac artery overstretch restenosis model. PMID:24400214

  16. Effects of FSH extracted from in vitro cultured anterior pituitary cells of male buffalo calves on body and testes weight, serum FSH and total cholesterol and hematological variables in male rabbits.

    PubMed

    Naveed, Muhammad Riaz; Ahmad, Nazir; Ahmad, Ijaz; Akhtar, Nafees; Ali, Shujait; Zubair, Muhammad; Murtaza, Saeed

    2014-11-30

    In this study, anterior pituitary glands were collected from 12 young male buffalo calves after slaughter, cultured with gonadotropin releasing hormone (GnRH) and estrogen stimulus and the extract obtained. Adult male rabbits (n = 15) were divided into three equal groups. Rabbits of Group A served as control; those of Groups B and C were given extract containing 4 and 8 mIU of follicle stimulating hormone (FSH), respectively twice daily for 3 weeks. Body weight of rabbits was recorded before and after treatment; blood samples were collected after treatment and analyzed for hemoglobin (Hb), red blood cell (RBC) count, white blood cell (WBC) count, packed cell volume (PCV), platelet counts, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH), while serum samples were analyzed for FSH and total cholesterol. Then, all rabbits were slaughtered, and weight of paired testes was recorded. Results showed that the values for weight gain, RBC count, WBC count, PCV and MCH did not differ among rabbits of three groups. Blood Hb was greater (P < 0.05) in rabbits of Group B than Group C. Testis weight, serum FSH, total cholesterol and blood platelets count were greater in rabbits of Groups B and C, while MCV was less in rabbits of Group C, compared to the control (P < 0.05). In conclusion, in vitro cultured cells of adenohypophysis from male buffalo calves showed FSH activity. This FSH increased testes size, serum FSH, total cholesterol and blood platelets counts and decreased MCV in rabbits. However, it had no effect on weight gain, RBC counts, WBC counts, PCV and MCH. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Molecular dynamics studies on the NMR structures of rabbit prion protein wild type and mutants: surface electrostatic charge distributions.

    PubMed

    Zhang, Jiapu; Wang, Feng; Zhang, Yuanli

    2015-01-01

    Prion diseases are invariably fatal and highly infectious neurodegenerative diseases that affect a wide variety of mammalian species such as sheep and goats, cattle, deer and elk, and humans. But for rabbits, studies have shown that they have a low susceptibility to be infected by prion diseases. This paper does molecular dynamics (MD) studies of rabbit NMR structures (of the wild type and its two mutants of two surface residues), in order to understand the specific mechanism of rabbit prion proteins (RaPrP(C)). Protein surface electrostatic charge distributions are specially focused to analyze the MD trajectories. This paper can conclude that surface electrostatic charge distributions indeed contribute to the structural stability of wild-type RaPrP(C); this may be useful for the medicinal treatment of prion diseases.

  18. EXTENDED STORAGE OF PLATELET-RICH PLASMA PREPARED PLATELET CONCENTRATES IN PLASMA OR PLASMALYTE

    PubMed Central

    Slichter, Sherrill J.; Bolgiano, Doug; Corson, Jill; Jones, Mary Kay; Christoffel, Todd

    2010-01-01

    Background Using bacterial detection or pathogen reduction, extended platelet storage may be licensed if platelet viability is maintained. FDA's post-storage platelet acceptance guidelines are that autologous stored platelet recoveries and survivals should be ≥66% and ≥58%, respectively, of each donor's fresh platelet data. Study Design And Methods Non-leukoreduced platelet concentrates were prepared from whole blood donations. Autologous platelet concentrates from 62 subjects were stored in 100% plasma (n=44) or 20% plasma/80% Plasmalyte (n=18), an acetate based, non-glucose containing crystalloid solution previously used for platelet storage.(1-3) Fresh platelets were obtained on the day the donor's stored platelets were to be transfused. The fresh and stored platelets were alternately radiolabeled with either 51Chromium or 111Indium, and in vitro measurements were performed on the stored platelets. Results FDA's platelet recovery criterion was met for 7 days of plasma storage, but platelet survivals maintained viability for only 6 days. Plasmalyte stored platelets did not meet either acceptance criteria after 6 days of storage. After 7 days of storage, platelet recoveries averaged 43 ± 4% and 30 ± 4% and survivals 4.1 ± 0.4 days and 2.0 ± 0.2 days for plasma and Plasmalyte-stored platelets, respectively (p=0.03 for recoveries and p<0.001 for survivals). Post-storage platelet recoveries correlated with the commonly-used in vitro platelet quality measurements of HSR and Annexin V binding, while survivals correlated with ESC, morphology score, and pH. Conclusion There is a progressive decrease in recoveries and survivals of plasma stored platelets over time. Platelet viability is better maintained in plasma than Plasmalyte. PMID:20456703

  19. Use of Platelet Rich Plasma in the Management of Periodontal Intra-Osseous Defects: A Clinical Study