The composite of bone marrow concentrate and PRP as an alternative to autologous bone grafting.

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Mohssen Hakimi

Full Text Available One possible alternative to the application of autologous bone grafts represents the use of autologous bone marrow concentrate (BMC. The purpose of our study was to evaluate the potency of autologous platelet-rich plasma (PRP in combination with BMC. In 32 mini-pigs a metaphyseal critical-size defect was surgically created at the proximal tibia. The animals were allocated to four treatment groups of eight animals each (1. BMC+CPG group, 2. BMC+CPG+PRP group, 3. autograft group, 4. CPG group. In the BMC+CPG group the defect was filled with autologous BMC in combination with calcium phosphate granules (CPG, whereas in the BMC+CPG+PRP group the defect was filled with the composite of autologous BMC, CPG and autologous PRP. In the autograft group the defect was filled with autologous cancellous graft, whereas in the CPG group the defect was filled with CPG solely. After 6 weeks radiological and histomorphometrical analysis showed significantly more new bone formation in the BMC+CPG+PRP group compared to the BMC+CPG group and the CPG group. There were no significant differences between the BMC+CPG+PRP group and the autograft group. In the PRP platelets were enriched significantly about 4.7-fold compared to native blood. In BMC the count of mononuclear cells increased significantly (3.5-fold compared to the bone marrow aspirate. This study demonstrates that the composite of BMC+CPG+PRP leads to a significantly higher bone regeneration of critical-size defects at the proximal tibia in mini-pigs than the use of BMC+CPG without PRP. Furthermore, within the limits of the present study the composite BMC+CPG+PRP represents a comparable alternative to autologous bone grafting.

The application of PRP combined with TCP in repairing avascular necrosis of the femoral head after femoral neck fracture in rabbit.

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Zhang, X-L; Wang, Y-M; Chu, K; Wang, Z-H; Liu, Y-H; Jiang, L-H; Chen, X; Zhou, Z-Y; Yin, G

2018-02-01

In view of the high occurrence of avascular necrosis of the femoral head (ANFH) after femoral neck fracture and the difficulties in the treatment, our work aimed to explore the effects of platelet-rich plasma (PRP) combined with tri-calcium phosphate (TCP) on the repair of ANFH after femoral neck fracture and to provide reference for clinical treatment. Thirty New Zealand white rabbits were randomly divided into control group, TCP group, and PRP+TCP group. The rabbit ANFH model was established and femoral head tissues were collected. HE staining was used for histological observation. Image analysis and statistical analysis were used to calculate the New Bone Area fraction (NBA %). The levels of bone morphogenetic protein (BMP)-7, transforming growth factor (TGF)-β1, basic fibroblast growth factor (bFGF), interleukin (IL)-6 and tumor necrosis factor (TNF)-a in serum were detected by Enzyme-Linked ImmunoSorbent Assay (ELISA). The new bone area of TCP group was significantly lower than that of PRP+TCP group (pPRP+TCP groups (pPRP+TCP group was higher than that in TCP group. TCP and PRP+TCP can both significantly reduce the content of IL-6 and TNF-a (pPRP+TCP group compared with the TCP group at 8 weeks after injection. PRP combined with TCP, which can promote new bone formation and inhibit inflammatory response, showed higher efficiency in repairing ANFH than internal fixation alone.

PrP N-terminal domain triggers PrPSc-like aggregation of Dpl

International Nuclear Information System (INIS)

Erlich, Paul; Cesbron, Jean-Yves; Lemaire-Vieille, Catherine; Curt, Aurelie; Andrieu, Jean-Pierre; Schoehn, Guy; Jamin, Marc; Gagnon, Jean

2008-01-01

Transmissible spongiform encephalopathies are fatal neurodegenerative disorders thought to be transmitted by self-perpetuating conformational conversion of a neuronal membrane glycoprotein (PrP C , for 'cellular prion protein') into an abnormal state (PrP Sc , for 'scrapie prion protein'). Doppel (Dpl) is a protein that shares significant biochemical and structural homology with PrP C . In contrast to its homologue PrP C , Dpl is unable to participate in prion disease progression or to achieve an abnormal PrP Sc -like state. We have constructed a chimeric mouse protein, composed of the N-terminal domain of PrP C (residues 23-125) and the C-terminal part of Dpl (residues 58-157). This chimeric protein displays PrP-like biochemical and structural features; when incubated in presence of NaCl, the α-helical monomer forms soluble β-sheet-rich oligomers which acquire partial resistance to pepsin proteolysis in vitro, as do PrP oligomers. Moreover, the presence of aggregates akin to protofibrils is observed in soluble oligomeric species by electron microscopy

Early Delivery of Misfolded PrP from ER to Lysosomes by Autophagy

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Cortes, Constanza J.; Qin, Kefeng; Norstrom, Eric M.; Green, William N.; Bindokas, Vytautas P.; Mastrianni, James A.

2013-01-01

Prion diseases are linked to the accumulation of a misfolded isoform (PrPSc) of prion protein (PrP). Evidence suggests that lysosomes are degradation endpoints and sites of the accumulation of PrPSc. We questioned whether lysosomes participate in the early quality control of newly generated misfolded PrP. We found PrP carrying the disease-associated T182A mutation (Mut-PrP) was delivered to lysosomes in a Golgi-independent manner. Time-lapse live cell imaging revealed early formation and uptake of GFP-tagged Mut-PrP aggregates into LysoTracker labeled vesicles. Compared with Wt-PrP, Mut-PrP expression was associated with an elevation in several markers of the autophagy-lysosomal pathway, and it extensively colocalized with the autophagosome-specific marker, LC3B. In autophagy deficient (ATG5−/−) mouse embryonic fibroblasts, or in normal cells treated with the autophagy-inhibitor 3-MA, Mut-PrP colocalization with lysosomes was reduced to a similar extent. Additionally, 3-MA selectively impaired the degradation of insoluble Mut-PrP, resulting in an increase in protease-resistant PrP, whereas the induction of autophagy by rapamycin reduced it. These findings suggest that autophagy might function as a quality control mechanism to limit the accumulation of misfolded PrP that normally leads to the generation of PrPSc. PMID:24454378

Purification and Fibrillation of Full-Length Recombinant PrP.

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Makarava, Natallia; Savtchenko, Regina; Baskakov, Ilia V

2017-01-01

Misfolding and aggregation of prion protein are related to several neurodegenerative diseases in humans such as Creutzfeldt-Jakob disease, fatal familial insomnia, and Gerstmann-Straussler-Scheinker disease. A growing number of applications in the prion field including assays for detection of PrP Sc and methods for production of PrP Sc de novo require recombinant prion protein (PrP) of high purity and quality. Here, we report an experimental procedure for expression and purification of full-length mammalian prion protein. This protocol has been proved to yield PrP of extremely high purity that lacks PrP adducts, oxidative modifications, or truncation, which is typically generated as a result of spontaneous oxidation or degradation. We also describe methods for preparation of amyloid fibrils from recombinant PrP in vitro. Recombinant PrP fibrils can be used as a noninfectious synthetic surrogate of PrP Sc for development of prion diagnostics including generation of PrP Sc -specific antibody.

CD36 participates in PrP(106-126-induced activation of microglia.

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Mohammed Kouadir

Full Text Available Microglial activation is a characteristic feature of the pathogenesis of prion diseases. The molecular mechanisms that underlie prion-induced microglial activation are not very well understood. In the present study, we investigated the role of the class B scavenger receptor CD36 in microglial activation induced by neurotoxic prion protein (PrP fragment 106-126 (PrP(106-126. We first examined the time course of CD36 mRNA expression upon exposure to PrP(106-126 in BV2 microglia. We then analyzed different parameters of microglial activation in PrP(106-126-treated cells in the presence or not of anti-CD36 monoclonal antibody (mAb. The cells were first incubated for 1 h with CD36 monoclonal antibody to block the CD36 receptor, and were then treated with neurotoxic prion peptides PrP(106-126. The results showed that PrP(106-126 treatment led to a rapid yet transitory increase in the mRNA expression of CD36, upregulated mRNA and protein levels of proinflammatory cytokines (IL-1β, IL-6 and TNF-α, increased iNOS expression and nitric oxide (NO production, stimulated the activation of NF-κB and caspase-1, and elevated Fyn activity. The blockade of CD36 had no effect on PrP(106-126-stimulated NF-κB activation and TNF-α protein release, abrogated the PrP(106-126-induced iNOS stimulation, downregulated IL-1β and IL-6 expression at both mRNA and protein levels as well as TNF-α mRNA expression, decreased NO production and Fyn phosphorylation, reduced caspase-1 cleavage induced by moderate PrP(106-126-treatment, but had no effect on caspase-1 activation after treatment with a high concentration of PrP(106-126. Together, these results suggest that CD36 is involved in PrP(106-126-induced microglial activation and that the participation of CD36 in the interaction between PrP(106-126 and microglia may be mediated by Src tyrosine kinases. Our findings provide new insights into the mechanisms underlying the activation of microglia by neurotoxic prion peptides

Long-term trends in invasive Haemophilus influenzae type B disease among indigenous Australian children following use of PRP-OMP and PRP-T vaccines.

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Menzies, Robert Ian; Bremner, Kyla Margaret; Wang, Han; Beard, Frank Hudson; McIntyre, Peter Bruce

2015-06-01

Among indigenous populations with high incidence and early onset of invasive Haemophilus influenzae type b (Hib) disease, PRP-OMP vaccines are used in the United States and PRP-T vaccines in Canada. In Australia, PRP-OMP vaccines were exclusively used in indigenous children from 1993 until they were replaced by PRP-T between late 2005 and 2009. Analytic descriptive study of 20 years of enhanced surveillance data (1993-2013) for invasive Hib disease in Australian children PRP-OMP period (1993-1996) to 6.2 (95% CI: 4.0, 9.2) and 4.7 (95% CI: 1.7, 10.3) in the later PRP-OMP (1996-2009) and PRP-T periods (2009-2013), respectively. The indigenous:nonindigenous incidence rate ratio increased to 43 (95% CI: 16, 145) and 58 (95% CI: 7, 2660) in the later PRP-OMP and PRP-T periods, respectively, more than 10-fold higher than in lesser-incidence Australian regions. We found no change in Hib incidence among indigenous Australian children living in high-incidence regions in the first 4 years following a change to PRP-T-containing combination vaccines. This may be of relevance to North American indigenous populations characterized by suboptimal living conditions and young age of onset for whom PRP-OMP continues to be recommended, such as Alaska Natives.

PRP and Articular Cartilage: A Clinical Update

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Rossi, Roberto; Castoldi, Filippo; Michielon, Gianni

2015-01-01

The convincing background of the recent studies, investigating the different potentials of platelet-rich plasma, offers the clinician an appealing alternative for the treatment of cartilage lesions and osteoarthritis. Recent evidences in literature have shown that PRP may be helpful both as an adjuvant for surgical treatment of cartilage defects and as a therapeutic tool by intra-articular injection in patients affected by osteoarthritis. In this review, the authors introduce the trophic and anti-inflammatory properties of PRP and the different products of the available platelet concentrates. Then, in a complex scenario made of a great number of clinical variables, they resume the current literature on the PRP applications in cartilage surgery as well as the use of intra-articular PRP injections for the conservative treatment of cartilage degenerative lesions and osteoarthritis in humans, available as both case series and comparative studies. The result of this review confirms the fascinating biological role of PRP, although many aspects yet remain to be clarified and the use of PRP in a clinical setting has to be considered still exploratory. PMID:26075244

PRP and Articular Cartilage: A Clinical Update

Directory of Open Access Journals (Sweden)

Antonio Marmotti

2015-01-01

Full Text Available The convincing background of the recent studies, investigating the different potentials of platelet-rich plasma, offers the clinician an appealing alternative for the treatment of cartilage lesions and osteoarthritis. Recent evidences in literature have shown that PRP may be helpful both as an adjuvant for surgical treatment of cartilage defects and as a therapeutic tool by intra-articular injection in patients affected by osteoarthritis. In this review, the authors introduce the trophic and anti-inflammatory properties of PRP and the different products of the available platelet concentrates. Then, in a complex scenario made of a great number of clinical variables, they resume the current literature on the PRP applications in cartilage surgery as well as the use of intra-articular PRP injections for the conservative treatment of cartilage degenerative lesions and osteoarthritis in humans, available as both case series and comparative studies. The result of this review confirms the fascinating biological role of PRP, although many aspects yet remain to be clarified and the use of PRP in a clinical setting has to be considered still exploratory.

Experimental Models of Inherited PrP Prion Diseases.

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Watts, Joel C; Prusiner, Stanley B

2017-11-01

The inherited prion protein (PrP) prion disorders, which include familial Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease, and fatal familial insomnia, constitute ∼10%-15% of all PrP prion disease cases in humans. Attempts to generate animal models of these disorders using transgenic mice expressing mutant PrP have produced variable results. Although many lines of mice develop spontaneous signs of neurological illness with accompanying prion disease-specific neuropathological changes, others do not. Furthermore, demonstrating the presence of protease-resistant PrP species and prion infectivity-two of the hallmarks of the PrP prion disorders-in the brains of spontaneously sick mice has proven particularly challenging. Here, we review the progress that has been made toward developing accurate mouse models of the inherited PrP prion disorders. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Portable Radiation Package (PRP) Instrument Handbook

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Reynolds, R Michael [Remote Measurements and Research Company, Seattle, WA (United States)

2017-08-03

The Portable Radiation Package (PRP) was developed to provide basic radiation information in locations such as ships at sea where proper exposure is remote and difficult, the platform is in motion, and azimuth alignment is not fixed. Development of the PRP began at Brookhaven National Laboratory (BNL) in the mid-1990s and versions of it were deployed on ships in the U.S. Department of Energy (DOE) Atmospheric Radiation Measurement (ARM) Climate Research Facility’s Nauru-99 project. The PRP was deployed on ships in support of the National Aeronautics and Space Administration (NASA) Sensor Intercomparison for Marine Biological and Interdisciplinary Ocean Studies (SIMBIOS) program. Over the years the measurements have remained the same while the post-processing data analysis, especially for the FRSR, has evolved. This document describes the next-generation Portable Radiation Package (PRP2) that was developed for the DOE ARM Facility, under contract no. 9F-31462 from Argonne National Laboratory (ANL). The PRP2 has the same scientific principles that were well validated in prior studies, but has upgraded electronic hardware. The PRP2 approach is completely modular, both in hardware and software. Each sensor input is treated as a separate serial stream into the data collection computer. In this way the operator has complete access to each component of the system for purposes of error checking, calibration, and maintenance. The resulting system is more reliable, easier to install in complex situations, and more amenable to upgrade.

Periodontal tissue regeneration with PRP incorporated gelatin hydrogel sponges

International Nuclear Information System (INIS)

Nakajima, Dai; Tabata, Yasuhiko; Sato, Soh

2015-01-01

Gelatin hydrogels have been designed and prepared for the controlled release of the transforming growth factor (TGF-b1) and the platelet-derived growth factor (PDGF-BB). PRP (Platelet rich plasma) contains many growth factors including the PDGF and TGF-b1. The objective of this study was to evaluate the regeneration of periodontal tissue following the controlled release of growth factors in PRP. For the periodontal ligament cells and osteoblast, PRP of different concentrations was added. The assessment of DNA, mitochondrial activity and ALP activity were measured. To evaluate the TGF-β1 release from PRP incorporated gelatin sponge, amounts of TGF-β1 in each supernatant sample were determined by the ELISA. Transplantation experiments to prepare a bone defect in a rat alveolar bone were an implanted gelatin sponge incorporated with different concentration PRP. In DNA assay and MTT assay, after the addition of PRP to the periodontal ligament cells and osteoblast, the cell count and mitochondrial activity had increased the most in the group with the addition of 5  ×  PRP. In the ALP assay, after the addition of PRP to the periodontal ligament cells, the cell activity had increased the most in the group with the addition of 3  ×  PRP. In the transplantation, the size of the bone regenerated in the defect with 3  ×  PRP incorporated gelatin sponge was larger than that of the other group. (paper)

Periodontal tissue regeneration with PRP incorporated gelatin hydrogel sponges.

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Nakajima, Dai; Tabata, Yasuhiko; Sato, Soh

2015-10-20

Gelatin hydrogels have been designed and prepared for the controlled release of the transforming growth factor (TGF-b1) and the platelet-derived growth factor (PDGF-BB). PRP (Platelet rich plasma) contains many growth factors including the PDGF and TGF-b1. The objective of this study was to evaluate the regeneration of periodontal tissue following the controlled release of growth factors in PRP. For the periodontal ligament cells and osteoblast, PRP of different concentrations was added. The assessment of DNA, mitochondrial activity and ALP activity were measured. To evaluate the TGF-β1 release from PRP incorporated gelatin sponge, amounts of TGF-β1 in each supernatant sample were determined by the ELISA. Transplantation experiments to prepare a bone defect in a rat alveolar bone were an implanted gelatin sponge incorporated with different concentration PRP. In DNA assay and MTT assay, after the addition of PRP to the periodontal ligament cells and osteoblast, the cell count and mitochondrial activity had increased the most in the group with the addition of 5  ×  PRP. In the ALP assay, after the addition of PRP to the periodontal ligament cells, the cell activity had increased the most in the group with the addition of 3  ×  PRP. In the transplantation, the size of the bone regenerated in the defect with 3  ×  PRP incorporated gelatin sponge was larger than that of the other group.

Redox induces diverse effects on recombinant human wild-type PrP and mutated PrP with inserted or deleted octarepeats.

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Shi, Qi; Chen, Cao; Zhang, Bao-Yun; Zhou, Wei; Xiao, Kang; Dong, Xiao-Ping

2018-04-01

Normal prion protein (PrP) contains two cysteines at amino acids 179 and 214, which may form intra‑ and interpeptide disulfide bonds. To determine the possible effects of this disulfide bridge on the biochemical features of PrP, prokaryotic recombinant human wild‑type PrP (PG5), and mutated PrPs with seven extra octarepeats (PG12) or with all five octarepeats removed (PG0), were subjected to redox in vitro. Sedimentation assays revealed a large portion of aggregation in redox‑treated PG5, but not in PG0 and PG12. Circular dichroism analysis detected increased β‑sheet and decreased α‑helix in PG5 subjected to redox, increased random‑coil and decreased β‑sheet in PG0, and increased random‑coil, but limited changes to β‑sheet content, in PG12. Thioflavin T fluorescence tests indicated that fluorescent value was increased in PG5 subjected to redox. In addition, proteinase K (PK) digestions indicated that PK resistance was stronger in PG12 and PG0 compared with in PG5; redox enhanced the PK resistance of all three PrP constructs, particularly PG0 and PG12. These data indicated that formation of a disulfide bond induces marked alterations in the secondary structure and biochemical characteristics of PrP. In addition, the octarepeat region within the PrP peptide markedly influences the effects of redox on the biochemical phenotypes of PrP, thus highlighting the importance of the number of octarepeats in the biological functions of PrP.

Glycan-deficient PrP stimulates VEGFR2 signaling via glycosaminoglycan.

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Gao, Zhenxing; Zhang, Huixia; Hu, Fei; Yang, Liheng; Yang, Xiaowen; Zhu, Ying; Sy, Man-Sun; Li, Chaoyang

2016-06-01

Whether the two N-linked glycans are important in prion, PrP, biology is unresolved. In Chinese hamster ovary (CHO) cells, the two glycans are clearly not important in the cell surface expression of transfected human PrP. Compared to fully-glycosylated PrP, glycan-deficient PrP preferentially partitions to lipid raft. In CHO cells glycan-deficient PrP also interacts with glycosaminoglycan (GAG) and vascular endothelial growth factor receptor 2 (VEGFR2), resulting in VEGFR2 activation and enhanced Akt phosphorylation. Accordingly, CHO cells expressing glycan-deficient PrP lacking the GAG binding motif or cells treated with heparinase to remove GAG show diminished Akt signaling. Being in lipid raft is critical, chimeric glycan-deficient PrP with CD4 transmembrane and cytoplasmic domains is absent in lipid raft and does not activate Akt signaling. CHO cells bearing glycan-deficient PrP also exhibit enhanced cellular adhesion and migration. Based on these findings, we propose a model in which glycan-deficient PrP, GAG, and VEGFR2 interact, activating VEGFR2 and resulting in changes in cellular behavior. Copyright © 2016 Elsevier Inc. All rights reserved.

PRP in OA knee - update, current confusions and future options.

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Dhillon, Mandeep S; Patel, Sandeep; John, Rakesh

2017-01-01

Positive results have been uniformly observed by various researchers for platelet-rich plasma (PRP) in early osteoarthritis (OA) knee in the past few years. PRP has clearly demonstrated its supremacy in comparison to hyaluronic acid (HA) and placebo in various clinical trials and is undoubtedly the best option available for symptomatic treatment in early OA. The release of growth factors from PRP occurs immediately and lasts for around three weeks and the clinical effect tends to wane down by the end of the year. Prolonged and sustained release of growth factors from platelets could possibly help in much better biological healing and sustained clinical effects. PRP in combination with biocompatible carriers could be one way of achieving this. Gelatin hydrogel PRP and chitosan PRP seem to be promising based on early in vitro studies and animal studies. PRP in combination with hyaluronic acid also seems to be additive. This article intends to discuss the present status of the PRP, confusions surrounding its use, upcoming trends and ideas for improvising PRP for use early OA knees based on available evidence. © The Authors, published by EDP Sciences, 2017.

Purification and Fibrillation of Full-Length Recombinant PrP

OpenAIRE

Makarava, Natallia; Baskakov, Ilia V.

2012-01-01

Misfolding and aggregation of prion protein (PrP) is related to several neurodegenerative diseases in humans such as Creutzfeldt–Jacob disease, fatal familial insomnia, and Gerstmann–Straussler–Sheinker disease. Certain applications in prion area require recombinant PrP of high purity and quality. Here, we report an experimental procedure for expression and purification of full-length mammalian PrP. This protocol has been proved to yield PrP of extremely high purity that lac...

Effects of platelet rich plasma (PRP) on human gingival fibroblast, osteoblast and periodontal ligament cell behaviour.

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Kobayashi, Eizaburo; Fujioka-Kobayashi, Masako; Sculean, Anton; Chappuis, Vivianne; Buser, Daniel; Schaller, Benoit; Dőri, Ferenc; Miron, Richard J

2017-06-02

The use of platelet rich plasma (PRP, GLO) has been used as an adjunct to various regenerative dental procedures. The aim of the present study was to characterize the influence of PRP on human gingival fibroblasts, periodontal ligament (PDL) cells and osteoblast cell behavior in vitro. Human gingival fibroblasts, PDL cells and osteoblasts were cultured with conditioned media from PRP and investigated for cell migration, proliferation and collagen1 (COL1) immunostaining. Furthermore, gingival fibroblasts were tested for genes encoding TGF-β, PDGF and COL1a whereas PDL cells and osteoblasts were additionally tested for alkaline phosphatase (ALP) activity, alizarin red staining and mRNA levels of osteoblast differentiation markers including Runx2, COL1a2, ALP and osteocalcin (OCN). It was first found that PRP significantly increased cell migration of all cells up to 4 fold. Furthermore, PRP increased cell proliferation at 3 and 5 days of gingival fibroblasts, and at 3 days for PDL cells, whereas no effect was observed on osteoblasts. Gingival fibroblasts cultured with PRP increased TGF-β, PDGF-B and COL1 mRNA levels at 7 days and further increased over 3-fold COL1 staining at 14 days. PDL cells cultured with PRP increased Runx2 mRNA levels but significantly down-regulated OCN mRNA levels at 3 days. No differences in COL1 staining or ALP staining were observed in PDL cells. Furthermore, PRP decreased mineralization of PDL cells at 14 days post seeding as assessed by alizarin red staining. In osteoblasts, PRP increased COL1 staining at 14 days, increased COL1 and ALP at 3 days, as well as increased ALP staining at 14 days. No significant differences were observed for alizarin red staining of osteoblasts following culture with PRP. The results demonstrate that PRP promoted gingival fibroblast migration, proliferation and mRNA expression of pro-wound healing molecules. While PRP induced PDL cells and osteoblast migration and proliferation, it tended to have

The differential effects of leukocyte-containing and pure platelet-rich plasma (PRP) on tendon stem/progenitor cells - implications of PRP application for the clinical treatment of tendon injuries.

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Zhou, Yiqin; Zhang, Jianying; Wu, Haishan; Hogan, MaCalus V; Wang, James H-C

2015-09-15

Platelet-rich plasma (PRP) is widely used to treat tendon injuries in clinics. These PRP preparations often contain white blood cells or leukocytes, and the precise cellular effects of leukocyte-rich PRP (L-PRP) on tendons are not well defined. Therefore, in this study, we determined the effects of L-PRP on tendon stem/progenitor cells (TSCs), which play a key role in tendon homeostasis and repair. TSCs isolated from the patellar tendons of rabbits were treated with L-PRP or P-PRP (pure PRP without leukocytes) in vitro, followed by measuring cell proliferation, stem cell marker expression, inflammatory gene expression, and anabolic and catabolic protein expression by using immunostaining, quantitative real-time polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay, respectively. Cell proliferation was induced by both L-PRP and P-PRP in a dose-dependent manner with maximum proliferation at a 10 % PRP dose. Both PRP treatments also induced differentiation of TSCs into active tenocytes. Nevertheless, the two types of PRP largely differed in several effects exerted on TSCs. L-PRP induced predominantly catabolic and inflammatory changes in differentiated tenocytes; its treatment increased the expression of catabolic marker genes, matrix metalloproteinase-1 (MMP-1), MMP-13, interleukin-1beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α), and their respective protein expression and prostaglandin E2 (PGE 2) production. In contrast, P-PRP mainly induced anabolic changes; that is, P-PRP increased the gene expression of anabolic genes, alpha-smooth muscle actin (α-SMA), collagen types I and III. These findings indicate that, while both L-PRP and P-PRP appear to be "safe" in inducing TSC differentiation into active tenocytes, L-PRP may be detrimental to the healing of injured tendons because it induces catabolic and inflammatory effects on tendon cells and may prolong the effects in healing tendons. On the other hand, when P-PRP is used to

Interaction between 14-3-3β and PrP influences the dimerization of 14-3-3 and fibrillization of PrP106-126.

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Han, Jun; Song, Qin-Qin; Sun, Peng; Zhang, Jin; Wang, Xu; Song, Juan; Li, Gong-Qi; Liu, Ying-Hui; Mei, Guo-Yong; Shi, Qi; Tian, Chan; Chen, Cao; Gao, Chen; Zhao, Bo; Dong, Xiao-Ping

2014-02-01

Proteins of the 14-3-3 family are universal participate in multiple cellular processes. However, their exact role in the pathogenesis of prion diseases remains unclear. In this study, we proposed that human PrP was able to form molecular complex with 14-3-3β. The domains responsible for the interactions between PrP and 14-3-3β were mapped at the segments of amino acid (aa) residues 106-126 within PrP and aa 1-38 within 14-3-3β. Homology modeling revealed that the key aa residues for molecular interaction were D22 and D23 in 14-3-3β as well as K110 in PrP. Mutations in these aa residues inhibited the interaction between the two proteins in vitro. Our results also showed that recombinant PrP encouraged 14-3-3β dimer formation, whereas PrP106-126 peptide inhibited it. Recombinant 14-3-3β disaggregated the mature PrP106-126 fibrils in vitro. Moreover, the PrP-14-3-3 protein complexes were observed in the brain tissues of normal and scrapie agent 263K infected hamsters. Colocalization of PrP and 14-3-3 was seen in the cytoplasm of human neuroblastoma cell line SH-SY5Y, as well as human cervical cancer cell line HeLa transiently expressing full-length human PrP. Our current data suggest the neuroprotection of PrPC and neuron damage caused by PrPSc may be associated with their functions of 14-3-3 dimerization regulation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Platelet-rich plasma (PRP) treatment of sports-related severe acute hamstring injuries.

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Guillodo, Yannick; Madouas, Gwénaelle; Simon, Thomas; Le Dauphin, Hermine; Saraux, Alain

2015-01-01

hamstring injury is the most common musculoskeletal disorder and one of the main causes of missed sporting events. Shortening the time to return to play (TTRTP) is a priority for athletes and sports medicine practitioners. platelet-rich plasma (PRP) injection at the site of severe acute hamstring injury increases the healing rate and shortens the TTRTP. Cohort study. all patients with ultrasonography and MRI evidence of severe acute hamstring injury between January 2012 and March 2014 were offered PRP treatment. Those who accepted received a single intramuscular PRP injection within 8 days post-injury; the other patients served as controls. The same standardized rehabilitation program was used in both groups. A physical examination and ultrasonography were performed 10 and 30 days post-injury, then a phone interview 120 days post-injury, to determine the TTRTP at the pre-injury level. of 34 patients, 15 received PRP and 19 did not. Mean TTRTP at the pre-injury level was 50.9±10.7 days in the PRP group and 52.8±15.7 days in the control group. The difference was not statistically significant. a single intramuscular PRP injection did not shorten the TTRTP in sports people with severe acute hamstring injuries.

Kartogenin with PRP promotes the formation of fibrocartilage zone in the tendon-bone interface.

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Zhou, Yiqin; Zhang, Jianying; Yang, Jinsong; Narava, Manoj; Zhao, Guangyi; Yuan, Ting; Wu, Haishan; Zheng, Nigel; Hogan, MaCalus V; Wang, James H-C

2017-12-01

Treatment of tendon-bone junction injuries is a challenge because tendon-bone interface often heals poorly and the fibrocartilage zone, which reduces stress concentration, at the interface is not formed. In this study, we used a compound called kartogenin (KGN) with platelet-rich plasma (PRP) to induce the formation of fibrocartilage zone in a rat tendon graft-bone tunnel model. The experimental rats received KGN-PRP or PRP injections in the tendon graft-bone tunnel interface. The control group received saline. After 4, 8 and 12 weeks, Safranin O staining of the tendon graft-bone tunnels revealed abundant proteoglycans in the KGN-PRP group indicating the formation of cartilage-like transition zone. Immunohistochemical and immuno-fluorescence staining revealed collagen types I (Col-I) and II (Col-II) in the newly formed fibrocartilage zone. Both fibrocartilage zone formation and maturation were healing time dependent. In contrast, the PRP and saline control groups had no cartilage-like tissues and minimal Col-I and Col-II staining. Some gaps were also present in the saline control group. Finally, pull-out strength in the KGN-PRP-treated group at 8 weeks was 1.4-fold higher than the PRP-treated group and 1.6-fold higher than the saline control group. These findings indicate that KGN, with PRP as a carrier, promotes the formation of fibrocartilage zone between the tendon graft and bone interface. Thus, KGN-PRP may be used as a convenient cell-free therapy in clinics to promote fibrocartilage zone formation in rotator calf repair and anterior cruciate ligament reconstruction, thereby enhancing the mechanical strength of the tendon-bone interface and hence the clinical outcome of these procedures. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Identification of PrP sequences essential for the interaction between the PrP polymers and Aβ peptide in a yeast-based assay

OpenAIRE

Rubel, Aleksandr A; Ryzhova, Tatyana A; Antonets, Kirill S; Chernoff, Yury O; Galkin, Alexey P

2013-01-01

Alzheimer disease is associated with the accumulation of oligomeric amyloid β peptide (Aβ), accompanied by synaptic dysfunction and neuronal death. Polymeric form of prion protein (PrP), PrPSc, is implicated in transmissible spongiform encephalopathies (TSEs). Recently, it was shown that the monomeric cellular form of PrP (PrPC), located on the neuron surface, binds Aβ oligomers (and possibly other β-rich conformers) via the PrP23–27 and PrP90–110 segments, acting as Aβ receptor. On the other...

PRP as an Adjunct to Rotator Cuff Tendon Repair.

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Barber, F Alan

2018-06-01

Arthroscopic rotator cuff repair is a commonly performed repair. Technical developments provide surgeons the tools to create biomechanically robust repairs. How can the biological response mirror the strong and stable surgery? Platelet-rich plasma (PRP) is a supraphysiological platelet concentration which may positively augment rotator cuff healing. Not all PRPs are the same. High leukocyte levels and thrombin activation may be detrimental to tendon healing. Thrombin activation triggers an immediate release of growth factors and may actually inhibit some parts of the healing response. Clear differences exist between liquid PRP (products released within hours after activation) and solid fibrin PRP which slowly releases factors over days. The heterogenicity data and grouping liquid and solid PRP together make systematic reviews confusing. Solid PRP fibrin constructs are often associated with increased tendon healing. PRP fibrin matrix offers the greatest promise for improving clinical success after rotator cuff tendon repair.

Lumbar Intradiskal Platelet-Rich Plasma (PRP) Injections: A Prospective, Double-Blind, Randomized Controlled Study.

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Tuakli-Wosornu, Yetsa A; Terry, Alon; Boachie-Adjei, Kwadwo; Harrison, Julian R; Gribbin, Caitlin K; LaSalle, Elizabeth E; Nguyen, Joseph T; Solomon, Jennifer L; Lutz, Gregory E

2016-01-01

To determine whether single injections of autologous platelet-rich plasma (PRP) into symptomatic degenerative intervertebral disks will improve participant-reported pain and function. Prospective, double-blind, randomized controlled study. Outpatient physiatric spine practice. Adults with chronic (≥6 months), moderate-to-severe lumbar diskogenic pain that was unresponsive to conservative treatment. Participants were randomized to receive intradiskal PRP or contrast agent after provocative diskography. Data on pain, physical function, and participant satisfaction were collected at 1 week, 4 weeks, 8 weeks, 6 months, and 1 year. Participants in the control group who did not improve at 8 weeks were offered the option to receive PRP and subsequently followed. Functional Rating Index (FRI), Numeric Rating Scale (NRS) for pain, the pain and physical function domains of the 36-item Short Form Health Survey, and the modified North American Spine Society (NASS) Outcome Questionnaire were used. Forty-seven participants (29 in the treatment group, 18 in the control group) were analyzed by an independent observer with a 92% follow-up rate. Over 8 weeks of follow-up, there were statistically significant improvements in participants who received intradiskal PRP with regards to pain (NRS Best Pain) (P = .02), function (FRI) (P = .03), and patient satisfaction (NASS Outcome Questionnaire) (P = .01) compared with controls. No adverse events of disk space infection, neurologic injury, or progressive herniation were reported following the injection of PRP. Participants who received intradiskal PRP showed significant improvements in FRI, NRS Best Pain, and NASS patient satisfaction scores over 8 weeks compared with controls. Those who received PRP maintained significant improvements in FRI scores through at least 1 year of follow-up. Although these results are promising, further studies are needed to define the subset of participants most likely to respond to biologic intradiskal

DEPA classification: a proposal for standardising PRP use and a retrospective application of available devices.

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Magalon, J; Chateau, A L; Bertrand, B; Louis, M L; Silvestre, A; Giraudo, L; Veran, J; Sabatier, F

2016-01-01

Significant biological differences in platelet-rich plasma (PRP) preparations have been highlighted and could explain the large variability in the clinical benefit of PRP reported in the literature. The scientific community now recommends the use of classification for PRP injection; however, these classifications are focused on platelet and leucocyte concentrations. This presents the disadvantages of (1) not taking into account the final volume of the preparation; (2) omitting the presence of red blood cells in PRP and (3) not assessing the efficiency of production. On the basis of standards classically used in the Cell Therapy field, we propose the DEPA (Dose of injected platelets, Efficiency of production, Purity of the PRP, Activation of the PRP) classification to extend the characterisation of the injected PRP preparation. We retrospectively applied this classification on 20 PRP preparations for which biological characteristics were available in the literature. Dose of injected platelets varies from 0.21 to 5.43 billion, corresponding to a 25-fold increase. Only a Magellan device was able to obtain an A score for this parameter. Assessments of the efficiency of production reveal that no device is able to recover more than 90% of platelets from the blood. Purity of the preparation reveals that a majority of the preparations are contaminated by red blood cells as only three devices reach an A score for this parameter, corresponding to a percentage of platelets compared with red blood cells and leucocytes over 90%. These findings should provide significant help to clinicians in selecting a system that meets their specific needs for a given indication.

Effect of platelet-rich plasma (PRP) concentration on proliferation, neurotrophic function and migration of Schwann cells in vitro.

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Zheng, Canbin; Zhu, Qingtang; Liu, Xiaolin; Huang, Xijun; He, Caifeng; Jiang, Li; Quan, Daping; Zhou, Xiang; Zhu, Zhaowei

2016-05-01

Platelet-rich plasma (PRP) contains various growth factors and appears to have the potential to promote peripheral nerve regeneration, but evidence is lacking regarding its biological effect on Schwann cells (SCs). The present study was designed to investigate the effect of PRP concentration on SCs in order to determine the plausibility of using this plasma-derived therapy for peripheral nerve injury. PRP was obtained from rats by double-step centrifugation and was characterized by determining platelet numbers and growth factor concentrations. Primary cultures of rat SCs were exposed to various concentrations of PRP (40%, 20%, 10%, 5% and 2.5%). Cell proliferation assays and flow cytometry were performed to study to assess SC proliferation. Quantitative real-time PCR and ELISA analysis were performed to determine the ability of PRP to induce SCs to produce nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF). Microchemotaxis assay was used to analyse the cell migration capacity. The results obtained indicated that the platelet concentration and growth factors in our PRP preparations were significantly higher than in whole blood. Cell culture experiments showed that 2.5-20% PRP significantly stimulated SC proliferation and migration compared to untreated controls in a dose-dependent manner. In addition, the expression and secretion of NGF and GDNF were significantly increased. However, the above effects of SCs were suppressed by high PRP concentrations (40%). In conclusion, the appropriate concentration of PRP had the potency to stimulate cell proliferation, induced the synthesis of neurotrophic factors and significantly increased migration of SCs dose-dependently. Copyright © 2013 John Wiley & Sons, Ltd. Copyright © 2013 John Wiley & Sons, Ltd.

Impact of local anaesthetics and needle calibres used for painless PRP injections on platelet functionality.

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Bausset, Olivier; Magalon, Jeremy; Giraudo, Laurent; Louis, Marie-Laure; Serratrice, Nicolas; Frere, Corrine; Magalon, Guy; Dignat-George, Françoise; Sabatier, Florence

2014-01-01

The platelet-rich plasma (PRP) is an autologous biotherapy commonly used for its healing properties. Once activated, platelets released a real "cocktail" of growth factor and cytokines implied in numerous regenerative processes. However the impact of medical practices associated to PRP therapeutic use on platelets functionality remains poorly known. we evaluated the in vitro effects of two commonly used local anesthetics (Xylocaine(*) and Naropin(*)) on PRP functionality. We also investigated the quantity and quality of PRP that passed through the smallest gauge needle commercialized. PRP from 9 healthy volunteers were prepared using our previously described home made purification protocol. Platelet aggregation capacity was evaluated by aggregometry assays and the growth factor release was determined by ELISA after platelet activation. We also evaluated the platelet activation status, reactivity and stability of platelets by flow cytometry using the P-selectin expression marker. the association of local anaesthetics with PRP injections resulted in a significant decrease of platelets functionality, assessed by their capacity of aggregating. Local anaesthetics did not interfere with the growth factor release. The different needle sizes and calibres tested for PRP injections did not influence the platelet functionality. the use of local anaesthetics to prevent pain during PRP injections could compromise the therapeutic potential of PRP. These results suggest using carefully local anaesthetics or limiting their use as often is possible. To minimize injection pain, we recommend using 30 G needles. These data will lead to clinical recommendations for painless and controlled PRP injections.

Comparison of the effect of activated or non-activated PRP in various concentrations on osteoblast and fibroblast cell line proliferation.

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Vahabi, Surena; Yadegari, Zahra; Mohammad-Rahimi, Hossein

2017-09-01

Platelet-rich plasma (PRP) contains growth factors which positively affect cell proliferation, cell differentiation, chemotaxis and intracellular matrix synthesis. All these processes are involved in wound healing and tissue regeneration; thus, PRP as a source of growth factors can be used in periodontal regenerative therapies. The purpose of the present study was to assess the effect of various concentrations of activated and non-activated PRP on proliferation of osteoblasts and fibroblasts in vitro. PRP was obtained from three healthy volunteers. 75, 50, 25, and 10% concentrations of f PRP were prepared by dilution in Dulbecco's modified Eagle's medium. In activated PRP groups, PRP concentrations were activated by adding calcium gluconate. Human gingival fibroblast (HGF) cell line and MG-63 (osteosarcoma) human osteoblast-like cell line were used in the study. The MTT proliferation assay was used to assess the effect of different types of PRP concentrates on proliferation of HGF and MG-63 cells, in 24, 48 and 72 h. After 24, 48, and 72 h, the proliferation rate of both cell lines was higher in the positive control group, except in 72 h in HGF cell lines, that 10% non-activated PRP group and 10 and 25% activated PRP groups has higher proliferation rate than the positive control group, which it was not significant. Proliferation rate in cells with 10% activated PRP was highest among samples containing PRP. The current study failed to show the significant effect of activated or non-activated PRP on proliferation of HGFs or MG-63 osteoblast-like cells. However, our results showed that activated PRP had a greater effect than non-activated PRP.

PrP aggregation can be seeded by pre-formed recombinant PrP amyloid fibrils without the replication of infectious prions.

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Barron, Rona M; King, Declan; Jeffrey, Martin; McGovern, Gillian; Agarwal, Sonya; Gill, Andrew C; Piccardo, Pedro

2016-10-01

Mammalian prions are unusual infectious agents, as they are thought to consist solely of aggregates of misfolded prion protein (PrP). Generation of synthetic prions, composed of recombinant PrP (recPrP) refolded into fibrils, has been utilised to address whether PrP aggregates are, indeed, infectious prions. In several reports, neurological disease similar to transmissible spongiform encephalopathy (TSE) has been described following inoculation and passage of various forms of fibrils in transgenic mice and hamsters. However, in studies described here, we show that inoculation of recPrP fibrils does not cause TSE disease, but, instead, seeds the formation of PrP amyloid plaques in PrP-P101L knock-in transgenic mice (101LL). Importantly, both WT-recPrP fibrils and 101L-recPrP fibrils can seed plaque formation, indicating that the fibrillar conformation, and not the primary sequence of PrP in the inoculum, is important in initiating seeding. No replication of infectious prions or TSE disease was observed following both primary inoculation and subsequent subpassage. These data, therefore, argue against recPrP fibrils being infectious prions and, instead, indicate that these pre-formed seeds are acting to accelerate the formation of PrP amyloid plaques in 101LL Tg mice. In addition, these data reproduce a phenotype which was previously observed in 101LL mice following inoculation with brain extract containing in vivo-generated PrP amyloid fibrils, which has not been shown for other synthetic prion models. These data are reminiscent of the "prion-like" spread of aggregated forms of the beta-amyloid peptide (Aβ), α-synuclein and tau observed following inoculation of transgenic mice with pre-formed seeds of each misfolded protein. Hence, even when the protein is PrP, misfolding and aggregation do not reproduce the full clinicopathological phenotype of disease. The initiation and spread of protein aggregation in transgenic mouse lines following inoculation with pre

Knee Osteoarthritis Injection Choices: Platelet- Rich Plasma (PRP versus Hyaluronic Acid (A one-year randomized clinical trial

Directory of Open Access Journals (Sweden)

Seyed Ahmad Raeissadat

2015-01-01

Full Text Available Introduction Knee osteoarthritis (OA is the most common articular disease. Different methods are used to alleviate the symptoms of patients with knee OA, including analgesics, physical therapy, exercise prescription, and intra-articular injections (glucocorticoids, hyaluronic acid [HA], etc. New studies have focused on modern therapeutic methods that stimulate cartilage healing process and improve the damage, including the use of platelet-rich plasma (PRP as a complex of growth factors. Due to the high incidence of OA and its consequences, we decided to study the long-term effect of intraarticular injection of PRP and HA on clinical outcome and quality of life of patients with knee OA. Method This non-placebo-controlled randomized clinical trial involved 160 patients affected by knee OA, grade 1–4 of Kellgren–Lawrence scale. In the PRP group ( n = 87, two intra-articular injections at 4-week interval were applied, and in the HA group ( n = 73, three doses of intra-articular injection at 1-week interval were applied. All patients were prospectively evaluated before and at 12 months after the treatment by Western Ontario and McMaster Universities Arthritis Index (WOMAC and SF-36 questionnaires. The results were analyzed using SPSS 16.1 software (RCT code: IRCT2014012113442N5. Results At the 12-month follow-up, WOMAC pain score and bodily pain significantly improved in both groups; however, better results were determined in the PRP group compared to the HA group ( P < 0.001. Other WOMAC and SF-36 parameters improved only in the PRP group. More improvement (but not statistically significant was achieved in patients with grade 2 OA in both the groups. Conclusion This study suggests that PRP injection is more efficacious than HA injection in reducing symptoms and improving quality of life and is a therapeutic option in select patients with knee OA who have not responded to conventional treatment.

Genetic human prion disease modelled in PrP transgenic Drosophila.

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Thackray, Alana M; Cardova, Alzbeta; Wolf, Hanna; Pradl, Lydia; Vorberg, Ina; Jackson, Walker S; Bujdoso, Raymond

2017-09-20

Inherited human prion diseases, such as fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD), are associated with autosomal dominant mutations in the human prion protein gene PRNP and accumulation of PrP Sc , an abnormal isomer of the normal host protein PrP C , in the brain of affected individuals. PrP Sc is the principal component of the transmissible neurotoxic prion agent. It is important to identify molecular pathways and cellular processes that regulate prion formation and prion-induced neurotoxicity. This will allow identification of possible therapeutic interventions for individuals with, or at risk from, genetic human prion disease. Increasingly, Drosophila has been used to model human neurodegenerative disease. An important unanswered question is whether genetic prion disease with concomitant spontaneous prion formation can be modelled in Drosophila We have used pUAST/PhiC31-mediated site-directed mutagenesis to generate Drosophila transgenic for murine or hamster PrP (prion protein) that carry single-codon mutations associated with genetic human prion disease. Mouse or hamster PrP harbouring an FFI (D178N) or fCJD (E200K) mutation showed mild Proteinase K resistance when expressed in Drosophila Adult Drosophila transgenic for FFI or fCJD variants of mouse or hamster PrP displayed a spontaneous decline in locomotor ability that increased in severity as the flies aged. Significantly, this mutant PrP-mediated neurotoxic fly phenotype was transferable to recipient Drosophila that expressed the wild-type form of the transgene. Collectively, our novel data are indicative of the spontaneous formation of a PrP-dependent neurotoxic phenotype in FFI- or CJD-PrP transgenic Drosophila and show that inherited human prion disease can be modelled in this invertebrate host. © 2017 The Author(s).

Comparison of the Efficacy of Homologous and Autologous Platelet-Rich Plasma (PRP) for Treating Androgenic Alopecia.

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Ince, Bilsev; Yildirim, Mehmet Emin Cem; Dadaci, Mehmet; Avunduk, Mustafa Cihat; Savaci, Nedim

2018-02-01

Androgenetic alopecia (AGA), the most common cause of hair loss in both sexes, accounts for 95% of all cases of hair loss. Although the literature has suggested that both nonactivated (n-PRP) and activated autologous (a-PRP) PRP can be used to treat AGA, we did not find any study investigating the use of homologous PRP (h-PRP) for this purpose. Also, to the best of our knowledge, there are no studies comparing the efficacy of h-PRP, a-PRP, or n-PRP on AGA therapy. The aim of this study was to compare the increase in hair density, average number of platelets, complications, preparation, and duration of application in the treatment of AGA using a-PRP, n-PRP, and h-PRP. Between 2014 and 2015, we studied male patients who had experienced increased hair loss in the last year. Patients were divided into three groups: Group 1 received n-PRP, Group 2 received active PRP, and Group 3 received h-PRP. For Group 1, PRP was prepared by a single centrifugation prepared from the patient's own blood. For Group 2, the PRP was prepared from the patient's own blood, but a second centrifugation was applied for platelet activation with calcium chloride. For Group 3, the PRP was prepared from pooled platelets with the same blood group as the patient from the blood center. PRP was injected at 1, 2, and 6 months. The hair density (n/cm 2 ) of each patient before and after injection was calculated. Each patient was assigned a fixed evaluation point at the time of application to calculate hair density. At 2, 6, and 12 months after the first treatment, the increase in hair density was calculated as 11.2, 26.1, and 32.4%, respectively, in Group 1; 8.1, 12.5, and 20.8%, respectively, in Group 2; and 16.09, 36.41, and 41.76%, respectively, in Group 3. The increase in hair density was statistically significantly greater in Group 1 than in Group 2 and more so in Group 3 than in both groups among all controls (p PRP was greater than with autologous PRP groups. We believe that h-PRP therapy can

Singlet ground-state fluctuations in praseodymium observed by muon spin relaxation in PrP and PrP0.9

International Nuclear Information System (INIS)

Noakes, D R; Waeppling, R; Kalvius, G M; Jr, M F White; Stronach, C E

2005-01-01

Muon spin relaxation (μSR) in the singlet ground-state compounds PrP and PrP 0.9 reveals the unusual situation of a Lorentzian local field distribution with fast-fluctuation-limit strong-collision dynamics, a case that does not show motional narrowing. Contrary to publications by others, where PrP 0.9 was asserted to have vacancy-induced spin-glass freezing, no spin-glass freezing is seen in PrP 0.9 or PrP down to ≤100mK. This was confirmed by magnetization measurements on these same samples. In both compounds, the muon spin relaxation rate does increase as temperature decreases, demonstrating increasing strength of the paramagnetic response. A Monte Carlo model of fluctuations of Pr ions out of their crystalline-electric-field singlet ground states into their magnetic excited states (and back down again) produces the strong-collision-dynamic Lorentzian relaxation functions observed at each individual temperature but not the observed temperature dependence. This model contains no exchange interaction, and so predicts decreasing paramagnetic response as the temperature decreases, contrary to the temperature dependence observed. Comparison of the simulations to the data suggests that the exchange interaction is causing the system to approach magnetic freezing (by mode softening), but fails to complete the process

Platelet-rich plasma (PRP) in dental and oral surgery: from the wound healing to bone regeneration.

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Albanese, Antonino; Licata, Maria E; Polizzi, Bianca; Campisi, Giuseppina

2013-06-13

Platelet-rich plasma (PRP) is a new approach to tissue regeneration and it is becoming a valuable adjunct to promote healing in many procedures in dental and oral surgery, especially in aging patients. PRP derives from the centrifugation of the patient's own blood and it contains growth factors that influence wound healing, thereby playing an important role in tissue repairing mechanisms. The use of PRP in surgical practice could have beneficial outcomes, reducing bleeding and enhancing soft tissue healing and bone regeneration. Studies conducted on humans have yielded promising results regarding the application of PRP to many dental and oral surgical procedures (i.e. tooth extractions, periodontal surgery, implant surgery). The use of PRP has also been proposed in the management of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with the aim of enhancing wound healing and bone maturation. The aims of this narrative review are: i) to describe the different uses of PRP in dental surgery (tooth extractions and periodontal surgery) and oral surgery (soft tissues and bone tissue surgery, implant surgery and BRONJ surgery); and ii) to discuss its efficacy, efficiency and risk/benefit ratio. This review suggests that the use of PRP in the alveolar socket after tooth extractions is certainly capable of improving soft tissue healing and positively influencing bone regeneration but the latter effect seems to decrease a few days after the extraction. PRP has produced better results in periodontal therapy in association with other materials than when it is used alone. Promising results have also been obtained in implant surgery, when PRP was used in isolation as a coating material. The combination of necrotic bone curettage and PRP application seem to be encouraging for the treatment of refractory BRONJ, as it has proven successful outcomes with minimal invasivity. Since PRP is free from potential risks for patients, not difficult to obtain and use, it can be employed

Platelet-rich plasma (PRP) in dental and oral surgery: from the wound healing to bone regeneration

Science.gov (United States)

2013-01-01

Platelet-rich plasma (PRP) is a new approach to tissue regeneration and it is becoming a valuable adjunct to promote healing in many procedures in dental and oral surgery, especially in aging patients. PRP derives from the centrifugation of the patient's own blood and it contains growth factors that influence wound healing, thereby playing an important role in tissue repairing mechanisms. The use of PRP in surgical practice could have beneficial outcomes, reducing bleeding and enhancing soft tissue healing and bone regeneration. Studies conducted on humans have yielded promising results regarding the application of PRP to many dental and oral surgical procedures (i.e. tooth extractions, periodontal surgery, implant surgery). The use of PRP has also been proposed in the management of bisphosphonate-related osteonecrosis of the jaw (BRONJ) with the aim of enhancing wound healing and bone maturation. The aims of this narrative review are: i) to describe the different uses of PRP in dental surgery (tooth extractions and periodontal surgery) and oral surgery (soft tissues and bone tissue surgery, implant surgery and BRONJ surgery); and ii) to discuss its efficacy, efficiency and risk/benefit ratio. This review suggests that the use of PRP in the alveolar socket after tooth extractions is certainly capable of improving soft tissue healing and positively influencing bone regeneration but the latter effect seems to decrease a few days after the extraction. PRP has produced better results in periodontal therapy in association with other materials than when it is used alone. Promising results have also been obtained in implant surgery, when PRP was used in isolation as a coating material. The combination of necrotic bone curettage and PRP application seem to be encouraging for the treatment of refractory BRONJ, as it has proven successful outcomes with minimal invasivity. Since PRP is free from potential risks for patients, not difficult to obtain and use, it can be employed

Cytosolically expressed PrP GPI-signal peptide interacts with mitochondria.

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Guizzunti, Gianni; Zurzolo, Chiara

2015-01-01

We previously reported that PrP GPI-anchor signal peptide (GPI-SP) is specifically degraded by the proteasome. Additionally, we showed that the point mutation P238S, responsible for a genetic form of prion diseases, while not affecting the GPI-anchoring process, results in the accumulation of PrP GPI-SP, suggesting the possibility that PrP GPI-anchor signal peptide could play a role in neurodegenerative prion diseases. We now show that PrP GPI-SP, when expressed as a cytosolic peptide, is able to localize to the mitochondria and to induce mitochondrial fragmentation and vacuolarization, followed by loss in mitochondrial membrane potential, ultimately resulting in apoptosis. Our results identify the GPI-SP of PrP as a novel candidate responsible for the impairment in mitochondrial function involved in the synaptic pathology observed in prion diseases, establishing a link between PrP GPI-SP accumulation and neuronal death.

Recombinant PrP and Its Contribution to Research on Transmissible Spongiform Encephalopathies.

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Charco, Jorge M; Eraña, Hasier; Venegas, Vanessa; García-Martínez, Sandra; López-Moreno, Rafael; González-Miranda, Ezequiel; Pérez-Castro, Miguel Ángel; Castilla, Joaquín

2017-12-14

The misfolding of the cellular prion protein (PrP C ) into the disease-associated isoform (PrP Sc ) and its accumulation as amyloid fibrils in the central nervous system is one of the central events in transmissible spongiform encephalopathies (TSEs). Due to the proteinaceous nature of the causal agent the molecular mechanisms of misfolding, interspecies transmission, neurotoxicity and strain phenomenon remain mostly ill-defined or unknown. Significant advances were made using in vivo and in cellula models, but the limitations of these, primarily due to their inherent complexity and the small amounts of PrP Sc that can be obtained, gave rise to the necessity of new model systems. The production of recombinant PrP using E. coli and subsequent induction of misfolding to the aberrant isoform using different techniques paved the way for the development of cell-free systems that complement the previous models. The generation of the first infectious recombinant prion proteins with identical properties of brain-derived PrP Sc increased the value of cell-free systems for research on TSEs. The versatility and ease of implementation of these models have made them invaluable for the study of the molecular mechanisms of prion formation and propagation, and have enabled improvements in diagnosis, high-throughput screening of putative anti-prion compounds and the design of novel therapeutic strategies. Here, we provide an overview of the resultant advances in the prion field due to the development of recombinant PrP and its use in cell-free systems.

Matrix metalloproteinase content and activity in low-platelet, low-leukocyte and high-platelet, high-leukocyte platelet rich plasma (PRP) and the biologic response to PRP by human ligament fibroblasts.

Science.gov (United States)

Pifer, Matthew A; Maerz, Tristan; Baker, Kevin C; Anderson, Kyle

2014-05-01

Recent work has shown the presence of catabolic cytokines in platelet-rich plasma (PRP), but little is known about endogenous catabolic proteases such as matrix metalloproteinases (MMPs). Hypothesis/ To quantify MMP content in 2 commercially available PRP preparation systems: Arthrex Double Syringe System autologous conditioned plasma (ACP) and Biomet GPS (GPS). The hypothesis was that MMPs are actively secreted from PRP immediately after preparation. Controlled laboratory study. PRP was prepared using either ACP (low platelet, low leukocyte) or GPS (high platelet, high leukocyte). MMP-2, MMP-3, and MMP-9 concentrations were measured using multiplex enzyme-linked immunosorbent assays for up to 6 days in 2 donors, and MMP activity was measured in 3 donors using kinetic activity kits able to detect the enzymatic cleavage of a fluorogenic peptide. Human ligament fibroblasts were cultured and exposed to both ACP and GPS from 1 donor each. MMP-2, -3, and -9 concentrations were assayed in culture media at 24 and 48 hours after exposure. GPS exhibited higher total MMP-2, -3, and -9 concentrations for up to 144 hours of release, while ACP had higher platelet-normalized MMP-2 and MMP-3 concentrations. GPS had significantly higher total and endogenous MMP-2 activity (P = .004 and .014, respectively), MMP-3 activity (P = .020 and .015, respectively), and MMP-9 activity (P = .004 and .002, respectively) compared with ACP. Once normalized to platelet count, differences in MMP activity were not significant between ACP and GPS. Compared with controls, cells stimulated with interleukin-1 beta (IL-1β) and treated with ACP showed significantly higher fold changes of MMP-2 (P = .001) and MMP-3 (P = .003) concentrations at 24 hours than did cells treated with GPS. Total MMP-9 content was higher in the media of GPS-treated, IL-1β-stimulated cells compared with ACP-treated cells (P = .001). At 48 hours, IL-1β-stimulated cells treated with GPS exhibited higher fold changes of MMP-2

An introduction to application of Platelet Rich Plasma (PRP in skin rejuvenation

Directory of Open Access Journals (Sweden)

Mahnaz Banihashemi

2014-04-01

Full Text Available Platelet-rich plasma (PRP is an autologous concentration of human platelets contained in a small volume of plasma characterized by haemostatic and tissue repairing effects. Tissue repairing effects and being enriched by various kind of growth factors, has made them the focus of attention for different procedures. PRP has been effective in bony defects, wound healing and recently for aesthetic procedures in plastic surgery. The purpose of this review is to evaluate and summarize the applications of PRP in the dermatology literature, with particular focus on rejuvenizaton process, advances and limitations of current PRP therapies. We studied literature related to PRP therapy, these include regeneration of soft tissue, skin aging mechanisms, as well as wound healing. Some studies have shown promising results, with favorable outcomes about PRP clinical application for skin rejuvenization. This article summarizes our current understanding regarding photoaging process and the role of PRP in the skin rejuvenization process. PRP has been shown to be useful in skin rejuvenization. Further studies are needed to elucidate both basic and clinical aspects of PRP therapies. In particular, platelet preparation methods, different application methods, platelet mechanism of action in rejuvenation field, interactions with the skin components, long-term efficacy and safety are necessary to be determined.

PLATELET-RICH PLASMA (PRP AND ITS APPLICATION IN THE TREATMENT OF CHRONIC AND HARD-TO-HEAL SKIN WOUNDS. A Review.

Directory of Open Access Journals (Sweden)

Tsvetan Sokolov

2015-12-01

Full Text Available In the last few years various methods are being applied in the use of platelet-rich plasma (PRP during treatment in different orthopedic disease. They allow improvement of local biological condition and regeneration of different types of tissues. PRP is a modern treatment strategy with worldwide recognition. There is a high concentration of platelet growth factors in small amounts of plasma. PRP and its various forms have become one of the best methods to support the healing process of various tissues. PRP is used in regenerative medicine, because it provides two of three components (growth factors and scaffolds necessary for complete tissue regeneration. The particular reason for the appearance of lesions is important in order to select an appropriate treatment method and technical application. PRP may be used for treatment of various chronic and hard-to-heal cutaneous wounds, especially when standard conventional therapy is not good enough and surgical treatment is not possible. It reduces the duration, cost of treatment and the hospital stay. There is reduction of wound pain after starting the treatment, reduced risk of blood-borne disease transmission, wound healing is restored, and local immunity is activated.

Comparative assessment of prophylactic transfusions of platelet concentrates obtained by the PRP or buffy-coat methods, in patients undergoing allogeneic hematopoietic stem cell transplantation.

Science.gov (United States)

Fernández-Muñoz, Hermógenes; Plaza, Eva M; Rivera-Caravaca, José Miguel; Candela, María José; Romera, Marta; De Arriba, Felipe; Lozano, María L; Vicente, Vicente; Heras, Inmaculada; Castilla-Llorente, Cristina; Rivera, José

2018-03-27

Whole blood-derived platelet concentrates can be obtained by the platelet-rich plasma (PRP-PCs) or the buffy-coat (BC-PCs) method. Few studies have shown that BC-PCs display lower in vitro platelet activation, but scarce information exists regarding transfusion efficacy. We have performed a retrospective study assessing platelet transfusion in patients undergoing allogeneic hematopoietic cell transplantation (AHCT) in our clinic, before and after the implementation of BC-PCs. We reviewed clinical records corresponding to 70 PRP-PCs and 86 BC-PCs prophylactic transfusions, which were performed to 55 AHCT patients. Transfusion efficacy was assessed by the 24-h post-transfusion corrected count increment (24-h CCI) and bleeding events. Clinical factors affecting transfusion outcome were also investigated. Clinical characteristics and the total number of platelet transfusions were similar among groups. Mean donor exposure was 5.8 and 5.0 in each single PRP-PCs and BC-PCs transfusion, respectively (p PRP-PCs (8.3[2.7-13.4] vs. 4.7[1.3-8.1]; p PRP-PCs transfusion (HR 4.54; 95% CI 1.72-12.01; p = 0.002). There were no differences between both groups regarding the bleeding events. In the AHCT setting, we hypothesize that BC-PCs transfusion, when compared to PRP-PCs, results in higher CCI and reduced donor exposure, but provides no significant benefit regarding bleeding outcome.

Transmission Properties of Human PrP 102L Prions Challenge the Relevance of Mouse Models of GSS.

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Asante, Emmanuel A; Grimshaw, Andrew; Smidak, Michelle; Jakubcova, Tatiana; Tomlinson, Andrew; Jeelani, Asif; Hamdan, Shyma; Powell, Caroline; Joiner, Susan; Linehan, Jacqueline M; Brandner, Sebastian; Wadsworth, Jonathan D F; Collinge, John

2015-07-01

Inherited prion disease (IPD) is caused by autosomal-dominant pathogenic mutations in the human prion protein (PrP) gene (PRNP). A proline to leucine substitution at PrP residue 102 (P102L) is classically associated with Gerstmann-Sträussler-Scheinker (GSS) disease but shows marked clinical and neuropathological variability within kindreds that may be caused by variable propagation of distinct prion strains generated from either PrP 102L or wild type PrP. To-date the transmission properties of prions propagated in P102L patients remain ill-defined. Multiple mouse models of GSS have focused on mutating the corresponding residue of murine PrP (P101L), however murine PrP 101L, a novel PrP primary structure, may not have the repertoire of pathogenic prion conformations necessary to accurately model the human disease. Here we describe the transmission properties of prions generated in human PrP 102L expressing transgenic mice that were generated after primary challenge with ex vivo human GSS P102L or classical CJD prions. We show that distinct strains of prions were generated in these mice dependent upon source of the inoculum (either GSS P102L or CJD brain) and have designated these GSS-102L and CJD-102L prions, respectively. GSS-102L prions have transmission properties distinct from all prion strains seen in sporadic and acquired human prion disease. Significantly, GSS-102L prions appear incapable of transmitting disease to conventional mice expressing wild type mouse PrP, which contrasts strikingly with the reported transmission properties of prions generated in GSS P102L-challenged mice expressing mouse PrP 101L. We conclude that future transgenic modeling of IPDs should focus exclusively on expression of mutant human PrP, as other approaches may generate novel experimental prion strains that are unrelated to human disease.

Performance related pay (PRP) to social workers in Danish Job Centres

DEFF Research Database (Denmark)

Flensborg Jensen, Maya; Rosdahl, Anders

This paper discusses two issues: - Why has some Danish local employment administrations introduced performance related pay (PRP) for social workers while others have not? - Does PRP to social workers imply better efforts to bring long-term recipients of social assistance into employment?......This paper discusses two issues: - Why has some Danish local employment administrations introduced performance related pay (PRP) for social workers while others have not? - Does PRP to social workers imply better efforts to bring long-term recipients of social assistance into employment?...

Ionic mechanisms of action of prion protein fragment PrP(106-126) in rat basal forebrain neurons.

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Alier, Kwai; Li, Zongming; Mactavish, David; Westaway, David; Jhamandas, Jack H

2010-08-01

Prion diseases are neurodegenerative disorders that are characterized by the presence of the misfolded prion protein (PrP). Neurotoxicity in these diseases may result from prion-induced modulation of ion channel function, changes in neuronal excitability, and consequent disruption of cellular homeostasis. We therefore examined PrP effects on a suite of potassium (K(+)) conductances that govern excitability of basal forebrain neurons. Our study examined the effects of a PrP fragment [PrP(106-126), 50 nM] on rat neurons using the patch clamp technique. In this paradigm, PrP(106-126) peptide, but not the "scrambled" sequence of PrP(106-126), evoked a reduction of whole-cell outward currents in a voltage range between -30 and +30 mV. Reduction of whole-cell outward currents was significantly attenuated in Ca(2+)-free external media and also in the presence of iberiotoxin, a blocker of calcium-activated potassium conductance. PrP(106-126) application also evoked a depression of the delayed rectifier (I(K)) and transient outward (I(A)) potassium currents. By using single cell RT-PCR, we identified the presence of two neuronal chemical phenotypes, GABAergic and cholinergic, in cells from which we recorded. Furthermore, cholinergic and GABAergic neurons were shown to express K(v)4.2 channels. Our data establish that the central region of PrP, defined by the PrP(106-126) peptide used at nanomolar concentrations, induces a reduction of specific K(+) channel conductances in basal forebrain neurons. These findings suggest novel links between PrP signalling partners inferred from genetic experiments, K(+) channels, and PrP-mediated neurotoxicity.

Recommendations for the Involvement of Patient Research Partners (PRP) in OMERACT Working Groups. A Report from the OMERACT 2014 Working Group on PRP.

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Cheung, Peter P; de Wit, Maarten; Bingham, Clifton O; Kirwan, John R; Leong, Amye; March, Lyn M; Montie, Pam; Scholte-Voshaar, Marieke; Gossec, Laure

2016-01-01

Patient participation in research is increasing; however, practical guidelines to enhance this participation are lacking. Specifically within the Outcome Measures in Rheumatology (OMERACT) organization, although patients have participated in OMERACT meetings since 2002, consensus about the procedures for involving patients in working groups has not been formalized. The objective is to develop a set of recommendations regarding patient research partner (PRP) involvement in research working groups. We conducted a systematic literature review on recommendations/guidelines of PRP involvement in research; elaborated a structured consensus process involving multiple participants to develop a set of recommendations; and sought endorsement of recommendations by OMERACT. In the 18 articles included in the literature review, there was general agreement on the broad concepts for recommendations covering PRP involvement in research although they were heterogeneous in detail. Most considered PRP involvement in all phases of research with early engagement, training, and support important, but details on the content were scarce. This review informed a larger consensus-building process regarding PRP inclusion in OMERACT research. Three overarching principles and 8 recommendations were developed, discussed, and refined at OMERACT 2014. The guiding principles were endorsed during the OMERACT plenary session. These recommendations for PRP involvement in OMERACT research reinforce the importance of patient participation throughout the research process as integral members. Although the applicability of the recommendations in other research contexts should be assessed, the generalizability is expected to be high. Future research should evaluate their implementation and their effect on outcome development.

Polymorphisms at Amino Acid Residues 141 and 154 Influence Conformational Variation in Ovine PrP

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Yang, Sujeong; Thackray, Alana M.; Hopkins, Lee; Monie, Tom P.; Burke, David F.; Bujdoso, Raymond

2014-01-01

Polymorphisms in ovine PrP at amino acid residues 141 and 154 are associated with susceptibility to ovine prion disease: Leu141Arg154 with classical scrapie and Phe141Arg154 and Leu141His154 with atypical scrapie. Classical scrapie is naturally transmissible between sheep, whereas this may not be the case with atypical scrapie. Critical amino acid residues will determine the range or stability of structural changes within the ovine prion protein or its functional interaction with potential cofactors, during conversion of PrPC to PrPSc in these different forms of scrapie disease. Here we computationally identified that regions of ovine PrP, including those near amino acid residues 141 and 154, displayed more conservation than expected based on local structural environment. Molecular dynamics simulations showed these conserved regions of ovine PrP displayed genotypic differences in conformational repertoire and amino acid side-chain interactions. Significantly, Leu141Arg154 PrP adopted an extended beta sheet arrangement in the N-terminal palindromic region more frequently than the Phe141Arg154 and Leu141His154 variants. We supported these computational observations experimentally using circular dichroism spectroscopy and immunobiochemical studies on ovine recombinant PrP. Collectively, our observations show amino acid residues 141 and 154 influence secondary structure and conformational change in ovine PrP that may correlate with different forms of scrapie. PMID:25126555

Immunogenicity and safety of a fully liquid aluminum phosphate adjuvanted Haemophilus influenzae type b PRP-CRM197-conjugate vaccine in healthy Japanese children: A phase III, randomized, observer-blind, multicenter, parallel-group study.

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Togashi, Takehiro; Mitsuya, Nodoka; Kogawara, Osamu; Sumino, Shuji; Takanami, Yohei; Sugizaki, Kayoko

2016-08-31

Broad use of monovalent Haemophilus influenzae type b (Hib) conjugate vaccines based on the capsular polysaccharide polyribosyl-ribitol phosphate (PRP), has significantly reduced invasive Hib disease burden in children worldwide, particularly in children aged vaccine has been widely used since the initiation of public funding programs followed by a routine vaccination designation in 2013. We compared the immunogenicity and safety of PRP conjugated to a non-toxic diphtheria toxin mutant (PRP-CRM197) vaccine with the PRP-T vaccine when administered subcutaneously to healthy Japanese children in a phase III study. Additionally, we evaluated the immunogenicity and safety profiles of a diphtheria-tetanus acellular pertussis (DTaP) combination vaccine when concomitantly administered with either PRP-CRM197 or PRP-T vaccines. The primary endpoint was the "long-term seroprotection rate", defined as the group proportion with anti-PRP antibody titers ⩾1.0μg/mL, after the primary series. Long-term seroprotection rates were 99.3% in the PRP-CRM197 group and 95.6% in the PRP-T group. The intergroup difference (PRP-CRM197 group - PRP-T group) was 3.7% (95% confidence interval: 0.099-7.336), demonstrating that PRP-CRM197 vaccine was non-inferior to PRP-T vaccine (pvaccination was higher in the PRP-CRM197 group than in PRP-T. Concomitant administration of PRP-CRM197 vaccine with DTaP vaccine showed no differences in terms of immunogenicity compared with concomitant vaccination with PRP-T vaccine and DTaP vaccine. Although CRM197 vaccine had higher local reactogenicity, overall, both Hib vaccines had acceptable safety and tolerability profiles. The immunogenicity of PRP-CRM197 vaccine administered subcutaneously as a three-dose primary series in children followed by a booster vaccination 1year after the primary series induced protective levels of Hib antibodies with no safety or tolerability concerns. Registered on ClinicalTrials.gov: NCT01379846. Copyright © 2016 The Authors

Tratamiento de quemaduras mediante plasma rico en plaquetas (PRP: parte I

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G. Rossani

2014-06-01

Full Text Available El objetivo del presente trabajo es determinar la eficacia clínica del plasma rico en plaquetas (PRP en las quemaduras de segundo grado. Estudiamos el tiempo requerido en la reepitelización del tejido dañado, la estancia hospitalaria asociada a la curación de las lesiones y la satisfacción del paciente. Realizamos un estudio prospectivo, observacional y longitudinal, en una muestra de 115 pacientes con quemaduras de segundo grado según la clasificación de Converse-Smith. Las lesiones fueron de menos de 48 horas de evolución, en diferentes zonas de cara y cuerpo. A todos los pacientes se les aplicó de forma ambulatoria PRP por goteo, completándose el tratamiento con la aplicación de gasas parafinadas. El estudio se realizó entre marzo de 2011 y agosto de 2013. Las quemaduras que evolucionaron mejor y de forma más rápida fueron las de cara, seguidas por las de abdomen y, por último, las de extremidades inferiores. En todas, el tiempo de epitelización fue un 30 % inferior que en quemaduras de similar extensión, profundidad y localización, en pacientes anteriormente tratados sin PRP. Los pacientes fueron atendidos ambulatoriamente cuando las lesiones lo permitieron, y si presentaban lesiones más extensas fueron hospitalizados. El tiempo de internamiento en estos casos se redujo como promedio 18 días con respecto al grupo no tratado con PRP. El tiempo de reepitelización, estancia hospitalaria y la satisfacción de los pacientes, alcanzaron significación estadística p< 0,05. En conclusión, creemos que el uso de PRP acorta el tiempo de recuperación en quemaduras de segundo grado, reduce el tiempo de hospitalización y conlleva un alto grado de satisfacción de los pacientes por los resultados obtenidos.

Mutant PrP Suppresses Glutamatergic Neurotransmission in Cerebellar Granule Neurons by Impairing Membrane Delivery of VGCC α2δ-1 Subunit

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Senatore, Assunta; Colleoni, Simona; Verderio, Claudia; Restelli, Elena; Morini, Raffaella; Condliffe, Steven B.; Bertani, Ilaria; Mantovani, Susanna; Canovi, Mara; Micotti, Edoardo; Forloni, Gianluigi; Dolphin, Annette C.; Matteoli, Michela; Gobbi, Marco; Chiesa, Roberto

2012-01-01

Summary How mutant prion protein (PrP) leads to neurological dysfunction in genetic prion diseases is unknown. Tg(PG14) mice synthesize a misfolded mutant PrP which is partially retained in the neuronal endoplasmic reticulum (ER). As these mice age, they develop ataxia and massive degeneration of cerebellar granule neurons (CGNs). Here, we report that motor behavioral deficits in Tg(PG14) mice emerge before neurodegeneration and are associated with defective glutamate exocytosis from granule neurons due to impaired calcium dynamics. We found that mutant PrP interacts with the voltage-gated calcium channel α2δ-1 subunit, which promotes the anterograde trafficking of the channel. Owing to ER retention of mutant PrP, α2δ-1 accumulates intracellularly, impairing delivery of the channel complex to the cell surface. Thus, mutant PrP disrupts cerebellar glutamatergic neurotransmission by reducing the number of functional channels in CGNs. These results link intracellular PrP retention to synaptic dysfunction, indicating new modalities of neurotoxicity and potential therapeutic strategies. PMID:22542184

The role of PRP and adipose tissue-derived keratinocytes on burn wound healing in diabetic rats.

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Hosseini Mansoub, Navid; Gürdal, Mehmet; Karadadaş, Elif; Kabadayi, Hilal; Vatansever, Seda; Ercan, Gulinnaz

2018-01-01

Introduction: Diabetic burn wounds and ulcers are significant complications of diabetic patients. The aim of this study is to investigate the use of platelet rich-plasma (PRP) and/or keratinocyte-like cells (KLCs) in diabetic thermal wound rat model and to evaluate EGF, FGF-2, TGF-β1, COL1α2, MCP-1 and VEGF-α as wound healing markers at gene expression level. Method: In this study, we used adipose tissue as the source of mesenchymal stem cells (MSCs) and differentiated MSCs into KLCs. KLCs were characterized and transferred to the burn areas on the dorsum of streptozotocine (STZ)-induced diabetic rats. We prepared PRP from rat blood and evaluated its effect alone or in combination with KLCs. On 3 rd , 7 th , 10 th and 14 th days after treatment, wound areas were measured and biopsy samples were excised from the wound areas of the KLCs and/or PRP-treated and untreated diabetic rats to analyze gene expression levels of wound healing markers by qPCR. Results: We observed that, wound contraction started earlier in the PRP and/or KLCs-treated groups in comparison to the control group. However, PRP and KLCs when applied in combination showed additive affect in wound healing. In all groups treated with KLCs and/or PRP, the gene expression levels of evaluated growth factors and COL1α2 increased, while MCP-1 levels decreased when compared to the untreated diabetic rats. In addition, the most prominent difference in qPCR results belongs to combined PRP and KLCs-treated group. Conclusion: We demonstrated that applying PRP and KLCs in combination has a greater potential for treatment of diabetic burn wounds.

Structural and functional analysis of the human spliceosomal DEAD-box helicase Prp28

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Möhlmann, Sina [Georg-August-University Göttingen, Justus-von-Liebig Weg 11, 37077 Göttingen (Germany); Mathew, Rebecca [Max-Planck-Institute for Biophysical Chemistry, Am Fassberg, 37077 Göttingen (Germany); Neumann, Piotr; Schmitt, Andreas [Georg-August-University Göttingen, Justus-von-Liebig Weg 11, 37077 Göttingen (Germany); Lührmann, Reinhard [Max-Planck-Institute for Biophysical Chemistry, Am Fassberg, 37077 Göttingen (Germany); Ficner, Ralf, E-mail: rficner@uni-goettingen.de [Georg-August-University Göttingen, Justus-von-Liebig Weg 11, 37077 Göttingen (Germany)

2014-06-01

The crystal structure of the helicase domain of the human spliceosomal DEAD-box protein Prp28 was solved by SAD. The binding of ADP and ATP by Prp28 was studied biochemically and analysed with regard to the crystal structure. The DEAD-box protein Prp28 is essential for pre-mRNA splicing as it plays a key role in the formation of an active spliceosome. Prp28 participates in the release of the U1 snRNP from the 5′-splice site during association of the U5·U4/U6 tri-snRNP, which is a crucial step in the transition from a pre-catalytic spliceosome to an activated spliceosome. Here, it is demonstrated that the purified helicase domain of human Prp28 (hPrp28ΔN) binds ADP, whereas binding of ATP and ATPase activity could not be detected. ATP binding could not be observed for purified full-length hPrp28 either, but within an assembled spliceosomal complex hPrp28 gains ATP-binding activity. In order to understand the structural basis for the ATP-binding deficiency of isolated hPrp28, the crystal structure of hPrp28ΔN was determined at 2.0 Å resolution. In the crystal the helicase domain adopts a wide-open conformation, as the two RecA-like domains are extraordinarily displaced from the productive ATPase conformation. Binding of ATP is hindered by a closed conformation of the P-loop, which occupies the space required for the γ-phosphate of ATP.

Ubiquitin Ligase gp78 Targets Unglycosylated Prion Protein PrP for Ubiquitylation and Degradation

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Shao, Jia; Choe, Vitnary; Cheng, Haili; Tsai, Yien Che; Weissman, Allan M.; Luo, Shiwen; Rao, Hai

2014-01-01

Prion protein PrP is a central player in several devastating neurodegenerative disorders, including mad cow disease and Creutzfeltd-Jacob disease. Conformational alteration of PrP into an aggregation-prone infectious form PrPSc can trigger pathogenic events. How levels of PrP are regulated is poorly understood. Human PrP is known to be degraded by the proteasome, but the specific proteolytic pathway responsible for PrP destruction remains elusive. Here, we demonstrate that the ubiquitin ligas...

The influence of using anticoagulants (EDTA and citrate acid 3.8% toward the quantity of Platelet Rich Plasma (PRP

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Lilies Anggarwati Astuti

2016-06-01

Full Text Available Platelet Rich Plasma (PRP is a blood concentrate that has a thrombocytes concentration several time higher than normal concentration of thrombocytes in normal human blood. PRP is a promising alternative to surgery with a safe and natural healing. The standard protocol for PRP preparation must be determined to get the right quantity and quality of the matrix of fibrin, leukocytes, platelets and growth factors. It could not be separated from the number of PRP produced. The use of PRP in the success of periodontal treatment would not be separated from methods to obtain it. To detect the influence of using anticoagulants (EDTA and citrate acid 3.8% toward the quantity of PRP. There are 41 subjects studied by taking 21 ml of venous blood in each of the seven tubes. Centrifugation performed twice with different speed, duration, use of anticoagulants then analyzed. This quantity between the two groups differed significantly between the PRP in EDTA group is higher 322.2 ml rather than citrate acid 3.8% group, then control group is higher 329.5 ml rather than citrate acid 3.8% group, while there is no difference between EDTA and control group. There is effect of the use of anticoagulants EDTA compared with citrate acid 3.8% in the quantity of PRP, and there was no effect using citrate acid 3.8% as anticoagulants in quantity of PRP.

Clinical-grade quality platelet-rich plasma releasate (PRP-R/SRGF) from CaCl2 -activated platelet concentrates promoted expansion of mesenchymal stromal cells.

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Borghese, C; Agostini, F; Durante, C; Colombatti, A; Mazzucato, M; Aldinucci, D

2016-08-01

The aim of our study was to test a platelet-rich plasma releasate (PRP-R/SRGF) from CaCl2 -activated platelets as a source of growth factors for the expansion of mesenchymal stromal cells (MSCs). PRP-R/SRGF, obtained with a low-cost procedure, is characterized by a reduced variability of growth factor release. PRP-R/SRGF is a clinical-grade quality solution obtained from CaCl2 -activated platelets. Its activity was evaluated by measuring the proliferation, the phenotype, the differentiation potential and the immunosuppressive properties of MSCs derived from bone marrow (BM) and adipose tissue (AT). PRP-R/SRGF was more active than FBS to expand BM- and AT-derived MSCs. PRP-R/SRGF treatment did not affect the expression of typical MSCs surface markers, neither MSCs differentiation potential nor their capability to inhibit activated T-cell proliferation. The clinical-grade PRP-R/SRGF may be used in the clinical setting for the expansion of MSCs. © 2016 International Society of Blood Transfusion.

Enhanced Osteogenic Differentiation of Mesenchymal Stem Cells on Electrospun PES/PVA/PRP Nanofibrous Scaffolds.

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Kashef-Saberi, Mahshid Sadat; Roodbari, Nasim Hayati; Parivar, Kazem; Vakilian, Saeid; Hanee-Ahvaz, Hana

2018-03-28

Over the last few decades, great advancements have been achieved in the field of bone tissue engineering (BTE). Containing a great number of growth factors needed in the process of osteogenesis, platelet rich plasma (PRP) has gained a great deal of attention. However, due to the contradictory results achieved in different studies, its effectiveness remains a mystery. Therefore, in this study, we investigated in vitro performance of co-electrospun PRP/poly ether sulfone/poly(vinyl) alcohol (PRP/PES/PVA) composite scaffolds for the osteogenic differentiation of human adipose-derived mesenchymal stem cells. The activated PRP was mixed with PVA solution to be used alongside PES solution for the electrospinning process. Fourier transform infrared spectroscopy, scanning electron microscopy and tensile tests were performed to evaluate the scaffolds. After confirmation of sustained release of protein, osteogenic potential of the co-electrospun PRP/polymer scaffolds was evaluated by measuring relative gene expression, calcium content, and alkaline phosphatase (ALP) activity. Alizarin red and Hematoxylin and Eosin staining were performed as well. The results of ALP activity and calcium content demonstrated the effectiveness of PRP when combined with PRP-incorporated scaffold in comparison with the other tested groups. In addition, the results of tensile mechanical testing indicated that addition of PRP improves the mechanical properties. Taking these results into account, it appears PES/PVA/PRP scaffold treated with PRP 5% enhances osteogenic differentiation most. In conclusion, incorporation of PRP into electrospun PES/PVA scaffold in this study had a positive influence on osteogenic differentiation of AdMSCs, and thus it may have great potential for BTE applications.

PRP: The Proven Solution for Cleaning Up Oil Spills

Science.gov (United States)

2006-01-01

The basic technology behind PRP is thousands of microcapsules, tiny balls of beeswax with hollow centers. Water cannot penetrate the microcapsule s cell, but oil is absorbed right into the beeswax spheres as they float on the water s surface. This way, the contaminants, chemical compounds that originally come from crude oil such as fuels, motor oils, or petroleum hydrocarbons, are caught before they settle. PRP works well as a loose powder for cleaning up contaminants in lakes and other ecologically fragile areas. The powder can be spread over a contaminated body of water or soil, and it will absorb contaminants, contain them in isolation, and dispose of them safely. In water, it is important that PRP floats and keeps the oil on the surface, because, even if oil exposure is not immediately lethal, it can cause long-term harm if allowed to settle. Bottom-dwelling fish exposed to compounds released after oil spills may develop liver disease, in addition to reproductive and growth problems. This use of PRP is especially effective for environmental cleanup in sensitive areas like coral reefs and mangroves.

Platelet rich plasma (PRP) induces chondroprotection via increasing autophagy, anti-inflammatory markers, and decreasing apoptosis in human osteoarthritic cartilage.

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Moussa, Mayssam; Lajeunesse, Daniel; Hilal, George; El Atat, Oula; Haykal, Gaby; Serhal, Rim; Chalhoub, Antonio; Khalil, Charbel; Alaaeddine, Nada

2017-03-01

Autophagy constitutes a defense mechanism to overcome aging and apoptosis in osteoarthritic cartilage. Several cytokines and transcription factors are linked to autophagy and play an important role in the degradative cascade in osteoarthritis (OA). Cell therapy such as platelet rich plasma (PRP) has recently emerged as a promising therapeutic tool for many diseases including OA. However, its mechanism of action on improving cartilage repair remains to be determined. The purpose of this study is to investigate the effect of PRP on osteoarthritic chondrocytes and to elucidate the mechanism by which PRP contributes to cartilage regeneration. Osteoarthritic chondrocytes were co-cultured with an increasing concentration of PRP obtained from healthy donors. The effect of PRP on the proliferation of chondrocytes was performed using cell counting and WST8 proliferation assays. Autophagy, apoptosis and intracellular level of IL-4, IL-10, and IL-13 were determined using flow cytometry analyses. Autophagy markers BECLIN and LC3II were also determined using quantitative polymerase chain reaction (qPCR). qPCR and ELISA were used to measure the expression of ADAMDTS-5, MMP3, MMP13, TIMP-1-2-3, aggregan, Collagen type 2, TGF-β, Cox-2, Il-6, FOXO1, FOXO3, and HIF-1 in tissues and co-cultured media. PRP increased significantly the proliferation of chondrocytes, decreased apoptosis and increased autophagy and its markers along with its regulators FOXO1, FOXO3 and HIF-1 in osteoarthritic chondrocytes. Furthermore, PRP caused a dose-dependent significant decrease in MMP3, MMP13, and ADAMTS-5, IL-6 and COX-2 while increasing TGF-β, aggregan, and collagen type 2, TIMPs and intracellular IL-4, IL-10, IL-13. These results suggest that PRP could be a potential therapeutic tool for the treatment of OA. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Multiple PRP injections are more effective than single injections and hyaluronic acid in knees with early osteoarthritis: a randomized, double-blind, placebo-controlled trial.

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Görmeli, Gökay; Görmeli, Cemile Ayşe; Ataoglu, Baybars; Çolak, Cemil; Aslantürk, Okan; Ertem, Kadir

2017-03-01

To compare the effectiveness of intraarticular (IA) multiple and single platelet-rich plasma (PRP) injections as well as hyaluronic acid (HA) injections in different stages of osteoarthritis (OA) of the knee. A total of 162 patients with different stages of knee OA were randomly divided into four groups receiving 3 IA doses of PRP, one dose of PRP, one dose of HA or a saline injection (control). Then, each group was subdivided into two groups: early OA (Kellgren-Lawrence grade 0 with cartilage degeneration or grade I-III) and advanced OA (Kellgren-Lawrence grade IV). The patients were evaluated before the injection and at the 6-month follow-ups using the EuroQol visual analogue scale (EQ-VAS) and International Knee Documentation Committee (IKDC) subjective scores. Adverse events and patient satisfaction were recorded. There was a statistically significant improvement in the IKDC and EQ-VAS scores in all the treatment groups compared with the control group. The knee scores of patients treated with three PRP injections were significantly better than those patients of the other groups. There was no significant difference in the scores of patients injected with one dose of PRP or HA. In the early OA subgroups, significantly better clinical results were achieved in the patients treated with three PRP injections, but there was no significant difference in the clinical results of patients with advanced OA among the treatment groups. The clinical results of this study suggest IA PRP and HA treatment for all stages of knee OA. For patients with early OA, multiple (3) PRP injections are useful in achieving better clinical results. For patients with advanced OA, multiple injections do not significantly improve the results of patients in any group. I.

Comparison between PRP, PRGF and PRF: lights and shadows in three similar but different protocols.

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Giannini, S; Cielo, A; Bonanome, L; Rastelli, C; Derla, C; Corpaci, F; Falisi, G

2015-01-01

The main goal of the modern surgery is to get a low invasiveness and a high rate of clinical healing: in the last years, it has been introduced the concept of a "regenerative surgery", and many techniques has been widely described in the literature. The most used are PRP, PRGF and PRF techniques. Aim of this research is to compare the three protocol of PRP, PRF and PRGF in their essential features, so to suggest to the practitioners the best blood product to use in the regenerative surgery. Among the advantages that shows the PRF, compared to PRP and PRGF, we can cite a greater simplicity of production for the absence of manipulation that leads to a reduced possibility of alteration of the protocol due to an error of the operator. The special texture of the PRF and its biological features shows clearly an interesting surgical versatility and all the characteristics that can support a faster tissues regeneration and high-quality clinical outcomes.

Comparison between Conventional Mechanical Fixation and Use of Autologous Platelet Rich Plasma (PRP) in Wound Beds Prior to Resurfacing with Split Thickness Skin Graft.

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P Waiker, Veena; Shivalingappa, Shanthakumar

2015-01-01

Platelet rich plasma is known for its hemostatic, adhesive and healing properties in view of the multiple growth factors released from the platelets to the site of wound. The primary objective of this study was to use autologous platelet rich plasma (PRP) in wound beds for anchorage of skin grafts instead of conventional methods like sutures, staplers or glue. In a single center based randomized controlled prospective study of nine months duration, 200 patients with wounds were divided into two equal groups. Autologous PRP was applied on wound beds in PRP group and conventional methods like staples/sutures used to anchor the skin grafts in a control group. Instant graft adherence to wound bed was statistically significant in the PRP group. Time of first post-graft inspection was delayed, and hematoma, graft edema, discharge from graft site, frequency of dressings and duration of stay in plastic surgery unit were significantly less in the PRP group. Autologous PRP ensured instant skin graft adherence to wound bed in comparison to conventional methods of anchorage. Hence, we recommend the use of autologous PRP routinely on wounds prior to resurfacing to ensure the benefits of early healing.

Mechanical and Controlled PRP Injections in Patients Affected by Androgenetic Alopecia.

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Gentile, Pietro; Garcovich, Simone; Scioli, Maria Giovanna; Bielli, Alessandra; Orlandi, Augusto; Cervelli, Valerio

2018-01-27

23 patients (18 male and 5 female) aged 21-70 years who displayed male pattern hair loss (MPHL) in Stage 1 to Stage 5 as determined by the Norwood-Hamilton classification scale, and female pattern hair loss (FPHL) in Stage 1 to Stage 2 as determined by the Ludwig classification scale, were treated with non-activated autologous platelet-rich plasma (A-PRP). Autologous blood (55 mL) was harvested using sodium citrate as an anticoagulant. A-PRP (23 mL) was produced for all cases using a closed system according to the transfusion service protocol. Following centrifugation (260 x g for 10 min) the A-PRP was inserted in a laser light selector device, and after the centrifugation, 9 mL of A-PRP was collected. The scalp of the patients affected by androgenetic alopecia (AGA) was divided into four areas (frontal, parietal, vertex, and occipital); local anesthesia was not performed. Interfollicular A-PRP injections (0.2 mL x cm 2 ) were performed by controlled and mechanical injections scheduled at a depth of 5 mm using a medical injector gun. Treatment sessions were performed with a 30-day interval. For each patient, three treatment sessions were performed. PRP was injected in the androgen-related areas of scalp affected by hair loss. Placebo (normal saline solution) was loaded in another syringe (10 mL) and injected on the adjacent side in a similar fashion.

Platelet-rich plasma (PRP for the treatment of vulvar lichen sclerosus in a premenopausal woman: A case report

Directory of Open Access Journals (Sweden)

D. Franic

2018-04-01

Full Text Available The use of platelet-rich plasma (PRP for the treatment of lichen sclerosus (LS in a 38-year-old premenopausal woman is reported. The diagnosis was confirmed histologically and the symptoms documented using the ICIQ Vaginal Symptoms Questionnaire (ICIQ-VS and the Female Sexual Function Index (FSFI questionnaire. PRP was prepared from autologous blood using the Regen Cellular Matrix Kit. PRP was administered twice over two months. Histology at follow-up one month after the second administration showed the epidermis was nearly normal and upper dermal cellularity had been restored. The patient was symptom-free and both her ICIQ-VS and her FSFI scores had improved significantly. PRP is a potential new treatment option for LS which needs further assessment in randomized controlled trials. Keywords: Platelet-rich plasma, Vulvar lichen sclerosus, Premenopause, Treatment

Platelet-rich plasma (PRP for acute muscle injury: a systematic review.

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Mohamad Shariff A Hamid

Full Text Available INTRODUCTION: Acute muscle injury is one of the commonest injuries that often result in loss of training and competition time. The best management for muscle injury has not been identified. Sports medicine practitioners used several approaches in attempt to accelerate time to recovery from muscle injury. More recently growing interest focussed on autologous blood product injection. METHODS: A literature search was conducted systematically using OvidMEDLINE, PubMed, EMBASE, SPORTDiscus and CINAHL databases to retrieve articles published until December 2012. Controlled trials and controlled laboratory studies comparing different strategies to promote early recovery of muscle injury were included. The methodological quality of studies was assessed. RESULTS: There are limited studies on the effects of PRP therapy for muscle injury. Three in vivo laboratory studies and one pilot human study were reviewed. The laboratory studies reported histological evidence on significant acceleration of muscle healing in animals treated with autologous conditioned serum (ACS, platelet-rich plasma (PRP and platelet rich fibrin matrix (PRFM. A pilot human study found athletes treated with repeated ACS injection recovers significantly faster than retrospective controls. CONCLUSION: Several in vivo laboratory studies suggest beneficial effects of ACS, PRP and PRFM in accelerating muscle recovery. Evidence to suggest similar effects on humans is however limited, as valuable information from robust human controlled trials is still not available at this moment. Hence, more studies of satisfactory methodological quality with platelet-rich plasma interventions on muscle injury are justified.

What About the Rheological Properties of PRP/Microfat Mixtures in Fat Grafting Procedure?

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Ghazouane, R; Bertrand, B; Philandrianos, C; Veran, J; Abellan, M; Francois, P; Velier, M; Orneto, C; Piccerelle, P; Magalon, J

2017-10-01

Fat grafting has emerged as a reference procedure in daily plastic surgery practice. Unpredictable fat resorption is the main clinical problem. For this purpose, the addition of PRP to enhance fat revascularization is now an easy and popular procedure. However, no consensus exists regarding the respective volume of fat and PRP used to obtain the ideal mixture. This study investigated the rheological properties of microfat mixed with different proportions of PRP. Results obtained were compared with commercialized hyaluronic acid fillers. Microfat and PRP preparations were performed using standardized techniques. Lipoaspirate residue and blood were obtained from six patients undergoing aesthetic facial microlipofilling. Elastic modulus G' and tan δ (proportion of elasticity versus fluidity) were obtained for the following conditions: microfat alone and microfat mixed with 10, 30 or 50% of PRP. An expected decrease in elastic modulus was observed by adding increase volumes of PRP. Two groups of products with different rheological properties were considered based on statistical differences highlighted regarding the value of G'. Mean tan δ varied from 0.20 ± 0.04 (microfat alone) to 0.28 ± 0.08 (50% microfat/50% PRP). Microfat mixed with 10% of PRP presents consistency comparable to stiffer fillers, whereas microfat mixed with 30 or 50% corresponds to softer fillers. Rheological differences were highlighted given the proportion of PRP added to the microfat. Further studies assessing the impact of increased doses of platelets in microfat/PRP mixtures on clinical outcomes should also be investigated. Our findings will help clinicians to choose a mixture that meets their specific needs for a given indication. 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.

Semisynthetic prion protein (PrP) variants carrying glycan mimics at position 181 and 197 do not form fibrils.

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Araman, Can; Thompson, Robert E; Wang, Siyao; Hackl, Stefanie; Payne, Richard J; Becker, Christian F W

2017-09-01

The prion protein (PrP) is an N -glycosylated protein attached to the outer leaflet of eukaryotic cell membranes via a glycosylphosphatidylinositol (GPI) anchor. Different prion strains have distinct glycosylation patterns and the extent of glycosylation of potentially pathogenic misfolded prion protein (PrP Sc ) has a major impact on several prion-related diseases (transmissible spongiform encephalopathies, TSEs). Based on these findings it is hypothesized that posttranslational modifications (PTMs) of PrP influence conversion of cellular prion protein (PrP C ) into PrP Sc and, as such, modified PrP variants are critical tools needed to investigate the impact of PTMs on the pathogenesis of TSEs. Here we report a semisynthetic approach to generate PrP variants modified with monodisperse polyethyleneglycol (PEG) units as mimics of N-glycans. Incorporating PEG at glycosylation sites 181 and 197 in PrP induced only small changes to the secondary structure when compared to unmodified, wildtype PrP. More importantly, in vitro aggregation was abrogated for all PEGylated PrP variants under conditions at which wildtype PrP aggregated. Furthermore, the addition of PEGylated PrP as low as 10 mol% to wildtype PrP completely blocked aggregation. A similar effect was observed for synthetic PEGylated PrP segments comprising amino acids 179-231 alone if these were added to wildtype PrP in aggregation assays. This behavior raises the question if large N-glycans interfere with aggregation in vivo and if PEGylated PrP peptides could serve as potential therapeutics.

PrP Conformational Transitions Alter Species Preference of a PrP-specific antibody

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Zou, W.Q.; Langeveld, J.P.M.; Xiao, X.; Chen, S.; McGeer, P.L.; Yuan, J.; Payne, M.C.; Kang, H.E.; McGeehan, J.M.; Sy, M.S.; Greenspan, N.S.; Kaplan, D.; Wang, G.X.; Parchi, P.; Hoover, E.A.; Kneale, G.; Telling, G.; Surewicz, W.; Kong, Q.; Guo, J.

2010-01-01

The epitope of the 3F4 antibody most commonly used in human prion disease diagnosis is believed to consist of residues Met-Lys-His-Met (MKHM) corresponding to human PrP-(109–112). This assumption is based mainly on the observation that 3F4 reacts with human and hamster PrP but not with PrP from

A call for a standard classification system for future biologic research: the rationale for new PRP nomenclature.

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Mautner, Kenneth; Malanga, Gerard A; Smith, Jay; Shiple, Brian; Ibrahim, Victor; Sampson, Steven; Bowen, Jay E

2015-04-01

Autologous cell therapies including platelet-rich plasma (PRP) and bone marrow concentrate (BMC) are increasingly popular options for soft tissue and joint-related diseases. Despite increased clinical application, conflicting research has been published regarding the efficacy of PRP, and few clinical publications pertaining to BMC are available. Preparations of PRP (and BMC) can vary in many areas, including platelet concentration, number of white blood cells, presence or absence of red blood cells, and activation status of the preparation. The potential effect of PRP characteristics on PRP efficacy is often not well understood by the treating clinician, and PRP characteristics, as well as the volume of PRP delivered, are unfortunately not included in the methods of many published research articles. It is essential to establish a standard reporting system for PRP that facilitates communication and the interpretation and synthesis of scientific investigations. Herein, the authors propose a new PRP classification system reflecting important PRP characteristics based on contemporary literature and recommend adoption of minimal standards for PRP reporting in scientific investigations. Widespread adoption of these recommendations will facilitate interpretation and comparison of clinical studies and promote scientifically based progress in the field of regenerative medicine. Copyright © 2015 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

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

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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.

Microbicidal properties of Leukocyte- and Platelet-Rich Plasma/Fibrin (L-PRP/L-PRF): new perspectives.

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Cieslik-Bielecka, A; Dohan Ehrenfest, D M; Lubkowska, A; Bielecki, T

2012-01-01

Platelets, as main actors of the first stage of the healing process, play an important role in tissue repair. Their granules contain many active substances, particularly over 30 growth factors with significant effects on the resident cells at the site of injury, such as mesenchymal stem cells, chondrocytes, fibroblasts, osteoblasts. This potential may be increased by the concentration of the platelets, using platelet-rich plasma/fibrin products. In the four families of platelet concentrates, 2 families contain also significant concentrations of leukocytes: L-PRP (Leukocyte- and Platelet-Rich Plasma) and L-PRF (Leukocyte- and Platelet-Rich Fibrin). Inductive properties of platelet concentrates were widely described. However, they present also antimicrobial effects. The antibacterial effects of L-PRP were highlighted in only a few in vitro studies. Strong activity comparable to gentamicin and oxacillin for L-PRP against methicillin susceptible Staphylococcus aureus (MSSA) was already demonstrated. L-PRP also inhibited the growth of methicillin resistant Staphylococcus aureus (MRSA) and Escherichia coli. Some authors also reported clinical observations about the reduction of infections and the induction of healing processes after the use of platelet concentrates in cardiac, orthopaedic, oral and maxillofacial surgery. However, very little is yet known about the antibacterial effects of these concentrates. In this manuscript, the current data about the antimicrobial agents and cells present in the platelet-rich plasma/fibrin are highlighted and discussed, in order to introduce this new key chapter of the platelet concentrate technology history.

Oxidation of Helix-3 methionines precedes the formation of PK resistant PrP.

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Tamar Canello

2010-07-01

Full Text Available While elucidating the peculiar epitope of the alpha-PrP mAb IPC2, we found that PrPSc exhibits the sulfoxidation of residue M213 as a covalent signature. Subsequent computational analysis predicted that the presence of sulfoxide groups at both Met residues 206 and 213 destabilize the alpha-fold, suggesting oxidation may facilitate the conversion of PrPC into PrPSc. To further study the effect of oxidation on prion formation, we generated pAbs to linear PrP peptides encompassing the Helix-3 region, as opposed to the non-linear complexed epitope of IPC2. We now show that pAbs, whose epitopes comprise Met residues, readily detected PrPC, but could not recognize most PrPSc bands unless they were vigorously reduced. Next, we showed that the alpha-Met pAbs did not recognize newly formed PrPSc, as is the case for the PK resistant PrP present in lines of prion infected cells. In addition, these reagents did not detect intermediate forms such as PK sensitive and partially aggregated PrPs present in infected brains. Finally, we show that PrP molecules harboring the pathogenic mutation E200K, which is linked to the most common form of familial CJD, may be spontaneously oxidized. We conclude that the oxidation of methionine residues in Helix-3 represents an early and important event in the conversion of PrPC to PrPSc. We believe that further investigation into the mechanism and role of PrP oxidation will be central in finally elucidating the mechanism by which a normal cell protein converts into a pathogenic entity that causes fatal brain degeneration.

Investigation of modified platelet-rich plasma (mPRP in promoting the proliferation and differentiation of dental pulp stem cells from deciduous teeth

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J. Wen

2016-01-01

Full Text Available Stem cells from human exfoliated deciduous teeth (SHEDs have great potential to treat various dental-related diseases in regenerative medicine. They are usually maintained with 10% fetal bovine serum (FBS in vitro. Modified platelet-rich plasma (mPRP would be a safe alternative to 10% FBS during SHEDs culture. Therefore, our study aimed to compare the proliferation and differentiation of SHEDs cultured in mPRP and FBS medium to explore an optimal concentration of mPRP for SHEDs maintenance. Platelets were harvested by automatic blood cell analyzer and activated by repeated liquid nitrogen freezing and thawing. The platelet-related cytokines were examined and analyzed by ELISA. SHEDs were extracted and cultured with different concentrations of mPRP or 10% FBS medium. Alkaline phosphatase (ALP activity was measured. Mineralization factors, RUNX2 and OCN, were measured by real-time PCR. SHEDs were characterized with mesenchymal stem cells (MSCs markers including vimentin, CD44, and CD105. mPRP at different concentrations (2, 5, 10, and 20% enhanced the growth of SHEDs. Moreover, mPRP significantly stimulated ALP activity and promoted expression of RUNX2 and OCN compared with 10% FBS. mPRP could efficiently facilitate proliferation and differentiation of SHEDs, and 2% mPRP would be an optimal substitute for 10% FBS during SHEDs expansion and differentiation in clinical scale manufacturing.

Expressions of pathologic markers in PRP based chondrogenic differentiation of human adipose derived stem cells.

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Pakfar, Arezou; Irani, Shiva; Hanaee-Ahvaz, Hana

2017-02-01

Optimization of the differentiation medium through using autologous factors such as PRP is of great consideration, but due to the complex, variable and undefined composition of PRP on one hand and lack of control over the absolute regulatory mechanisms in in vitro conditions or disrupted and different mechanisms in diseased tissue microenvironments in in vivo conditions on the other hand, it is complicated and rather unpredictable to get the desired effects of PRP making it inevitable to monitor the possible pathologic or undesired differentiation pathways and therapeutic effects of PRP. Therefore, in this study the probable potential of PRP on inducing calcification, inflammation and angiogenesis in chondrogenically-differentiated cells was investigated. The expressions of chondrogenic, inflammatory, osteogenic and angiogenic markers from TGFβ or PRP-treated cells during chondrogenic differentiation of human adipose-derived stem cells (ADSCs) was evaluated. Expressions of Collagen II (Col II), Aggrecan, Sox9 and Runx2 were quantified using q-RT PCR. Expression of Col II and X was investigated by immunocytochemistry as well. Glycosaminoglycans (GAGs) production was also determined by GAG assay. Possible angiogenic/inflammatory potential was determined by quantitatively measuring the secreted VEGF, TNFα and phosphorylated VEGFR2 via ELISA. In addition, the calcification of the construct was monitored by measuring ALP activity and calcium deposition. Our data showed that PRP positively induced chondrogenesis; meanwhile the secretion of angiogenic and inflammatory markers was decreased. VEGFR2 phosphorylation and ALP activity had a decreasing trend, but tissue mineralization was enhanced upon treating with PRP. Although reduction in inflammatory/angiogenic potential of the chondrogenically differentiated constructs highlights the superior effectiveness of PRP in comparison to TGFβ for chondrogenic differentiation, yet further improvement of the PRP

Platelet-rich plasma (PRP) and adipose-derived mesenchymal stem cells: stimulatory effects on proliferation and migration of fibroblasts and keratinocytes in vitro.

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Stessuk, Talita; Puzzi, Maria Beatriz; Chaim, Elinton Adami; Alves, Paulo César Martins; de Paula, Erich Vinicius; Forte, Andresa; Izumizawa, Juliana Massae; Oliveira, Carolina Caliári; Frei, Fernando; Ribeiro-Paes, João Tadeu

2016-09-01

The clinical use of tissue engineering associated with cell therapy is considered a new alternative therapy for the repair of chronic lesions with potential application in different medical areas, mostly in orthopedic and dermatological diseases. Platelet-rich plasma (PRP) is a rich source of growth factors and cytokines important for wound healing. Adipose-derived mesenchymal stem cells (ADSCs) have shown potential to accelerate the resolution of ulcers, to stimulate cell proliferation, and to benefit the quality of skin repair. This study aims to determine the effect of PRP and conditioned medium (CM) from ADSC on fibroblast and keratinocyte proliferation in vitro. Migration and proliferation assays were performed to evaluate the growth of fibroblasts and keratinocytes in the presence of PRP, CM, and CM + PRP. Significant proliferative stimulation was observed after 48 h of culture (p PRP, 100 % CM, and 25 % PRP + 25 % CM, if compared with control. Keratinocyte proliferation was stimulated after 48 h in cultures with 25, 50, and 100 % CM, and growth was compared with controls. The migration assay detected a significant migratory stimulus in fibroblasts cultured with 10 % PRP + 10 % CM after 48 h. These in vitro results suggest that PRP and ADSC have therapeutic potential for healing and re-epithelialization of chronic wounds in vivo.

Effect of Platelet-Rich Plasma (PRP versus Autologous Whole Blood on Pain and Function Improvement in Tennis Elbow: A Randomized Clinical Trial

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Seyed Ahmad Raeissadat

2014-01-01

Full Text Available Background. Autologous whole blood and platelet-rich plasma (PRP have been both suggested to treat chronic tennis elbow. The aim of the present study was to compare the effects of PRP versus autologous whole blood local injection in chronic tennis elbow. Methods. Forty patients with tennis elbow were randomly divided into 2 groups. Group 1 was treated with a single injection of 2 mL of autologous PRP and group 2 with 2 mL of autologous blood. Tennis elbow strap, stretching, and strengthening exercises were administered for both groups during a 2-month followup. Pain and functional improvements were assessed using visual analog scale (VAS, modified Mayo Clinic performance index for the elbow, and pressure pain threshold (PPT at 0, 4, and 8 weeks. Results. All pain and functional variables including VAS, PPT, and Mayo scores improved significantly in both groups 4 weeks after injection. No statistically significant difference was noted between groups regarding pain scores in 4-week follow-up examination (P>0.05. At 8-week reevaluations, VAS and Mayo scores improved only in PRP group (P<0.05. Conclusion. PRP and autologous whole blood injections are both effective to treat chronic lateral epicondylitis. PRP might be slightly superior in 8-week followup. However, further studies are suggested to get definite conclusion.

Platelet rich plasma (PRP) induces chondroprotection via increasing autophagy, anti-inflammatory markers, and decreasing apoptosis in human osteoarthritic cartilage

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Moussa, Mayssam, E-mail: Moussa-mayssam@hotmail.com [Regenerative medicine and inflammation Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); Lajeunesse, Daniel, E-mail: daniel.lajeunesse@umontreal.ca [Research Centre in Osteoarthritis, Research Centre in Monteral University (Canada); Hilal, George, E-mail: George2266@gmail.com [Cancer and metabolism Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); El Atat, Oula, E-mail: oulaatat@hotmail.com [Regenerative medicine and inflammation Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); Haykal, Gaby, E-mail: Gaby.haykal@hdf.usj.edu.lb [Hotel Dieu de France, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); Serhal, Rim, E-mail: rim.basbous@gmail.com [Regenerative medicine and inflammation Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); Chalhoub, Antonio, E-mail: Mava.o@hotmail.com [Carantina Hospital, Beirut (Lebanon); Khalil, Charbel, E-mail: charbelk3@hotmail.com [Regenerative medicine and inflammation Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon); Alaaeddine, Nada, E-mail: Nada.aladdin@gmail.com [Regenerative medicine and inflammation Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut (Lebanon)

2017-03-01

Objectives: Autophagy constitutes a defense mechanism to overcome aging and apoptosis in osteoarthritic cartilage. Several cytokines and transcription factors are linked to autophagy and play an important role in the degradative cascade in osteoarthritis (OA). Cell therapy such as platelet rich plasma (PRP) has recently emerged as a promising therapeutic tool for many diseases including OA. However, its mechanism of action on improving cartilage repair remains to be determined. The purpose of this study is to investigate the effect of PRP on osteoarthritic chondrocytes and to elucidate the mechanism by which PRP contributes to cartilage regeneration. Methods: Osteoarthritic chondrocytes were co-cultured with an increasing concentration of PRP obtained from healthy donors. The effect of PRP on the proliferation of chondrocytes was performed using cell counting and WST8 proliferation assays. Autophagy, apoptosis and intracellular level of IL-4, IL-10, and IL-13 were determined using flow cytometry analyses. Autophagy markers BECLIN and LC3II were also determined using quantitative polymerase chain reaction (qPCR). qPCR and ELISA were used to measure the expression of ADAMDTS-5, MMP3, MMP13, TIMP-1–2–3, aggregan, Collagen type 2, TGF-β, Cox-2, Il-6, FOXO1, FOXO3, and HIF-1 in tissues and co-cultured media. Results: PRP increased significantly the proliferation of chondrocytes, decreased apoptosis and increased autophagy and its markers along with its regulators FOXO1, FOXO3 and HIF-1 in osteoarthritic chondrocytes. Furthermore, PRP caused a dose-dependent significant decrease in MMP3, MMP13, and ADAMTS-5, IL-6 and COX-2 while increasing TGF-β, aggregan, and collagen type 2, TIMPs and intracellular IL-4, IL-10, IL-13. Conclusion: These results suggest that PRP could be a potential therapeutic tool for the treatment of OA. - Highlights: • Platelet Rich Plasma is suggested as a new treatment for osteoarthritis. • The proposed therapeutic effect is

Platelet rich plasma (PRP) induces chondroprotection via increasing autophagy, anti-inflammatory markers, and decreasing apoptosis in human osteoarthritic cartilage

International Nuclear Information System (INIS)

Moussa, Mayssam; Lajeunesse, Daniel; Hilal, George; El Atat, Oula; Haykal, Gaby; Serhal, Rim; Chalhoub, Antonio; Khalil, Charbel; Alaaeddine, Nada

2017-01-01

Objectives: Autophagy constitutes a defense mechanism to overcome aging and apoptosis in osteoarthritic cartilage. Several cytokines and transcription factors are linked to autophagy and play an important role in the degradative cascade in osteoarthritis (OA). Cell therapy such as platelet rich plasma (PRP) has recently emerged as a promising therapeutic tool for many diseases including OA. However, its mechanism of action on improving cartilage repair remains to be determined. The purpose of this study is to investigate the effect of PRP on osteoarthritic chondrocytes and to elucidate the mechanism by which PRP contributes to cartilage regeneration. Methods: Osteoarthritic chondrocytes were co-cultured with an increasing concentration of PRP obtained from healthy donors. The effect of PRP on the proliferation of chondrocytes was performed using cell counting and WST8 proliferation assays. Autophagy, apoptosis and intracellular level of IL-4, IL-10, and IL-13 were determined using flow cytometry analyses. Autophagy markers BECLIN and LC3II were also determined using quantitative polymerase chain reaction (qPCR). qPCR and ELISA were used to measure the expression of ADAMDTS-5, MMP3, MMP13, TIMP-1–2–3, aggregan, Collagen type 2, TGF-β, Cox-2, Il-6, FOXO1, FOXO3, and HIF-1 in tissues and co-cultured media. Results: PRP increased significantly the proliferation of chondrocytes, decreased apoptosis and increased autophagy and its markers along with its regulators FOXO1, FOXO3 and HIF-1 in osteoarthritic chondrocytes. Furthermore, PRP caused a dose-dependent significant decrease in MMP3, MMP13, and ADAMTS-5, IL-6 and COX-2 while increasing TGF-β, aggregan, and collagen type 2, TIMPs and intracellular IL-4, IL-10, IL-13. Conclusion: These results suggest that PRP could be a potential therapeutic tool for the treatment of OA. - Highlights: • Platelet Rich Plasma is suggested as a new treatment for osteoarthritis. • The proposed therapeutic effect is

In Vitro Studies on the Degradability, Bioactivity, and Cell Differentiation of PRP/AZ31B Mg Alloys Composite Scaffold

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Jian Zou

2017-01-01

Full Text Available In recent years, more and more methods have been developed to improve the bioactivity of the biodegradable materials in bone tissue regeneration. In present study, we used rat mesenchymal stem cells (rMSCs to evaluate the outcomes of Mg alloys (AZ31B, Magnesium, and Aluminum and Platelet-rich plasma (PRP/Mg alloys on rMSCs biocompatibility and osteogenic differentiation. Water absorption experiments indicated that both bare AZ31B and PRP/AZ31B were capable of absorbing large amounts of water. But the water absorption ratio for PRP/AZ31B was significantly higher than that for bare AZ31B. The degradability experiments implied that both samples degraded at same speed. rMSCs on the surface of AZ31B distributed more and better than those on the AZ31B scaffold. In ALP activity experiment, the activity of rMSCs on the PRP/AZ31B was markedly higher than that on the AZ31B scaffolds on the 7th day and 14th day. qRT-PCR also showed that OPN and OCN were expressed in both samples. OPN and OCN expression in PRP/AZ31B sample were higher than those in bare AZ31B samples. In summary, the in vitro study implied that AZ31B combined with PRP could remarkably improve cell seeding, attachment, proliferation, and differentiation.

Platelet rich plasma injections for lateral epicondylitis of the elbow reduce the need for surgical intervention.

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Hastie, Graham; Soufi, Mazen; Wilson, James; Roy, Bibhas

2018-03-01

We aimed to assess the effectiveness of PRP injections in lateral epicondylitis of the elbow as it was felt after PRP introduction the numbers of patients requiring surgery for had reduced. We conducted a retrospective review of cases from the 1 st January 2008 to 31st December 2015. The numbers of patients undergoing surgical release and the numbers of patients requiring PRP injections were recorded each year and the numbers of patients requiring surgery was compared pre and post PRP injection to ascertain if PRP introduction reduced surgical intervention. Prior to PRP, a yearly mean of 12.75 patients underwent surgery, since PRP this reduced to 4.25 patients, P lateral epicondylitis of the elbow, not only a safe but also very effective tool in reducing symptoms and have shown it has reduced the need for surgical intervention in this difficult cohort of patients.

A Comparison of Platelet Count and Enrichment Percentages in the Platelet Rich Plasma (PRP) Obtained Following Preparation by Three Different Methods.

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Sabarish, Ram; Lavu, Vamsi; Rao, Suresh Ranga

2015-02-01

Platelet rich plasma (PRP) represents an easily accessible and rich source of autologous growth factors. Different manual methods for the preparation of PRP have been suggested. Lacuna in knowledge exists about the efficacy of PRP preparation by these different manual methods. This study was performed to determine the effects of centrifugation rate revolutions per minute (RPM) and time on the platelet count and enrichment percentages in the concentrates obtained following the three different manual methods of PRP preparation. In vitro experimental study. This was an experimental study in which platelet concentration was assessed in the PRP prepared by three different protocols as suggested by Marx R (method 1), Okuda K (method 2) and Landesberg R (method 3). A total of 60 peripheral blood samples, (n=20 per method) were obtained from healthy volunteers. Baseline platelet count was assessed for all the subjects following which PRP was prepared. The platelet count in the PRP was determined using coulter counter (Sysmex XT 2000i). The mean of the platelet count obtained and their enrichment percentage were calculated and intergroup comparison was done (Tukey's HSD test). The number of platelets and enrichment percentage in PRP prepared by method 1 was higher compared to method 2 and method 3; this difference in platelet concentrates was found to be statistically significant (p < 0.05). The centrifugation rate and time appear to be important parameters, which influence the platelet yield. Method 1 which had lower centrifugation rate and time yielded a greater platelet count and enrichment percentage.

Splicing Factor Prp8 Interacts With NES(AR) and Regulates Androgen Receptor in Prostate Cancer Cells.

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Wang, Dan; Nguyen, Minh M; Masoodi, Khalid Z; Singh, Prabhpreet; Jing, Yifeng; O'Malley, Katherine; Dar, Javid A; Dhir, Rajiv; Wang, Zhou

2015-12-01

Androgen receptor (AR) plays a pivotal role in the development of primary as well as advanced castration-resistant prostate cancer. Previous work in our lab identified a novel nuclear export signal (NES) (NES(AR)) in AR ligand-binding domain essential for AR nucleocytoplasmic trafficking. By characterizing the localization of green fluorescence protein (GFP)-tagged NES(AR), we designed and executed a yeast mutagenesis screen and isolated 7 yeast mutants that failed to display the NES(AR) export function. One of those mutants was identified as the splicing factor pre-mRNA processing factor 8 (Prp8). We further showed that Prp8 could regulate NES(AR) function using short hairpin RNA knockdown of Prp8 coupled with a rapamycin export assay in mammalian cells and knockdown of Prp8 could induce nuclear accumulation of GFP-tagged AR in PC3 cells. Prp8 expression was decreased in castration-resistant LuCaP35 xenograft tumors as compared with androgen-sensitive xenografts. Laser capture microdissection and quantitative PCR showed Prp8 mRNA levels were decreased in human prostate cancer specimens with high Gleason scores. In prostate cancer cells, coimmunoprecipitation and deletion mutagenesis revealed a physical interaction between Prp8 and AR mainly mediated by NES(AR). Luciferase assay with prostate specific antigen promoter-driven reporter demonstrated that Prp8 regulated AR transcription activity in prostate cancer cells. Interestingly, Prp8 knockdown also increased polyubiquitination of endogenous AR. This may be 1 possible mechanism by which it modulates AR activity. These results show that Prp8 is a novel AR cofactor that interacts with NES(AR) and regulates AR function in prostate cancer cells.

Characterization of barley Prp1 gene and its expression during seed development and under abiotic stress.

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Jiang, Qian-Tao; Liu, Tao; Ma, Jian; Wei, Yu-Ming; Lu, Zhen-Xiang; Lan, Xiu-Jin; Dai, Shou-Fen; Zheng, You-Liang

2011-10-01

The pre-mRNA processing (Prp1) gene encodes a spliceosomal protein. It was firstly identified in fission yeast and plays a regular role during spliceosome activation and cell cycle. Plant Prp1 genes have only been identified from rice, Sorghum and Arabidopsis thaliana. In this study, we reported the identification and isolation of a novel Prp1 gene from barley, and further explored its expressional pattern by using real-time quantitative RTPCR, promoter prediction and analysis of microarray data. The putative barley Prp1 protein has a similar primary structure features to those of other known Prp1 protein in this family. The results of amino acid comparison indicated that Prp1 protein of barley and other plant species has a highly conserved 30 termnal region while their 50 sequences greatly varied. The results of expressional analysis revealed that the expression level of barley Prp1 gene is always stable in different vegetative tissues, except it is up-regulated at the mid- and late stages of seed development or under the condition of cold stress. This kind of expressional pattern for barley Prp1 is also supported by our results of comparison of microarray data from barley, rice and Arabidopsis. For the molecular mechanism of its expressional pattern, we conclude that the expression of Prp1 gene may be up-regulated by the increase of pre-mRNAs and not be constitutive or ubiquitous.

Can platelet-rich plasma (PRP) improve bone healing? A comparison between the theory and experimental outcomes.

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Malhotra, Angad; Pelletier, Matthew H; Yu, Yan; Walsh, William R

2013-02-01

The increased concentration of platelets within platelet-rich plasma (PRP) provides a vehicle to deliver supra-physiologic concentrations of growth factors to an injury site, possibly accelerating or otherwise improving connective tissue regeneration. This potential benefit has led to the application of PRP in several applications; however, inconsistent results have limited widespread adoption in bone healing. This review provides a core understanding of the bone healing mechanisms, and corresponds this to the factors present in PRP. In addition, the current state of the art of PRP preparation, the key aspects that may influence its effectiveness, and treatment outcomes as they relate specifically to bone defect healing are presented. Although PRP does have a sound scientific basis, its use for bone healing appears only beneficial when used in combination with osteoconductive scaffolds; however, neither allograft nor autograft appear to be appropriate carriers. Aggressive processing techniques and very high concentrations of PRP may not improve healing outcomes. Moreover, many other variables exist in PRP preparation and use that influence its efficacy; the effect of these variables should be understood when considering PRP use. This review includes the essentials of what has been established, what is currently missing in the literature, and recommendations for future directions.

Evaluation of Not-Activated and Activated PRP in Hair Loss Treatment: Role of Growth Factor and Cytokine Concentrations Obtained by Different Collection Systems

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Pietro Gentile

2017-02-01

Full Text Available Platelet rich plasma (PRP was tested as a potential therapy for androgenetic alopecia (AGA through two different clinical protocols in which one population (18 participants received half-head treatment with autologous non-activated PRP (A-PRP produced by CPunT Preparation System (Biomed Device, Modena, Italy and the other half-head with placebo, and a second separated population in which all participants (n = 6, 3 participants per group received treatment with calcium-activated PRP (AA-PRP produced from one of two different PRP collection devices (Regen Blood Cell Therapy or Arthrex Angel System. For the A-PRP study, three treatments were administered over 30-day intervals. Trichoscan analysis of patients, three months post-treatment, showed a clinical improvement in the number of hairs in the target area (36 ± 3 hairs and in total hair density (65±  5 hair cm2, whereas negligible improvements in hair count (1.1±  1.4 hairs and density (1.9 ± 10.2 hair cm2 were seen in the region of the scalp that received placebo. Microscopic evaluation conducted two weeks after treatment showed also an increase in epidermal thickness, Ki67+ keratinocytes, and in the number of follicles. The AA-PRP treatment groups received a singular set of injections, and six months after the treatments were administered, notable differences in clinical outcomes were obtained from the two PRP collection devices (+90 ± 6 hair cm2 versus -73 ± 30 hair cm2 hair densities, Regen versus Arthrex. Growth factor concentrations in AA-PRP prepared from the two collection devices did not differ significantly upon calcium activation.

Evaluation of Not-Activated and Activated PRP in Hair Loss Treatment: Role of Growth Factor and Cytokine Concentrations Obtained by Different Collection Systems.

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Gentile, Pietro; Cole, John P; Cole, Megan A; Garcovich, Simone; Bielli, Alessandra; Scioli, Maria Giovanna; Orlandi, Augusto; Insalaco, Chiara; Cervelli, Valerio

2017-02-14

Platelet rich plasma (PRP) was tested as a potential therapy for androgenetic alopecia (AGA) through two different clinical protocols in which one population (18 participants) received half-head treatment with autologous non-activated PRP (A-PRP) produced by CPunT Preparation System (Biomed Device, Modena, Italy) and the other half-head with placebo, and a second separated population in which all participants (n = 6, 3 participants per group) received treatment with calcium-activated PRP (AA-PRP) produced from one of two different PRP collection devices (Regen Blood Cell Therapy or Arthrex Angel System). For the A-PRP study, three treatments were administered over 30-day intervals. Trichoscan analysis of patients, three months post-treatment, showed a clinical improvement in the number of hairs in the target area (36 ± 3 hairs) and in total hair density (65±  5 hair cm2), whereas negligible improvements in hair count (1.1±  1.4 hairs) and density (1.9 ± 10.2 hair cm2) were seen in the region of the scalp that received placebo. Microscopic evaluation conducted two weeks after treatment showed also an increase in epidermal thickness, Ki67+ keratinocytes, and in the number of follicles. The AA-PRP treatment groups received a singular set of injections, and six months after the treatments were administered, notable differences in clinical outcomes were obtained from the two PRP collection devices (+90 ± 6 hair cm2 versus -73 ± 30 hair cm2 hair densities, Regen versus Arthrex). Growth factor concentrations in AA-PRP prepared from the two collection devices did not differ significantly upon calcium activation.

Mouse homologue of yeast Prp19 interacts with mouse SUG1, the regulatory subunit of 26S proteasome

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Sihn, Choong-Ryoul; Cho, Si Young; Lee, Jeong Ho; Lee, Tae Ryong; Kim, Sang Hoon

2007-01-01

Yeast Prp19 has been shown to involve in pre-mRNA splicing and DNA repair as well as being an ubiquitin ligase. Mammalian homologue of yeast Prp19 also plays on similar functional activities in cells. In the present study, we isolated mouse SUG1 (mSUG1) as binding partner of mouse Prp19 (mPrp19) by the yeast two-hybrid system. We confirmed the interaction of mPrp9 with mSUG1 by GST pull-down assay and co-immunoprecipitation assay. The N-terminus of mPrp19 including U-box domain was associated with the C-terminus of mSUG1. Although, mSUG1 is a regulatory subunit of 26S proteasome, mPrp19 was not degraded in the proteasome-dependent pathway. Interestingly, GFP-mPrp19 fusion protein was co-localized with mSUG1 protein in cytoplasm as the formation of the speckle-like structures in the presence of a proteasome inhibitor MG132. In addition, the activity of proteasome was increased in cells transfected with mPrp19. Taken together, these results suggest that mPrp19 involves the regulation of protein turnover and may transport its substrates to 26S proteasome through mSUG1 protein

A comparison between platelet-rich plasma (PRP and hyaluronate acid on the healing of cartilage defects.

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Ji Liu

Full Text Available Platelet-rich plasma (PRP has offered great promise for the treatment of cartilage degradation, and has been proved to have positive effects on the restoration of cartilage lesions. But no comparative work has been done between PRP and hyaluronate acid (HA concerning their restoring effect on cartilage defect, especially by means of animal experiments and histologic assessments. The purpose of the study was to compare the therapeutic effects of P-PRP and HA on osteoarthritis in rabbit knees. Thirty rabbits were used to establish the animal models by creating a cartilage defect of 5 mm in diameter on the condyles of the femurs, and were randomly divided into three groups: the P-PRP group, HA group and the control group. Then each group was treated with P-PRP, HA or saline solution, respectively. Six and twelve weeks later the rabbits were sacrificed and the samples were collected. The platelet number, the concentrations of growth factors of P-PRP and whole blood, and the IL-1β concentration in the joint fluid were investigated, and the histological assessment of the cartilage were performed according to Mankin's scoring system. Micro-CT was also used to evaluate the restoration of subchondral bone. The platelet concentration in P-PRP is 6.8 fold of that in the whole blood. The IL-1β level in the P-PRP group was lower than in the HA group (p<0.01 and in the control group (p<0.01. The restoration of the defected cartilage as well as the subchondral bone was better in the P-PRP group than in the HA group or the control group (P<0.05. Our data showed that P-PRP is better than HA in promoting the restoration of the cartilage and alleviating the arthritis caused by cartilage damage.

Effect of intralesional platelet-rich plasma (PRP) treatment on clinical and ultrasonographic parameters in equine naturally occurring superficial digital flexor tendinopathies - a randomized prospective controlled clinical trial.

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Geburek, Florian; Gaus, Moritz; van Schie, Hans T M; Rohn, Karl; Stadler, Peter M

2016-09-07

Regenerative and anti-inflammatory effects on tendinopathies have been attributed to blood-derived biologicals. To date the evidence for the efficacy of autologous platelet-rich plasma (PRP) treatment of naturally occurring equine tendinopathies is limited. The purpose of this placebo-controlled clinical trial was to describe the effect of a single treatment of equine superficial digital flexor tendon (SDFT) disease with PRP on clinical and ultrasonographic parameters. Twenty horses with naturally occurring tendinopathies of forelimb SDFTs were randomly assigned to the PRP-treated group (n = 10) or control group (n = 10) after clinical and ultrasonographic examination. The SDFTs received an intralesional treatment with autologous PRP or were injected with saline, respectively (day 0). All horses participated in a standardized exercise programme and were re-examined clinically, with B-mode ultrasonography (5 times at regular intervals) and ultrasound tissue characterization (week 12 and 24 after treatment) until week 24. Long-term performance was estimated via telephone inquiry. Compared to day 0, lameness decreased significantly by week 8 after treatment with PRP and by week 12 in the control group. Ultrasonographically there was no difference in the summarized cross sectional area between the groups at any time point. Ultrasound tissue characterization showed that echo types representing disorganized matrix decreased significantly throughout the observation period in the PRP-treated group. Echo type II, representing discontinuous fascicles, not yet aligned into lines of stress was significantly higher 24 weeks after PRP treatment. Eighty percent of the PRP treated horses reached their previous or a higher level of performance after 12 months compared to 50 % in the CG. After 24 months these proportions were 60 % and 50 %, respectively. A single intralesional treatment with PRP up to 8 weeks after onset of clinical signs of tendinopathy contributes

Experimental conditions and monitoring items of the prototype repository project (PRP). Research document

International Nuclear Information System (INIS)

Sugita, Yutaka; Ito, Akira; Kawakami, Susumu

2003-03-01

Various experiments are ongoing in the underground research facility 'the Hard Rock Laboratory (HRL)' of SKB in Sweden for the geological disposal of the high-level radioactive waste. International joint project Prototype Repository Project (PRP) is one of the experiments in the HRL which has some engineered barrier systems and to study the coupled behavior happening in and around the engineered barrier system. JNC has joined this international joint project PRP to obtain the information of the coupled behavior on such systematic engineered barrier system and to apply the JNC's coupled THMC analytical code to the prediction and back analysis of the PRP. The analytical code will be verified through these analyses in this project. JNC can apply the verified analytical code to assess the coupled behavior in Japan. This report summarizes the experimental conditions and monitoring items of the PRP. (author)

On the importance of Task 1 and error performance measures in PRP dual-task studies

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Strobach, Tilo; Schütz, Anja; Schubert, Torsten

2015-01-01

The psychological refractory period (PRP) paradigm is a dominant research tool in the literature on dual-task performance. In this paradigm a first and second component task (i.e., Task 1 and Task 2) are presented with variable stimulus onset asynchronies (SOAs) and priority to perform Task 1. The main indicator of dual-task impairment in PRP situations is an increasing Task 2-RT with decreasing SOAs. This impairment is typically explained with some task components being processed strictly sequentially in the context of the prominent central bottleneck theory. This assumption could implicitly suggest that processes of Task 1 are unaffected by Task 2 and bottleneck processing, i.e., decreasing SOAs do not increase reaction times (RTs) and error rates of the first task. The aim of the present review is to assess whether PRP dual-task studies included both RT and error data presentations and statistical analyses and whether studies including both data types (i.e., RTs and error rates) show data consistent with this assumption (i.e., decreasing SOAs and unaffected RTs and/or error rates in Task 1). This review demonstrates that, in contrast to RT presentations and analyses, error data is underrepresented in a substantial number of studies. Furthermore, a substantial number of studies with RT and error data showed a statistically significant impairment of Task 1 performance with decreasing SOA. Thus, these studies produced data that is not primarily consistent with the strong assumption that processes of Task 1 are unaffected by Task 2 and bottleneck processing in the context of PRP dual-task situations; this calls for a more careful report and analysis of Task 1 performance in PRP studies and for a more careful consideration of theories proposing additions to the bottleneck assumption, which are sufficiently general to explain Task 1 and Task 2 effects. PMID:25904890

On the importance of Task 1 and error performance measures in PRP dual-task studies.

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Strobach, Tilo; Schütz, Anja; Schubert, Torsten

2015-01-01

The psychological refractory period (PRP) paradigm is a dominant research tool in the literature on dual-task performance. In this paradigm a first and second component task (i.e., Task 1 and Task 2) are presented with variable stimulus onset asynchronies (SOAs) and priority to perform Task 1. The main indicator of dual-task impairment in PRP situations is an increasing Task 2-RT with decreasing SOAs. This impairment is typically explained with some task components being processed strictly sequentially in the context of the prominent central bottleneck theory. This assumption could implicitly suggest that processes of Task 1 are unaffected by Task 2 and bottleneck processing, i.e., decreasing SOAs do not increase reaction times (RTs) and error rates of the first task. The aim of the present review is to assess whether PRP dual-task studies included both RT and error data presentations and statistical analyses and whether studies including both data types (i.e., RTs and error rates) show data consistent with this assumption (i.e., decreasing SOAs and unaffected RTs and/or error rates in Task 1). This review demonstrates that, in contrast to RT presentations and analyses, error data is underrepresented in a substantial number of studies. Furthermore, a substantial number of studies with RT and error data showed a statistically significant impairment of Task 1 performance with decreasing SOA. Thus, these studies produced data that is not primarily consistent with the strong assumption that processes of Task 1 are unaffected by Task 2 and bottleneck processing in the context of PRP dual-task situations; this calls for a more careful report and analysis of Task 1 performance in PRP studies and for a more careful consideration of theories proposing additions to the bottleneck assumption, which are sufficiently general to explain Task 1 and Task 2 effects.

On the importance of Task 1 and error performance measures in PRP dual-task studies

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Tilo eStrobach

2015-04-01

Full Text Available The Psychological Refractory Period (PRP paradigm is a dominant research tool in the literature on dual-task performance. In this paradigm a first and second component task (i.e., Task 1 and 2 are presented with variable stimulus onset asynchronies (SOAs and priority to perform Task 1. The main indicator of dual-task impairment in PRP situations is an increasing Task 2-RT with decreasing SOAs. This impairment is typically explained with some task components being processed strictly sequentially in the context of the prominent central bottleneck theory. This assumption could implicitly suggest that processes of Task 1 are unaffected by Task 2 and bottleneck processing, i.e. decreasing SOAs do not increase RTs and error rates of the first task. The aim of the present review is to assess whether PRP dual-task studies included both RT and error data presentations and statistical analyses and whether studies including both data types (i.e., RTs and error rates show data consistent with this assumption (i.e., decreasing SOAs and unaffected RTs and/ or error rates in Task 1. This review demonstrates that, in contrast to RT presentations and analyses, error data is underrepresented in a substantial number of studies. Furthermore, a substantial number of studies with RT and error data showed a statistically significant impairment of Task 1 performance with decreasing SOA. Thus, these studies produced data that is not primarily consistent with the strong assumption that processes of Task 1 are unaffected by Task 2 and bottleneck processing in the context of PRP dual-task situations; this calls for a more careful report and analysis of Task 1 performance in PRP studies and for a more careful consideration of theories proposing additions to the bottleneck assumption, which are sufficiently general to explain Task 1 and Task 2 effects.

PrP mRNA and protein expression in brain and PrP(c) in CSF in Creutzfeldt-Jakob disease MM1 and VV2.

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Llorens, Franc; Ansoleaga, Belén; Garcia-Esparcia, Paula; Zafar, Saima; Grau-Rivera, Oriol; López-González, Irene; Blanco, Rosi; Carmona, Margarita; Yagüe, Jordi; Nos, Carlos; Del Río, José Antonio; Gelpí, Ellen; Zerr, Inga; Ferrer, Isidre

2013-01-01

Creutzfeldt-Jakob disease (CJD) is a heterogenic neurodegenerative disorder associated with abnormal post-translational processing of cellular prion protein (PrP(c)). CJD displays distinctive clinical and pathological features which correlate with the genotype at the codon 129 (methionine or valine: M or V respectively) in the prion protein gene and with size of the protease-resistant core of the abnormal prion protein PrP(sc) (type 1: 20/21 kDa and type 2: 19 kDa). MM1 and VV2 are the most common sporadic CJD (sCJD) subtypes. PrP mRNA expression levels in the frontal cortex and cerebellum are reduced in sCJD in a form subtype-dependent. Total PrP protein levels and PrP(sc) levels in the frontal cortex and cerebellum accumulate differentially in sCJD MM1 and sCJD VV2 with no relation between PrP(sc) deposition and spongiform degeneration and neuron loss, but with microgliosis, and IL6 and TNF-α response. In the CSF, reduced PrP(c), the only form present in this compartment, occurs in sCJD MM1 and VV2. PrP mRNA expression is also reduced in the frontal cortex in advanced stages of Alzheimer disease, Lewy body disease, progressive supranuclear palsy, and frontotemporal lobe degeneration, but PrP(c) levels in brain varies from one disease to another. Reduced PrP(c) levels in CSF correlate with PrP mRNA expression in brain, which in turn reflects severity of degeneration in sCJD.

The Effect of Platelet-Rich Plasma (PRP on Improvement in Pain and Symptoms of Shoulder Subacromial Impingement Syndrome

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Parisa Nejati

2015-08-01

Full Text Available Abstract Background: Subacromial impingement is one of the most common complaints of shoulder. Treatments include avoiding of painful activities, oral anti-pain drugs, physical therapy modalities, corticosteroid injection and exercise therapy. Some studies have shown that platelet- rich plasma(PRP is effective on tendinitis and tearing of tendons, ligaments and muscles, but evidence that has proved PRP as a conservative treatment in shoulder pathologies is very limited. This study aims to investigate the effect of PRP injection on relieving pain and improving daily function of patients with shoulder impingement syndrome. Materials and Methods: In this clinical trial study, patients older than 40 with pain more than three months were included. If they had three of four positive diagnostic clinical tests of shoulder impingement that were confirmed by shoulder MRI, could be injected PRP twice. The time between injections was 1 month. Pain was measured by visual analog scale (VAS and function was measured by two questionnaires named disabilities of the arm, shoulder and hand (DASH and western Ontario rotator cuff index (WORC. Range of motion (ROM of shoulder was measured in five directions by goniometry . All of these parameters were evaluated before intervention and in 1, 3, 6 months later. Results: with due attention to a six-month folloe-up, PRR injection was effective in pain reduction and improvement of patient's function (p<0.05. Shoulder Rom increased in all directions except external rotation and the power of shoulder muscles was evidently improved statistically in flexion, abduction and internal toration. Conclusion: PRP injection could effectively reduce pain and improve daily activities in patients with shoulder impingement syndrome.

Autologous US-guided PRP injection versus US-guided focal extracorporeal shock wave therapy for chronic lateral epicondylitis: A minimum of 2-year follow-up retrospective comparative study.

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Alessio-Mazzola, Mattia; Repetto, Ilaria; Biti, Besmir; Trentini, Roberto; Formica, Matteo; Felli, Lamberto

2018-01-01

To compare the efficacy of two independent groups of patients treated with ultrasound (US)-guided extracorporeal shock wave (ESW) therapy and with US-guided injection of platelet-rich plasma (PRP) for chronic lateral epicondylitis (LE) with a minimum of 2-year follow-up. We retrospectively evaluated 63 patients treated for chronic LE (31 patients with autologous US-guided PRP injection and 32 patients with US-guided focal ESW therapy) from 2009 to 2014. All the patients were evaluated by means of Roles-Maudsley (RM) score, quick Disabilities of Arm, Shoulder, and Hand (QuickDASH) score, visual analogic scale (VAS) and patient-rated tennis elbow evaluation (PRTEE) to retrospectively assess the pain relief, level of activity, the self-reported function and subjective satisfaction at minimum of 2-year follow-up. Both US-guided autologous PRP injection and US-guided focal ESW administration proved effective in chronic LE with significant improvement in the QuickDASH, VAS, RM and PRTEE scores ( p 0.05). The mean time between treatment and symptom resolution was significantly shorter for the PRP treatment ( p = 0.0212); furthermore, the mean time to return to the normal activities was quicker for PRP group ( p = 0.0119). Both PRP injection and ESW therapy are feasible and safe options for the treatment of chronic LE with low risk of complications and with good long-term follow-up results. US-guided PRP injection has quick efficacy when compared with US-guided focal ESW therapy.

Using PRP and human amniotic fluid combination for osteogenesis in rabbit socket preservation

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Amir Hossein Moradi

2015-01-01

Full Text Available Introduction: Platelet-rich plasma (PRP is used as an adjunct treatment during periodontal grafting surgery because of its capability of enhancing healing process. Amniotic fluid is a rich source of growth factors and hyaluronic acid (HA and a good point to study its properties of wound healing and bone formation. The aim of this study was to evaluate the osteogenic properties of a combination of amniotic fluid and PRP in rabbit′s dental socket preservation. Materials and Methods: The study population consisted of 24 healthy male laboratory rabbits (average weight 3,125 ± 185 gr that were randomly allocated into four groups. PRP for the first group, human amniotic fluid (HAF for the second group, a combination of PRP and HAF (PRHA for the third group was used. In the fourth (control group, no biomaterial was used. In each group, half of the rabbits were sacrificed at 4 weeks following surgery and the rest were sacrificed after 8 weeks. Histological analysis of biopsies of the sockets was performed using hematoxylin and eosin (H&E staining. Data were analyzed using Statistical Package for the Social Sciences (SPSS software (version 16 and P-value <0.05 was considered significance. Results: All three experimental groups showed positive effect on bone formation in terms of area of trabecular bone and number of osteocytes and also vessel formation. Socket preservation using HAF and PRHA showed the highest impact on bone formation. Socket preservation using HAF also had the highest impact on vessel formation. Conclusion: PRHA and HAF appear to be useful for enhancing bone formation. Since there was no difference between HAF and PRHA, it seems beneficial to use HAF due to its simplicity of application.

Interaction between Shadoo and PrP Affects the PrP-Folding Pathway.

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Ciric, Danica; Richard, Charles-Adrien; Moudjou, Mohammed; Chapuis, Jérôme; Sibille, Pierre; Daude, Nathalie; Westaway, David; Adrover, Miguel; Béringue, Vincent; Martin, Davy; Rezaei, Human

2015-06-01

Prion diseases are characterized by conformational changes of a cellular prion protein (PrP(C)) into a β-sheet-enriched and aggregated conformer (PrP(Sc)). Shadoo (Sho), a member of the prion protein family, is expressed in the central nervous system (CNS) and is highly conserved among vertebrates. On the basis of histoanatomical colocalization and sequence similarities, it is suspected that Sho and PrP may be functionally related. The downregulation of Sho expression during prion pathology and the direct interaction between Sho and PrP, as revealed by two-hybrid analysis, suggest a relationship between Sho and prion replication. Using biochemical and biophysical approaches, we demonstrate that Sho forms a 1:1 complex with full-length PrP with a dissociation constant in the micromolar range, and this interaction consequently modifies the PrP-folding pathway. Using a truncated PrP that mimics the C-terminal C1 fragment, an allosteric binding behavior with a Hill number of 4 was observed, suggesting that at least a tetramerization state occurs. A cell-based prion titration assay performed with different concentrations of Sho revealed an increase in the PrP(Sc) conversion rate in the presence of Sho. Collectively, our observations suggest that Sho can affect the prion replication process by (i) acting as a holdase and (ii) interfering with the dominant-negative inhibitor effect of the C1 fragment. Since the inception of the prion theory, the search for a cofactor involved in the conversion process has been an active field of research. Although the PrP interactome presents a broad landscape, candidates corresponding to specific criteria for cofactors are currently missing. Here, we describe for the first time that Sho can affect PrP structural dynamics and therefore increase the prion conversion rate. A biochemical characterization of Sho-PrP indicates that Sho acts as an ATP-independent holdase. Copyright © 2015, American Society for Microbiology. All Rights

Is Platelet-Rich Plasma (PRP) Effective in the Treatment of Acute Muscle Injuries? A Systematic Review and Meta-Analysis.

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Grassi, Alberto; Napoli, Francesca; Romandini, Iacopo; Samuelsson, Kristian; Zaffagnini, Stefano; Candrian, Christian; Filardo, Giuseppe

2018-04-01

Muscle lesions account for one-third of sport-related injuries, thus representing a substantial problem for both players and their teams. The use of platelet-rich plasma (PRP) injections is rapidly growing in clinical practice, prompted by an unmet clinical need with a large commercial market. However, after early reports of positive preliminary experience, higher quality studies recently questioned the real benefit provided by PRP injections to promote muscle healing and return to sport. To evaluate the effect of platelet-rich plasma (PRP) injections on outcomes following acute muscle injuries. Meta-analysis of randomized, controlled trials (RCTs), Level I. PubMed (MEDLINE), Cochrane (CENTRAL), Web of Science, clinicaltrials.gov, who.int, isrctn.com, greylit.org, opengrey.eu. RCTs investigating the effect of PRP for the treatment of acute muscle injuries against at least one control group including patients treated with placebo injection or physical therapy. The outcomes evaluated were time to return to sport, re-injuries, complications, pain, muscle strength, range of motion (ROM)/flexibility, muscle function, and imaging. Six studies, involving 374 patients, were included in the meta-analysis. The time to return to sport evaluated in all six studies was significantly shorter in patients treated with PRP (mean difference = - 7.17 days). However, if only the double-blind studies (n = 2) or studies including only hamstring injuries (n = 3) were considered, non-significant differences were found. Re-injuries (relative risk = - 0.03) and complications (relative risk = 0.01) were also similar between the two groups (p > 0.05), nor were any substantial differences found regarding pain, muscle strength, ROM/flexibility, muscle function, and imaging. The performance bias was high risk due to the lack of patient blinding in four studies. The quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) was

Is PRP useful in alveolar cleft reconstruction? Platelet-rich plasma in secondary alveoloplasty.

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Luaces-Rey, Ramon; Arenaz-Búa, Jorge; Lopez-Cedrún-Cembranos, José-Luis; Herrero-Patiño, Susana; Sironvalle-Soliva, Sheyla; Iglesias-Candal, Emma; Pombo-Castro, María

2010-07-01

Cleft lip and palate is a congenital facial malformation with an established treatment protocol. Mixed dentition period is the best moment for correct maxillary bone defect with an alveoloplasty. The aim of this surgical procedure is to facilitate dental eruption, re-establish maxillary arch, close any oro-nasal communication, give support to nasal ala, and in some cases allow dental rehabilitation with osteointegrated implants. Twenty cleft patients who underwent secondary alveoloplasty were included. In 10 of them autogenous bone graft were used and in other 10 autogenous bone and platelet-rich plasma (PRP) obtained from autogenous blood. Bone formation was compared by digital orthopantomography made on immediate post-operatory and 3 and 6 months after the surgery. No significant differences were found between both therapeutic groups on bone regeneration. We do not find justified the use of PRP for alveoloplasty in cleft patients' treatment protocol.

Effect of Use of Platelet-Rich Plasma (PRP) in Skin with Intrinsic Aging Process.

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Charles-de-Sá, Luiz; Gontijo-de-Amorim, Natale Ferreira; Takiya, Christina Maeda; Borojevic, Radovan; Benati, Donatella; Bernardi, Paolo; Sbarbati, Andrea; Rigotti, Gino

2018-02-15

In previous papers, we demonstrated that the treatment of human photoaged skin with stromal-vascular fraction-enriched fat or expanded adipose-derived stem cells showed a decrease of elastosis and the appearance of new oxytalan elastic fibers in dermis and an increase in the vascular network. The utilization of fat plus platelet-rich plasma (PRP) led to an increase in the vascular permeability and reactivity of the nervous component. The purpose of this study was to analyze the histologic and ultrastructural changes of human skin after the injection of only PRP in the retroauricular area that was not exposed to sun and did not present the photoaging process, in comparison with our previous results. This study was performed in 13 patients who were candidates for facelift and whose ages ranged between 45 and 65 years. The PRP injection was performed in the mastoidea area. Fragments of skin were removed before and 3 months after treatment and analyzed by optical and electron microscopy. After the injection of PRP, we observed an increase of reticular dermis thickness because of the deposition of elastic fibers and collagen, with a fibrotic aspect. A modified pattern of adipose tissue was also found at the dermohypodermal junction. Significative regenerative aspects were not found at histologic and ultrastructural analysis. The presence of foci of moderate inflammation and microangiopathy were observed. Treatment with PRP increased reticular dermis thickness with a fibrotic aspect. In the long term, the presence of inflammation and microangiopathy caused by PRP injection could lead to trophic alteration of the skin and the precocious aging process. © 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com

Distribution, recovery and concentration of platelets and leukocytes in L-PRP prepared by centrifugation.

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de Melo, Bruna Alice Gomes; Martins Shimojo, Andréa Arruda; Marcelino Perez, Amanda Gomes; Duarte Lana, José Fabio Santos; Andrade Santana, Maria Helena

2018-01-01

Platelet-rich plasma (PRP) is an autologous product prepared from whole blood (WB) that is widely used in regenerative medicine. In clinical practice, discontinuous centrifugation is used for both hand- and machine-prepared PRP. However, separation of WB fractions via centrifugation is a complex process, and the lack of clear mechanisms limits the understanding and evaluation of PRP preparation methods This paper focuses on the distribution, recovery and concentration factor of platelets and leukocytes in L-PRP (leukocyte and platelet-rich plasma) to define a concentration pattern for these blood components due to centrifugation conditions. WB collected from three healthy donors was centrifuged for 10min at 50-800 xg in a first step and then at 400 xg in a second step. The results from the first centrifugation step showed most platelets to be distributed in the upper layer (UL) and the buffy coat (BC), with approximately 14.5±5.2% retained in the bottom layer (BL). Most leukocytes were present in the BL. The greatest platelet recoveries from L-PRP were obtained at up to 150 xg (88.5±16.9%). The cumulative concentration factors with respect to the WB from the second centrifugation step were 6 and 1.2 for platelets and leukocytes, respectively. Thus, the concentration patterns delineated three centrifugation ranges with platelet/leukocyte ratios of 205±18, 325±15 and 107±4 and lymphocyte/granulocyte ratios of 1.54±0.74, 0.90±0.08 and 0.42±0.07. These findings contribute to a scientifically based standardization of L-PRP preparations. Copyright © 2017 Elsevier B.V. All rights reserved.

PrP P102L and Nearby Lysine Mutations Promote Spontaneous In Vitro Formation of Transmissible Prions.

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Kraus, Allison; Raymond, Gregory J; Race, Brent; Campbell, Katrina J; Hughson, Andrew G; Anson, Kelsie J; Raymond, Lynne D; Caughey, Byron

2017-11-01

Accumulation of fibrillar protein aggregates is a hallmark of many diseases. While numerous proteins form fibrils by prion-like seeded polymerization in vitro , only some are transmissible and pathogenic in vivo To probe the structural features that confer transmissibility to prion protein (PrP) fibrils, we have analyzed synthetic PrP amyloids with or without the human prion disease-associated P102L mutation. The formation of infectious prions from PrP molecules in vitro has required cofactors and/or unphysiological denaturing conditions. Here, we demonstrate that, under physiologically compatible conditions without cofactors, the P102L mutation in recombinant hamster PrP promoted prion formation when seeded by minute amounts of scrapie prions in vitro Surprisingly, combination of the P102L mutation with charge-neutralizing substitutions of four nearby lysines promoted spontaneous prion formation. When inoculated into hamsters, both of these types of synthetic prions initiated substantial accumulation of prion seeding activity and protease-resistant PrP without transmissible spongiform encephalopathy (TSE) clinical signs or notable glial activation. Our evidence suggests that PrP's centrally located proline and lysine residues act as conformational switches in the in vitro formation of transmissible PrP amyloids. IMPORTANCE Many diseases involve the damaging accumulation of specific misfolded proteins in thread-like aggregates. These threads (fibrils) are capable of growing on the ends by seeding the refolding and incorporation of the normal form of the given protein. In many cases such aggregates can be infectious and propagate like prions when transmitted from one individual host to another. Some transmitted aggregates can cause fatal disease, as with human iatrogenic prion diseases, while other aggregates appear to be relatively innocuous. The factors that distinguish infectious and pathogenic protein aggregates from more innocuous ones are poorly understood

Na+/K+-ATPase is present in scrapie-associated fibrils, modulates PrP misfolding in vitro and links PrP function and dysfunction.

Directory of Open Access Journals (Sweden)

James F Graham

Full Text Available Transmissible spongiform encephalopathies are characterised by widespread deposition of fibrillar and/or plaque-like forms of the prion protein. These aggregated forms are produced by misfolding of the normal prion protein, PrP(C, to the disease-associated form, PrP(Sc, through mechanisms that remain elusive but which require either direct or indirect interaction between PrP(C and PrP(Sc isoforms. A wealth of evidence implicates other non-PrP molecules as active participants in the misfolding process, to catalyse and direct the conformational conversion of PrP(C or to provide a scaffold ensuring correct alignment of PrP(C and PrP(Sc during conversion. Such molecules may be specific to different scrapie strains to facilitate differential prion protein misfolding. Since molecular cofactors may become integrated into the growing protein fibril during prion conversion, we have investigated the proteins contained in prion disease-specific deposits by shotgun proteomics of scrapie-associated fibrils (SAF from mice infected with 3 different strains of mouse-passaged scrapie. Concomitant use of negative control preparations allowed us to identify and discount proteins that are enriched non-specifically by the SAF isolation protocol. We found several proteins that co-purified specifically with SAF from infected brains but none of these were reproducibly and demonstrably specific for particular scrapie strains. The α-chain of Na(+/K(+-ATPase was common to SAF from all 3 strains and we tested the ability of this protein to modulate in vitro misfolding of recombinant PrP. Na(+/K(+-ATPase enhanced the efficiency of disease-specific conversion of recombinant PrP suggesting that it may act as a molecular cofactor. Consistent with previous results, the same protein inhibited fibrillisation kinetics of recombinant PrP. Since functional interactions between PrP(C and Na(+/K(+-ATPase have previously been reported in astrocytes, our data highlight this molecule as

Protein misfolding cyclic amplification induces the conversion of recombinant prion protein to PrP oligomers causing neuronal apoptosis.

Science.gov (United States)

Yuan, Zhen; Yang, Lifeng; Chen, Baian; Zhu, Ting; Hassan, Mohammad Farooque; Yin, Xiaomin; Zhou, Xiangmei; Zhao, Deming

2015-06-01

The formation of neurotoxic prion protein (PrP) oligomers is thought to be a key step in the development of prion diseases. Recently, it was determined that the sonication and shaking of recombinant PrP can convert PrP monomers into β-state oligomers. Herein, we demonstrate that β-state oligomeric PrP can be generated through protein misfolding cyclic amplification from recombinant full-length hamster, human, rabbit, and mutated rabbit PrP, and that these oligomers can be used for subsequent research into the mechanisms of PrP-induced neurotoxicity. We have characterized protein misfolding cyclic amplification-induced monomer-to-oligomer conversion of PrP from three species using western blotting, circular dichroism, size-exclusion chromatography, and resistance to proteinase K (PK) digestion. We have further shown that all of the resulting β-oligomers are toxic to primary mouse cortical neurons independent of the presence of PrP(C) in the neurons, whereas the corresponding monomeric PrP were not toxic. In addition, we found that this toxicity is the result of oligomer-induced apoptosis via regulation of Bcl-2, Bax, and caspase-3 in both wild-type and PrP(-/-) cortical neurons. It is our hope that these results may contribute to our understanding of prion transformation within the brain. We found that β-state oligomeric PrPs can be generated through protein misfolding cyclic amplification (PMCA) from recombinant full-length hamster, human, rabbit, and mutated rabbit PrP. β-oligomers are toxic to primary mouse cortical neurons independent of the presence of PrP(C) in the neurons, while the corresponding monomeric PrPs were not toxic. This toxicity is the result of oligomers-induced apoptosis via regulation of Bcl-2, Bax, and caspase-3. These results may contribute to our understanding of prion transformation within the brain. © 2015 International Society for Neurochemistry.

Evaluation of the effect of platelet rich plasma (PRP) on enhancement of bone healing in diaphyseal bone defects by radiography and computed tomography

International Nuclear Information System (INIS)

Özak, Ahmet; Yardimci, Cenk; Nİsbet, Özlem H.; Bayrak, İlkay Koray; Nİsbet, Cevat

2010-01-01

The effect of platelet-rich plasma (PRP) with autogenous cancellous bone graft on enhancement of bone healing in diaphyseal bone defects was evaluated. A 4-mm defect was created in the middiaphysis of the tibias of 20 rabbits. Rabbits were divided into two groups of ten animals each: only autogenous cancellous graft, PRP and autogenous cancellous graft. In animals of group 1, only autogenous cancellous grafts, and to those in group 2, PRP and autogenous cancellous grafts, were applied to the defect. Radiographical and computed tomography (CT) views were taken and evaluated on postoperative days 0, 15, 30, 60, and 90. According to the bone formation, union, and remodeling scores, group 1 had better scores than group 2 on days 30, 60, and 90. The density was significantly increased on day 60 than on days 0, 15, and 30 in group 1. In conclusion, it was evaluated that PRP could not enhance the bone regeneration in diaphyseal defects when used with autogenous cancellous bone graft

In vitro study of the role of thrombin in platelet rich plasma (PRP) preparation: utility for gel formation and impact in growth factors release.

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Huber, Stephany Cares; Cunha Júnior, José Luiz Rosenberis; Montalvão, Silmara; da Silva, Letícia Queiroz; Paffaro, Aline Urban; da Silva, Francesca Aparecida Ramos; Rodrigues, Bruno Lima; Lana, José Fabio Santos Duarte; Annichino-Bizzacchi, Joyce Maria

2016-01-01

The use of PRP has been studied for different fields, with promising results in regenerative medicine. Until now, there is no study in the literature evaluating thrombin levels in serum, used as autologous thrombin preparation. Therefore, in the present study we evaluated the role played by different thrombin concentrations in PRP and the impact in the release of growth factors. Also, different activators for PRP gel formation were evaluated. Thrombin levels were measured in different autologous preparations: serum, L-PRP (PRP rich in leukocytes) and T-PRP (thrombin produced through PRP added calcium gluconate). L-PRP was prepared according to the literature, with platelets and leukocytes being quantified. The effect of autologous thrombin associated or not with calcium in PRP gel was determined by measuring the time of gel formation. The relationship between thrombin concentration and release of growth factors was determined by growth factors (PDGF-AA, VEGF and EGF) multiplex analysis. A similar concentration of thrombin was observed in serum, L-PRP and T-PRP (8.13 nM, 8.63 nM and 7.56 nM, respectively) with a high variation between individuals (CV%: 35.07, 43 and 58.42, respectively). T-PRP and serum with calcium chloride showed similar results in time to promote gel formation. The increase of thrombin concentrations (2.66, 8 and 24 nM) did not promote an increase in growth factor release. The technique of using serum as a thrombin source proved to be the most efficient and reproducible for promoting PRP gel formation, with some advantages when compared to other activation methods, as this technique is easier and quicker with no need of consuming part of PRP. Noteworthy, PRP activation using different thrombin concentrations did not promote a higher release of growth factors, appearing not to be necessary when PRP is used as a suspension.

Truncated forms of the prion protein PrP demonstrate the need for complexity in prion structure

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Wan, William; Stöhr, Jan; Kendall, Amy; Stubbs, Gerald

2015-09-01

Self-propagation of aberrant protein folds is the defining characteristic of prions. Knowing the structural basis of self-propagation is essential to understanding prions and their related diseases. Prion rods are amyloid fibrils, but not all amyloids are prions. Prions have been remarkably intractable to structural studies, so many investigators have preferred to work with peptide fragments, particularly in the case of the mammalian prion protein PrP. We compared the structures of a number of fragments of PrP by X-ray fiber diffraction, and found that although all of the peptides adopted amyloid conformations, only the larger fragments adopted conformations that modeled the complexity of self-propagating prions, and even these fragments did not always adopt the PrP structure. It appears that the relatively complex structure of the prion form of PrP is not accessible to short model peptides, and that self-propagation may be tied to a level of structural complexity unobtainable in simple model systems. The larger fragments of PrP, however, are useful to illustrate the phenomenon of deformed templating (heterogeneous seeding), which has important biological consequences.

Truncated forms of the prion protein PrP demonstrate the need for complexity in prion structure.

Science.gov (United States)

Wan, William; Stöhr, Jan; Kendall, Amy; Stubbs, Gerald

2015-01-01

Self-propagation of aberrant protein folds is the defining characteristic of prions. Knowing the structural basis of self-propagation is essential to understanding prions and their related diseases. Prion rods are amyloid fibrils, but not all amyloids are prions. Prions have been remarkably intractable to structural studies, so many investigators have preferred to work with peptide fragments, particularly in the case of the mammalian prion protein PrP. We compared the structures of a number of fragments of PrP by X-ray fiber diffraction, and found that although all of the peptides adopted amyloid conformations, only the larger fragments adopted conformations that modeled the complexity of self-propagating prions, and even these fragments did not always adopt the PrP structure. It appears that the relatively complex structure of the prion form of PrP is not accessible to short model peptides, and that self-propagation may be tied to a level of structural complexity unobtainable in simple model systems. The larger fragments of PrP, however, are useful to illustrate the phenomenon of deformed templating (heterogeneous seeding), which has important biological consequences.

Glycosylphosphatidylinositol Anchor Modification Machinery Deficiency Is Responsible for the Formation of Pro-Prion Protein (PrP) in BxPC-3 Protein and Increases Cancer Cell Motility*

Science.gov (United States)

Yang, Liheng; Gao, Zhenxing; Hu, Lipeng; Wu, Guiru; Yang, Xiaowen; Zhang, Lihua; Zhu, Ying; Wong, Boon-Seng; Xin, Wei; Sy, Man-Sun; Li, Chaoyang

2016-01-01

The normal cellular prion protein (PrP) is a glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein. However, in pancreatic ductal adenocarcinoma cell lines, such as BxPC-3, PrP exists as a pro-PrP retaining its glycosylphosphatidylinositol (GPI) peptide signaling sequence. Here, we report the identification of another pancreatic ductal adenocarcinoma cell line, AsPC-1, which expresses a mature GPI-anchored PrP. Comparison of the 24 genes involved in the GPI anchor modification pathway between AsPC-1 and BxPC-3 revealed 15 of the 24 genes, including PGAP1 and PIG-F, were down-regulated in the latter cells. We also identified six missense mutations in DPM2, PIG-C, PIG-N, and PIG-P alongside eight silent mutations. When BxPC-3 cells were fused with Chinese hamster ovary (CHO) cells, which lack endogenous PrP, pro-PrP was successfully converted into mature GPI-anchored PrP. Expression of the individual gene, such as PGAP1, PIG-F, or PIG-C, into BxPC-3 cells does not result in phosphoinositide-specific phospholipase C sensitivity of PrP. However, when PIG-F but not PIG-P is expressed in PGAP1-expressing BxPC-3 cells, PrP on the surface of the cells becomes phosphoinositide-specific phospholipase C-sensitive. Thus, low expression of PIG-F and PGAP1 is the major factor contributing to the accumulation of pro-PrP. More importantly, BxPC-3 cells expressing GPI-anchored PrP migrate much slower than BxPC-3 cells bearing pro-PrP. In addition, GPI-anchored PrP-bearing AsPC-1 cells also migrate slower than pro-PrP bearing BxPC-3 cells, although both cells express filamin A. “Knocking out” PRNP in BxPC-3 cell drastically reduces its migration. Collectively, these results show that multiple gene irregularity in BxPC-3 cells is responsible for the formation of pro-PrP, and binding of pro-PrP to filamin A contributes to enhanced tumor cell motility. PMID:26683373

PRP19 transforms into a sensor of RPA-ssDNA after DNA damage and drives ATR activation via a ubiquitin-mediated circuitry.

Science.gov (United States)

Maréchal, Alexandre; Li, Ju-Mei; Ji, Xiao Ye; Wu, Ching-Shyi; Yazinski, Stephanie A; Nguyen, Hai Dang; Liu, Shizhou; Jiménez, Amanda E; Jin, Jianping; Zou, Lee

2014-01-23

PRP19 is a ubiquitin ligase involved in pre-mRNA splicing and the DNA damage response (DDR). Although the role for PRP19 in splicing is well characterized, its role in the DDR remains elusive. Through a proteomic screen for proteins that interact with RPA-coated single-stranded DNA (RPA-ssDNA), we identified PRP19 as a sensor of DNA damage. PRP19 directly binds RPA and localizes to DNA damage sites via RPA, promoting RPA ubiquitylation in a DNA-damage-induced manner. PRP19 facilitates the accumulation of ATRIP, the regulatory partner of the ataxia telangiectasia mutated and Rad3-related (ATR) kinase, at DNA damage sites. Depletion of PRP19 compromised the phosphorylation of ATR substrates, recovery of stalled replication forks, and progression of replication forks on damaged DNA. Importantly, PRP19 mutants that cannot bind RPA or function as an E3 ligase failed to support the ATR response, revealing that PRP19 drives ATR activation by acting as an RPA-ssDNA-sensing ubiquitin ligase during the DDR. Copyright © 2014 Elsevier Inc. All rights reserved.

Reduced response of splenocytes after mitogen-stimulation in the prion protein (PrP) gene-deficient mouse: PrPLP/Doppel production and cerebral degeneration

International Nuclear Information System (INIS)

Kim, Chi-Kyeong; Hirose, Yuko; Sakudo, Akikazu; Takeyama, Natsumi; Kang, Chung-Boo; Taniuchi, Yojiro; Matsumoto, Yoshitsugu; Itohara, Shigeyoshi; Sakaguchi, Suehiro; Onodera, Takashi

2007-01-01

Splenocytes of wild-type (Prnp +/+ ) and prion protein gene-deficient (Prnp -/- ) mice were treated with various activation stimuli such as T cell mitogen concanavalin A (ConA), phorbol 12-myristate 13-acetate (PMA) + ionomycin (Io), or B cell mitogen lipopolysaccharide (LPS). Cellular prion protein (PrP C ) expression was enhanced following ConA stimulation, but not PMA + Io or LPS in Prnp +/+ splenocytes. Rikn Prnp -/- splenocytes elicited lower cell proliferations than Prnp +/+ or Zrch I Prnp -/- splenocytes after LPS stimulation and showed sporadic nerve cells in the cerebral cortex and deeper structure. Around the degenerated nerve cells, mild vacuolation in the neuropil was observed. This neural alteration correlated well to the suppressed response of B cells in the spleen. The finding that discrete lesions within the central nervous systems induced marked modulation of immune function probably indicates the existence of a delicately balanced neural-endocrine network by PrP C and PrPLP/Doppel

Site enforcement tracking system (SETS): PRP listing by site for region 9

International Nuclear Information System (INIS)

1993-04-01

When expending Superfund monies at a CERCLA (Comprehensive Environmental Response, Compensation and Liability Act) site, EPA must conduct a search to identify parties with potential financial responsibility for remediation of uncontrolled hazardous waste sites. EPA regional Superfund Waste Management Staff issue a notice letter to the potentially responsible party (PRP). Data from the notice letter is used to form the Site Enforcement Tracking System (SETS). The data includes PRP name and address, a company contact person, the date the notice was issued, and the related CERCLA site name and identification number

Site enforcement tracking system (SETS): PRP listing by site for region 8

International Nuclear Information System (INIS)

1993-04-01

When expending Superfund monies at a CERCLA (Comprehensive Environmental Response, Compensation and Liability Act) site, EPA must conduct a search to identify parties with potential financial responsibility for remediation of uncontrolled hazardous waste sites. EPA regional Superfund Waste Management Staff issue a notice letter to the potentially responsible party (PRP). Data from the notice letter is used to form the Site Enforcement Tracking System (SETS). The data includes PRP name and address, a company contact person, the date the notice was issued, and the related CERCLA site name and identification number

Site enforcement tracking system (SETS): PRP listing by site for region 10

International Nuclear Information System (INIS)

1993-04-01

When expending Superfund monies at a CERCLA (Comprehensive Environmental Response, Compensation and Liability Act) site, EPA must conduct a search to identify parties with potential financial responsibility for remediation of uncontrolled hazardous waste sites. EPA regional Superfund Waste Management Staff issue a notice letter to the potentially responsible party (PRP). Data from the notice letter is used to form the Site Enforcement Tracking System (SETS). The data includes PRP name and address, a company contact person, the date the notice was issued, and the related CERCLA site name and identification number

Site enforcement tracking system (SETS): PRP listing by site for region 3

International Nuclear Information System (INIS)

1993-04-01

When expending Superfund monies at a CERCLA (Comprehensive Environmental Response, Compensation and Liability Act) site, EPA must conduct a search to identify parties with potential financial responsibility for remediation of uncontrolled hazardous waste sites. EPA regional Superfund Waste Management Staff issue a notice letter to the potentially responsible party (PRP). Data from the notice letter is used to form the Site Enforcement Tracking System (SETS). The data includes PRP name and address, a company contact person, the date the notice was issued, and the related CERCLA site name and identification number

Site enforcement tracking system (SETS): PRP listing by site for region 2

International Nuclear Information System (INIS)

1993-04-01

When expending Superfund monies at a CERCLA (Comprehensive Environmental Response, Compensation and Liability Act) site, EPA must conduct a search to identify parties with potential financial responsibility for remediation of uncontrolled hazardous waste sites. EPA regional Superfund Waste Management Staff issue a notice letter to the potentially responsible party (PRP). Data from the notice letter is used to form the Site Enforcement Tracking System (SETS). The data includes PRP name and address, a company contact person, the date the notice was issued, and the related CERCLA site name and identification number

Site enforcement tracking system (SETS): PRP listing by site for region 5

International Nuclear Information System (INIS)

1993-04-01

When expending Superfund monies at a CERCLA (Comprehensive Environmental Response, Compensation and Liability Act) site, EPA must conduct a search to identify parties with potential financial responsibility for remediation of uncontrolled hazardous waste sites. EPA regional Superfund Waste Management Staff issue a notice letter to the potentially responsible party (PRP). Data from the notice letter is used to form the Site Enforcement Tracking System (SETS). The data includes PRP name and address, a company contact person, the date the notice was issued, and the related CERCLA site name and identification number

Site enforcement tracking system (SETS): PRP listing by site for region 6

International Nuclear Information System (INIS)

1993-04-01

When expending Superfund monies at a CERCLA (Comprehensive Environmental Response, Compensation and Liability Act) site, EPA must conduct a search to identify parties with potential financial responsibility for remediation of uncontrolled hazardous waste sites. EPA regional Superfund Waste Management Staff issue a notice letter to the potentially responsible party (PRP). Data from the notice letter is used to form the Site Enforcement Tracking System (SETS). The data includes PRP name and address, a company contact person, the date the notice was issued, and the related CERCLA site name and identification number

Small kinetochore associated protein (SKAP promotes UV-induced cell apoptosis through negatively regulating pre-mRNA processing factor 19 (Prp19.

Directory of Open Access Journals (Sweden)

Shan Lu

Full Text Available Apoptosis is a regulated cellular suicide program that is critical for the development and maintenance of healthy tissues. Previous studies have shown that small kinetochore associated protein (SKAP cooperates with kinetochore and mitotic spindle proteins to regulate mitosis. However, the role of SKAP in apoptosis has not been investigated. We have identified a new interaction involving SKAP, and we propose a mechanism through which SKAP regulates cell apoptosis. Our experiments demonstrate that both overexpression and knockdown of SKAP sensitize cells to UV-induced apoptosis. Further study has revealed that SKAP interacts with Pre-mRNA processing Factor 19 (Prp19. We find that UV-induced apoptosis can be inhibited by ectopic expression of Prp19, whereas silencing Prp19 has the opposite effect. Additionally, SKAP negatively regulates the protein levels of Prp19, whereas Prp19 does not alter SKAP expression. Finally, rescue experiments demonstrate that the pro-apoptotic role of SKAP is executed through Prp19. Taken together, these findings suggest that SKAP promotes UV-induced cell apoptosis by negatively regulating the anti-apoptotic protein Prp19.

Prion disease susceptibility is affected by β-structure folding propensity and local side-chain interactions in PrP

Science.gov (United States)

Khan, M. Qasim; Sweeting, Braden; Mulligan, Vikram Khipple; Arslan, Pharhad Eli; Cashman, Neil R.; Pai, Emil F.; Chakrabartty, Avijit

2010-01-01

Prion diseases occur when the normally α-helical prion protein (PrP) converts to a pathological β-structured state with prion infectivity (PrPSc). Exposure to PrPSc from other mammals can catalyze this conversion. Evidence from experimental and accidental transmission of prions suggests that mammals vary in their prion disease susceptibility: Hamsters and mice show relatively high susceptibility, whereas rabbits, horses, and dogs show low susceptibility. Using a novel approach to quantify conformational states of PrP by circular dichroism (CD), we find that prion susceptibility tracks with the intrinsic propensity of mammalian PrP to convert from the native, α-helical state to a cytotoxic β-structured state, which exists in a monomer–octamer equilibrium. It has been controversial whether β-structured monomers exist at acidic pH; sedimentation equilibrium and dual-wavelength CD evidence is presented for an equilibrium between a β-structured monomer and octamer in some acidic pH conditions. Our X-ray crystallographic structure of rabbit PrP has identified a key helix-capping motif implicated in the low prion disease susceptibility of rabbits. Removal of this capping motif increases the β-structure folding propensity of rabbit PrP to match that of PrP from mouse, a species more susceptible to prion disease. PMID:21041683

Prion disease susceptibility is affected by beta-structure folding propensity and local side-chain interactions in PrP.

Science.gov (United States)

Khan, M Qasim; Sweeting, Braden; Mulligan, Vikram Khipple; Arslan, Pharhad Eli; Cashman, Neil R; Pai, Emil F; Chakrabartty, Avijit

2010-11-16

Prion diseases occur when the normally α-helical prion protein (PrP) converts to a pathological β-structured state with prion infectivity (PrP(Sc)). Exposure to PrP(Sc) from other mammals can catalyze this conversion. Evidence from experimental and accidental transmission of prions suggests that mammals vary in their prion disease susceptibility: Hamsters and mice show relatively high susceptibility, whereas rabbits, horses, and dogs show low susceptibility. Using a novel approach to quantify conformational states of PrP by circular dichroism (CD), we find that prion susceptibility tracks with the intrinsic propensity of mammalian PrP to convert from the native, α-helical state to a cytotoxic β-structured state, which exists in a monomer-octamer equilibrium. It has been controversial whether β-structured monomers exist at acidic pH; sedimentation equilibrium and dual-wavelength CD evidence is presented for an equilibrium between a β-structured monomer and octamer in some acidic pH conditions. Our X-ray crystallographic structure of rabbit PrP has identified a key helix-capping motif implicated in the low prion disease susceptibility of rabbits. Removal of this capping motif increases the β-structure folding propensity of rabbit PrP to match that of PrP from mouse, a species more susceptible to prion disease.

Familial CJD Associated PrP Mutants within Transmembrane Region Induced Ctm-PrP Retention in ER and Triggered Apoptosis by ER Stress in SH-SY5Y Cells

Science.gov (United States)

Wang, Xin; Shi, Qi; Xu, Kun; Gao, Chen; Chen, Cao; Li, Xiao-Li; Wang, Gui-Rong; Tian, Chan; Han, Jun; Dong, Xiao-Ping

2011-01-01

Background Genetic prion diseases are linked to point and inserted mutations in the prion protein (PrP) gene that are presumed to favor conversion of the cellular isoform of PrP (PrPC) to the pathogenic one (PrPSc). The pathogenic mechanisms and the subcellular sites of the conversion are not completely understood. Here we introduce several PRNP gene mutations (such as, PrP-KDEL, PrP-3AV, PrP-A117V, PrP-G114V, PrP-P102L and PrP-E200K) into the cultured cells in order to explore the pathogenic mechanism of familial prion disease. Methodology/Principal Findings To address the roles of aberrant retention of PrP in endoplasmic reticulum (ER), the recombinant plasmids expressing full-length human PrP tailed with an ER signal peptide at the COOH-terminal (PrP-KDEL) and PrP with three amino acids exchange in transmembrane region (PrP-3AV) were constructed. In the preparations of transient transfections, 18-kD COOH-terminal proteolytic resistant fragments (Ctm-PrP) were detected in the cells expressing PrP-KDEL and PrP-3AV. Analyses of the cell viabilities in the presences of tunicamycin and brefeldin A revealed that expressions of PrP-KDEL and PrP-3AV sensitized the transfected cells to ER stress stimuli. Western blots and RT-PCR identified the clear alternations of ER stress associated events in the cells expressing PrP-KDEL and PrP-3AV that induced ER mediated apoptosis by CHOP and capase-12 apoptosis pathway. Moreover, several familial CJD related PrP mutants were transiently introduced into the cultured cells. Only the mutants within the transmembrane region (G114V and A117V) induced the formation of Ctm-PrP and caused the ER stress, while the mutants outside the transmembrane region (P102L and E200K) failed. Conclusions/Significance The data indicate that the retention of PrP in ER through formation of Ctm-PrP results in ER stress and cell apoptosis. The cytopathic activities caused by different familial CJD associated PrP mutants may vary, among them the mutants

Familial CJD associated PrP mutants within transmembrane region induced Ctm-PrP retention in ER and triggered apoptosis by ER stress in SH-SY5Y cells.

Directory of Open Access Journals (Sweden)

Xin Wang

Full Text Available BACKGROUND: Genetic prion diseases are linked to point and inserted mutations in the prion protein (PrP gene that are presumed to favor conversion of the cellular isoform of PrP (PrP(C to the pathogenic one (PrP(Sc. The pathogenic mechanisms and the subcellular sites of the conversion are not completely understood. Here we introduce several PRNP gene mutations (such as, PrP-KDEL, PrP-3AV, PrP-A117V, PrP-G114V, PrP-P102L and PrP-E200K into the cultured cells in order to explore the pathogenic mechanism of familial prion disease. METHODOLOGY/PRINCIPAL FINDINGS: To address the roles of aberrant retention of PrP in endoplasmic reticulum (ER, the recombinant plasmids expressing full-length human PrP tailed with an ER signal peptide at the COOH-terminal (PrP-KDEL and PrP with three amino acids exchange in transmembrane region (PrP-3AV were constructed. In the preparations of transient transfections, 18-kD COOH-terminal proteolytic resistant fragments (Ctm-PrP were detected in the cells expressing PrP-KDEL and PrP-3AV. Analyses of the cell viabilities in the presences of tunicamycin and brefeldin A revealed that expressions of PrP-KDEL and PrP-3AV sensitized the transfected cells to ER stress stimuli. Western blots and RT-PCR identified the clear alternations of ER stress associated events in the cells expressing PrP-KDEL and PrP-3AV that induced ER mediated apoptosis by CHOP and caspase-12 apoptosis pathway. Moreover, several familial CJD related PrP mutants were transiently introduced into the cultured cells. Only the mutants within the transmembrane region (G114V and A117V induced the formation of Ctm-PrP and caused the ER stress, while the mutants outside the transmembrane region (P102L and E200K failed. CONCLUSIONS/SIGNIFICANCE: The data indicate that the retention of PrP in ER through formation of Ctm-PrP results in ER stress and cell apoptosis. The cytopathic activities caused by different familial CJD associated PrP mutants may vary, among them

Increasing platelet concentrations in leukocyte-reduced platelet-rich plasma decrease collagen gene synthesis in tendons.

Science.gov (United States)

Boswell, Stacie G; Schnabel, Lauren V; Mohammed, Hussni O; Sundman, Emily A; Minas, Tom; Fortier, Lisa A

2014-01-01

Platelet-rich plasma (PRP) is used for the treatment of tendinopathy. There are numerous PRP preparations, and the optimal combination of platelets and leukocytes is not known. Within leukocyte-reduced PRP (lrPRP), there is a plateau effect of platelet concentration, with increasing platelet concentrations being detrimental to extracellular matrix synthesis. Controlled laboratory study. Different formulations of lrPRP with respect to the platelet:leukocyte ratio were generated from venous blood of 8 horses. Explants of the superficial digital flexor tendon were cultured in lrPRP products for 96 hours. Platelet-derived growth factor-BB (PDGF-BB), tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), and interleukin-1β (IL-1β) concentrations were determined in the media by enzyme-linked immunosorbent assay. Gene expression in tendon tissue for collagen type I and III (COL1A1 and COL3A1, respectively), matrix metalloproteinase-3 and -13 (MMP-3 and MMP-13, respectively), cartilage oligomeric matrix protein (COMP), and IL-1β was determined. Data were divided into 3 groups of lrPRP based on the ratio of platelets:leukocytes and evaluated to determine the effect of platelet concentration. Complete blood counts verified leukocyte reduction and platelet enrichment in all PRP preparations. In the lrPRP preparation, the anabolic growth factors PDGF-BB and TGF-β1 were increased with increasing platelet concentrations, and the catabolic cytokine IL-1β was decreased with increasing platelet concentrations. Increasing the platelet concentration resulted in a significant reduction in COL1A1 and COL3A1 synthesis in tendons. Increasing the platelet concentration within lrPRP preparations results in the delivery of more anabolic growth factors and less proinflammatory cytokines, but the biological effect on tendons is diminished metabolism as indicated by a decrease in the synthesis of both COL1A1 and COL3A1. Together, this information suggests that

Functional assessment of autologous platelet-rich plasma (PRP) after long-term storage at -20 °C without any preservation agent.

Science.gov (United States)

Hosnuter, Mubin; Aslan, Cem; Isik, Daghan; Caliskan, Gorkem; Arslan, Banu; Durgun, Mustafa

2017-08-01

Platelet-rich plasma (PRP) is increasingly being used in the treatment of chronic wounds, pathologies of the musculoskeletal system, and in cosmetic medicine; however, the preparation of platelet-rich plasma is both time-consuming and requires invasive intervention. Additional costs are introduced if special equipment is used during preparation. The aim of the present study is to test whether autologous platelet-rich plasma (PRP) preserves the feature of growth factor release when stored at -20 °C after preparation. Autologous PRP concentrates were prepared using whole blood samples obtained from 20 healthy subjects and divided into three parts to form three groups. Epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), platelet derived growth factor-AB (PDGF-AB), insulin-like growth factor 1 (IGF-1), transforming growth factor-beta (TGF-β), and P-Selectin levels were immediately analysed in the control group. The other groups were defined as the experimental groups and were stored at -20 °C and analysed on the 7th and the 14th days. The same growth factors were tested in the experimental groups. The growth factors (EGF, VEGF, PDGF-AB, IGF-1, TGF-β) and P-selectin levels were significantly decreased in the autologous PRP samples stored at -20 °C compared to the control group. The growth factor levels on days 7 and 14 suggest that autologous PRP can be stored at -20 °C without preservative agents, although in vivo studies are required in order to evaluate the clinical efficacy of the detected growth factor levels.

Reduced Hyperpolarization-Activated Current Contributes to Enhanced Intrinsic Excitability in Cultured Hippocampal Neurons from PrP(-/-) Mice.

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Fan, Jing; Stemkowski, Patrick L; Gandini, Maria A; Black, Stefanie A; Zhang, Zizhen; Souza, Ivana A; Chen, Lina; Zamponi, Gerald W

2016-01-01

Genetic ablation of cellular prion protein (PrP(C)) has been linked to increased neuronal excitability and synaptic activity in the hippocampus. We have previously shown that synaptic activity in hippocampi of PrP-null mice is increased due to enhanced N-methyl-D-aspartate receptor (NMDAR) function. Here, we focused on the effect of PRNP gene knock-out (KO) on intrinsic neuronal excitability, and in particular, the underlying ionic mechanism in hippocampal neurons cultured from P0 mouse pups. We found that the absence of PrP(C) profoundly affected the firing properties of cultured hippocampal neurons in the presence of synaptic blockers. The membrane impedance was greater in PrP-null neurons, and this difference was abolished by the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker ZD7288 (100 μM). HCN channel activity appeared to be functionally regulated by PrP(C). The amplitude of voltage sag, a characteristic of activating HCN channel current (I h), was decreased in null mice. Moreover, I h peak current was reduced, along with a hyperpolarizing shift in activation gating and slower kinetics. However, neither HCN1 nor HCN2 formed a biochemical complex with PrP(C). These results suggest that the absence of PrP downregulates the activity of HCN channels through activation of a cell signaling pathway rather than through direct interactions. This in turn contributes to an increase in membrane impedance to potentiate neuronal excitability.

Glycosylphosphatidylinositol Anchor Modification Machinery Deficiency Is Responsible for the Formation of Pro-Prion Protein (PrP) in BxPC-3 Protein and Increases Cancer Cell Motility.

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Yang, Liheng; Gao, Zhenxing; Hu, Lipeng; Wu, Guiru; Yang, Xiaowen; Zhang, Lihua; Zhu, Ying; Wong, Boon-Seng; Xin, Wei; Sy, Man-Sun; Li, Chaoyang

2016-02-19

The normal cellular prion protein (PrP) is a glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein. However, in pancreatic ductal adenocarcinoma cell lines, such as BxPC-3, PrP exists as a pro-PrP retaining its glycosylphosphatidylinositol (GPI) peptide signaling sequence. Here, we report the identification of another pancreatic ductal adenocarcinoma cell line, AsPC-1, which expresses a mature GPI-anchored PrP. Comparison of the 24 genes involved in the GPI anchor modification pathway between AsPC-1 and BxPC-3 revealed 15 of the 24 genes, including PGAP1 and PIG-F, were down-regulated in the latter cells. We also identified six missense mutations in DPM2, PIG-C, PIG-N, and PIG-P alongside eight silent mutations. When BxPC-3 cells were fused with Chinese hamster ovary (CHO) cells, which lack endogenous PrP, pro-PrP was successfully converted into mature GPI-anchored PrP. Expression of the individual gene, such as PGAP1, PIG-F, or PIG-C, into BxPC-3 cells does not result in phosphoinositide-specific phospholipase C sensitivity of PrP. However, when PIG-F but not PIG-P is expressed in PGAP1-expressing BxPC-3 cells, PrP on the surface of the cells becomes phosphoinositide-specific phospholipase C-sensitive. Thus, low expression of PIG-F and PGAP1 is the major factor contributing to the accumulation of pro-PrP. More importantly, BxPC-3 cells expressing GPI-anchored PrP migrate much slower than BxPC-3 cells bearing pro-PrP. In addition, GPI-anchored PrP-bearing AsPC-1 cells also migrate slower than pro-PrP bearing BxPC-3 cells, although both cells express filamin A. "Knocking out" PRNP in BxPC-3 cell drastically reduces its migration. Collectively, these results show that multiple gene irregularity in BxPC-3 cells is responsible for the formation of pro-PrP, and binding of pro-PrP to filamin A contributes to enhanced tumor cell motility. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Platelet-Rich Plasma (PRP Rinses for the Treatment of Non-Responding Oral Lichen Planus: A Case Report

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Elisabetta Merigo

2018-02-01

Full Text Available Platelet-rich plasma (PRP has been proposed for different applications in the medical field and in maxillofacial surgery thanks to its many growth factors, such as epidermal growth factor (EGF, fibroblast growth factor (FGF, and keratinocyte growth factor (KGF. Oral lichen planus (OLP is a disease that affects the oral mucosa in a chronic way. This disease frequently worsens the quality of life of patients, particularly when clinical manifestations are of the erythematous or erosive/ulcerative type. The properties of PRP that are supported by scientific literature in both oral medicine and other medical fields have suggested the introduction of PRP in clinical practice for the medical treatment of different soft tissues diseases, such as when OLP patients do not respond to conventional therapies, or when conventional treatments have some contraindications or side effects. The aim of this work is to describe the use of PRP used as an oral rinse for the treatment of a patient diagnosed as affected by OLP at the Dentistry, Special Needs and Maxillo-Facial Surgery Unit of the Hospital of Piacenza. PRP protocol was started after the failure of conventional therapies based on the use of topical and systemic corticosteroids, hydroxychloroquine, and low-level laser therapy applications.

Platelet-Rich Plasma (PRP) Rinses for the Treatment of Non-Responding Oral Lichen Planus: A Case Report.

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Merigo, Elisabetta; Oppici, Aldo; Parlatore, Anna; Cella, Luigi; Clini, Fabio; Fontana, Matteo; Fornaini, Carlo

2018-02-06

Platelet-rich plasma (PRP) has been proposed for different applications in the medical field and in maxillofacial surgery thanks to its many growth factors, such as epidermal growth factor (EGF), fibroblast growth factor (FGF), and keratinocyte growth factor (KGF). Oral lichen planus (OLP) is a disease that affects the oral mucosa in a chronic way. This disease frequently worsens the quality of life of patients, particularly when clinical manifestations are of the erythematous or erosive/ulcerative type. The properties of PRP that are supported by scientific literature in both oral medicine and other medical fields have suggested the introduction of PRP in clinical practice for the medical treatment of different soft tissues diseases, such as when OLP patients do not respond to conventional therapies, or when conventional treatments have some contraindications or side effects. The aim of this work is to describe the use of PRP used as an oral rinse for the treatment of a patient diagnosed as affected by OLP at the Dentistry, Special Needs and Maxillo-Facial Surgery Unit of the Hospital of Piacenza. PRP protocol was started after the failure of conventional therapies based on the use of topical and systemic corticosteroids, hydroxychloroquine, and low-level laser therapy applications.

Behavior of Gingival Fibroblasts on Titanium Implant Surfaces in Combination with either Injectable-PRF or PRP

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Xuzhu Wang

2017-02-01

Full Text Available Various strategies have been employed to speed tissue regeneration using bioactive molecules. Interestingly, platelet concentrates derived from a patient’s own blood have been utilized as a regenerative strategy in recent years. In the present study, a novel liquid platelet formulation prepared without the use of anti-coagulants (injectable-platelet-rich fibrin, i-PRF was compared to standard platelet-rich plasma (PRP with gingival fibroblasts cultured on smooth and roughened titanium implant surfaces. Standard PRP and i-PRF (centrifuged at 700 rpm (60× g for 3 min were compared by assays for fibroblast biocompatibility, migration, adhesion, proliferation, as well as expression of platelet-derived growth factor (PDGF, transforming growth factor-β (TGF-β, collagen1 (COL1 and fibronectin (FN. The results demonstrate that i-PRF induced significantly higher cell migration, as well as higher messenger RNA (mRNA levels of PDGF, TGF-β, collagen1 and fibronectin when compared to PRP. Furthermore, collagen1 synthesis was highest in the i-PRF group. These findings demonstrate that liquid platelet concentrates can be formulated without the use of anticoagulants and present much translational potential for future research. Future animal and clinical trials are now necessary to further investigate the potential of utilizing i-PRF for soft tissue regenerative protocols in combination with various biomaterials.

Study of PrP - I heterogeneous equilibrium

International Nuclear Information System (INIS)

Vasil'eva, I.G.; Mironov, K.E.; Tarasenko, A.D.

1976-01-01

Using static methods the authors have measured the equilibrium vapor pressure in the system PrP+I 2 at different temperatures and different initial iodine concentrations. The equilibrium reactions in the system have been determined. The reaction of PrP with iodine is irreversible. The content of PrI 3 and I 2 in the gas phase is negligible. The pressure in the system is determined by the partial pressure of phosphorus

Successful treatment of radiation retinopathy with panretinal photocoagulation (PRP) in a patient of orbital MALT lymphoma

International Nuclear Information System (INIS)

Okamoto, Hiroyuki; Chikuda, Makoto; Kadoya, Kouji

2012-01-01

Report a case of satisfactory progress radiation retinopathy after radiation for mucosa-associated lymphoid tissue (MALT) lymphoma. A 26-year-old male patient, referred to our department for lacrimal sac tumor. Biopsy was done by otolaryngology and radiation therapy was performed (total irradiation of 41.4 Gy) as pathological examination revealed MALT lymphoma. Soft exudates and macula edema appeared in posterior pole of the right fundus after radiotherapy. Right vision became 0.5 because of macula edema, and panretinal photocoagulation (PRP) was performed. After PRP, macula edema withdrew and right vision improved to 1.2. It is suggested that the fundus must be monitored after radiation therapy, and early treatment, such as PRP is effective in radiation retinopathy. (author)

Characterization of PhPRP1, a histidine domain arabinogalactan protein from Petunia hybrida pistils.

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Twomey, Megan C; Brooks, Jenna K; Corey, Jillaine M; Singh-Cundy, Anu

2013-10-15

An arabinogalactan protein, PhPRP1, was purified from Petunia hybrida pistils and shown to be orthologous to TTS-1 and TTS-2 from Nicotiana tabacum and NaTTS from Nicotiana alata. Sequence comparisons among these proteins, and CaPRP1 from Capsicum annuum, reveal a conserved histidine-rich domain and two hypervariable domains. Immunoblots show that TTS-1 and PhPRP1 are also expressed in vegetative tissues of tobacco and petunia respectively. In contrast to the molecular mass heterogeneity displayed by the pistil proteins, the different isoforms found in seedlings, roots, and leaves each has a discrete size (37, 80, 160, and 200 kDa) on SDS-PAGE gels. On the basis of their chemistry, distinctive domain architecture, and the unique pattern of expression, we have named this group of proteins HD-AGPs (histidine domain-arabinogalactan proteins). Copyright © 2013 Elsevier GmbH. All rights reserved.

Prion propagation in cells expressing PrP glycosylation mutants.

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Salamat, Muhammad K; Dron, Michel; Chapuis, Jérôme; Langevin, Christelle; Laude, Hubert

2011-04-01

Infection by prions involves conversion of a host-encoded cell surface protein (PrP(C)) to a disease-related isoform (PrP(Sc)). PrP(C) carries two glycosylation sites variably occupied by complex N-glycans, which have been suggested by previous studies to influence the susceptibility to these diseases and to determine characteristics of prion strains. We used the Rov cell system, which is susceptible to sheep prions, to generate a series of PrP(C) glycosylation mutants with mutations at one or both attachment sites. We examined their subcellular trafficking and ability to convert into PrP(Sc) and to sustain stable prion propagation in the absence of wild-type PrP. The susceptibility to infection of mutants monoglycosylated at either site differed dramatically depending on the amino acid substitution. Aglycosylated double mutants showed overaccumulation in the Golgi compartment and failed to be infected. Introduction of an ectopic glycosylation site near the N terminus fully restored cell surface expression of PrP but not convertibility into PrP(Sc), while PrP(C) with three glycosylation sites conferred cell permissiveness to infection similarly to the wild type. In contrast, predominantly aglycosylated molecules with nonmutated N-glycosylation sequons, produced in cells expressing glycosylphosphatidylinositol-anchorless PrP(C), were able to form infectious PrP(Sc). Together our findings suggest that glycosylation is important for efficient trafficking of anchored PrP to the cell surface and sustained prion propagation. However, properly trafficked glycosylation mutants were not necessarily prone to conversion, thus making it difficult in such studies to discern whether the amino acid changes or glycan chain removal most influences the permissiveness to prion infection.

Superior integrin activating capacity and higher adhesion to fibrinogen matrix in buffy coat-derived platelet concentrates (PCs) compared to PRP-PCs.

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Beshkar, Pezhman; Hosseini, Ehteramolsadat; Ghasemzadeh, Mehran

2018-02-01

Regardless of different sources, methods or devices which are applied for preparation of therapeutic platelets, these products are generally isolated from whole blood by the sedimentation techniques which are based on PRP or buffy coat (BC) separation. As a general fact, platelet preparation and storage are also associated with some deleterious changes that known as platelet storage lesion (PSL). Although these alternations in platelet functional activity are aggravated during storage, whether technical issues within preparation can affect integrin activation and platelet adhesion to fibrinogen were investigated in this study. PRP- and BC-platelet concentrates (PCs) were subjected to flowcytometry analysis to examine the expression of platelet activation marker, P-selectin as well as active confirmation of the GPIIb/IIIa (α IIb β 3 ) on day 0, 1, 3 and 5 post-storage. Platelet adhesion to fibrinogen matrix was evaluated by fluorescence microscopy. Glucose concentration and LDH activity were also measured by colorimetric methods. The increasing P-selectin expression during storage was in a reverse correlation with PAC-1 binding (r = -0.67; p = .001). PRP-PCs showed the higher level of P-selectin expression than BC-PCs, whereas the levels of PAC-1 binding and platelet adhesion to fibrinogen matrix were significantly lower in PRP-PCs. Higher levels of active confirmation of the GPIIb/IIIa in BC-PCs were also associated with greater concentration of glucose in these products. We demonstrated the superior capacities of integrin activation and adhesion to fibrinogen for BC-PCs compared to those of PRP-PCs. These findings may provide more advantages for BC method of platelet preparation. Copyright © 2017 Elsevier Ltd. All rights reserved.

A fully liquid DTaP-IPV-HB-PRP-T hexavalent vaccine for primary and booster vaccination of healthy Turkish infants and toddlers

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Ceyhan, Mehmet; Yıldırım, İnci; Tezer, Hasan; Devrim, İlker; Feroldi, Emmanuel

2017-08-23

Background/aim: Immunogenicity and safety of a primary series of a fully liquid, hexavalent DTaP-IPV-HB-PRP-T vaccine given at 2, 3, and 4 months of age compared to licensed comparators and a DTaP-IPV-HB-PRP-T booster at 15?18 months were evaluated. Materials and methods: This was a Phase III, randomized, open-label trial. Primary series (no hepatitis B [HB] at birth) of DTaP-IPV-HB-PRP-T (N = 155) (group 1) or licensed control vaccines (DTaP-IPV//PRP-T and standalone HB: N = 155) (group 2) and DTaP-IPV-HB-PRP-T booster were administered. Noninferiority was evaluated 1 month postprimary series for anti-HB seroprotection (SP). All other analyses were descriptive. Safety was assessed from parental reports. Results: Postprimary series noninferiority of anti-HB ≥ 10 mIU/mL was demonstrated for the DTaP-IPV-HB-PRP-T vaccine (94.0%) compared to the licensed control (96.1%). Postprimary series primary SP and seroconversion (SC) rates were high and similar for both groups. Antibody persistence (prebooster) was high for each antigen and similar between groups except for HB, which was lower for DTaP-IPV-HB-PRP-T than for standalone HB. For each antigen except HB, DTaP-IPV-HB-PRP-T booster responses were high and similar in each group. Safety was good for primary and booster series and similar between groups. Conclusion: The DTaP-IPV-HB-PRP-T vaccine is immunogenic and safe when administered in a challenging primary series schedule without HB vaccination at birth.

Platelet-rich plasma: why intra-articular? A systematic review of preclinical studies and clinical evidence on PRP for joint degeneration.

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Filardo, G; Kon, E; Roffi, A; Di Matteo, B; Merli, M L; Marcacci, M

2015-09-01

The aim of this review was to analyze the available evidence on the clinical application of this biological approach for the injective treatment of cartilage lesions and joint degeneration, together with preclinical studies to support the rationale for the use of platelet concentrates, to shed some light and give indications on what to treat and what to expect from intra-articular injections of platelet-rich plasma (PRP). All in vitro, in vivo preclinical and clinical studies on PRP injective treatment in the English language concerning the effect of PRP on cartilage, synovial tissue, menisci, and mesenchymal stem cells were considered. A systematic review on the PubMed database was performed using the following words: (platelet-rich plasma or PRP or platelet concentrate or platelet lysate or platelet supernatant) and (cartilage or chondrocytes or synoviocytes or menisci or mesenchymal stem cells). Fifty-nine articles met the inclusion criteria: 26 were in vitro, 9 were in vivo, 2 were both in vivo and in vitro, and 22 were clinical studies. The analysis showed an increasing number of published studies over time. Preclinical evidence supports the use of PRP injections that might promote a favourable environment for joint tissues healing. Only a few high-quality clinical trials have been published, which showed a clinical improvement limited over time and mainly documented in younger patients not affected by advanced knee degeneration. Besides the limits and sometimes controversial findings, the preclinical literature shows an overall support toward this PRP application. An intra-articular injection does not just target cartilage; instead, PRP might influence the entire joint environment, leading to a short-term clinical improvement. Many biological variables might influence the clinical outcome and have to be studied to optimize PRP injective treatment of cartilage degeneration and osteoarthritis.

Two New PRP Conjugate Gradient Algorithms for Minimization Optimization Models.

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Yuan, Gonglin; Duan, Xiabin; Liu, Wenjie; Wang, Xiaoliang; Cui, Zengru; Sheng, Zhou

2015-01-01

Two new PRP conjugate Algorithms are proposed in this paper based on two modified PRP conjugate gradient methods: the first algorithm is proposed for solving unconstrained optimization problems, and the second algorithm is proposed for solving nonlinear equations. The first method contains two aspects of information: function value and gradient value. The two methods both possess some good properties, as follows: 1) βk ≥ 0 2) the search direction has the trust region property without the use of any line search method 3) the search direction has sufficient descent property without the use of any line search method. Under some suitable conditions, we establish the global convergence of the two algorithms. We conduct numerical experiments to evaluate our algorithms. The numerical results indicate that the first algorithm is effective and competitive for solving unconstrained optimization problems and that the second algorithm is effective for solving large-scale nonlinear equations.

Autologous platelet-rich plasma reduces transfusions during ascending aortic arch repair: a prospective, randomized, controlled trial.

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Zhou, Shao Feng; Estrera, Anthony L; Loubser, Paul; Ignacio, Craig; Panthayi, Sreelatha; Miller, Charles; Sheinbaum, Roy; Safi, Hazim J

2015-04-01

Blood conservation using autologous platelet-rich plasma (aPRP), a technique of whole blood harvest that separates red blood cells from plasma and platelets before cardiopulmonary bypass with retransfusion of the preserved platelets after completion of cardiopulmonary bypass, has not been studied extensively. We sought to prospectively determine whether aPRP reduces blood transfusions during ascending and transverse aortic arch repair. We randomly assigned 80 patients undergoing elective ascending and transverse aortic arch repair using deep hypothermic circulatory arrest to receive either aPRP (n = 38) or no aPRP (n = 42). Volume of aPRP retransfused was 726 ± 124 mL. The primary end point was transfusion amount. Secondary end points were death, stroke, renal failure, pulmonary failure, and transfusion costs. Perioperative transfusion rate was defined as blood transfusions given during surgery and up to 72 hours afterward. The surgeon and intensivist were blinded to the treatment arm. Because an anesthesiologist initiated the protocol, the surgeon was not aware of aPRP collection, as this occurred only after the sterile drape was in place. In addition, because cell salvage was performed on all cases, differentiation in perfusionist activities (during spinning of aPRP) was not evident. Platelet, fresh frozen plasma, and cryoprecipitate intraoperative transfusions were performed only after heparin was reversed and the patient was judged as coagulopathic on the basis of associated criteria: cryoprecipitate transfusion for fibrinogen level less than 150 μg/dL, platelet transfusion for platelet count less than 80,000, and fresh frozen plasma when thromboelastogram test was suggestive or a partial thromboplastin time was greater than 55 seconds, and prothrombin time was greater than 1.6 seconds. Early mortality, stroke, and respiratory complications were similar between groups. Only acute renal failure was reduced in the aPRP group, 7% versus 0% (p platelets by 56

Quantification of platelets and platelet derived growth factors from platelet-rich-plasma (PRP) prepared at different centrifugal force (g) and time.

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Arora, Satyam; Doda, Veena; Kotwal, Urvershi; Dogra, Mitu

2016-02-01

Platelet derived biomaterials represent a key source of cytokines and growth factors extensively used for tissue regeneration; wound healing and tissue repair. Our study was to quantify platelets and growth factors released by PRP when prepared at different centrifugal force (g) and time. Our study was approved by the institutional ethical committee. One hundred millilitres of whole blood (WB) was collected in bag with CPDA as the anticoagulant(AC); (14 mL for 100 mL WB ratio). Nine aliquots of 10 mL each were made from the bag and set of three aliquots were made a group. PRP was prepared at varying centrifugal force (group A: -110 g, group B: -208 g & group C: -440 g) & time (1: -5 min, 2: -10 min & 3: -20 min). Contents of each PRP prepared were analysed. Commercial sandwich ELISA kits were used to quantify the concentrations of CD62P (Diaclone SAS; France), Platelet derived growth factors-AB (Qayee-Bio; China), transforming growth factor-β1 (DRG; Germany) and vascular endothelial growth factor (Boster Immuno Leader; USA) released in each PRP prepared. Eight volunteers were enrolled in the study (24-30 years). The baseline blood counts of all the volunteers were comparable (p ≥ 0.05). Mean ± SD of platelet yield of all nine groups ranged from 17.2 ± 4.2% to 78.7 ± 5.7%. Each PRP was activated with calcified thromboplastin to quantify the growth factors released by them. Significantly higher (p < 0.05) transforming growth factor-β1 and vascular endothelial growth factor were released compared to the baseline. Our study highlights the variation in both force (g) and time results in changes at cellular level and growth factor concentrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

PRP: a FORTRAN IV interactive plotting program

Science.gov (United States)

Andrew, A. S.; Linde, J.

A computer program, PRP, has been designed to plot any arithmetic combination selected from a set of major and trace element data on a y- x graph. y and x are defined and entered as a program string (y, x) which is interpreted sequentially. Operators ( +, -, ∗, /, ( unary) , square root, log 10, In c, antilog 10, exponential, integer, absolute value, (,),,) and integer or real numbers may be included. Axis lengths and scales are determined by the user. Five different plotting symbols are available.

A fully liquid DTaP-IPV-Hep B-PRP-T hexavalent vaccine for primary and booster vaccination of healthy Mexican children.

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Aquino, Amalia Guadalupe Becerra; Brito, Maricruz Gutiérrez; Doniz, Carlos E Aranza; Herrera, Juan Francisco Galán; Macias, Mercedes; Zambrano, Betzana; Plennevaux, Eric; Santos-Lima, Eduardo

2012-10-05

To evaluate an investigational, fully liquid hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-hepatitis B-Haemophilus influenzae type b (DTaP-IPV-Hep B-PRP-T: Hexaxim™) vaccine for primary and booster vaccination of healthy children in Mexico. Infants (N=1189) were randomized to receive one of three lots of the DTaP-IPV-Hep B-PRP-T vaccine or a licensed hexavalent control vaccine (Infanrix™ hexa) for primary vaccination at 2, 4 and 6 months. All participants who completed the primary series and agreed to participate in the booster part of the study received a dose of the investigational vaccine at 15-18 months of age. Validated serological assays and parental reports were used to assess immunogenicity and safety, respectively. Post-primary vaccination, ≥95.8% of participants in both the DTaP-IPV-Hep B-PRP-T and control groups were seroprotected (SP) against diphtheria, tetanus, poliovirus, hepatitis B and PRP, or had seroconverted (SC) to the pertussis toxin (PT) and filamentous hemagglutinin (FHA) pertussis antigens. The SP/SC rates induced by the three DTaP-IPV-Hep B-PRP-T lots were equivalent. No differences in SP/SC rates were observed between the pooled lots of investigational vaccine and the control vaccine. Antibody persistence at 15-18 months was comparable between groups, with strong increases in all antibody concentrations post-DTaP-IPV-Hep B-PRP-T booster. Both vaccines were well tolerated for primary vaccination, as was the booster dose of DTaP-IPV-Hep B-PRP-T. These study findings confirm the suitability of the combined, fully liquid DTaP-IPV-Hep B-PRP-T vaccine for inclusion in routine childhood vaccination schedules. Copyright © 2012 Elsevier Ltd. All rights reserved.

Two New PRP Conjugate Gradient Algorithms for Minimization Optimization Models.

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Gonglin Yuan

Full Text Available Two new PRP conjugate Algorithms are proposed in this paper based on two modified PRP conjugate gradient methods: the first algorithm is proposed for solving unconstrained optimization problems, and the second algorithm is proposed for solving nonlinear equations. The first method contains two aspects of information: function value and gradient value. The two methods both possess some good properties, as follows: 1 βk ≥ 0 2 the search direction has the trust region property without the use of any line search method 3 the search direction has sufficient descent property without the use of any line search method. Under some suitable conditions, we establish the global convergence of the two algorithms. We conduct numerical experiments to evaluate our algorithms. The numerical results indicate that the first algorithm is effective and competitive for solving unconstrained optimization problems and that the second algorithm is effective for solving large-scale nonlinear equations.

Substitutions of PrP N-terminal histidine residues modulate scrapie disease pathogenesis and incubation time in transgenic mice.

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Eigenbrod, Sabina; Frick, Petra; Bertsch, Uwe; Mitteregger-Kretzschmar, Gerda; Mielke, Janina; Maringer, Marko; Piening, Niklas; Hepp, Alexander; Daude, Nathalie; Windl, Otto; Levin, Johannes; Giese, Armin; Sakthivelu, Vignesh; Tatzelt, Jörg; Kretzschmar, Hans; Westaway, David

2017-01-01

Prion diseases have been linked to impaired copper homeostasis and copper induced-oxidative damage to the brain. Divalent metal ions, such as Cu2+ and Zn2+, bind to cellular prion protein (PrPC) at octapeptide repeat (OR) and non-OR sites within the N-terminal half of the protein but information on the impact of such binding on conversion to the misfolded isoform often derives from studies using either OR and non-OR peptides or bacterially-expressed recombinant PrP. Here we created new transgenic mouse lines expressing PrP with disrupted copper binding sites within all four histidine-containing OR's (sites 1-4, H60G, H68G, H76G, H84G, "TetraH>G" allele) or at site 5 (composed of residues His-95 and His-110; "H95G" allele) and monitored the formation of misfolded PrP in vivo. Novel transgenic mice expressing PrP(TetraH>G) at levels comparable to wild-type (wt) controls were susceptible to mouse-adapted scrapie strain RML but showed significantly prolonged incubation times. In contrast, amino acid replacement at residue 95 accelerated disease progression in corresponding PrP(H95G) mice. Neuropathological lesions in terminally ill transgenic mice were similar to scrapie-infected wt controls, but less severe. The pattern of PrPSc deposition, however, was not synaptic as seen in wt animals, but instead dense globular plaque-like accumulations of PrPSc in TgPrP(TetraH>G) mice and diffuse PrPSc deposition in (TgPrP(H95G) mice), were observed throughout all brain sections. We conclude that OR and site 5 histidine substitutions have divergent phenotypic impacts and that cis interactions between the OR region and the site 5 region modulate pathogenic outcomes by affecting the PrP globular domain.

Prion Propagation in Cells Expressing PrP Glycosylation Mutants ▿

Science.gov (United States)

Salamat, Muhammad K.; Dron, Michel; Chapuis, Jérôme; Langevin, Christelle; Laude, Hubert

2011-01-01

Infection by prions involves conversion of a host-encoded cell surface protein (PrPC) to a disease-related isoform (PrPSc). PrPC carries two glycosylation sites variably occupied by complex N-glycans, which have been suggested by previous studies to influence the susceptibility to these diseases and to determine characteristics of prion strains. We used the Rov cell system, which is susceptible to sheep prions, to generate a series of PrPC glycosylation mutants with mutations at one or both attachment sites. We examined their subcellular trafficking and ability to convert into PrPSc and to sustain stable prion propagation in the absence of wild-type PrP. The susceptibility to infection of mutants monoglycosylated at either site differed dramatically depending on the amino acid substitution. Aglycosylated double mutants showed overaccumulation in the Golgi compartment and failed to be infected. Introduction of an ectopic glycosylation site near the N terminus fully restored cell surface expression of PrP but not convertibility into PrPSc, while PrPC with three glycosylation sites conferred cell permissiveness to infection similarly to the wild type. In contrast, predominantly aglycosylated molecules with nonmutated N-glycosylation sequons, produced in cells expressing glycosylphosphatidylinositol-anchorless PrPC, were able to form infectious PrPSc. Together our findings suggest that glycosylation is important for efficient trafficking of anchored PrP to the cell surface and sustained prion propagation. However, properly trafficked glycosylation mutants were not necessarily prone to conversion, thus making it difficult in such studies to discern whether the amino acid changes or glycan chain removal most influences the permissiveness to prion infection. PMID:21248032

PrPST, a Soluble, Protease Resistant and Truncated PrP Form Features in the Pathogenesis of a Genetic Prion Disease

Science.gov (United States)

Frid, Kati; Binyamin, Orli; Gabizon, Ruth

2013-01-01

While the conversion of PrPC into PrPSc in the transmissible form of prion disease requires a preexisting PrPSc seed, in genetic prion disease accumulation of disease related PrP could be associated with biochemical and metabolic modifications resulting from the designated PrP mutation. To investigate this possibility, we looked into the time related changes of PrP proteins in the brains of TgMHu2ME199K/wt mice, a line modeling for heterozygous genetic prion disease linked to the E200K PrP mutation. We found that while oligomeric entities of mutant E199KPrP exist at all ages, aggregates of wt PrP in the same brains presented only in advanced disease, indicating a late onset conversion process. We also show that most PK resistant PrP in TgMHu2ME199K mice is soluble and truncated (PrPST), a pathogenic form never before associated with prion disease. We next looked into brain samples from E200K patients and found that both PK resistant PrPs, PrPST as in TgMHu2ME199K mice, and “classical” PrPSc as in infectious prion diseases, coincide in the patient's post mortem brains. We hypothesize that aberrant metabolism of mutant PrPs may result in the formation of previously unknown forms of the prion protein and that these may be central for the fatal outcome of the genetic prion condition. PMID:23922744

Exercise and the platelet activator calcium chloride both influence the growth factor content of platelet-rich plasma (PRP): overlooked biochemical factors that could influence PRP treatment

NARCIS (Netherlands)

Hamilton, Bruce; Tol, Johannes L.; Knez, Wade; Chalabi, Hakim

2015-01-01

There is strong evidence that exercise affects platelet haemostasis factors, but this potential effect on growth factor concentrations in platelet-rich plasma (PRP) has never been studied. In addition, there is a paucity of studies focusing on the effects of activating agents used in conjunction

Effects of the Pathogenic Mutation A117V and the Protective Mutation H111S on the Folding and Aggregation of PrP106-126: Insights from Replica Exchange Molecular Dynamics Simulations.

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Lulu Ning

Full Text Available The fragment 106-126 of prion protein exhibits similar properties to full-length prion. Experiments have shown that the A117V mutation enhances the aggregation of PrP106-126, while the H111S mutation abolishes the assembly. However, the mechanism of the change in the aggregation behavior of PrP106-126 upon the two mutations is not fully understood. In this study, replica exchange molecular dynamics simulations were performed to investigate the conformational ensemble of the WT PrP106-126 and its two mutants A117V and H111S. The obtained results indicate that the three species are all intrinsically disordered but they have distinct morphological differences. The A117V mutant has a higher propensity to form β-hairpin structures than the WT, while the H111S mutant has a higher population of helical structures. Furthermore, the A117V mutation increases the hydrophobic solvent accessible surface areas of PrP106-126 and the H111S mutation reduces the exposure of hydrophobic residues. It can be concluded that the difference in populations of β-hairpin structures and the change of hydrophobic solvent accessible areas may induce the different aggregation behaviors of the A117V and the H111S mutated PrP106-126. Understanding why the two mutations have contrary effects on the aggregation of PrP106-126 is very meaningful for further elucidation of the mechanism underlying aggregation and design of inhibitor against aggregation process.

Split face comparative study of microneedling with PRP versus microneedling with vitamin C in treating atrophic post acne scars

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Simran Chawla

2014-01-01

Full Text Available Introduction: Acne scars are largely preventable complications of acne. 95% of the scars occur over the face thus impacting the quality of life. Correction of scars is the priority for acne patients. Materials and Methods: Thirty patients with post acne atrophic facial scars attending the OPD during the period from April to October 2013 were offered four sittings of microneedling with PRP on one side and microneedling with vitamin C on other side of the face at an interval of 1 month. Results: Twenty-seven out of the total 30 patients completed the treatment schedule. Two patients were lost to follow up and one dropped out of the study due to severe PIH. Mean age of the patients was 27.5 years. Out of 30 patients, 23 achieved reduction in scarring by one or two grades. Excellent response was seen in five (18.5% patients with platelet-rich plasma (PRP as compared to two (7% patients who received treatment with vitamin C according to physician′s assessment. As far as up gradation by 1 score is considered, i.e., good response, it was similar in both cases. Vitamin C did not prove to be as efficacious as PRP since 10 (37% patients had poor response in vitamin C-treated area compared to only 6 (22.2% patients who underwent PRP therapy, but vitamin C proved to be efficacious in dealing with post inflammatory hyper-pigmentation secondary to acne. Patients were more satisfied with PRP as compared to vitamin C. The results were evaluated and statistical analysis was done using SPSS 16.0.2. Conclusions: Overall results were better with microneedling and PRP. Vitamin C combined with microneedling also showed improvement with respect to firmness and smoothness of skin; as well as post inflammatory hyper-pigmentation. Microneedling combined with PRP proved to be good in treating boxcar and rolling scars but had limited efficacy in dealing with ice pick scars.

Dynamic Contacts of U2, RES, Cwc25, Prp8 and Prp45 Proteins with the Pre-mRNA Branch-Site and 3' Splice Site during Catalytic Activation and Step 1 Catalysis in Yeast Spliceosomes.

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Cornelius Schneider

Full Text Available Little is known about contacts in the spliceosome between proteins and intron nucleotides surrounding the pre-mRNA branch-site and their dynamics during splicing. We investigated protein-pre-mRNA interactions by UV-induced crosslinking of purified yeast B(act spliceosomes formed on site-specifically labeled pre-mRNA, and analyzed their changes after conversion to catalytically-activated B* and step 1 C complexes, using a purified splicing system. Contacts between nucleotides upstream and downstream of the branch-site and the U2 SF3a/b proteins Prp9, Prp11, Hsh49, Cus1 and Hsh155 were detected, demonstrating that these interactions are evolutionarily conserved. The RES proteins Pml1 and Bud13 were shown to contact the intron downstream of the branch-site. A comparison of the B(act crosslinking pattern versus that of B* and C complexes revealed that U2 and RES protein interactions with the intron are dynamic. Upon step 1 catalysis, Cwc25 contacts with the branch-site region, and enhanced crosslinks of Prp8 and Prp45 with nucleotides surrounding the branch-site were observed. Cwc25's step 1 promoting activity was not dependent on its interaction with pre-mRNA, indicating it acts via protein-protein interactions. These studies provide important insights into the spliceosome's protein-pre-mRNA network and reveal novel RNP remodeling events during the catalytic activation of the spliceosome and step 1 of splicing.

On the extent of homogeneity region of PrP phase in the system praseodymium-phosphorus

International Nuclear Information System (INIS)

Mironov, K.E.

1984-01-01

For constructed by ion type compounds in the metal or metalloid systems homogeneity region boundary position can be observed at different compositions depending on which side the approximation to it occurs: on the metal or compound side. As an example the PrP homogeneity region in the praseodymium-phosphorus system is considered. An assumption is made on the prevalence of this phenomenon among rare earth monopnictides and monochalcogenides. For the PrP phase it is indicated that the monophopshide cell parameter depends on content of impurities in the initial metal, oxygen, in particular

PrP protein is associated with follicular dendritic cells of spleens and lymph nodes in uninfected and scrapie-infected mice

NARCIS (Netherlands)

McBride, P. A.; Eikelenboom, P.; Kraal, G.; Fraser, H.; Bruce, M. E.

1992-01-01

Abnormal forms of a host protein, PrP, accumulate in the central nervous system in scrapie-affected animals. Here, PrP protein was detected immunocytochemically in tissue sections of spleen, lymph node, Peyer's patches, thymus, and pancreas from uninfected mice and from mice infected with a range of

In search of a consensus terminology in the field of platelet concentrates for surgical use: platelet-rich plasma (PRP), platelet-rich fibrin (PRF), fibrin gel polymerization and leukocytes.

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Dohan Ehrenfest, David M; Bielecki, Tomasz; Mishra, Allan; Borzini, Piero; Inchingolo, Francesco; Sammartino, Gilberto; Rasmusson, Lars; Everts, Peter A

2012-06-01

In the field of platelet concentrates for surgical use, most products are termed Platelet-Rich Plasma (PRP). Unfortunately, this term is very general and incomplete, leading to many confusions in the scientific database. In this article, a panel of experts discusses this issue and proposes an accurate and simple terminology system for platelet concentrates for surgical use. Four main categories of products can be easily defined, depending on their leukocyte content and fibrin architecture: Pure Platelet-Rich Plasma (P-PRP), such as cell separator PRP, Vivostat PRF or Anitua's PRGF; Leukocyteand Platelet-Rich Plasma (L-PRP), such as Curasan, Regen, Plateltex, SmartPReP, PCCS, Magellan, Angel or GPS PRP; Pure Plaletet-Rich Fibrin (P-PRF), such as Fibrinet; and Leukocyte- and Platelet-Rich Fibrin (L-PRF), such as Choukroun's PRF. P-PRP and L-PRP refer to the unactivated liquid form of these products, their activated versions being respectively named P-PRP gels and L-PRP gels. The purpose of this search for a terminology consensus is to plead for a more serious characterization of these products. Researchers have to be aware of the complex nature of these living biomaterials, in order to avoid misunderstandings and erroneous conclusions. Understanding the biomaterials or believing in the magic of growth factors ? From this choice depends the future of the field.

Superfund TIO videos. Set B. Basics of administrative law, and prp search process: PRP search, information exchange and access. Part 3. Audio-Visual

International Nuclear Information System (INIS)

1990-01-01

The videotape is divided into two sections. Section 1 identifies the various types of administrative hearings, including quasi-legislative, quasi-judicial, and hybrid types. Section 2 provides an overview of the PRP search process; explains how and when to issue Section 104(e) letters and administrative subpoenas; outlines the enforcement authorities available in cases of non-compliance; and describes the types of information that can be released to PRPs

Adjunctive Platelet-Rich Plasma (PRP in Infrabony Regenerative Treatment: A Systematic Review and RCT’s Meta-Analysis

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Mubashir Saleem

2018-01-01

Full Text Available Background and Objective. The purpose of this study was to highlight the clinical performance of platelet-rich plasma (PRP used as an adjunctive tool for regeneration in infrabony periodontal defects using different biomaterials or performing different surgical flap approaches. Comparative evaluation of main clinical outcomes as probing pocket depth reduction, clinical attachment gain, and recession reduction with and without the use of PRP has been analysed. Materials and Methods. According to the focused question, an electronic and hand searching has been performed up to December 2016. From a batch of 73 articles, the selection strategy and Jadad quality assessment led us to include 15 studies for the meta-analysis. Results. Despite the high heterogeneity found and the lack of complete data regarding the selected clinical outcomes, a comparative analysis has been possible by the categorization of used biomaterials and surgical flap approaches. This method led us to observe the best performance of grafts with the use of adjunctive PRP in CAL gain and PPD reduction. No difference has been outlined with a specific surgical flap. Conclusions. Although PRP is considered a cheap and patient’s derived growth factor, the not conclusive data reported would suggest that its use in addition to bone substitutes could be of some clinical benefit in the regenerative treatment of infrabony defects. Clinical Relevance. This systematic review was intended to sort out the huge controversial debate in the field about the possible use of PRP in regenerative surgery in infrabony defect. The clinical relevance of using blood-borne growth factors to conventional procedures is effective as these could determine a better performance and outcomes despite the surgical approach adopted and limit the use of additional biomaterials for the blood clot stabilization.

PrP(ST), a soluble, protease resistant and truncated PrP form features in the pathogenesis of a genetic prion disease.

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Friedman-Levi, Yael; Mizrahi, Michal; Frid, Kati; Binyamin, Orli; Gabizon, Ruth

2013-01-01

While the conversion of PrP(C) into PrP(Sc) in the transmissible form of prion disease requires a preexisting PrP(Sc) seed, in genetic prion disease accumulation of disease related PrP could be associated with biochemical and metabolic modifications resulting from the designated PrP mutation. To investigate this possibility, we looked into the time related changes of PrP proteins in the brains of TgMHu2ME199K/wt mice, a line modeling for heterozygous genetic prion disease linked to the E200K PrP mutation. We found that while oligomeric entities of mutant E199KPrP exist at all ages, aggregates of wt PrP in the same brains presented only in advanced disease, indicating a late onset conversion process. We also show that most PK resistant PrP in TgMHu2ME199K mice is soluble and truncated (PrP(ST)), a pathogenic form never before associated with prion disease. We next looked into brain samples from E200K patients and found that both PK resistant PrPs, PrP(ST) as in TgMHu2ME199K mice, and "classical" PrP(Sc) as in infectious prion diseases, coincide in the patient's post mortem brains. We hypothesize that aberrant metabolism of mutant PrPs may result in the formation of previously unknown forms of the prion protein and that these may be central for the fatal outcome of the genetic prion condition.

PrP(ST, a soluble, protease resistant and truncated PrP form features in the pathogenesis of a genetic prion disease.

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Yael Friedman-Levi

Full Text Available While the conversion of PrP(C into PrP(Sc in the transmissible form of prion disease requires a preexisting PrP(Sc seed, in genetic prion disease accumulation of disease related PrP could be associated with biochemical and metabolic modifications resulting from the designated PrP mutation. To investigate this possibility, we looked into the time related changes of PrP proteins in the brains of TgMHu2ME199K/wt mice, a line modeling for heterozygous genetic prion disease linked to the E200K PrP mutation. We found that while oligomeric entities of mutant E199KPrP exist at all ages, aggregates of wt PrP in the same brains presented only in advanced disease, indicating a late onset conversion process. We also show that most PK resistant PrP in TgMHu2ME199K mice is soluble and truncated (PrP(ST, a pathogenic form never before associated with prion disease. We next looked into brain samples from E200K patients and found that both PK resistant PrPs, PrP(ST as in TgMHu2ME199K mice, and "classical" PrP(Sc as in infectious prion diseases, coincide in the patient's post mortem brains. We hypothesize that aberrant metabolism of mutant PrPs may result in the formation of previously unknown forms of the prion protein and that these may be central for the fatal outcome of the genetic prion condition.

A Randomized, Controlled Study of DTaP-IPV-HB-PRP-T, a Fully Liquid Hexavalent Vaccine, Administered in a 3-, 5- and 11- to 12-month Schedule.

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Vesikari, Timo; Silfverdal, Sven-Arne; Jordanov, Emilia; Feroldi, Emmanuel

2017-01-01

To assess the immunogenicity and safety of a fully liquid, ready-to-use hexavalent DTaP-IPV-HB-PRP-T vaccine when administered in a 2 + 1 schedule at 3, 5 and 11-12 months of age. Phase III, randomized, active-controlled, observer-blind, multicenter study. Infants were randomized to receive DTaP-IPV-HB-PRP-T (N = 275) or a licensed control hexavalent vaccine (DTaP-IPV-HB//PRP~T: N = 275), both given in coadministration with Prevenar 13. Serum was analyzed for immune responses to all vaccine antigens. Noninferiority of DTaP-IPV-HB-PRP-T to the control vaccine was tested at completion of the primary series using predefined seroprotection (SP) rate and vaccine response (VR) rates. Safety was assessed using parental reports. Noninferiority of DTaP-IPV-HB-PRP-T to the control vaccine was demonstrated postdose 3 for each antigen, and the SP (for D, T, poliovirus 1, 2 and 3, hepatitis B and polyribosylribitol phosphate) and VR rates (for pertussis toxin and filamentous hemagglutinin) were high in each group. SP rates for D, T, polio 1, 2, 3 and VR rates for pertussis toxin and filamentous hemagglutinin were similar in each group. For hepatitis B, SP rate was slightly higher for DTaP-IPV-HB//PRP~T (99.6%) than DTaP-IPV-HB-PRP-T (96.4%), and for PRP, SP rate was higher for DTaP-IPV-HB-PRP-T (93.5%) than DTaP-IPV-HB//PRP~T (85.2%). For Prevenar 13, the SP rate was high for each serotype and similar for both groups. All vaccines were well tolerated. These study findings confirm the safety and immunogenicity and thus the suitability of this fully liquid hexavalent vaccine for administration in a 2 + 1 schedule.

Polo-like kinase 3 (PLK3) mediates the clearance of the accumulated PrP mutants transiently expressed in cultured cells and pathogenic PrP(Sc) in prion infected cell line via protein interaction.

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Wang, Hui; Tian, Chan; Fan, Xue-Yu; Chen, Li-Na; Lv, Yan; Sun, Jing; Zhao, Yang-Jing; Zhang, Lu-bin; Wang, Jing; Shi, Qi; Gao, Chen; Chen, Cao; Shao, Qi-Xiang; Dong, Xiao-Ping

2015-05-01

Polo-like kinases (PLKs) family has long been known to be critical for cell cycle and recent studies have pointed to new dimensions of PLKs function in the nervous system. Our previous study has verified that the levels of PLK3 in the brain are severely downregulated in prion-related diseases. However, the associations of PLKs with prion protein remain unclear. In the present study, we confirmed that PrP protein constitutively interacts with PLK3 as determined by both in vitro and in vivo assays. Both the kinase domain and polo-box domain of PLK3 were proved to bind PrP proteins expressed in mammalian cell lines. Overexpression of PLK3 did not affect the level of wild-type PrP, but significantly decreased the levels of the mutated PrPs in cultured cells. The kinase domain appeared to be responsible for the clearance of abnormally aggregated PrPs, but this function seemed to be independent of its kinase activity. RNA-mediated knockdown of PLK3 obviously aggravated the accumulation of cytosolic PrPs. Moreover, PLK3 overexpression in a scrapie infected cell line caused notable reduce of PrP(Sc) level in a dose-dependent manner, but had minimal effect on the expression of PrP(C) in its normal partner cell line. Our findings here confirmed the molecular interaction between PLK3 and PrP and outlined the regulatory activity of PLK3 on the degradation of abnormal PrPs, even its pathogenic isoform PrP(Sc). We, therefore, assume that the recovery of PLK3 in the early stage of prion infection may be helpful to prevent the toxic accumulation of PrP(Sc) in the brain tissues. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evidence for a central role of PrP helix 2 in the nucleation of amyloid fibrils.

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Honda, Ryo; Kuwata, Kazuo

2018-02-01

Amyloid fibrils are filamentous protein aggregates associated with the pathogenesis of a wide variety of human diseases. The formation of such aggregates typically follows nucleation-dependent kinetics, wherein the assembly and structural conversion of amyloidogenic proteins into oligomeric aggregates (nuclei) is the rate-limiting step of the overall reaction. In this study, we sought to gain structural insights into the oligomeric nuclei of the human prion protein (PrP) by preparing a series of deletion mutants lacking 14-44 of the C-terminal 107 residues of PrP and examined the kinetics and thermodynamics of these mutants in amyloid formation. An analysis of the experimental data using the concepts of the Φ-value analysis indicated that the helix 2 region (residues 168-196) acquires an amyloid-like β-sheet during nucleation, whereas the other regions preserves a relatively disordered structure in the nuclei. This finding suggests that the helix 2 region serves as the nucleation site for the assembly of amyloid fibrils.-Honda, R., Kuwata, K. Evidence for a central role of PrP helix 2 in the nucleation of amyloid fibrils.

A modified three-term PRP conjugate gradient algorithm for optimization models.

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Wu, Yanlin

2017-01-01

The nonlinear conjugate gradient (CG) algorithm is a very effective method for optimization, especially for large-scale problems, because of its low memory requirement and simplicity. Zhang et al. (IMA J. Numer. Anal. 26:629-649, 2006) firstly propose a three-term CG algorithm based on the well known Polak-Ribière-Polyak (PRP) formula for unconstrained optimization, where their method has the sufficient descent property without any line search technique. They proved the global convergence of the Armijo line search but this fails for the Wolfe line search technique. Inspired by their method, we will make a further study and give a modified three-term PRP CG algorithm. The presented method possesses the following features: (1) The sufficient descent property also holds without any line search technique; (2) the trust region property of the search direction is automatically satisfied; (3) the steplengh is bounded from below; (4) the global convergence will be established under the Wolfe line search. Numerical results show that the new algorithm is more effective than that of the normal method.

CONTAMINATED PROBLEMATIC SKIN WOUNDS IN DIABETIC PATIENTS TREATED WITH AUTOLOGOUS PLATELET-RICH PLASMA (PRP: A case series study

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Tsvetan Sokolov

2016-03-01

Full Text Available OBJECTIVE: To study the effect of platelet-rich plasma (PRP on contaminated problematic skin ulcers in patients with diabetes. MATERIAL AND METHODS: A total of 6 patients had been treated within the period from 2012 to 2014; they had various types of problematic wounds and diabetes type 2. Patients’ distribution by sex was as follows: 1 man and 5 women; mean age- 68 years. Ulcer types: acute (2 patients, hard-to-heal (2 patients and chronic (2 patients ulcers. The mean size of the skin and soft tissue defect was 9,5 cm2. Pathogenic microflora was isolated in 4 patients - S. aureus in three and Е. Coli in one. Based on a scheme developed by us, all cases were treated by administering platelet-rich plasma, derived by PRGF Endoret system. Follow-up period was within 4 – 6 months (4,5 on average. We used platelet rich plasma derived by PRGF Endoret system, applied on the wound bed on a weekly basis. RESULTS: Application of PRP allowed successful closure of all wounds. There were no complications associated with treatment of PRP. Epithelialization of the wound took 15 weeks on average for all patients. One patient presented with hyperkeratosis. Initial score of followed wounds, based on the scales are as follows: Total wound score – 10 p. Total anatomic score – 8 p. Total score – 15 p. at the initial stage. At the end of the treatment period scores were as follows - 0 p., which means excellent results CONCLUSION: We believe that the application of PRP may become optimal therapy in the treatment of contaminated problematic wounds in diabetic patients. PRP not only stimulates wound healing, but also has antimicrobial properties, which may contribute to the prevention of infections.

Growth factor and pro-inflammatory cytokine contents in platelet-rich plasma (PRP), plasma rich in growth factors (PRGF), advanced platelet-rich fibrin (A-PRF), and concentrated growth factors (CGF).

Science.gov (United States)

Masuki, Hideo; Okudera, Toshimitsu; Watanebe, Taisuke; Suzuki, Masashi; Nishiyama, Kazuhiko; Okudera, Hajime; Nakata, Koh; Uematsu, Kohya; Su, Chen-Yao; Kawase, Tomoyuki

2016-12-01

The development of platelet-rich fibrin (PRF) drastically simplified the preparation procedure of platelet-concentrated biomaterials, such as platelet-rich plasma (PRP), and facilitated their clinical application. PRF's clinical effectiveness has often been demonstrated in pre-clinical and clinical studies; however, it is still controversial whether growth factors are significantly concentrated in PRF preparations to facilitate wound healing and tissue regeneration. To address this matter, we performed a comparative study of growth factor contents in PRP and its derivatives, such as advanced PRF (A-PRF) and concentrated growth factors (CGF). PRP and its derivatives were prepared from the same peripheral blood samples collected from healthy donors. A-PRF and CGF preparations were homogenized and centrifuged to produce extracts. Platelet and white blood cell counts in A-PRF and CGF preparations were determined by subtracting those counts in red blood cell fractions, supernatant acellular serum fractions, and A-PRF/CGF exudate fractions from those counts of whole blood samples. Concentrations of growth factors (TGF-β1, PDGF-BB, VEGF) and pro-inflammatory cytokines (IL-1β, IL-6) were determined using ELISA kits. Compared to PRP preparations, both A-PRF and CGF extracts contained compatible or higher levels of platelets and platelet-derived growth factors. In a cell proliferation assay, both A-PRF and CGF extracts significantly stimulated the proliferation of human periosteal cells without significant reduction at higher doses. These data clearly demonstrate that both A-PRF and CGF preparations contain significant amounts of growth factors capable of stimulating periosteal cell proliferation, suggesting that A-PRF and CGF preparations function not only as a scaffolding material but also as a reservoir to deliver certain growth factors at the site of application.

The folding mechanism and key metastable state identification of the PrP127-147 monomer studied by molecular dynamics simulations and Markov state model analysis.

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Zhou, Shuangyan; Wang, Qianqian; Wang, Yuwei; Yao, Xiaojun; Han, Wei; Liu, Huanxiang

2017-05-10

The structural transition of prion proteins from a native α-helix (PrP C ) to a misfolded β-sheet-rich conformation (PrP Sc ) is believed to be the main cause of a number of prion diseases in humans and animals. Understanding the molecular basis of misfolding and aggregation of prion proteins will be valuable for unveiling the etiology of prion diseases. However, due to the limitation of conventional experimental techniques and the heterogeneous property of oligomers, little is known about the molecular architecture of misfolded PrP Sc and the mechanism of structural transition from PrP C to PrP Sc . The prion fragment 127-147 (PrP127-147) has been reported to be a critical region for PrP Sc formation in Gerstmann-Straussler-Scheinker (GSS) syndrome and thus has been used as a model for the study of prion aggregation. In the present study, we employ molecular dynamics (MD) simulation techniques to study the conformational change of this fragment that could be relevant to the PrP C -PrP Sc transition. Employing extensive replica exchange molecular dynamics (REMD) and conventional MD simulations, we sample a huge number of conformations of PrP127-147. Using the Markov state model (MSM), we identify the metastable conformational states of this fragment and the kinetic network of transitions between the states. The resulting MSM reveals that disordered random-coiled conformations are the dominant structures. A key metastable folded state with typical extended β-sheet structures is identified with Pro137 being located in a turn region, consistent with a previous experimental report. Conformational analysis reveals that intrapeptide hydrophobic interaction and two key residue interactions, including Arg136-His140 and Pro137-His140, contribute a lot to the formation of ordered extended β-sheet states. However, network pathway analysis from the most populated disordered state indicates that the formation of extended β-sheet states is quite slow (at the millisecond

A Randomized Controlled Study of a Fully Liquid DTaP-IPV-HB-PRP-T Hexavalent Vaccine for Primary and Booster Vaccinations of Healthy Infants and Toddlers in Latin America.

Science.gov (United States)

López, Pío; Arguedas Mohs, Adriano; Abdelnour Vásquez, Arturo; Consuelo-Miranda, Maria; Feroldi, Emmanuel; Noriega, Fernando; Jordanov, Emilia; B Chir, Siham; Zambrano, Betzana

2017-11-01

Hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-hepatitis B-Haemophilus influenzae type b (DTaP-IPV-HB-PRP-T)-containing vaccines are increasingly the standard of care. This study evaluated the primary series (NCT01177722) and booster (NCT01444781) of a fully liquid DTaP-IPV-HB-PRP-T vaccine in Latin America. Infants (N = 1375) received hepatitis B vaccine at birth and were randomized to one of 3 batches of the investigational DTaP-IPV-HB-PRP-T or licensed control vaccine (DTaP-HB-IPV//PRP-T) at 2-4 to 6 months of age, coadministered with 7-valent pneumococcal conjugate vaccine (PCV7) (2-4-6 months) and rotavirus vaccine (2-4 months). A booster of either DTaP-IPV-HB-PRP-T or control was given at 12-24 months, coadministered with PCV7. Immunogenicity was assessed by validated assays and safety from parental reports. Primary series seroprotection and vaccine response rates were equivalent for DTaP-IPV-HB-PRP-T batches. For pooled batches, noninferiority to the control vaccine was demonstrated for each antigen. There were no descriptive differences in antibody persistence or booster response between DTaP-IPV-HB-PRP-T and the control. The booster responses to either vaccine following DTaP-IPV-HB-PRP-T primary series or to DTaP-IPV-HB-PRP-T following a control vaccine primary series were similar. The anti-aP component (filamentous hemagglutinin [FHA] and pertussis toxin [PT]) vaccine response and anti-Haemophilus influenzae type b (PRP) series seroprotection (≥0.15 µg/mL) rates were ≥73.0% after 2 primary series doses. Antipyretics had no effect on the immune response, and an extra (oral) polio vaccination had no effect on the antipolio booster response. Responses to PCV7 and rotavirus vaccine were similar for each coadministration. There were no safety concerns observed with any vaccine. These results confirm the suitability of the fully liquid DTaP-IPV-HB-PRP-T vaccine for primary and booster vaccination of infants.

Tendinopathies and platelet-rich plasma (PRP: from pre-clinical experiments to therapeutic use

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Kaux JF

2015-05-01

Full Text Available Objectives: The restorative properties of platelets, through the local release of growth factors, are used in various medical areas. This article reviews fundamental and clinical research relating to platelet-rich plasma applied to tendinous lesions. Materials and method: Articles in French and English, published between 1 January 2012 and 31 December 2014. dealing with PRP and tendons were searched for using the Medline and Scopus data bases. Results: Forty-seven articles were identified which addressed pre-clinical and clinical studies: 27 relating to in vitro and in vivo animal studies and 20 relating to human studies. Of these, five addressed lateral epicondylitis, two addressed rotator cuff tendinopathies, ten dealt with patellar tendinopathies and three looked at Achilles tendinopathies. Conclusions: The majority of pre-clinical studies show that PRP stimulates the tendon's healing process. However, clinical series remain more controversial and level 1, controlled, randomised studies are still needed.

The α-helical C-terminal domain of full-length recombinant PrP converts to an in-register parallel β-sheet structure in PrP fibrils: evidence from solid state nuclear magnetic resonance.

Science.gov (United States)

Tycko, Robert; Savtchenko, Regina; Ostapchenko, Valeriy G; Makarava, Natallia; Baskakov, Ilia V

2010-11-09

We report the results of solid state nuclear magnetic resonance (NMR) measurements on amyloid fibrils formed by the full-length prion protein PrP (residues 23−231, Syrian hamster sequence). Measurements of intermolecular 13C−13C dipole−dipole couplings in selectively carbonyl-labeled samples indicate that β-sheets in these fibrils have an in-register parallel structure, as previously observed in amyloid fibrils associated with Alzheimer’s disease and type 2 diabetes and in yeast prion fibrils. Two-dimensional 13C−13C and 15N−13C solid state NMR spectra of a uniformly 15N- and 13C-labeled sample indicate that a relatively small fraction of the full sequence, localized to the C-terminal end, forms the structurally ordered, immobilized core. Although unique site-specific assignments of the solid state NMR signals cannot be obtained from these spectra, analysis with a Monte Carlo/simulated annealing algorithm suggests that the core is comprised primarily of residues in the 173−224 range. These results are consistent with earlier electron paramagnetic resonance studies of fibrils formed by residues 90−231 of the human PrP sequence, formed under somewhat different conditions [Cobb, N. J., Sonnichsen, F. D., McHaourab, H., and Surewicz, W. K. (2007) Proc. Natl. Acad. Sci. U.S.A. 104, 18946−18951], suggesting that an in-register parallel β-sheet structure formed by the C-terminal end may be a general feature of PrP fibrils prepared in vitro.

Role of Ultrasound Guided Platelet-Rich Plasma (PRP Injection in Treatment of Lateral Epicondylitis

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Enass M. Khattab

2017-06-01

Conclusion: We concluded that US-guided platelet-rich plasma (PRP injection for treatment of lateral epicondylitis was a safe, minimally invasive and effective procedure in improving the sonographic and pathological changes of common extensor tendon (CET.

Exceptions to the PRP Effect? A Comparison of Prepared and Unconditioned Reflexes

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Janczyk, Markus; Pfister, Roland; Wallmeier, Gloria; Kunde, Wilfried

2014-01-01

Psychological research has documented again and again marked performance decrements whenever humans perform 2 or more tasks at the same time. In fact, the available evidence seems to suggest that any type of behavior is subject to such limitations. The present experiments employed the psychological refractory period (PRP) paradigm to identify a…

A DTAP–IPV//PRP~T VACCINE: A REVIEW OF 16 YEARS’ CLINICAL EXPERIENCE

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Stanley A. Plotkin

2012-01-01

Full Text Available Owing to their low reactogenicity, confirmed efficacy and availability in combination vaccines, acellular pertussis (aP-inactivated poliovirus (IPV combined vaccines are now included in various national immunization programs worldwide. We provide an overview of 16 years of clinical experience with a diphtheria (D, tetanus (T, aP, IPV and Haemophilus influenzae type b (Hib polysaccharide conjugated to tetanus protein (PRP~T combined vaccine (DTaP–IPV//PRP~T — Pentaxim, Sanofi Pasteur, France. Good immunogenicity has been demonstrated after primary vaccination with Pentaxim, regardless of the population ethnicity and primary vaccination schedule. A booster vaccination in the second year of life also resulted in a high immune response for each antigen. Furthermore, 10 years of national surveillance in Sweden has demonstrated the effectiveness of Pentaxim in controlling pertussis. As is the case for other aP-containing combined vaccines, Pentaxim is well tolerated, with the safety profile being better than for whole-cell pertussiscontaining combination vaccines for primary and booster vaccinations.

Identification of seven haplotypes of the caprine PrP gene at codons 127, 142, 154, 211, 222 and 240 in French Alpine and Saanen breeds and their association with classical scrapie.

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Barillet, F; Mariat, D; Amigues, Y; Faugeras, R; Caillat, H; Moazami-Goudarzi, K; Rupp, R; Babilliot, J M; Lacroux, C; Lugan, S; Schelcher, F; Chartier, C; Corbière, F; Andréoletti, O; Perrin-Chauvineau, C

2009-03-01

In sheep, susceptibility to scrapie is mainly influenced by polymorphisms of the PrP gene. In goats, there are to date few data related to scrapie susceptibility association with PrP gene polymorphisms. In this study, we first investigated PrP gene polymorphisms of the French Alpine and Saanen breeds. Based on PrP gene open reading frame sequencing of artificial insemination bucks (n=404), six encoding mutations were identified at codons 127, 142, 154, 211, 222 and 240. However, only seven haplotypes could be detected: four (GIH(154)RQS, GIRQ(211)QS, GIRRK(222)S and GIRRQP(240)) derived from the wild-type allele (G(127)I(142)R(154)R(211)Q(222)S(240)) by a single-codon mutation, and two (S(127)IRRQP(240) and GM(142)RRQP(240)) by a double-codon mutation. A case-control study was then implemented in a highly affected Alpine and Saanen breed herd (90 cases/164 controls). Mutations at codon 142 (I/M), 154 (R/H), 211 (R/Q) and 222 (Q/K) were found to induce a significant degree of protection towards natural scrapie infection. Compared with the baseline homozygote wild-type genotype I(142)R(154)R(211)Q(222)/IRRQ goats, the odds of scrapie cases in IRQ(211)Q/IRRQ and IRRK(222)/IRRQ heterozygous animals were significantly lower [odds ratio (OR)=0.133, PFrench Alpine and Saanen breeds were low (0.5-18.5 %), which prevent us from assessing the influence of all the possible genotypes in natural exposure conditions.

Impact of strong selection for the PrP major gene on genetic variability of four French sheep breeds (Open Access publication

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Pantano Thais

2008-11-01

Full Text Available Abstract Effective selection on the PrP gene has been implemented since October 2001 in all French sheep breeds. After four years, the ARR "resistant" allele frequency increased by about 35% in young males. The aim of this study was to evaluate the impact of this strong selection on genetic variability. It is focussed on four French sheep breeds and based on the comparison of two groups of 94 animals within each breed: the first group of animals was born before the selection began, and the second, 3–4 years later. Genetic variability was assessed using genealogical and molecular data (29 microsatellite markers. The expected loss of genetic variability on the PrP gene was confirmed. Moreover, among the five markers located in the PrP region, only the three closest ones were affected. The evolution of the number of alleles, heterozygote deficiency within population, expected heterozygosity and the Reynolds distances agreed with the criteria from pedigree and pointed out that neutral genetic variability was not much affected. This trend depended on breed, i.e. on their initial states (population size, PrP frequencies and on the selection strategies for improving scrapie resistance while carrying out selection for production traits.

Semisynthetic prion protein (PrP) variants carrying glycan mimics at position 181 and 197 do not form fibrils† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc02719b Click here for additional data file.

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Araman, Can; Thompson, Robert E.; Wang, Siyao; Hackl, Stefanie; Payne, Richard J.

2017-01-01

The prion protein (PrP) is an N-glycosylated protein attached to the outer leaflet of eukaryotic cell membranes via a glycosylphosphatidylinositol (GPI) anchor. Different prion strains have distinct glycosylation patterns and the extent of glycosylation of potentially pathogenic misfolded prion protein (PrPSc) has a major impact on several prion-related diseases (transmissible spongiform encephalopathies, TSEs). Based on these findings it is hypothesized that posttranslational modifications (PTMs) of PrP influence conversion of cellular prion protein (PrPC) into PrPSc and, as such, modified PrP variants are critical tools needed to investigate the impact of PTMs on the pathogenesis of TSEs. Here we report a semisynthetic approach to generate PrP variants modified with monodisperse polyethyleneglycol (PEG) units as mimics of N-glycans. Incorporating PEG at glycosylation sites 181 and 197 in PrP induced only small changes to the secondary structure when compared to unmodified, wildtype PrP. More importantly, in vitro aggregation was abrogated for all PEGylated PrP variants under conditions at which wildtype PrP aggregated. Furthermore, the addition of PEGylated PrP as low as 10 mol% to wildtype PrP completely blocked aggregation. A similar effect was observed for synthetic PEGylated PrP segments comprising amino acids 179–231 alone if these were added to wildtype PrP in aggregation assays. This behavior raises the question if large N-glycans interfere with aggregation in vivo and if PEGylated PrP peptides could serve as potential therapeutics. PMID:28989689

No effects of PRP on ultrasonographic tendon structure and neovascularisation in chronic midportion Achilles tendinopathy

NARCIS (Netherlands)

de Vos, R. J.; Weir, A.; Tol, J. L.; Verhaar, J. A. N.; Weinans, H.; van Schie, H. T. M.

2011-01-01

To assess whether a platelet-rich plasma (PRP) injection leads to an enhanced tendon structure and neovascularisation, measured with ultrasonographic techniques, in chronic midportion Achilles tendinopathy. Double-blind, randomised, placebo-controlled clinical trial. Sports medical department of The

Combined use of bone marrow-derived mesenchymal stromal cells (BM-MSCs) and platelet rich plasma (PRP) stimulates proliferation and differentiation of myoblasts in vitro: new therapeutic perspectives for skeletal muscle repair/regeneration.

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Sassoli, Chiara; Vallone, Larissa; Tani, Alessia; Chellini, Flaminia; Nosi, Daniele; Zecchi-Orlandini, Sandra

2018-02-05

Satellite cell-mediated skeletal muscle repair/regeneration is compromised in cases of extended damage. Bone marrow mesenchymal stromal cells (BM-MSCs) hold promise for muscle healing but some criticisms hamper their clinical application, including the need to avoid animal serum contamination for expansion and the scarce survival after transplant. In this context, platelet-rich plasma (PRP) could offer advantages. Here, we compare the effects of PRP or standard culture media on C2C12 myoblast, satellite cell and BM-MSC viability, survival, proliferation and myogenic differentiation and evaluate PRP/BM-MSC combination effects in promoting myogenic differentiation. PRP induced an increase of mitochondrial activity and Ki67 expression comparable or even greater than that elicited by standard media and promoted AKT signaling activation in myoblasts and BM-MSCs and Notch-1 pathway activation in BM-MSCs. It stimulated MyoD, myogenin, α-sarcomeric actin and MMP-2 expression in myoblasts and satellite cell activation. Notably, PRP/BM-MSC combination was more effective than PRP alone. We found that BM-MSCs influenced myoblast responses through a paracrine activation of AKT signaling, contributing to shed light on BM-MSC action mechanisms. Our results suggest that PRP represents a good serum substitute for BM-MSC manipulation in vitro and could be beneficial towards transplanted cells in vivo. Moreover, it might influence muscle resident progenitors' fate, thus favoring the endogenous repair/regeneration mechanisms. Finally, within the limitations of an in vitro experimentation, this study provides an experimental background for considering the PRP/BM-MSC combination as a potential therapeutic tool for skeletal muscle damage, combining the beneficial effects of BM-MSCs and PRP on muscle tissue, while potentiating BM-MSC functionality.

Intra-articular platelet-rich plasma (PRP) injections for treating knee pain associated with osteoarthritis of the knee in the Japanese population: a phase I and IIa clinical trial.

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Taniguchi, Yu; Yoshioka, Tomokazu; Kanamori, Akihiro; Aoto, Katsuya; Sugaya, Hisashi; Yamazaki, Masashi

2018-02-01

Intra-articular platelet-rich plasma (PRP) injection has been found to be effective for treating osteoarthritis in patients from Western countries; however, the safety and efficacy of PRP have not been sufficiently investigated in Japanese patients. The present study aimed to evaluate the safety and feasibility of intra-articular PRP injection in Japanese patients with knee osteoarthritis. PRP without white blood cells was prepared using a single-spin centrifuge (PRGF-Endoret; BTI Biotechnology Institute, Vitoria, Spain). A 6-mL PRP volume was injected in the knee joint three times at 1 week intervals. All patients were prospectively evaluated before intervention and at 1, 3, and 6 months after the treatment. Adverse events, the Visual Analog Scale (VAS) pain score, Japanese Knee Osteoarthritis Measure (JKOM) score and Japanese Orthopedic Association score were evaluated. Ten patients (all women; average age, 60.6 years) were treated. Only minor adverse events after injection were noted, and symptoms resolved within 48 hours after the injection. The average VAS pain scores were 71.6 mm and 18.4 mm at baseline and the 6-month follow-up, respectively (P PRP injection likely represents a safe treatment option for Japanese patients with mild-to-moderate knee osteoarthritis, and has the potential to relieve pain for up to 6 months, but further study is needed to verify the efficacy.

Intra-articular Hyaluronic Acid (HA) and Platelet Rich Plasma (PRP) injection versus Hyaluronic acid (HA) injection alone in Patients with Grade III and IV Knee Osteoarthritis (OA): A Retrospective Study on Functional Outcome.

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Saturveithan, C; Premganesh, G; Fakhrizzaki, S; Mahathir, M; Karuna, K; Rauf, K; William, H; Akmal, H; Sivapathasundaram, N; Jaspreet, K

2016-07-01

Introduction: Intra-articular hyaluronic acid (HA) is widely utilized in the treatment of knee osteoarthritis whereas platelet rich plasma (PRP) enhances the regeneration of articular cartilage. This study analyses the efficacy of HA and PRP in grade III and IV knee osteoarthritis. Methodology: This is a cross sectional study with retrospective review of 64 patients (101 knees) which includes 56 knees injected with HA+ PRP, and 45 knees with HA only. Results: During the post six months International Knee Documentation Committee (IKDC) evaluation, HA+PRP group showed marked improvement of 24.33 compared to 12.15 in HA group. Decrement in visual analogue score (VAS) in HA+PRP was 1.9 compared to 0.8 in HA group. Conclusion: We propose intra-articular HA and PRP injections as an optional treatment modality in Grade III and IV knee osteoarthritis in terms of functional outcome and pain control for up to six months when arthroplasty is not an option.

Intra-articular Hyaluronic Acid (HA and Platelet Rich Plasma (PRP injection versus Hyaluronic acid (HA injection alone in Patients with Grade III and IV Knee Osteoarthritis (OA: A Retrospective Study on Functional Outcome

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Saturveithan C

2016-07-01

Full Text Available Introduction: Intra-articular hyaluronic acid (HA is widely utilized in the treatment of knee osteoarthritis whereas platelet rich plasma (PRP enhances the regeneration of articular cartilage. This study analyses the efficacy of HA and PRP in grade III and IV knee osteoarthritis. Methodology: This is a cross sectional study with retrospective review of 64 patients (101 knees which includes 56 knees injected with HA+ PRP, and 45 knees with HA only. Results: During the post six months International Knee Documentation Committee (IKDC evaluation, HA+PRP group showed marked improvement of 24.33 compared to 12.15 in HA group. Decrement in visual analogue score (VAS in HA+PRP was 1.9 compared to 0.8 in HA group. Conclusion: We propose intra-articular HA and PRP injections as an optional treatment modality in Grade III and IV knee osteoarthritis in terms of functional outcome and pain control for up to six months when arthroplasty is not an option.

Effects of in vivo applications of peripheral blood-derived mesenchymal stromal cells (PB-MSCs) and platlet-rich plasma (PRP) on experimentally injured deep digital flexor tendons of sheep.

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Martinello, Tiziana; Bronzini, Ilaria; Perazzi, Anna; Testoni, Stefania; De Benedictis, Gulia Maria; Negro, Alessandro; Caporale, Giovanni; Mascarello, Francesco; Iacopetti, Ilaria; Patruno, Marco

2013-02-01

Tendon injuries, degenerative tendinopathies, and overuse tendinitis are common in races horses. Novel therapies aim to restore tendon functionality by means of cell-based therapy, growth factor delivery, and tissue engineering approaches. This study examined the use of autologous mesenchymal stromal cells derived from peripheral blood (PB-MSCs), platelet-rich plasma (PRP) and a combination of both for ameliorating experimental lesions on deep digital flexor tendons (DDFT) of Bergamasca sheep. In particular, testing the combination of blood-derived MSCs and PRP in an experimental animal model represents one of the few studies exploring a putative synergistic action of these treatments. Effectiveness of treatments was evaluated at 30 and 120 days comparing clinical, ultrasonographic, and histological features together with immunohistochemical expression of collagen types 1 and 3, and cartilage oligomeric matrix protein (COMP). Significant differences were found between treated groups and their corresponding controls (placebo) regarding tendon morphology and extracellular matrix (ECM) composition. However, our results indicate that the combined use of PRP and MSCs did not produce an additive or synergistic regenerative response and highlighted the predominant effect of MSCs on tendon healing, enhanced tissue remodeling and improved structural organization. Copyright © 2012 Orthopaedic Research Society.

Crystallization and preliminary X-ray diffraction analysis of the C-terminal domain of the human spliceosomal DExD/H-box protein hPrp22

International Nuclear Information System (INIS)

Kudlinzki, Denis; Nagel, Christian; Ficner, Ralf

2009-01-01

The cloning, purification and crystallization of the C-terminal domain of human hPrp22 are reported. This communication also contains data for the preliminary X-ray diffraction analysis. The Homo sapiens DExD/H-box protein hPrp22 is a crucial component of the eukaryotic pre-mRNA splicing machinery. Within the splicing cycle, it is involved in the ligation of exons and generation of the lariat and it additionally catalyzes the release of mature mRNA from the spliceosomal U5 snRNP. The yeast homologue of this protein, yPrp22, shows ATP-dependent RNA-helicase activity and is capable of unwinding RNA/RNA duplex molecules. A truncated construct coding for residues 950–1183 of human Prp22, comprising the structurally and functionally uncharacterized C-terminal domain, was cloned into an Escherichia coli expression vector. The protein was subsequently overproduced, purified and crystallized. The crystals obtained diffracted to 2.1 Å resolution, belonged to the tetragonal space group P4 1 2 1 2 or P4 3 2 1 2, with unit-cell parameters a = b = 78.2, c = 88.4 Å, and contained one molecule in the asymmetric unit

Tratamiento de quemaduras mediante plasma rico en plaquetas (PRP): parte I

OpenAIRE

G. Rossani; I. Hernández; J.M. Alcolea; R. Castro-Sierra; W. Pérez-Soto; M.A. Trelles

2014-01-01

El objetivo del presente trabajo es determinar la eficacia clínica del plasma rico en plaquetas (PRP) en las quemaduras de segundo grado. Estudiamos el tiempo requerido en la reepitelización del tejido dañado, la estancia hospitalaria asociada a la curación de las lesiones y la satisfacción del paciente. Realizamos un estudio prospectivo, observacional y longitudinal, en una muestra de 115 pacientes con quemaduras de segundo grado según la clasificación de Converse-Smith. Las lesiones fueron ...

Cytoplasmic viral RNA-dependent RNA polymerase disrupts the intracellular splicing machinery by entering the nucleus and interfering with Prp8.

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Yen-Chin Liu

2014-06-01

Full Text Available The primary role of cytoplasmic viral RNA-dependent RNA polymerase (RdRp is viral genome replication in the cellular cytoplasm. However, picornaviral RdRp denoted 3D polymerase (3D(pol also enters the host nucleus, where its function remains unclear. In this study, we describe a novel mechanism of viral attack in which 3D(pol enters the nucleus through the nuclear localization signal (NLS and targets the pre-mRNA processing factor 8 (Prp8 to block pre-mRNA splicing and mRNA synthesis. The fingers domain of 3D(pol associates with the C-terminal region of Prp8, which contains the Jab1/MPN domain, and interferes in the second catalytic step, resulting in the accumulation of the lariat form of the splicing intermediate. Endogenous pre-mRNAs trapped by the Prp8-3D(pol complex in enterovirus-infected cells were identified and classed into groups associated with cell growth, proliferation, and differentiation. Our results suggest that picornaviral RdRp disrupts pre-mRNA splicing processes, that differs from viral protease shutting off cellular transcription and translation which contributes to the pathogenesis of viral infection.

The Effect of Autologous Activated Platelet Rich Plasma (AA-PRP Injection on Pattern Hair Loss: Clinical and Histomorphometric Evaluation

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V. Cervelli

2014-01-01

Full Text Available To investigate the safety and clinical efficacy of AA-PRP injections for pattern hair loss. AA-PRP, prepared from a small volume of blood, was injected on half of the selected patients’ scalps with pattern hair loss. The other half was treated with placebo. Three treatments were given for each patient, with intervals of 1 month. The endpoints were hair re-growth, hair dystrophy as measured by dermoscopy, burning or itching sensation, and cell proliferation as measured by Ki-67 evaluation. At the end of the 3 cycles of treatment, the patients presented clinical improvement in the mean number of hairs, with a mean increase of 18.0 hairs in the target area, and a mean increase in total hair density of 27.7 ( number of hairs/cm2 compared with baseline values. Microscopic evaluation showed the increase of epidermis thickness and of the number of hair follicles two weeks after the last AA-PRP treatment compared to baseline value (P<0.05. We also observed an increase of Ki67+ keratinocytes of epidermis and of hair follicular bulge cells and a slight increase of small blood vessels around hair follicles in the treated skin compared to baseline (P<0.05.

Inhibition of IL-1β Signaling Normalizes NMDA-Dependent Neurotransmission and Reduces Seizure Susceptibility in a Mouse Model of Creutzfeldt-Jakob Disease.

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Bertani, Ilaria; Iori, Valentina; Trusel, Massimo; Maroso, Mattia; Foray, Claudia; Mantovani, Susanna; Tonini, Raffaella; Vezzani, Annamaria; Chiesa, Roberto

2017-10-25

Creutzfeldt-Jakob disease (CJD) is a neurodegenerative disorder caused by prion protein (PrP) misfolding, clinically recognized by cognitive and motor deficits, electroencephalographic abnormalities, and seizures. Its neurophysiological bases are not known. To assess the potential involvement of NMDA receptor (NMDAR) dysfunction, we analyzed NMDA-dependent synaptic plasticity in hippocampal slices from Tg(CJD) mice, which model a genetic form of CJD. Because PrP depletion may result in functional upregulation of NMDARs, we also analyzed PrP knock-out (KO) mice. Long-term potentiation (LTP) at the Schaffer collateral-commissural synapses in the CA1 area of ∼100-d-old Tg(CJD) mice was comparable to that of wild-type (WT) controls, but there was an inversion of metaplasticity, with increased GluN2B phosphorylation, which is indicative of enhanced NMDAR activation. Similar but less marked changes were seen in PrP KO mice. At ∼300 d of age, the magnitude of LTP increased in Tg(CJD) mice but decreased in PrP KO mice, indicating divergent changes in hippocampal synaptic responsiveness. Tg(CJD) but not PrP KO mice were intrinsically more susceptible than WT controls to focal hippocampal seizures induced by kainic acid. IL-1β-positive astrocytes increased in the Tg(CJD) hippocampus, and blocking IL-1 receptor signaling restored normal synaptic responses and reduced seizure susceptibility. These results indicate that alterations in NMDA-dependent glutamatergic transmission in Tg(CJD) mice do not depend solely on PrP functional loss. Moreover, astrocytic IL-1β plays a role in the enhanced synaptic responsiveness and seizure susceptibility, suggesting that targeting IL-1β signaling may offer a novel symptomatic treatment for CJD. SIGNIFICANCE STATEMENT Dementia and myoclonic jerks develop in individuals with Creutzfeldt-Jakob disease (CJD), an incurable brain disorder caused by alterations in prion protein structure. These individuals are prone to seizures and have high

Efficacy of Platelet-Rich-Plasma (PRP and Highly Purified Bovine Xenograft (Laddec® Combination in Bone Regeneration after Cyst Enucleation: Radiological and Histological Evaluation

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Sabrina Pappalardo

2013-10-01

Full Text Available Objectives: The purpose of the present study was to evaluate the efficacy of adding platelet-rich plasma (PRP to a new highly purified bovine allograft (Laddec® in the bone regeneration of cystic bony defects augmented following cystectomy.Material and Methods: Study sample included 20 patients undergoing cystectomy in which the bone defect was filled with PRP and Laddec®. All patients were examined with periapical radiographs before operation and at follow-up. After 3 months, at re-entry surgery for implant placement, bone core was taken for histological and histomorphometric analysis.Results: The postoperative successive radiographs showed a good regeneration of bone in the height of bony defects with application of PRP to bone graft. By the first postoperative month, about 48% of the defect was filled, which gradually increased in each month and showed about 90% of defect-fill by 6 months. Histological and histomorphometric analysis, showed a significant presence of bone tissue and vessels, with newly formed bone in contact with anorganic bone particles. The mean volume of vital bone was 68 ± 1.6% and the mean percentage of vital bone was 48 ± 2.4%. The mean percentage of inorganic particles in tissues was 20 ± 1.2% of the total volume. All the samples analyzed did not evidence the presence of inflammatory cells.Conclusions: The results of this study showed how the use of Laddec® in association with platelet-rich plasma allows bone regeneration and has a potential for routine clinical use for regeneration of cystic bony defects.

Sucralfate significantly reduces ciprofloxacin concentrations in serum.

OpenAIRE

Garrelts, J C; Godley, P J; Peterie, J D; Gerlach, E H; Yakshe, C C

1990-01-01

The effect of sucralfate on the bioavailability of ciprofloxacin was evaluated in eight healthy subjects utilizing a randomized, crossover design. The area under the concentration-time curve from 0 to 12 h was reduced from 8.8 to 1.1 micrograms.h/ml by sucralfate (P less than 0.005). Similarly, the maximum concentration of ciprofloxacin in serum was reduced from 2.0 to 0.2 micrograms/ml (P less than 0.005). We conclude that concurrent ingestion of sucralfate significantly reduces the concentr...

Use of autologous platelet rich plasma (PRP) in stopping massive hemoptysis at the Lung Center of the Philippines: a pilot study.

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Sarmiento, Armand Gregorio C; Danguilan, Jose Luis J; Mariano, Zenaida M; Barzaga, Maria Teresa A

2017-01-01

The purpose of this study is to determine the effect of using autologous platelet rich plasma (PRP) in patients having massive hemoptysis within a period of one week. This is a prospective cohort study involving 20 consecutive patients admitted who met the criteria for massive hemoptysis from July to October 2011. After stabilizing the patient, fiberoptic bronchoscopy (FOB) was performed for localization of bleeding within 6 hours from diagnosis. A 50mL of blood was extracted from the patient whom was to be used for autologous PRP concentrate. After identifying the anatomic site of bleeding, autologous PRP concentrate was instilled on the affected bronchus and was allowed to stay for 5 minutes after instillation. Patients were then monitored from the time the bleeding stopped in the first 24 hours, 2 days and 7 days respectively. Mean age of the study population with massive hemoptysis was 47 years old (SD 17.3). Majority of cases were male 18 out of 20 (90%) and smokers 14 (70%) with a normal BMI (75%). Identification of bleeding site was more commonly seen on the right upper lobe 9 out of 20 (45%). Overall, 14 out of 20 patients (70%) were reported to have stopped bleeding immediately. Subsequent hospital days showed that 8 out of 20 patients (40%) had no hemoptysis. However, one [1] post-tuberculosis (TB) bronchiectatic patient had recurrence of massive hemoptysis, approximately 250 mL per expectorate, expired within the 7 days observation and one patient had lobectomy on the 2nd day. The rest had non-massive hemoptysis wherein their expectorations were only streaks of blood. Moreover, there was one [1] patient who had recurrence of massive hemoptysis 1 week after autologous PRP infusion and was eventually intubated. Majority of the subjects, eleven [11] were diagnosed to have post-TB bronchiectasis. The rest of the patients were worked-up prior to operation. Overall, it was observed that the use of autologous PRP was able to stop bleeding in 40% of the study

Emergence of two prion subtypes in ovine PrP transgenic mice infected with human MM2-cortical Creutzfeldt-Jakob disease prions.

Science.gov (United States)

Chapuis, Jérôme; Moudjou, Mohammed; Reine, Fabienne; Herzog, Laetitia; Jaumain, Emilie; Chapuis, Céline; Quadrio, Isabelle; Boulliat, Jacques; Perret-Liaudet, Armand; Dron, Michel; Laude, Hubert; Rezaei, Human; Béringue, Vincent

2016-02-05

Mammalian prions are proteinaceous pathogens responsible for a broad range of fatal neurodegenerative diseases in humans and animals. These diseases can occur spontaneously, such as Creutzfeldt-Jakob disease (CJD) in humans, or be acquired or inherited. Prions are primarily formed of macromolecular assemblies of the disease-associated prion protein PrP(Sc), a misfolded isoform of the host-encoded prion protein PrP(C). Within defined host-species, prions can exist as conformational variants or strains. Based on both the M/V polymorphism at codon 129 of PrP and the electrophoretic signature of PrP(Sc) in the brain, sporadic CJD is classified in different subtypes, which may encode different strains. A transmission barrier, the mechanism of which remains unknown, limits prion cross-species propagation. To adapt to the new host, prions have the capacity to 'mutate' conformationally, leading to the emergence of a variant with new biological properties. Here, we transmitted experimentally one rare subtype of human CJD, designated cortical MM2 (129 MM with type 2 PrP(Sc)), to transgenic mice overexpressing either human or the VRQ allele of ovine PrP(C). In marked contrast with the reported absence of transmission to knock-in mice expressing physiological levels of human PrP, this subtype transmitted faithfully to mice overexpressing human PrP, and exhibited unique strain features. Onto the ovine PrP sequence, the cortical MM2 subtype abruptly evolved on second passage, thereby allowing emergence of a pair of strain variants with distinct PrP(Sc) biochemical characteristics and differing tropism for the central and lymphoid tissues. These two strain components exhibited remarkably distinct replicative properties in cell-free amplification assay, allowing the 'physical' cloning of the minor, lymphotropic component, and subsequent isolation in ovine PrP mice and RK13 cells. Here, we provide in-depth assessment of the transmissibility and evolution of one rare subtype of

Prion Protein Does Not Confer Resistance to Hippocampus-Derived Zpl Cells against the Toxic Effects of Cu2+, Mn2+, Zn2+ and Co2+ Not Supporting a General Protective Role for PrP in Transition Metal Induced Toxicity.

Science.gov (United States)

Cingaram, Pradeep Kumar Reddy; Nyeste, Antal; Dondapati, Divya Teja; Fodor, Elfrieda; Welker, Ervin

2015-01-01

The interactions of transition metals with the prion protein (PrP) are well-documented and characterized, however, there is no consensus on their role in either the physiology of PrP or PrP-related neurodegenerative disorders. PrP has been reported to protect cells from the toxic stimuli of metals. By employing a cell viability assay, we examined the effects of various concentrations of Cu2+, Zn2+, Mn2+, and Co2+ on Zpl (Prnp-/-) and ZW (Prnp+/+) hippocampus-derived mouse neuronal cells. Prnp-/- Zpl cells were more sensitive to all four metals than PrP-expressing Zw cells. However, when we introduced PrP or only the empty vector into Zpl cells, we could not discern any protective effect associated with the presence of PrP. This observation was further corroborated when assessing the toxic effect of metals by propidium-iodide staining and fluorescence activated cell sorting analysis. Thus, our results on this mouse cell culture model do not seem to support a strong protective role for PrP against transition metal toxicity and also emphasize the necessity of extreme care when comparing cells derived from PrP knock-out and wild type mice.

Absence of Evidence for a Causal Link between Bovine Spongiform Encephalopathy Strain Variant L-BSE and Known Forms of Sporadic Creutzfeldt-Jakob Disease in Human PrP Transgenic Mice.

Science.gov (United States)

Jaumain, Emilie; Quadrio, Isabelle; Herzog, Laetitia; Reine, Fabienne; Rezaei, Human; Andréoletti, Olivier; Laude, Hubert; Perret-Liaudet, Armand; Haïk, Stéphane; Béringue, Vincent

2016-12-01

Prions are proteinaceous pathogens responsible for subacute spongiform encephalopathies in animals and humans. The prions responsible for bovine spongiform encephalopathy (BSE) are zoonotic agents, causing variant Creutzfeldt-Jakob disease (CJD) in humans. The transfer of prions between species is limited by a species barrier, which is thought to reflect structural incompatibilities between the host cellular prion protein (PrP C ) and the infecting pathological PrP assemblies (PrP Sc ) constituting the prion. A BSE strain variant, designated L-BSE and responsible for atypical, supposedly spontaneous forms of prion diseases in aged cattle, demonstrates zoonotic potential, as evidenced by its capacity to propagate more easily than classical BSE in transgenic mice expressing human PrP C and in nonhuman primates. In humanized mice, L-BSE propagates without any apparent species barrier and shares similar biochemical PrP Sc signatures with the CJD subtype designated MM2-cortical, thus opening the possibility that certain CJD cases classified as sporadic may actually originate from L-type BSE cross-transmission. To address this issue, we compared the biological properties of L-BSE and those of a panel of CJD subtypes representative of the human prion strain diversity using standard strain-typing criteria in human PrP transgenic mice. We found no evidence that L-BSE causes a known form of sporadic CJD. Since the quasi-extinction of classical BSE, atypical BSE forms are the sole BSE variants circulating in cattle worldwide. They are observed in rare cases of old cattle, making them difficult to detect. Extrapolation of our results suggests that L-BSE may propagate in humans as an unrecognized form of CJD, and we urge both the continued utilization of precautionary measures to eliminate these agents from the human food chain and active surveillance for CJD phenotypes in the general population. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

PLATELET-RICH PLASMA (PRP FOR THE TREATMENT OF PROBLEMATIC SKIN WOUNDS

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Tsvetan Sokolov

2016-12-01

Full Text Available OBJECTIVE: To show platelet-rich plasma (PRP application of problematic skin wounds and to evaluate the results from the treatment. MATERIAL AND METHODS: A total of 31 patients with problematic skin wounds had been treated at the clinic for a period of five years (from May 2010 to September 2015 with the following patient sex ratio: male patients– 13 and female patients– 18. Average age– 46,5 (22-82. Patients with Type 2 Diabetes– 10, with decubitus ulcers– 2, traumatic– 29, with infection– 12, acute– 15, chronic– 16. Based on a scheme developed by us, all cases were treated by administering platelet-rich plasma, derived by PRGF Endoret system. Follow-up period was within 4 – 6 months (4,5 on average. We used platelet rich plasma derived by PRGF Endoret system, applied on the wound bed on a weekly basis. RESULTS: The results have been evaluated based on the following functional scoring systems - Total wound score, Total anatomic score and Total score (20. The baseline values at the very beginning of the follow-up period were as follows: Total wound score – 10 p.; Total anatomic score – 8 p., Total score – 15 p. By the end of the treatment period the score was 0 p., which means excellent results, i.e. complete healing of the wounds. CONCLUSION: We believe that the application of PRP may become optimal therapy in the treatment of difficult to heal wounds around joints, bone, subject tendons, plantar surface of the foot, etc., as it opens new perspectives in the field of human tissue regeneration.

Does Platelet-Rich Plasma Freeze-Thawing Influence Growth Factor Release and Their Effects on Chondrocytes and Synoviocytes?

Directory of Open Access Journals (Sweden)

Alice Roffi

2014-01-01

Full Text Available PRP cryopreservation remains a controversial point. Our purpose was to investigate the effect of freezing/thawing on PRP molecule release, and its effects on the metabolism of chondrocytes and synoviocytes. PRP was prepared from 10 volunteers, and a half volume underwent one freezing/thawing cycle. IL-1β, HGF, PDGF AB/BB, TGF-β1, and VEGF were assayed 1 hour and 7 days after activation. Culture media of chondrocytes and synoviocytes were supplemented with fresh or frozen PRP, and, at 7 days, proliferation, gene expression, and secreted proteins levels were evaluated. Results showed that in the freeze-thawed PRP the immediate and delayed molecule releases were similar or slightly lower than those in fresh PRP. TGF-β1 and PDGF AB/BB concentrations were significantly reduced after freezing both at 1 hour and at 7 days, whereas HGF concentration was significantly lower in frozen PRP at 7 days. In fresh PRP IL-1β and HGF concentrations underwent a significant further increase after 7 days. Similar gene expression was found in chondrocytes cultured with both PRPs, whereas in synoviocytes HGF gene expression was higher in frozen PRP. PRP cryopreservation is a safe procedure, which sufficiently preserves PRP quality and its ability to induce proliferation and the production of ECM components in chondrocytes and synoviocytes.

Efectividad del PRP en el tratamiento de la artrosis de rodilla: Estudio de casos

OpenAIRE

Fernández Valverde, Noelia; Fidalgo González, Verónica

2016-01-01

La artrosis es una enfermedad degenerativa de elevada prevalencia para la cual, en la actualidad, no hay tratamiento curativo. Una de las localizaciones más frecuentes es la rodilla. La utilización de infiltraciones de plasma rico en plaquetas constituye una alternativa en el tratamiento de esta patología. Objetivo: demostrar la efectividad y la seguridad de las infiltraciones con PRP en el tratamiento de pacientes con artrosis de rodilla. Resultado: este trabajo muestra una...

Functions for fission yeast splicing factors SpSlu7 and SpPrp18 in alternative splice-site choice and stress-specific regulated splicing.

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Geetha Melangath

Full Text Available Budding yeast spliceosomal factors ScSlu7 and ScPrp18 interact and mediate intron 3'ss choice during second step pre-mRNA splicing. The fission yeast genome with abundant multi-intronic transcripts, degenerate splice signals and SR proteins is an apt unicellular fungal model to deduce roles for core spliceosomal factors in alternative splice-site choice, intron retention and to study the cellular implications of regulated splicing. From our custom microarray data we deduce a stringent reproducible subset of S. pombe alternative events. We examined the role of factors SpSlu7 or SpPrp18 for these splice events and investigated the relationship to growth phase and stress. Wild-type log and stationary phase cells showed ats1+ exon 3 skipped and intron 3 retained transcripts. Interestingly the non-consensus 5'ss in ats1+ intron 3 caused SpSlu7 and SpPrp18 dependent intron retention. We validated the use of an alternative 5'ss in dtd1+ intron 1 and of an upstream alternative 3'ss in DUF3074 intron 1. The dtd1+ intron 1 non-canonical 5'ss yielded an alternative mRNA whose levels increased in stationary phase. Utilization of dtd1+ intron 1 sub-optimal 5' ss required functional SpPrp18 and SpSlu7 while compromise in SpSlu7 function alone hampered the selection of the DUF3074 intron 1 non canonical 3'ss. We analysed the relative abundance of these splice isoforms during mild thermal, oxidative and heavy metal stress and found stress-specific splice patterns for ats1+ and DUF3074 intron 1 some of which were SpSlu7 and SpPrp18 dependent. By studying ats1+ splice isoforms during compromised transcription elongation rates in wild-type, spslu7-2 and spprp18-5 mutant cells we found dynamic and intron context-specific effects in splice-site choice. Our work thus shows the combinatorial effects of splice site strength, core splicing factor functions and transcription elongation kinetics to dictate alternative splice patterns which in turn serve as an additional

PRP Comments for ICF Q1/Q2 FY17 Experiments 3/10/16

Energy Technology Data Exchange (ETDEWEB)

Kauffman, R. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2016-04-14

The PRP generally endorsed the Program plan during the short time for discussions. We agree that the strategy to develop a hohlraum that is symmetric and has low laser-plasma instabilities and to develop an alternative method for supporting the capsule is the best path forward for making progress in understanding ignition performance. The Program is oriented toward a milestone in 2020 for “determining the efficacy of NIF for ignition and credible physics-scaling to multi-megajoule yields for all ICF approaches.” We are concerned that the time and resources are not sufficient to vet all of the various approaches that are being pursued to make an informed decision by this date. For NIF to meet this goal, a process will be needed to to select the most promising paths forward. We recommend that the Program develop this process for selecting the path forward to optimize resources. We were glad to see that the direct drive program took our comments under consideration. We think that the proposed experiments have the program headed in a better direction. The PRP had only a short time to discuss the detailed experimental proposals. The following are comments on the detailed proposals. We did not have time to discuss them as a group. They represent individual opinions and provided to you as feedback to your proposals.

Integrity of Helix 2-Helix 3 Domain of the PrP Protein Is Not Mandatory for Prion Replication*

Science.gov (United States)

Salamat, Khalid; Moudjou, Mohammed; Chapuis, Jérôme; Herzog, Laetitia; Jaumain, Emilie; Béringue, Vincent; Rezaei, Human; Pastore, Annalisa; Laude, Hubert; Dron, Michel

2012-01-01

The process of prion conversion is not yet well understood at the molecular level. The regions critical for the conformational change of PrP remain mostly debated and the extent of sequence change acceptable for prion conversion is poorly documented. To achieve progress on these issues, we applied a reverse genetic approach using the Rov cell system. This allowed us to test the susceptibility of a number of insertion mutants to conversion into prion in the absence of wild-type PrP molecules. We were able to propagate several prions with 8 to 16 extra amino acids, including a polyglycine stretch and His or FLAG tags, inserted in the middle of the protease-resistant fragment. These results demonstrate the possibility to increase the length of the loop between helices H2 and H3 up to 4-fold, without preventing prion replication. They also indicate that this loop probably remains unstructured in PrPSc. We also showed that bona fide prions can be produced following insertion of octapeptides in the two C-terminal turns of H2. These insertions do not interfere with the overall fold of the H2-H3 domain indicating that the highly conserved sequence of the terminal part of H2 is not critical for the conversion. Altogether these data showed that the amplitude of modifications acceptable for prion conversion in the core of the globular domain of PrP is much greater than one might have assumed. These observations should help to refine structural models of PrPSc and elucidate the conformational changes underlying prions generation. PMID:22511770

Integrity of helix 2-helix 3 domain of the PrP protein is not mandatory for prion replication.

Science.gov (United States)

Salamat, Khalid; Moudjou, Mohammed; Chapuis, Jérôme; Herzog, Laetitia; Jaumain, Emilie; Béringue, Vincent; Rezaei, Human; Pastore, Annalisa; Laude, Hubert; Dron, Michel

2012-06-01

The process of prion conversion is not yet well understood at the molecular level. The regions critical for the conformational change of PrP remain mostly debated and the extent of sequence change acceptable for prion conversion is poorly documented. To achieve progress on these issues, we applied a reverse genetic approach using the Rov cell system. This allowed us to test the susceptibility of a number of insertion mutants to conversion into prion in the absence of wild-type PrP molecules. We were able to propagate several prions with 8 to 16 extra amino acids, including a polyglycine stretch and His or FLAG tags, inserted in the middle of the protease-resistant fragment. These results demonstrate the possibility to increase the length of the loop between helices H2 and H3 up to 4-fold, without preventing prion replication. They also indicate that this loop probably remains unstructured in PrP(Sc). We also showed that bona fide prions can be produced following insertion of octapeptides in the two C-terminal turns of H2. These insertions do not interfere with the overall fold of the H2-H3 domain indicating that the highly conserved sequence of the terminal part of H2 is not critical for the conversion. Altogether these data showed that the amplitude of modifications acceptable for prion conversion in the core of the globular domain of PrP is much greater than one might have assumed. These observations should help to refine structural models of PrP(Sc) and elucidate the conformational changes underlying prions generation.

Prediction and optimization of the recovery rate in centrifugal separation of platelet-rich plasma (PRP)

Science.gov (United States)

Piao, Linfeng; Park, Hyungmin; Jo, Chris

2016-11-01

We present a theoretical model of the recovery rate of platelet and white blood cell in the process of centrifugal separation of platelet-rich plasma (PRP). For the practically used conditions in the field, the separation process is modeled as a one-dimensional particle sedimentation; a quasi-linear partial differential equation is derived based on the kinematic-wave theory. This is solved to determine the interface positions between supernatant-suspension and suspension-sediment, used to estimate the recovery rate of the plasma. While correcting the Brown's hypothesis (1989) claiming that the platelet recovery is linearly proportional to that of plasma, we propose a new correlation model for prediction of the platelet recovery, which is a function of the volume of whole blood, centrifugal acceleration and time. For a range of practical parameters, such as hematocrit, volume of whole blood and centrifugation (time and acceleration), the predicted recovery rate shows a good agreement with available clinical data. We propose that this model is further used to optimize the preparation method of PRP that satisfies the customized case. Supported by a Grant (MPSS-CG-2016-02) through the Disaster and Safety Management Institute funded by Ministry of Public Safety and Security of Korean government.

A novel Gerstmann-Sträussler-Scheinker disease mutation defines a precursor for amyloidogenic 8 kDa PrP fragments and reveals N-terminal structural changes shared by other GSS alleles

Science.gov (United States)

Mercer, Robert C. C.; Fu, Ze-Lin; Mays, Charles E.; Gapeshina, Hristina; Wohlgemuth, Serene L.; Acevedo-Morantes, Claudia Y.; Cashman, Neil R.; Coulthart, Michael B.; Jansen, Gerard H.; Stepanova, Maria

2018-01-01

To explore pathogenesis in a young Gerstmann-Sträussler-Scheinker Disease (GSS) patient, the corresponding mutation, an eight-residue duplication in the hydrophobic region (HR), was inserted into the wild type mouse PrP gene. Transgenic (Tg) mouse lines expressing this mutation (Tg.HRdup) developed spontaneous neurologic syndromes and brain extracts hastened disease in low-expressor Tg.HRdup mice, suggesting de novo formation of prions. While Tg.HRdup mice exhibited spongiform change, PrP aggregates and the anticipated GSS hallmark of a proteinase K (PK)-resistant 8 kDa fragment deriving from the center of PrP, the LGGLGGYV insertion also imparted alterations in PrP's unstructured N-terminus, resulting in a 16 kDa species following thermolysin exposure. This species comprises a plausible precursor to the 8 kDa PK-resistant fragment and its detection in adolescent Tg.HRdup mice suggests that an early start to accumulation could account for early disease of the index case. A 16 kDa thermolysin-resistant signature was also found in GSS patients with P102L, A117V, H187R and F198S alleles and has coordinates similar to GSS stop codon mutations. Our data suggest a novel shared pathway of GSS pathogenesis that is fundamentally distinct from that producing structural alterations in the C-terminus of PrP, as observed in other prion diseases such as Creutzfeldt-Jakob Disease and scrapie. PMID:29338055

Platelet rich Plasma in Achilles Tendon Healing 2 (PATH-2) trial: protocol for a multicentre, participant and assessor-blinded, parallel-group randomised clinical trial comparing platelet-rich plasma (PRP) injection versus placebo injection for Achilles tendon rupture.

Science.gov (United States)

Alsousou, Joseph; Keene, David J; Hulley, Philippa A; Harrison, Paul; Wagland, Susan; Byrne, Christopher; Schlüssel, Michael Maia; Dutton, Susan J; Lamb, Sarah E; Willett, Keith

2017-11-16

Achilles tendon injuries give rise to substantial long-lasting morbidity and pose considerable challenges for clinicians and patients during the lengthy healing period. Current treatment strategies struggle to curb the burden of this injury on health systems and society due to lengthy rehabilitation, work absence and reinjury risk. Platelet-rich plasma (PRP) is an autologous preparation that has been shown to improve the mechanobiological properties of tendons in laboratory and animal studies. The use of PRP in musculoskeletal injuries is on the increase despite the lack of adequately powered clinical studies. This is a multicentre randomised controlled trial to evaluate the efficacy and mechanism of PRP in patients with acute Achilles tendon rupture (ATR). All adults with acute ATR presenting within 12 days of the injury who are to be treated non-operatively are eligible. A total of 230 consenting patients will be randomly allocated via a remote web-based service to receive PRP injection or placebo injection to the site of the injury. All participants will be blinded to the intervention and will receive standardised rehabilitation to reduce efficacy interference.Participants will be followed up with blinded assessments of muscle-tendon function, quality of life, pain and overall patient's functional goals at 4, 7, 13, 24 weeks and 24 months post-treatment. The primary outcome is the heel-rise endurance test (HRET), which will be supervised by a blinded assessor at 24 weeks. A subgroup of 16 participants in one centre will have needle biopsy under ultrasound guidance at 6 weeks. Blood and PRP will be analysed for cell count, platelet activation and growth factor concentrations. The protocol has been approved by the Oxfordshire Research Ethics Committee (Oxfordshire Research Ethics Committee A, reference no 14/SC/1333). The trial will be reported in accordance with the CONSORT statement and published in peer-reviewed scientific journals. ISRCTN: 54992179, assigned

Concomitant administration of a fully liquid, ready-to-use DTaP-IPV-HB-PRP-T hexavalent vaccine with a meningococcal serogroup C conjugate vaccine in infants.

Science.gov (United States)

Vesikari, Timo; Borrow, Ray; Da Costa, Xavier; Richard, Patrick; Eymin, Cécile; Boisnard, Florence; Lockhart, Stephen

2017-01-11

DTaP-IPV-HB-PRP-T or hexavalent vaccines are indicated for primary and booster vaccination of infants and toddlers against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and invasive diseases caused by Haemophilus influenzae type b (Hib). The present study evaluates the safety and immunogenicity of a ready-to-use hexavalent vaccine when co-administered with a meningococcal serogroup C conjugate (MenC) vaccine in infants. This was a phase III, open-label, randomised, multicentre study conducted in Finland. Healthy infants, aged 46-74days (n=350), were randomised in a ratio of 1:1 to receive DTaP-IPV-HB-PRP-T vaccine at two, three and four months, either with a MenC vaccine co-administered at two and four months (Group 1; n=175) or without MenC vaccine (Group 2; n=175). All infants also received routine rotavirus and 13-valent pneumococcal conjugate vaccines. The proportion of participants with an anti-HBs concentration ⩾10mIU/mL assessed one month after the third dose of DTaP-IPV-HB-PRP-T vaccine was 97.5% [95%CI: 93.1-99.3] in the coadministration group and 96.1% [95%CI: 91.8-98.6] in the group without MenC vaccine. The proportion of participants with an anti-MenC SBA titre ⩾8 assessed one month after the second dose of MenC vaccine was 100% in the coadministration group. Both primary objectives were achieved. Secondary immunogenicity and safety analyses showed that co-administration of DTaP-IPV-HB-PRP-T and MenC vaccines did not impact the immune response to the antigens of each of the two vaccines. All vaccines were well tolerated and the safety profile of DTaP-IPV-HB-PRP-T vaccine was similar in both groups. ClinicalTrials.gov identifier: NCT01839175; EudraCT number: 2012-005547-24. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

CLINICAL RESULTS FROM THE TREATMENT OF CHRONIC SKIN WOUNDS WITH PLATELET RICH PLASMA (PRP

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Pencho Kossev

2015-12-01

Full Text Available PURPOSE: To show platelet rich plasma (PRP application of chronic skin wounds and to evaluate the results from the treatment. MATERIAL AND METHODS: A total of 14 patients with problematic skin wounds had been treated at the clinic for a period of five years (from May 2009 to December 2014 with the following patient sex ratio: male patients - 5 and female patients - 9. Average age - 48,5 (30-76. Patients with Type 2 Diabetes - 4, with decubitus ulcers - 6, traumatic - 8, with infection - 5. Based on a scheme developed by us, all cases were treated by administering platelet-rich plasma, derived by PRGF Endoret system. Follow-up period was within 4 - 6 months (4,5 on average. RESULTS: The results have been evaluated based on the following functional scoring systems - Total wound score, Total anatomic score and Total score (20. The baseline values at the very beginning of the follow-up period were as follows: Total wound score - 12 p.; Total anatomic score - 10 p., Total score - 17 p. By the end of the treatment period the score was 0 p., which means excellent results, i.e. complete healing of the wounds. CONCLUSION: We believe that the application of PRP may become optimal therapy in the treatment of difficult to heal wounds around joints, bone, subject tendons, plantar surface of the foot, etc., as it opens new perspectives in the field of human tissue regeneration.

PrP expression, PrPSc accumulation and innervation of splenic compartments in sheep experimentally infected with scrapie.

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Randi Sørby

Full Text Available BACKGROUND: In prion disease, the peripheral expression of PrP(C is necessary for the transfer of infectivity to the central nervous system. The spleen is involved in neuroinvasion and neural dissemination in prion diseases but the nature of this involvement is not known. The present study undertook the investigation of the spatial relationship between sites of PrP(Sc accumulation, localisation of nerve fibres and PrP(C expression in the tissue compartments of the spleen of scrapie-inoculated and control sheep. METHODOLOGY/PRINCIPAL FINDINGS: Laser microdissection and quantitative PCR were used to determine PrP mRNA levels and results were compared with immunohistochemical protocols to distinguish PrP(C and PrP(Sc in tissue compartments of the spleen. In sheep experimentally infected with scrapie, the major sites of accumulation of PrP(Sc in the spleen, namely the lymphoid nodules and the marginal zone, expressed low levels of PrP mRNA. Double immunohistochemical labelling for PrP(Sc and the pan-nerve fibre marker, PGP, was used to evaluate the density of innervation of splenic tissue compartments and the intimacy of association between PrP(Sc and nerves. Some nerve fibres were observed to accompany blood vessels into the PrP(Sc-laden germinal centres. However, the close association between nerves and PrP(Sc was most apparent in the marginal zone. Other sites of close association were adjacent to the wall of the central artery of PALS and the outer rim of germinal centres. CONCLUSIONS/SIGNIFICANCE: The findings suggest that the degree of PrP(Sc accumulation does not depend on the expression level of PrP(C. Though several splenic compartments may contribute to neuroinvasion, the marginal zone may play a central role in being the compartment with most apparent association between nerves and PrP(Sc.

Protecting effect of PrP codons M142 and K222 in goats orally challenged with bovine spongiform encephalopathy prions.

Science.gov (United States)

Fast, C; Goldmann, W; Berthon, P; Tauscher, K; Andréoletti, O; Lantier, I; Rossignol, C; Bossers, A; Jacobs, J G; Hunter, N; Groschup, M H; Lantier, F; Langeveld, J P M

2017-09-19

Breeding towards genetic resistance to prion disease is effective in eliminating scrapie. In sheep, classical forms of scrapie have been eradicated almost completely in several countries by breeding programs using a prion protein (PrP) gene (PRNP) amino acid polymorphism. For goats, field and experimental studies have provided evidence for several amino acid polymorphisms that are associated with resistance to scrapie, but only limited data are available concerning the susceptibility of caprine PRNP genotypes to BSE. In this study, goat kids representing five PRNP genotypes based on three polymorphisms (M142, Q211 and K222 and the wild type I142, R211 and Q222) were orally challenged with bovine or goat BSE. Wild type goats were killed with clinical signs between 24-28 months post inoculation (mpi) to both challenges, and goats with genotype R/Q211 succumbed between 29-36 mpi. I/M142 goats developed clinical signs at 44-45 mpi and M/M142 goats remained healthy until euthanasia at 48 mpi. None of the Q/K222 goats showed definite clinical signs. Taken together the highest attack ratios were seen in wild type and R/Q211 goats, and the lowest in I/M142, M/M142 and Q/K222. In all genotype groups, one or more goats remained healthy within the incubation period in both challenges and without detectable PrP deposition in the tissues. Our data show that both the K222 and M142 polymorphisms lengthen the incubation period significantly compared to wild type animals, but only K222 was associated with a significant increase in resistance to BSE infection after oral exposure to both BSE sources.

Protective Effect of Platelet Rich Plasma on Experimental Ischemia/Reperfusion Injury in Rat Ovary.

Science.gov (United States)

Bakacak, Murat; Bostanci, Mehmet Suhha; İnanc, Fatma; Yaylali, Asli; Serin, Salih; Attar, Rukset; Yildirim, Gazi; Yildirim, Ozge Kizilkale

2016-01-01

Ovarian torsion is a common cause of local ischemic damage, reduced follicular activity and infertility. Platelet-rich plasma (PRP) contains growth factors with demonstrated cytoprotective properties; so we evaluated PRP efficacy in a rat ischemia/reperfusion (I/R) model. Sixty adult female Sprague-Dawley albino rats were randomly assigned to 6 groups of 8 animals each: Sham, Ischemia, I/R, Sham + PRP, I + PRP and I/R + PRP; and the remaining 12 used to prepare PRP. Ischemia groups were subjected to bilateral adnexal torsion for 3 h, while I/R and I/R + PRP groups received subsequent detorsion for 3 h. Intraperitoneal PRP was administered 30 min prior to ischemia (Ischemia + PRP) or reperfusion (I/R + PRP). Total oxidant status (TOS), oxidative stress index (OSI) and total ovarian histopathological scores were higher in Ischemia and I/R groups than in the Sham group (p OSI and histopathological scores in I + PRP and I/R + PRP groups compared to the corresponding Ischemia and I/R groups (p OSI (r = 0.877, p < 0.001). Peritoneal vascular endothelial growth factor was significantly higher in PRP-treated groups than corresponding untreated groups (p < 0.05). PRP is effective for the prevention of ischemia and reperfusion damage in rat ovary. © 2015 S. Karger AG, Basel.

Amidation and structure relaxation abolish the neurotoxicity of the prion peptide PrP106-126 in vivo and in vitro

DEFF Research Database (Denmark)

Bergstrøm, Linda Alice; Hvass, Henriette Cordes; Zsurger, N.

2005-01-01

One of the major pathological hallmarks of transmissible spongiform encephalopathies (TSEs) is the accumulation of a pathogenic (scrapie) isoform (PrPSc) of the cellular prion protein (PrPC) primarily in the central nervous system. The synthetic prion peptide PrP106-126 shares many characteristics...

PrP0\\0 mice show behavioral abnormalities that suggest PrPC has a role in maintaining the cytoskeleton.

Science.gov (United States)

Background/Introduction. PrPC is highly conserved among mammals, but its natural function is unclear. Prnp ablated mice (PrP0/0) appear to develop normally and are able to reproduce. These observations seem to indicate that the gene is not essential for viability, in spite of it being highly conse...

Evaluation of subcutaneous infiltration of autologous platelet-rich plasma on skin-wound healing in dogs.

Science.gov (United States)

Farghali, Haithem A; AbdElKader, Naglaa A; Khattab, Marwa S; AbuBakr, Huda O

2017-04-28

Platelet-rich plasma (PRP) is known to be rich in growth factors and cytokines, which are crucial to the healing process. This study investigate the effect of subcutaneous (S/C) infiltration of autologous PRP at the wound boundaries on wound epithelization and contraction. Five adult male mongrel dogs were used. Bilateral acute full thickness skin wounds (3 cm diameter) were created on the thorax symmetrically. Right side wounds were subcutaneously infiltrated with activated PRP at day 0 and then every week for three consecutive weeks. The left wound was left as control. Wound contraction and epithelization were clinically evaluated. Expression of collagen type I (COLI) A2, (COLIA2),histopathology and immunohistochemical (IHC) staining of COLI α1 (COLIA1) were performed on skin biopsies at first, second and third weeks. The catalase activity, malondialdehyde (MDA) concentration and matrix metalloproteinase (MMP) 9 (MMP-9) activity were assessed in wound fluid samples. All data were analysed statistically. The epithelization percent significantly increased in the PRP-treated wound at week 3. Collagen was well organized in the PRP-treated wounds compared with control wounds at week 3. The COLIA2 expression and intensity of COLIA1 significantly increased in PRP-treated wounds. MDA concentration was significantly decreased in PRP-treated wound at week 3. The catalase activity exhibited no difference between PRP treated and untreated wounds. The activity of MMP-9 reached its peak at the second week and was significantly high in the PRP-treated group. S/C infiltration of autologous PRP at the wound margins enhances the wound epithelization and reduces the scar tissue formation. © 2017 The Author(s).

Evaluation of the effect of platelet-rich plasma on recovery after ablative fractional photothermolysis.

Science.gov (United States)

Kim, Haena; Gallo, Julio

2015-01-01

Despite the advantages and reduced recovery time of ablative fractional photothermolysis, patients still seek adjuvant treatments to reduce healing time and facilitate their return to normal social and work activity. Platelet-rich plasma (PRP) has been used for many applications in various surgical fields for its ability to improve wound healing, hemostasis, and graft survival. To determine whether PRP will be an effective adjunctive treatment to fractional carbon dioxide resurfacing and reduce healing time and duration of adverse effects. Prospective blinded study of male and female patients 18 years or older and with Fitzpatrick skin types I to IV performed at Miami Institute for Age Management and Intervention. Using a fractional carbon dioxide laser (60 mJ at 150 Hz), a 1-cm2 area was treated on each forearm of every patient. Immediately after the laser treatment, patients were randomized to receive PRP in the right or left forearm and saline in the other forearm. Pictures of each forearm were taken immediately after injection of PRP and then on a daily basis until reepithelialization (eschar formation) occurred. Posttreatment erythema, edema, and reepithelialization. Significant improvement in posttreatment erythema was observed in PRP-treated arms across 94 comparisons in 15 patients. Improvement was defined as the erythema rating of the untreated arm minus the erythema rating of the PRP-treated arm. The mean (standard error of the mean) improvement in grade was 0.26 (0.092; t statistic, 2.83; P = .003). A mean (standard error of the mean) improvement in edema grade of 0.13 (0.059) was also significant across 94 comparisons (t statistic, 2.20; P = .02). Our preliminary results suggest that PRP can objectively reduce erythema and edema following carbon dioxide fractional laser treatment. Most importantly, patients themselves have noticed a reduction in the common posttreatment effects: erythema, edema, pruritus, and discomfort. We anticipate that PRP

Low fraction of the 222K PrP variant in the protease-resistant moiety of PrPres in heterozygous scrapie positive goats.

Science.gov (United States)

Mazza, Maria; Guglielmetti, Chiara; Ingravalle, Francesco; Brusadore, Sonia; Langeveld, Jan P M; Ekateriniadou, Loukia V; Andréoletti, Olivier; Casalone, Cristina; Acutis, Pier Luigi

2017-07-01

The presence of lysine (K) at codon 222 has been associated with resistance to classical scrapie in goats, but few scrapie cases have been identified in 222Q/K animals. To investigate the contribution of the 222K variant to PrPres formation in natural and experimental Q/K scrapie cases, we applied an immunoblotting method based on the use of two different monoclonal antibodies, F99/97.6.1 and SAF84, chosen for their different affinities to 222K and 222Q PrP variants. Our finding that PrPres seems to be formed nearly totally by the 222Q variant provides evidence that the 222K PrP variant confers resistance to conversion to PrPres formation and reinforces the view that this mutation has a protective role against classical scrapie in goats.

Nuestra experiencia en el tratamiento de úlceras crónicas mediante PRF-Vivostat®: Serie de 10 casos Our experience in the treatment of chronic ulcers by PRP-Vivostat®: Series of 10 cases

Directory of Open Access Journals (Sweden)

E. Monclús Fuertes

2009-06-01

Full Text Available Pretendemos mostrar nuestra experiencia clínica en el manejo de úlceras crónicas de distinta etiología, mediante tratamiento conservador con gel rico en fibrina autóloga más factores de crecimiento plaquetarios o PRP, experiencia que reafirma los buenos resultados obtenidos en estudios anteriores referentes a Cirugía Plástica, Estética y Reparadora El hecho diferencial de nuestro estudio es el trato de las lesiones única y exclusivamente con PRP, sin otros tratamientos adyuvantes como es habitual en otros estudios acerca de este tema Entre los años 2002 y 2007 tratamos con PRP 10 pacientes con historia de fallo en los tratamientos convencionales, con una edad media de 65.6 años. Se realizaron entre 3 y 5 sesiones por paciente, espaciadas por una semana. El método de obtención elegido fue el sistema VIVOSTAT® (MBA Group. Se realizó un control fotográfico en cada sesión. Realizamos un seguimiento visual de las lesiones (pretratamiento- postratamiento, valorándolas según una modificación de la escala de Valbonesi et al a la que llamamos "Escala de Zaragoza", siendo el resultado pobre en 1 paciente, regular en 2, bueno en 5 y excelente en 2. El uso de PRP para úlceras crónicas en pacientes refractarios a otro tipo de tratamientos, tanto conservadores como quirúrgicos, es actualmente una alternativa real para conseguir una mejoría evidente e incluso la curación completa de las lesiones.The aim of this study is to evaluate our clinical experience in the management of chronic ulcers by conservative treatment with autologous fibrin-rich gel further platelet growth factors or PRP. This experience reaffirms the good results obtained in earlier studies relating to Plastic, Reconstructive and Aesthetic Surgery; moreover, the strength of our study is the use of PRP as the only treatment of such injuries, without other adjuvant treatments as usual in other works on this topic. From 2002 to 2007, we treated with PRP 10 patients with a

Platelet-Rich Plasma (PRP) Rinses for the Treatment of Non-Responding Oral Lichen Planus: A Case Report

OpenAIRE

Elisabetta Merigo; Aldo Oppici; Anna Parlatore; Luigi Cella; Fabio Clini; Matteo Fontana; Carlo Fornaini

2018-01-01

Platelet-rich plasma (PRP) has been proposed for different applications in the medical field and in maxillofacial surgery thanks to its many growth factors, such as epidermal growth factor (EGF), fibroblast growth factor (FGF), and keratinocyte growth factor (KGF). Oral lichen planus (OLP) is a disease that affects the oral mucosa in a chronic way. This disease frequently worsens the quality of life of patients, particularly when clinical manifestations are of the erythematous or erosive/ulce...

Gait Changes Vary Among Horses with Naturally Occurring Osteoarthritis Following Intra-articular Administration of Autologous Platelet Rich Plasma

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Mustajab Hussain Mirza

2016-04-01

Full Text Available Mechanisms to reduce lameness associated with osteoarthritis (OA are vital to equine health and performance. This study was designed to quantify response to autologous, intra-articular platelet-rich plasma (PRP in horses with OA. Kinetic gait analysis was performed on 12 horses with unilateral forelimb lameness and OA in the same limb before and after intra-articular anesthesia (IAA. Radiographs and kinetic data were obtained before, 6 and 16 weeks after PRP administration to same joint 4 weeks after IAA. Statistical evaluations included filtration effect on platelet concentration, relationship between kinetic variable changes after IAA versus PRP in the affected limb, and associations between response to PRP and response to IAA, platelet concentration and radiographic OA. A positive response to IAA or PRP was defined as ≥5% improvement in peak vertical force, vertical impulse or breaking impulse of the affected limb. Out of 10 horses that responded to IAA, 4 responded to PRP at both time points and 2 responded at one. Of 2 horses that did not respond to IAA, one responded to PRP at both time points. Filtration increased platelet concentration significantly. The relationship between kinetic variable alterations of the affected limb after IAA and PRP was not significant, and response to PRP was not associated with response to IAA, platelet concentration or radiographic OA. Changes in kinetic variables following IAA in joints with naturally occurring OA provide a custom standard to assess intra-articular therapy. Kinetic gait changes after intra-articular PRP are variable in horses with moderate to severe forelimb OA.

A general method for the purification of synthetic oligodeoxyribonucleotides containing strong secondary structure by reversed-phase high-performance liquid chromatography on PRP-1 resin.

Science.gov (United States)

Germann, M W; Pon, R T; van de Sande, J H

1987-09-01

Synthetic 5'-dimethoxytritylated oligodeoxyribonucleotides, which contained strong secondary structure, were satisfactorily denatured and purified by reversed-phase HPLC on PRP-1 columns when strongly alkaline conditions (0.05 M NaOH) were employed. This procedure was suitable for the purification of hairpin structures, e.g., d(CG)nT4(CG)n (n = 4, 5, 6), and oligo(dG) sequences, e.g., d(G)24, as well as oligodeoxyribonucleotide probes which contained degenerate base sites. Oligodeoxyribonucleotides as long as 50 bases in length were purified. Recovery of injected oligonucleotides was typically 90% or better. The high capacity of the PRP-1 resin also allowed purification to be performed on a preparative scale (2-8 mg per injection). Enzymatic degradation and HPLC analysis indicated that no modification of the heterocyclic bases occurred under the alkaline conditions described.

Evaluation of a group cognitive-behavioral depression prevention program for young adolescents: a randomized effectiveness trial.

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Gillham, Jane E; Reivich, Karen J; Brunwasser, Steven M; Freres, Derek R; Chajon, Norma D; Kash-Macdonald, V Megan; Chaplin, Tara M; Abenavoli, Rachel M; Matlin, Samantha L; Gallop, Robert J; Seligman, Martin E P

2012-01-01

Depression is a common psychological problem in adolescence. Recent research suggests that group cognitive-behavioral interventions can reduce and prevent symptoms of depression in youth. Few studies have tested the effectiveness of such interventions when delivered by school teachers and counselors (as opposed to research team staff). We evaluated the effectiveness of the Penn Resiliency Program for adolescents (PRP-A), a school-based group intervention that targets cognitive behavioral risk factors for depression. We randomly assigned 408 middle school students (ages 10-15) to one of three conditions: PRP-A, PRP-AP (in which adolescents participated in PRP-A and parents were invited to attend a parent intervention component), or a school-as-usual control. Adolescents completed measures of depression and anxiety symptoms, cognitive style, and coping at baseline, immediately after the intervention, and at 6-month follow-up. PRP-A reduced depression symptoms relative to the school as usual control. Baseline levels of hopelessness moderated intervention effects. Among participants with average and high levels of hopelessness, PRP (A and AP) significantly improved depression symptoms, anxiety symptoms, hopelessness, and active coping relative to control. Among participants with low baseline hopelessness, we found no intervention effects. PRP-AP was not more effective than PRP-A alone. We found no intervention effects on clinical levels of depression or anxiety. These findings suggest that cognitive-behavioral interventions can be beneficial when delivered by school teachers and counselors. These interventions may be most helpful to students with elevated hopelessness.

Safety and Efficacy of Intra-articular Injection of Platelet-Rich Plasma in Patients With Ankle Osteoarthritis.

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Fukawa, Taisuke; Yamaguchi, Satoshi; Akatsu, Yorikazu; Yamamoto, Yohei; Akagi, Ryuichiro; Sasho, Takahisa

2017-06-01

An intra-articular injection of platelet-rich plasma (PRP) may be an effective treatment for osteoarthritis (OA). However, its efficacy in ankle OA has not been investigated yet. The purpose of this study was to assess the safety and efficacy of an intra-articular injection of PRP in patients with ankle OA during a 24-week period. Twenty ankles of 20 patients with varus-type ankle OA who received intra-articular injections of PRP were evaluated. PRP was extracted from whole blood by using the double-spin technique. Three injections of 2-mL PRP were administered to the ankle at an interval of 2 weeks under ultrasonographic guidance. Adverse events and efficacy were assessed at 4, 12, and 24 weeks after the last injection. Clinical outcomes were assessed by using the visual analog scale (VAS) for pain, the Japanese Society for Surgery of the Foot (JSSF) ankle/hindfoot scale, and the Self-Administered Foot Evaluation Questionnaire (SAFE-Q). No serious adverse effects were observed during the follow-up period. The VAS and JSSF scale scores significantly decreased from baseline to 4, 12, and 24 weeks after treatment ( P SAFE-Q significantly improved from baseline to 12 weeks after treatment ( P = .04). Overall, the amount of pain reduction was maximal at 12 weeks after the last injection, and the effect was reduced at 24 weeks. The patients with late-stage OA had worse scores in all outcomes than those with early-stage OA. Intra-articular injections of PRP resulted in no serious adverse effects and significantly reduced pain in the patients with ankle OA. PRP treatment can be safe and effective and may be an option in the treatment of ankle OA. Level IV, case series.

Platelet rich plasma versus laser therapy in lateral epicondylitis of elbow

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Gyaneshwar Tonk

2014-01-01

Conclusions: Treatment of patients with chronic lateral epicondylitis with PRP extract reduced pain and significantly increased function, exceeding the effect of low level laser therapy on long term followup. Low-level laser therapy is better in the short term period, but on long term followup injection PRP therapy is better than laser therapy in lateral epicondylitis.

Analysis of autologous platelet-rich plasma during ascending and transverse aortic arch surgery.

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Zhou, Shao-Feng; Estrera, Anthony L; Miller, Charles C; Ignacio, Craig; Panthayi, Sreelatha; Loubser, Paul; Sagun, Dean L; Sheinbaum, Roy; Safi, Hazim J

2013-05-01

Coagulopathy is a common complication after ascending and transverse arch aortic surgery with profound hypothermic circuit arrest (PHCA). Blood conservation strategies to reduce transfusion have been ongoing and involve multiple treatment modalities in modern cardiac surgery. The purpose of this study is to evaluate the effectiveness of autologous platelet-rich plasma (aPRP) as a blood conservation technique to reduce blood transfusion in ascending and arch aortic surgery. Between 2003 and 2009, we retrospectively reviewed 685 cases of ascending aorta and transverse arch repair using PHCA. A total of 287 patients in which aPRP was used (aPRP group) were compared with 398 patients who did have aPRP (non-aPRP group). Perioperative transfusion requirements and clinical outcomes that included early mortality, postoperative stroke, renal dysfunction, prolonged ventilation, coagulopathy, and length of postoperative intensive care unit stay were analyzed. The data were analyzed by mean and frequency for continuous variables and qualitative variables. To account for potential selection bias, 2 types of propensity analysis were performed. In both unadjusted and adjusted analysis, perioperative transfusions were fewer in the aPRP group compared with the non-aPRP group: (3.9 units fewer packed red blood cells, 4.5 units fewer fresh frozen plasma, 7.9 units fewer platelets, and 6.8 units fewer cryoprecipitate). In all analyses, postoperative morbidity (stroke, duration of mechanical ventilation, and intensive care unit stay) were significantly improved. Hospital mortality rate was not significantly decreased. The utilization of aPRP was associated with a reduction in allogeneic blood transfusions as well as a decrease in early postoperative morbidity during repairs of the ascending and transverse arch aorta using PHCA. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Ovine recombinant PrP as an inhibitor of ruminant prion propagation in vitro.

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Workman, Rob G; Maddison, Ben C; Gough, Kevin C

2017-07-04

Prion diseases are fatal and incurable neurodegenerative diseases of humans and animals. Despite years of research, no therapeutic agents have been developed that can effectively manage or reverse disease progression. Recently it has been identified that recombinant prion proteins (rPrP) expressed in bacteria can act as inhibitors of prion replication within the in vitro prion replication system protein misfolding cyclic amplification (PMCA). Here, within PMCA reactions amplifying a range of ruminant prions including distinct Prnp genotypes/host species and distinct prion strains, recombinant ovine VRQ PrP displayed consistent inhibition of prion replication and produced IC50 values of 122 and 171 nM for ovine scrapie and bovine BSE replication, respectively. These findings illustrate the therapeutic potential of rPrPs with distinct TSE diseases.

Platelet rich plasma versus laser therapy in lateral epicondylitis of elbow.

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Tonk, Gyaneshwar; Kumar, Anish; Gupta, Amit

2014-07-01

Platelet rich plasma (PRP) extract has shown to be a general stimulation for repair and currently used widely in various sports injury. A prospective observational study was done to assess the efficacy of autologous PRP injection in lateral epicondylitis of elbow, and compare the result with low level laser therapy. The trial was conducted at a tertiary care center for a period of 2 years. Eighty-one patients with chronic lateral epicondylitis were divided into two groups. PRP group (n = 39) and laser therapy group (n = 42). The primary analysis included Nirschl pain score, local tenderness, pain on wrist extension, grip strength, elbow swelling were clinically assessed at different interval of followup (minimum followup: 52 weeks) and; clinical and functional outcome evaluated at final followup. The statistical analysis were done. The mean Nirschl pain score decreased significantly from baseline in PRP when compared with low level laser therapy (P ≤ 0.05). Treatment of patients with chronic lateral epicondylitis with PRP extract reduced pain and significantly increased function, exceeding the effect of low level laser therapy on long term followup. Low-level laser therapy is better in the short term period, but on long term followup injection PRP therapy is better than laser therapy in lateral epicondylitis.

Critical significance of the region between Helix 1 and 2 for efficient dominant-negative inhibition by conversion-incompetent prion protein.

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Yuzuru Taguchi

Full Text Available Prion diseases are fatal infectious neurodegenerative disorders in man and animals associated with the accumulation of the pathogenic isoform PrP(Sc of the host-encoded prion protein (PrP(c. A profound conformational change of PrP(c underlies formation of PrP(Sc and prion propagation involves conversion of PrP(c substrate by direct interaction with PrP(Sc template. Identifying the interfaces and modalities of inter-molecular interactions of PrPs will highly advance our understanding of prion propagation in particular and of prion-like mechanisms in general. To identify the region critical for inter-molecular interactions of PrP, we exploited here dominant-negative inhibition (DNI effects of conversion-incompetent, internally-deleted PrP (ΔPrP on co-expressed conversion-competent PrP. We created a series of ΔPrPs with different lengths of deletions in the region between first and second α-helix (H1∼H2 which was recently postulated to be of importance in prion species barrier and PrP fibril formation. As previously reported, ΔPrPs uniformly exhibited aberrant properties including detergent insolubility, limited protease digestion resistance, high-mannose type N-linked glycans, and intracellular localization. Although formerly controversial, we demonstrate here that ΔPrPs have a GPI anchor attached. Surprisingly, despite very similar biochemical and cell-biological properties, DNI efficiencies of ΔPrPs varied significantly, dependant on location and inversely correlated with the size of deletion. This data demonstrates that H1∼H2 and the region C-terminal to it are critically important for efficient DNI. It also suggests that this region is involved in PrP-PrP interaction and conversion of PrP(C into PrP(Sc. To reconcile the paradox of how an intracellular PrP can exert DNI, we demonstrate that ΔPrPs are subject to both proteasomal and lysosomal/autophagic degradation pathways. Using autophagy pathways ΔPrPs obtain access to the locale

Wound Healing Activity of a New Formulation from Platelet Lysate

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Akram Jamshidzadeh

2016-03-01

Full Text Available Platelet-rich plasma (PRP is an attractive preparation in regenerative medicine due to its potential role in the healing process in different experimental models. This study was designed to investigate the wound healing activity of a new formulation of PRP. Different gel-based formulations of PRP were prepared. Open excision wounds were made on the back of male Sprague-Dawley rats, and PRP gel was administered topically once daily until the wounds healed completely (12 days. The results revealed that the tested PRP formulation significantly accelerated the wound healing process by increasing the wound contraction, tissue granulization, vascularization, and collagen regeneration. Interestingly, this study showed that there were no significant differences between the PRP and its gel-based formulation in all the above mentioned parameters. Although this investigation showed that PRP formulation had significant wound healing effects, the PRP gel-based formulation also had significant wound healing properties. This might indicate the wound healing properties of the PRP gel ingredients in the current investigation.

Assessment of the efficacy and safety of single platelet-rich plasma injection on different types and grades of facial wrinkles.

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Elnehrawy, Naema Y; Ibrahim, Zeinab A; Eltoukhy, Azza M; Nagy, Hala M

2017-03-01

Platelet-rich plasma (PRP) is considered as a growing modality for tissue regeneration and a developing research area for clinicians and researchers. PRP injection treatment provides supraphysiological concentrations of growth factors that may help in accelerated tissue remodeling and regeneration. To evaluate the efficacy and safety of single autologous PRP intradermal injection for treatment of facial wrinkles and for facial rejuvenation. A total of 20 subjects with different types of facial wrinkles were included in this study. All subjects received single PRP intradermal injection and were clinically assessed before and after treatment for a period of 8 weeks using Wrinkle Severity Rating Scale (WSRS), Skin Homogeneity and Texture (SHnT) Scale, Physician Assessment Scale, and Subject Satisfaction Scale. The mean value of WSRS reduced from 2.90 ± 0.91 before treatment to 2.10 ± 0.79 after 8 weeks of treatment. The most significant results were with younger subjects that have mild and moderate wrinkles of the nasolabial folds (NLFs). Fourteen of seventeen subjects with NLFs showed more than 25% improvement in their appearance. Side effects of PRP treatment were minimal to mild and with excellent tolerability. Single PRP intradermal injection is well tolerated and capable of rejuvenating the face and producing a significant correction of wrinkles especially the NLFs. © 2016 Wiley Periodicals, Inc.

Soluble vascular endothelial growth factor in various blood transfusion components

DEFF Research Database (Denmark)

Nielsen, Hans Jørgen; Werther, K; Mynster, T

1999-01-01

of sVEGF was determined in nonfiltered and prestorage white cell-reduced whole blood (WB), buffy coat-depleted saline-adenine-glucose-mannitol (SAGM) blood, platelet-rich plasma (PRP), and buffy coat-derived platelet (BCP) pools obtained from volunteer, healthy blood donors. As a control, total content......-123) ng per mL in lysed cells. In SAGM blood, the median total sVEGF content was 25.3 (3.3-48.4) ng per unit in nonfiltered units and undetectable in white cell-reduced units. Median total sVEGF content was 29.2 (24.8-124.9) ng per unit in nonfiltered PRP and 28.7 (24.5-118.6) ng per unit in white cell......-reduced PRP. The sVEGF accumulated significantly in WB, SAGM blood, and BCP pools, depending on the storage time. CONCLUSION: The sVEGF (isotype 165) appears to be present in various blood transfusion components, depending on storage time....

Modification of Pulsed Electric Field Conditions Results in Distinct Activation Profiles of Platelet-Rich Plasma.

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Frelinger, Andrew L; Gerrits, Anja J; Garner, Allen L; Torres, Andrew S; Caiafa, Antonio; Morton, Christine A; Berny-Lang, Michelle A; Carmichael, Sabrina L; Neculaes, V Bogdan; Michelson, Alan D

2016-01-01

Activated autologous platelet-rich plasma (PRP) used in therapeutic wound healing applications is poorly characterized and standardized. Using pulsed electric fields (PEF) to activate platelets may reduce variability and eliminate complications associated with the use of bovine thrombin. We previously reported that exposing PRP to sub-microsecond duration, high electric field (SMHEF) pulses generates a greater number of platelet-derived microparticles, increased expression of prothrombotic platelet surfaces, and differential release of growth factors compared to thrombin. Moreover, the platelet releasate produced by SMHEF pulses induced greater cell proliferation than plasma. To determine whether sub-microsecond duration, low electric field (SMLEF) bipolar pulses results in differential activation of PRP compared to SMHEF, with respect to profiles of activation markers, growth factor release, and cell proliferation capacity. PRP activation by SMLEF bipolar pulses was compared to SMHEF pulses and bovine thrombin. PRP was prepared using the Harvest SmartPreP2 System from acid citrate dextrose anticoagulated healthy donor blood. PEF activation by either SMHEF or SMLEF pulses was performed using a standard electroporation cuvette preloaded with CaCl2 and a prototype instrument designed to take into account the electrical properties of PRP. Flow cytometry was used to assess platelet surface P-selectin expression, and annexin V binding. Platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), endothelial growth factor (EGF) and platelet factor 4 (PF4), and were measured by ELISA. The ability of supernatants to stimulate proliferation of human epithelial cells in culture was also evaluated. Controls included vehicle-treated, unactivated PRP and PRP with 10 mM CaCl2 activated with 1 U/mL bovine thrombin. PRP activated with SMLEF bipolar pulses or thrombin had similar light scatter profiles, consistent with the presence of platelet

Modification of Pulsed Electric Field Conditions Results in Distinct Activation Profiles of Platelet-Rich Plasma.

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Andrew L Frelinger

Full Text Available Activated autologous platelet-rich plasma (PRP used in therapeutic wound healing applications is poorly characterized and standardized. Using pulsed electric fields (PEF to activate platelets may reduce variability and eliminate complications associated with the use of bovine thrombin. We previously reported that exposing PRP to sub-microsecond duration, high electric field (SMHEF pulses generates a greater number of platelet-derived microparticles, increased expression of prothrombotic platelet surfaces, and differential release of growth factors compared to thrombin. Moreover, the platelet releasate produced by SMHEF pulses induced greater cell proliferation than plasma.To determine whether sub-microsecond duration, low electric field (SMLEF bipolar pulses results in differential activation of PRP compared to SMHEF, with respect to profiles of activation markers, growth factor release, and cell proliferation capacity.PRP activation by SMLEF bipolar pulses was compared to SMHEF pulses and bovine thrombin. PRP was prepared using the Harvest SmartPreP2 System from acid citrate dextrose anticoagulated healthy donor blood. PEF activation by either SMHEF or SMLEF pulses was performed using a standard electroporation cuvette preloaded with CaCl2 and a prototype instrument designed to take into account the electrical properties of PRP. Flow cytometry was used to assess platelet surface P-selectin expression, and annexin V binding. Platelet-derived growth factor (PDGF, vascular endothelial growth factor (VEGF, endothelial growth factor (EGF and platelet factor 4 (PF4, and were measured by ELISA. The ability of supernatants to stimulate proliferation of human epithelial cells in culture was also evaluated. Controls included vehicle-treated, unactivated PRP and PRP with 10 mM CaCl2 activated with 1 U/mL bovine thrombin.PRP activated with SMLEF bipolar pulses or thrombin had similar light scatter profiles, consistent with the presence of platelet

Efficacy of platelet-rich plasma in arthroscopic repair of full-thickness rotator cuff tears: a meta-analysis.

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Cai, You-zhi; Zhang, Chi; Lin, Xiang-jin

2015-12-01

The use of platelet-rich plasma (PRP) is an innovative clinical therapy, especially in arthroscopic rotator cuff repair. The purpose of this study was to compare the clinical improvement and tendon-to-bone healing with and without PRP therapy in arthroscopic rotator cuff repair. A systematic search was done in the major medical databases to evaluate the studies using PRP therapy (PRP+) or with no PRP (PRP-) for the treatment of patients with rotator cuff tears. We reviewed clinical scores such as the Constant score, the American Shoulder and Elbow Surgeons score, the University of California at Los Angeles (UCLA) Shoulder Rating Scale, the Simple Shoulder Test, and the failure-to-heal rate by magnetic resonance imaging between PRP+ and PRP- groups. Five studies included in this review were used for a meta-analysis based on data availability. There were no statistically significant differences between PRP+ and PRP- groups for overall outcome scores (P > .05). However, the PRP+ group exhibited better healing rates postoperatively than the PRP- group (P = .03) in small/moderate full-thickness tears. The use of PRP therapy in full-thickness rotator cuff repairs showed no statistically significant difference compared with no PRP therapy in clinical outcome scores, but the failure-to-heal rate was significantly decreased when PRP was used for treatment of small-to-moderately sized tears. PRP therapy may improve tendon-to-bone healing in patients with small or moderate rotator cuff tears. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Melatonin Promotes Apoptosis of Oxaliplatin-resistant Colorectal Cancer Cells Through Inhibition of Cellular Prion Protein.

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Lee, Jun Hee; Yoon, Yeo Min; Han, Yong-Seok; Yun, Chul Won; Lee, Sang Hun

2018-04-01

Drug resistance restricts the efficacy of chemotherapy in colorectal cancer. However, the detailed molecular mechanism of drug resistance in colorectal cancer cells remains unclear. The level of cellular prion protein (PrP C ) in oxaliplatin-resistant colorectal cancer (SNU-C5/Oxal-R) cells was assessed. PrP C level in SNU-C5/Oxal-R cells was significantly increased compared to that in wild-type (SNU-C5) cells. Superoxide dismutase and catalase activities were higher in SNU-C5/Oxal-R cells than in SNU-C5 cells. Treatment of SNU-C5/Oxal-R cells with oxaliplatin and melatonin reduced PrP C expression, while suppressing antioxidant enzyme activity and increasing superoxide anion generation. In SNU-C5/Oxal-R cells, endoplasmic reticulum stress and apoptosis were significantly increased following co-treatment with oxaliplatin and melatonin compared to treatment with oxaliplatin alone. Co-treatment with oxaliplatin and melatonin increased endoplasmic reticulum stress in and apoptosis of SNU-C5/Oxal-R cells through inhibition of PrP C , suggesting that PrP C could be a key molecule in oxaliplatin resistance of colorectal cancer cells. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Autologous neural progenitor cell transplantation into newborn mice modeling for E200K genetic prion disease delays disease progression.

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Frid, Kati; Binyamin, Orli; Fainstein, Nina; Keller, Guy; Ben-Hur, Tamir; Gabizon, Ruth

2018-05-01

TgMHu2ME199K mice, a transgenic line mimicking genetic prion disease, are born healthy and gradually deteriorate to a terminal neurological condition concomitant with the accumulation of disease-related PrP. To investigate whether transplantation of neural progenitor cells (NPCs) to these mice can delay disease aggravation, we first tested the properties of mutant PrP in homogenates and enriched NPCs from TgMHu2ME199K embryos, as compared to PrP in sick TgMHu2ME199K brains. Next, we tested the clinical effect of NPCs transplantation into newborn TgMHu2ME199K mice. We show that mutant PrP does not convert into a disease-related isoform while in progenitor cells. Most important, transplantation of both wild type and transgenic NPCs significantly delayed the progression of spontaneous prion disease in TgMHu2ME199K mice. While the strong clinical effect was not accompanied by a reduced accumulation of disease-related PrP, treated mouse brains presented a significant reduction in amyloid glycosaminoglycans and preservation of neurogenesis levels, indicating a strong neuroprotective effect. These results may encourage the investigation of new pathways for treatment in these terrible diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

Robust nonlinear PID-like fuzzy logic control of a planar parallel (2PRP-PPR) manipulator.

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Londhe, P S; Singh, Yogesh; Santhakumar, M; Patre, B M; Waghmare, L M

2016-07-01

In this paper, a robust nonlinear proportional-integral-derivative (PID)-like fuzzy control scheme is presented and applied to complex trajectory tracking control of a 2PRP-PPR (P-prismatic, R-revolute) planar parallel manipulator (motion platform) with three degrees-of-freedom (DOF) in the presence of parameter uncertainties and external disturbances. The proposed control law consists of mainly two parts: first part uses a feed forward term to enhance the control activity and estimated perturbed term to compensate for the unknown effects namely external disturbances and unmodeled dynamics, and the second part uses a PID-like fuzzy logic control as a feedback portion to enhance the overall closed-loop stability of the system. Experimental results are presented to show the effectiveness of the proposed control scheme. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

The significance of reduced respiratory chain enzyme activities: clinical, biochemical and radiological associations.

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Mordekar, S R; Guthrie, P; Bonham, J R; Olpin, S E; Hargreaves, I; Baxter, P S

2006-03-01

Mitochondrial diseases are an important group of neurometabolic disorders in children with varied clinical presentations and diagnosis that can be difficult to confirm. To report the significance of reduced respiratory chain enzyme (RCE) activity in muscle biopsy samples from children. Retrospective odds ratio was used to compare clinical and biochemical features, DNA studies, neuroimaging, and muscle biopsies in 18 children with and 48 without reduced RCE activity. Children with reduced RCE activity were significantly more likely to have consanguineous parents, to present with acute encephalopathy and lactic acidaemia and/or within the first year of life; to have an axonal neuropathy, CSF lactate >4 mmol/l; and/or to have signal change in the basal ganglia. There were positive associations with a maternal family history of possible mitochondrial cytopathy; a presentation with failure to thrive and lactic acidaemia, ragged red fibres, reduced fibroblast fatty acid oxidation and with an abnormal allopurinol loading test. There was no association with ophthalmic abnormalities, deafness, epilepsy or myopathy. The association of these clinical, biochemical and radiological features with reduced RCE activity suggests a possible causative link.

Four-phonon scattering significantly reduces intrinsic thermal conductivity of solids

Science.gov (United States)

Feng, Tianli; Lindsay, Lucas; Ruan, Xiulin

2017-10-01

For decades, the three-phonon scattering process has been considered to govern thermal transport in solids, while the role of higher-order four-phonon scattering has been persistently unclear and so ignored. However, recent quantitative calculations of three-phonon scattering have often shown a significant overestimation of thermal conductivity as compared to experimental values. In this Rapid Communication we show that four-phonon scattering is generally important in solids and can remedy such discrepancies. For silicon and diamond, the predicted thermal conductivity is reduced by 30% at 1000 K after including four-phonon scattering, bringing predictions in excellent agreement with measurements. For the projected ultrahigh-thermal conductivity material, zinc-blende BAs, a competitor of diamond as a heat sink material, four-phonon scattering is found to be strikingly strong as three-phonon processes have an extremely limited phase space for scattering. The four-phonon scattering reduces the predicted thermal conductivity from 2200 to 1400 W/m K at room temperature. The reduction at 1000 K is 60%. We also find that optical phonon scattering rates are largely affected, being important in applications such as phonon bottlenecks in equilibrating electronic excitations. Recognizing that four-phonon scattering is expensive to calculate, in the end we provide some guidelines on how to quickly assess the significance of four-phonon scattering, based on energy surface anharmonicity and the scattering phase space. Our work clears the decades-long fundamental question of the significance of higher-order scattering, and points out ways to improve thermoelectrics, thermal barrier coatings, nuclear materials, and radiative heat transfer.

CCS and SOD1 mRNA are reduced after copper supplementation in peripheral mononuclear cells of individuals with high serum ceruloplasmin concentration.

Science.gov (United States)

Suazo, Miriam; Olivares, Felipe; Mendez, Marco A; Pulgar, Rodrigo; Prohaska, Joseph R; Arredondo, Miguel; Pizarro, Fernando; Olivares, Manuel; Araya, Magdalena; González, Mauricio

2008-04-01

The limits of copper homeostatic regulation in humans are not known, making it difficult to define the milder effects of early copper excess. Furthermore, a robust assay to facilitate the detection of early stages of copper excess is needed. To address these issues, we assessed changes in relative mRNA abundance of methallothionein 2A (MT2A), prion (PrP), amyloid precursor-like protein 2 (APLP2), Cu/Zn superoxide dismutase (SOD1) and its copper chaperone (CCS) in peripheral mononuclear cells (PMNCs) from healthy adults representing the 5% highest and lowest extremes in the distribution curve of serum ceruloplasmin (Cp) concentrations of 800 individuals. The intracellular Cu content was also determined. PMNCs were isolated from individuals before and after exposure to a single daily dose of 10 mg Cu (as CuSO(4)) for 2 months. Results showed that although there were fluctuations in serum Cp values of the samples assessed before copper exposure, no significant differences were observed in cell copper content or in the relative abundance of MT2A, PrP and APLP2 transcripts in PMNCs. Also, these values were not modified after copper supplementation. However, CCS and SOD1 mRNA levels were reduced in PMNCs after copper supplementation in the individuals with the high Cp values, suggesting that they should be further explored as biomarkers of moderate copper overload in humans.

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

Science.gov (United States)

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.

Effect of Platelet-Rich Plasma and Bioactive Glass Powder for the Improvement of Rotator Cuff Tendon-to-Bone Healing in a Rabbit Model

Directory of Open Access Journals (Sweden)

Yang Wu

2014-11-01

Full Text Available 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.

The effects of platelet-rich plasma on recovery time and aesthetic outcome in facial rejuvenation: preliminary retrospective observations.

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Willemsen, Joep C N; van der Lei, Berend; Vermeulen, Karin M; Stevens, Hieronymus P J D

2014-10-01

This study focused on the possible effect of platelet-rich plasma (PRP) on recovery time and aesthetic outcome after facial rejuvenation. We conducted a retrospective analysis with regard to recovery time and the aesthetic improvement after treatment among four groups of patients: those treated with fat grafting only (Group I), those treated with fat grafting and PRP (Group II), those treated with a minimal access cranial suspension (MACS)-lift and fat grafting (Group III), and those treated with a MACS-lift, fat grafting, and PRP (Group IV). For the first part of this study, i.e., evaluation of recovery time after surgery, the following selection criteria were used: nonsmoking females, aged 35-65 years, with a complete documented follow-up. In total, 82 patients were included in the evaluation of patient-reported recovery time. For the second part of the study, i.e., evaluation of potential differences in aesthetic outcome, the records of these 82 patients were screened for the presence of pre- and postoperative standardized photographs in three views (AP, lateral, and oblique), leaving 37 patients to evaluate. A questionnaire was developed to evaluate the aesthetic outcome in all four groups of patients. This questionnaire was given to an expert panel that consisted of ten plastic surgeons. The addition of PRP to a lipofilling procedure resulted in a significant drop in the number of days needed to recover before returning to work or to restart social activities [Group I (no PRP) took 18.9 days vs Group II (PRP) took 13.2 days, p = 0.019]. There seemed to be no effect when PRP was added to a MACS-lift + lipofilling procedure. Also, the aesthetic outcome of the lipofilling and MACS-lift + lipofilling groups that received PRP (Groups II and IV) was significantly better than the groups without PRP (Groups I and III). Adding PRP to facial lipofilling reduces recovery time and improves the overall aesthetic outcome of a MACS-lift. This journal requires that

Prion protein modulates glucose homeostasis by altering intracellular iron.

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Ashok, Ajay; Singh, Neena

2018-04-26

The prion protein (PrP C ), a mainly neuronal protein, is known to modulate glucose homeostasis in mouse models. We explored the underlying mechanism in mouse models and the human pancreatic β-cell line 1.1B4. We report expression of PrP C on mouse pancreatic β-cells, where it promoted uptake of iron through divalent-metal-transporters. Accordingly, pancreatic iron stores in PrP knockout mice (PrP -/- ) were significantly lower than wild type (PrP +/+ ) controls. Silencing of PrP C in 1.1B4 cells resulted in significant depletion of intracellular (IC) iron, and remarkably, upregulation of glucose transporter GLUT2 and insulin. Iron overloading, on the other hand, resulted in downregulation of GLUT2 and insulin in a PrP C -dependent manner. Similar observations were noted in the brain, liver, and neuroretina of iron overloaded PrP +/+ but not PrP -/- mice, indicating PrP C -mediated modulation of insulin and glucose homeostasis through iron. Peripheral challenge with glucose and insulin revealed blunting of the response in iron-overloaded PrP +/+ relative to PrP -/- mice, suggesting that PrP C -mediated modulation of IC iron influences both secretion and sensitivity of peripheral organs to insulin. These observations have implications for Alzheimer's disease and diabetic retinopathy, known complications of type-2-diabetes associated with brain and ocular iron-dyshomeostasis.

Effects of FlAsH/Tetracysteine (TC) tag on PrP proteolysis and PrPres formation by TC-scanning

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Taguchi, Yuzuru; Hohsfield, Lindsay A.; Hollister, Jason R.

2014-01-01

The FlAsH/tetracysteine (FlAsH/TC) tag is a powerful tool for fluorescent labeling of proteins. However, even small tags such as FlAsH/TC could alter the behavior of the tagged proteins, especially if the insertion occurs at internal sites. Defining the influence of FlAsH/TC on nearby protein-protein interactions might aid in selecting appropriate positions for internal TC insertions and allow the exploitation of serial FlAsH/TC insertions (TC-scanning) as a probe to characterize sites of protein-protein interaction. To explore this application in the context of substrate-protease interactions, we analyzed the effect of FlAsH/TC insertions on proteolysis of cellular prion protein (PrPsen) in in vitro reactions and generation of the C1 metabolic fragment of PrPsen in live neuroblastoma cells. The influence of FlAsH/TC insertion was evaluated by TC-scanning across the cleavage sites of each protease. The results showed that FlAsH/TC inhibited protease cleavage only within limited ranges of the cleavage sites that varied from about 1 to 6 residues-wide depending on the protease, providing an estimate of the PrP residues interacting with each protease. TC-scanning was also used to probe a different type of protein-protein interaction, the conformational conversion of FlAsH-PrPsen to the prion disease-associated isoform, PrPres. PrP constructs with FlAsH/TC insertions at residues 90–96 but not 97–101 were converted to FlAsH-PrPres, identifying a boundary separating loosely versus compactly folded regions of PrPres. Our observations demonstrate that TC-scanning with the FlAsH/TC tag can be a versatile method for probing protein-protein interactions and folding processes. PMID:23943295

Low fraction of the 222K PrP variant in the protease-resistant moiety of PrPres in heterozygous scrapie positive goats

OpenAIRE

Mazza, Maria; Guglielmetti, Chiara; Ingravalle, Francesco; Brusadore, Sonia; Langeveld, Jan P. M.; Ekateriniadou, Loukia V.; Andréoletti, Olivier; Casalone, Cristina; Acutis, Pier Luigi

2017-01-01

The presence of lysine (K) at codon 222 has been associated with resistance to classical scrapie in goats, but few scrapie cases have been identified in 222Q/K animals. To investigate the contribution of the 222K variant to PrPres formation in natural and experimental Q/K scrapie cases, we applied an immunoblotting method based on the use of two different monoclonal antibodies, F99/97.6.1 and SAF84, chosen for their different affinities to 222K and 222Q PrP variants. Our finding that PrPres s...

A randomized controlled experimental study of the efficacy of platelet-rich plasma and hyaluronic acid for the prevention of adhesion formation in a rat uterine horn model.

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Oz, Murat; Cetinkaya, Nilufer; Bas, Sevda; Korkmaz, Elmas; Ozgu, Emre; Terzioglu, Gokay Serdar; Buyukkagnici, Umran; Akbay, Serap; Caydere, Muzaffer; Gungor, Tayfun

2016-09-01

Platelet-rich plasma (PRP) has been known to possess an efficacy in tissue regeneration. The aim of this study was to determine the role of PRP on post-operative adhesion formation in an experimental rat study. Thirty Sprague-Dawley rats were randomly divided into control, hyaluronic acid, and PRP treatment groups and operated on for uterine horn adhesion modeling. Blood was collected to produce a PRP with platelet counts of 688 × 10(3)/μL, and 1 ml of either hyaluronic acid gel or PRP was administered over the standard lesions, while the control group received no medication. The evaluation of post-operative adhesions was done on the 30th post-operative day. The location, extent, type, and tenacity of adhesions as well as total adhesion scores, tissue inflammation, fibrosis and transforming growth factor-1beta (TGF-1β) expressions were evaluated. The total adhesion score was significantly lower in the PRP group (3.2 ± 1.5) compared with the hyaluronic acid (5.0 ± 1.3) and control (8.1 ± 1.7) groups. The extent of the adhesions was significantly lower in the PRP group. There was no significant difference in the type and tenacity of adhesions between the hyaluronic acid and the PRP group. The level of inflammation was significantly higher in the control group than the others, while there was no difference between the PRP and hyaluronic acid groups. TGF-1β expression was significantly lesser in the PRP group than the control and hyaluronic acid groups. PRP is more effective than hyaluronic acid treatment in preventing post-operative adhesion formation in an experimental rat uterine horn adhesion model.

Preventing adolescents’ externalizing and internalizing symptoms: Effects of the Penn Resiliency Program

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J. J. Cutuli

2013-11-01

Full Text Available This study reports secondary outcome analyses from a past study of the Penn Resiliency Program (PRP, a cognitive-behavioral depression prevention program for middle-school aged children. Middle school students (N = 697 were randomly assigned to PRP, PEP (an alternate intervention, or control conditions. Gillham et al., (2007 reported analyses examining PRP’s effects on average and clinical levels of depression symptoms. We examine PRP’s effects on parent-, teacher-, and self-reports of adolescents’ externalizing and broader internalizing (depression/anxiety, somatic complaints, and social withdrawal symptoms over three years of follow-up. Relative to no intervention control, PRP reduced parent-reports of adolescents’ internalizing symptoms beginning at the first assessment after the intervention and persisting for most of the follow-up assessments. PRP also reduced parent-reported conduct problems relative to no-intervention. There was no evidence that the PRP program produced an effect on teacher- or self-report of adolescents’ symptoms. Overall, PRP did not reduce symptoms relative to the alternate intervention, although there is a suggestion of a delayed effect for conduct problems. These findings are discussed with attention to developmental trajectories and the importance of interventions that address common risk factors for diverse forms of negative outcomes.

Regenerative therapies for equine degenerative joint disease: a preliminary study.

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Sarah Broeckx

Full Text Available Degenerative joint disease (DJD is a major cause of reduced athletic function and retirement in equine performers. For this reason, regenerative therapies for DJD have gained increasing interest. Platelet-rich plasma (PRP and mesenchymal stem cells (MSCs were isolated from a 6-year-old donor horse. MSCs were either used in their native state or after chondrogenic induction. In an initial study, 20 horses with naturally occurring DJD in the fetlock joint were divided in 4 groups and injected with the following: 1 PRP; 2 MSCs; 3 MSCs and PRP; or 4 chondrogenic induced MSCs and PRP. The horses were then evaluated by means of a clinical scoring system after 6 weeks (T1, 12 weeks (T2, 6 months (T3 and 12 months (T4 post injection. In a second study, 30 horses with the same medical background were randomly assigned to one of the two combination therapies and evaluated at T1. The protein expression profile of native MSCs was found to be negative for major histocompatibility (MHC II and p63, low in MHC I and positive for Ki67, collagen type II (Col II and Vimentin. Chondrogenic induction resulted in increased mRNA expression of aggrecan, Col II and cartilage oligomeric matrix protein (COMP as well as in increased protein expression of p63 and glycosaminoglycan, but in decreased protein expression of Ki67. The combined use of PRP and MSCs significantly improved the functionality and sustainability of damaged joints from 6 weeks until 12 months after treatment, compared to PRP treatment alone. The highest short-term clinical evolution scores were obtained with chondrogenic induced MSCs and PRP. This study reports successful in vitro chondrogenic induction of equine MSCs. In vivo application of (induced MSCs together with PRP in horses suffering from DJD in the fetlock joint resulted in a significant clinical improvement until 12 months after treatment.

Reduction of pain via platelet-rich plasma in split-thickness skin graft donor sites: a series of matched pairs

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Miller, John D.; Rankin, Timothy M.; Hua, Natalie T.; Ontiveros, Tina; Giovinco, Nicholas A.; Mills, Joseph L.; Armstrong, David G.

2015-01-01

In the past decade, autologous platelet-rich plasma (PRP) therapy has seen increasingly widespread integration into medical specialties. PRP application is known to accelerate wound epithelialization rates, and may also reduce postoperative wound site pain. Recently, we observed an increase in patient satisfaction following PRP gel (Angel, Cytomedix, Rockville, MD) application to split-thickness skin graft (STSG) donor sites. We assessed all patients known to our university-based hospital service who underwent multiple STSGs up to the year 2014, with at least one treated with topical PRP. Based on these criteria, five patients aged 48.4±17.6 (80% male) were identified who could serve as their own control, with mean time of 4.4±5.1 years between operations. In both therapies, initial dressing changes occurred on postoperative day (POD) 7, with donor site pain measured by Likert visual pain scale. Paired t-tests compared the size and thickness of harvested skin graft and patient pain level, and STSG thickness and surface area were comparable between control and PRP interventions (p>0.05 for all). Donor site pain was reduced from an average of 7.2 (±2.6) to 3 (±3.7), an average reduction in pain of 4.2 (standard error 1.1, p=0.0098) following PRP use. Based on these results, the authors suggest PRP as a beneficial adjunct for reducing donor site pain following STSG harvest. PMID:25623477

Reduction of pain via platelet-rich plasma in split-thickness skin graft donor sites: a series of matched pairs

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John D. Miller

2015-01-01

Full Text Available In the past decade, autologous platelet-rich plasma (PRP therapy has seen increasingly widespread integration into medical specialties. PRP application is known to accelerate wound epithelialization rates, and may also reduce postoperative wound site pain. Recently, we observed an increase in patient satisfaction following PRP gel (Angel, Cytomedix, Rockville, MD application to split-thickness skin graft (STSG donor sites. We assessed all patients known to our university-based hospital service who underwent multiple STSGs up to the year 2014, with at least one treated with topical PRP. Based on these criteria, five patients aged 48.4±17.6 (80% male were identified who could serve as their own control, with mean time of 4.4±5.1 years between operations. In both therapies, initial dressing changes occurred on postoperative day (POD 7, with donor site pain measured by Likert visual pain scale. Paired t-tests compared the size and thickness of harvested skin graft and patient pain level, and STSG thickness and surface area were comparable between control and PRP interventions (p>0.05 for all. Donor site pain was reduced from an average of 7.2 (±2.6 to 3 (±3.7, an average reduction in pain of 4.2 (standard error 1.1, p=0.0098 following PRP use. Based on these results, the authors suggest PRP as a beneficial adjunct for reducing donor site pain following STSG harvest.

Platelet-rich-plasmapheresis for minimising peri-operative allogeneic blood transfusion.

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Carless, Paul A; Rubens, Fraser D; Anthony, Danielle M; O'Connell, Dianne; Henry, David A

2011-03-16

Concerns regarding the safety of transfused blood have generated considerable enthusiasm for the use of technologies intended to reduce the use of allogeneic blood (blood from an unrelated donor). Platelet-rich plasmapheresis (PRP) offers an alternative approach to blood conservation. To examine the evidence for the efficacy of PRP in reducing peri-operative allogeneic red blood cell (RBC) transfusion, and the evidence for any effect on clinical outcomes such as mortality and re-operation rates. We identified studies by searching MEDLINE (1950 to 2009), EMBASE (1980 to 2009), The Cochrane Library (Issue 1, 2009), the Internet (to March 2009) and the reference lists of published articles, reports, and reviews. Controlled parallel group trials in which adult patients, scheduled for non-urgent surgery, were randomised to PRP, or to a control group which did not receive the intervention. Primary outcomes measured were: the number of patients exposed to allogeneic RBC transfusion, and the amount of RBC transfused. Other outcomes measured were: the number of patients exposed to allogeneic platelet transfusions, fresh frozen plasma, and cryoprecipitate, blood loss, re-operation for bleeding, post-operative complications (thrombosis), mortality, and length of hospital stay. Treatment effects were pooled using a random-effects model. Trial quality was assessed using criteria proposed by Schulz et al (Schulz 1995). Twenty-two trials of PRP were identified that reported data for the number of patients exposed to allogeneic RBC transfusion. These trials evaluated a total of 1589 patients. The relative risk (RR) of exposure to allogeneic blood transfusion in those patients randomised to PRP was 0.73 (95%CI 0.59 to 0.90), equating to a relative risk reduction (RRR) of 27% and a risk difference (RD) of 19% (95%CI 10% to 29%). However, significant heterogeneity of treatment effect was observed (p transfused (weighted mean difference [WMD] -0.69, 95%CI -1.93 to 0.56 units). Trials

Protocolo para obtenção do plasma rico em plaquetas de cães

OpenAIRE

Ferreira, Vanessa Borges costa [UNESP

2012-01-01

Biotechnology as the platelet-rich plasma (PRP) have been widely used in tissue repair, aiming to accelerate the healing of wounds. The potencial of PRP to reduce the recovery time of injuries depends on the concentration of platelets, its function and their growth factors. The lack of protocols for obtaining PRP in dogs, combined with variations of the same, hinders the use of biotech. The aim of this study was to test three different protocols for obtaining PRP and verify effectiveness in d...

Enhancement of abdominal wall defect repair using allogenic platelet-rich plasma with commercial polyester/cotton fabric (Damour) in a canine model

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ABOUELNASR, Khaled; HAMED, Mohamed; LASHEN, Samah; EL-ADL, Mohamed; ELTAYSH, Rasha; TAGAWA, Michihito

2017-01-01

Platelet-rich plasma (PRP) has an important role in musculoskeletal surgery; however, it has been underutilized for accelerating the healing of abdominal wall defects in veterinary practice. Therefore, the aim of this study was to evaluate the use of commercial polyester/cotton fabric (Damour) as a new composite mesh for the repair of experimentally induced abdominal wall defects in canine models, and to investigate the possible role of PRP for improving such repair and reducing allied complications. For this purpose, abdominal wall defects were created in 24 healthy mongrel dogs and then repaired with mesh alone (control group) or mesh and allogenic PRP (PRP group). Dogs were euthanized after 2 or 4 months for gross examination of implantation site, detection of adhesion score and hernia recurrence. Moreover, tissue samples were collected for histological and gene expression analyses for neovascularization, collagen formation and tissue incorporation. Hernia recurrence was not recorded in PRP-treated dogs that also displayed significantly more neovascularization and less severe adhesion to the underlings (1.08 ± 0.51) in comparison to control group (2.08 ± 0.99). Histological and molecular evaluation confirmed the gross findings that collagen deposition, new vessel formation, and overexpression of angiogenic and myofibroplastic genes (COL1α1, COL3α1, VEGF and TGFβ1) were observed more frequently in the PRP group, at both time points. In conclusion, we found that addition of allogenic PRP to Damour mesh enhanced neovessel formation, and increased tissue deposition and incorporation, with subsequent reduction of peritoneal adhesion and recurrence rate. PMID:28603214

A Comparative Study of Retinal Function in Rabbits after Panretinal Selective Retina Therapy versus Conventional Panretinal Photocoagulation

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Young Gun Park

2015-01-01

Full Text Available Purpose. This study evaluates functional changes in electroretinographic findings after selective retina therapy (SRT compared to panretinal photocoagulation (PRP in rabbits. Methods. The right eyes of 12 Chinchilla rabbits received 200 laser treatment spots. The right eyes of six rabbits received SRT (SRT group, whereas the other six animals were treated using PRP on the right eye (PRP group. The eyes were investigated using full-field ERG 1 hour and 3 weeks after treatment. Histologic exam to assess the tissue response of lasers was performed on 3 weeks. Results. No significant changes in the mean ROD or CR b-wave amplitudes of the SRT lesions were evident, compared to baseline, 1 h after laser treatment (p=0.372 and 0.278, resp.. In addition, the OPs and 30 Hz flickers of the SRT lesions were not significantly altered (p=0.17 and 0.243, resp.. At 3 weeks, similar results were found. Comparing the two groups, the ROD b-wave amplitude was reduced in the PRP and SRT groups to 60.04±4.2% and 92.32±6.43% of baseline (p<0.001. Histologically, there was no visible photoreceptor alterations on week 3. Conclusions. SRT in rabbit eyes induced less functional loss than PRP in both rod-mediated retinal function and cone-mediated retinal function. In addition, SRT irradiated eyes had no functional loss compared to its control.

Dodecylphosphocholine Micelles Induce Amyloid Formation of the PrP(110-136 Peptide via an α-Helical Metastable Conformation.

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Simon Sauvé

Full Text Available A peptide encompassing the conserved hydrophobic region and the first β-strand of the prion protein (PrP(110-136 shown to interact with the surface of dodecylphosphocholine micelles adopts an α-helical conformation that is localized below the head-group layer. This surface-bound peptide has a half-life of one day, and readily initiates the formation of amyloid fibrils. The presence of the latter was confirmed using birefringence microscopy upon Congo red binding and thioflavin T-binding induced fluorescence. The observation of this metastable α-helical conformer provides a unique snapshot of the early steps of the inter-conversion pathway. These findings together with the body of evidence from the prion literature allowed us to propose a mechanism for the conversion of PrPC to amyloid material.

Male circumcision significantly reduces prevalence and load of genital anaerobic bacteria.

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Liu, Cindy M; Hungate, Bruce A; Tobian, Aaron A R; Serwadda, David; Ravel, Jacques; Lester, Richard; Kigozi, Godfrey; Aziz, Maliha; Galiwango, Ronald M; Nalugoda, Fred; Contente-Cuomo, Tania L; Wawer, Maria J; Keim, Paul; Gray, Ronald H; Price, Lance B

2013-04-16

Male circumcision reduces female-to-male HIV transmission. Hypothesized mechanisms for this protective effect include decreased HIV target cell recruitment and activation due to changes in the penis microbiome. We compared the coronal sulcus microbiota of men from a group of uncircumcised controls (n = 77) and from a circumcised intervention group (n = 79) at enrollment and year 1 follow-up in a randomized circumcision trial in Rakai, Uganda. We characterized microbiota using16S rRNA gene-based quantitative PCR (qPCR) and pyrosequencing, log response ratio (LRR), Bayesian classification, nonmetric multidimensional scaling (nMDS), and permutational multivariate analysis of variance (PerMANOVA). At baseline, men in both study arms had comparable coronal sulcus microbiota; however, by year 1, circumcision decreased the total bacterial load and reduced microbiota biodiversity. Specifically, the prevalence and absolute abundance of 12 anaerobic bacterial taxa decreased significantly in the circumcised men. While aerobic bacterial taxa also increased postcircumcision, these gains were minor. The reduction in anaerobes may partly account for the effects of circumcision on reduced HIV acquisition. The bacterial changes identified in this study may play an important role in the HIV risk reduction conferred by male circumcision. Decreasing the load of specific anaerobes could reduce HIV target cell recruitment to the foreskin. Understanding the mechanisms that underlie the benefits of male circumcision could help to identify new intervention strategies for decreasing HIV transmission, applicable to populations with high HIV prevalence where male circumcision is culturally less acceptable.

Efeito do Plasma Rico em Plaquetas na apoptose pós-traumática de condrócitos Effect of Platelet-Rich Plasma on impact-induced chondrocyte apoptosis

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Márcia Uchôa de Rezende

2011-04-01

Full Text Available OBJETIVO: Avaliar se a injeção intra-articular de Plasma rico em plaquetas (PRP pode reduzir a apoptose pós-traumática de condrócitos. MÉTODOS: Foi desenvolvido um estudo experimental duplo-cego com quatro joelhos de coelhos adultos. Após a anestesia, os animais foram submetidos à contusão padronizada dos joelhos. Depois foi injetado 1ml de PRP humano nos dois joelhos esquerdos e 1ml de solução fisiológica (SF nos dois joelhos direitos. Os dois coelhos foram mantidos no mesmo ambiente sob controle de temperatura, de atividades diárias e de alimentação. A eutanásia dos animais ocorreu dez dias após a intervenção e foram realizadas biópsias da cartilagem de cada joelho. As peças foram preparadas para análise em microscopia eletrônica (ME. RESULTADOS: Quatro preparados para ME foram obtidos, cada um correspondendo a um joelho. Os joelhos-PRP apresentaram as taxas de apoptose de 47,62% (50/105 e de 48,36% (59/122, respectivamente. Nos joelhos-SF as taxas de apoptose foram, respectivamente, 56,67% (17/30 e 70,40% (88/125. A diferença do índice de apoptose nos joelhos-PRP (48,02% e nos joelhos-SF (67,74% foi significante (pOBJECTIVE: To evaluate if the injection of intra-articular platelet-rich plasma (PRP can reduce impact-induced chondrocyte apoptosis. METHODS: A double-blind experimental study was developed in four knees of two adult rabbits. Each knee was injured after anesthesia. Subsequently, 1ml PRP was injected in the right knees and 1ml of normal saline (NS in the left knees. The animals were euthanized ten days after the intervention. All cartilage was removed from the 4 knees and prepared for analysis in electron microscopy (EM. RESULTS: Four EM samples were obtained. The PRP-injected knees showed apoptosis rates of 47,62% (50/105 and 48,36% (59/122, respectively. NS-injected knees showed 56.67% (17/30 and 70.40% (88/125 of apoptosis. PRP-injected knees had statistically significant less apoptosis (48.02% than NS

Effect of platelet-rich plasma on fibrocartilage, cartilage, and bone repair in temporomandibular joint.

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Kütük, Nükhet; Baş, Burcu; Soylu, Emrah; Gönen, Zeynep Burçin; Yilmaz, Canay; Balcioğlu, Esra; Özdamar, Saim; Alkan, Alper

2014-02-01

The purpose of the present study was to explore the potential use of platelet-rich-plasma (PRP) in the treatment of temporomandibular joint osteoarthritis (TMJ-OA). Surgical defects were created bilaterally on the condylar fibrocartilage, hyaline cartilage, and bone to induce an osteoarthritic TMJ in rabbits. PRP was applied to the right joints of the rabbits (PRP group), and the left joints received physiologic saline (control group). After 4 weeks, the rabbits were sacrificed for histologic and scanning electron microscopy (SEM) examinations. The data were analyzed statistically. The new bone regeneration was significantly greater in the PRP group (P fibrocartilage and hyaline cartilage was greater in the PRP group, no statistically significant difference was found between the 2 groups. SEM showed better ultrastructural architecture of the collagen fibrils in the PRP group. PRP might enhance the regeneration of bone in TMJ-OA. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Quilting after mastectomy significantly reduces seroma formation

African Journals Online (AJOL)

reduce or prevent seroma formation among mastectomy patients ... of this prospective study is to evaluate the effect of surgical quilting ... Seroma was more common in smokers (p=0.003) and was not decreased by the .... explain its aetiology.

The influence of platelet-rich plasma on the healing of extraction sockets: an explorative randomised clinical trial.

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Alissa, Rami; Esposito, Marco; Horner, Keith; Oliver, Richard

2010-01-01

=0.03), and food stagnation in the operation area (P=0.03). The difference between groups was not statistically significant for patient satisfaction with the treatment (P=0.31). Regarding complications, two dry sockets and one acutely inflamed alveolus occurred in patients of the control group, which determined a borderline statistically significant difference in favour of the PRP group (P=0.06). Soft tissue healing was significantly better in patients treated with PRP (P=0.03). Radiographic evaluation carried out by the two blinded examiners revealed a statistically significant difference (P=0.01) for sockets with dense homogeneous trabecular pattern, a borderline statistically significant difference in the trabecular pattern for bone volume (P=0.06) favouring PRP use, and no significant differences for trabecular separation (P=0.66), trabecular length (P=0.16), trabecular width (P=0.16) and trabecular number (P=0.38). PRP may have some benefits in reducing complications such as alveolar osteitis and improving healing of soft tissue of extraction sockets. There were insufficient data to support the use of PRP to promote bone healing or to enhance the quality of life of patients following tooth extraction, although the sample size was too small to detect statistically significant differences.

Increased infectivity of anchorless mouse scrapie prions in transgenic mice overexpressing human prion protein.

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Race, Brent; Phillips, Katie; Meade-White, Kimberly; Striebel, James; Chesebro, Bruce

2015-06-01

Prion protein (PrP) is found in all mammals, mostly as a glycoprotein anchored to the plasma membrane by a C-terminal glycosylphosphatidylinositol (GPI) linkage. Following prion infection, host protease-sensitive prion protein (PrPsen or PrPC) is converted into an abnormal, disease-associated, protease-resistant form (PrPres). Biochemical characteristics, such as the PrP amino acid sequence, and posttranslational modifications, such as glycosylation and GPI anchoring, can affect the transmissibility of prions as well as the biochemical properties of the PrPres generated. Previous in vivo studies on the effects of GPI anchoring on prion infectivity have not examined cross-species transmission. In this study, we tested the effect of lack of GPI anchoring on a species barrier model using mice expressing human PrP. In this model, anchorless 22L prions derived from tg44 mice were more infectious than 22L prions derived from C57BL/10 mice when tested in tg66 transgenic mice, which expressed wild-type anchored human PrP at 8- to 16-fold above normal. Thus, the lack of the GPI anchor on the PrPres from tg44 mice appeared to reduce the effect of the mouse-human PrP species barrier. In contrast, neither source of prions induced disease in tgRM transgenic mice, which expressed human PrP at 2- to 4-fold above normal. Prion protein (PrP) is found in all mammals, usually attached to cells by an anchor molecule called GPI. Following prion infection, PrP is converted into a disease-associated form (PrPres). While most prion diseases are species specific, this finding is not consistent, and species barriers differ in strength. The amino acid sequence of PrP varies among species, and this variability affects prion species barriers. However, other PrP modifications, including glycosylation and GPI anchoring, may also influence cross-species infectivity. We studied the effect of PrP GPI anchoring using a mouse-to-human species barrier model. Experiments showed that prions produced by

Effect of High-Volume Injection, Platelet-Rich Plasma, and Sham Treatment in Chronic Midportion Achilles Tendinopathy: A Randomized Double-Blinded Prospective Study.

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Boesen, Anders Ploug; Hansen, Rudi; Boesen, Morten Ilum; Malliaras, Peter; Langberg, Henning

2017-07-01

Injection therapies are often considered alongside exercise for chronic midportion Achilles tendinopathy (AT), although evidence of their efficacy is sparse. To determine whether eccentric training in combination with high-volume injection (HVI) or platelet-rich plasma (PRP) injections improves outcomes in AT. Randomized controlled trial; Level of evidence, 1. A total of 60 men (age, 18-59 years) with chronic (>3 months) AT were included and followed for 6 months (n = 57). All participants performed eccentric training combined with either (1) one HVI (steroid, saline, and local anesthetic), (2) four PRP injections each 14 days apart, or (3) placebo (a few drops of saline under the skin). Randomization was stratified for age, function, and symptom severity (Victorian Institute of Sports Assessment-Achilles [VISA-A]). Outcomes included function and symptoms (VISA-A), self-reported tendon pain during activity (visual analog pain scale [VAS]), tendon thickness and intratendinous vascularity (ultrasonographic imaging and Doppler signal), and muscle function (heel-rise test). Outcomes were assessed at baseline and at 6, 12, and 24 weeks of follow-up. VISA-A scores improved in all groups at all time points ( P Tendon thickness showed a significant decrease only in HVI and PRP groups during the intervention, and this was greater in the HVI versus PRP and placebo groups at 6 and 12 weeks ( P eccentric training in chronic AT seems more effective in reducing pain, improving activity level, and reducing tendon thickness and intratendinous vascularity than eccentric training alone. HVI may be more effective in improving outcomes of chronic AT than PRP in the short term. Registration: NCT02417987 ( ClinicalTrials.gov identifier).

Platelet-Rich Plasma Preparation Types Show Impact on Chondrogenic Differentiation, Migration, and Proliferation of Human Subchondral Mesenchymal Progenitor Cells.

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Kreuz, Peter Cornelius; Krüger, Jan Philipp; Metzlaff, Sebastian; Freymann, Undine; Endres, Michaela; Pruss, Axel; Petersen, Wolf; Kaps, Christian

2015-10-01

To evaluate the chondrogenic potential of platelet concentrates on human subchondral mesenchymal progenitor cells (MPCs) as assessed by histomorphometric analysis of proteoglycans and type II collagen. Furthermore, the migratory and proliferative effect of platelet concentrates were assessed. Platelet-rich plasma (PRP) was prepared using preparation kits (Autologous Conditioned Plasma [ACP] Kit [Arthrex, Naples, FL]; Regen ACR-C Kit [Regen Lab, Le Mont-Sur-Lausanne, Switzerland]; and Dr.PRP Kit [Rmedica, Seoul, Republic of Korea]) by apheresis (PRP-A) and by centrifugation (PRP-C). In contrast to clinical application, freeze-and-thaw cycles were subsequently performed to activate platelets and to prevent medium coagulation by residual fibrinogen in vitro. MPCs were harvested from the cortico-spongious bone of femoral heads. Chondrogenic differentiation of MPCs was induced in high-density pellet cultures and evaluated by histochemical staining of typical cartilage matrix components. Migration of MPCs was assessed using a chemotaxis assay, and proliferation activity was measured by DNA content. MPCs cultured in the presence of 5% ACP, Regen, or Dr.PRP formed fibrous tissue, whereas MPCs stimulated with 5% PRP-A or PRP-C developed compact and dense cartilaginous tissue rich in type II collagen and proteoglycans. All platelet concentrates significantly (ACP, P = .00041; Regen, P = .00029; Dr.PRP, P = .00051; PRP-A, P platelet concentrates but one (Dr.PRP, P = .63) showed a proliferative effect on MPCs, as shown by significant increases (ACP, P = .027; Regen, P = .0029; PRP-A, P = .00021; and PRP-C, P = .00069) in DNA content. Platelet concentrates obtained by different preparation methods exhibit different potentials to stimulate chondrogenic differentiation, migration, and proliferation of MPCs. Platelet concentrates obtained by commercially available preparation kits failed to induce chondrogenic differentiation of MPCs, whereas highly standardized PRP

The effect of corticosteroid versus platelet-rich plasma injection therapies for the management of lateral epicondylitis: A systematic review

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Ben-Nafa, Walid; Munro, Wendy

2018-01-01

Introduction: Lateral epicondylitis is a common musculoskeletal disorder of the upper limb. Corticosteroid injection has been widely used as a major mode of treatment. However, better understanding of the pathophysiology of the disease led to a major change in treating the disease, with new options including platelet-rich plasma (PRP) are currently used. Objectives/research aim: To systematically evaluate the effect of corticosteroid versus PRP injections for the treatment of LE. Hypothesis: PRP injections provide longer-term therapeutic effect and less rate of complications compared to corticosteroid injection. Level of evidence: Level 2 evidence (4 included studies are of level 1 evidence, 1 study of level 2 evidence). Design: Systematic Review (according to PRISMA guidelines). Methods: Eleven databases used to search for relevant primary studies comparing the effects of corticosteroid and PRP injections for the treatment of LE. Quality appraisal of studies performed using Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0, CASP Randomised Controlled Trial Checklist, and SIGN Methodology Checklist 2. Results: 732 papers were identified. Five randomised controlled trials (250 Patients) met the inclusion criteria. Clinical findings: Corticosteroid injections provided rapid symptomatic improvement with maximum effect at 6/8/8 weeks before symptoms recurrence, whereas PRP showed slower ongoing improvements up to 24/52/104 weeks(3 studies). Corticosteroid showed more rapid symptomatic improvement of symptoms compared to PRP up to the study end-point of 3 months(1 study). Comparable therapeutic effects of corticosteroid and PRP were observed at 6 weeks(1 study). Ultrasonographic Findings: (1) Doppler activity decreased more significantly in patients who received corticosteroid compared to PRP. (2) Reduced tendon thickness and more patients with cortical erosion noted in corticosteroid group whereas increased tendon thickness and less number of

Defibrillator charging before rhythm analysis significantly reduces hands-off time during resuscitation

DEFF Research Database (Denmark)

Hansen, L. K.; Folkestad, L.; Brabrand, M.

2013-01-01

BACKGROUND: Our objective was to reduce hands-off time during cardiopulmonary resuscitation as increased hands-off time leads to higher mortality. METHODS: The European Resuscitation Council (ERC) 2005 and ERC 2010 guidelines were compared with an alternative sequence (ALT). Pulseless ventricular...... physicians were included. All had prior experience in advanced life support. Chest compressions were shorter interrupted using ALT (mean, 6.7 vs 13.0 seconds). Analyzing data for ventricular tachycardia scenarios only, hands-off time was shorter using ALT (mean, 7.1 vs 18.2 seconds). In ERC 2010 vs ALT, 12...... physicians were included. Two physicians had not prior experience in advanced life support. Hands-off time was reduced using ALT (mean, 3.9 vs 5.6 seconds). Looking solely at ventricular tachycardia scenarios, hands-off time was shortened using ALT (mean, 4.5 vs 7.6 seconds). No significant reduction...

A high-throughput microfluidic approach for 1000-fold leukocyte reduction of platelet-rich plasma

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Xia, Hui; Strachan, Briony C.; Gifford, Sean C.; Shevkoplyas, Sergey S.

2016-10-01

Leukocyte reduction of donated blood products substantially reduces the risk of a number of transfusion-related complications. Current ‘leukoreduction’ filters operate by trapping leukocytes within specialized filtration material, while allowing desired blood components to pass through. However, the continuous release of inflammatory cytokines from the retained leukocytes, as well as the potential for platelet activation and clogging, are significant drawbacks of conventional ‘dead end’ filtration. To address these limitations, here we demonstrate our newly-developed ‘controlled incremental filtration’ (CIF) approach to perform high-throughput microfluidic removal of leukocytes from platelet-rich plasma (PRP) in a continuous flow regime. Leukocytes are separated from platelets within the PRP by progressively syphoning clarified PRP away from the concentrated leukocyte flowstream. Filtrate PRP collected from an optimally-designed CIF device typically showed a ~1000-fold (i.e. 99.9%) reduction in leukocyte concentration, while recovering >80% of the original platelets, at volumetric throughputs of ~1 mL/min. These results suggest that the CIF approach will enable users in many fields to now apply the advantages of microfluidic devices to particle separation, even for applications requiring macroscale flowrates.

Effects of washed platelets vs platelet-rich plasma on the proliferation and mineralization of rat dental pulp cells.

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Zhang, L; Xie, Y H; Lin, B R

2015-08-14

We examined the effects of washed platelets (WPLTs) and platelet-rich plasma (PRP) on the proliferation and mineralization of rat dental pulp cells. Rat dental pulp cells were separated, cultured, and identified. Medium containing 1, 10, 100, or 500 mL/L PRP or WPLTs was added to 4th generation cells. The MTS method was used to determine cell proliferation. Alizarin red staining was used to observe the formation of mineralized nodules after cell mineralization and induction for 10 and 20 days under different culture conditions, and the areas of the mineralized nodules formed 20 days after induction were computed. The addition of 1, 10, and 100 mL/L WPLTs or PRP significantly promoted rat dental pulp cell proliferation (P 0.05). Under the same concentrations, no significant differences on cell proliferation were observed between WPLT and PRP treatments (P > 0.05 in all groups). After 10 days mineralization and culture, the 100 and 500 mL/L WPLT and PRP group positive nodule rates were significantly higher than those of the low concentration and the control groups (P < 0.05). After 20 days, the areas of the mineralized nodules formed in the 100 and 500 mL/L WPLT and PRP groups were significantly larger than those in the control group (P < 0.05). These results demonstrate that both WPLTs and PRP are equally able to significantly promote the proliferation and calcification of rat dental pulp cells under a certain range of concentrations.

The effect of platelet-rich plasma on clinical outcomes in lateral epicondylitis.

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Ahmad, Zafar; Brooks, Roger; Kang, Sertaz-Niel; Weaver, Holly; Nunney, Ian; Tytherleigh-Strong, Graham; Rushton, Neil

2013-11-01

To evaluate the evidence for application of platelet-rich plasma (PRP) in lateral epicondylitis. We carried out a systematic review of the current evidence on the effects of PRP in lateral epicondylitis on clinical outcomes. We performed a comprehensive search of the PubMed, Medline, Cochrane, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Embase databases using various combinations of the commercial names of each PRP preparation and "lateral epicondylitis" (with its associated terms), looking specifically at human studies. Data validity was assessed and collected on clinical outcome. Nine studies met the inclusion criteria, of which 5 were randomized controlled trials. Two cohort studies showed that PRP improved clinical satisfaction scores. One case-control study showed that PRP yielded a significantly greater improvement in symptoms compared with bupivacaine. Two randomized controlled trials compared the effect of injections of PRP and blood. Only 1 of the studies noted a significant difference at the 6-week time point. Three randomized controlled trials compared corticosteroids with PRP. Two of the smaller trials, which had follow-up periods of 6 weeks and 3 months, showed no significant difference between treatment groups. The largest randomized controlled trial found that PRP had significant benefit compared with corticosteroids with regard to pain and Disabilities of the Arm, Shoulder and Hand scores at 1- and 2-year time points. This review highlights the limited but evolving evidence for the use of PRP in lateral epicondylitis; however, further research is required to understand the concentration and preparation that facilitate the best clinical outcome. Characterizing the timing of the intervention would optimize the health economics behind the decision to treat for the patient and health care provider. Level III, systematic review of Level I to III studies. Copyright © 2013 Arthroscopy Association of North America. Published by

Sodium-Reduced Meat and Poultry Products Contain a Significant Amount of Potassium from Food Additives.

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Parpia, Arti Sharma; Goldstein, Marc B; Arcand, JoAnne; Cho, France; L'Abbé, Mary R; Darling, Pauline B

2018-05-01

counterparts (mean difference [95% CI]: 486 [334-638]; Padditives appearing on the product label ingredient list, did not significantly differ between the two groups. Potassium additives are frequently added to sodium-reduced MPPs in amounts that significantly contribute to the potassium load for patients with impaired renal handling of potassium caused by chronic kidney disease and certain medications. Patients requiring potassium restriction should be counseled to be cautious regarding the potassium content of sodium-reduced MPPs and encouraged to make food choices accordingly. Copyright © 2018 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Membrane Disruption Mechanism of a Prion Peptide (106-126) Investigated by Atomic Force Microscopy, Raman and Electron Paramagnetic Resonance Spectroscopy.

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Pan, Jianjun; Sahoo, Prasana K; Dalzini, Annalisa; Hayati, Zahra; Aryal, Chinta M; Teng, Peng; Cai, Jianfeng; Rodriguez Gutierrez, Humberto; Song, Likai

2017-05-18

A fragment of the human prion protein spanning residues 106-126 (PrP106-126) recapitulates many essential properties of the disease-causing protein such as amyloidogenicity and cytotoxicity. PrP106-126 has an amphipathic characteristic that resembles many antimicrobial peptides (AMPs). Therefore, the toxic effect of PrP106-126 could arise from a direct association of monomeric peptides with the membrane matrix. Several experimental approaches are employed to scrutinize the impacts of monomeric PrP106-126 on model lipid membranes. Porous defects in planar bilayers are observed by using solution atomic force microscopy. Adding cholesterol does not impede defect formation. A force spectroscopy experiment shows that PrP106-126 reduces Young's modulus of planar lipid bilayers. We use Raman microspectroscopy to study the effect of PrP106-126 on lipid atomic vibrational dynamics. For phosphatidylcholine lipids, PrP106-126 disorders the intrachain conformation, while the interchain interaction is not altered; for phosphatidylethanolamine lipids, PrP106-126 increases the interchain interaction, while the intrachain conformational order remains similar. We explain the observed differences by considering different modes of peptide insertion. Finally, electron paramagnetic resonance spectroscopy shows that PrP106-126 progressively decreases the orientational order of lipid acyl chains in magnetically aligned bicelles. Together, our experimental data support the proposition that monomeric PrP106-126 can disrupt lipid membranes by using similar mechanisms found in AMPs.

Developing a New HSR Switching Node (SwitchBox for Improving Traffic Performance in HSR Networks

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Nguyen Xuan Tien

2016-01-01

Full Text Available High availability is crucial for industrial Ethernet networks as well as Ethernet-based control systems such as automation networks and substation automation systems (SAS. Since standard Ethernet does not support fault tolerance capability, the high availability of Ethernet networks can be increased by using redundancy protocols. Various redundancy protocols for Ethernet networks have been developed and standardized, such as rapid spanning tree protocol (RSTP, media redundancy protocol (MRP, parallel redundancy protocol (PRP, high-availability seamless redundancy (HSR and others. RSTP and MRP have switchover delay drawbacks. PRP provides zero recovery time, but requires a duplicate network infrastructure. HSR operation is similar to PRP, but HSR uses a single network. However, the standard HSR protocol is mainly applied to ring-based topologies and generates excessively unnecessary redundant traffic in the network. In this paper, we develop a new switching node for the HSR protocol, called SwitchBox, which is used in HSR networks in order to support any network topology and significantly reduce redundant network traffic, including unicast, multicast and broadcast traffic, compared with standard HSR. By using the SwitchBox, HSR not only provides seamless communications with zero switchover time in case of failure, but it is also easily applied to any network topology and significantly reduces unnecessary redundant traffic in HSR networks.

Basic characteristics of plasma rich in growth factors (PRGF): blood cell components and biological effects.

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Nishiyama, Kazuhiko; Okudera, Toshimitsu; Watanabe, Taisuke; Isobe, Kazushige; Suzuki, Masashi; Masuki, Hideo; Okudera, Hajime; Uematsu, Kohya; Nakata, Koh; Kawase, Tomoyuki

2016-11-01

Platelet-rich plasma (PRP) is widely used in regenerative medicine because of its high concentrations of various growth factors and platelets. However, the distribution of blood cell components has not been investigated in either PRP or other PRP derivatives. In this study, we focused on plasma rich in growth factors (PRGF), a PRP derivative, and analyzed the distributions of platelets and white blood cells (WBCs). Peripheral blood samples were collected from healthy volunteers ( N  = 14) and centrifuged to prepare PRGF and PRP. Blood cells were counted using an automated hematology analyzer. The effects of PRP and PRGF preparations on cell proliferation were determined using human periosteal cells. In the PRGF preparations, both red blood cells and WBCs were almost completely eliminated, and platelets were concentrated by 2.84-fold, whereas in the PRP preparations, both platelets and WBCs were similarly concentrated by 8.79- and 5.51-fold, respectively. Platelet counts in the PRGF preparations were positively correlated with platelet counts in the whole blood samples, while the platelet concentration rate was negatively correlated with red blood cell counts in the whole blood samples. In contrast, platelet counts and concentration rates in the PRP preparations were significantly influenced by WBC counts in whole blood samples. The PRP preparations, but not the PRGF preparations, significantly suppressed cell growth at higher doses in vitro. Therefore, these results suggest that PRGF preparations can clearly be distinguished from PRP preparations by both inclusion of WBCs and dose-dependent stimulation of periosteal cell proliferation in vitro.

Autologous Pure Platelet-Rich Plasma Dermal Injections for Facial Skin Rejuvenation: Clinical, Instrumental, and Flow Cytometry Assessment.

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Cameli, Norma; Mariano, Maria; Cordone, Iole; Abril, Elva; Masi, Serena; Foddai, Maria Laura

2017-06-01

Platelet-rich plasma (PRP) is an emerging treatment in dermatology recently proposed for skin rejuvenation. To evaluate the efficacy and safety of autologous pure PRP dermal injections on facial skin rejuvenation, investigating the cellularity of PRP samples. Twelve patients underwent 3 sessions of PRP injection at 1-month intervals. The clinical and instrumental outcomes were evaluated before (T0) and 1 month (T1) after the end of treatment by means of transepidermal water loss, corneometry, Cutometer, Visioscan, and Visioface. A flow cytometry characterization on PRP and peripheral blood (PB) samples was performed. Clinical and patient evaluation showed improvement of skin texture. Skin gross elasticity, skin smoothness parameters, skin barrier function, and capacitance were significantly improved. No difference between PRP and PB lymphocyte immunological asset was observed. A leukocyte population (mainly CD3) and neutrophils depletion were documented in all the PRP samples. This instrumental study demonstrated that PRP poor in leukocytes can provide objective improvements in skin biostimulation. Flow cytometry showed no variability among the PRP samples using a reproducible separation system and a low content in proinflammatory cells. Although a pilot study, it may be helpful for future investigations on PRP cellularity.

Clinical impact of platelet rich plasma in treatment of gingival recessions

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Aleksić Zoran

2008-01-01

Full Text Available Introduction Root coverage supported with complete regeneration of lost periodontal tissues represents the ultimate goal of gingival recession treatment. Objective This study was designed to evaluate clinical effectiveness of platelet rich plasma gel (PRP with connective tissue graft (CTG in the treatment of gingival recession. METHOD 15 gingival recessions Miller class I or II were treated with CTG and PRP (group PRP. Connective tissue graft was harvested from the premolar region using trap door technique. After elevation of the flap, the regional bone and root surface were smeared with activated PRP gel. CTG was also irrigated with PRP gel before placement over the exposed root surface and local bone. Fixed CTG was covered with a coronally advanced flap. The same number of gingival recessions were treated with CTG in combination with the coronally advanced flap with no PRP gel (group TVT. Clinical recordings included recession depth (RD, probing depth (PD, clinical attachment level (CAL and keratinized tissue width (KT before and 1 year after mucogingival surgical treatment. Results Mean value of RD was significantly decreased from 4.93±0.86 mm to 0.60±0.37 (p<0.01 with CTG and PRP and from 4.76±0.74 mm to 0.63±0.29 mm (p<0.01 in CTG group. This difference was not statistically significant. Results of the keratinized tissue width showed significant increase from 0.88± 0.30 mm presurgery to 3.78±0.49 mm (p<0.01 six months after treatment in PRP group and from 0.90±0.34 mm to 3.15±0.41 in TVT group (p<0.01. This difference was statistically significant (p>0.05. No statistically significant differences were observed between treatment groups in CAL and PD. Conclusion Clinical results validate both procedures as effective and highly predictable surgical techniques in solving gingival recession problem. Histological evaluation may confirm advantage of PRP use related to regeneration of periodontal tissues. .

A chimpanzee recognizes synthetic speech with significantly reduced acoustic cues to phonetic content.

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Heimbauer, Lisa A; Beran, Michael J; Owren, Michael J

2011-07-26

A long-standing debate concerns whether humans are specialized for speech perception, which some researchers argue is demonstrated by the ability to understand synthetic speech with significantly reduced acoustic cues to phonetic content. We tested a chimpanzee (Pan troglodytes) that recognizes 128 spoken words, asking whether she could understand such speech. Three experiments presented 48 individual words, with the animal selecting a corresponding visuographic symbol from among four alternatives. Experiment 1 tested spectrally reduced, noise-vocoded (NV) synthesis, originally developed to simulate input received by human cochlear-implant users. Experiment 2 tested "impossibly unspeechlike" sine-wave (SW) synthesis, which reduces speech to just three moving tones. Although receiving only intermittent and noncontingent reward, the chimpanzee performed well above chance level, including when hearing synthetic versions for the first time. Recognition of SW words was least accurate but improved in experiment 3 when natural words in the same session were rewarded. The chimpanzee was more accurate with NV than SW versions, as were 32 human participants hearing these items. The chimpanzee's ability to spontaneously recognize acoustically reduced synthetic words suggests that experience rather than specialization is critical for speech-perception capabilities that some have suggested are uniquely human. Copyright © 2011 Elsevier Ltd. All rights reserved.

Leukocyte Inclusion within a Platelet Rich Plasma-Derived Fibrin Scaffold Stimulates a More Pro-Inflammatory Environment and Alters Fibrin Properties

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Anitua, Eduardo; Zalduendo, Mar; Troya, María; Padilla, Sabino; Orive, Gorka

2015-01-01

One of the main differences among platelet-rich plasma (PRP) products is the inclusion of leukocytes that may affect the biological efficacy of these autologous preparations. The purpose of this study was to evaluate whether the addition of leukocytes modified the morphological, biomechanical and biological properties of PRP under normal and inflammatory conditions. The release of pro-inflammatory cytokines from plasma rich in growth factors (PRGF) and leukocyte-platelet rich plasma (L-PRP) scaffolds was determined by enzyme-linked immunosorbent assay (ELISA) and was significantly increased under an inflammatory condition when leukocytes were included in the PRP. Fibroblasts and osteoblasts treated with L-PRP, under an inflammatory situation, underwent a greater activation of NFĸB pathway, proliferated significantly less and secreted a higher concentration of pro-inflammatory cytokines. These cellular events were assessed through Western blot and fluorimetric and ELISA methods, respectively. Therefore, the inclusion of leukocytes induced significantly higher pro-inflammatory conditions. PMID:25823008

Leukocyte inclusion within a platelet rich plasma-derived fibrin scaffold stimulates a more pro-inflammatory environment and alters fibrin properties.

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Eduardo Anitua

Full Text Available One of the main differences among platelet-rich plasma (PRP products is the inclusion of leukocytes that may affect the biological efficacy of these autologous preparations. The purpose of this study was to evaluate whether the addition of leukocytes modified the morphological, biomechanical and biological properties of PRP under normal and inflammatory conditions. The release of pro-inflammatory cytokines from plasma rich in growth factors (PRGF and leukocyte-platelet rich plasma (L-PRP scaffolds was determined by enzyme-linked immunosorbent assay (ELISA and was significantly increased under an inflammatory condition when leukocytes were included in the PRP. Fibroblasts and osteoblasts treated with L-PRP, under an inflammatory situation, underwent a greater activation of NFĸB pathway, proliferated significantly less and secreted a higher concentration of pro-inflammatory cytokines. These cellular events were assessed through Western blot and fluorimetric and ELISA methods, respectively. Therefore, the inclusion of leukocytes induced significantly higher pro-inflammatory conditions.

Intensity-modulated radiotherapy significantly reduces xerostomia compared with conventional radiotherapy

International Nuclear Information System (INIS)

Braam, Petra M.; Terhaard, Chris H.J. M.D.; Roesink, Judith M.; Raaijmakers, Cornelis P.J.

2006-01-01

Purpose: Xerostomia is a severe complication after radiotherapy for oropharyngeal cancer, as the salivary glands are in close proximity with the primary tumor. Intensity-modulated radiotherapy (IMRT) offers theoretical advantages for normal tissue sparing. A Phase II study was conducted to determine the value of IMRT for salivary output preservation compared with conventional radiotherapy (CRT). Methods and Materials: A total of 56 patients with oropharyngeal cancer were prospectively evaluated. Of these, 30 patients were treated with IMRT and 26 with CRT. Stimulated parotid salivary flow was measured before, 6 weeks, and 6 months after treatment. A complication was defined as a stimulated parotid flow rate <25% of the preradiotherapy flow rate. Results: The mean dose to the parotid glands was 48.1 Gy (SD 14 Gy) for CRT and 33.7 Gy (SD 10 Gy) for IMRT (p < 0.005). The mean parotid flow ratio 6 weeks and 6 months after treatment was respectively 41% and 64% for IMRT and respectively 11% and 18% for CRT. As a result, 6 weeks after treatment, the number of parotid flow complications was significantly lower after IMRT (55%) than after CRT (87%) (p = 0.002). The number of complications 6 months after treatment was 56% for IMRT and 81% for CRT (p = 0.04). Conclusions: IMRT significantly reduces the number of parotid flow complications for patients with oropharyngeal cancer

Peroxiredoxin 6 promotes upregulation of the prion protein (PrP in neuronal cells of prion-infected mice

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Wagner Wibke

2012-12-01

Full Text Available Abstract Background It has been widely established that the conversion of the cellular prion protein (PrPC into its abnormal isoform (PrPSc is responsible for the development of transmissible spongiform encephalopathies (TSEs. However, the knowledge of the detailed molecular mechanisms and direct functional consequences within the cell is rare. In this study, we aimed at the identification of deregulated proteins which might be involved in prion pathogenesis. Findings Apolipoprotein E and peroxiredoxin 6 (PRDX6 were identified as upregulated proteins in brains of scrapie-infected mice and cultured neuronal cell lines. Downregulation of PrP gene expression using specific siRNA did not result in a decrease of PRDX6 amounts. Interestingly, selective siRNA targeting PRDX6 or overexpression of PRDX6 controlled PrPC and PrPSc protein amounts in neuronal cells. Conclusions Besides its possible function as a novel marker protein in the diagnosis of TSEs, PDRX6 represents an attractive target molecule in putative pharmacological intervention strategies in the future.

Prion Protein Devoid of the Octapeptide Repeat Region Delays Bovine Spongiform Encephalopathy Pathogenesis in Mice.

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Hara, Hideyuki; Miyata, Hironori; Das, Nandita Rani; Chida, Junji; Yoshimochi, Tatenobu; Uchiyama, Keiji; Watanabe, Hitomi; Kondoh, Gen; Yokoyama, Takashi; Sakaguchi, Suehiro

2018-01-01

Conformational conversion of the cellular isoform of prion protein, PrP C , into the abnormally folded, amyloidogenic isoform, PrP Sc , is a key pathogenic event in prion diseases, including Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy (BSE) in animals. We previously reported that the octapeptide repeat (OR) region could be dispensable for converting PrP C into PrP Sc after infection with RML prions. We demonstrated that mice transgenically expressing mouse PrP with deletion of the OR region on the PrP knockout background, designated Tg(PrPΔOR)/ Prnp 0 / 0 mice, did not show reduced susceptibility to RML scrapie prions, with abundant accumulation of PrP Sc ΔOR in their brains. We show here that Tg(PrPΔOR)/ Prnp 0 / 0 mice were highly resistant to BSE prions, developing the disease with markedly elongated incubation times after infection with BSE prions. The conversion of PrPΔOR into PrP Sc ΔOR was markedly delayed in their brains. These results suggest that the OR region may have a crucial role in the conversion of PrP C into PrP Sc after infection with BSE prions. However, Tg(PrPΔOR)/ Prnp 0 / 0 mice remained susceptible to RML and 22L scrapie prions, developing the disease without elongated incubation times after infection with RML and 22L prions. PrP Sc ΔOR accumulated only slightly less in the brains of RML- or 22L-infected Tg(PrPΔOR)/ Prnp 0 / 0 mice than PrP Sc in control wild-type mice. Taken together, these results indicate that the OR region of PrP C could play a differential role in the pathogenesis of BSE prions and RML or 22L scrapie prions. IMPORTANCE Structure-function relationship studies of PrP C conformational conversion into PrP Sc are worthwhile to understand the mechanism of the conversion of PrP C into PrP Sc We show here that, by inoculating Tg(PrPΔOR)/ Prnp 0 / 0 mice with the three different strains of RML, 22L, and BSE prions, the OR region could play a differential role in the conversion of

Antigenic characterization of an abnormal isoform of prion protein using a new diverse panel of monoclonal antibodies

International Nuclear Information System (INIS)

Kim, Chan-Lan; Umetani, Atsushi; Matsui, Toshio; Ishiguro, Naotaka; Shinagawa, Morikazu; Horiuchi, Motohiro

2004-01-01

We established a panel of monoclonal antibodies (mAbs) against prion protein (PrP) by immunizing PrP gene-ablated mice with the pathogenic isoform of prion protein (PrP Sc ) or recombinant prion protein (rPrP). The mAbs could be divided into at least 10 groups by fine epitope analyses using mutant rPrPs and pepspot analysis. Seven linear epitopes, lying within residues 56-90, 119-127, 137-143, 143-149, 147-151, 163-169, and 219-229, were defined by seven groups of mAbs, although the remaining three groups of mAbs recognized discontinuous epitopes. We attempted to examine whether any of these epitopes are located on the accessible surface of PrP Sc . However, no mAbs reacted with protease-treated PrP Sc purified from scrapie-affected mice, even when PrP Sc was dispersed into a detergent-lipid protein complex, to reduce the size of PrP Sc aggregates. In contrast, denaturation of PrP Sc by guanidine hydrochloride efficiently exposed all of the epitopes. This suggests that any epitope recognized by this panel of mAbs is buried within the PrP Sc aggregates. Alternatively, if the corresponding region(s) are on the surface of PrP Sc , the region(s) may be folded into conformations to which the mAbs cannot bind. The reactivity of a panel of mAb also showed that the state of PrP Sc aggregation influenced the denaturation process, and the sensitivity to denaturation appeared to vary between epitopes. Our results demonstrate that this new panel of well-characterized mAbs will be valuable for studying the biochemistry and biophysics of PrP molecules as well as for the immuno-diagnosis of prion diseases

Systematic review of the use of platelet-rich plasma in aesthetic dermatology.

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Leo, Michael S; Kumar, Alur S; Kirit, Raj; Konathan, Rajyalaxmi; Sivamani, Raja K

2015-12-01

Platelet-rich plasma (PRP) is a highly concentrated autologous solution of plasma prepared from a patient's own blood. PRP contains platelets that are purported to release numerous growth factors that may be valuable in numerous dermatologic applications. Here, we review systematically the clinical cosmetic applications of PRP including: androgenetic alopecia, scar revision, acne scars, skin rejuvenation, dermal augmentation, and striae distensae to understand the potential and best practices for PRP use. A systematic search was conducted on three databases: Pubmed, Embase, and Web of Science. Publications were included if they were in English, investigated the clinical applications of PRP in aesthetic dermatology and reported clinical results either as case reports or clinical studies. There were a total of 22 manuscripts that fulfilled these criteria. Four evaluated hair-related applications, eight evaluated the treatment of scars and postprocedure recovery, eight evaluated skin rejuvenation and dermal augmentation, and two evaluated treatment of striae distensae. PRP is a relatively new treatment modality with studies suggesting its utility in aesthetic dermatology. The combination of PRP with other therapies is particularly interesting. Future studies should include controls, including incorporation of split-face comparisons, to reduce intersubject variability. © 2015 Wiley Periodicals, Inc.

The effectiveness of platelet-rich plasma on the skin wound healing process: A comparative experimental study in sheep

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Daikh Badis

2018-06-01

Full Text Available Aim: The therapeutic evaluation of the biological effect of platelet-rich plasma (PRP used as a surgical adjunct to maintain the inflammatory process and to potentiate tissue healing, make the subject of recent research in regenerative medicine. This study was designed to evaluate the healing activity of PRP by its topical application on the skin experimentally injured in a sheep model. Materials and Methods: The study was conducted on 9 adult and clinically healthy males sheep. PRP was obtained by a protocol of double centrifugation of whole blood from each animal. After sterile skin preparation, full-thickness excisional wounds (20 mm x 20 mm were created on the back of each animal. The animals were randomly divided into three equal groups of three sheep for each. In Group I, the wounds were treated with PRP, in Group II; wounds were treated with Asiaticoside; in Group III, wounds were treated with saline solution. The different treatments were administered topically every 3 days. Morphometric measurements of the contraction surface of the wounds and histopathological biopsies were carried out at the 3rd, 7th, 14th, 21st, and 28th days of healing. Results: The results of the morphometric data obtained revealed that it was significant differences recorded at the 7th and 14th day of healing in favor for animals of Group I. Semi-quantitative histopathological evaluation showed that PRP reduces inflammation during 3 first days post-surgical and promotes epithelialization in 3 weeks of healing. Conclusion: We concluded that topical administration of PRP obtained by double centrifugation protocol could potentially improve the skin healing process in sheep.

PrPC displays an essential protective role from oxidative stress in an astrocyte cell line derived from PrPC knockout mice

International Nuclear Information System (INIS)

Bertuchi, Fernanda R.; Bourgeon, Dominique M.G.; Landemberger, Michele C.; Martins, Vilma R.; Cerchiaro, Giselle

2012-01-01

Highlights: ► PrP C in solution acts as a radical scavenger. ► PrP C reduces hydrogen peroxide toxicity in astrocytes. ► Increase in ROS disrupted the cell cycle in the PrP C -knockout astrocytes. ► PrP C prevents the cell death independently of an SOD-like activity. -- Abstract: The PrP C protein, which is especially present in the cellular membrane of nervous system cells, has been extensively studied for its controversial antioxidant activity. In this study, we elucidated the free radical scavenger activity of purified murine PrP C in solution and its participation as a cell protector in astrocytes that were subjected to treatment with an oxidant. In vitro and using an EPR spin-trapping technique, we observed that PrP C decreased the oxidation of the DMPO trap in a Fenton reaction system (Cu 2+ /ascorbate/H 2 O 2 ), which was demonstrated by approximately 70% less DMPO/OH · . In cultured PrP C -knockout astrocytes from mice, the absence of PrP C caused an increase in intracellular ROS (reactive oxygen species) generation during the first 3 h of H 2 O 2 treatment. This rapid increase in ROS disrupted the cell cycle in the PrP C -knockout astrocytes, which increased the population of cells in the sub-G1 phase when compared with cultured wild-type astrocytes. We conclude that PrP C in solution acts as a radical scavenger, and in astrocytes, it is essential for protection from oxidative stress caused by an external chemical agent, which is a likely condition in human neurodegenerative CNS disorders and pathological conditions such as ischemia.

Plasminogen stimulates propagation of protease-resistant prion protein in vitro.

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Mays, Charles E; Ryou, Chongsuk

2010-12-01

To clarify the role of plasminogen as a cofactor for prion propagation, we conducted functional assays using a cell-free prion protein (PrP) conversion assay termed protein misfolding cyclic amplification (PMCA) and prion-infected cell lines. Here, we report that plasminogen stimulates propagation of the protease-resistant scrapie PrP (PrP(Sc)). Compared to control PMCA conducted without plasminogen, addition of plasminogen in PMCA using wild-type brain material significantly increased PrP conversion, with an EC(50) = ∼56 nM. PrP conversion in PMCA was substantially less efficient with plasminogen-deficient brain material than with wild-type material. The activity stimulating PrP conversion was specific for plasminogen and conserved in its kringle domains. Such activity was abrogated by modification of plasminogen structure and interference of PrP-plasminogen interaction. Kinetic analysis of PrP(Sc) generation demonstrated that the presence of plasminogen in PMCA enhanced the PrP(Sc) production rate to ∼0.97 U/μl/h and reduced turnover time to ∼1 h compared to those (∼0.4 U/μl/h and ∼2.5 h) obtained without supplementation. Furthermore, as observed in PMCA, plasminogen and kringles promoted PrP(Sc) propagation in ScN2a and Elk 21(+) cells. Our results demonstrate that plasminogen functions in stimulating conversion processes and represents the first cellular protein cofactor that enhances the hypothetical mechanism of prion propagation.

Polysaccharides Extracted from Rhizoma Pleionis Have Antitumor Properties In Vitro and in an H22 Mouse Hepatoma Ascites Model In Vivo

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Yukun Fang

2018-05-01

Full Text Available Malignant ascites is a highly severe and intractable complication of advanced or recurrent malignant tumors that is often immunotherapy-resistant. Rhizoma Pleionis is widely used in traditional medicine as an antimicrobial and anticancer agent, but its effectiveness in treating malignant ascites is unclear. In the current study, we investigated the effect of polysaccharides isolated from Rhizoma Pleionis (PRP on murine hepatocarcinoma H22 cells in an ascites model. We have found that the main components of PRP, that presented a relative molecular weight of 383.57 kDa, were mannose and glucose. We also found that PRP reduced the occurrence of abdominal ascites and increased survival in our mouse model. An immune response in the ascites tumor model was observed by performing a lymphocytes proliferation experiment and an E-rosette test. The ratios of CD8+ cytotoxic T cells and NK cells in the spleen were examined by flow cytometry, and the mRNA expression of Foxp3+in CD4+CD25+ (T regulatory Tregs was measured by RT-PCR (reverse transcription-polymerase chain reaction. The levels of the cytokines TNF-α (tumor necrosis factor, VEGF (vascular endothelial growth factor, IL-2 (interleukin, and IFN-γ (interferon in the serum and ascites supernatants were measured by ELISA. The expression of Foxp3 and Stat3 in peritoneal cells in the mouse model was measured by immunocytochemistry. The results indicated that PRP increased H22 tumor cell apoptosis in vivo by activating and enhancing the immune response. Furthermore, the effects of PRP on the proliferation of H22 cells were assessed by the CCK8 assay, Hoechest 33258, and TUNEL staining in vitro. We found that PRP suppressed the proliferation of H22 tumor cells but had no effect on BRL (Big rat liver -3A rat hepatoma normal cells in vitro. Next, we investigated the underlying immunological mechanism by which PRP inhibits malignant ascites. PRP induced tumor cell apoptosis by inhibiting the Jak1–Stat3

The Use of Platelet-Rich and Platelet-Poor Plasma to Enhance Differentiation of Skeletal Myoblasts: Implications for the Use of Autologous Blood Products for Muscle Regeneration.

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Miroshnychenko, Olga; Chang, Wen-Teh; Dragoo, Jason L

2017-03-01

Platelet-rich plasma (PRP) has been used to augment tissue repair and regeneration after musculoskeletal injury. However, there is increasing clinical evidence that PRP does not show a consistent clinical effect. Purpose/Hypothesis: This study aimed to compare the effects of the following non-neutrophil-containing (leukocyte-poor) plasma fractions on human skeletal muscle myoblast (HSMM) differentiation: (1) PRP, (2) modified PRP (Mod-PRP), in which transforming growth factor β1 (TGF-β1) and myostatin (MSTN) were depleted, and (3) platelet-poor plasma (PPP). The hypothesis was that leukocyte-poor PRP would lead to myoblast proliferation (not differentiation), whereas certain modifications of PRP preparations would increase myoblast differentiation, which is necessary for skeletal muscle regeneration. Controlled laboratory study. Blood from 7 human donors was individually processed to simultaneously create leukocyte-poor fractions: PRP, Mod-PRP, PPP, and secondarily spun PRP and Mod-PRP (PRP ss and Mod-PRP ss , respectively). Mod-PRP was produced by removing TGF-β1 and MSTN from PRP using antibodies attached to sterile beads, while a second-stage centrifugal spin of PRP was performed to remove platelets. The biologics were individually added to cell culture groups. Analysis for induction into myoblast differentiation pathways included Western blot analysis, reverse-transcription polymerase chain reaction, and immunohistochemistry, as well as confocal microscopy to assess polynucleated myotubule formation. HSMMs cultured with PRP showed an increase in proliferation but no evidence of differentiation. Western blot analysis confirmed that MSTN and TGF-β1 could be decreased in Mod-PRP using antibody-coated beads, but this modification mildly improved myoblast differentiation. However, cell culture with PPP, PRP ss , and Mod-PRP ss led to a decreased proliferation rate but a significant induction of myoblast differentiation verified by increased multinucleated

Temporal and spatial expression of TGF-beta1 in an Achilles tendon section model after application of platelet-rich plasma.

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Lyras, Dimitrios N; Kazakos, Konstantinos; Tryfonidis, Marios; Agrogiannis, George; Botaitis, Sotirios; Kokka, Anna; Drosos, George; Tilkeridis, Konstantinos; Verettas, Dionysios

2010-09-01

To investigate the effect of platelet-rich plasma (PRP) on TGF-beta1 expression during tendon healing. We used 48 skeletally mature New Zealand White rabbits. 24 rabbits received the PRP, and 24 rabbits served as an untreated control group. Equal numbers of animals were sacrificed at 1st, 2nd, 3rd, and 4th week. The surgical procedure involved a transverse incision to transect the Achilles tendon. A volume of 1ml of PRP was then injected into the tendon mass in the PRP group. Histological and immunohistochemical evaluations with an anti-TGF-beta primary antibody were performed. The pattern of expression of TGF-beta1 in the PRP group was characterized by a significant upregulation during the first 2 weeks and subsequently significant downregulation in the 3rd and 4th week in comparison with the controls. Our results suggest that PRP may affect the tendon healing process by altering the expression of TGF-beta1. Copyright (c) 2009 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

Intratendon Delivery of Leukocyte-Poor Platelet-Rich Plasma Improves Healing Compared With Leukocyte-Rich Platelet-Rich Plasma in a Rabbit Achilles Tendinopathy Model.

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Yan, Ruijian; Gu, Yanjia; Ran, Jisheng; Hu, Yejun; Zheng, Zefeng; Zeng, Mengfeng; Heng, Boon Chin; Chen, Xiao; Yin, Zi; Chen, Weishan; Shen, Weiliang; Ouyang, Hongwei

2017-07-01

Chronic tendinopathy is a commonly occurring clinical problem that affects both athletes and inactive middle-aged patients. Although some studies have shown that different platelet-rich plasma (PRP) preparations could exert various therapeutic effects in vitro, the role of leukocytes in PRP has not yet been defined under tendinopathy conditions in vivo. This study compared the effects of the intratendon delivery of leukocyte-poor PRP (Lp-PRP) versus leukocyte-rich PRP (Lr-PRP) in a rabbit chronic tendinopathy model in vivo. Controlled laboratory study. Four weeks after a local injection of collagenase in the Achilles tendon, the following treatments were randomly administered on the lesions: injections of (1) 200 μL of Lp-PRP (n = 8), (2) 200 μL of Lr-PRP (n = 8), or (3) 200 μL of saline (n = 8). Healing outcomes were assessed at 4 weeks after therapy with magnetic resonance imaging (MRI), cytokine quantification, real-time polymerase chain reaction analysis of gene expression, histology, and transmission electron microscopy (TEM). MRI revealed that the Lr-PRP and saline groups displayed higher signal intensities compared with the Lp-PRP group with T2 mapping. Histologically, the Lp-PRP group displayed significantly better general scores compared with the Lr-PRP ( P = .001) and saline ( P tendon healing and is a preferable option for the clinical treatment of tendinopathy. PRP is widely used in the clinical management of chronic tendinopathy. However, the clinical results are ambiguous. It is imperative to understand the influence of leukocytes on PRP-mediated tissue healing in vivo, which could facilitate the better clinical management of chronic tendinopathy. Further studies are needed to translate our findings to the clinical setting.

Effects of an injectable platelet-rich fibrin on osteoblast behavior and bone tissue formation in comparison to platelet-rich plasma.

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Wang, Xuzhu; Zhang, Yufeng; Choukroun, Joseph; Ghanaati, Shahram; Miron, Richard J

2018-01-01

Platelet-rich plasma (PRP) has been utilized for many years as a regenerative agent capable of inducing vascularization of various tissues using blood-derived growth factors. Despite this, drawbacks mostly related to the additional use of anti-coagulants found in PRP have been shown to inhibit the wound healing process. For these reasons, a novel platelet concentrate has recently been developed with no additives by utilizing lower centrifugation speeds. The purpose of this study was therefore to investigate osteoblast behavior of this novel therapy (injectable-platelet-rich fibrin; i-PRF, 100% natural with no additives) when compared to traditional PRP. Human primary osteoblasts were cultured with either i-PRF or PRP and compared to control tissue culture plastic. A live/dead assay, migration assay as well as a cell adhesion/proliferation assay were investigated. Furthermore, osteoblast differentiation was assessed by alkaline phosphatase (ALP), alizarin red and osteocalcin staining, as well as real-time PCR for genes encoding Runx2, ALP, collagen1 and osteocalcin. The results showed that all cells had high survival rates throughout the entire study period irrespective of culture-conditions. While PRP induced a significant 2-fold increase in osteoblast migration, i-PRF demonstrated a 3-fold increase in migration when compared to control tissue-culture plastic and PRP. While no differences were observed for cell attachment, i-PRF induced a significantly higher proliferation rate at three and five days when compared to PRP. Furthermore, i-PRF induced significantly greater ALP staining at 7 days and alizarin red staining at 14 days. A significant increase in mRNA levels of ALP, Runx2 and osteocalcin, as well as immunofluorescent staining of osteocalcin was also observed in the i-PRF group when compared to PRP. In conclusion, the results from the present study favored the use of the naturally-formulated i-PRF when compared to traditional PRP with anti

An evaluation of platelet-rich plasma without thrombin activation with or without anorganic bone mineral in the treatment of human periodontal intrabony defects.

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Rodrigues, Silvia V; Acharya, Anirudh B; Thakur, Srinath L

2011-01-01

The efficacy of platelet-rich plasma (PRP) in periodontal regeneration is not well understood and the definite clinical viability of blood derived platelets lacks clarity. Also, the use of thrombin for platelet activation is disputed. Hence, the purpose of this study was to evaluate the efficacy of blood derived platelets without thrombin activation, alone or in combination with bovine anorganic bone mineral (ABM), in the treatment of human periodontal intrabony defects. PRP was prepared using a simple tabletop centrifuge and activated using calcium chloride without the addition of thrombin. This PRP was used alone (in Group A) and in combination with bovine ABM (in Group B) in the treatment of human periodontal angular defects. Both the control and the test groups showed definite improvement in clinical parameters. On comparison, however, there was a statistically significant improvement in the probing pocket depths and relative attachment level in Group B over Group A at 3 and 6 months intervals, whereas at the end of 9 months this difference was not statistically significant. There was no statistically significant difference between the groups with respect to the relative defect depth. Within the limitations of this study and the type of PRP used, i.e. without thrombin mediated activation, it can be concluded that both PRP and PRP combined with bovine ABM results in significant clinical improvement. Albeit statistically insignificant, there is a preponderance of better clinical results with the addition of ABM to PRP. Further studies need to be carried out on a larger sample size to confirm the results of the present study.

Ultrasound-Guided Injection of Platelet-Rich Plasma and Hyaluronic Acid, Separately and in Combination, for Hip Osteoarthritis: A Randomized Controlled Study.

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Dallari, Dante; Stagni, Cesare; Rani, Nicola; Sabbioni, Giacomo; Pelotti, Patrizia; Torricelli, Paola; Tschon, Matilde; Giavaresi, Gianluca

2016-03-01

The effectiveness of intra-articular platelet-rich plasma (PRP) injections has been evaluated in knee chondroplasty and osteoarthritis (OA); however, little evidence of its efficacy in hip OA exists. To compare the therapeutic efficacy of autologous PRP, hyaluronic acid (HA), or a combination of both (PRP+HA) in hip OA. Randomized controlled trial; Level of evidence, 1. Patients aged between 18 and 65 years who were treated with outpatient surgery and who had hip OA and pain intensity at baseline of >20 on a 100-mm visual analog scale (VAS) were recruited for this study. Exclusion criteria were extensive surgery; presence of excessive deformities; or rheumatic, infective, cardiovascular, or immune system disorders. The primary outcome measure was a change in pain intensity as assessed by the VAS at 2, 6, and 12 months after treatment. Secondary outcome measures were the Harris Hip Score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and concentration of growth factors in PRP and their correlation with clinical outcomes. Clinical outcomes were evaluated by assessors and collectors blinded to the type of treatment administered. A total of 111 patients were randomly assigned to 3 groups and received 3 weekly injections of either PRP (44 patients), PRP+HA (31 patients), or HA (36 patients). At all follow-ups, the PRP group had the lowest VAS scores. In particular, at 6-month follow-up, the mean VAS score was 21 (95% CI, 15-28) in the PRP group, 35 (95% CI, 26-45) in the PRP+HA group, and 44 (95% CI, 36-52) in the HA group (P injections offer a significant clinical improvement in patients with hip OA without relevant side effects. The benefit was significantly more stable up to 12 months as compared with the other tested treatments. The addition of PRP+HA did not lead to a significant improvement in pain symptoms. © 2016 The Author(s).

Effect of platelet rich plasma and fibrin sealant on facial nerve regeneration in a rat model.

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Farrag, Tarik Y; Lehar, Mohamed; Verhaegen, Pauline; Carson, Kathryn A; Byrne, Patrick J

2007-01-01

To investigate the effects of platelet rich plasma (PRP) and fibrin sealant (FS) on facial nerve regeneration. Prospective, randomized, and controlled animal study. Experiments involved the transection and repair of facial nerve of 49 male adult rats. Seven groups were created dependant on the method of repair: suture; PRP (with/without suture); platelet poor plasma (PPP) (with/without suture); and FS (with/without suture) groups. Each method of repair was applied immediately after the nerve transection. The outcomes measured were: 1) observation of gross recovery of vibrissae movements within 8-week period after nerve transection and repair using a 5-point scale and comparing the left (test) side with the right (control) side; 2) comparisons of facial nerve motor action potentials (MAP) recorded before and 8 weeks after nerve transection and repair, including both the transected and control (untreated) nerves; 3) histologic evaluation of axons counts and the area of the axons. Vibrissae movement observation: the inclusion of suturing resulted in overall improved outcomes. This was found for comparisons of the suture group with PRP group; PRP with/without suture groups; and PPP with/without suture groups (P .05). The movement recovery of the suture group was significantly better than the FS group (P = .014). The recovery of function of the PRP groups was better than that of the FS groups, although this did not reach statistical significance (P = .09). Electrophysiologic testing: there was a significantly better performance of the suture group when compared with the PRP and PPP without suture groups in nerve conduction velocity (P facial nerve axotomy models occurred when the nerve ends were sutured together. At the same time, the data demonstrated a measurable neurotrophic effect when PRP was present, with the most favorable results seen with PRP added to suture. There was an improved functional outcome with the use of PRP in comparison with FS or no bioactive

Evaluation of low-level laser therapy, platelet-rich plasma, and their combination on the healing of Achilles tendon in rabbits.

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Allahverdi, Amin; Sharifi, Davood; Takhtfooladi, Mohammad Ashrafzadeh; Hesaraki, Saeed; Khansari, Mohammadreza; Dorbeh, Shahab Sarrout

2015-05-01

Tendon repair is still one of the challenges for rehabilitation. Various treatments for tendon injuries have been used in recent decade. This study was established to investigate the effects of low-level laser therapy (LLLT), platelet-rich plasma (PRP) treatment alone, and using combined method on the healing of Achilles tendon in rabbits. Seventy-two healthy mature male white New Zealand rabbits were divided randomly into four groups of 18 animals each: control: partial tenotomy with no treatment, only 1 mL normal saline was injected on days 1, 8, and 15 at the site of splitting; PRP: partial tenotomy with PRP treatment on days 1, 8, and 15 at the site of splitting; LLLT: partial tenotomy with LLLT (K30 hand-held probe, AZOR, Technica, Russia, 650 nm, 30 mW, surface area = 1 cm(2), 60 S/cm(2), energy density = 1.8 J/cm(2)) for 15 consecutive days; LLLT + PRP: partial tenotomy with LLLT + PRP. At the end of trial, the rabbits were euthanatized and tendon specimens were harvested and were submitted for histopathological evaluation, hydroxyproline levels, and biomechanical measurement. The Tukey post hoc test was performed. The results for these parameters showed that PRP or LLLT alone has significant advantages over untreated animals (P  0.05) between the two groups of LLLT and PRP. However, the treatments combining PRP and LLLT showed significant results in comparison of PRP or LLLT alone (P tendon decreases by using the two therapies combined.

Reducing system of parameters and the Cohen–Macaulay property

Indian Academy of Sciences (India)

X), where X is a subset of R and that for a prime ideal P of R we have P ∈ Ass M iff PRP ∈ Ass MP . Moreover we define. Assh M := {P ∈ Ass M | dim R/P = d}. For undefined terminology we refer to the standard literature (e.g. [E]). DEFINITION 1.

Evaluation of effects of platelet-rich plasma on human facial skin.

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Yuksel, Esra Pancar; Sahin, Gokhan; Aydin, Fatma; Senturk, Nilgun; Turanli, Ahmet Yasar

2014-10-01

Platelet-rich plasma (PRP) has been used for rapid healing and tissue regeneration in many fields of medicine. This study was conducted to evaluate the effects of PRP application procedure on human facial skin. PRP was applied thrice at 2-week intervals on the face of ten healthy volunteers. It was applied to individual's forehead, malar area, and jaw by a dermaroller, and injected using a 27-gauge injector into the wrinkles of crow's feet. Participants were asked to grade on a scale from 0 to 5 for general appearance, skin firmness-sagging, wrinkle state and pigmentation disorder of their own face before each PRP procedure and 3 months after the last PRP procedure. While volunteers were evaluating their own face, they were also assessed by three different dermatologists at the same time by the same five-point scale. There was statistically significant difference regarding the general appearance, skin firmness-sagging and wrinkle state according to the grading scale of the patients before and after three PRP applications. Whereas there was only statistically significant difference for the skin firmness-sagging according to the assessment of the dermatologists. PRP application could be considered as an effective procedure for facial skin rejuvenation.

Platelet-rich plasma for arthroscopic repair of medium to large rotator cuff tears: a randomized controlled trial.

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Jo, Chris Hyunchul; Shin, Ji Sun; Shin, Won Hyoung; Lee, Seung Yeon; Yoon, Kang Sup; Shin, Sue

2015-09-01

Two main questions about the use of platelet-rich plasma (PRP) for regeneration purposes are its effect on the speed of healing and the quality of healing. Despite recent numerous studies, evidence is still lacking in this area, especially in a representative patient population with medium to large rotator cuff tears. To assess the efficacy of PRP augmentation on the speed and quality of healing in patients undergoing arthroscopic repair for medium to large rotator cuff tears. Randomized controlled trial; Level of evidence, 1. A total of 74 patients scheduled for arthroscopic repair of medium to large rotator cuff tears were randomly assigned to undergo either PRP-augmented repair (PRP group) or conventional repair (conventional group). In the PRP group, 3 PRP gels (3 × 3 mL) were applied to each patient between the torn end and the greater tuberosity. The primary outcome was the Constant score at 3 months after surgery. Secondary outcome measures included the visual analog scale (VAS) for pain, range of motion (ROM), muscle strength, overall satisfaction and function, functional scores, retear rate, and change in the cross-sectional area (CSA) of the supraspinatus muscle. There was no difference between the 2 groups in the Constant score at 3 months (P > .05). The 2 groups had similar results on the VAS for pain, ROM, muscle strength, overall satisfaction and function, and other functional scores (all P > .05) except for the VAS for worst pain (P = .043). The retear rate of the PRP group (3.0%) was significantly lower than that of the conventional group (20.0%) (P = .032). The change in 1-year postoperative and immediately postoperative CSAs was significantly different between the 2 groups: -36.76 ± 45.31 mm(2) in the PRP group versus -67.47 ± 47.26 mm(2) in the conventional group (P = .014). Compared with repairs without PRP augmentation, the current PRP preparation and application methods for medium to large rotator cuff repairs significantly improved the

A study on the Regenerative Effect of Platelets Rich Plasma on Experimentally Induced Hepatic Damage In Albino Rats.

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Shoeib, Heba Mamdoh; Keshk, Walaa Arafa; Foda, Abdallah Mahmoud; Abo El Noeman, Saad El-Deen Abd Elfatah

2018-02-14

Hepatic fibrosis is a worldwide health problem with significant morbidity and mortality. Currently, there is no effective therapy for hepatic fibrosis. So that the present study was aimed to evaluate the possible regenerative effect of Platelet-rich plasma (PRP) against thioacetamide (TAA) induced hepatic damage. Eighty albino rats were included; 40 were used for PRP preparation and 40 were randomly divided into four groups. Group I (control group); group II (PRP control); group III (TAA- intoxicated in a dose of 200 mg ∕ kg body weight/twice weekly for 7 weeks, intra-peritoneal and group IV (TAA-intoxicated+ PRP treated). Macrophage inflammatory protein-1α (MIP-1α) and cyclic adenosine monophosphate (cAMP) were immunoassayed in addition to peroxinitrite level, NADPH-quinine oxido-reductase-1 (NQO1) enzyme activity and liver function. PRP treatment showed significant improvement in hepatic function, decreased MIP-1α and peroxinitrite level. Meanwhile, significant increase in NQO1 enzyme activity and cAMP level were observed. The histopathological results confirmed the laboratory results with improvement of hepatic architecture except for some inflammatory cellular infiltrates. PRP has the ability to protect against TAA-induced liver damage possibly by improving redox status, liver histopathological architecture, disruption of the inflammatory and fibrotic response induced by TAA.

Prospective Randomized Evaluation of Intraoperative Application of Autologous Platelet-Rich Plasma on Surgical Site Infection or Delayed Wound Healing.

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SanGiovanni, Thomas P; Kiebzak, Gary M

2016-05-01

Prevention of surgical site infections and the reduction of wound-related complication rates have become increasingly emphasized by hospital task groups and government agencies given the degree of economic burden it places on the health care system. Platelet-rich plasma (PRP) contains growth factors and other biomolecules that promote endogenous microbicidal activity. We hypothesized that PRP would help prevent postoperative infection and delayed wound healing (DWH). We randomized patients having foot or ankle surgery to the treatment group receiving intraoperative PRP (applied to operative field) and platelet-poor plasma at closing (PPP, on the sutured skin) or the control group (no PRP/PPP). The incidence of deep surgical site infection and DWH (collectively called endpoints) was compared between groups (n = 250/group). PRP had a mean 5.3-fold platelet concentration compared to whole blood, with concentrated white blood cells. Mean age (±SD) of patients was 52 years (±15), 65% were women. Minor and major operative procedures were included. Patients were followed for 60 days. Seventy controls had PRP prepared for assay of growth factors. Procedure mix, ASA scores, mean operative times, and comorbidity mix were similar between groups. The primary result was no difference in number of endpoints between groups: 19 patients in the PRP group (7.6%) versus 18 controls (7.2%). Endpoints were deep surgical site infections in 2 PRP/PPP patients and 1 control, and DWH in 17 PRP/PPP patients and 17 controls. Analysis of PRP samples revealed a large variation in growth factor concentrations between patients. Intraoperative application of PRP/PPP did not reduce the incidence of postoperative infection or DWH. Growth factor profiles varied greatly between patients, suggesting that the potentially therapeutic treatment delivered was not consistent from patient-to-patient. Level I, prospective randomized trial. © The Author(s) 2015.

[The study of anticoagulants selection in platelet-rich plasma preparation].

Science.gov (United States)

Hua, Lei; Lai, Gui; Zhenjun, Liu; Guie, Ma

2015-07-01

To investigate the effect of the anticoagulants on PRP quality, so as to clarify the appropriate anticoagulant used in PRP production. The microstructure change of platelets collected via heparin, citrate, acid citrate dextrose (ACD) and citrate-theophylline-adenosine-dipyridamole ( CTAD) was observed by TEM following time course. The extent of spontaneous activation of platelets in four groups was detected by measuring sP-selectin in plasma. The TGF-β1 release amount of activated PRP of four groups was measured. CTAD is superior to other anticoagulants in maintaining the integrity of platelet structures for a long time and preventing platelet spontaneous activation. ACD slightly surpassed heparin and citrate in above two aspects. ACD-PRP and CTAD-PRP released significantly more TGF-β1 compared with heparin and citrate. The PRP quality and biological effects were strongly associated with the type of Anticoagulants. ACD and CTAD are optimal anticoagulants in PRP production for they can maintain platelet viability at a high level.

Enhanced Sternal Healing via Platelet-Rich Plasma and Biodegradable Gelatin Hydrogel.

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Shibata, Masafumi; Takagi, Gen; Kudo, Mitsuhiro; Kurita, Jiro; Kawamoto, Yoko; Miyagi, Yasuo; Kanazashi, Mikimoto; Sakatani, Takashi; Naito, Zenya; Tabata, Yasuhiko; Miyamoto, Masaaki; Nitta, Takashi

2018-05-16

Platelet-rich plasma (PRP) contains numerous growth factors and promotes bone fracture healing. The aim of this study was to evaluate the effectiveness of the controlled release of PRP from biodegradable gelatin hydrogel for promoting healing in a rabbit ischemic sternal model. PRP was prepared from the whole blood of a Japanese white rabbit. Sixteen rabbits were randomized into four groups (each n = 4) and all underwent median sternotomy and bilateral internal thoracic artery removal. Before the sternum was closed, the following solutions were applied between the sternum incisions in three of the groups: 30 mg of gelatin hydrogel incorporating 300 μL of phosphate-buffered saline, 300 μL of a solution form of PRP, or 30 mg of gelatin hydrogel incorporating 300 μL of PRP (PRP+Gel). The fourth group acted as a control. Sternal healing was evaluated by histology and micro-computed tomography 7 days after the intervention. The PRP+Gel group showed a significantly higher proportion of fibrosis within the fracture area (an indicator of sternal healing) than the other groups and a significantly higher mean intensity of osteocalcin. These results indicate that the controlled release of PRP from locally applied gelatin hydrogel was markedly effective in enhancing sternal healing in the early postoperative period. This novel therapy could potentially help prevent complications such as deep sternal wound infection and could result in early postoperative ambulation after median sternotomy.

Combination of platelet-rich plasma within periodontal ligament stem cell sheets enhances cell differentiation and matrix production.

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Xu, Qiu; Li, Bei; Yuan, Lin; Dong, Zhiwei; Zhang, Hao; Wang, Han; Sun, Jin; Ge, Song; Jin, Yan

2017-03-01

The longstanding goal of periodontal therapy is to regenerate periodontal tissues. Although platelet-rich plasma (PRP) has been gaining increasing popularity for use in the orofacial region, whether PRP is useful for periodontal regeneration is still unknown. The purpose of this study was to determine whether a mixture of periodontal ligament stem cell (PDLSC) sheets and PRP promoted bone regeneration, one of the most important measurement indices of periodontal tissue regenerative capability in vitro and in vivo. In this study, we evaluated the effects of different doses of PRP on the differentiation of human PDLSCs. Then cell sheet formation, extracellular matrix deposition and osteogenic gene expression in response to different doses of PRP treatment during sheet grafting was investigated. Furthermore, we implanted PDLSC sheets treated with 1% PRP subcutaneously into immunocompromised mice to evaluate their bone-regenerative capability. The results revealed that 1% PRP significantly enhanced the osteogenic differentiation of PDLSCs. Based on the production of extracellular matrix proteins, the results of scanning electron microscopy and the expression of the osteogenic genes ALP, Runx2, Col-1 and OCN, the provision of 1% PRP for PDLSC sheets was the most effective PRP administration mode for cell sheet formation. The results of in vivo transplantation showed that 1% PRP-mediated PDLSC sheets exhibited better periodontal tissue regenerative capability than those obtained without PRP intervention. These data suggest that a suitable concentration of PRP stimulation may enhance extracellular matrix production and positively affect cell behaviour in PDLSC sheets. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

Nano-CL-20/HMX Cocrystal Explosive for Significantly Reduced Mechanical Sensitivity

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Chongwei An

2017-01-01

Full Text Available Spray drying method was used to prepare cocrystals of hexanitrohexaazaisowurtzitane (CL-20 and cyclotetramethylene tetranitramine (HMX. Raw materials and cocrystals were characterized using scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, Raman spectroscopy, and Fourier transform infrared spectroscopy. Impact and friction sensitivity of cocrystals were tested and analyzed. Results show that, after preparation by spray drying method, microparticles were spherical in shape and 0.5–5 µm in size. Particles formed aggregates of numerous tiny plate-like cocrystals, whereas CL-20/HMX cocrystals had thicknesses of below 100 nm. Cocrystals were formed by C–H⋯O bonding between –NO2 (CL-20 and –CH2– (HMX. Nanococrystal explosives exhibited drop height of 47.3 cm, and friction demonstrated explosion probability of 64%. Compared with raw HMX, cocrystals displayed significantly reduced mechanical sensitivity.

Bioactivity of freeze-dried platelet-rich plasma in an adsorbed form on a biodegradable polymer material.

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Nakajima, Yu; Kawase, Tomoyuki; Kobayashi, Mito; Okuda, Kazuhiro; Wolff, Larry F; Yoshie, Hiromasa

2012-01-01

Owing to the necessity for the immediate preparation from patients' blood, autologous platelet-rich plasma (PRP) limits its clinical applicability. To address this concern and respond to emergency care and other unpredictable uses, we have developed a freeze-dried PRP in an adsorbed form on a biodegradable polymer material (Polyglactin 910). On the polymer filaments of PRP mesh, which was prepared by coating the polymer mesh with human fresh PRP and subsequent freeze-drying, platelets were incorporated, and related growth factors were preserved at high levels. This new PRP mesh preparation significantly and reproducibly stimulated the proliferation of human periodontal ligament cells in vitro and neovascularization in a chorioallantoic membrane assay. A full-thickness skin defect model in a diabetic mouse demonstrated the PRP mesh, although prepared from human blood, substantially facilitated angiogenesis, granulation tissue formation, and re-epithelialization without inducing severe inflammation in vivo. These data demonstrate that our new PRP mesh preparation functions as a bioactive material to facilitate tissue repair/regeneration. Therefore, we suggest that this bioactive material, composed of allogeneic PRP, could be clinically used as a promising alternative in emergency care or at times when autologous PRP is not prepared immediately before application.

Platelet-rich plasma-containing fragmin-protamine micro-nanoparticles promote epithelialization and angiogenesis in split-thickness skin graft donor sites.

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Takabayashi, Yuki; Ishihara, Masayuki; Sumi, Yuki; Takikawa, Makoto; Nakamura, Shingo; Kiyosawa, Tomoharu

2015-01-01

Platelet-rich plasma (PRP) contains multiple growth factors, and fragmin-protamine micro-nanoparticles (F-P M-NPs) significantly enhance and stabilize growth factors. The purpose of this study was to evaluate the effects of PRP-containing F-P M-NPs (PRP&F-P M-NPs) on wound repair in split-thickness skin graft (STSG-) donor sites (DS). A total of 56 inbred male rats were anesthetized and split-thickness skin graft donor site (STSG-DS) were created with a Padgett dermatome. PRP&F-P M-NPs, F-P M-NPs, PRP, and saline (control) were then intradermally injected evenly into the STSG-DSs. On 3, 4, 5, 7, and 10 d after creation of STSG-DS, skin sample sections were stained with hematoxylin and eosin to evaluate reepithelialization and angiogenesis. Treatment of STSG-DS with PRP&F-P M-NPs effectively promoted epithelialization and new vessel formation compared with those treated with PRP, F-P M-NPs, and control (saline). The intradermal injection of PRP&F-P M-NPs promotes epithelialization and angiogenesis in STSG-DS wounds. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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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.

Evaluation of 3D-Printed Polycaprolactone Scaffolds Coated with Freeze-Dried Platelet-Rich Plasma for Bone Regeneration

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Junda Li

2017-07-01

Full Text Available Three-dimensional printing is one of the most promising techniques for the manufacturing of scaffolds for bone tissue engineering. However, a pure scaffold is limited by its biological properties. Platelet-rich plasma (PRP has been shown to have the potential to improve the osteogenic effect. In this study, we improved the biological properties of scaffolds by coating 3D-printed polycaprolactone (PCL scaffolds with freeze-dried and traditionally prepared PRP, and we evaluated these scaffolds through in vitro and in vivo experiments. In vitro, we evaluated the interaction between dental pulp stem cells (DPSCs and the scaffolds by measuring cell proliferation, alkaline phosphatase (ALP activity, and osteogenic differentiation. The results showed that freeze-dried PRP significantly enhanced ALP activity and the mRNA expression levels of osteogenic genes (ALP, RUNX2 (runt-related gene-2, OCN (osteocalcin, OPN (osteopontin of DPSCs (p < 0.05. In vivo, 5 mm calvarial defects were created, and the PRP-PCL scaffolds were implanted. The data showed that compared with traditional PRP-PCL scaffolds or bare PCL scaffolds, the freeze-dried PRP-PCL scaffolds induced significantly greater bone formation (p < 0.05. All these data suggest that coating 3D-printed PCL scaffolds with freeze-dried PRP can promote greater osteogenic differentiation of DPSCs and induce more bone formation, which may have great potential in future clinical applications.

Increasing platelet concentration in platelet-rich plasma inhibits anterior cruciate ligament cell function in three-dimensional culture.

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Yoshida, Ryu; Cheng, Mingyu; Murray, Martha M

2014-02-01

Tissue engineering is one new strategy being developed to treat ACL ruptures. One such approach is bio-enhanced ACL repair, where a suture repair is supplemented with a bio-active scaffold containing platelets. However, the optimal concentration of platelets to stimulate ACL healing is not known. We hypothesized that increasing platelet concentrations in the scaffold would enhance critical cell behaviors. Porcine ACL fibroblasts were obtained from explant culture and suspended in platelet poor plasma (PPP), 1× platelet-rich plasma (PRP), 3× PRP, 5× PRP, or phosphate buffered saline (PBS). The cell suspensions were cultured in a 3D collagen scaffold. Cellular metabolism (MTT assay), apoptosis (TUNEL assay), and gene expression for type I and type III collagen were measured. 1× PRP significantly outperformed 5× PRP in all parameters studied: Type I and III collagen gene expression, apoptosis prevention, and cell metabolism stimulation. ACL fibroblasts cultured with 1× PRP had the highest type I and type III collagen gene expression. 1× PRP and PPP groups had the highest cell metabolism and lowest apoptosis rates. Concentration of platelets had significant effects on the behavior of ACL fibroblasts; thus, it is an important parameter that should be specified in clinical or basic science studies. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Evaluation of two platelet-rich plasma processing methods and two platelet-activation techniques for use in llamas and alpacas.

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Semevolos, Stacy A; Youngblood, Cori D; Grissom, Stephanie K; Gorman, M Elena; Larson, Maureen K

2016-11-01

OBJECTIVE To evaluate 2 processing methods (commercial kit vs conical tube centrifugation) for preparing platelet rich plasma (PRP) for use in llamas and alpacas. SAMPLES Blood samples (30 mL each) aseptically collected from 6 healthy llamas and 6 healthy alpacas. PROCEDURES PRP was prepared from blood samples by use of a commercial kit and by double-step conical tube centrifugation. A CBC was performed for blood and PRP samples. Platelets in PRP samples were activated by means of a freeze-thaw method with or without 23mM CaCl 2 , and concentrations of platelet-derived growth factor-BB and transforming growth factor-β 1 were measured. Values were compared between processing methods and camelid species. RESULTS Blood CBC values for llamas and alpacas were similar. The commercial kit yielded a significantly greater degree of platelet enrichment (mean increase, 8.5 fold vs 2.8 fold) and WBC enrichment (mean increase, 3.7 fold vs 1.9 fold) than did conical tube centrifugation. Llamas had a significantly greater degree of platelet enrichment than alpacas by either processing method. No difference in WBC enrichment was identified between species. Concentrations of both growth factors were significantly greater in PRP samples obtained by use of the commercial kit versus those obtained by conical tube centrifugation. CONCLUSIONS AND CLINICAL RELEVANCE For blood samples from camelids, the commercial kit yielded a PRP product with a higher platelet and WBC concentration than achieved by conical tube centrifugation. Optimal PRP platelet and WBC concentrations for various applications need to be determined for llamas and alpacas.

Epidemiology, Treatment Efficacy, and Anxiety Aspects of Music Students Affected by Playing-Related Pain: A Retrospective Evaluation with Follow-up.

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Ioannou, Christos I; Hafer, Julia; Lee, André; Altenmüller, Eckart

2018-03-01

Playing-related pain (PRP) is a common problem among music students. We retrospectively assessed epidemiological factors that contributed to the manifestation of PRP and evaluated the efficacy of treatment methods used by affected music students. The long-term course of PRP symptoms was also examined, along with current (today) levels of trait anxieties. Demographic and epidemiological data of 186 music students who visited the musicians' outpatient clinic over a 5-year period were retrieved. Of these students, 122 had been diagnosed with PRP and were invited to participate (response rate 61.5%) in a follow-up online survey to: a) estimate the long-term course of their PRP symptoms, b) assess the efficacy of treatment methods they used, and c) assess their current trait anxiety (general and performance-related) using two standardized psychodiagnostic questionnaires. Two-thirds of music students who sought medical care were affected by PRP, with most being affected during their first year of studies, and with 69% having acute rather than chronic pain. The sudden increase in practice time was the main triggering factor for PRP (but not for non-PRP-related problems). Concerning the course of PRP, almost all students recovered or improved significantly. Students reported that "active" treatment methods (e.g., physical activities) were more effective than "passive" methods (e.g., oral medications). Psychodiagnostic questionnaires indicated that about 40% of PRP-affected students currently had increased levels of trait anxieties (music and non-music related), possibly warranting further medical assistance. PRP in music students occurs mainly at the beginning of their studies and has a good prognosis, although recovery may be lengthy. It is necessary to provide students with early information about PRP and about the multidimensional treatment framework that allows for individualized care of PRP in affected music students.

The significance of sensory appeal for reduced meat consumption.

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Tucker, Corrina A

2014-10-01

Reducing meat (over-)consumption as a way to help address environmental deterioration will require a range of strategies, and any such strategies will benefit from understanding how individuals might respond to various meat consumption practices. To investigate how New Zealanders perceive such a range of practices, in this instance in vitro meat, eating nose-to-tail, entomophagy and reducing meat consumption, focus groups involving a total of 69 participants were held around the country. While it is the damaging environmental implications of intensive farming practices and the projected continuation of increasing global consumer demand for meat products that has propelled this research, when asked to consider variations on the conventional meat-centric diet common to many New Zealanders, it was the sensory appeal of the areas considered that was deemed most problematic. While an ecological rationale for considering these 'meat' alternatives was recognised and considered important by most, transforming this value into action looks far less promising given the recurrent sensory objections to consuming different protein-based foods or of reducing meat consumption. This article considers the responses of focus group participants in relation to each of the dietary practices outlined, and offers suggestions on ways to encourage a more environmentally viable diet. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comparative Analysis of Different Platelet Lysates and Platelet Rich Preparations to Stimulate Tendon Cell Biology: An In Vitro Study

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Franka Klatte-Schulz

2018-01-01

Full Text Available The poor healing potential of tendons is still a clinical problem, and the use of Platelet Rich Plasma (PRP was hypothesized to stimulate healing. As the efficacy of PRPs remains unproven, platelet lysate (PL could be an alternative with its main advantages of storage and characterization before use. Five different blood products were prepared from 16 male donors: human serum, two PRPs (Arthrex, (PRP-ACP; RegenLab (PRP-BCT, platelet concentrate (apheresis, PC, and PL (freezing-thawing destruction of PC. Additionally, ten commercial allogenic PLs (AlloPL from pooled donors were tested. The highest concentration of most growth factors was found in AlloPL, whereas the release of growth factors lasted longer in the other products. PRP-ACP, PRP-BCT, and PC significantly increased cell viability of human tenocyte-like cells, whereas PC and AlloPL increased Col1A1 expression and PRP-BCT increased Col3A1 expression. MMP-1, IL-1β, and HGF expression was significantly increased and Scleraxis expression decreased by most blood products. COX1 expression significantly decreased by PC and AlloPL. No clear positive effects on tendon cell biology could be shown, which might partially explain the weak outcome results in clinical practice. Pooled PL seemed to have the most beneficial effects and might be the future in using blood products for tendon tissue regeneration.

Development of a Porcine Delayed Wound-Healing Model and Its Use in Testing a Novel Cell-Based Therapy

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Hadad, Ivan; Johnstone, Brian H.; Brabham, Jeffrey G.; Blanton, Matthew W.; Rogers, Pamela I.; Fellers, Cory; Solomon, James L.; Merfeld-Clauss, Stephanie; DesRosiers, Colleen M.; Dynlacht, Joseph R.; Coleman, John J.; March, Keith L.

2010-01-01

Purpose: A delayed full-thickness wound-healing model was developed and used for examining the capacity of adipose-derived stem cells (ASCs), either alone or in platelet-rich fibrin gels, to promote healing. Methods and Materials: Four pigs received electron beam radiation to the dorsal skin surface. Five weeks after radiation, subcutaneous fat was harvested from nonirradiated areas and processed to yield ASCs. Two weeks later, 28 to 30 full-thickness 1.5-cm 2 wounds were made in irradiated and nonirradiated skin. Wounds were treated with either saline solution, ASCs in saline solution, platelet-rich plasma (PRP) fibrin gel, ASCs in PRP, or non-autologous green fluorescence protein-labeled ASCs. Results: The single radiation dose produced a significant loss of dermal microvasculature density (75%) by 7 weeks. There was a significant difference in the rate of healing between irradiated and nonirradiated skin treated with saline solution. The ASCs in PRP-treated wounds exhibited a significant 11.2% improvement in wound healing compared with saline solution. Enhancement was dependent on the combination of ASCs and PRP, because neither ASCs nor PRP alone had an effect. Conclusions: We have created a model that simulates the clinically relevant late radiation effects of delayed wound healing. Using this model, we showed that a combination of ASCs and PRP improves the healing rates of perfusion-depleted tissues, possibly through enhancing local levels of growth factors.

Extracorporeal Shockwave Therapy Increases Growth Factor Release from Equine Platelet-Rich Plasma In Vitro

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Kathryn A. Seabaugh

2017-12-01

Full Text Available IntroductionExtracorporeal shockwave therapy (ESWT and platelet-rich plasma (PRP are common treatments for soft tissue injuries in horses. Shockwave triggers cell specific responses to promote healing. Growth factors released from PRP also promote healing. It has been hypothesized that greater growth factor release would amplify the healing process. The combination of ESWT and PRP could promote healing in injured tendons and ligaments in the horse. The objective of this study was to determine if application of shockwaves to PRP samples increases the concentration of transforming growth factor-β1 (TGF-β1 and platelet-derived growth factor ββ (PDGF-ββ released from the platelets in vitro.Materials and methodsPRP was produced from blood drawn from six horses. The PRP from each horse was exposed to the following treatments: (1 positive control (freeze-thaw cycle, (2 untreated negative control, or shockwaves with either (3 a “standard probe” (ESWT-S with a 2 cm focal width and medium energy density or (4 a “power probe” (ESWT-P with a 1 cm focal width and high energy density. After each treatment, the samples were centrifuged, and the supernatant was harvested. The supernatant was then used for growth factor quantification via commercially available ELISA kits for TGF-β1 and PDGF-ββ.ResultsConcentrations of TGF-β1 and PDGF-ββ in PRP that underwent a freeze-thaw cycle were significantly increased compared with all other treatments. Both ESWT-S and ESWT-P resulted in significantly increased TGF-β1 concentrations, 46 and 33%, respectively, when compared with the negative control. Both ESWT-S and ESWT-P resulted in significantly increased PDGF-ββ concentrations, 219 and 190%, respectively, when compared with the negative control.DiscussionThese data indicate that the application of ESWT to PRP increases the expression of growth factors in vitro. This suggests that the combination therapy of local PRP injection followed by ESWT

Interactive videogame as rehabilitation tool of patients with chronic respiratory diseases: preliminary results of a feasibility study.

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Mazzoleni, Stefano; Montagnani, Giulia; Vagheggini, Guido; Buono, Lorenzo; Moretti, Francesca; Dario, Paolo; Ambrosino, Nicolino

2014-10-01

To evaluate the effectiveness of an interactive videogame (IV) system in addition to a supervised pulmonary rehabilitation programme (PRP) in patients with chronic respiratory diseases. Randomised Controlled Trial comparing standard PRP (20 patients, control group: CG), and PRP + sessions of interactive videogame-aided exercises (20 patients, experimental group: EG). Lung and respiratory muscle function, arterial blood gases, exercise capacity, dyspnoea, health status and health-related quality of life (HRQL) and emotional response were measured before and after PRP. A questionnaire on acceptability of the PRP was administered. Exercise capacity, dyspnoea and HRQL significantly improved in both groups after the PRP, whereas the EG showed a greater improvement in six-minute walk test and transitional dyspnoea index than the CG. No difference in psychological status or acceptability of PRP was observed between the two groups. The addition of IV training was more effective for improving some parameters of exercise tolerance and dyspnoea, although did not result in better psychological status nor it was better accepted than the standard PRP in patients with chronic respiratory diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

Mutation directional selection sheds light on prion pathogenesis

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Shen, Liang; Ji, Hong-Fang

2011-01-01

Highlights: → Most pathogenic mutations possess strong directional selection, i.e., enhancing hydrophobicity or decreasing negative and increasing positive charge. → Mutation-induced changes may strengthen the interactions between PrP and facilitating factors. → The findings also have significant implications for exploring potential regions involved in the conformational transition from PrP C to PrP Sc . -- Abstract: As mutations in the PRNP gene account for human hereditary prion diseases (PrDs), it is crucial to elucidating how these mutations affect the central pathogenic conformational transition of normal cellular prion protein (PrP C ) to abnormal scrapie isoform (PrP Sc ). Many studies proposed that these pathogenic mutations may make PrP more susceptible to conformational change through altering its structure stability. By evaluating the most recent observations regarding pathogenic mutations, it was found that the pathogenic mutations do not exert a uniform effect on the thermodynamic stability of the human PrP's structure. Through analyzing the reported PrDs-related mutations, we found that 25 out of 27 mutations possess strong directional selection, i.e., enhancing hydrophobicity or decreasing negative and increasing positive charge. Based on the triggering role reported by previous studies of facilitating factors in PrP C conversion, e.g., lipid and polyanion, we proposed that the mutation-induced changes may strengthen the interaction between PrP and facilitating factors, which will accelerate PrP conversion and cause PrDs.

[Assessment study on a set of platelet-rich plasma preparation].

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Li, Ming; Zhang, Changqing; Yuan, Ting; Chen, Shengbao; Lü, Ruju

2011-01-01

To calculate the recovery rate and enrichment factor and to analyse the correlation by measuring the concentrations of platelets, leukocyte, and growth factors in platelet-rich plasma (PRP) so as to evaluate the feasibility and stability of a set of PRP preparation. The peripheral blood (40 mL) was collected from 30 volunteers accorded with the inclusion criteria, and then 4 mL PRP was prepared using the package produced by Shandong Weigao Group Medical Polymer Company Limited. Automatic hematology analyzer was used to count the concentrations of platelets and leukocyte in whole blood and PRP. The enrichment factor and recovery rate of platelets or leukocyte were calculated; the platelet and leukocyte concentrations of male and female volunteers were measured, respectively. The concentrations of platelet-derived growth factor (PDGF), transforming growth factor beta (TGF-beta), and vascular endothelial growth factor (VEGF) were assayed by ELISA. The platelet concentrations of whole blood and PRP were (131.40 +/- 29.44) x 10(9)/L and (819.47 +/- 136.32) x 10(9)/L, respectively, showing significant difference (t = 27.020, P = 0.000). The recovery rate of platelets was 60.85% +/- 8.97%, and the enrichment factor was 6.40 +/- 1.06. The leukocyte concentrations of whole blood and PRP were (5.57 +/- 1.91) x 10(12)/L and (32.20 +/- 10.42) x 10(12)/L, respectively, showing significant difference (t = 13.780, P = 0.000). The recovery rate of leukocyte was 58.30% +/- 19.24%, and the enrichment factor was 6.10 +/- 1.93. The concentrations of platelets and leukocyte in PRP were positively correlated with the platelet concentration (r = 0.652, P = 0.000) and leukocyte concentration (r = 0.460, P = 0.011) in whole blood. The concentrations of platelet and leukocyte in PRP between male and female were not significantly different (P > 0.05). The concentrations of PDGF, TGF-beta, and VEGF in PRP were (698.15 +/- 64.48), (681.36 +/- 65.90), and (1071.55 +/- 106.04) ng/mL, which were

High-frequency permeability of electroplated CoNiFe and CoNiFe-C alloys

International Nuclear Information System (INIS)

Rhen, Fernando M.F.; McCloskey, Paul; O'Donnell, Terence; Roy, Saibal

2008-01-01

We have investigated CoNiFe and CoNiFe-C electrodeposited by pulse reverse plating (PRP) and direct current (DC) techniques. CoNiFe(PRP) films with composition Co 59.4 Fe 27.7 Ni 12.8 show coercivity of 95 A m -1 (1.2 Oe) and magnetization saturation flux (μ 0 M s ) of 1.8 T. Resistivity of CoNiFe (PRP) is about 24 μΩ cm and permeability remains almost constant μ r ' ∼475 up to 30 MHz with a quality factor (Q) larger than 10. Additionally, the permeability spectra analysis shows that CoNiFe exhibits a classical eddy current loss at zero bias field and ferromagnetic resonance (FMR) when biased with 0.05 T. Furthermore, a crossover between eddy current and FMR loss is observed for CoNiFe-PRP when baised with 0.05 T. DC and PRP plated CoNiFe-C, which have resistivity and permeability of 85, 38 μΩ cm, μ r '=165 and 35 with Q>10 up to 320 MHz, respectively, showed only ferromagnetic resonance losses. The ferromagnetic resonance peaks in CoNiFe and CoNiFe-C are broad and resembles a Gaussian distribution of FMR frequencies. The incorporation of C to CoNiFe reduces eddy current loss, but also reduces the FMR frequency

Intraarticular injection autologous platelet-rich plasma and bone marrow concentrate in a goat osteoarthritis model.

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Wang, Zhen; Zhai, Chenjun; Fei, Hao; Hu, Junzheng; Cui, Weiding; Wang, Zhen; Li, Zeng; Fan, Weimin

2018-02-21

To evaluate the effects of intraarticular injections of autologous platelet-rich plasma (PRP) or bone marrow concentrate (BMC) on osteoarthritis (OA), 24 adult goats were equally divided into control (Ctrl), saline (NS), PRP, and BMC groups, and OA was induced by surgery in NS, PRP, and BMC groups. Autologous PRP and BMC were obtained from whole blood and bone marrow aspirates, respectively. The data revealed, platelets were increased in BMC by 1.8-fold, monocytes by 5.6-fold, TGF-β1 by 7.7-fold, and IGF-1 by 3.6-fold (p BMC were administered by intraarticular injection once every 4 weeks, three consecutive times. After the animals were sacrificed, inflammatory cytokines in the synovial fluid was measured, and bone and cartilage degeneration progression was observed by macroscopy, histology, and immunohistochemistry. Compared with the NS group, the level of inflammatory cytokines was reduced in the PRP and BMC groups (p BMC treated groups (p BMC group showed greater cartilage protection and less ECM loss than the PRP group (p BMC has therapeutic efficacy in a goat osteoarthritis model, with the greater benefit in terms of cartilage protection being observed in the BMC-treated group than PRP. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Relationship of cytokine levels and clinical effect on platelet-rich plasma-treated lateral epicondylitis.

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Lim, Wonbong; Park, Sang H; Kim, Bora; Kang, Sin W; Lee, Jung W; Moon, Young L

2018-03-01

Lateral epicondylitis (LE) is difficult to manage and can result in significant patient morbidity. Currently, the clinical use of platelet-rich plasma (PRP) for painful tendons has received attention, but its efficacy remains controversial. This study aimed to investigate the clinical effects of PRP and its biological components. A total of 156 patients with LE were randomly divided into group 1, treated with a single injection of 2-ml autologous PRP, and group 2, treated with a control received only physical therapy without injection. Both groups used a tennis elbow strap and performed stretching and strengthening exercises during 24 weeks' follow-up. Pain and functional improvements were assessed using the visual analog scale (VAS), Modified Mayo Clinic Performance Index for the elbow, and magnetic resonance imaging (MRI). White blood cell count, platelet count, and levels of platelet-derived growth factor-AB (PDGF-AB), PDGF-BB, transforming growth factor-β (TGF-β), vascular endothelial growth factor, epithelial growth factor, and interleukin-1 β in PRP were measured and investigated for statistical correlation with the clinical score. At 24 weeks, all pain and functional variables, including VAS score, Mayo Clinic performance scores, and MRI grade, improved significantly in group 1 (p < 0.05). PDGF-AB, PDGF-BB, and TGF-β levels were more significantly increased in PRP than in whole blood. TGF-β level significantly correlated with Mayo Clinic performance score and MRI grade improvement. Thus, TGF-β level in PRP is considered to play a pivotal role in tendon healing. These results may contribute to identifying the best protocol for PRP application in tendinopathies. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:913-920, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Effect of two different preparations of platelet-rich plasma on synoviocytes.

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Assirelli, Elisa; Filardo, Giuseppe; Mariani, Erminia; Kon, Elizaveta; Roffi, Alice; Vaccaro, Franca; Marcacci, Maurilio; Facchini, Andrea; Pulsatelli, Lia

2015-09-01

To analyse the modifications induced by two different platelet-rich plasma (PRP) preparations on osteoarthritis (OA) synoviocytes, by documenting changes in gene expression of factors involved in joint physiopathology. OA synoviocytes were cultured for 7 days in medium with different concentrations of either P-PRP (a pure platelet concentrate without leucocytes but with a limited number of platelets), L-PRP (a higher platelet concentrate containing leucocytes) or platelet-poor plasma (PPP). Gene expression of interleukin (IL)-1beta, IL-6, IL-8/CXCL8, tumour necrosis factor alpha, IL-10, IL-4, IL-13, metalloproteinase-13, tissue inhibitor of metalloproteinase (TIMP)-1, (TIMP)-3, (TIMP)-4, vascular endothelial growth factor, transforming growth factor beta1, fibroblast growth factor (FGF)-2, hepatocyte growth factor (HGF), hyaluronic acid (HA) synthases (HAS)-1, (HAS)-2, and (HAS)-3 was analysed by RT-PCR. HA production was determined in culture supernatants by ELISA. IL-1β, IL-8 and FGF-2 were significantly induced by L-PRP compared to both P-PRP and PPP; HGF was down-modulated by L-PRP versus both P-PRP and PPP, and an inverse dose-response influence was shown for all preparations. Expression level of TIMP-4 was lower in the presence of L-PRP compared with P-PRP. HA production and HAS gene expression did not seem to be modulated by PRP. L-PRP is able to sustain the up-regulation of proinflammatory factors, (IL-1beta, IL-8 and FGF-2), together with a down-modulation of HGF and TIMP-4 expression, two factors that have been recognized as anti-catabolic mediators in cartilage, thus supporting the need to further optimize the PRP preparations to be applied in clinical practice.

Platelet rich plasma versus steroid on lateral epicondylitis: meta-analysis of randomized clinical trials.

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Mi, Bobin; Liu, Guohui; Zhou, Wu; Lv, Huijuan; Liu, Yi; Wu, Qipeng; Liu, Jing

2017-05-01

Lateral epicondylitis (LE) is a common tendinopathy for which an effective treatment is still unknown. The purpose of this meta-analysis was to compare the effectiveness of platelet rich plasma (PRP) vs steroid in reducing pain and improving function of the elbow in the treatment of LE. A systematic search of the literature was conducted to identify related articles published from January 1980 to September 2016 in Pubmed, Embase, the Cochrane Library and SpringerLink. All studies that compared PRP with steroid administration on LE were included. Main outcomes were collected and analyzed by the Review Manager 5.1. Eight randomized controlled trials (RCTs) that involved 511 patients met the criteria. This meta-analysis showed that there was no significant difference in pain relief in the short-term (2 to 4 weeks: SMD = 1.02, P = .03; 6 to 8 weeks: SMD = .73, P = .24) and the intermediate-term (12 weeks: SMD = -0.28, P = .35). Steroid exhibited a better efficacy of function in the short-term (2 to 4 weeks: SMD = .61, P < .001; 6 to 8 weeks: SMD = .53, P < .001). However, PRP was superior to steroid for pain relief in the long-term (half year: SMD = -1.6, P < .001; one year: SMD = -1.45, P < .001), and also for function improving in the intermediate-term (12 weeks: SMD = -0.53, P < .001) and the long-term (half year: SMD = -0.56, P < .001; one year: SMD = -0.7, P < .001). No serious adverse effects of treatment were observed in the two groups. Treatment of patients with LE by steroid could slightly relieve pain and significantly improve function of elbow in the short-term (2 to 4 weeks, 6 to 8 weeks). PRP appears to be more effective in relieving pain and improving function in the intermediate-term (12 weeks) and long-term (half year and one year). Considering the long-term effectiveness of PRP, we recommend PRP as the preferred option for LE.

The influence of environmental variables on platelet concentration in horse platelet-rich plasma.

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Rinnovati, Riccardo; Romagnoli, Noemi; Gentilini, Fabio; Lambertini, Carlotta; Spadari, Alessandro

2016-07-04

Platelet-rich plasma (PRP) commonly refers to blood products which contain a higher platelet (PLT) concentration as compared to normal plasma. Autologous PRP has been shown to be safe and effective in promoting the natural processes of soft tissue healing or reconstruction in humans and horses. Variability in PLT concentration has been observed in practice between PRP preparations from different patients or from the same individual under different conditions. A change in PLT concentration could modify PRP efficacy in routine applications. The aim of this study was to test the influence of environmental, individual and agonistic variables on the PLT concentration of PRP in horses. Six healthy Standardbred mares were exposed to six different variables with a one-week washout period between variables, and PRP was subsequently obtained from each horse. The variables were time of withdrawal during the day (morning/evening), hydration status (overhydration/dehydration) treatment with anti-inflammatory drugs and training periods on a treadmill. The platelet concentration was significantly higher in horses treated with a non-steroidal anti-inflammatory drug (P = 0.03). The leukocyte concentration increased 2-9 fold with respect to whole blood in the PRP which was obtained after exposure to all the variable considered. Environmental variation in platelet concentration should be taken into consideration during PRP preparation.

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

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Kyun Ho Shin

2015-01-01

Full Text Available 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.

Platelet-rich plasma plus bioactive glass in the treatment of intra-bony defects: a study in dogs

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Marcelo Diniz Carvalho

2011-02-01

Full Text Available OBJECTIVE: This study was designed to evaluate, histomorphometrically, the association of platelet-rich plasma (PRP and bioactive glass (BG in the treatment of periodontal intrabony defects. MATERIAL AND METHODS: Nine mongrel dogs were included in the study. Three-wall intrabony defects were surgically created at the mesial and distal aspect of first mandibular molar and exposed to plaque accumulation for 1 month. The defects were randomly assigned to the groups: control, BG, PRP, PRP+BG. Dogs were sacrificed 90 days after the surgeries. The histometric parameters evaluated were: length of sulcular and junctional epithelium, connective tissue adaptation, new cementum, new bone, defect extension and area of new bone filling the defect. RESULTS: A superior area of new bone was observed in PRP+BG and BG (13.80±2.32 mm² and 15.63±2.64 mm², respectively when compared to the other groups (8.19±1.46 mm² and 8.81±1.47 mm² for control and PRP, respectively. No statistically significant differences were observed in the remaining parameters. CONCLUSIONS: Within the limits of this study, it may be concluded that PRP failed to provide statistically significant improvements in the histometric parameters.

A conceptual study on the formulation of a permeable reactive pavement with activated carbon additives for controlling the fate of non-point source environmental organic contaminants.

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Huang, Shengyi; Liang, Chenju

2018-02-01

To take advantage of the road pavement network where non-point source (NPS) pollution such as benzene, toluene, ethyl-benzene, and xylene (BTEX) from vehicle traffic exhaust via wet and dry atmospheric deposition occurs, the asphalt pavement may be used as a media to control the NPS pollution. An experiment to prepare an adsorptive porous reactive pavement (PRP) was initiated to explore the potential to reduce environmental NPS vehicle pollution. The PRP was prepared and studied as follows: various activated carbons (AC) were initially screened to determine if they were suitable as an additive in the porous asphalt mixture; various mixtures of a selected AC were incorporated with the design of porous asphalt concrete (PAC) to produce PRP, and the PRP formulations were tested to ensure that they comply with the required specifications; qualified specimens were subsequently tested to determine their adsorption capacity for BTEX in aqueous solution, as compared to conventional PAC. The PRP08 and PRP16 samples, named for the design formulations of 0.8% and 1.6% of AC (by wt. in the formulation), exhibited low asphalt drain-down and low abrasion loss and also met all regulated specifications. The BTEX adsorption capacity measurements of PRP08 and PRP16 were 33-46%, 36-51%, 20-22%, and 6-8% respectively, higher than those obtained from PACs. Based on the test results, PRPs showed good physical performance and adsorption and may be considered as a potential method for controlling the transport of NPS vehicle pollutants. Copyright © 2017 Elsevier Ltd. All rights reserved.

INFLUENCE OF INTRAMUSCULAR APPLICATION OF AUTOLOGOUS CONDITIONED PLASMA ON SYSTEMIC CIRCULATING IGF-1

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Gert Schippinger

2011-09-01

Full Text Available Platelet-rich plasma (PRP to increase levels of platelets and growth factors has been used for the treatment of sports injuries suggesting to improve healing and regeneration. This method offers some potential especially for elite athletes. However, the insulin like growth factor-1 (IGF-1 is prohibited by the World Anti Doping Agency and, in addition, there may be a possible link between increased levels of IGF-1 and cancer risk. Aim of the study was to evaluate a systemic increase of IGF-1 after local intramuscular administration of PRP in young healthy moderately trained male subjects. Blood samples were drawn and PRP preparation was performed by means of centrifugation. Enriched plasma was injected into the gluteus muscle. Venous blood was collected and serum prepared before as well as after 0.5, 3 and 24 hours after PRP administration. IGF-1 analysis was performed applying an ELISA test kit. No significant systemic increase of mean IGF-1 was found after the PRP injection. Only one subject showed an increase after 24 h, but all IGF-1 values were found within reference limits. We conclude that a single intramuscular application of PRP does not significantly increase systemic IGF-1 levels. Therefore, a single application of PRP is safe with respect to systemic IGF-1 response and cancer risk and this should be allowed for treatment of muscle injuries in elite athletes

Effect of local administration of platelet-rich plasma and guided tissue regeneration on the level of bone resorption in early dental implant insertion

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Duka Miloš

2008-01-01

Full Text Available Background/Aim. Osseointegration is a result of cellular migration, differentiation, bone formation, and bone remodeling on the surface of an implant. Each of these processes depends on platelets and blood coagulum. Platelet-rich plasma (PRP is used to improve osseointegration and stability of implants. The aim of the research was to test the influence that PRP and guided tissue regeneration in bone defects have on bone defect filling and the level of bone resorption in early implant insertion. Methods. This experimental study included 10 dogs. A total of 40 BCT implants were inserted, 4 in each dog (two on the left side and two on the right side, with guided tissue regeneration. Radiologic analyses were done immediately after the insertion and 10 weeks after the insertion. Bone defect filling was measured by a graduated probe 10 weeks after the implant insertion. The following protocols were tested: I - PRP in combination with bovine deproteinized bone (BDB and resorptive membrane of bovine origin (RBDM, II - BDB + RBDM, III - PRP + RBDM and IV - RBDM. Results. The applied protocols affected differently the bone defect filling and the level of bone resorption. Significantly better results (the lowest bone resorption were achieved with protocol I (PRP + BDB + RBDM in comparison with protocols III (PRP + RBDM and IV (RBDM, but not with protocol II (BDB + RBDM. On the other hand, no significant difference was found among protocols II (BDB + RBDM, III (PRP + RBDM and IV (RBDM in the level of bone tissue resorption. Conslusion. The bone defect filling was largest and the level of bone resorption was lowest in the protocol with PRP applied in combination with BDB and RBDM.

Loss of anti-Bax function in Gerstmann-Sträussler-Scheinker syndrome-associated prion protein mutants.

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Julie Jodoin

2009-08-01

Full Text Available Previously, we have shown the loss of anti-Bax function in Creutzfeldt Jakob disease (CJD-associated prion protein (PrP mutants that are unable to generate cytosolic PrP (CyPrP. To determine if the anti-Bax function of PrP modulates the manifestation of prion diseases, we further investigated the anti-Bax function of eight familial Gerstmann-Sträussler-Scheinker Syndrome (GSS-associated PrP mutants. These PrP mutants contained their respective methionine ((M or valine ((V at codon 129. All of the mutants lost their ability to prevent Bax-mediated chromatin condensation or DNA fragmentation in primary human neurons. In the breast carcinoma MCF-7 cells, the F198S(V, D202N(V, P102L(V and Q217R(V retained, whereas the P102L(M, P105L(V, Y145stop(M and Q212P(M PrP mutants lost their ability to inhibit Bax-mediated condensed chromatin. The inhibition of Bax-mediated condensed chromatin depended on the ability of the mutants to generate cytosolic PrP. However, except for the P102L(V, none of the mutants significantly inhibited Bax-mediated caspase activation. These results show that the cytosolic PrP generated from the GSS mutants is not as efficient as wild type PrP in inhibiting Bax-mediated cell death. Furthermore, these results indicate that the anti-Bax function is also disrupted in GSS-associated PrP mutants and is not associated with the difference between CJD and GSS.

Liposomal Encapsulation for Systemic Delivery of Propranolol via Transdermal Iontophoresis Improves Bone Microarchitecture in Ovariectomized Rats.

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Teong, Benjamin; Kuo, Shyh Ming; Tsai, Wei-Hsin; Ho, Mei-Ling; Chen, Chung-Hwan; Huang, Han Hsiang

2017-04-13

The stimulatory effects of liposomal propranolol (PRP) on proliferation and differentiation of human osteoblastic cells suggested that the prepared liposomes-encapsulated PRP exerts anabolic effects on bone in vivo. Iontophoresis provides merits such as sustained release of drugs and circumvention of first pass metabolism. This study further investigated and evaluated the anti-osteoporotic effects of liposomal PRP in ovariectomized (OVX) rats via iontophoresis. Rats subjected to OVX were administered with pure or liposomal PRP via iontophoresis or subcutaneous injection twice a week for 12 weeks. Changes in the microarchitecture at the proximal tibia and the fourth lumbar spine were assessed between pure or liposomal PRP treated and non-treated groups using micro-computed tomography. Administration of liposomal PRP at low dose (0.05 mg/kg) via iontophoresis over 2-fold elevated ratio between bone volume and total tissue volume (BV/TV) in proximal tibia to 9.0% whereas treatment with liposomal PRP at low and high (0.5 mg/kg) doses via subcutaneous injection resulted in smaller increases in BV/TV. Significant improvement of BV/TV and bone mineral density (BMD) was also found in the fourth lumbar spine when low-dose liposomal PRP was iontophoretically administered. Iontophoretic low-dose liposomal PRP also elevated trabecular numbers in tibia and trabecular thickness in spine. Enhancement of bone microarchitecture volumes has highlighted that liposomal formulation with transdermal iontophoresis is promising for PRP treatment at the lower dose and with longer duration than its clinical therapeutic range and duration to exhibit optimal effects against bone loss in vivo.

Ocular pulse amplitude after panretinal photocoagulation in normotensive eyes with proliferative diabetic retinopathy.

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Bozic, Marija M; Karadzic, Jelena B; Kovacevic, Igor M; Marjanovic, Ivan S

2017-06-26

To assess the effect of panretinal laser photocoagulation on ocular pulse amplitude (OPA) in normotensive eyes with proliferative diabetic retinopathy. Prospectively, we performed unilateral argon laser panretinal photocoagulation (PRP) in 30 patients with diabetes mellitus type II and previously untreated bilateral proliferative diabetic retinopathy. Before and 7 and 30 days after the treatment, OPA was measured using dynamic contour tonometer. Compared with the untreated contralateral eyes, laser photocoagulation led to a reduction of OPA. Ocular pulse amplitude did not significantly differ in photocoagulated eyes 7 days after the treatment, but there was a significant difference in OPA 30 days after the treatment. The decrease in OPA values was 15% 7 days after PRP and 40% 30 days after PRP. Ocular pulse amplitude reduction after PRP indirectly informs us about choriocapillary closure, already reported in previous studies.

Plateletpheresis before redo CABG diminishes excessive blood transfusion.

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Christenson, J T; Reuse, J; Badel, P; Simonet, F; Schmuziger, M

1996-11-01

Blood conservation remains an important element for patients undergoing cardiac operations with cardiopulmonary bypass. Preoperative platelet-rich plasma (PRP) harvest is an autologous blood conservation method. The efficacy of preoperative PRP harvest and post-cardiopulmonary bypass reinfusion on postoperative bleeding and need for postoperative blood transfusion was evaluated in patients undergoing redo coronary artery bypass grafting in a prospective, randomized manner. All adult patients admitted for redo coronary artery bypass grafting entered into the study. The PRP harvest aim was 20% or more of the total estimated circulating platelets. Immediately preoperatively three sequestration cycles were performed. The PRP was reinfused after weaning from cardiopulmonary bypass. One hundred seven parameters/patient were recorded. There were 20 patients in the RPR group and 20 controls (without PRP harvest). Patient characteristics, operative data, and preoperative hematologic parameters did not differ between the groups. In the PRP group, the mean platelet count in the PRP was 864 +/- 139 x 10(3)/microL, and the platelet yield was 27% +/- 5% (range, 20% to 37%). The average total chest tube blood loss was 423 mL (PRP) compared with 1,462 mL (controls; p platelets and reinfusion of the PRP after cardiopulmonary bypass resulted in significantly less postoperative blood loss and decreased fluid and blood transfusion requirements compared with controls. Postextubation gas exchange, ventilation time, and time required in the intensive care unit were also better, and the method was found cost-effective.

Estudo do método da extração da camada leucoplaquetária na produção de hemocomponentes: avaliação laboratorial A study of the Buffy-coat extraction method for blood component processing: laboratorial analysis

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Mario I. Serinolli

2004-01-01

Full Text Available Dentre os métodos para a obtenção de hemocomponentes destaca-se o método do plasma rico em plaquetas (PRP e o método da extração da camada leucoplaquetária (ECLP. Este estudo tem por objetivo comparar os métodos do PRP e da ECLP na produção de hemocomponentes. Foram processadas 88 bolsas de sangue total (ST pelo método do PRP, 130 bolsas triplas pelo método da ECLP (ECLPT e 215 bolsas coletadas em bolsas quádruplas pelo método da ECLP (ECLPQ com o uso de extrator automático. Encontramos diferença estatisticamente significante na quantidade de Hb total /unidade entre ECLPT e ECLPQ (p=0,005 e entre ECLPT e PRP (p=0,007 no ST. Houve diferença estatisticamente entre ECLPT e ECLPQ (pThe most commonly used methods for blood component processing are the "plasma rich in platelets method" (PRP, and the Buffy-coat extraction method (BC.The purpose of this study was to compare these two methods in the processing of blood components. Eighty-eight whole blood units (WB were processed by the PRP method, 130 blood units were processed by the BC triple blood bag method (BCT and 215 blood units were collected in quadruple blood bags by the BC method (BCQ using an automatic extractor. A statistically significant difference was observed in the number in the total Hb per unit of WB between the BCT and BCQ methods (p=0.005 and between the BCT and PRP methods (p=0.007. There were also statistically significant differences between the BCT and BCQ methods (p<0.001 and between BCQ and PRP methods (p<0.001 in relation to leukocytes/mL. In the RBC concentrates, we found statistically significant differences between the PRP method and both the BCT and BCQ methods in respect to hematocrit levels, Hb recovery, total Hb, leukocytes, leukocyte depletion, platelets and platelet depletion (p<0.001 in all cases. We also found statistically significant differences between the PRP, BCT and BCQ methods for the volume, platelet recovery, and leukocyte depletion (p<0

Contributions for classification of platelet rich plasma - proposal of a new classification: MARSPILL.

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Lana, Jose Fabio Santos Duarte; Purita, Joseph; Paulus, Christian; Huber, Stephany Cares; Rodrigues, Bruno Lima; Rodrigues, Ana Amélia; Santana, Maria Helena; Madureira, João Lopo; Malheiros Luzo, Ângela Cristina; Belangero, William Dias; Annichino-Bizzacchi, Joyce Maria

2017-07-01

Platelet-rich plasma (PRP) has emerged as a significant therapy used in medical conditions with heterogeneous results. There are some important classifications to try to standardize the PRP procedure. The aim of this report is to describe PRP contents studying celular and molecular components, and also propose a new classification for PRP. The main focus is on mononuclear cells, which comprise progenitor cells and monocytes. In addition, there are important variables related to PRP application incorporated in this study, which are the harvest method, activation, red blood cells, number of spins, image guidance, leukocytes number and light activation. The other focus is the discussion about progenitor cells presence on peripherial blood which are interesting due to neovasculogenesis and proliferation. The function of monocytes (in tissue-macrophages) are discussed here and also its plasticity, a potential property for regenerative medicine treatments.

Platelet-rich plasma and adipose-derived mesenchymal stem cells for regenerative medicine-associated treatments in bottlenose dolphins (Tursiops truncatus.

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Richard J Griffeth

Full Text Available Dolphins exhibit an extraordinary capacity to heal deep soft tissue injuries. Nevertheless, accelerated wound healing in wild or captive dolphins would minimize infection and other side effects associated with open wounds in marine animals. Here, we propose the use of a biological-based therapy for wound healing in dolphins by the application of platelet-rich plasma (PRP. Blood samples were collected from 9 different dolphins and a specific and simple protocol which concentrates platelets greater than two times that of whole blood was developed. As opposed to a commonly employed human protocol for PRP preparation, a single centrifugation for 3 minutes at 900 rpm resulted in the best condition for the concentration of dolphin platelets. By FACS analysis, dolphin platelets showed reactivity to platelet cell-surface marker CD41. Analysis by electron microscopy revealed that dolphin platelets were larger in size than human platelets. These findings may explain the need to reduce the duration and speed of centrifugation of whole blood from dolphins to obtain a 2-fold increase and maintain proper morphology of the platelets. For the first time, levels of several growth factors from activated dolphin platelets were quantified. Compared to humans, concentrations of PDGF-BB were not different, while TGFβ and VEGF-A were significantly lower in dolphins. Additionally, adipose tissue was obtained from cadaveric dolphins found along the Spanish Mediterranean coast, and adipose-derived mesenchymal stem cells (ASCs were successfully isolated, amplified, and characterized. When dolphin ASCs were treated with 2.5 or 5% dolphin PRP they exhibited significant increased proliferation and improved phagocytotic activity, indicating that in culture, PRP may improve the regenerative capacity of ASCs. Taken together, we show an effective and well-defined protocol for efficient PRP isolation. This protocol alone or in combination with ASCs, may constitute the basis of a

Effect of activated autologous platelet-rich plasma on proliferation and osteogenic differentiation of human adipose-derived stem cells in vitro

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Xu, Fang-Tian; Li, Hong-Mian; Yin, Qing-Shui; Liang, Zhi-Jie; Huang, Min-Hong; Chi, Guang-Yi; Huang, Lu; Liu, Da-Lie; Nan, Hua

2015-01-01

To investigate whether activated autologous platelet-rich plasma (PRP) can promote proliferation and osteogenic differentiation of human adipose-derived stem cells (hASCs) in vitro. hASCs were isolated from lipo-aspirates, and characterized by specific cell markers and multilineage differentiation capacity after culturing to the 3rd passage. PRP was collected and activated from human peripheral blood of the same patient. Cultured hASCs were treated with normal osteogenic inductive media alone (group A, control) or osteogenic inductive media plus 5%, 10%, 20%, 40%PRP (group B, C, D, E, respectively). Cell proliferation was assessed by CCK-8 assay. mRNA expression of osteogenic marker genes including alkaline phosphatase (ALP), osteopontin (OPN), osteocalcin (OCN) and core binding factor alpha 1 (Cbfa1) were determined by Real-Time Quantitative PCR Analysis (qPCR). Data revealed that different concentrations of activated autologous PRP significantly promoted hASCs growth in the proliferation phase compared to the without PRP group and resulted in a dose-response relationship. At 7-d and 14-d time point of the osteogenic induced stage, ALP activity in PRP groups gradually increased with the increasing of concentrations of PRP and showed that dose-response relationship. At 21-d time point of the osteogenic induced stage, PRP groups make much more mineralization and mRNA relative expression of ALP, OPN, OCN and Cbfa1 than that without PRP groups and show that dose-response relationship. This study indicated that different concentrations of activated autologous PRP can promote cell proliferation at earlier stage and promote osteogenic differentiation at later stage of hASCs in vitro. Moreover, it displayed a dose-dependent effect of activated autologous PRP on cell proliferation and osteogenic differentiation of hASCs in vitro. PMID:25901195

Platelet-rich plasma for chronic lateral epicondylitis: is one injection sufficient?

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Glanzmann, Michael C; Audigé, Laurent

2015-12-01

Chronic lateral epicondylitis is generally treated using nonsurgical methods including physiotherapy and infiltrations of cortisone or platelet-rich plasma (PRP). The latter is known for its simple application as well as associated low risk of adverse events, which lend to its widespread use in treating various musculoskeletal conditions. There is limited evidence on the effectiveness of PRP injections to optimally treat chronic lateral epicondylitis. This study explored the effectiveness of single or repeated injections for patients with symptoms that spanned 6 months or more and were unresponsive to alternate conservative measures. Patients with chronic lateral epicondylitis received PRP injections in 4-week intervals that were complemented with standardized physical therapy. Patient-reported outcomes based on the patient-rated elbow evaluation (PREE), quick disabilities of the arm, shoulder and hand (qDASH), and EuroQol (five dimensions) 3-level version (EQ5D3L) questionnaires were documented at each visit including 6 months after the first injection. These outcomes were compared between patients receiving 1 vs. 2 or 3 PRP injections. Sixty-two patients received one (n = 36) or more (n = 26) PRP injections. The mean baseline to 6-month follow-up scores of the PREE and qDASH questionnaires improved significantly from 54.0 to 23.0 and 50.3 to 20.7, respectively. The mean baseline EQ5D3L-visual analogue scale score improved from 62.5 to 82.9 by 6 months post-injection. These outcomes did not significantly differ between the patients who received varying numbers of injections. Patients with chronic lateral epicondylitis reported significant pain relief and gain in function as well as quality of life 6 months after localized PRP treatment. A single PRP injection may be sufficient.

Concentration-dependent effect of platelet-rich plasma on keratinocyte and fibroblast wound healing.

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Xian, Law Jia; Chowdhury, Shiplu Roy; Bin Saim, Aminuddin; Idrus, Ruszymah Bt Hj

2015-03-01

Platelet-rich plasma (PRP) has been found to contain a high concentration of growth factors that are present during the process of healing. Studies conducted found that application of PRP accelerates wound healing. In this study, we characterized the skin cell suspension harvested using the co-isolation technique and evaluated the effects of PRP (10% and 20%, v/v) on co-cultured keratinocytes and fibroblasts in terms of wound healing. Human keratinocytes and fibroblasts were harvested via co-isolation technique and separated via differential trypsinization. These cells were then indirectly co-cultured in medium supplemented with 10% or 20% PRP for 3 days without medium change for analysis of wound-healing potential. The wound-healing potential of keratinocytes and fibroblasts was evaluated in terms of growth property, migratory property, extracellular matrix gene expression and soluble factor secretion. The co-isolation technique yielded a skin cell population dominated by fibroblasts and keratinocytes, with a small amount of melanocytes. Comparison between the 10% and 20% PRP cultures showed that the 10% PRP culture exhibited higher keratinocyte apparent specific growth rate, and secretion of hepatocyte growth factor, monocyte chemoattractant protein-1, epithelial-derived neutrophil-activating protein 78 and vascular endothelial growth factor A, whereas the 20% PRP culture has significantly higher collagen type 1 and collagen type 3 expressions and produced more granulocyte-macrophage colony-stimulating factor. PRP concentration modulates keratinocyte and fibroblast wound healing potential, whereby the 10% PRP promotes wound remodeling, whereas the 20% PRP enhances inflammation and collagen deposition. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Differential effects of platelet rich plasma and washed platelets on the proliferation of mouse MSC cells.

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Duan, Jianmin; Kuang, Wei; Tan, Jiali; Li, Hongtao; Zhang, Yi; Hirotaka, Kikuchi; Tadashi, Katayama

2011-04-01

Multipotent mesenchymal stem cell (MSC) therapies are being tested clinically for a variety of disorders. However, despite the remarkable clinical advancements in this field, most applications still use traditional culture media containing fetal bovine serum. Platelet-rich plasma (PRP) appears as a novel application for tissue engineering and its effect on bone healing is thought to be mainly dependent on the proliferation promoting function, with the molecular mechanisms largely unknown. In this study, mouse osteogenic progenitor mesenchymal stem cells (MSCs) were cultured in PRP or washed platelet (WPLT)-treated wells or in untreated wells, and analyzed on cycloxygenase 2 (COX2) expression (qRT-PCR), cell growth (MTT assay) and cell differentiation (alkaline phosphatase activity). The results showed that PRP and WPLT stimulated cell growth similarly in the first 6 days, together with the steady induction of COX2 and PGE2. 10 μmol/l celecoxib (an inhibitor of COX2) significantly inhibited the pro-proliferation effects. Interestingly, WPLT had stronger effects than PRP in proliferation at the later time points (6-9 days). ALP activity assay and collagen 1a expression revealed PRP had a mild but statistically significant pro-differentiation effect, while no obvious effects observed in WLPT group. In summary, PRP stimulates initial growth of MSCs in a COX2 partially dependent manner and the less obvious osteogenic differentiation promoting effects of WPLT strongly indicates WPLT rather than the PRP should be the optional choice for expanding MSCs in vitro for clinical use.

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

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Oscar Rubini Ávila

Full Text Available 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.

Prevalence of periradicular periodontitis in a Scottish subpopulation found on CBCT images.

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Dutta, A; Smith-Jack, F; Saunders, W P

2014-09-01

To investigate the prevalence of periradicular periodontitis (PRP) using cone-beam computed tomography (CBCT) scans in a retrospective cross-sectional epidemiological study in a Scottish subpopulation. Of the 319 CBCT scans performed at Dundee Dental Hospital between November 2009 and July 2012, 245 dentate scans of patients over 18 years of age were included and 3595 teeth examined. Odds ratios were calculated, and the association between root filling and posts with PRP was determined. Radiological signs of PRP were detected in 209 teeth (5.8%) in 96 patients (male = 53, female = 43) of which 145 (69.4%) were measurable and 64 (30.6%) appeared as periapical widening. Most lesions were seen in the 46-55-year age group and in maxillary anterior teeth (35.4%); 47.4% (n = 81) of the total root filled teeth (n = 171) had PRP. Of the root filled teeth with lesions, approximately half (50.6%) had an inadequate root filling. Teeth with crowns, but not root filled, accounted for 17.7% of PRP. Periapical changes were detected on a high proportion of teeth with post-retained crowns (70.7%). The presence of a root filling was significantly associated with PRP (z = 17.689 P Scottish subpopulation was 5.8%. The presence of a root filling or a post-retained crown was significantly associated with the presence of PRP as determined by CBCT scans. The prevalence of periradicular disease in root filled teeth remains high in the Scottish population. © 2013 International Endodontic Journal. Published by John Wiley & Sons Ltd.

A Systematic Review of Autologous Platelet-Rich Plasma and Fat Graft Preparation Methods.

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Luck, Joshua; Smith, Oliver J; Mosahebi, Afshin

2017-12-01

The addition of platelet-rich plasma (PRP) to adipose tissue may improve fat graft survival, although graft retention rates vary markedly between studies. To what extent this outcome heterogeneity reflects differing methodological factors remains unknown. This systematic review aims to synthesize and critically review methodological approaches to autologous PRP and fat cotransplantation in both human and animal studies. In accordance with PRISMA guidelines, Ovid MEDLINE, Scopus, and Cochrane Library databases were searched from inception to April 2017. Data were extracted from all in vivo studies involving autologous PRP and fat cotransplantation. A secondary aim was to assess reporting of technical detail; authors were not contacted to provide missing data. From 335 articles, 23 studies were included in the qualitative synthesis. Some 21 were performed in humans and 2 in rabbits. Six studies were randomized control trials; the remainder reported on observational data. Methods of PRP extraction and activation varied markedly between studies. Fat graft preparation was comparatively more consistent. Methods of PRP and fat mixing differed significantly, especially with regards to relative volume/volume ratios. Our study represents the first systematic review of methodological factors in autologous PRP and fat cotransplantation. It demonstrates that technical factors in graft preparation and administration vary significantly between in vivo studies. Such methodological heterogeneity may explain observed differences in experimental and clinical outcomes. Reporting of key procedural information is inconsistent and often inadequate. These issues make meaningful evaluation of the PRP-enhanced fat grafting literature difficult and may limit its translation into clinical practice.

The effect of platelet rich plasma from bone marrow aspirate with added bone morphogenetic protein-2 on the Achilles tendon-bone junction in rabbits.

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Kim, Hak Jun; Nam, Hyok-Woo; Hur, Chang-Yong; Park, Misu; Yang, Hee Seok; Kim, Byung-Soo; Park, Jung-Ho

2011-12-01

To determine if exogenously injected bone marrow derived platelet-rich plasma (PRP) plus bone morphogenetic protein (BMP)-2 could accelerate the healing of bone-tendon junction injuries and increase the junction holding strength during the early regeneration period. A direct injury model of the bone-tendon junction was made using an Achilles tendon-calcaneus bone junction in a rabbit. In the PRP/BMP-2/fibrin group, 0.05 mL of bone marrow derived PRP and 100 ng/mL of BMP-2 both incorporated into 0.1 mL of fibrin glue were injected into Achilles tendon-calcaneus bone junctions. The effect of the intervention was tested by comparing the results of an intervention group to a control group. The results of biomechanical testing, and histological and gross analyses were compared between the 2 groups at the following time points after surgery: 2 weeks, 4 weeks, and 8 weeks. Histologic examinations showed that woven bone developed in tendon-bone junctions at 2 weeks after surgery in the PRP/BMP-2/fibrin group. Mechanical test results showed no significant difference between the PRP/BMP-2/fibrin and control groups at 2 and 4 weeks after surgery, but the mean maximal load in the PRP/BMP-2/fibrin group was significantly higher than in the control group (p rabbit model of tendon-bone junction injury.

Comparative study of the efficacy of Platelet-rich plasma combined with carboxytherapy vs its use with fractional carbon dioxide laser in atrophic acne scars.

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Al Taweel, Abdul-Aziz Ibrahim; Al Refae, Abdul-Aziz Abdul-Salam; Hamed, Ahmed Mohamed; Kamal, Asmaa Mostafa

2018-04-22

Acne scars are a major concerning problem to all acne patients affecting their quality of life. Platelet-rich plasma (PRP) and fractional CO 2 laser are innovative treatment modalities for acne scars. Carboxytherapy can also be used to improve scar tissue through the increase in collagen deposition and reorganization, and the improvement in skin texture and tone. The aim of this work was to compare the efficacy, safety, and complications of the intradermal injection of PRP combined with carboxytherapy and PRP combined with fractional CO 2 laser, in the treatment of atrophic acne scars. Forty patients with atrophic acne scars were divided into 2 groups. Group A included 20 patients and was subjected to three fractional CO 2 laser sessions combined with PRP injection. Group B included 20 patients and was subjected to three sessions of carboxytherapy combined with PRP injection. Both fractional CO 2 laser and carboxytherapy combined with PRP showed improvement in acne scars and patients' satisfaction but the improvement with fractional CO 2 laser was significantly better than carboxytherapy but with more side effects. Improvement of acne scars was noted in both treatment modalities with obvious higher and statistically significant results in favor of fractional CO 2 laser but with more side effects. Carboxytherapy is a promising tool in treatment of acne scars with less complication. © 2018 Wiley Periodicals, Inc.

A pilot weight reduction program over one year significantly reduced DNA strand breaks in obese subjects

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Karl-Heinz Wagner

2015-05-01

Conclusion: A sustainable lifestyle change under supervision including physical activity and diet quality over a period of one year was not only responsible to reduce body weight and BMI but also led to significant reduction in all parameters of the comet assay. These results underline the importance of body weight reduction and highlight the positive changes in DNA stability.

Bone Marrow Aspirate Concentrate versus Platelet Rich Plasma to Enhance Osseous Integration Potential for Osteochondral Allografts.

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Stoker, Aaron M; Baumann, Charles A; Stannard, James P; Cook, James L

2018-04-01

Fresh osteochondral allograft (OCA) transplantation is an attractive treatment option for symptomatic articular cartilage lesions in young, healthy patients. Since a lack of OCA bone integration can be a cause of treatment failure, methods for speeding and enhancing OCA bone integration to mitigate this potential complication are highly desirable. This study sought to determine and compare the potential of bone marrow aspirate concentrate (BMC) and leukoreduced platelet rich plasma (PRP) to repopulate the osseous portion of an OCA with cells and deliver osteogenic proteins. It was hypothesized that BMC would have significantly higher colony forming units (CFUs)/mL and seed the osseous portion of OCA with more cells than PRP. Finally, we hypothesized that the media of BMC and PRP treated OCAs would have significantly higher concentrations of osteogenic proteins compared with negative control OCAs. Cylindrical OCAs ( n  = 36) created from tissue stored for 21 days were treated with BMC ( n  = 12) or PRP ( n  = 12) obtained for 6 dogs, or left untreated as a negative control ( n  = 12). After treatment, OCAs were cultured for 7 or 14 days. Media were collected for analysis of osteogenic biomarker concentration. Samples of each BMC and PRP were tested for CFU concentration. On day 7 or 14, the grafts were assessed for cell surface adhesion and penetration using fluorescent microscopy. Significant differences in CFU and media biomarker concentration between the groups were determined using one-way analysis of variance (ANOVA) and Tukey's post-hoc test with the significance set at p  BMC had viable cells detectable on the osseous portion of the allografts at day 7 and 14 of culture. BMC samples had a significantly higher ( p  = 0.029) CFU/mL compared with PRP samples. At day 3 and/or 7 of culture, the concentration of several osteogenic proteins was significantly higher in both BMC and PRP samples. Autogenous BMC can be used to deliver both a cell

Therapeutic efficacy of connective tissue autotransplants with periosteum and platelet rich plasma in the management of gingival recession

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Jovičić Bojan

2013-01-01

Full Text Available Background/Aim. Gingival recession progression in clinical practaice has influenced the development of various surgical procedures and techniques for solving esthetic imperfections and subjective difficulties coused by gingival recession. The aim of this study was to verify efficacy of surgical procedures and to compare both of surgical procedures through the keratinized tissue width. Methods. The study included 20 teeth with gingival recesion, Müller class I and II. Ten teeth with gingival recession were treated with connective tissue autotransplants with periosteum in combination with coronary guided surgical flap (CTG group. On the contralateral side 10 teeth with gingival recession were treated with the same surgical procedures but in combination with platelet-rich plasma (CTGPRP group. We measured the keratinized tissue width. For statistical significance we used the Student's t-test. Results. The study reveled a statistical significance in reducing vertical deepress of recession by both used treatments. Root deepness in CTG and CTG-PRP group was 90% and 93.5%, respectively. With both surgical techniques we achieved larger zone of keratinized gingiva but with a wide zone of keratinized tissue in CTG - the PRP group. Conclusion. The concept regeneration technique with PRP and with the stimulating influence of platele activated growth factors results in the regeneration of deep periodontal tissue as an important prerequisite for the successful treatment of gingival recession.

The Chondrogenic Induction Potential for Bone Marrow-Derived Stem Cells between Autologous Platelet-Rich Plasma and Common Chondrogenic Induction Agents: A Preliminary Comparative Study

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Shan-zheng Wang

2015-01-01

Full Text Available The interests in platelet-rich plasma (PRP and their application in stem cell therapy have contributed to a better understanding of the basic biology of the prochondrogenesis effect on bone marrow-derived stem cells (BMSCs. We aimed at comparing the effect of autologous PRP with common chondrogenic induction agents (CCIAs on the chondrogenic differentiation of BMSCs. Rabbit BMSCs were isolated and characterized by flow cytometry and differentiated towards adipocytes and osteoblasts. The chondrogenic response of BMSCs to autologous PRP and CCIAs which included transforming growth factor-β1 (TGF-β1, dexamethasone (DEX, and vitamin C (Vc was examined by cell pellet culture. The isolated BMSCs after two passages highly expressed CD29 and CD44 but minimally expressed CD45. The osteogenic and adipogenic differentiation potentials of the isolated BMSCs were also confirmed. Compared with common CCIAs, autologous PRP significantly upregulated the chondrogenic related gene expression, including Col-2, AGC, and Sox-9. Osteogenic related gene expression, including Col-1 and OCN, was not of statistical significance between these two groups. Thus, our data shows that, compared with common chondrogenic induction agents, autologous PRP can be more effective in promoting the chondrogenesis of BMSCs.

The effect of platelet-rich plasma on osseous healing in dogs undergoing high tibial osteotomy.

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Samuel P Franklin

Full Text Available The purpose of this study was to investigate whether platelet-rich plasma (PRP enhances osseous healing in conjunction with a high tibial osteotomy in dogs.Randomized controlled trial.Sixty-four client-owned pet dogs with naturally occurring rupture of the anterior cruciate ligament and that were to be treated with a high tibial osteotomy (tibial plateau leveling osteotomy were randomized into the treatment or control group. Dogs in the treatment group received autologous platelet-rich plasma activated with calcium chloride and bovine thrombin to produce a well-formed PRP gel that was placed into the osteotomy at the time of surgery. Dogs in the control group received saline lavage of the osteotomy. All dogs had the osteotomy stabilized with identical titanium alloy implants and all aspects of the surgical procedure and post-operative care were identical among dogs of the two groups. Bone healing was assessed at exactly 28, 49, and 70 days after surgery with radiography and ultrasonography and with MRI at day 28. The effect of PRP on bone healing was assessed using a repeated measures analysis of covariance with radiographic and ultrasonographic data and using a t-test with the MRI data.Sixty dogs completed the study. There were no significant differences in age, weight, or gender distribution between the treatment and control groups. Twenty-seven dogs were treated with PRP and 33 were in the control group. The average platelet concentration of the PRP was 1.37x106 platelets/μL (±489x103 with a leukocyte concentration of 5.45x103/μL (±3.5x103. All dogs demonstrated progressive healing over time and achieved clinically successful outcomes. Time since surgery and patient age were significant predictors of radiographic healing and time since surgery was a significant predictor of ultrasonographic assessment of healing. There was no significant effect of PRP treatment as assessed radiographically, ultrasonographically, or with MRI.The PRP used

Intra-Articular Injections of Platelet-Rich Plasma versus Hyaluronic Acid in the Treatment of Osteoarthritic Knee Pain: A Randomized Clinical Trial in the Context of the Spanish National Health Care System.

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Montañez-Heredia, Elvira; Irízar, Sofia; Huertas, Pedro J; Otero, Esperanza; Del Valle, Marta; Prat, Isidro; Díaz-Gallardo, Macarena S; Perán, Macarena; Marchal, Juan A; Hernandez-Lamas, María Del Carmen

2016-07-02

Intra-articular injection of platelet-rich plasma (PRP) has been established as a suitable treatment for knee osteoarthritis. Here, we present a double-blind randomized controlled clinical trial, conducted in a public Hospital of the Spanish National Health Care System, to evaluate the efficacy of injecting autologous PRP versus hyaluronic acid (HA) in knee osteoarthritis. PRP was manufactured in Malaga's Regional Blood Center (Spain). Patients that met the eligibility criteria were randomized into a PRP group or a HA group. Pain and functional improvements were assessed pre- and post-treatment (three and six months follow-up) using the Visual Analogue Scale (VAS); the Knee and Osteoarthritis Outcome System (KOOS) scale and the European Quality of Life scale (EUROQOL). Both groups presented pain reduction at six months. The VAS scores for the PRP group improved by at least 50% from their initial value, particularly at three months following the final infiltration, with results resembling those of the HA group at six months. PRP was more effective in patients with lower osteoarthritis grades. Both treatments improved pain in knee osteoarthritis patients without statistically significant differences between them. However, PRP injection was proved to improve pain three months after the final infiltration and to be more effective in lower osteoarthritis grades.

A serum and platelet-rich plasma serotonin assay using liquid chromatography tandem mass spectrometry for monitoring of neuroendocrine tumor patients.

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Korse, Catharina M; Buning-Kager, Johanna C G M; Linders, Theodora C; Heijboer, Annemieke C; van den Broek, Daan; Tesselaar, Margot E T; van Tellingen, Olaf; van Rossum, Huub H

2017-06-01

Serotonin is used for the diagnosis and follow-up of neuroendocrine tumors (NET). We describe the analytical and clinical validation of a liquid chromatography tandem mass spectrometry (LC-MS/MS) based serotonin assay for serum and platelet-rich plasma (PRP). An LC-MS/MS based method for serum and PRP serotonin was validated by determination of assay imprecision, carry-over, linearity, interference, recovery, sample stability and a matrix/method comparison of serum and PRP serotonin was made with whole blood serotonin. Furthermore, upper limits of normal were determined and serotonin concentrations of healthy individuals, 14 NET patients without evidence of disease and 51 NET patients with evidence of disease were compared. For serum and PRP fractions, total assay imprecision was serotonin upper limit of normal were 5.5nmol/10 9 platelet and 5.1nmol/10 9 platelet, respectively. NET patients with confirmed evidence of disease had significantly higher serum and PRP serotonin levels when compared to NET patients without evidence of disease and healthy volunteers. LC-MS/MS based serum and PRP serotonin assays were developed with suitable analytical characteristics. Furthermore, serum and PRP serotonin was found to be useful for monitoring NET patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of diabetic retinopathy and panretinal photocoagulation on retinal nerve fiber layer and optic nerve appearance.

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Lim, Michele C; Tanimoto, Suzana A; Furlani, Bruno A; Lum, Brent; Pinto, Luciano M; Eliason, David; Prata, Tiago S; Brandt, James D; Morse, Lawrence S; Park, Susanna S; Melo, Luiz A S

2009-07-01

To determine if panretinal photocoagulation (PRP) alters retinal nerve fiber layer (RNFL) thickness and optic nerve appearance. Patients with diabetes who did and did not undergo PRP and nondiabetic control subjects were enrolled in a prospective study. Participants underwent optical coherence tomography of the peripapillary retina and optic nerve. Stereoscopic optic nerve photographs were graded in a masked fashion. Ninety-four eyes of 48 healthy individuals, 89 eyes of 55 diabetic patients who did not undergo PRP, and 37 eyes of 24 subjects with diabetes who underwent PRP were included in this study. Eyes that had been treated with PRP had thinner peripapillary RNFL compared with the other groups; this was statistically significantly different in the inferior (P = .004) and nasal (P = .003) regions. Optic nerve cupping did not increase with severity of disease classification, but the proportion of optic nerves graded as suspicious for glaucoma or as having nonglaucomatous optic neuropathy did (P = .008). These grading categories were associated with thinner RNFL measurements. Diabetic eyes that have been treated with PRP have thinner RNFL than nondiabetic eyes. Optic nerves in eyes treated with PRP are more likely to be graded as abnormal, but their appearance is not necessarily glaucomatous and may be related to thinning of the RNFL.

Study of platelet-rich plasma injections in the treatment of androgenetic alopecia through an one-year period

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Maria-Angeliki Gkini

2014-01-01

Full Text Available Background: Platelet-rich plasma (PRP is defined as an autologous concentration of plasma with a greater count of platelets than that of whole blood. Its action depends on the released growth factors from platelets. It has been investigated and used in numerous fields of medicine. Recently, PRP has received growing attention as a potential therapeutic tool for hair loss. Aims: To evaluate the efficacy and safety of PRP injections in the scalp of patients with androgenetic alopecia. Settings and Design: Prospective cohort study. Materials and Methods: 20 patients, 18 males and 2 females, with androgenetic alopecia were enrolled in the study. PRP was prepared using a single spin method (Regenlab SA. Upon activation, it was injected in the androgen-related areas of scalp. Three treatment sessions were performed with an interval of 21 days and a booster session at 6 months following the onset of therapy. Statistical Analysis: Statistical analysis of the data was performed using the Statistical Package for the Social Sciences (SPSS, version 19.0 (IBM, NY, USA. Results: Hair loss reduced and at 3 months it reached normal levels. Hair density reached a peak at 3 months (170.70 ± 37.81, P < 0.001. At 6 months and at 1 year, it was significantly increased, 156.25 ± 37.75 (P < 0.001 and 153.70 ± 39.92 (P < 0.001 respectively, comparing to baseline. Patients were satisfied with a mean result rating of 7.1 on a scale of 1-10. No remarkable adverse effects were noted. Conclusions: Our data suggest that PRP injections may have a positive therapeutic effect on male and female pattern hair loss without remarkable major side effects. Further studies are needed to confirm its efficacy.

Hop/STI1 modulates retinal proliferation and cell death independent of PrPC

International Nuclear Information System (INIS)

Arruda-Carvalho, Maithe; Njaine, Brian; Silveira, Mariana S.; Linden, Rafael; Chiarini, Luciana B.

2007-01-01

Hop/STI1 is a co-chaperone adaptor protein for Hsp70/Hsp90 complexes. Hop/STI1 is found extracellularly and modulates cell death and differentiation through interaction with the prion protein (PrP C ). Here, we investigated the expression of hop/STI1 and its role upon cell proliferation and cell death in the developing retina. Hop/STI1 is more expressed in developing rat retina than in the mature tissue. Hop/STI1 blocks retinal cell death in the neuroblastic layer (NBL) in a PrP C dependent manner, but failed to protect ganglion cells against axotomy-induced cell death. An antibody raised against hop/STI1 (α-STI1) blocked both ganglion cell and NBL cell death independent of PrP C . cAMP/PKA, ERK, PI3K and PKC signaling pathways were not involved in these effects. Hop/STI1 treatment reduced proliferation, while α-STI1 increased proliferation in the developing retina, both independent of PrP C . We conclude that hop/STI1 can modulate both proliferation and cell death in the developing retina independent of PrP C

Single-Spot Yellow Laser Versus Conventional Green Laser on Panretinal Photocoagulation: Patient Pain Scores and Preferences.

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González-Saldivar, Gerardo; Rojas-Juárez, Sergio; Espinosa-Soto, Itzel; Sánchez-Ramos, Jorge; Jaurieta-Hinojosa, Noel; Ramírez-Estudillo, Abel

2017-11-01

Panretinal photocoagulation (PRP) is the mainstay therapy for proliferative diabetic retinopathy. Pain during and after its application is a complication that affects patients' therapeutic adherence. This study aimed to compare pain perception and patient preference for the 577-nm yellow laser (YL-577) (LIGHTL as 577; LIGHTMED, San Clemente, CA) and the conventional 532-nm green laser (GL-532) (Purepoint Laser; Alcon, Fort Worth, TX) with PRP. A total of 92 patient eyes with proliferative diabetic retinopathy treated with PRP were randomly assigned to receive both GL-532 and YL-577 (184 eyes) - one on each eye, with the order of application randomized, as well. Afterward, verbal rapid answer and visual analogue scale (VAS) scores for pain perception and patient preference were evaluated. VAS score was 7 ± 2 for the GL-532 group compared to 5 ± 3 in the YL-577 group (P = .001). Overall, 75% of the patients preferred YL-577 therapy if they were to receive a second PRP session. The use of YL-577 as an alternative approach for PRP reduces pain perception and is preferred by patients. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:902-905.]. Copyright 2017, SLACK Incorporated.

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

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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. Copyright: © Singapore Medical Association

Assess the effectiveness of nimesulide in reducing pain in panretinal photocoagulation%尼美舒利在全视网膜光凝术中镇痛效果分析

Institute of Scientific and Technical Information of China (English)

程华; 李良平; 程显芹

2013-01-01

was 1.1111±0.7511,(P ＞0.05).The mean pain level for group nimesulide was 7.8167±3.4046 and group placebo was 8.6778±3.5499,(P ＞0.05).There was no significant difference for pain levels between nimesulide instilled and placebo eyes (P ＞0.05).Conclusions Pre-emptive analgesia with nimesulide dose not significantly reduces pain associated with PRP.

Expansion of the octarepeat domain alters the misfolding pathway but not the folding pathway of the prion protein.

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Leliveld, S Rutger; Stitz, Lothar; Korth, Carsten

2008-06-10

A misfolded conformation of the prion protein (PrP), PrP (Sc), is the essential component of prions, the infectious agents that cause transmissible neurodegenerative diseases. Insertional mutations that lead to an increase in the number of octarepeats (ORs) in PrP are linked to familial human prion disease. In this study, we investigated how expansion of the OR domain causes PrP to favor a prion-like conformation. Therefore, we compared the conformational and aggregation modulating properties of wild-type versus expanded OR domains, either as a fusion construct with the protein G B1 domain (GB1-OR) or as an integral part of full-length mouse PrP (MoPrP). Using circular dichroism spectroscopy, we first demonstrated that ORs are not unfolded but exist as an ensemble of three distinct conformers: polyproline helix-like, beta-turn, and "Trp-related". Domain expansion had little effect on the conformation of GB1-OR fusion proteins. When part of MoPrP however, OR domain expansion changed PrP's folding landscape, not by hampering the production of native alpha-helical monomers but by greatly reducing the propensity to form amyloid and by altering the assembly of misfolded, beta-rich aggregates. These features may relate to subtle pH-dependent conformational differences between wild-type and mutant monomers. In conclusion, we propose that PrP insertional mutations are pathogenic because they enhance specific misfolding pathways of PrP rather than by undermining native folding. This idea was supported by a trial bioassay in transgenic mice overexpressing wild-type MoPrP, where intracerebral injection of recombinant MoPrP with an expanded OR domain but not wild-type MoPrP caused prion disease.

Reduced bone mineral density is not associated with significantly reduced bone quality in men and women practicing long-term calorie restriction with adequate nutrition.

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Villareal, Dennis T; Kotyk, John J; Armamento-Villareal, Reina C; Kenguva, Venkata; Seaman, Pamela; Shahar, Allon; Wald, Michael J; Kleerekoper, Michael; Fontana, Luigi

2011-02-01

Calorie restriction (CR) reduces bone quantity but not bone quality in rodents. Nothing is known regarding the long-term effects of CR with adequate intake of vitamin and minerals on bone quantity and quality in middle-aged lean individuals. In this study, we evaluated body composition, bone mineral density (BMD), and serum markers of bone turnover and inflammation in 32 volunteers who had been eating a CR diet (approximately 35% less calories than controls) for an average of 6.8 ± 5.2 years (mean age 52.7 ± 10.3 years) and 32 age- and sex-matched sedentary controls eating Western diets (WD). In a subgroup of 10 CR and 10 WD volunteers, we also measured trabecular bone (TB) microarchitecture of the distal radius using high-resolution magnetic resonance imaging. We found that the CR volunteers had significantly lower body mass index than the WD volunteers (18.9 ± 1.2 vs. 26.5 ± 2.2 kg m(-2) ; P = 0.0001). BMD of the lumbar spine (0.870 ± 0.11 vs. 1.138 ± 0.12 g cm(-2) , P = 0.0001) and hip (0.806 ± 0.12 vs. 1.047 ± 0.12 g cm(-2) , P = 0.0001) was also lower in the CR than in the WD group. Serum C-terminal telopeptide and bone-specific alkaline phosphatase concentration were similar between groups, while serum C-reactive protein (0.19 ± 0.26 vs. 1.46 ± 1.56 mg L(-1) , P = 0.0001) was lower in the CR group. Trabecular bone microarchitecture parameters such as the erosion index (0.916 ± 0.087 vs. 0.877 ± 0.088; P = 0.739) and surface-to-curve ratio (10.3 ± 1.4 vs. 12.1 ± 2.1, P = 0.440) were not significantly different between groups. These findings suggest that markedly reduced BMD is not associated with significantly reduced bone quality in middle-aged men and women practicing long-term calorie restriction with adequate nutrition.

Antimicrobial effect of platelet-rich plasma and platelet-rich fibrin.

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Badade, Pallavi S; Mahale, Swapna A; Panjwani, Alisha A; Vaidya, Prutha D; Warang, Ayushya D

2016-01-01

Platelet concentrates have been extensively used in a variety of medical fields to promote soft- and hard-tissue regeneration. The significance behind their use lies in the abundance of growth factors (GFs) in platelets α-granules that promote wound healing. Other than releasing a pool of GFs upon activation, platelets also have many features that indicate their role in the anti-infective host defense. The aim of this study is to evaluate the antimicrobial activities of platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) against periodontal disease-associated bacteria. Blood samples were obtained from ten adult male patients. PRP and PRF were procured using centrifugation. The antimicrobial activity of PRP and PRF was evaluated by microbial culturing using bacterial strains of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. P. gingivalis and A. actinomycetemcomitans were inhibited by PRP but not by PRF. PRP is a potentially useful substance in the fight against periodontal pathogens. This might represent a valuable property in adjunct to the enhancement of tissue regeneration.

Autologous platelet-rich plasma compared with whole blood for the treatment of chronic plantar fasciitis; a comparative clinical trial

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Babak Vahdatpour

2016-01-01

Conclusions: Significant improvement in pain and function, as well as decrease in plantar fascia thickness, was observed by intralesional injection of the PRP and WB in patients with chronic PF. The study results indicate similar effectiveness between PRP and WB for the treatment of chronic PF in short-term.

The effect of autologous activated platelet-rich plasma injection on female pattern hair loss: A randomized placebo-controlled study.

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Tawfik, Abeer Attia; Osman, Mai Abdel Raouf

2018-02-01

Hair is an essential part of a woman's appearance and attractiveness. This is reflected in the predominantly psychological morbidity that can be associated with female pattern hair loss. Platelet-rich plasma(PRP) has been used in numerous fields of medicine. Recently, PRP has received growing attention as a potential therapeutic tool for hair loss. To evaluate the efficacy and safety of autologous platelet-rich plasma in the treatment of female pattern hair loss. Thirty female patients with female pattern hair loss were randomly assigned to receive autologous PRP injection into a selected area, and another area was injected with normal saline as a placebo. Sessions were performed weekly for a maximum total of four sessions. Patients were followed up 6 months after the end of last session. The outcome was assessed both subjectively and objectively. There was a statistical significant difference between PRP and placebo areas (Phair density and hair thickness as measured by a folliscope. The hair pull test became negative in PRP-injected areas in 25 patients (83%) with average number of three hairs. Global pictures showed a significant improvement in hair volume and quality together with a high overall patient satisfaction in PRP-injected sites, and these results were maintained during the 6-month follow- up. Platelet-rich plasma injections can be regarded as an alternative for the treatment of female pattern hair loss with minimal morbidity and a low cost-to-benefit ratio. © 2017 Wiley Periodicals, Inc.

Platelet-rich plasma enhances the integration of bioengineered cartilage with native tissue in an in vitro model.

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Sermer, Corey; Kandel, Rita; Anderson, Jesse; Hurtig, Mark; Theodoropoulos, John

2018-02-01

Current therapies for cartilage repair can be limited by an inability of the repair tissue to integrate with host tissue. Thus, there is interest in developing approaches to enhance integration. We have previously shown that platelet-rich plasma (PRP) improves cartilage tissue formation. This raised the question as to whether PRP could promote cartilage integration. Chondrocytes were isolated from cartilage harvested from bovine joints, seeded on a porous bone substitute and grown in vitro to form an osteochondral-like implant. After 7 days, the biphasic construct was soaked in PRP for 30 min before implantation into the core of a donut-shaped biphasic explant of native cartilage and bone. Controls were not soaked in PRP. The implant-explant construct was cultured for 2-4 weeks. PRP-soaked bioengineered implants integrated with host tissue in 73% of samples, whereas controls only integrated in 19% of samples. The integration strength, as determined by a push-out test, was significantly increased in the PRP-soaked implant group (219 ± 35.4 kPa) compared with controls (72.0 ± 28.5 kPa). This correlated with an increase in glycosaminoglycan and collagen accumulation in the region of integration in the PRP-treated implant group, compared with untreated controls. Immunohistochemical studies revealed that the integration zone contained collagen type II and aggrecan. The cells at the zone of integration in the PRP-soaked group had a 3.5-fold increase in matrix metalloproteinase-13 gene expression compared with controls. These results suggest that PRP-soaked bioengineered cartilage implants may be a better approach for cartilage repair due to enhanced integration. Copyright © 2017 John Wiley & Sons, Ltd.

Combination of platelet rich plasma in fractional carbon dioxide laser treatment increased clinical efficacy of for acne scar by enhancement of collagen production and modulation of laser-induced inflammation.

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Min, Seonguk; Yoon, Ji Young; Park, Seon Yong; Moon, Jungyoon; Kwon, Hyuck Hoon; Suh, Dae Hun

2018-04-01

Platelet-rich plasma (PRP) which contains large amounts of growth factors has been tried to enhance therapeutic efficacy of laser treatment for acne scar with unknown underlying mechanism. The present study was conducted to investigate the molecular mechanism of increased clinical efficacy of PRP when combined with fractional laser treatment for treating acne scars. Subjects with mild to moderate acne scars were treated with two sessions of fractional CO 2 laser therapy given with and without co-administration of PRP. Skin biopsy specimens were obtained at baseline, 1, 3, 7, and 28 days for investigation of molecular profiles associated with skin changes produced by laser plus PRP treatment. The PRP treatment increased clinical efficacy with decreased severity of adverse effects such as erythema, swelling and oozing. Productions of TGFβ1 and TGFβ3 proteins were more highly elevated on the PRP-treated side of the face compared to the control side at day 28. Furthermore, PRP-treated side showed significant increase of c-myc, TIMP, and HGF expression. Experimental fibroblast culture model was also used. PRP administration after laser irradiation increased expressions of p-Akt, TGFβ1, TGFβ3, β-catenin, collagen 1, and collagen 3 in both dose-dependent and time dependent manners in fibroblast. Moreover, we acquired clinical and histological data through randomized control clinical trial. Taken together with human study results combined with the data from cell experiments we suggest that PRP treatment increased fibrogenetic molecules induced by fractional CO 2 laser, which have association with clinical effect. Lasers Surg. Med. 50:302-310, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Effects of three blood derived products on equine corneal cells, an in vitro study.

Science.gov (United States)

Rushton, J O; Kammergruber, E; Tichy, A; Egerbacher, M; Nell, B; Gabner, S

2018-05-01

Despite advances in therapy of corneal ulcerative diseases in horses, a vast number of cases require surgical intervention, due to poor response to treatment. Topical application of serum has been used for many years, based on its anticollagenolytic properties and the presence of growth factors promoting corneal wound healing. However, although other blood derived products i.e. platelet rich plasma (PRP), plasma rich in growth factors (PRGF) have been widely used in equine orthopaedics and in human ophthalmology, no reports of the effects of these blood derived products exist in equine ophthalmology. To determine in vitro effects of PRGF and PRP on equine corneal cells compared with serum. Prospective controlled cohort study. Blood from 35 healthy horses was used to produce serum, PRGF (Endoret ® ), and PRP (E-PET™). Limbal- and stromal cells were isolated from healthy corneas of six horses and treated with 20% serum, 20% PRGF or 20% PRP. Proliferation rates and migration capacity were analysed in single cell cultures as well as co-culture systems. Cell proliferation increased with PRP treatment, remained constant in PRGF treated cells, and declined upon serum treatment over a period of 48 h. Migration capacity was significantly enhanced with PRP treatment, compared with PRGF treatment. Intact leucocytes, mainly eosinophils, were only detected in PRP. Due to the study design use of autologous blood products on corneal cells was not possible. The results demonstrate beneficial effects of PRP on proliferation as well as migration capacity of equine corneal cells in vitro. In vivo studies are warranted to determine further beneficial effects of PRP in horses with corneal ulcers. © 2017 EVJ Ltd.

Application of platelet-rich plasma in plastic surgery: clinical and in vitro evaluation.

Science.gov (United States)

Cervelli, Valerio; Gentile, Pietro; Scioli, Maria Giovanna; Grimaldi, Monica; Casciani, Carlo Umberto; Spagnoli, Luigi Giusto; Orlandi, Augusto

2009-12-01

The clinical use of platelet-rich plasma (PRP) for a wide variety of application has been reportedly employed most prevalently in problematic wounds, maxillofacial and hemi-facial atrophy, Romberg Syndrome, and diabetic foot ulcers. To our knowledge, PRP has never been described in the enhancement of fat grafting during tissue-engineering application in vivo. The authors describe the preparation of PRP and its use in a series of 43 patients who underwent plastic, reconstructive, and maxillofacial surgery for chronic lower extremity ulcers (n = 18) and multiple facial applications (n = 25). PRP mixed with fat grafting was used in 76% patients affected by multiple facial diseases and in 88.9% patients affected by lower extremity ulcers. PRP injection alone was used in the remaining patients. The authors observed that after a 7.1-week and 9.7-week (average) course of twice-daily wound treatment with PRP suspended on a collagen base, 61.1% and 88.9% of chronic lower extremity ulcers underwent to 100% reepithelization compared with 40% and 60% of controls (n = 10) treated with hyaluronic acid and collagen medication. In patients treated with reconstructing three-dimensional projection of face by fat grafting and PRP, we observed a 70% maintenance of contour restoring and three-dimensional volume after 1 year compared to only 31% of controls (n = 10) treated with fat grafting alone. In vitro, PRP induced a significant increase in the number of adipose-tissue-derived stem cells compared to control cultures. These results documented that PRP accelerates chronic skin ulcer reepithelization and improves maintenance and function of fat graft in patients who underwent plastic reconstructive surgery, possibly by stimulating adipose-tissue-derived stem cell proliferation.

Cloning, tissue distribution and effects of fasting on pituitary adenylate cyclase-activating polypeptide in largemouth bass

Science.gov (United States)

Li, Shengjie; Han, Linqiang; Bai, Junjie; Ma, Dongmei; Quan, Yingchun; Fan, Jiajia; Jiang, Peng; Yu, Lingyun

2015-03-01

Pituitary adenylate cyclase activating polypeptide (PACAP) has a wide range of biological functions. We cloned the full-length cDNAs encoding PACAP and PACAP-related peptide (PRP) from the brain of largemouth bass ( Micropterus salmoides) and used real-time quantitative PCR to detect PRP-PACAP mRNA expression. The PRP-PACAP cDNA has two variants expressed via alternative splicing: a long form, which encodes both PRP and PACAP, and a short form, which encodes only PACAP. Sequence analysis results are consistent with a higher conservation of PACAP than PRP peptide sequences. The expression of PACAP-long and PACAP-short transcripts was highest in the forebrain, followed by the medulla, midbrain, pituitary, stomach, cerebellum, intestine, and kidney; however, these transcripts were either absent or were weakly expressed in the muscle, spleen, gill, heart, fatty tissue, and liver. The level of PACAP-short transcript expression was significantly higher than expression of the long transcript in the forebrain, cerebella, pituitary and intestine, but lower than that of the long transcript in the stomach. PACAP-long and PACAP-short transcripts were first detected at the blastula stage of embryogenesis, and the level of expression increased markedly between the muscular contraction stage and 3 d post hatch (dph). The expression of PACAP-long and PACAP-short transcripts decreased significantly in the brain following 4 d fasting compared with the control diet group. The down-regulation effect was enhanced as fasting continued. Conversely, expression levels increased significantly after 3 d of re-feeding. Our results suggest that PRP-PACAP acts as an important factor in appetite regulation in largemouth bass.

Mindfulness significantly reduces self-reported levels of anxiety and depression

DEFF Research Database (Denmark)

Würtzen, Hanne; Dalton, Susanne Oksbjerg; Elsass, Peter

2013-01-01

INTRODUCTION: As the incidence of and survival from breast cancer continue to raise, interventions to reduce anxiety and depression before, during and after treatment are needed. Previous studies have reported positive effects of a structured 8-week group mindfulness-based stress reduction program...

Incubation of human blood fractions leads to changes in apparent miRNA abundance

DEFF Research Database (Denmark)

Skovgaard, Kerstin; Jørgensen, Stine Thuen; Heegaard, Peter M. H.

in significant changes in the abundance of miR-21, miR-155, Let-7c and Let 7f in plasma, miR-21, miR-23a and miR-150 in RBC and miR-15b, miR-126, miR155 and Let-7g in PBMC, while no change was seen in PRP and PMN. Interestingly, in the samples incubated with glass beads, no miRNAs were significantly affected...... in plasma, RBC, PBMC and PMN, while expression of miR-25, miR15a, miR-126 and miR223 was significantly changed in PRP. Thus, PRP, as the only blood fraction depended on stimulation to change its miRNA profile upon incubation. For the other fractions, stimulation either leveled out the changes induced...

Reduced content of chloroatranol and atranol in oak moss absolute significantly reduces the elicitation potential of this fragrance material.

Science.gov (United States)

Andersen, Flemming; Andersen, Kirsten H; Bernois, Armand; Brault, Christophe; Bruze, Magnus; Eudes, Hervé; Gadras, Catherine; Signoret, Anne-Cécile J; Mose, Kristian F; Müller, Boris P; Toulemonde, Bernard; Andersen, Klaus Ejner

2015-02-01

Oak moss absolute, an extract from the lichen Evernia prunastri, is a valued perfume ingredient but contains extreme allergens. To compare the elicitation properties of two preparations of oak moss absolute: 'classic oak moss', the historically used preparation, and 'new oak moss', with reduced contents of the major allergens atranol and chloroatranol. The two preparations were compared in randomized double-blinded repeated open application tests and serial dilution patch tests in 30 oak moss-sensitive volunteers and 30 non-allergic control subjects. In both test models, new oak moss elicited significantly less allergic contact dermatitis in oak moss-sensitive subjects than classic oak moss. The control subjects did not react to either of the preparations. New oak moss is still a fragrance allergen, but elicits less allergic contact dermatitis in previously oak moss-sensitized individuals, suggesting that new oak moss is less allergenic to non-sensitized individuals. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Interleukin-6, Creatine Kinase, and Antioxidant Enzyme Activities following Platelet-Rich Plasma Treatment on Muscle Injury: A Pilot Study

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Lingling Lai

2016-06-01

Full Text Available The aim of this study was to investigate the effect of autologous platelet-rich plasma (PRP treatment alongside rehabilitation compared with rehabilitation alone on inflammatory cytokine (interleukin-6, IL-6, creatine kinase muscle type (CKM, and antioxidant enzymes (superoxide dismutase, SOD; catalase, CAT following hamstring injury. This study was a randomised control trial. Participants diagnosed with grade-2 acute hamstring injury (n=16 were divided into 2 groups of PRP treatment with rehabilitation program (PRP-T and rehabilitation program (CON. Blood samples were collected at baseline, and 2 fortnightly for the various biochemical assessments. Participants were certified to have recovered upon fulfilling return to play (RTP criteria. Level of IL-6 and the activities of CKM, SOD, and CAT were measured. PRP-T group benefited from earlier time to RTP with significantly lower IL-6 level and CAT activity compared to CON group. There was no significant difference in CKM and SOD activities between the groups, though a trend of lower values in all variables was observed at week 4 compared to week 0. PRP treatment potentially improves muscle healing process by altering both the inflammatory and oxidative responses, hence hastens time to RTP. KEY WORDS:  Autologous, blood injection, rehabilitation, sports injury, hamstring injury

Comparison of Local Injection of Platelet Rich Plasma and Corticosteroids in the Treatment of Lateral Epicondylitis of Humerus.

Science.gov (United States)

Yadav, Raman; Kothari, S Y; Borah, Diganta

2015-07-01

Lateral epicondylitis or Tennis Elbow is one of the most common causes of upper extremity pain with various treatment options. Platelet-rich plasma (PRP) offers a new option for the treatment of lateral epicondylitis. This study was conducted with an aim to compare the efficacy of PRP versus methyl-prednisolone local injection in patients with lateral epicondylitis. Sixty five patients with lateral epicondylitis were included in the study and randomized into two groups. Group A was treated with single injection of 1ml PRP with absolute platelet count of at least 1 million platelets/ mm(3). Group B was treated with single injection of 1ml (40mg) methyl-prednisolone. Pain, grip strength and functional improvements were assessed using visual analogue scale, dynamometer and quick Disabilities of the Arm, Shoulder and Hand scale respectively at baseline, 15 days, 1 month and 3 months. Sixty patients completed the follow up. All assessment parameters improved significantly in both the Groups at each follow up compared to baseline. At the end of three months group A showed significantly better improvement as compared to Group B. PRP and methyl-prenisolone both are effective in the treatment of lateral epicondylitis. However, PRP is a superior treatment option for longer duration efficacy.

Enhanced Tendon-to-Bone Healing of Chronic Rotator Cuff Tears by Bone Marrow Aspirate Concentrate in a Rabbit Model

Science.gov (United States)

Liu, Xiao Ning; Yang, Cheol-Jung; Kim, Ji Eui; Du, Zhen Wu; Ren, Ming; Zhang, Wei; Zhao, Hong Yu; Kim, Kyung Ok

2018-01-01

Background To evaluate the influence of bone marrow aspirate concentrate (BMAC) on tendon-to-bone healing in a rabbit rotator cuff model and to characterize the composition of growth factors in BMAC. Methods In this in vivo study, 40 rabbits were allocated into five groups: control (C), repair + saline (RS), repair + platelet-rich plasma (PRP; RP), repair + BMAC (RB) and repair + PRP + BMAC (RPB). A tear model was created by supraspinatus tendon transection at the footprint. Six weeks after transection, the torn tendon was repaired along with BMAC or PRP administration. Six weeks after repair, shoulder samples were harvested for biomechanical and histological testing. Ten rabbits were used for processing PRP and BMAC, followed by analysis of blood cell composition and the levels of growth factors in vitro. Results The ultimate load-to-failure was significantly higher in RPB group compared to RS group (p = 0.025). BMAC-treated groups showed higher values of biomechanical properties than RS group. The histology of BMAC-treated samples showed better collagen fiber continuity and orientation than RS group. BMAC contained significantly higher levels of the several growth factors than PRP. Conclusions Locally administered BMAC enhanced tendon-to-bone healing and has potential for clinical applications. PMID:29564054

Platelet-Rich Plasma in the Treatment of Subcutaneous Venous Access Device Scars: A Head-to-Head Patient Survey

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C. Eichler

2015-01-01

Full Text Available Introduction. Platelet-rich plasma (PRP is a product widely used in sports medicine, tissue repair, and general surgery. A recent meta-analysis showed this product to be beneficial when introduced into a wound area, be it intra-articular (i.e., joint-injections or direct introduction onto the wound surface. Methods. Between the years of 2012 and 2014 a questionnaire evaluating surgical outcome after port (venous access device removal was answered by 100 patients in the control group and 20 patients in a PRP group, leading to a total of 120 patients in this single center, retrospective, subjective outcome evaluation. Results. No statistical difference was shown in postsurgical complication rates, postsurgical pain, decreased mobility, and overall quality of life. A significant difference was shown in overall patient satisfaction and the desire to further improve port area scarring. Results differed significantly in favor of the PRP group. Interestingly, approximately 40.2% of patients are dissatisfied with the surgical outcome after port removal in the control group. This result, though surprising, may be improved to 10% dissatisfaction when a PRP product is used. Conclusion. PRP products such as Arthrex ACP are safe to use and present an additional option in improving surgical outcome.

Effect of Human Serum and 2 Different Types of Platelet Concentrates on Human Meniscus Cell Migration, Proliferation, and Matrix Formation.

Science.gov (United States)

Freymann, Undine; Metzlaff, Sebastian; Krüger, Jan-Philipp; Hirsh, Glen; Endres, Michaela; Petersen, Wolf; Kaps, Christian

2016-06-01

To evaluate the effect of 10% human serum (HS), 5% platelet-rich plasma (PRP), and 5% autologous conditioned plasma (ACP) on migration, proliferation, and extracellular matrix (ECM) synthesis of human meniscus cells. Cell migration and proliferation on stimulation with HS, PRP, and ACP were assessed by chemotaxis assays and measurement of genomic DNA content. Meniscus cells were cultivated in pellets stimulated with 10% HS, 5% PRP, or 5% ACP. Meniscal ECM formation was evaluated by histochemical staining of collagen type I, type II, and proteoglycans and by analysis of fibrochondrocyte marker gene expression. Human meniscus cells were significantly attracted by all 3 blood-derived products (10% HS and 5% ACP: P = .0001, 5% PRP: P = .0002). Cell proliferation at day 9 was significantly increased on stimulation with 10% HS (P = .0001) and 5% PRP (P = .0002) compared with 5% ACP and controls. Meniscus cell pellet cultures showed the formation of a well-structured meniscal ECM with deposition of collagen type I, type II, and proteoglycans on stimulation with 10% HS, whereas 5% PRP or 5% ACP resulted in the formation of an inhomogeneous and more fibrous ECM. Stimulation with 10% HS and 5% ACP showed a significant induction of fibrochondrocyte marker genes such as aggrecan (HS: P = .0002, ACP: P = .0147), cartilage oligomeric matrix protein (HS: P = .0002, ACP: P = .0005), and biglycan (HS: P = .0002, ACP: P = .0003), whereas PRP showed no inducing effect. Among all tested blood-derived products, only stimulation with HS showed the formation of a meniscal ECM as well as positive cell proliferating and migrating effects in vitro. Regarding a potential biological repair of nonvascular meniscus lesions, our results may point toward the use of HS as a beneficial augment in regenerative meniscus repair approaches. Our findings may suggest that HS might be a beneficial augment for meniscus repair. Copyright © 2016 Arthroscopy Association of North America. Published

Next-generation nozzle check valve significantly reduces operating costs

Energy Technology Data Exchange (ETDEWEB)

Roorda, O. [SMX International, Toronto, ON (Canada)

2009-01-15

Check valves perform an important function in preventing reverse flow and protecting plant and mechanical equipment. However, the variety of different types of valves and extreme differences in performance even within one type can change maintenance requirements and life cycle costs, amounting to millions of dollars over the typical 15-year design life of piping components. A next-generation non-slam nozzle check valve which prevents return flow has greatly reduced operating costs by protecting the mechanical equipment in a piping system. This article described the check valve varieties such as the swing check valve, a dual-plate check valve, and nozzle check valves. Advancements in optimized design of a non-slam nozzle check valve were also discussed, with particular reference to computer flow modelling such as computational fluid dynamics; computer stress modelling such as finite element analysis; and flow testing (using rapid prototype development and flow loop testing), both to improve dynamic performance and reduce hydraulic losses. The benefits of maximized dynamic performance and minimized pressure loss from the new designed valve were also outlined. It was concluded that this latest non-slam nozzle check valve design has potential applications in natural gas, liquefied natural gas, and oil pipelines, including subsea applications, as well as refineries, and petrochemical plants among others, and is suitable for horizontal and vertical installation. The result of this next-generation nozzle check valve design is not only superior performance, and effective protection of mechanical equipment but also minimized life cycle costs. 1 fig.

Anti-aggregation action of ultraviolet irradiation on platelet-rich plasma in the presence of antioxidants

International Nuclear Information System (INIS)

Roshchupkin, D.I.; Anosov, A.K.; Potapenko, A.Ya.

1983-01-01

UV irradiation of platelet-rich plasma (PRP) results in the inhibition of ADP-induced platelet aggregation. This is accounted for by the long-living photoproducts formed in plasma. Platelets destruct these photoproducts in the dark after irradiation. Lipid antioxidants α-tocopherol and BHT administered in PRP before irradiation reduce the anti-aggregation effect of UV light. Lipid photo-peroxidation is supposed to be responsible for the anti-aggregation effect of UV irradiation on platelet-rich plasma. (Auth.)

Anti-aggregation action of ultraviolet irradiation on platelet-rich plasma in the presence of antioxidants

International Nuclear Information System (INIS)

Roshchupkin, D.I.; Anosov, A.K.; Potapenko, A.Ya.

1983-01-01

UV irradiation of platelet-rich plasma (PRP) results in the inhibition of ADP-induced platelets aggregation. This is accounted for by the long-living photoproducts formed in plasma. Platelets destruct these photoproducts in the dark after irradiation. Lipid antioxidants α-tocopherol and BHT administered in PRP before irradiation reduce the anti-aggregation effect of UV light. Lipid photo-peroxidation is supposed to be responsible for the anti-aggregation effect of UV irradiation on platelet-rich plasma. (Auth.)

Comparison of the platelet-rich plasma and buffy coat protocols for preparation of canine platelet concentrates.

Science.gov (United States)

Hoareau, Guillaume L; Jandrey, Karl E; Burges, Julie; Bremer, Daphne; Tablin, Fern

2014-12-01

Platelet (PLT) concentrates (PC) can be produced via the buffy coat (BC) or platelet-rich plasma (PRP) protocols. The 2 methods have not been compared with canine blood. The aims of the study were to compare the PLT, WBC, and RBC concentrations, in vitro PLT function, and markers of platelet storage lesion (PSL) in canine PC generated by 2 different protocols, and determine microbial growth throughout storage. PC from 8 healthy donor dogs were produced using 2 standard protocols, PRP and BC. PLT, WBC, and RBC counts, optical aggregometry assays, and PSL markers (pH, pCO2 , HCO3 , lactate and glucose concentrations, and LDH activity) were determined on storage days 0, 1, 3, 5, and 7. Aerobic and anaerobic bacterial cultures were also performed. Mean PLT counts were comparable between protocols and remained stable throughout storage up to day 7, while median WBC and RBC counts on day 0 were significantly higher in the BC-PC group (17,800 WBCs/μL; 195,000 RBCs/μL) than in the PRP-PC group (200 WBCs/μL; 10,000 RBCs/μL) (P = .012). In PRP-PC aggregometry, the median slope and amplitude in response to γ-thrombin and convulxin (+ ADP) were significantly decreased, and virtually absent in BC-PC during storage. PSL markers (lactate, LDH activity) were higher in BC-PC. Aerobic bacterial growth was observed in 2 PRP-PC and 1 BC-PC. This in vitro study suggests that PRP-PC had lesser WBC and RBC contamination and superior PLT function compared with BC-PC. In vivo studies are required to address safety and efficacy of PRP-PC. © 2014 American Society for Veterinary Clinical Pathology.

The Use of Adipose Derived Progenitor Cells and Platelet Rich Plasma Combination for the Treatment of Supraspinatus Tendinopathy in 55 Dogs: A Retrospective Study

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Sherman Orye Canapp

2016-09-01

Full Text Available Objective: To report clinical findings and outcomes for 55 dogs with supraspinatus tendinopathy treated with adipose derived progenitor cells and platelet rich plasma therapy.Methods: Medical records of client-owned dogs diagnosed with supraspinatus tendinopathy that were treated with adipose derived progenitor cells and platelet rich plasma (ADPC-PRP combination therapy were reviewed from 2006-2013. Data collected included signalment, medical history, limb involvement, prior treatments, physical and orthopedic examination, objective temporospatial gait analysis findings, diagnostic imaging results (radiography, magnetic resonance imaging, musculoskeletal ultrasonography, arthroscopy findings, and outcome. Results: Following ultrasound-guided injection of ADPC-PRP, objective gait analysis was available on 25 of the 55 dogs at 90 days post ADPC-PRP therapy. Following treatment, a significant increase in total pressure index percentage (TPI% was noted in the injured (treated forelimb at 90 days post treatment (p = 0.036. At 90 days following treatment, 88% of cases had no significant difference in TPI% of the injured limb to the contralateral limb. The remaining 12% of cases had significantly improved (p=0.036. Bilateral shoulder diagnostic musculoskeletal ultrasound revealed a significant reduction in tendon size (CSA in the treated tendon at 90 days following treatment when compared to the initial CSA (p=0.005. All cases showed significant improvement in fiber pattern of the affected supraspinatus tendon by the ultrasound shoulder pathology rating scale.Clinical Relevance: These findings suggest that ADPC-PRP therapy should be considered for dogs with supraspinatus tendinopathy.Abbreviations:ST: supraspinatus tendinopathyADPC: adipose derived progenitor cellsMSC: mesenchymal stem cellsPRP: platelet rich plasmaTPI%: total pressure index percentage

Effect of PR interval prolongation on long-term outcomes in patients with left bundle branch block vs non-left bundle branch block morphologies undergoing cardiac resynchronization therapy.

Science.gov (United States)

Rickard, John; Karim, Mohammad; Baranowski, Bryan; Cantillon, Daniel; Spragg, David; Tang, W H Wilson; Niebauer, Mark; Grimm, Richard; Trulock, Kevin; Wilkoff, Bruce; Varma, Niraj

2017-10-01

Although the influence of QRS duration (QRSd) and/or bundle branch block morphology on outcomes of cardiac resynchronization therapy (CRT) have been well studied, the effect of PR interval remains uncertain. The purpose of this study was to evaluate the impact of PR prolongation (PRp) before CRT on long-term outcomes, specifically taking into account bundle branch block morphology and QRSd. We extracted clinical data on consecutive patients undergoing CRT. Multivariate models were constructed to analyze the effect of PRp (≥200 ms) on the combined endpoint of death, heart transplant, or left ventricular assist device. Kaplan-Meier curves were constructed stratifying patients based on bundle branch block and QRSd (dichotomized by 150 ms). Of the 472 patients who met inclusion criteria, 197 (41.7%) had PR interval ≥200 ms. During follow-up (mean 5.1 ± 2.6 years) there were 214 endpoints, of which 109 (23.1%) occurred in patients with PRp. In multivariate analysis, PRp was independently associated with worsened outcomes (hazard ratio 1.34, 95% confidence interval 1.01-1.77, P = .04). When stratified by bundle branch block morphology, PRp was significantly associated with worsened outcomes (log-rank P <.001) in patients with LBBB but not in those with non-LBBB (log-rank P = .55). Among patients with LBBB, stratified by QRSd, patients without PRp had improved outcomes compared to those with PRp independent of QRSd (log-rank P <.001). PRp is an independent predictor of impaired long-term outcome after CRT among patients with LBBB but not in non-LBBB patients. Notably, among LBBB patients, PRp is a more important predictor than QRSd in assessing long-term outcomes. Copyright © 2017. Published by Elsevier Inc.

Intriguing model significantly reduces boarding of psychiatric patients, need for inpatient hospitalization.

Science.gov (United States)

2015-01-01

As new approaches to the care of psychiatric emergencies emerge, one solution is gaining particular traction. Under the Alameda model, which has been put into practice in Alameda County, CA, patients who are brought to regional EDs with emergency psychiatric issues are quickly transferred to a designated emergency psychiatric facility as soon as they are medically stabilized. This alleviates boarding problems in area EDs while also quickly connecting patients with specialized care. With data in hand on the model's effectiveness, developers believe the approach could alleviate boarding problems in other communities as well. The model is funded by through a billing code established by California's Medicaid program for crisis stabilization services. Currently, only 22% of the patients brought to the emergency psychiatric facility ultimately need to be hospitalized; the other 78% are able to go home or to an alternative situation. In a 30-day study of the model, involving five community hospitals in Alameda County, CA, researchers found that ED boarding times were as much as 80% lower than comparable ED averages, and that patients were stabilized at least 75% of the time, significantly reducing the need for inpatient hospitalization.

Significant association between sulfate-reducing bacteria and uranium-reducing microbial communities as revealed by a combined massively parallel sequencing-indicator species approach.

Science.gov (United States)

Cardenas, Erick; Wu, Wei-Min; Leigh, Mary Beth; Carley, Jack; Carroll, Sue; Gentry, Terry; Luo, Jian; Watson, David; Gu, Baohua; Ginder-Vogel, Matthew; Kitanidis, Peter K; Jardine, Philip M; Zhou, Jizhong; Criddle, Craig S; Marsh, Terence L; Tiedje, James M

2010-10-01

Massively parallel sequencing has provided a more affordable and high-throughput method to study microbial communities, although it has mostly been used in an exploratory fashion. We combined pyrosequencing with a strict indicator species statistical analysis to test if bacteria specifically responded to ethanol injection that successfully promoted dissimilatory uranium(VI) reduction in the subsurface of a uranium contamination plume at the Oak Ridge Field Research Center in Tennessee. Remediation was achieved with a hydraulic flow control consisting of an inner loop, where ethanol was injected, and an outer loop for flow-field protection. This strategy reduced uranium concentrations in groundwater to levels below 0.126 μM and created geochemical gradients in electron donors from the inner-loop injection well toward the outer loop and downgradient flow path. Our analysis with 15 sediment samples from the entire test area found significant indicator species that showed a high degree of adaptation to the three different hydrochemical-created conditions. Castellaniella and Rhodanobacter characterized areas with low pH, heavy metals, and low bioactivity, while sulfate-, Fe(III)-, and U(VI)-reducing bacteria (Desulfovibrio, Anaeromyxobacter, and Desulfosporosinus) were indicators of areas where U(VI) reduction occurred. The abundance of these bacteria, as well as the Fe(III) and U(VI) reducer Geobacter, correlated with the hydraulic connectivity to the substrate injection site, suggesting that the selected populations were a direct response to electron donor addition by the groundwater flow path. A false-discovery-rate approach was implemented to discard false-positive results by chance, given the large amount of data compared.

Use of autologous platelet-rich plasma in complete cleft palate repair.

Science.gov (United States)

El-Anwar, Mohammad Waheed; Nofal, Ahmed Abdel Fattah; Khalifa, Mohamed; Quriba, Amal Saeed

2016-07-01

Evaluate the effect of topical application of autologous platelet-rich plasma (PRP) in primary repair of complete cleft palate and then compare the result with another group of patients using the same surgical technique, without application of PRP with regard to the incidence of oronasal fistula, velopharyngeal closure, and grade of nasality. Case control study. This study was carried on 44 children with complete cleft palate with age range from 12 to 23 months. The children were divided into two age- and gender-matched groups: All children were subjected to the same technique of V-Y pushback repair of the complete cleft palate. In group A (22 children), the PRP prepared from the patient was topically applied between the nasal and oral mucosa layer during palatoplasty, whereas in group B (22 children) the PRP was not applied. All cases were recovered smoothly without problems. In group A, no oronasal fistula was reported, whereas in group B three patients (13.6%) had postoperative fistulae and two patients (9.1%) needed revision palatoplasty. At 6 months postoperative assessment, group A (with PRP application) showed significantly better grade of nasality (P = 0.024) and better endoscopic velopharyngeal closure (P = 0.016) than group B. Usage of autologous PRP in complete cleft palate repair is simple; effective; can decrease the incidence of oronasal fistula; and also significantly improves the grade of nasality and velopharyngeal closure, which decreases the need of further surgical intervention in cleft palate patients. 3b. Laryngoscope, 126:1524-1528, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Platelet concentration in platelet concentrates and periodontal regeneration-unscrambling the ambiguity

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A Suchetha

2015-01-01

Full Text Available Context: Platelet-rich-plasma (PRP and Platelet-rich-fibrin (PRF are extensively used autologous platelet concentrates in periodontal regeneration, and PRF has a better efficacy as compared to PRP. The rationale for this difference has often been attributed to the difference in the structure of the fibrin matrix. However, the effect of concentration of platelets on the regenerative potential of these concentrates is obscure. Aims: The study was conducted to evaluate and compare, clinically and radiographically, the efficacy of PRF and PRP in the treatment of periodontal endosseous defects and to assess the effect of platelet concentration on periodontal regeneration. Materials and Methods: Twenty intrabony defects were selected and divided into two groups randomly by the coin toss method. Group I received PRP and Group II subjects were treated with PRF. The platelet counts in PRP and PRF were analyzed. Clinical and radiological parameters were assessed at baseline and 3, 6, and 9 months postoperatively. Statistical Analysis: Kruskal–Wallis Chi-square test, Wilcoxon signed rank test, t-test, and Spearman's rank correlation were used for statistical analysis of data. Results: There was statistically significant improvement in all the parameters in the two groups except in relation to gingival recession. There was a statistically significant difference between the platelet count in Group I and Group II (P = 0.002. Conclusion: PRP and PRF appear to have nearly comparable effects in terms of periodontal regeneration. The concentration of platelets appears to play a paradoxical role in regeneration. The regenerative potential of platelets appears to be optimal within a limited range.

Evaluation of carboxytherapy and platelet-rich plasma in treatment of periorbital hyperpigmentation: A comparative clinical trial.

Science.gov (United States)

Nofal, Eman; Elkot, Reham; Nofal, Ahmad; Eldesoky, Fatma; Shehata, Shymaa; Sami, Maha

2018-01-03

Management of periorbital hyperpigmentation (POH) is still a therapeutic challenge. Although different therapeutic modalities are available, the outcomes of most of them are unsatisfactory. To investigate and compare the efficacy and safety of two new modalities in the treatment of POH; the platelet rich plasma (PRP) and the carboxytherapy. The study included 30 patients with POH. Every patient was subjected to seven intradermal injections of PRP on the left periorbital area with 2 week intervals between sessions and carboxytherapy on the right area with 1 week interval apart. Assessments were done by investigators' assessment, visual analogue scale by both patients and doctors, and patients' satisfaction. Side effects were reported. All patients completed the sessions in the carboxy-treated side. In the PRP-treated side, 10 patients refused to complete all sessions because of intolerable side effects. Significant improvement in POH was achieved in both sides (P ≤ .0001). The improvement was comparable with no statistically significant difference between both modalities. Side effects in the carboxy treated side were mild and well tolerated by all patients while they were relatively severe, and persisted for days after sessions in the PRP-treated side. Both PRP and carboxytherapy are relatively effective and their efficacy is comparable in treatment of POH. Carboxtherapy is simple and slightly more effective modality and well tolerated than PRP. We believe that both modalities are promising but not the ideal solutions of the POH problem which is caused by multifactorial etiology. © 2018 Wiley Periodicals, Inc.

Lime and Phosphate Amendment Can Significantly Reduce Uptake of Cd and Pb by Field-Grown Rice

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Rongbo Xiao

2017-03-01

Full Text Available Agricultural soils are suffering from increasing heavy metal pollution, among which, paddy soil polluted by heavy metals is frequently reported and has elicited great public concern. In this study, we carried out field experiments on paddy soil around a Pb-Zn mine to study amelioration effects of four soil amendments on uptake of Cd and Pb by rice, and to make recommendations for paddy soil heavy metal remediation, particularly for combined pollution of Cd and Pb. The results showed that all the four treatments can significantly reduce the Cd and Pb content in the late rice grain compared with the early rice, among which, the combination amendment of lime and phosphate had the best remediation effects where rice grain Cd content was reduced by 85% and 61%, respectively, for the late rice and the early rice, and by 30% in the late rice grain for Pb. The high reduction effects under the Ca + P treatment might be attributed to increase of soil pH from 5.5 to 6.7. We also found that influence of the Ca + P treatment on rice production was insignificant, while the available Cd and Pb content in soil was reduced by 16.5% and 11.7%, respectively.

The roles of the conserved tyrosine in the β2-α2 loop of the prion protein.

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Huang, Danzhi; Caflisch, Amedeo

2015-01-01

Prions cause neurodegenerative diseases for which no cure exists. Despite decades of research activities the function of the prion protein (PrP) in mammalians is not known. Moreover, little is known on the molecular mechanisms of the self-assembly of the PrP from its monomeric state (cellular PrP, PrP(C)) to the multimeric state. The latter state includes the toxic species (scrapie PrP, PrP(Sc)) knowledge of which would facilitate the development of drugs against prion diseases. Here we analyze the role of a tyrosine residue (Y169) which is strictly conserved in mammalian PrPs. Nuclear magnetic resonance (NMR) spectroscopy studies of many mammalian PrP(C) proteins have provided evidence of a conformational equilibrium between a 3(10)-helical turn and a type I β turn conformation in the β2-α2 loop (residues 165-175). In vitro cell-free experiments of the seeded conversion of PrP(C) indicate that non-aromatic residues at position 169 reduce the formation of proteinase K-resistant PrP. Recent molecular dynamics (MD) simulations of monomeric PrP and several single-point mutants show that Y169 stabilizes the 3(10)-helical turn conformation more than single-point mutants at position 169 or residues in contact with it. In the 3(10)-helical turn conformation the hydrophobic and aggregation-prone segment 169-YSNQNNF-175 is buried and thus not-available for self-assembly. From the combined analysis of simulation and experimental results it emerges that Y169 is an aggregation gatekeeper with a twofold role. Mutations related to 3 human prion diseases are interpreted on the basis of the gatekeeper role in the monomeric state. Another potential role of the Y169 side chain is the stabilization of the ordered aggregates, i.e., reduction of frangibility of filamentous protofibrils and fibrils, which is likely to reduce the generation of toxic species.

Prion protein inhibits microtubule assembly by inducing tubulin oligomerization

International Nuclear Information System (INIS)

Nieznanski, Krzysztof; Podlubnaya, Zoya A.; Nieznanska, Hanna

2006-01-01

A growing body of evidence points to an association of prion protein (PrP) with microtubular cytoskeleton. Recently, direct binding of PrP to tubulin has also been found. In this work, using standard light scattering measurements, sedimentation experiments, and electron microscopy, we show for First time the effect of a direct interaction between these proteins on tubulin polymerization. We demonstrate that full-length recombinant PrP induces a rapid increase in the turbidity of tubulin diluted below the critical concentration for microtubule assembly. This effect requires magnesium ions and is weakened by NaCl. Moreover, the PrP-induced light scattering structures of tubulin are cold-stable. In preparations of diluted tubulin incubated with PrP, electron microscopy revealed the presence of ∼50 nm disc-shaped structures not reported so far. These unique tubulin oligomers may form large aggregates. The effect of PrP is more pronounced under the conditions promoting microtubule formation. In these tubulin samples, PrP induces formation of the above oligomers associated with short protofilaments and sheets of protofilaments into aggregates. Noticeably, this is accompanied by a significant reduction of the number and length of microtubules. Hence, we postulate that prion protein may act as an inhibitor of microtubule assembly by inducing formation of stable tubulin oligomers

An evidence-based evaluation on the use of platelet rich plasma in orthopedics – a review of the literature

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Hussain Nasir

2017-01-01

Full Text Available Within orthopedics, the use of platelet-rich plasma (PRP has been rapidly increasing in popularity, however, its true effectiveness has yet to be fully established. Several studies find that injecting PRP to the site of injury does not provide any significant benefit with respect to clinical outcomes; however, many others report the contrary. Due to the conflicting evidence and multiple meta-analyses conducted on the topic, a literature review of high-quality evidence on the use of PRP for common orthopaedic conditions was performed. Thus far, the evidence appears to suggest that PRP may provide some benefit in patients who present with knee osteoarthritis or lateral epicondylitis. On the other hand, evidence appears to be inconsistent or shows a minimal benefit for PRP usage in rotator cuff repair, patellar and Achilles tendinopathies, hamstring injuries, anterior cruciate ligament (ACL repair, and medial epicondylitis. There is limited confidence in the conclusions from the published meta-analyses due to issues with statistical pooling, and limited subgroup analyses exploring the substantial heterogeneity across studies. Evidence-based clinicians considering the use of PRP in their patients with musculoskeletal injuries should be weary that the literature appears to be inconsistent and thus far, inconclusive.

Platelet-rich plasma injection is more effective than hyaluronic acid in the treatment of knee osteoarthritis.

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Say, F; Gürler, D; Yener, K; Bülbül, M; Malkoc, M

2013-01-01

There is increasing use of platelet-rich plasma (PRP) in orthopaedics as it is a simple, cheap and minimally invasive technique. This study aimed to compare the effects of the use of PRP and hyaluronic acid (HA) injections in the knee of patients diagnosed with and being followed-up for degenerative arthritis. This prospective study included 90 patients with complaints of knee pain with findings of mild or moderate degenerative arthritis. In the PRP group (n=45), one intra-articular injection was applied and in the HA group (n=45), three doses of intra-articular injection were applied. Clinical evaluation was made by Knee Injury and Osteoarthritis Outcome Score (KOOS) and a visual pain scale. No severe adverse events was observed. Statistically significant better results in the KOOS score and visual pain scale was determined in PRP group than HA group at 3 months and 6 months follow up. The cost of the application for the PRP group was lower than that of the HA group. The results of this study have shown the application of single dose PRP to be a safe, effective and low-cost method for treating OA. However, further studies are required for a more clear result.

Antimicrobial activity of pure platelet-rich plasma against microorganisms isolated from oral cavity.

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Drago, Lorenzo; Bortolin, Monica; Vassena, Christian; Taschieri, Silvio; Del Fabbro, Massimo

2013-02-25

Autologous platelet concentrates (PCs) have been extensively used in a variety of medical fields to promote soft and hard tissue regeneration. The significance behind their use lies in the abundance of growth factors in platelets α-granules that promotes wound healing. In addition, antibacterial properties of PCs against various bacteria have been recently pointed out. In this study, the antimicrobial effect of pure platelet-rich plasma (P-PRP) was evaluated against oral cavity microorganisms such as Enterococcus faecalis, Candida albicans, Streptococcus agalactiae, Streptococcus oralis and Pseudomonas aeruginosa. Blood samples were obtained from 17 patients who underwent oral surgery procedures involving the use of P-PRP. The antibacterial activity of P-PRP, evaluated as the minimum inhibitory concentration (MIC), was determined through the microdilution twofold serial method. P-PRP inhibited the growth of Enterococcus faecalis, Candida albicans, Streptococcus agalactiae and Streptococcus oralis, but not of Pseudomonas aeruginosa strains. P-PRP is a potentially useful substance in the fight against postoperative infections. This might represent a valuable property in adjunct to the enhancement of tissue regeneration.

Ex vivo expansion of bone marrow stromal cells by platelet-rich plasma: a promising strategy in maxillo-facial surgery.

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Oliva, A; Passaro, I; Di Pasquale, R; Di Feo, A; Criscuolo, M; Zappia, V; Della Ragione, F; D'Amato, S; Annunziata, M; Guida, L

2005-01-01

The aim of our study is to evaluate in vitro the response of bone marrow stromal cells (BMSCs) to platelet-rich plasma (PRP), in order to clarify the potential role of their combined use in a preclinical phase preceding BMSCs transplantation for bone repair and regeneration procedures. The incubation of BMSCs with PRP promoted a remarkable, dose- and time- dependent, growth stimulation, that was paralleled to a strong increase in the quantity of type I collagen and to a significant decrease in the activity of the early osteoblastic differentiation marker, alkaline phosphatase (AP). Once PRP was removed and osteogenic inducers were added, AP returned to levels comparable to the control, while the late phenotypic markers, osteocalcin and matrix calcification, were enhanced to higher levels than in controls. Our data demonstrate that PRP induces a remarkable ex vivo enrichment of BMSCs maintaining their differentiative potential. Thus PRP represents a valid preclinical tool for obtaining an effective, rapid and safe ex vivo expansion of BMSCs prior to their clinical utilization in bone engineering.

AN INVESTIGATION OF THE HYPOTHESES FOR FORMATION OF THE PLATY-RIDGED-POLYGONIZED TERRAIN IN ELYSIUM PLANITIA, MARS

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Z. Yue

2017-07-01

Full Text Available The origin of the platy-ridged-polygonized (PRP terrains on Martian surface has long been debated. The terrain has generally been classified as water, pack ice, or basalt lava related flow. The crater counting results of the PRP terrains suggest they are geologically very young; therefore, they are significant in understanding the recent evolution of Mars. This work evaluated the current hypotheses through detailed analysis of the distribution and microtopographies with the High Resolution Imaging Science Experiment (HiRISE images for the PRP terrains in Elysium Planitia, Mars. Quantitative measurements and statistics of the typical features of the PRP terrains were also made. In addition, we also found an analog site in Tarim Basin in Xinjiang, China. Our results suggest that mud flow is responsible for the formation of the PRP terrains on the Mars surface, although the hypothesis of low-viscosity basalt lava floods cannot be completely excluded. This finding implies that a regional environment suitable for liquid water may have existed in recent geologic time, which has great importance for future Mars scientific exploration.

Activation of human natural killer cells by the soluble form of cellular prion protein

International Nuclear Information System (INIS)

Seong, Yeon-Jae; Sung, Pil Soo; Jang, Young-Soon; Choi, Young Joon; Park, Bum-Chan; Park, Su-Hyung; Park, Young Woo; Shin, Eui-Cheol

2015-01-01

Cellular prion protein (PrP C ) is widely expressed in various cell types, including cells of the immune system. However, the specific roles of PrP C in the immune system have not been clearly elucidated. In the present study, we investigated the effects of a soluble form of recombinant PrP C protein on human natural killer (NK) cells. Recombinant soluble PrP C protein was generated by fusion of human PrP C with the Fc portion of human IgG 1 (PrP C -Fc). PrP C -Fc binds to the surface of human NK cells, particularly to CD56 dim NK cells. PrP C -Fc induced the production of cytokines and chemokines and the degranulation of granzyme B from NK cells. In addition, PrP C -Fc facilitated the IL-15-induced proliferation of NK cells. PrP C -Fc induced phosphorylation of ERK-1/2 and JNK in NK cells, and inhibitors of the ERK or the JNK pathways abrogated PrP C -Fc-induced cytokine production in NK cells. In conclusion, the soluble form of recombinant PrP C -Fc protein activates human NK cells via the ERK and JNK signaling pathways. - Highlights: • Recombinant soluble PrP C (PrP C -Fc) was generated by fusion of human PrP C with IgG1 Fc portion. • PrP C -Fc protein induces the production of cytokines and degranulation from human NK cells. • PrP C -Fc protein enhances the IL-15-induced proliferation of human NK cells. • PrP C -Fc protein activates human NK cells via the ERK and JNK signaling pathways

Incorporation of catalytic dehydrogenation into fischer-tropsch synthesis to significantly reduce carbon dioxide emissions

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Huffman, Gerald P.

2012-11-13

A new method of producing liquid transportation fuels from coal and other hydrocarbons that significantly reduces carbon dioxide emissions by combining Fischer-Tropsch synthesis with catalytic dehydrogenation is claimed. Catalytic dehydrogenation (CDH) of the gaseous products (C1-C4) of Fischer-Tropsch synthesis (FTS) can produce large quantities of hydrogen while converting the carbon to multi-walled carbon nanotubes (MWCNT). Incorporation of CDH into a FTS-CDH plant converting coal to liquid fuels can eliminate all or most of the CO.sub.2 emissions from the water-gas shift (WGS) reaction that is currently used to elevate the H.sub.2 level of coal-derived syngas for FTS. Additionally, the FTS-CDH process saves large amounts of water used by the WGS reaction and produces a valuable by-product, MWCNT.

Microparticle counts in platelet-rich and platelet-free plasma, effect of centrifugation and sample-processing protocols.

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Chandler, Wayne L

2013-03-01

This study provides the first estimates of microparticle numbers in platelet-rich plasma (PRP) from normal individuals, closer to in-vivo levels, using higher-resolution flow cytometry. We measured platelet (CD41+) and annexin V+ microparticles in fresh and frozen aliquots of PRP, platelet-poor plasma, platelet-free plasma (PFP), and microparticles isolated by high-speed centrifugation. PRP from healthy individuals contained 730,000/μl total microparticles based on light-scattering measurements. A median of 27,000/μl microparticles in PRP were of platelet origin and 120,000/μl annexin V+, and of these, 24,000/μl were dual-positive procoagulant platelet microparticles. Double centrifugation of PRP removed 99% of platelets, but also 80% of annexin V+ CD41+, 93% of annexin V+ CD41-, and 58% of annexin V- CD41+ microparticles. Loss of microparticles with centrifugation varied from individual to individual. Microparticle counts after isolation by centrifugation and double washing were not significantly different than counts in the original PFP sample, but lower than in PRP. Freeze-thawing of PFP had no effect on platelet microparticle counts, but slightly increased annexin V+, CD41- counts. Freeze-thawing of isolated washed microparticles resulted in a 30-50% increase in annexin V+ microparticles. PRP contains large numbers of cellular microparticles, including platelet and annexin V+ microparticles, which are lost to varying degrees when PRP is double centrifuged to remove platelets. Microparticles remaining in PFP can be recovered by high-speed centrifugation without loss compared to the original PFP sample. Freeze-thawing has variable effects on microparticle counts depending on the sample preparation used.