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Sample records for prp significantly reduced

  1. Intra-articular laser treatment plus Platelet Rich Plasma (PRP) significantly reduces pain in many patients who had failed prior PRP treatment

    Science.gov (United States)

    Prodromos, Chadwick C.; Finkle, Susan; Dawes, Alexander; Dizon, Angelo

    2018-02-01

    INTRODUCTION: In our practice Platelet Rich Plasma (PRP) injections effectively reduce pain in most but not all arthritic patients. However, for patients who fail PRP treatment, no good alternative currently exists except total joint replacement surgery. Low level laser therapy (LLLT) on the surface of the skin has not been helpful for arthritis patients in our experience. However, we hypothesized that intra-articular laser treatment would be an effective augmentation to PRP injection and would increase its efficacy in patients who had failed prior PRP injection alone. METHODS: We offered Intra-articular Low Level Laser Therapy (IAL) treatment in conjunction with repeat PRP injection to patients who had received no benefit from PRP injection alone at our center. They were the treatment group. They were not charged for PRP or IAL. They also served as a historical control group since they had all had failed PRP treatment alone. 28 patients (30 joints) accepted treatment after informed consent. 22 knees, 4 hips, 2 shoulder glenohumeral joints and 1 first carpo-metacarpal (1st CMC) joint were treated RESULTS: All patients were followed up at 1 month and no adverse events were seen from the treatment. At 6 months post treatment 46% of patients had good outcomes, and at 1 year 17% still showed improvement after treatment. 11 patients failed treatment and went on to joint replacement. DISCUSSION: A single treatment of IAL with PRP salvaged 46% of patients who had failed PRP treatment alone, allowing avoidance of surgery and good pain control.

  2. Oxidation reduces the fibrillation but not the neurotoxicity of the prion peptide PrP106-126

    DEFF Research Database (Denmark)

    Bergstrøm, Linda Alice; Chabry, J.; Bastholm, L.

    2007-01-01

    There is increasing evidence that soluble oligomers of misfolded protein may play a role in the pathogenesis of protein misfolding diseases including the transmissible spongiform encephalopathies (TSE) where the protein involved is the prion protein, PrP. The effect of oxidation on fibrillation...... tendency and neurotoxicity of different molecular variants of the prion peptide PrP106-126 was investigated. It was found that methionine oxidation significantly reduced amyloid fibril formation and proteinase K resistance, but it did not reduce (but rather increase slightly) the neurotoxicity...

  3. Effectiveness of PRP Injection in Reducing Recovery Time of Acute Hamstring Injury: A Critically Appraised Topic.

    Science.gov (United States)

    Manduca, Mary Lynn; Straub, Stephen J

    2017-07-17

    Clinical Scenario Hamstring strains are common athletic injuries, with a high recurrence rate (34%). 2 Recently, platelet-rich-plasma (PRP) injections have gained popularity as a potential treatment option to accelerate healing of hamstring injury. 3 Focused Clinical Question Does the combination of PRP injection and rehabilitation decrease recovery time of acute hamstring injury as compared to rehabilitation alone in collegiate athletes? Summary of Key Findings A literature search resulted in three randomized controlled trials (RCT). One study showed benefits in various outcome measures with PRP, compared to rehabilitation alone, while two showed no benefits. One study reported improved pain, ultrasonography regenerative indications, and recovery time with PRP injection following acute hamstring injury 1 , however, larger studies have shown no benefits. 7-9 The literature demonstrates conflicting evidence regarding benefits of PRP injections in hamstring injuries. Clinical Bottom Line At this time, PRP injections cannot be recommended as having value for hamstring injuries, compared to rehabilitation alone. Strength of Recommendation Due to inconsistent or limited quality patient-oriented evidence in existing literature, the strength of this recommendation is grade B, based on the Strength of Recommendation Taxonomy (SORT). 7 .

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

    Science.gov (United States)

    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.

  5. Hyperuricemic PRP in Tendon Cells

    Directory of Open Access Journals (Sweden)

    I. Andia

    2014-01-01

    Full Text Available Platelet-rich plasma (PRP is injected within tendons to stimulate healing. Metabolic alterations such as the metabolic syndrome, diabetes, or hyperuricemia could hinder the therapeutic effect of PRP. We hypothesise that tendon cells sense high levels of uric acid and this could modify their response to PRP. Tendon cells were treated with allogeneic PRPs for 96 hours. Hyperuricemic PRP did not hinder the proliferative actions of PRP. The gene expression pattern of inflammatory molecules in response to PRP showed absence of IL-1b and COX1 and modest expression of IL6, IL8, COX2, and TGF-b1. IL8 and IL6 proteins were secreted by tendon cells treated with PRP. The synthesis of IL6 and IL8 proteins induced by PRP is decreased significantly in the presence of hyperuricemia (P = 0.017 and P = 0.012, resp.. Concerning extracellular matrix, PRP-treated tendon cells displayed high type-1 collagen, moderate type-3 collagen, decorin, and hyaluronan synthase-2 expression and modest expression of scleraxis. Hyperuricemia modified the expression pattern of extracellular matrix proteins, upregulating COL1 (P = 0.036 and COMP (P = 0.012 and downregulating HAS2 (P = 0.012. Positive correlations between TGF-b1 and type-1 collagen (R = 0.905, P = 0.002 and aggrecan (R = 0.833, P = 0.010 and negative correlations between TGF-b1 and IL6 synthesis (R = −0.857, P = 0.007 and COX2 (R = −0.810, P = 0.015 were found.

  6. 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...

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. Autologous platelet-rich plasma (PRP) in chronic penile lichen sclerosus: the impact on tissue repair and patient quality of life.

    Science.gov (United States)

    Casabona, Francesco; Gambelli, Ilaria; Casabona, Federica; Santi, Pierluigi; Santori, Gregorio; Baldelli, Ilaria

    2017-04-01

    Lichen sclerosus (LS) is a chronic inflammatory skin condition that frequently involves the anogenital region. Ongoing research is focused on finding more effective treatments for tissue repair and reducing symptoms. The aim of this study is to evaluate the effectiveness of platelet-rich plasma (PRP) local injections in penile LS. Forty-five male patients affected by penile LS underwent injections of autologous PRP in the affected skin areas. Age at diagnosis and at first treatment, number of treatments, clinical conditions (phimosis, splitting, inflammation, synechiae, meatus stenosis), symptoms (pain, burning, itching), and functional impairment were considered. Treatment efficacy was also evaluated through the Investigator's Global Assessment (IGA) on a six-point Likert scale and the Dermatology Life Quality Index (DLQI). The patient age at LS diagnosis was 36.20 ± 9.19 years, while the mean age at the first PRP treatment was 42.96 ± 11.32 years (p PRP injections, it was observed in all patients a significant improvement in clinical conditions, with reduction/disappearance of symptoms. Topical steroid therapy, interrupted before PRP treatment, was not restarted by any patient. Only one patient underwent a later circumcision procedure. Both IGA scale and DLQI score showed a significant difference (p PRP treatment. PRP treatment in penile LS seems to be helpful to regenerate scarring, reduce symptoms, and improve patient quality of life. Further studies are necessary to evaluate long-term results.

  12. Quantitating PrP Polymorphisms Present in Prions from Heterozygous Scrapie-Infected Sheep.

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    Silva, Christopher J; Erickson-Beltran, Melissa L; Hui, Colleen; Badiola, Juan José; Nicholson, Eric M; Requena, Jesús R; Bolea, Rosa

    2017-01-03

    Scrapie is a prion (PrP Sc ) disease of sheep. The incubation period of sheep scrapie is strongly influenced by polymorphisms at positions 136, 154, and 171 of a sheep's normal cellular prion protein (PrP C ). Chymotrypsin was used to digest sheep recombinant PrP to identify a set of characteristic peptides [M 132 LGSXMSRPL 141 (X = A or V), Y 153 XENMY 158 (X,= H or R), and Y 166 RPVDXY 172 (X = H, K, Q, or R)] that could be used to detect and quantitate polymorphisms at positions 136, 154, and 171 of sheep PrP C or PrP Sc . These peptides were used to develop a multiple reaction monitoring method (MRM) to detect the amounts of a particular polymorphism in a sample of PrP Sc isolated from sheep heterozygous for their PrP C proteins. The limit of detection for these peptides was less than 50 attomole. Spinal cord tissue from heterozygous (ARQ/VRQ or ARH/ARQ) scrapie-infected Rasa Aragonesa sheep was analyzed using this MRM method. Both sets of heterozygotes show the presence of both polymorphisms in PrP Sc . This was true for samples containing both proteinase K (PK)-sensitive and PK-resistant PrP Sc and samples containing only the PK-resistant PrP Sc . These results show that heterozygous animals contain PrP Sc that is composed of significant amounts of both PrP polymorphisms.

  13. Platlet Rich Plasma (PRP) Improves Fat Grafting Outcomes.

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    Modarressi, Ali

    2013-01-01

    Autologous fat transfer offers many qualities of a ideal soft tissue filler. Main advantages of fat grafting ensue from the fact that the lipoaspirate tissue is an abundant source of regenerative pluripotential cells. However, the reported rates of fat cell survival vary greatly in the medical literature (10-90%). Different techniques of harvesting, processing, and reinjecting the fat cells are so claimed to be responsible for these differences, without any agreement concerning the best way to process. To address this important disadvantage, we propose the addition of autologous platelet rich plasma (PRP) which is known as a natural reservoir of growth factors stimulating tissue repair and regeneration. This approach is completely autologous and immediately employed without any type of preconditioning. Platelets rich plasma (PRP) preparation included bleeding of 8 ml of blood from patient's peripheral vein in Regen Lab© tubes containing sodium citrate anticoagulant. The whole blood was centrifugated at 1500 g during 3 min. As Regen-tubes contained a special gel separator, 99 % of red blood cells were discarded from the plasma at the bottom of the gel, and >90% of platelets were harvested in 4 ml of plasma on the top of the gel, called the platelet-rich plasma (PRP). The purified fat prepared by Coleman technique was mixed with different amount of PRP for in vitro, in vivo (mice) and clinical experiments: >50% of PRP for skin rejuvenation, superficial scars correction, infraorbital region, ..., and for 20% of PRP with 80% of purified fat for deep filler indication (nasolabial folds, lips, or soft tissue defect). In vitro studies demonstrated that PRP increased fat cells survival rate and stem cells differentiation. Animal models showed that fat graft survival rate was significantly increased by addition of PRP. Several clinical cases confirmed the improvement of wound healing and fat grafting survival in facial reconstruction and aesthetic cases by association of

  14. Can PRP effectively treat injured tendons?

    Science.gov (United States)

    Wang, James H-C

    2014-01-01

    PRP is widely used to treat tendon and other tissue injuries in orthopaedics and sports medicine; however, the efficacy of PRP treatment on injured tendons is highly controversial. In this commentary, I reason that there are many PRP- and patient-related factors that influence the outcomes of PRP treatment on injured tendons. Therefore, more basic science studies are needed to understand the mechanism of PRP on injured tendons. Finally, I suggest that better understanding of the PRP action mechanism will lead to better use of PRP for the effective treatment of tendon injuries in clinics.

  15. Phase diagram of Pr-P system

    International Nuclear Information System (INIS)

    Mironov, K.E.

    1981-01-01

    An area of the Pr-P system, adjoining to the Pr ordinate, is plotted up by the DTA method. Presence of P solid solution in Pr is established. Data on thermal stability of PrP, PrP 2 , PrP 5 and PrP 7 are generalized. The diagram of phase transformations in Pr-P system is plotted up proceeding from the whole complex of the data, presented. A supposition is made on a possible formation of solid solutions between the highest polyphosphide and phosphorus [ru

  16. 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.

  17. HGF Mediates the Anti-inflammatory Effects of PRP on Injured Tendons

    Science.gov (United States)

    Zhang, Jianying; Middleton, Kellie K.; Fu, Freddie H.; Im, Hee-Jeong; Wang, James H-C.

    2013-01-01

    Platelet-rich plasma (PRP) containing hepatocyte growth factor (HGF) and other growth factors are widely used in orthopaedic/sports medicine to repair injured tendons. While PRP treatment is reported to decrease pain in patients with tendon injury, the mechanism of this effect is not clear. Tendon pain is often associated with tendon inflammation, and HGF is known to protect tissues from inflammatory damages. Therefore, we hypothesized that HGF in PRP causes the anti-inflammatory effects. To test this hypothesis, we performed in vitro experiments on rabbit tendon cells and in vivo experiments on a mouse Achilles tendon injury model. We found that addition of PRP or HGF decreased gene expression of COX-1, COX-2, and mPGES-1, induced by the treatment of tendon cells in vitro with IL-1β. Further, the treatment of tendon cell cultures with HGF antibodies reduced the suppressive effects of PRP or HGF on IL-1β-induced COX-1, COX-2, and mPGES-1 gene expressions. Treatment with PRP or HGF almost completely blocked the cellular production of PGE2 and the expression of COX proteins. Finally, injection of PRP or HGF into wounded mouse Achilles tendons in vivo decreased PGE2 production in the tendinous tissues. Injection of platelet-poor plasma (PPP) however, did not reduce PGE2 levels in the wounded tendons, but the injection of HGF antibody inhibited the effects of PRP and HGF. Further, injection of PRP or HGF also decreased COX-1 and COX-2 proteins. These results indicate that PRP exerts anti-inflammatory effects on injured tendons through HGF. This study provides basic scientific evidence to support the use of PRP to treat injured tendons because PRP can reduce inflammation and thereby reduce the associated pain caused by high levels of PGE2. PMID:23840657

  18. HGF mediates the anti-inflammatory effects of PRP on injured tendons.

    Directory of Open Access Journals (Sweden)

    Jianying Zhang

    Full Text Available Platelet-rich plasma (PRP containing hepatocyte growth factor (HGF and other growth factors are widely used in orthopaedic/sports medicine to repair injured tendons. While PRP treatment is reported to decrease pain in patients with tendon injury, the mechanism of this effect is not clear. Tendon pain is often associated with tendon inflammation, and HGF is known to protect tissues from inflammatory damages. Therefore, we hypothesized that HGF in PRP causes the anti-inflammatory effects. To test this hypothesis, we performed in vitro experiments on rabbit tendon cells and in vivo experiments on a mouse Achilles tendon injury model. We found that addition of PRP or HGF decreased gene expression of COX-1, COX-2, and mPGES-1, induced by the treatment of tendon cells in vitro with IL-1β. Further, the treatment of tendon cell cultures with HGF antibodies reduced the suppressive effects of PRP or HGF on IL-1β-induced COX-1, COX-2, and mPGES-1 gene expressions. Treatment with PRP or HGF almost completely blocked the cellular production of PGE2 and the expression of COX proteins. Finally, injection of PRP or HGF into wounded mouse Achilles tendons in vivo decreased PGE2 production in the tendinous tissues. Injection of platelet-poor plasma (PPP however, did not reduce PGE2 levels in the wounded tendons, but the injection of HGF antibody inhibited the effects of PRP and HGF. Further, injection of PRP or HGF also decreased COX-1 and COX-2 proteins. These results indicate that PRP exerts anti-inflammatory effects on injured tendons through HGF. This study provides basic scientific evidence to support the use of PRP to treat injured tendons because PRP can reduce inflammation and thereby reduce the associated pain caused by high levels of PGE2.

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

    Science.gov (United States)

    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.

  20. 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.

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

    Science.gov (United States)

    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

  2. [Platelet rich plasma (PRP): potentialities and techniques of extraction].

    Science.gov (United States)

    Pacifici, L; Casella, F; Maggiore, C

    2002-01-01

    This paper describes the various techniques of platelet-rich plasma (PRP) extraction codified in recent years and their use potential is evaluated. PRP is one of the techniques with which at the moment it is attempted to modulate and facilitate the cure of a wound. The use of PRP is based on the theoretical premise that by concentrating platelets the effects of the growth factors (PDGF, TGF-beta, IGF-I and -II) so released will be increased. Marx's original technique is described above all. This prescribes the sampling of a unit of blood (450-500 ml) and the use of a cell separator. We then analysed the technique of Marx and Hannon in which the quantity of blood sampled is reduced to 150 ml, and the two simplified techniques of the Sacchi and Bellanda group. Finally, a new PRP extraction technique is described. We conclude that platelet gel allows access to autologous growth factors which by definition are neither toxic nor immunogenic and are capable of accelerating the normal processes of bone regeneration. PRP can thus be considered a useful instrument for increasing the quality and final quantity of regenerated bone in oral and maxillo-facial surgery operations.

  3. Cytosolic PrP Can Participate in Prion-Mediated Toxicity

    Science.gov (United States)

    Thackray, Alana M.; Zhang, Chang; Arndt, Tina

    2014-01-01

    ABSTRACT Prion diseases are characterized by a conformational change in the normal host protein PrPC. While the majority of mature PrPC is tethered to the plasma membrane by a glycosylphosphatidylinositol anchor, topological variants of this protein can arise during its biosynthesis. Here we have generated Drosophila transgenic for cytosolic ovine PrP in order to investigate its toxic potential in flies in the absence or presence of exogenous ovine prions. While cytosolic ovine PrP expressed in Drosophila was predominantly detergent insoluble and showed resistance to low concentrations of proteinase K, it was not overtly detrimental to the flies. However, Drosophila transgenic for cytosolic PrP expression exposed to classical or atypical scrapie prion inocula showed a faster decrease in locomotor activity than similar flies exposed to scrapie-free material. The susceptibility to classical scrapie inocula could be assessed in Drosophila transgenic for panneuronal expression of cytosolic PrP, whereas susceptibility to atypical scrapie required ubiquitous PrP expression. Significantly, the toxic phenotype induced by ovine scrapie in cytosolic PrP transgenic Drosophila was transmissible to recipient PrP transgenic flies. These data show that while cytosolic PrP expression does not adversely affect Drosophila, this topological PrP variant can participate in the generation of transmissible scrapie-induced toxicity. These observations also show that PrP transgenic Drosophila are susceptible to classical and atypical scrapie prion strains and highlight the utility of this invertebrate host as a model of mammalian prion disease. IMPORTANCE During prion diseases, the host protein PrPC converts into an abnormal conformer, PrPSc, a process coupled to the generation of transmissible prions and neurotoxicity. While PrPC is principally a glycosylphosphatidylinositol-anchored membrane protein, the role of topological variants, such as cytosolic PrP, in prion-mediated toxicity and

  4. Enhanced healing of mitomycin C-treated healing-impaired wounds in rats with PRP-containing fragmin/protamine microparticles (PRP&F/P MPs).

    Science.gov (United States)

    Takikawa, Megumi; Ishihara, Masayuki; Takabayashi, Yuki; Sumi, Yuki; Takikawa, Makoto; Yoshida, Ryuichi; Nakamura, Shingo; Hattori, Hidemi; Yanagibayashi, Satoshi; Yamamoto, Naoto; Kiyosawa, Tomoharu

    2015-04-13

    The purpose of this study was to evaluate the accelerating effects of platelet-rich plasma-containing (PRP&) fragmin/protamine microparticles (F/P MPs) for repairing mitomycin C-treated healing-impaired wounds. Staining with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL-staining) showed that apoptosis of dermal fibroblast cells (DFCs) and epidermal keratinocyte cells (EKCs) were significantly induced in the skin of the mitomycin C-treated rats. Full-thickness skin defects were made on the back of rats and mitomycin C was applied on the wounds to prepare a healing-impaired wound. After washing out the mitomycin C, saline (control), F/P MPs alone, PRP alone, and PRP&F/P MPs were injected around the wounds. The rats were later euthanised and histological sections of the wounds were then prepared at indicated time periods after the treatment. These results indicated the numbers of large, medium, and small capillary lumens 7 days after injection of PRP&F/P MPs were significantly higher than those after injection of PRP or F/P MPs alone. Furthermore, epithelium and granulation tissue formations were significantly stimulated in the healing-impaired wounds treated with PRP&F/P MPs 3, 7 and 14 days after injection of PRP&F/P MPs.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  8. PrP Knockout Cells Expressing Transmembrane PrP Resist Prion Infection.

    Science.gov (United States)

    Marshall, Karen E; Hughson, Andrew; Vascellari, Sarah; Priola, Suzette A; Sakudo, Akikazu; Onodera, Takashi; Baron, Gerald S

    2017-01-15

    Glycosylphosphatidylinositol (GPI) anchoring of the prion protein (PrP C ) influences PrP C misfolding into the disease-associated isoform, PrP res , as well as prion propagation and infectivity. GPI proteins are found in cholesterol- and sphingolipid-rich membrane regions called rafts. Exchanging the GPI anchor for a nonraft transmembrane sequence redirects PrP C away from rafts. Previous studies showed that nonraft transmembrane PrP C variants resist conversion to PrP res when transfected into scrapie-infected N2a neuroblastoma cells, likely due to segregation of transmembrane PrP C and GPI-anchored PrP res in distinct membrane environments. Thus, it remained unclear whether transmembrane PrP C might convert to PrP res if seeded by an exogenous source of PrP res not associated with host cell rafts and without the potential influence of endogenous expression of GPI-anchored PrP C To further explore these questions, constructs containing either a C-terminal wild-type GPI anchor signal sequence or a nonraft transmembrane sequence containing a flexible linker were expressed in a cell line derived from PrP knockout hippocampal neurons, NpL2. NpL2 cells have physiological similarities to primary neurons, representing a novel and advantageous model for studying transmissible spongiform encephalopathy (TSE) infection. Cells were infected with inocula from multiple prion strains and in different biochemical states (i.e., membrane bound as in brain microsomes from wild-type mice or purified GPI-anchorless amyloid fibrils). Only GPI-anchored PrP C supported persistent PrP res propagation. Our data provide strong evidence that in cell culture GPI anchor-directed membrane association of PrP C is required for persistent PrP res propagation, implicating raft microdomains as a location for conversion. Mechanisms of prion propagation, and what makes them transmissible, are poorly understood. Glycosylphosphatidylinositol (GPI) membrane anchoring of the prion protein (PrP C

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  11. PRP for Degenerative Cartilage Disease: A Systematic Review of Clinical Studies.

    Science.gov (United States)

    Laver, Lior; Marom, Niv; Dnyanesh, Lad; Mei-Dan, Omer; Espregueira-Mendes, João; Gobbi, Alberto

    2017-10-01

    To explore the utilization of platelet-rich plasma (PRP) for degenerative cartilage processes and evaluate whether there is sufficient evidence to better define its potential effects. Systematic literature reviews were conducted in PubMed/MEDLINE and Cochrane electronic databases till May 2015, using the keywords "platelet-rich plasma OR PRP OR autologous conditioned plasma OR ACP AND cartilage OR chondrocyte OR chondrogenesis OR osteoarthritis (OA) OR arthritis." The final result yielded 29 articles. Twenty-six studies examined PRP administration for knee OA and 3 involved PRP administration for hip OA. The results included 9 prospective randomized controlled trials (RCTs) (8 knee and 1 hip), 4 prospective comparative studies, 14 case series, and 2 retrospective comparative studies. Hyaluronic acid (HA) was used as a control in 11 studies (7 RCTs, 2 prospective comparative studies, and 2 retrospective cohort). Overall, all RCTs reported on improved symptoms compared to baseline scores. Only 2 RCTs-one for knee and one for hip-did not report significant superiority of PRP compared to the control group (HA). Nine out of 11 HA controlled studies showed significant better results in the PRP groups. A trend toward better results for PRP injections in patients with early knee OA and young age was observed; however, lack of uniformity was evident in terms of indications, inclusion criteria, and pathology definitions in the different studies. Current clinical evidence supports the benefit in PRP treatment for knee and hip OA, proven to temporarily relieve pain and improve function of the involved joint with superior results compared with several alternative treatments. Further research to establish the optimal preparation protocol and characteristics of PRP injections for OA is needed.

  12. 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  15. PRP and Articular Cartilage: A Clinical Update

    Science.gov (United States)

    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

  16. 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.

  17. Portable Radiation Package (PRP) Instrument Handbook

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. The significance of sensory appeal for reduced meat consumption.

    Science.gov (United States)

    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.

  19. 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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  2. PA positioning significantly reduces testicular dose during sacroiliac joint radiography

    Energy Technology Data Exchange (ETDEWEB)

    Mekis, Nejc [Faculty of Health Sciences, University of Ljubljana (Slovenia); Mc Entee, Mark F., E-mail: mark.mcentee@ucd.i [School of Medicine and Medical Science, University College Dublin 4 (Ireland); Stegnar, Peter [Jozef Stefan International Postgraduate School, Ljubljana (Slovenia)

    2010-11-15

    Radiation dose to the testes in the antero-posterior (AP) and postero-anterior (PA) projection of the sacroiliac joint (SIJ) was measured with and without a scrotal shield. Entrance surface dose, the dose received by the testicles and the dose area product (DAP) was used. DAP measurements revealed the dose received by the phantom in the PA position is 12.6% lower than the AP (p {<=} 0.009) with no statistically significant reduction in image quality (p {<=} 0.483). The dose received by the testes in the PA projection in SIJ imaging is 93.1% lower than the AP projection when not using protection (p {<=} 0.020) and 94.9% lower with protection (p {<=} 0.019). The dose received by the testicles was not changed by the use of a scrotal shield in the AP position (p {<=} 0.559); but was lowered by its use in the PA (p {<=} 0.058). Use of the PA projection in SIJ imaging significantly lowers, the dose received by the testes compared to the AP projection without significant loss of image quality.

  3. PA positioning significantly reduces testicular dose during sacroiliac joint radiography

    International Nuclear Information System (INIS)

    Mekis, Nejc; Mc Entee, Mark F.; Stegnar, Peter

    2010-01-01

    Radiation dose to the testes in the antero-posterior (AP) and postero-anterior (PA) projection of the sacroiliac joint (SIJ) was measured with and without a scrotal shield. Entrance surface dose, the dose received by the testicles and the dose area product (DAP) was used. DAP measurements revealed the dose received by the phantom in the PA position is 12.6% lower than the AP (p ≤ 0.009) with no statistically significant reduction in image quality (p ≤ 0.483). The dose received by the testes in the PA projection in SIJ imaging is 93.1% lower than the AP projection when not using protection (p ≤ 0.020) and 94.9% lower with protection (p ≤ 0.019). The dose received by the testicles was not changed by the use of a scrotal shield in the AP position (p ≤ 0.559); but was lowered by its use in the PA (p ≤ 0.058). Use of the PA projection in SIJ imaging significantly lowers, the dose received by the testes compared to the AP projection without significant loss of image quality.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  7. Prion protein (PrP) gene-knockout cell lines: insight into functions of the PrP

    OpenAIRE

    Sakudo, Akikazu; Onodera, Takashi

    2015-01-01

    Elucidation of prion protein (PrP) functions is crucial to fully understand prion diseases. A major approach to studying PrP functions is the use of PrP gene-knockout (Prnp ?/?) mice. So far, six types of Prnp ?/? mice have been generated, demonstrating the promiscuous functions of PrP. Recently, other PrP family members, such as Doppel and Shadoo, have been found. However, information obtained from comparative studies of structural and functional analyses of these PrP family proteins do not ...

  8. Comparison of hyaluronic acid and PRP intra-articular injection with combined intra-articular and intraosseous PRP injections to treat patients with knee osteoarthritis.

    Science.gov (United States)

    Su, Ke; Bai, Yuming; Wang, Jun; Zhang, Haisen; Liu, Hao; Ma, Shiyun

    2018-05-01

    The aim of this study was to evaluate the benefit provided by intraosseous infiltration combined with intra-articular injection of platelet-rich plasma to treat mild and moderate stages of knee joint degeneration (Kellgren-Lawrence score II-III) compared with other treatments, specifically intra-articular injection of PRP and of HA. Eighty-six patients with grade II to grade III knee OA according to the Kellgren-Lawrence classification were randomly assigned to intra-articular combined with intraosseous injection of PRP (group A), intra-articular PRP (group B), or intra-articular HA (group C). Patients in group A received intra-articular combined with intraosseous injection of PRP (administered twice, 2 weeks apart). Patients in group B received intra-articular injection of PRP every 14 days. Patients in group C received a series of five intra-articular injections of HA every 7 days. All patients were evaluated using the Visual Analogue Scale (VAS) and Western Ontario and McMaster Universities (WOMAC) score before the treatment and at 1, 3, 6, 12, and 18 months after treatment. There were significant improvements at the end of the 1st month. Notably, group A patients had significantly superior VAS and WOMAC scores than were observed in groups B and C. The VAS scores were similar in groups B and group C after the 6th month. Regarding the WOMAC scores, groups B and C differed at the 1st, 3rd, 6th, and 12th months; however, no significant difference was observed at the 18th month. The combination of intraosseous with intra-articular injections of PRP resulted in a significantly superior clinical outcome, with sustained lower VAS and WOMAC scores and improvement in quality of life within 18 months.

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

    Science.gov (United States)

    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.

  10. Early Delivery of Misfolded PrP from ER to Lysosomes by Autophagy

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  12. 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.

  13. Periodontal tissue regeneration with PRP incorporated gelatin hydrogel sponges.

    Science.gov (United States)

    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.

  14. 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)

  15. Prion protein (PrP) gene-knockout cell lines: insight into functions of the PrP

    Science.gov (United States)

    Sakudo, Akikazu; Onodera, Takashi

    2015-01-01

    Elucidation of prion protein (PrP) functions is crucial to fully understand prion diseases. A major approach to studying PrP functions is the use of PrP gene-knockout (Prnp−/−) mice. So far, six types of Prnp−/− mice have been generated, demonstrating the promiscuous functions of PrP. Recently, other PrP family members, such as Doppel and Shadoo, have been found. However, information obtained from comparative studies of structural and functional analyses of these PrP family proteins do not fully reveal PrP functions. Recently, varieties of Prnp−/− cell lines established from Prnp−/− mice have contributed to the analysis of PrP functions. In this mini-review, we focus on Prnp−/− cell lines and summarize currently available Prnp−/− cell lines and their characterizations. In addition, we introduce the recent advances in the methodology of cell line generation with knockout or knockdown of the PrP gene. We also discuss how these cell lines have provided valuable insights into PrP functions and show future perspectives. PMID:25642423

  16. Experimental Models of Inherited PrP Prion Diseases.

    Science.gov (United States)

    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.

  17. PRP as an Adjunct to Rotator Cuff Tendon Repair.

    Science.gov (United States)

    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.

  18. 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

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

    Science.gov (United States)

    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.

  20. Genetic human prion disease modelled in PrP transgenic Drosophila.

    Science.gov (United States)

    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).

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

    Science.gov (United States)

    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.

  2. 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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  8. 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.

  9. Acetylcholinesterase triggers the aggregation of PrP 106-126

    International Nuclear Information System (INIS)

    Pera, M.; Roman, S.; Ratia, M.; Camps, P.; Munoz-Torrero, D.; Colombo, L.; Manzoni, C.; Salmona, M.; Badia, A.; Clos, M.V.

    2006-01-01

    Acetylcholinesterase (AChE), a senile plaque component, promotes amyloid-β-protein (Aβ) fibril formation in vitro. The presence of prion protein (PrP) in Alzheimer's disease (AD) senile plaques prompted us to assess if AChE could trigger the PrP peptides aggregation as well. Consequently, the efficacy of AChE on the PrP peptide spanning-residues 106-126 aggregation containing a coumarin fluorescence probe (coumarin-PrP 106-126) was studied. Kinetics of coumarin-PrP 106-126 aggregation showed a significant increase of maximum size of aggregates (MSA), which was dependent on AChE concentration. AChE-PrP 106-126 aggregates showed the tinctorial and optical amyloid properties as determined by polarized light and electronic microscopy analysis. A remarkable inhibition of MSA was obtained with propidium iodide, suggesting that AChE triggers PrP 106-126 and Aβ aggregation through a similar mechanism. Huprines (AChE inhibitors) also significantly decreased MSA induced by AChE as well, unveiling the potential interest for some AChE inhibitors as a novel class of potential anti-prion drugs

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  19. A pilot weight reduction program over one year significantly reduced DNA strand breaks in obese subjects

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. 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.

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  9. 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  17. 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...

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  1. 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.

  2. 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...

  3. 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.

  4. Incorporation of catalytic dehydrogenation into fischer-tropsch synthesis to significantly reduce carbon dioxide emissions

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    NARCIS (Netherlands)

    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

  7. Implementation of standardized follow-up care significantly reduces peritonitis in children on chronic peritoneal dialysis.

    Science.gov (United States)

    Neu, Alicia M; Richardson, Troy; Lawlor, John; Stuart, Jayne; Newland, Jason; McAfee, Nancy; Warady, Bradley A

    2016-06-01

    The Standardizing Care to improve Outcomes in Pediatric End stage renal disease (SCOPE) Collaborative aims to reduce peritonitis rates in pediatric chronic peritoneal dialysis patients by increasing implementation of standardized care practices. To assess this, monthly care bundle compliance and annualized monthly peritonitis rates were evaluated from 24 SCOPE centers that were participating at collaborative launch and that provided peritonitis rates for the 13 months prior to launch. Changes in bundle compliance were assessed using either a logistic regression model or a generalized linear mixed model. Changes in average annualized peritonitis rates over time were illustrated using the latter model. In the first 36 months of the collaborative, 644 patients with 7977 follow-up encounters were included. The likelihood of compliance with follow-up care practices increased significantly (odds ratio 1.15, 95% confidence interval 1.10, 1.19). Mean monthly peritonitis rates significantly decreased from 0.63 episodes per patient year (95% confidence interval 0.43, 0.92) prelaunch to 0.42 (95% confidence interval 0.31, 0.57) at 36 months postlaunch. A sensitivity analysis confirmed that as mean follow-up compliance increased, peritonitis rates decreased, reaching statistical significance at 80% at which point the prelaunch rate was 42% higher than the rate in the months following achievement of 80% compliance. In its first 3 years, the SCOPE Collaborative has increased the implementation of standardized follow-up care and demonstrated a significant reduction in average monthly peritonitis rates. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  8. 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

  9. Induction-heating MOCVD reactor with significantly improved heating efficiency and reduced harmful magnetic coupling

    KAUST Repository

    Li, Kuang-Hui; Alotaibi, Hamad S.; Sun, Haiding; Lin, Ronghui; Guo, Wenzhe; Torres-Castanedo, Carlos G.; Liu, Kaikai; Galan, Sergio V.; Li, Xiaohang

    2018-01-01

    In a conventional induction-heating III-nitride metalorganic chemical vapor deposition (MOCVD) reactor, the induction coil is outside the chamber. Therefore, the magnetic field does not couple with the susceptor well, leading to compromised heating efficiency and harmful coupling with the gas inlet and thus possible overheating. Hence, the gas inlet has to be at a minimum distance away from the susceptor. Because of the elongated flow path, premature reactions can be more severe, particularly between Al- and B-containing precursors and NH3. Here, we propose a structure that can significantly improve the heating efficiency and allow the gas inlet to be closer to the susceptor. Specifically, the induction coil is designed to surround the vertical cylinder of a T-shaped susceptor comprising the cylinder and a top horizontal plate holding the wafer substrate within the reactor. Therefore, the cylinder coupled most magnetic field to serve as the thermal source for the plate. Furthermore, the plate can block and thus significantly reduce the uncoupled magnetic field above the susceptor, thereby allowing the gas inlet to be closer. The results show approximately 140% and 2.6 times increase in the heating and susceptor coupling efficiencies, respectively, as well as a 90% reduction in the harmful magnetic flux on the gas inlet.

  10. Induction-heating MOCVD reactor with significantly improved heating efficiency and reduced harmful magnetic coupling

    KAUST Repository

    Li, Kuang-Hui

    2018-02-23

    In a conventional induction-heating III-nitride metalorganic chemical vapor deposition (MOCVD) reactor, the induction coil is outside the chamber. Therefore, the magnetic field does not couple with the susceptor well, leading to compromised heating efficiency and harmful coupling with the gas inlet and thus possible overheating. Hence, the gas inlet has to be at a minimum distance away from the susceptor. Because of the elongated flow path, premature reactions can be more severe, particularly between Al- and B-containing precursors and NH3. Here, we propose a structure that can significantly improve the heating efficiency and allow the gas inlet to be closer to the susceptor. Specifically, the induction coil is designed to surround the vertical cylinder of a T-shaped susceptor comprising the cylinder and a top horizontal plate holding the wafer substrate within the reactor. Therefore, the cylinder coupled most magnetic field to serve as the thermal source for the plate. Furthermore, the plate can block and thus significantly reduce the uncoupled magnetic field above the susceptor, thereby allowing the gas inlet to be closer. The results show approximately 140% and 2.6 times increase in the heating and susceptor coupling efficiencies, respectively, as well as a 90% reduction in the harmful magnetic flux on the gas inlet.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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.

  13. Using lytic bacteriophages to eliminate or significantly reduce contamination of food by foodborne bacterial pathogens.

    Science.gov (United States)

    Sulakvelidze, Alexander

    2013-10-01

    Bacteriophages (also called 'phages') are viruses that kill bacteria. They are arguably the oldest (3 billion years old, by some estimates) and most ubiquitous (total number estimated to be 10(30) -10(32) ) known organisms on Earth. Phages play a key role in maintaining microbial balance in every ecosystem where bacteria exist, and they are part of the normal microflora of all fresh, unprocessed foods. Interest in various practical applications of bacteriophages has been gaining momentum recently, with perhaps the most attention focused on using them to improve food safety. That approach, called 'phage biocontrol', typically includes three main types of applications: (i) using phages to treat domesticated livestock in order to reduce their intestinal colonization with, and shedding of, specific bacterial pathogens; (ii) treatments for decontaminating inanimate surfaces in food-processing facilities and other food establishments, so that foods processed on those surfaces are not cross-contaminated with the targeted pathogens; and (iii) post-harvest treatments involving direct applications of phages onto the harvested foods. This mini-review primarily focuses on the last type of intervention, which has been gaining the most momentum recently. Indeed, the results of recent studies dealing with improving food safety, and several recent regulatory approvals of various commercial phage preparations developed for post-harvest food safety applications, strongly support the idea that lytic phages may provide a safe, environmentally-friendly, and effective approach for significantly reducing contamination of various foods with foodborne bacterial pathogens. However, some important technical and nontechnical problems may need to be addressed before phage biocontrol protocols can become an integral part of routine food safety intervention strategies implemented by food industries in the USA. © 2013 Society of Chemical Industry.

  14. Pharmacological kynurenine 3-monooxygenase enzyme inhibition significantly reduces neuropathic pain in a rat model.

    Science.gov (United States)

    Rojewska, Ewelina; Piotrowska, Anna; Makuch, Wioletta; Przewlocka, Barbara; Mika, Joanna

    2016-03-01

    Recent studies have highlighted the involvement of the kynurenine pathway in the pathology of neurodegenerative diseases, but the role of this system in neuropathic pain requires further extensive research. Therefore, the aim of our study was to examine the role of kynurenine 3-monooxygenase (Kmo), an enzyme that is important in this pathway, in a rat model of neuropathy after chronic constriction injury (CCI) to the sciatic nerve. For the first time, we demonstrated that the injury-induced increase in the Kmo mRNA levels in the spinal cord and the dorsal root ganglia (DRG) was reduced by chronic administration of the microglial inhibitor minocycline and that this effect paralleled a decrease in the intensity of neuropathy. Further, minocycline administration alleviated the lipopolysaccharide (LPS)-induced upregulation of Kmo mRNA expression in microglial cell cultures. Moreover, we demonstrated that not only indirect inhibition of Kmo using minocycline but also direct inhibition using Kmo inhibitors (Ro61-6048 and JM6) decreased neuropathic pain intensity on the third and the seventh days after CCI. Chronic Ro61-6048 administration diminished the protein levels of IBA-1, IL-6, IL-1beta and NOS2 in the spinal cord and/or the DRG. Both Kmo inhibitors potentiated the analgesic properties of morphine. In summary, our data suggest that in neuropathic pain model, inhibiting Kmo function significantly reduces pain symptoms and enhances the effectiveness of morphine. The results of our studies show that the kynurenine pathway is an important mediator of neuropathic pain pathology and indicate that Kmo represents a novel pharmacological target for the treatment of neuropathy. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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.

  16. 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...

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

    OpenAIRE

    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...

  18. 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.

  19. Significantly reduced hypoxemic events in morbidly obese patients undergoing gastrointestinal endoscopy: Predictors and practice effect

    Directory of Open Access Journals (Sweden)

    Basavana Gouda Goudra

    2014-01-01

    Full Text Available Background: Providing anesthesia for gastrointestinal (GI endoscopy procedures in morbidly obese patients is a challenge for a variety of reasons. The negative impact of obesity on the respiratory system combined with a need to share the upper airway and necessity to preserve the spontaneous ventilation, together add to difficulties. Materials and Methods: This retrospective cohort study included patients with a body mass index (BMI >40 kg/m 2 that underwent out-patient GI endoscopy between September 2010 and February 2011. Patient data was analyzed for procedure, airway management technique as well as hypoxemic and cardiovascular events. Results: A total of 119 patients met the inclusion criteria. Our innovative airway management technique resulted in a lower rate of intraoperative hypoxemic events compared with any published data available. Frequency of desaturation episodes showed statistically significant relation to previous history of obstructive sleep apnea (OSA. These desaturation episodes were found to be statistically independent of increasing BMI of patients. Conclusion: Pre-operative history of OSA irrespective of associated BMI values can be potentially used as a predictor of intra-procedural desaturation. With suitable modification of anesthesia technique, it is possible to reduce the incidence of adverse respiratory events in morbidly obese patients undergoing GI endoscopy procedures, thereby avoiding the need for endotracheal intubation.

  20. Significantly reduced hypoxemic events in morbidly obese patients undergoing gastrointestinal endoscopy: Predictors and practice effect.

    Science.gov (United States)

    Goudra, Basavana Gouda; Singh, Preet Mohinder; Penugonda, Lakshmi C; Speck, Rebecca M; Sinha, Ashish C

    2014-01-01

    Providing anesthesia for gastrointestinal (GI) endoscopy procedures in morbidly obese patients is a challenge for a variety of reasons. The negative impact of obesity on the respiratory system combined with a need to share the upper airway and necessity to preserve the spontaneous ventilation, together add to difficulties. This retrospective cohort study included patients with a body mass index (BMI) >40 kg/m(2) that underwent out-patient GI endoscopy between September 2010 and February 2011. Patient data was analyzed for procedure, airway management technique as well as hypoxemic and cardiovascular events. A total of 119 patients met the inclusion criteria. Our innovative airway management technique resulted in a lower rate of intraoperative hypoxemic events compared with any published data available. Frequency of desaturation episodes showed statistically significant relation to previous history of obstructive sleep apnea (OSA). These desaturation episodes were found to be statistically independent of increasing BMI of patients. Pre-operative history of OSA irrespective of associated BMI values can be potentially used as a predictor of intra-procedural desaturation. With suitable modification of anesthesia technique, it is possible to reduce the incidence of adverse respiratory events in morbidly obese patients undergoing GI endoscopy procedures, thereby avoiding the need for endotracheal intubation.

  1. 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

  2. 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

  3. Environmental program with operational cases to reduce risk to the marine environment significantly

    International Nuclear Information System (INIS)

    Cline, J.T.; Forde, R.

    1991-01-01

    In this paper Amoco Norway Oil Company's environmental program is detailed, followed by example operational programs and achievements aimed to minimize environmental risks to the marine environment at Valhall platform. With a corporate goal to be a leader in protecting the environment, the appropriate strategies and policies that form the basis of the environmental management system are incorporated in the quality assurance programs. Also, included in the program are necessary organizational structures, responsibilities of environmental affairs and line organization personnel, compliance procedures and a waste task force obliged to implement operations improvements. An internal environmental audit system has been initiated, in addition to corporate level audits, which, when communicated to the line organization closes the environmental management loop through experience feed back. Environmental projects underway are significantly decreasing the extent and/or risk of pollution from offshore activities. The cradle to grave responsibility is assumed with waste separated offshore and onshore followed by disposal in audited sites. A $5 MM program is underway to control produced oily solids and reduce oil in produced water aiming to less than 20 ppm. When oil-based mud is used in deeper hole sections, drill solids disposed at sea average less than 60 g oil/kg dry cuttings using appropriate shaker screens, and a washing/centrifuge system to remove fines. Certain oily liquid wastes are being injected down hole whereas previously they were burned using a mud burner. Finally, a program is underway with a goal to eliminate sea discharge of oil on cuttings through injection disposal of oily wastes, drilling with alternative muds such as a cationic water base mud, and/or proper onshore disposal of oily wastes

  4. Simultaneous bilateral stereotactic procedure for deep brain stimulation implants: a significant step for reducing operation time.

    Science.gov (United States)

    Fonoff, Erich Talamoni; Azevedo, Angelo; Angelos, Jairo Silva Dos; Martinez, Raquel Chacon Ruiz; Navarro, Jessie; Reis, Paul Rodrigo; Sepulveda, Miguel Ernesto San Martin; Cury, Rubens Gisbert; Ghilardi, Maria Gabriela Dos Santos; Teixeira, Manoel Jacobsen; Lopez, William Omar Contreras

    2016-07-01

    OBJECT Currently, bilateral procedures involve 2 sequential implants in each of the hemispheres. The present report demonstrates the feasibility of simultaneous bilateral procedures during the implantation of deep brain stimulation (DBS) leads. METHODS Fifty-seven patients with movement disorders underwent bilateral DBS implantation in the same study period. The authors compared the time required for the surgical implantation of deep brain electrodes in 2 randomly assigned groups. One group of 28 patients underwent traditional sequential electrode implantation, and the other 29 patients underwent simultaneous bilateral implantation. Clinical outcomes of the patients with Parkinson's disease (PD) who had undergone DBS implantation of the subthalamic nucleus using either of the 2 techniques were compared. RESULTS Overall, a reduction of 38.51% in total operating time for the simultaneous bilateral group (136.4 ± 20.93 minutes) as compared with that for the traditional consecutive approach (220.3 ± 27.58 minutes) was observed. Regarding clinical outcomes in the PD patients who underwent subthalamic nucleus DBS implantation, comparing the preoperative off-medication condition with the off-medication/on-stimulation condition 1 year after the surgery in both procedure groups, there was a mean 47.8% ± 9.5% improvement in the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) score in the simultaneous group, while the sequential group experienced 47.5% ± 15.8% improvement (p = 0.96). Moreover, a marked reduction in the levodopa-equivalent dose from preoperatively to postoperatively was similar in these 2 groups. The simultaneous bilateral procedure presented major advantages over the traditional sequential approach, with a shorter total operating time. CONCLUSIONS A simultaneous stereotactic approach significantly reduces the operation time in bilateral DBS procedures, resulting in decreased microrecording time, contributing to the optimization of functional

  5. Two New PRP Conjugate Gradient Algorithms for Minimization Optimization Models.

    Directory of Open Access Journals (Sweden)

    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.

  6. Two New PRP Conjugate Gradient Algorithms for Minimization Optimization Models.

    Science.gov (United States)

    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.

  7. 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

  8. Soil nitrate reducing processes drivers, mechanisms for spatial variation, and significance for nitrous oxide production

    OpenAIRE

    Giles, M.; Morley, N.; Baggs, E.M.; Daniell, T.J.

    2012-01-01

    The microbial processes of denitrification and dissimilatory nitrate reduction to ammonium\\ud (DNRA) are two important nitrate reducing mechanisms in soil, which are responsible for\\ud the loss of nitrate (NO−\\ud 3 ) and production of the potent greenhouse gas, nitrous oxide (N2O).\\ud A number of factors are known to control these processes, including O2 concentrations and\\ud moisture content, N, C, pH, and the size and community structure of nitrate reducing organisms\\ud responsible for the ...

  9. Pegasus project. DLC coating and low viscosity oil reduce energy losses significantly

    Energy Technology Data Exchange (ETDEWEB)

    Doerwald, Dave; Jacobs, Ruud [Hauzer Techno Coating (Netherlands). Tribological Coatings

    2012-03-15

    Pegasus, the flying horse from Greek mythology, is a suitable name for the research project initiated by a German automotive OEM with participation of Hauzer Techno Coating and several automotive suppliers. It will enable future automotive vehicles to reduce fuel consumption without losing power. The project described in this article focuses on the rear differential, because reducing friction here can contribute considerably to efficiency improvement of the whole vehicle. Surfaces, coating and oil viscosity have been investigated and interesting conclusions have been reached. (orig.)

  10. 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...

  11. Soil nitrate reducing processes – drivers, mechanisms for spatial variation, and significance for nitrous oxide production

    Science.gov (United States)

    Giles, Madeline; Morley, Nicholas; Baggs, Elizabeth M.; Daniell, Tim J.

    2012-01-01

    The microbial processes of denitrification and dissimilatory nitrate reduction to ammonium (DNRA) are two important nitrate reducing mechanisms in soil, which are responsible for the loss of nitrate (NO3−) and production of the potent greenhouse gas, nitrous oxide (N2O). A number of factors are known to control these processes, including O2 concentrations and moisture content, N, C, pH, and the size and community structure of nitrate reducing organisms responsible for the processes. There is an increasing understanding associated with many of these controls on flux through the nitrogen cycle in soil systems. However, there remains uncertainty about how the nitrate reducing communities are linked to environmental variables and the flux of products from these processes. The high spatial variability of environmental controls and microbial communities across small sub centimeter areas of soil may prove to be critical in determining why an understanding of the links between biotic and abiotic controls has proved elusive. This spatial effect is often overlooked as a driver of nitrate reducing processes. An increased knowledge of the effects of spatial heterogeneity in soil on nitrate reduction processes will be fundamental in understanding the drivers, location, and potential for N2O production from soils. PMID:23264770

  12. Soil nitrate reducing processes – drivers, mechanisms for spatial variation and significance for nitrous oxide production

    Directory of Open Access Journals (Sweden)

    Madeline Eleanore Giles

    2012-12-01

    Full Text Available The microbial processes of denitrification and dissimilatory nitrate reduction to ammonium (DNRA are two important nitrate reducing mechanisms in soil, which are responsible for the loss of nitrate (NO3-¬ and production of the potent greenhouse gas, nitrous oxide (N2O. A number of factors are known to control these processes, including O2 concentrations and moisture content, N, C, pH and the size and community structure of nitrate reducing organisms responsible for the processes. There is an increasing understanding associated with many of these controls on flux through the nitrogen cycle in soil systems. However, there remains uncertainty about how the nitrate reducing communities are linked to environmental variables and the flux of products from these processes. The high spatial variability of environmental controls and microbial communities across small sub cm areas of soil may prove to be critical in determining why an understanding of the links between biotic and abiotic controls has proved elusive. This spatial effect is often overlooked as a driver of nitrate reducing processes. An increased knowledge of the effects of spatial heterogeneity in soil on nitrate reduction processes will be fundamental in understanding the drivers, location and potential for N2O production from soils.

  13. Soil nitrate reducing processes - drivers, mechanisms for spatial variation, and significance for nitrous oxide production.

    Science.gov (United States)

    Giles, Madeline; Morley, Nicholas; Baggs, Elizabeth M; Daniell, Tim J

    2012-01-01

    The microbial processes of denitrification and dissimilatory nitrate reduction to ammonium (DNRA) are two important nitrate reducing mechanisms in soil, which are responsible for the loss of nitrate ([Formula: see text]) and production of the potent greenhouse gas, nitrous oxide (N(2)O). A number of factors are known to control these processes, including O(2) concentrations and moisture content, N, C, pH, and the size and community structure of nitrate reducing organisms responsible for the processes. There is an increasing understanding associated with many of these controls on flux through the nitrogen cycle in soil systems. However, there remains uncertainty about how the nitrate reducing communities are linked to environmental variables and the flux of products from these processes. The high spatial variability of environmental controls and microbial communities across small sub centimeter areas of soil may prove to be critical in determining why an understanding of the links between biotic and abiotic controls has proved elusive. This spatial effect is often overlooked as a driver of nitrate reducing processes. An increased knowledge of the effects of spatial heterogeneity in soil on nitrate reduction processes will be fundamental in understanding the drivers, location, and potential for N(2)O production from soils.

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

    Science.gov (United States)

    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.

  15. Reducing dysfunctional beliefs about sleep does not significantly improve insomnia in cognitive behavioral therapy.

    Science.gov (United States)

    Okajima, Isa; Nakajima, Shun; Ochi, Moeko; Inoue, Yuichi

    2014-01-01

    The present study examined to examine whether improvement of insomnia is mediated by a reduction in sleep-related dysfunctional beliefs through cognitive behavioral therapy for insomnia. In total, 64 patients with chronic insomnia received cognitive behavioral therapy for insomnia consisting of 6 biweekly individual treatment sessions of 50 minutes in length. Participants were asked to complete the Athens Insomnia Scale and the Dysfunctional Beliefs and Attitudes about Sleep scale both at the baseline and at the end of treatment. The results showed that although cognitive behavioral therapy for insomnia greatly reduced individuals' scores on both scales, the decrease in dysfunctional beliefs and attitudes about sleep with treatment did not seem to mediate improvement in insomnia. The findings suggest that sleep-related dysfunctional beliefs endorsed by patients with chronic insomnia may be attenuated by cognitive behavioral therapy for insomnia, but changes in such beliefs are not likely to play a crucial role in reducing the severity of insomnia.

  16. 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

  17. The Evolution of Polymer Composition during PHA Accumulation: The Significance of Reducing Equivalents

    Directory of Open Access Journals (Sweden)

    Liliana Montano-Herrera

    2017-03-01

    Full Text Available This paper presents a systematic investigation into monomer development during mixed culture Polyhydroxyalkanoates (PHA accumulation involving concurrent active biomass growth and polymer storage. A series of mixed culture PHA accumulation experiments, using several different substrate-feeding strategies, was carried out. The feedstock comprised volatile fatty acids, which were applied as single carbon sources, as mixtures, or in series, using a fed-batch feed-on-demand controlled bioprocess. A dynamic trend in active biomass growth as well as polymer composition was observed. The observations were consistent over replicate accumulations. Metabolic flux analysis (MFA was used to investigate metabolic activity through time. It was concluded that carbon flux, and consequently copolymer composition, could be linked with how reducing equivalents are generated.

  18. Significantly reduced c-axis thermal diffusivity of graphene-based papers

    Science.gov (United States)

    Han, Meng; Xie, Yangsu; Liu, Jing; Zhang, Jingchao; Wang, Xinwei

    2018-06-01

    Owing to their very high thermal conductivity as well as large surface-to-volume ratio, graphene-based films/papers have been proposed as promising candidates of lightweight thermal interface materials and lateral heat spreaders. In this work, we study the cross-plane (c-axis) thermal conductivity (k c ) and diffusivity (α c ) of two typical graphene-based papers, which are partially reduced graphene paper (PRGP) and graphene oxide paper (GOP), and compare their thermal properties with highly-reduced graphene paper and graphite. The determined α c of PRGP varies from (1.02 ± 0.09) × 10‑7 m2 s‑1 at 295 K to (2.31 ± 0.18) × 10‑7 m2 s‑1 at 12 K. This low α c is mainly attributed to the strong phonon scattering at the grain boundaries and defect centers due to the small grain sizes and high-level defects. For GOP, α c varies from (1.52 ± 0.05) × 10‑7 m2 s‑1 at 295 K to (2.28 ± 0.08) × 10‑7 m2 s‑1 at 12.5 K. The cross-plane thermal transport of GOP is attributed to the high density of functional groups between carbon layers which provide weak thermal transport tunnels across the layers in the absence of direct energy coupling among layers. This work sheds light on the understanding and optimizing of nanostructure of graphene-based paper-like materials for desired thermal performance.

  19. Technological significances to reduce the material problems. Feasibility of heat flux reduction

    International Nuclear Information System (INIS)

    Yamazaki, Seiichiro; Shimada, Michiya.

    1994-01-01

    For a divertor plate in a fusion power reactor, a high temperature coolant must be used for heat removal to keep thermal efficiency high. It makes the temperature and thermal stress of wall materials higher than the design limits. Issues of the coolant itself, e.g. burnout of high temperature water, will also become a serious problem. Sputtering erosion of the surface material will be a great concern of its lifetime. Therefore, it is necessary to reduce the heat and particle loads to the divertor plate technologically. The feasibility of some technological methods of heat reduction, such as separatrix sweeping, is discussed. As one of the most promising ideas, the methods of radiative cooling of the divertor plasma are summarized based on the recent results of large tokamaks. The feasibility of remote radiative cooling and gas divertor is discussed. The ideas are considered in recent design studies of tokamak power reactors and experimental reactors. By way of example, conceptual designs of divertor plate for the steady state tokamak power reactor are described. (author)

  20. Glycan-deficient PrP stimulates VEGFR2 signaling via glycosaminoglycan.

    Science.gov (United States)

    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.

  1. Purification and Fibrillation of Full-Length Recombinant PrP.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  3. 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.

  4. 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?...

  5. Prion propagation in cells expressing PrP glycosylation mutants.

    Science.gov (United States)

    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.

  6. Thrombolysis significantly reduces transient myocardial ischaemia following first acute myocardial infarction

    DEFF Research Database (Denmark)

    Mickley, H; Pless, P; Nielsen, J R

    1992-01-01

    In order to investigate whether thrombolysis affects residual myocardial ischaemia, we prospectively performed a predischarge maximal exercise test and early out-of-hospital ambulatory ST segment monitoring in 123 consecutive men surviving a first acute myocardial infarction (AMI). Seventy......-four patients fulfilled our criteria for thrombolysis, but only the last 35 patients included received thrombolytic therapy. As thrombolysis was not available in our Department at the start of the study, the first 39 patients included were conservatively treated (controls). No significant differences...... in baseline clinical characteristics were found between the two groups. In-hospital atrial fibrillation and digoxin therapy was more prevalent in controls (P less than 0.05). During exercise, thrombolysed patients reached a higher maximal work capacity compared with controls: 160 +/- 41 vs 139 +/- 34 W (P...

  7. Selenium Supplementation Significantly Reduces Thyroid Autoantibody Levels in Patients with Chronic Autoimmune Thyroiditis

    DEFF Research Database (Denmark)

    Wichman, Johanna Eva Märta; Winther, Kristian Hillert; Bonnema, Steen Joop

    2016-01-01

    BACKGROUND: Selenium supplementation may decrease circulating thyroid autoantibodies in patients with chronic autoimmune thyroiditis (AIT), but the available trials are heterogenous. This study expands and critically reappraises the knowledge on this topic. METHODS: A literature search identified...... 3366 records. Controlled trials in adults (≥18 years of age) with AIT, comparing selenium with or without levothyroxine (LT4), versus placebo and/or LT4, were eligible. Assessed outcomes were serum thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) autoantibody levels, and immunomodulatory effects...... and LT4-untreated. Heterogeneity was estimated using I(2), and quality of evidence was assessed per outcome, using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines. RESULTS: In LT4-treated populations, the selenium group had significantly lower TPOAb levels after...

  8. A case of gastric endocrine cell carcinoma which was significantly reduced in size by radiotherapy

    International Nuclear Information System (INIS)

    Azakami, Kiyoshi; Nishida, Kouji; Tanikawa, Ken

    2016-01-01

    In 2010, the World Health Organization classified gastric neuroendocrine tumors (NETs) into three types: NET grade (G) 1, NET G2 and neuroendocrine carcinoma (NEC). NECs are associated with a very poor prognosis. The patient was an 84-year-old female who was initially diagnosed by gastrointestinal endoscope with type 3 advanced gastric cancer with stenosis of the gastric cardia. Her overall status and performance status did not allow for operations or intensive chemotherapy. Palliative radiotherapy was performed and resulted in a significant reduction in the size of the tumor as well as the improvement of the obstructive symptoms. She died 9 months after radiotherapy. An autopsy provided a definitive diagnosis of gastric endocrine cell carcinoma, and the effectiveness of radiotherapy was pathologically-confirmed. Palliative radiotherapy may be a useful treatment option for providing symptom relief, especially for old patients with unresectable advanced gastric neuroendocrine carcinoma. (author)

  9. Ad libitum Mediterranean and Low Fat Diets both Significantly Reduce Hepatic Steatosis: a Randomized Controlled Trial.

    Science.gov (United States)

    Properzi, Catherine; O'Sullivan, Therese A; Sherriff, Jill L; Ching, Helena L; Jeffrey, Garry P; Buckley, Rachel F; Tibballs, Jonathan; MacQuillan, Gerry C; Garas, George; Adams, Leon A

    2018-05-05

    Although diet induced weight loss is first-line treatment for patients with non-alcoholic fatty liver disease (NAFLD), long-term maintenance is difficult. The optimal diet for either improvement in NAFLD or associated cardio-metabolic risk factors regardless of weight loss, is unknown. We examined the effect of two ad libitum isocaloric diets [Mediterranean (MD) or Low Fat (LF)] on hepatic steatosis and cardio-metabolic risk factors. Subjects with NAFLD were randomized to a 12-week blinded dietary intervention (MD vs LF). Hepatic steatosis was determined via magnetic resonance spectroscopy (MRS). From a total of 56 subjects enrolled, 49 subjects completed the intervention and 48 were included for analysis. During the intervention, subjects on the MD had significantly higher total and monounsaturated fat but lower carbohydrate and sodium intakes compared to LF subjects (pfat reduction between the groups (p=0.32), with mean (SD) relative reductions of 25.0% (±25.3%) in LF and 32.4% (±25.5%) in MD. Liver enzymes also improved significantly in both groups. Weight loss was minimal and not different between groups [-1.6 (±2.1)kg in LF vs -2.1 (±2.5)kg in MD, (p=0.52)]. Within-group improvements in the Framingham risk score, total cholesterol, serum triglyceride, and HbA1c were observed in the MD (all pvs. 64%, p=0.048). Ad libitum low fat and Mediterranean diets both improve hepatic steatosis to a similar degree. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

  10. Social networking strategies that aim to reduce obesity have achieved significant although modest results.

    Science.gov (United States)

    Ashrafian, Hutan; Toma, Tania; Harling, Leanne; Kerr, Karen; Athanasiou, Thanos; Darzi, Ara

    2014-09-01

    The global epidemic of obesity continues to escalate. Obesity accounts for an increasing proportion of the international socioeconomic burden of noncommunicable disease. Online social networking services provide an effective medium through which information may be exchanged between obese and overweight patients and their health care providers, potentially contributing to superior weight-loss outcomes. We performed a systematic review and meta-analysis to assess the role of these services in modifying body mass index (BMI). Our analysis of twelve studies found that interventions using social networking services produced a modest but significant 0.64 percent reduction in BMI from baseline for the 941 people who participated in the studies' interventions. We recommend that social networking services that target obesity should be the subject of further clinical trials. Additionally, we recommend that policy makers adopt reforms that promote the use of anti-obesity social networking services, facilitate multistakeholder partnerships in such services, and create a supportive environment to confront obesity and its associated noncommunicable diseases. Project HOPE—The People-to-People Health Foundation, Inc.

  11. Targeting Heparin to Collagen within Extracellular Matrix Significantly Reduces Thrombogenicity and Improves Endothelialization of Decellularized Tissues.

    Science.gov (United States)

    Jiang, Bin; Suen, Rachel; Wertheim, Jason A; Ameer, Guillermo A

    2016-12-12

    Thrombosis within small-diameter vascular grafts limits the development of bioartificial, engineered vascular conduits, especially those derived from extracellular matrix (ECM). Here we describe an easy-to-implement strategy to chemically modify vascular ECM by covalently linking a collagen binding peptide (CBP) to heparin to form a heparin derivative (CBP-heparin) that selectively binds a subset of collagens. Modification of ECM with CBP-heparin leads to increased deposition of functional heparin (by ∼7.2-fold measured by glycosaminoglycan composition) and a corresponding reduction in platelet binding (>70%) and whole blood clotting (>80%) onto the ECM. Furthermore, addition of CBP-heparin to the ECM stabilizes long-term endothelial cell attachment to the lumen of ECM-derived vascular conduits, potentially through recruitment of heparin-binding growth factors that ultimately improve the durability of endothelialization in vitro. Overall, our findings provide a simple yet effective method to increase deposition of functional heparin on the surface of ECM-based vascular grafts and thereby minimize thrombogenicity of decellularized tissue, overcoming a significant challenge in tissue engineering of bioartificial vessels and vascularized organs.

  12. Thyroid function appears to be significantly reduced in Space-borne MDS mice

    Science.gov (United States)

    Saverio Ambesi-Impiombato, Francesco; Curcio, Francesco; Fontanini, Elisabetta; Perrella, Giuseppina; Spelat, Renza; Zambito, Anna Maria; Damaskopoulou, Eleni; Peverini, Manola; Albi, Elisabetta

    It is known that prolonged space flights induced changes in human cardiovascular, muscu-loskeletal and nervous systems whose function is regulated by the thyroid gland but, until now, no data were reported about thyroid damage during space missions. We have demonstrated in vitro that, during space missions (Italian Soyuz Mission "ENEIDE" in 2005, Shuttle STS-120 "ESPERIA" in 2007), thyroid in vitro cultured cells did not respond to thyroid stimulating hor-mone (TSH) treatment; they appeared healthy and alive, despite their being in a pro-apopotic state characterised by a variation of sphingomyelin metabolism and consequent increase in ce-ramide content. The insensitivity to TSH was largely due to a rearrangement of specific cell membrane microdomains, acting as platforms for TSH-receptor (TEXUS-44 mission in 2008). To study if these effects were present also in vivo, as part of the Mouse Drawer System (MDS) Tissue Sharing Program, we performed experiments in mice maintained onboard the Interna-tional Space Station during the long-duration (90 days) exploration mission STS-129. After return to earth, the thyroids isolated from the 3 animals were in part immediately frozen to study the morphological modification in space and in part immediately used to study the effect of TSH treatment. For this purpose small fragments of tissue were treated with 10-7 or 10-8 M TSH for 1 hour by using untreated fragments as controls. Then the fragments were fixed with absolute ethanol for 10 min at room temperature and centrifuged for 20 min. at 3000 x g. The supernatants were used for cAMP analysis whereas the pellet were used for protein amount determination and for immunoblotting analysis of TSH-receptor, sphingomyelinase and sphingomyelin-synthase. The results showed a modification of the thyroid structure and also the values of cAMP production after treatment with 10-7 M TSH for 1 hour were significantly lower than those obtained in Earth's gravity. The treatment with TSH

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  2. 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.

    Science.gov (United States)

    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

  3. 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

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

    Science.gov (United States)

    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

  5. 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.

    Science.gov (United States)

    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.

  6. Interaction between FOXO1A-209 Genotype and Tea Drinking is Significantly Associated with Reduced Mortality at Advanced Ages

    DEFF Research Database (Denmark)

    Zeng, Yi; Chen, Huashuai; Ni, Ting

    2016-01-01

    Based on the genotypic/phenotypic data from Chinese Longitudinal Healthy Longevity Survey (CLHLS) and Cox proportional hazard model, the present study demonstrates that interactions between carrying FOXO1A-209 genotypes and tea drinking are significantly associated with lower risk of mortality...... at advanced ages. Such significant association is replicated in two independent Han Chinese CLHLS cohorts (p =0.028-0.048 in the discovery and replication cohorts, and p =0.003-0.016 in the combined dataset). We found the associations between tea drinking and reduced mortality are much stronger among carriers...... of the FOXO1A-209 genotype compared to non-carriers, and drinking tea is associated with a reversal of the negative effects of carrying FOXO1A-209 minor alleles, that is, from a substantially increased mortality risk to substantially reduced mortality risk at advanced ages. The impacts are considerably...

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

    Science.gov (United States)

    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.

  8. 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.

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

    Science.gov (United States)

    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.

  10. 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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  13. A Recombinant Multi-Stage Vaccine against Paratuberculosis Significantly Reduces Bacterial Level in Tissues without Interference in Diagnostics

    DEFF Research Database (Denmark)

    Jungersen, Gregers; Thakur, Aneesh; Aagaard, C.

    , PPDj-specific IFN-γ responses or positive PPDa or PPDb skin tests developed in vaccinees. Antibodies and cell-mediated immune responses were developed against FET11 antigens, however. At necropsy 8 or 12 months of age, relative Map burden was determined in a number of gut tissues by quantitative IS900...... PCR and revealed significantly reduced levels of Map and reduced histopathology. Diagnostic tests for antibody responses and cell-mediated immune responses, used as surrogates of infection, corroborated the observed vaccine efficacy: Five of seven non‐vaccinated calves seroconverted in ID Screen......-γ assay responses from 40 to 52 weeks compared to non-vaccinated calves. These results indicate the FET11 vaccine can be used to accelerate eradication of paratuberculosis while surveillance or test-and-manage control programs for tuberculosis and Johne’s disease remain in place. Funded by EMIDA ERA...

  14. 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)

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

  17. Lime and Phosphate Amendment Can Significantly Reduce Uptake of Cd and Pb by Field-Grown Rice

    Directory of Open Access Journals (Sweden)

    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.

  18. Cytosolically expressed PrP GPI-signal peptide interacts with mitochondria.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  20. Reduced bone mineral density is not associated with significantly reduced bone quality in men and women practicing long-term calorie restriction with adequate nutrition.

    Science.gov (United States)

    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.

  1. Smoking cessation programmes in radon affected areas: can they make a significant contribution to reducing radon-induced lung cancers?

    International Nuclear Information System (INIS)

    Denman, A.R.; Groves-Kirkby, C.J.; Timson, K.; Shield, G.; Rogers, S.; Phillips, P.S.

    2008-01-01

    Domestic radon levels in parts of the UK are sufficiently high to increase the risk of lung cancer in the occupants. Public health campaigns in Northamptonshire, a designated radon affected area with 6.3% of homes having average radon levels over the UK action level of 200 Bq m -3 , have encouraged householders to test for radon and then to carry out remediation in their homes, but have been only partially successful. Only 40% of Northamptonshire houses have been tested, and only 15% of householders finding raised levels proceed to remediate. Of those who did remediate, only 9% smoked, compared to a countywide average of 28.8%. This is unfortunate, since radon and smoking combine to place the individual at higher risk by a factor of around 4, and suggests that current strategies to reduce domestic radon exposure are not reaching those most at risk. During 2004-5, the NHS Stop Smoking Services in Northamptonshire assisted 2,808 smokers to quit to the 4-week stage, with some 30% of 4-week quitters remaining quitters at 1 year. We consider whether smoking cessation campaigns make significant contributions to radon risk reduction on their own, by assessing individual occupants' risk of developing lung cancer from knowledge of their age, gender, and smoking habits, together with he radon level in their house. The results demonstrate that smoking cessation programmes have significant added value in radon affected areas, and contribute a greater health benefit than reducing radon levels in the smokers' homes, whilst they remain smokers. Additionally, results are presented from a questionnaire-based survey of quitters, addressing their reasons for seeking help in quitting smoking, and whether knowledge of radon risks influenced this decision. The impact of these findings on future public health campaigns to reduce the impact of radon and smoking are discussed. (author)

  2. Lipid Replacement Therapy Drink Containing a Glycophospholipid Formulation Rapidly and Significantly Reduces Fatigue While Improving Energy and Mental Clarity

    Directory of Open Access Journals (Sweden)

    Robert Settineri

    2011-08-01

    Full Text Available Background: Fatigue is the most common complaint of patients seeking general medical care and is often treated with stimulants. It is also important in various physical activities of relatively healthy men and women, such as sports performance. Recent clinical trials using patients with chronic fatigue have shown the benefit of Lipid Replacement Therapy in restoring mitochondrial electron transport function and reducing moderate to severe chronic fatigue. Methods: Lipid Replacement Therapy was administered for the first time as an all-natural functional food drink (60 ml containing polyunsaturated glycophospholipids but devoid of stimulants or herbs to reduce fatigue. This preliminary study used the Piper Fatigue Survey instrument as well as a supplemental questionnaire to assess the effects of the glycophospholipid drink on fatigue and the acceptability of the test drink in adult men and women. A volunteer group of 29 subjects of mean age 56.2±4.5 years with various fatigue levels were randomly recruited in a clinical health fair setting to participate in an afternoon open label trial on the effects of the test drink. Results: Using the Piper Fatigue instrument overall fatigue among participants was reduced within the 3-hour seminar by a mean of 39.6% (p<0.0001. All of the subcategories of fatigue showed significant reductions. Some subjects responded within 15 minutes, and the majority responded within one hour with increased energy and activity and perceived improvements in cognitive function, mental clarity and focus. The test drink was determined to be quite acceptable in terms of taste and appearance. There were no adverse events from the energy drink during the study.Functional Foods in Health and Disease 2011; 8:245-254Conclusions: The Lipid Replacement Therapy functional food drink appeared to be a safe, acceptable and potentially useful new method to reduce fatigue, sustain energy and improve perceptions of mental function.

  3. 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.

    2010-01-01

    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. PMID:20729318

  4. 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.

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

    International Nuclear Information System (INIS)

    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

  6. Reducing Eating Disorder Onset in a Very High Risk Sample with Significant Comorbid Depression: A Randomized Controlled Trial

    Science.gov (United States)

    Taylor, C. Barr; Kass, Andrea E.; Trockel, Mickey; Cunning, Darby; Weisman, Hannah; Bailey, Jakki; Sinton, Meghan; Aspen, Vandana; Schecthman, Kenneth; Jacobi, Corinna; Wilfley, Denise E.

    2015-01-01

    Objective Eating disorders (EDs) are serious problems among college-age women and may be preventable. An indicated on-line eating disorder (ED) intervention, designed to reduce ED and comorbid pathology, was evaluated. Method 206 women (M age = 20 ± 1.8 years; 51% White/Caucasian, 11% African American, 10% Hispanic, 21% Asian/Asian American, 7% other) at very high risk for ED onset (i.e., with high weight/shape concerns plus a history of being teased, current or lifetime depression, and/or non-clinical levels of compensatory behaviors) were randomized to a 10-week, Internet-based, cognitive-behavioral intervention or wait-list control. Assessments included the Eating Disorder Examination (EDE to assess ED onset), EDE-Questionnaire, Structured Clinical Interview for DSM Disorders, and Beck Depression Inventory-II. Results ED attitudes and behaviors improved more in the intervention than control group (p = 0.02, d = 0.31); although ED onset rate was 27% lower, this difference was not significant (p = 0.28, NNT = 15). In the subgroup with highest shape concerns, ED onset rate was significantly lower in the intervention than control group (20% versus 42%, p = 0.025, NNT = 5). For the 27 individuals with depression at baseline, depressive symptomatology improved more in the intervention than control group (p = 0.016, d = 0.96); although ED onset rate was lower in the intervention than control group, this difference was not significant (25% versus 57%, NNT = 4). Conclusions An inexpensive, easily disseminated intervention might reduce ED onset among those at highest risk. Low adoption rates need to be addressed in future research. PMID:26795936

  7. Reducing eating disorder onset in a very high risk sample with significant comorbid depression: A randomized controlled trial.

    Science.gov (United States)

    Taylor, C Barr; Kass, Andrea E; Trockel, Mickey; Cunning, Darby; Weisman, Hannah; Bailey, Jakki; Sinton, Meghan; Aspen, Vandana; Schecthman, Kenneth; Jacobi, Corinna; Wilfley, Denise E

    2016-05-01

    Eating disorders (EDs) are serious problems among college-age women and may be preventable. An indicated online eating disorder (ED) intervention, designed to reduce ED and comorbid pathology, was evaluated. 206 women (M age = 20 ± 1.8 years; 51% White/Caucasian, 11% African American, 10% Hispanic, 21% Asian/Asian American, 7% other) at very high risk for ED onset (i.e., with high weight/shape concerns plus a history of being teased, current or lifetime depression, and/or nonclinical levels of compensatory behaviors) were randomized to a 10-week, Internet-based, cognitive-behavioral intervention or waitlist control. Assessments included the Eating Disorder Examination (EDE, to assess ED onset), EDE-Questionnaire, Structured Clinical Interview for DSM Disorders, and Beck Depression Inventory-II. ED attitudes and behaviors improved more in the intervention than control group (p = .02, d = 0.31); although ED onset rate was 27% lower, this difference was not significant (p = .28, NNT = 15). In the subgroup with highest shape concerns, ED onset rate was significantly lower in the intervention than control group (20% vs. 42%, p = .025, NNT = 5). For the 27 individuals with depression at baseline, depressive symptomatology improved more in the intervention than control group (p = .016, d = 0.96); although ED onset rate was lower in the intervention than control group, this difference was not significant (25% vs. 57%, NNT = 4). An inexpensive, easily disseminated intervention might reduce ED onset among those at highest risk. Low adoption rates need to be addressed in future research. (c) 2016 APA, all rights reserved).

  8. Potent corticosteroid cream (mometasone furoate) significantly reduces acute radiation dermatitis: results from a double-blind, randomized study

    International Nuclear Information System (INIS)

    Bostroem, Aasa; Lindman, Henrik; Swartling, Carl; Berne, Berit; Bergh, Jonas

    2001-01-01

    Purpose: Radiation-induced dermatitis is a very common side effect of radiation therapy, and may necessitate interruption of the therapy. There is a substantial lack of evidence-based treatments for this condition. The aim of this study was to investigate the effect of mometasone furoate cream (MMF) on radiation dermatitis in a prospective, double-blind, randomized study. Material and methods: The study comprised 49 patients with node-negative breast cancer. They were operated on with sector resection and scheduled for postoperative radiotherapy using photons with identical radiation qualities and dosage to the breast parenchyma. The patients were randomized to receive either MMF or emollient cream. The cream was applied on the irradiated skin twice a week from the start of radiotherapy until the 12th fraction (24 Gy) and thereafter once daily until 3 weeks after completion of radiation. Both groups additionally received non-blinded emollient cream daily. The intensity of the acute radiation dermatitis was evaluated on a weekly basis regarding erythema and pigmentation, using a reflectance spectrophotometer together with visual scoring of the skin reactions. Results: MMF in combination with emollient cream treatment significantly decreased acute radiation dermatitis (P=0.0033) compared with emollient cream alone. There was no significant difference in pigmentation between the two groups. Conclusions: Adding MMF, a potent topical corticosteroid, to an emollient cream is statistically significantly more effective than emollient cream alone in reducing acute radiation dermatitis

  9. Reduced frontal and occipital lobe asymmetry on the CT-scans of schizophrenic patients. Its specificity and clinical significance

    International Nuclear Information System (INIS)

    Falkai, P.; Schneider, T.; Greve, B.; Klieser, E.; Bogerts, B.

    1995-01-01

    Frontal and occipital lobe widths were determined in the computed tomographic (CT) scans of 135 schizophrenic patients, 158 neuro psychiatrically healthy and 102 psychiatric control subjects, including patients with affective psychosis, neurosis and schizoaffective psychosis. Most healthy right-handed subjects demonstrate a relative enlargement of the right frontal as well as left occipital lobe compared to the opposite hemisphere. These normal frontal and occipital lobe asymmetries were selectively reduced in schizophrenics (f.: 5%, p < .0005; o.: 3%, p < .05), irrespective of the pathophysiological subgroup. Schizophrenic neuroleptic non-responders revealed a significant reduction of frontal lobe asymmetry (3%, p < .05), while no correlation between BPRS-sub scores and disturbed cerebral laterality could be detected. In sum the present study demonstrates the disturbed cerebral lateralisation in schizophrenic patients supporting the hypothesis of interrupted early brain development in schizophrenia. (author)

  10. 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

  11. Walking with a four wheeled walker (rollator) significantly reduces EMG lower-limb muscle activity in healthy subjects.

    Science.gov (United States)

    Suica, Zorica; Romkes, Jacqueline; Tal, Amir; Maguire, Clare

    2016-01-01

    To investigate the immediate effect of four-wheeled- walker(rollator)walking on lower-limb muscle activity and trunk-sway in healthy subjects. In this cross-sectional design electromyographic (EMG) data was collected in six lower-limb muscle groups and trunk-sway was measured as peak-to-peak angular displacement of the centre-of-mass (level L2/3) in the sagittal and frontal-planes using the SwayStar balance system. 19 subjects walked at self-selected speed firstly without a rollator then in randomised order 1. with rollator 2. with rollator with increased weight-bearing. Rollator-walking caused statistically significant reductions in EMG activity in lower-limb muscle groups and effect-sizes were medium to large. Increased weight-bearing increased the effect. Trunk-sway in the sagittal and frontal-planes showed no statistically significant difference between conditions. Rollator-walking reduces lower-limb muscle activity but trunk-sway remains unchanged as stability is likely gained through forces generated by the upper-limbs. Short-term stability is gained but the long-term effect is unclear and requires investigation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Modest hypoxia significantly reduces triglyceride content and lipid droplet size in 3T3-L1 adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Takeshi, E-mail: thashimo@fc.ritsumei.ac.jp [Faculty of Sport and Health Science, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan); Yokokawa, Takumi; Endo, Yuriko [Faculty of Sport and Health Science, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan); Iwanaka, Nobumasa [Ritsumeikan Global Innovation Research Organization, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan); Higashida, Kazuhiko [Faculty of Sport and Health Science, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan); Faculty of Sport Science, Waseda University, 2-579-15 Mikajima, Tokorozawa, Saitama 359-1192 (Japan); Taguchi, Sadayoshi [Faculty of Sport and Health Science, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan)

    2013-10-11

    Highlights: •Long-term hypoxia decreased the size of LDs and lipid storage in 3T3-L1 adipocytes. •Long-term hypoxia increased basal lipolysis in 3T3-L1 adipocytes. •Hypoxia decreased lipid-associated proteins in 3T3-L1 adipocytes. •Hypoxia decreased basal glucose uptake and lipogenic proteins in 3T3-L1 adipocytes. •Hypoxia-mediated lipogenesis may be an attractive therapeutic target against obesity. -- Abstract: Background: A previous study has demonstrated that endurance training under hypoxia results in a greater reduction in body fat mass compared to exercise under normoxia. However, the cellular and molecular mechanisms that underlie this hypoxia-mediated reduction in fat mass remain uncertain. Here, we examine the effects of modest hypoxia on adipocyte function. Methods: Differentiated 3T3-L1 adipocytes were incubated at 5% O{sub 2} for 1 week (long-term hypoxia, HL) or one day (short-term hypoxia, HS) and compared with a normoxia control (NC). Results: HL, but not HS, resulted in a significant reduction in lipid droplet size and triglyceride content (by 50%) compared to NC (p < 0.01). As estimated by glycerol release, isoproterenol-induced lipolysis was significantly lowered by hypoxia, whereas the release of free fatty acids under the basal condition was prominently enhanced with HL compared to NC or HS (p < 0.01). Lipolysis-associated proteins, such as perilipin 1 and hormone-sensitive lipase, were unchanged, whereas adipose triglyceride lipase and its activator protein CGI-58 were decreased with HL in comparison to NC. Interestingly, such lipogenic proteins as fatty acid synthase, lipin-1, and peroxisome proliferator-activated receptor gamma were decreased. Furthermore, the uptake of glucose, the major precursor of 3-glycerol phosphate for triglyceride synthesis, was significantly reduced in HL compared to NC or HS (p < 0.01). Conclusion: We conclude that hypoxia has a direct impact on reducing the triglyceride content and lipid droplet size via

  13. Modest hypoxia significantly reduces triglyceride content and lipid droplet size in 3T3-L1 adipocytes

    International Nuclear Information System (INIS)

    Hashimoto, Takeshi; Yokokawa, Takumi; Endo, Yuriko; Iwanaka, Nobumasa; Higashida, Kazuhiko; Taguchi, Sadayoshi

    2013-01-01

    Highlights: •Long-term hypoxia decreased the size of LDs and lipid storage in 3T3-L1 adipocytes. •Long-term hypoxia increased basal lipolysis in 3T3-L1 adipocytes. •Hypoxia decreased lipid-associated proteins in 3T3-L1 adipocytes. •Hypoxia decreased basal glucose uptake and lipogenic proteins in 3T3-L1 adipocytes. •Hypoxia-mediated lipogenesis may be an attractive therapeutic target against obesity. -- Abstract: Background: A previous study has demonstrated that endurance training under hypoxia results in a greater reduction in body fat mass compared to exercise under normoxia. However, the cellular and molecular mechanisms that underlie this hypoxia-mediated reduction in fat mass remain uncertain. Here, we examine the effects of modest hypoxia on adipocyte function. Methods: Differentiated 3T3-L1 adipocytes were incubated at 5% O 2 for 1 week (long-term hypoxia, HL) or one day (short-term hypoxia, HS) and compared with a normoxia control (NC). Results: HL, but not HS, resulted in a significant reduction in lipid droplet size and triglyceride content (by 50%) compared to NC (p < 0.01). As estimated by glycerol release, isoproterenol-induced lipolysis was significantly lowered by hypoxia, whereas the release of free fatty acids under the basal condition was prominently enhanced with HL compared to NC or HS (p < 0.01). Lipolysis-associated proteins, such as perilipin 1 and hormone-sensitive lipase, were unchanged, whereas adipose triglyceride lipase and its activator protein CGI-58 were decreased with HL in comparison to NC. Interestingly, such lipogenic proteins as fatty acid synthase, lipin-1, and peroxisome proliferator-activated receptor gamma were decreased. Furthermore, the uptake of glucose, the major precursor of 3-glycerol phosphate for triglyceride synthesis, was significantly reduced in HL compared to NC or HS (p < 0.01). Conclusion: We conclude that hypoxia has a direct impact on reducing the triglyceride content and lipid droplet size via

  14. 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.

  15. A pilot study: Horticulture-related activities significantly reduce stress levels and salivary cortisol concentration of maladjusted elementary school children.

    Science.gov (United States)

    Lee, Min Jung; Oh, Wook; Jang, Ja Soon; Lee, Ju Young

    2018-04-01

    The effects of three horticulture-related activities (HRAs), including floral arranging, planting, and flower pressing were compared to see if they influenced changes on a stress scale and on salivary cortisol concentrations (SCC) in maladjusted elementary school children. Twenty maladjusted elementary school children were randomly assigned either to an experimental or control group. The control group carried out individual favorite indoor activities under the supervision of a teacher. Simultaneously, the ten children in the experimental group participated in a HRA program consisting of flower arrangement (FA), planting (P), and flower pressing (PF) activities, in which the other ten children in the control group did not take part. During nine sessions, the activities were completed as follows: FA-FA-FA, P-P-P, and PF-PF-PF; each session lasted 40 min and took place once a week. For the quantitative analysis of salivary cortisol, saliva was collected from the experimental group one week before the HRAs and immediately after the activities for 9 consecutive weeks at the same time each session. In the experimental group, stress scores of interpersonal relationship, school life, personal problems, and home life decreased after the HRAs by 1.3, 1.8, 4.2, and 1.3 points, respectively. In particular, the stress score of school life was significantly reduced (P < 0.01). In addition, from the investigation of the SCCs for the children before and after repeating HRAs three times, it was found that flower arrangement, planting, and flower pressing activities reduced the SCCs by ≥37% compared to the SCCs prior to taking part in the HRAs. These results indicate that HRAs are associated with a reduction in the stress levels of maladjusted elementary school children. Copyright © 2018. Published by Elsevier Ltd.

  16. Cerebral Embolic Protection During Transcatheter Aortic Valve Replacement Significantly Reduces Death and Stroke Compared With Unprotected Procedures.

    Science.gov (United States)

    Seeger, Julia; Gonska, Birgid; Otto, Markus; Rottbauer, Wolfgang; Wöhrle, Jochen

    2017-11-27

    The aim of this study was to evaluate the impact of cerebral embolic protection on stroke-free survival in patients undergoing transcatheter aortic valve replacement (TAVR). Imaging data on cerebral embolic protection devices have demonstrated a significant reduction in number and volume of cerebral lesions. A total of 802 consecutive patients were enrolled. The Sentinel cerebral embolic protection device (Claret Medical Inc., Santa Rosa, California) was used in 34.9% (n = 280) of consecutive patients. In 65.1% (n = 522) of patients TAVR was performed in the identical setting except without cerebral embolic protection. Neurological follow-up was done within 7 days post-procedure. The primary endpoint was a composite of all-cause mortality or all-stroke according to Valve Academic Research Consortium-2 criteria within 7 days. Propensity score matching was performed to account for possible confounders. Both filters of the device were successfully positioned in 280 of 305 (91.8%) consecutive patients. With use of cerebral embolic protection rate of disabling and nondisabling stroke was significantly reduced from 4.6% to 1.4% (p = 0.03; odds ratio: 0.29, 95% confidence interval: 0.10 to 0.93) in the propensity-matched population (n = 560). The primary endpoint occurred significantly less frequently, with 2.1% (n = 6 of 280) in the protected group compared with 6.8% (n = 19 of 280) in the control group (p = 0.01; odds ratio: 0.30; 95% confidence interval: 0.12 to 0.77). In multivariable analysis Society of Thoracic Surgeons score for mortality (p = 0.02) and TAVR without protection (p = 0.02) were independent predictors for the primary endpoint. In patients undergoing TAVR use of a cerebral embolic protection device demonstrated a significant higher rate of stroke-free survival compared with unprotected TAVR. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  17. Dermal application of nitric oxide releasing acidified nitrite-containing liniments significantly reduces blood pressure in humans.

    Science.gov (United States)

    Opländer, Christian; Volkmar, Christine M; Paunel-Görgülü, Adnana; Fritsch, Thomas; van Faassen, Ernst E; Mürtz, Manfred; Grieb, Gerrit; Bozkurt, Ahmet; Hemmrich, Karsten; Windolf, Joachim; Suschek, Christoph V

    2012-02-15

    Vascular ischemic diseases, hypertension, and other systemic hemodynamic and vascular disorders may be the result of impaired bioavailability of nitric oxide (NO). NO but also its active derivates like nitrite or nitroso compounds are important effector and signal molecules with vasodilating properties. Our previous findings point to a therapeutical potential of cutaneous administration of NO in the treatment of systemic hemodynamic disorders. Unfortunately, no reliable data are available on the mechanisms, kinetics and biological responses of dermal application of nitric oxide in humans in vivo. The aim of the study was to close this gap and to explore the therapeutical potential of dermal nitric oxide application. We characterized with human skin in vitro and in vivo the capacity of NO, applied in a NO-releasing acidified form of nitrite-containing liniments, to penetrate the epidermis and to influence local as well as systemic hemodynamic parameters. We found that dermal application of NO led to a very rapid and significant transepidermal translocation of NO into the underlying tissue. Depending on the size of treated skin area, this translocation manifests itself through a significant systemic increase of the NO derivates nitrite and nitroso compounds, respectively. In parallel, this translocation was accompanied by an increased systemic vasodilatation and blood flow as well as reduced blood pressure. We here give evidence that in humans dermal application of NO has a therapeutic potential for systemic hemodynamic disorders that might arise from local or systemic insufficient availability of NO or its bio-active NO derivates, respectively. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Significant change of local atomic configurations at surface of reduced activation Eurofer steels induced by hydrogenation treatments

    Energy Technology Data Exchange (ETDEWEB)

    Greculeasa, S.G.; Palade, P.; Schinteie, G. [National Institute for Materials Physics, P.O. Box MG-7, 77125, Bucharest-Magurele (Romania); Kuncser, A.; Stanciu, A. [National Institute for Materials Physics, P.O. Box MG-7, 77125, Bucharest-Magurele (Romania); University of Bucharest, Faculty of Physics, 77125, Bucharest-Magurele (Romania); Lungu, G.A. [National Institute for Materials Physics, P.O. Box MG-7, 77125, Bucharest-Magurele (Romania); Porosnicu, C.; Lungu, C.P. [National Institute for Laser, Plasma and Radiation Physics, 77125, Bucharest-Magurele (Romania); Kuncser, V., E-mail: kuncser@infim.ro [National Institute for Materials Physics, P.O. Box MG-7, 77125, Bucharest-Magurele (Romania)

    2017-04-30

    Highlights: • Engineering of Eurofer slab properties by hydrogenation treatments. • Hydrogenation modifies significantly the local atomic configurations at the surface. • Hydrogenation increases the expulsion of the Cr atoms toward the very surface. • Approaching binomial atomic distribution by hydrogenation in the next surface 100 nm. - Abstract: Reduced-activation steels such as Eurofer alloys are candidates for supporting plasma facing components in tokamak-like nuclear fusion reactors. In order to investigate the impact of hydrogen/deuterium insertion in their crystalline lattice, annealing treatments in hydrogen atmosphere have been applied on Eurofer slabs. The resulting samples have been analyzed with respect to local structure and atomic configuration both before and after successive annealing treatments, by X-ray diffractometry (XRD), scanning electron microscopy and energy dispersive spectroscopy (SEM-EDS), X-ray photoelectron spectroscopy (XPS) and conversion electron Mössbauer spectroscopy (CEMS). The corroborated data point out for a bcc type structure of the non-hydrogenated alloy, with an average alloy composition approaching Fe{sub 0.9}Cr{sub 0.1} along a depth of about 100 nm. EDS elemental maps do not indicate surface inhomogeneities in concentration whereas the Mössbauer spectra prove significant deviations from a homogeneous alloying. The hydrogenation increases the expulsion of the Cr atoms toward the surface layer and decreases their oxidation, with considerable influence on the surface properties of the steel. The hydrogenation treatment is therefore proposed as a potential alternative for a convenient engineering of the surface of different Fe-Cr based alloys.

  19. Optical trapping of nanoparticles with significantly reduced laser powers by using counter-propagating beams (Presentation Recording)

    Science.gov (United States)

    Zhao, Chenglong; LeBrun, Thomas W.

    2015-08-01

    Gold nanoparticles (GNP) have wide applications ranging from nanoscale heating to cancer therapy and biological sensing. Optical trapping of GNPs as small as 18 nm has been successfully achieved with laser power as high as 855 mW, but such high powers can damage trapped particles (particularly biological systems) as well heat the fluid, thereby destabilizing the trap. In this article, we show that counter propagating beams (CPB) can successfully trap GNP with laser powers reduced by a factor of 50 compared to that with a single beam. The trapping position of a GNP inside a counter-propagating trap can be easily modulated by either changing the relative power or position of the two beams. Furthermore, we find that under our conditions while a single-beam most stably traps a single particle, the counter-propagating beam can more easily trap multiple particles. This (CPB) trap is compatible with the feedback control system we recently demonstrated to increase the trapping lifetimes of nanoparticles by more than an order of magnitude. Thus, we believe that the future development of advanced trapping techniques combining counter-propagating traps together with control systems should significantly extend the capabilities of optical manipulation of nanoparticles for prototyping and testing 3D nanodevices and bio-sensing.

  20. 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

  1. 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

    2016-02-19

    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.

  2. New scanning technique using Adaptive Statistical lterative Reconstruction (ASIR) significantly reduced the radiation dose of cardiac CT

    International Nuclear Information System (INIS)

    Tumur, Odgerel; Soon, Kean; Brown, Fraser; Mykytowycz, Marcus

    2013-01-01

    The aims of our study were to evaluate the effect of application of Adaptive Statistical Iterative Reconstruction (ASIR) algorithm on the radiation dose of coronary computed tomography angiography (CCTA) and its effects on image quality of CCTA and to evaluate the effects of various patient and CT scanning factors on the radiation dose of CCTA. This was a retrospective study that included 347 consecutive patients who underwent CCTA at a tertiary university teaching hospital between 1 July 2009 and 20 September 2011. Analysis was performed comparing patient demographics, scan characteristics, radiation dose and image quality in two groups of patients in whom conventional Filtered Back Projection (FBP) or ASIR was used for image reconstruction. There were 238 patients in the FBP group and 109 patients in the ASIR group. There was no difference between the groups in the use of prospective gating, scan length or tube voltage. In ASIR group, significantly lower tube current was used compared with FBP group, 550mA (450–600) vs. 650mA (500–711.25) (median (interquartile range)), respectively, P<0.001. There was 27% effective radiation dose reduction in the ASIR group compared with FBP group, 4.29mSv (2.84–6.02) vs. 5.84mSv (3.88–8.39) (median (interquartile range)), respectively, P<0.001. Although ASIR was associated with increased image noise compared with FBP (39.93±10.22 vs. 37.63±18.79 (mean ±standard deviation), respectively, P<001), it did not affect the signal intensity, signal-to-noise ratio, contrast-to-noise ratio or the diagnostic quality of CCTA. Application of ASIR reduces the radiation dose of CCTA without affecting the image quality.

  3. New scanning technique using Adaptive Statistical Iterative Reconstruction (ASIR) significantly reduced the radiation dose of cardiac CT.

    Science.gov (United States)

    Tumur, Odgerel; Soon, Kean; Brown, Fraser; Mykytowycz, Marcus

    2013-06-01

    The aims of our study were to evaluate the effect of application of Adaptive Statistical Iterative Reconstruction (ASIR) algorithm on the radiation dose of coronary computed tomography angiography (CCTA) and its effects on image quality of CCTA and to evaluate the effects of various patient and CT scanning factors on the radiation dose of CCTA. This was a retrospective study that included 347 consecutive patients who underwent CCTA at a tertiary university teaching hospital between 1 July 2009 and 20 September 2011. Analysis was performed comparing patient demographics, scan characteristics, radiation dose and image quality in two groups of patients in whom conventional Filtered Back Projection (FBP) or ASIR was used for image reconstruction. There were 238 patients in the FBP group and 109 patients in the ASIR group. There was no difference between the groups in the use of prospective gating, scan length or tube voltage. In ASIR group, significantly lower tube current was used compared with FBP group, 550 mA (450-600) vs. 650 mA (500-711.25) (median (interquartile range)), respectively, P ASIR group compared with FBP group, 4.29 mSv (2.84-6.02) vs. 5.84 mSv (3.88-8.39) (median (interquartile range)), respectively, P ASIR was associated with increased image noise compared with FBP (39.93 ± 10.22 vs. 37.63 ± 18.79 (mean ± standard deviation), respectively, P ASIR reduces the radiation dose of CCTA without affecting the image quality. © 2013 The Authors. Journal of Medical Imaging and Radiation Oncology © 2013 The Royal Australian and New Zealand College of Radiologists.

  4. Secukinumab Significantly Reduces Psoriasis-Related Work Impairment and Indirect Costs Compared With Ustekinumab and Etanercept in the United Kingdom.

    Science.gov (United States)

    Warren, R B; Halliday, A; Graham, C N; Gilloteau, I; Miles, L; McBride, D

    2018-05-30

    Psoriasis causes work productivity impairment that increases with disease severity. Whether differential treatment efficacy translates into differential indirect cost savings is unknown. To assess work hours lost and indirect costs associated with secukinumab versus ustekinumab and etanercept in the United Kingdom (UK). This was a post hoc analysis of work impairment data collected in the CLEAR study (secukinumab vs. ustekinumab) and applied to the FIXTURE study (secukinumab vs. etanercept). Weighted weekly and annual average indirect costs per patient per treatment were calculated from (1) overall work impairment derived from Work Productivity and Activity Impairment data collected in CLEAR at 16 and 52 weeks by Psoriasis Area and Severity Index (PASI) response level; (2) weekly/annual work productivity loss by PASI response level; (3) weekly and annual indirect costs by PASI response level, based on hours of work productivity loss; and (4) weighted average indirect costs for each treatment. In the primary analysis, work impairment data for employed patients in CLEAR at Week 16 were used to compare secukinumab and ustekinumab. Secondary analyses were conducted at different timepoints and with patient cohorts, including FIXTURE. In CLEAR, 452 patients (67%) were employed at baseline. At Week 16, percentages of weekly work impairment/mean hours lost decreased with higher PASI: PASI hours; PASI 50-74: 13.3%/4.45 hours; PASI 75-89: 6.4%/2.14 hours; PASI ≥90: 4.9%/1.65 hours. Weighted mean weekly/annual work hours lost were significantly lower for secukinumab than ustekinumab (1.96/102.51 vs. 2.40/125.12; P=0.0006). Results were consistent for secukinumab versus etanercept (2.29/119.67 vs. 3.59/187.17; Ρreduced work impairment and associated indirect costs of psoriasis compared with ustekinumab and etanercept at Week 16 through 52 in the UK. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  5. 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)

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. Oxidation of naturally reduced uranium in aquifer sediments by dissolved oxygen and its potential significance to uranium plume persistence

    Science.gov (United States)

    Davis, J. A.; Smith, R. L.; Bohlke, J. K.; Jemison, N.; Xiang, H.; Repert, D. A.; Yuan, X.; Williams, K. H.

    2015-12-01

    The occurrence of naturally reduced zones is common in alluvial aquifers in the western U.S.A. due to the burial of woody debris in flood plains. Such reduced zones are usually heterogeneously dispersed in these aquifers and characterized by high concentrations of organic carbon, reduced mineral phases, and reduced forms of metals, including uranium(IV). The persistence of high concentrations of dissolved uranium(VI) at uranium-contaminated aquifers on the Colorado Plateau has been attributed to slow oxidation of insoluble uranium(IV) mineral phases found in association with these reducing zones, although there is little understanding of the relative importance of various potential oxidants. Four field experiments were conducted within an alluvial aquifer adjacent to the Colorado River near Rifle, CO, wherein groundwater associated with the naturally reduced zones was pumped into a gas-impermeable tank, mixed with a conservative tracer (Br-), bubbled with a gas phase composed of 97% O2 and 3% CO2, and then returned to the subsurface in the same well from which it was withdrawn. Within minutes of re-injection of the oxygenated groundwater, dissolved uranium(VI) concentrations increased from less than 1 μM to greater than 2.5 μM, demonstrating that oxygen can be an important oxidant for uranium in such field systems if supplied to the naturally reduced zones. Dissolved Fe(II) concentrations decreased to the detection limit, but increases in sulfate could not be detected due to high background concentrations. Changes in nitrogen species concentrations were variable. The results contrast with other laboratory and field results in which oxygen was introduced to systems containing high concentrations of mackinawite (FeS), rather than the more crystalline iron sulfides found in aged, naturally reduced zones. The flux of oxygen to the naturally reduced zones in the alluvial aquifers occurs mainly through interactions between groundwater and gas phases at the water table

  17. 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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  20. Vaccination of pigs two weeks before infection significantly reduces transmission of foot-and-mouth disease virus

    NARCIS (Netherlands)

    Eble, P.L.; Bouma, A.; Bruin, de M.G.M.; Hemert-Kluitenberg, van F.; Oirschot, van J.T.; Dekker, A.

    2004-01-01

    The objective of this study was to investigate whether and at what time interval could vaccination reduce transmission of foot-and-Mouth disease virus (FMDV) among pigs. Reduction of virus transmission by vaccination was determined experimentally. Transmission of FMDV was studied in three groups of

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  4. ClusterSignificance: A bioconductor package facilitating statistical analysis of class cluster separations in dimensionality reduced data

    DEFF Research Database (Denmark)

    Serviss, Jason T.; Gådin, Jesper R.; Eriksson, Per

    2017-01-01

    , e.g. genes in a specific pathway, alone can separate samples into these established classes. Despite this, the evaluation of class separations is often subjective and performed via visualization. Here we present the ClusterSignificance package; a set of tools designed to assess the statistical...... significance of class separations downstream of dimensionality reduction algorithms. In addition, we demonstrate the design and utility of the ClusterSignificance package and utilize it to determine the importance of long non-coding RNA expression in the identity of multiple hematological malignancies....

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

    Science.gov (United States)

    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…

  6. 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

  7. A novel multi-stage subunit vaccine against paratuberculosis induces significant immunity and reduces bacterial burden in tissues (P4304)

    DEFF Research Database (Denmark)

    Thakur, Aneesh; Aagaard, Claus; Riber, Ulla

    2013-01-01

    Effective control of paratuberculosis is hindered by lack of a vaccine preventing infection, transmission and without diagnostic interference with tuberculosis. We have developed a novel multi-stage recombinant subunit vaccine in which a fusion of four early expressed MAP antigens is combined...... characterized by a significant containment of bacterial burden in gut tissues compared to non-vaccinated animals. There was no cross-reaction with bovine tuberculosis in vaccinated animals. This novel multi-stage vaccine has the potential to become a marker vaccine for paratuberculosis....

  8. Reduced expression of circRNA hsa_circ_0003159 in gastric cancer and its clinical significance.

    Science.gov (United States)

    Tian, Mengqian; Chen, Ruoyu; Li, Tianwen; Xiao, Bingxiu

    2018-03-01

    Circular RNAs (circRNAs) play a crucial role in the occurrence of several diseases including cancers. However, little is known about circRNAs' diagnostic values for gastric cancer, one of the worldwide most common diseases of mortality. The hsa_circ_0003159 levels in 108 paired gastric cancer tissues and adjacent non-tumorous tissues from surgical patients with gastric cancer were first detected by real-time quantitative reverse transcription-polymerase chain reaction. Then, the relationships between hsa_circ_0003159 expression levels in gastric cancer tissues and the clinicopathological factors of patients with gastric cancer were analyzed. Finally, its diagnostic value was evaluated through the receiver operating characteristic curve. Compared with paired adjacent non-tumorous tissues, hsa_circ_0003159 expression was significantly down-regulated in gastric cancer tissues. What is more, we found that hsa_circ_0003159 expression levels were significantly negatively associated with gender, distal metastasis, and tumor-node-metastasis stage. All of the results suggest that hsa_circ_0003159 may be a potential cancer marker of patients with gastric cancer. © 2017 Wiley Periodicals, Inc.

  9. β-Hydroxy-β-methylbutyrate (HMB) supplementation and resistance exercise significantly reduce abdominal adiposity in healthy elderly men.

    Science.gov (United States)

    Stout, Jeffrey R; Fukuda, David H; Kendall, Kristina L; Smith-Ryan, Abbie E; Moon, Jordan R; Hoffman, Jay R

    2015-04-01

    The effects of 12-weeks of HMB ingestion and resistance training (RT) on abdominal adiposity were examined in 48 men (66-78 yrs). All participants were randomly assigned to 1 of 4 groups: no-training placebo (NT-PL), HMB only (NT-HMB), RT with PL (RT-PL), or HMB with RT (RT-HMB). DXA was used to estimate abdominal fat mass (AFM) by placing the region of interest over the L1-L4 region of the spine. Outcomes were assessed by ANCOVA, with Bonferroni-corrected pairwise comparisons. Baseline AFM values were used as the covariate. The ANCOVA indicated a significant difference (p = 0.013) between group means for the adjusted posttest AFM values (mean (kg) ± SE: NT-PL = 2.59 ± 0.06; NT-HMB = 2.59 ± 0.61; RT-PL = 2.59 ± 0.62; RT-HMB = 2.34 ± 0.61). The pairwise comparisons indicated that AFM following the intervention period in the RT-HMB group was significantly less than NT-PL (p = 0.013), NT-HMB (p = 0.011), and RT-PL (p = 0.010). These data suggested that HMB in combination with 12 weeks of RT decreased AFM in elderly men. Copyright © 2015. Published by Elsevier Inc.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Wind Erosion Caused by Land Use Changes Significantly Reduces Ecosystem Carbon Storage and Carbon Sequestration Potentials in Grassland

    Science.gov (United States)

    Li, P.; Chi, Y. G.; Wang, J.; Liu, L.

    2017-12-01

    Wind erosion exerts a fundamental influence on the biotic and abiotic processes associated with ecosystem carbon (C) cycle. However, how wind erosion under different land use scenarios will affect ecosystem C balance and its capacity for future C sequestration are poorly quantified. Here, we established an experiment in a temperate steppe in Inner Mongolia, and simulated different intensity of land uses: control, 50% of aboveground vegetation removal (50R), 100% vegetation removal (100R) and tillage (TI). We monitored lateral and vertical carbon flux components and soil characteristics from 2013 to 2016. Our study reveals three key findings relating to the driving factors, the magnitude and consequence of wind erosion on ecosystem C balance: (1) Frequency of heavy wind exerts a fundamental control over the severity of soil erosion, and its interaction with precipitation and vegetation characteristics explained 69% variation in erosion intensity. (2) With increases in land use intensity, the lateral C flux induced by wind erosion increased rapidly, equivalent to 33%, 86%, 111% and 183% of the net ecosystem exchange of the control site under control, 50R, 100R and TI sites, respectively. (3) After three years' treatment, erosion induced decrease in fine fractions led to 31%, 43%, 85% of permanent loss of C sequestration potential in the surface 5cm soil for 50R, 100R and TI sites. Overall, our study demonstrates that lateral C flux associated with wind erosion is too large to be ignored. The loss of C-enriched fine particles not only reduces current ecosystem C content, but also results in irreversible loss of future soil C sequestration potential. The dynamic soil characteristics need be considered when projecting future ecosystem C balance in aeolian landscape. We also propose that to maintain the sustainability of grassland ecosystems, land managers should focus on implementing appropriate land use rather than rely on subsequent managements on degraded soils.

  12. Postoperative Stiffness Requiring Manipulation Under Anesthesia Is Significantly Reduced After Simultaneous Versus Staged Bilateral Total Knee Arthroplasty.

    Science.gov (United States)

    Meehan, John P; Monazzam, Shafagh; Miles, Troy; Danielsen, Beate; White, Richard H

    2017-12-20

    adjust for relevant risk factors, the 90-day odds ratio (OR) of undergoing manipulation after simultaneous bilateral TKA was significantly lower than that for unilateral TKA (OR = 0.70; 95% confidence interval [CI], 0.57 to 0.86) and staged bilateral TKA (OR = 0.71; 95% CI, 0.57 to 0.90). Similarly, at 180 days, the odds of undergoing manipulation were significantly lower after simultaneous bilateral TKA than after both unilateral TKA (OR = 0.71; 95% CI, 0.59 to 0.84) and staged bilateral TKA (OR = 0.76; 95% CI, 0.63 to 0.93). The frequency of manipulation was significantly associated with younger age, fewer comorbidities, black race, and the absence of obesity. Although the ORs were small (close to 1), simultaneous bilateral TKA had a significantly decreased rate of stiffness requiring manipulation under anesthesia at 90 days and 180 days after knee replacement compared with that after staged bilateral TKA and unilateral TKA. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

  13. 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.

  14. Significance of surface functionalization of Gold Nanorods for reduced effect on IgG stability and minimization of cytotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Alex, Sruthi Ann; Rajiv, Sundaramoorthy [Centre for Nanobiotechnology, VIT University, Vellore (India); Chakravarty, Sujay [UGC-DAE CSR, Kalpakkam, Node, Kokilamedu (India); Chandrasekaran, N. [Centre for Nanobiotechnology, VIT University, Vellore (India); Mukherjee, Amitava, E-mail: amit.mookerjea@gmail.com [Centre for Nanobiotechnology, VIT University, Vellore (India)

    2017-02-01

    side effect of AuNRs by modifying capping. • Polymer-coated AuNRs safe for in vitro assays, but hamper protein functioning. • PEG-AuNRs reduced toxicity to lymphocyte cells and lesser effect on IgG. • Highlights importance of neutral PEGylated particles for theranostic applications.

  15. Significance of surface functionalization of Gold Nanorods for reduced effect on IgG stability and minimization of cytotoxicity

    International Nuclear Information System (INIS)

    Alex, Sruthi Ann; Rajiv, Sundaramoorthy; Chakravarty, Sujay; Chandrasekaran, N.; Mukherjee, Amitava

    2017-01-01

    side effect of AuNRs by modifying capping. • Polymer-coated AuNRs safe for in vitro assays, but hamper protein functioning. • PEG-AuNRs reduced toxicity to lymphocyte cells and lesser effect on IgG. • Highlights importance of neutral PEGylated particles for theranostic applications.

  16. [Intra-Articular Application of Tranexamic Acid Significantly Reduces Blood Loss and Transfusion Requirement in Primary Total Knee Arthroplasty].

    Science.gov (United States)

    Lošťák, J; Gallo, J; Špička, J; Langová, K

    2016-01-01

    PURPOSE OF THE STUDY The aim of this prospective study was to investigate the effect of topical application of tranexamic acid (TXA, Exacyl) on the amount of post-operative blood loss, and blood transfusion requirement in patients undergoing primary total knee arthroplasty (TKA). Attention was paid to early complications potentially associated with TXA administration, such as haematoma, wound exudate, or knee swelling. In addition, the economic benefit of TXA treatment was also taken into account. MATERIAL AND METHODS The study included 238 patients (85 men and 153 women) who underwent primary total knee arthroplasty (TKA) at our department between January 2013 and November 2015. A group of 119 patients (41 men and 78 women) received intraarticular TXA injections according to the treatment protocol (TXA group). A control group matched in basic characteristics to the TXA group also consisted of 119 patients. The average age in the TXA group was 69.8 years, and the most frequent indication for TKA surgery was primary knee osteoarthritis (81.5%). In each patient, post-operative volume of blood lost from drains and total blood loss including hidden blood loss were recorded, as well as post-operative haemoglobin and haematocrit levels. On discharge of each patient from hospital, the size and site of a haematoma; wound exudate, if present after post-operative day 4; joint swelling; range of motion and early revision surgery, if performed, were evaluated. Requirements of analgesic drugs after surgery were also recorded. RESULTS In the TXA group, blood losses from drains were significantly lower than in the control group (456.7 ± 270.8 vs 640.5 ±448.2; p = 0.004). The median value for blood losses from drains was lower by 22% and the average value for total blood loss, including hidden losses, was also lower than in the control group (762.4 ± 345.2 ml vs 995.5 ± 457.3 ml). The difference in the total amount of blood loss between the two groups was significant (p = 0

  17. Weight loss significantly reduces serum lipocalin-2 levels in overweight and obese women with polycystic ovary syndrome.

    Science.gov (United States)

    Koiou, Ekaterini; Tziomalos, Konstantinos; Katsikis, Ilias; Kandaraki, Eleni A; Kalaitzakis, Emmanuil; Delkos, Dimitrios; Vosnakis, Christos; Panidis, Dimitrios

    2012-01-01

    Serum lipocalin-2 levels are elevated in obese patients. We assessed serum lipocalin-2 levels in polycystic ovary syndrome (PCOS) and the effects of weight loss or metformin on these levels. Forty-seven overweight/obese patients with PCOS [body mass index (BMI) >27 kg/m(2)] were instructed to follow a low-calorie diet, to exercise and were given orlistat or sibutramine for 6 months. Twenty-five normal weight patients with PCOS (BMI weight and 25 overweight/obese healthy female volunteers comprised the control groups. Serum lipocalin-2 levels did not differ between overweight/obese patients with PCOS and overweight/obese controls (p = 0.258), or between normal weight patients with PCOS and normal weight controls (p = 0.878). Lipocalin-2 levels were higher in overweight/obese patients with PCOS than in normal weight patients with PCOS (p weight loss resulted in a fall in lipocalin-2 levels (p weight patients with PCOS, treatment with metformin did not affect lipocalin-2 levels (p = 0.484). In conclusion, PCOS per se is not associated with elevated lipocalin-2 levels. Weight loss induces a significant reduction in lipocalin-2 levels in overweight/obese patients with PCOS.

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

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    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

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

    Science.gov (United States)

    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

  20. 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.

  1. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  3. From meatless Mondays to meatless Sundays: motivations for meat reduction among vegetarians and semi-vegetarians who mildly or significantly reduce their meat intake.

    Science.gov (United States)

    De Backer, Charlotte J S; Hudders, Liselot

    2014-01-01

    This study explores vegetarians' and semi-vegetarians' motives for reducing their meat intake. Participants are categorized as vegetarians (remove all meat from their diet); semi-vegetarians (significantly reduce meat intake: at least three days a week); or light semi-vegetarians (mildly reduce meat intake: once or twice a week). Most differences appear between vegetarians and both groups of semi-vegetarians. Animal-rights and ecological concerns, together with taste preferences, predict vegetarianism, while an increase in health motives increases the odds of being semi-vegetarian. Even within each group, subgroups with different motives appear, and it is recommended that future researchers pay more attention to these differences.

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

    Science.gov (United States)

    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

  5. 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.

  6. 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.

  7. 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.

    Science.gov (United States)

    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.

  8. 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

  9. 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 ...

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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.

    Science.gov (United States)

    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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

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

    Science.gov (United States)

    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.

  20. Prenatal prochloraz treatment significantly increases pregnancy length and reduces offspring weight but does not affect social-olfactory memory in rats

    DEFF Research Database (Denmark)

    Dmytriyeva, Oksana; Klementiev, Boris; Berezin, Vladimir

    2013-01-01

    Metabolites of the commonly used imidazole fungicide prochloraz are androgen receptor antagonists. They have been shown to block androgen-driven development and compromise reproductive function. We tested the effect of prochloraz on cognitive behavior following exposure to this fungicide during...... the perinatal period. Pregnant Wistar rats were administered a 200mg/kg dose of prochloraz on gestational day (GD) 7, GD11, and GD15. The social recognition test (SRT) was performed on 7-week-old male rat offspring. We found an increase in pregnancy length and a significantly reduced pup weight on PND15 and PND...

  1. 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

  2. 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

  3. 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.

  4. 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

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

    Science.gov (United States)

    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

  6. The effectiveness of the anti-CD11d treatment is reduced in rat models of spinal cord injury that produce significant levels of intraspinal hemorrhage.

    Science.gov (United States)

    Geremia, N M; Hryciw, T; Bao, F; Streijger, F; Okon, E; Lee, J H T; Weaver, L C; Dekaban, G A; Kwon, B K; Brown, A

    2017-09-01

    We have previously reported that administration of a CD11d monoclonal antibody (mAb) improves recovery in a clip-compression model of SCI. In this model the CD11d mAb reduces the infiltration of activated leukocytes into the injured spinal cord (as indicated by reduced intraspinal MPO). However not all anti-inflammatory strategies have reported beneficial results, suggesting that success of the CD11d mAb treatment may depend on the type or severity of the injury. We therefore tested the CD11d mAb treatment in a rat hemi-contusion model of cervical SCI. In contrast to its effects in the clip-compression model, the CD11d mAb treatment did not improve forelimb function nor did it significantly reduce MPO levels in the hemi-contused cord. To determine if the disparate results using the CD11d mAb were due to the biomechanical nature of the cord injury (compression SCI versus contusion SCI) or to the spinal level of the injury (12th thoracic level versus cervical) we further evaluated the CD11d mAb treatment after a T12 contusion SCI. In contrast to the T12 clip compression SCI, the CD11d mAb treatment did not improve locomotor recovery or significantly reduce MPO levels after T12 contusion SCI. Lesion analyses revealed increased levels of hemorrhage after contusion SCI compared to clip-compression SCI. SCI that is accompanied by increased intraspinal hemorrhage would be predicted to be refractory to the CD11d mAb therapy as this approach targets leukocyte diapedesis through the intact vasculature. These results suggest that the disparate results of the anti-CD11d treatment in contusion and clip-compression models of SCI are due to the different pathophysiological mechanisms that dominate these two types of spinal cord injuries. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  7. 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.

    Science.gov (United States)

    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.

  8. Hypoxis hemerocallidea Significantly Reduced Hyperglycaemia and Hyperglycaemic-Induced Oxidative Stress in the Liver and Kidney Tissues of Streptozotocin-Induced Diabetic Male Wistar Rats

    Directory of Open Access Journals (Sweden)

    Oluwafemi O. Oguntibeju

    2016-01-01

    Full Text Available Background. Hypoxis hemerocallidea is a native plant that grows in the Southern African regions and is well known for its beneficial medicinal effects in the treatment of diabetes, cancer, and high blood pressure. Aim. This study evaluated the effects of Hypoxis hemerocallidea on oxidative stress biomarkers, hepatic injury, and other selected biomarkers in the liver and kidneys of healthy nondiabetic and streptozotocin- (STZ- induced diabetic male Wistar rats. Materials and Methods. Rats were injected intraperitoneally with 50 mg/kg of STZ to induce diabetes. The plant extract-Hypoxis hemerocallidea (200 mg/kg or 800 mg/kg aqueous solution was administered (daily orally for 6 weeks. Antioxidant activities were analysed using a Multiskan Spectrum plate reader while other serum biomarkers were measured using the RANDOX chemistry analyser. Results. Both dosages (200 mg/kg and 800 mg/kg of Hypoxis hemerocallidea significantly reduced the blood glucose levels in STZ-induced diabetic groups. Activities of liver enzymes were increased in the diabetic control and in the diabetic group treated with 800 mg/kg, whereas the 200 mg/kg dosage ameliorated hepatic injury. In the hepatic tissue, the oxygen radical absorbance capacity (ORAC, ferric reducing antioxidant power (FRAP, catalase, and total glutathione were reduced in the diabetic control group. However treatment with both doses improved the antioxidant status. The FRAP and the catalase activities in the kidney were elevated in the STZ-induced diabetic group treated with 800 mg/kg of the extract possibly due to compensatory responses. Conclusion. Hypoxis hemerocallidea demonstrated antihyperglycemic and antioxidant effects especially in the liver tissue.

  9. Prenatal prochloraz treatment significantly increases pregnancy length and reduces offspring weight but does not affect social-olfactory memory in rats.

    Science.gov (United States)

    Dmytriyeva, Oksana; Klementiev, Boris; Berezin, Vladimir; Bock, Elisabeth

    2013-07-01

    Metabolites of the commonly used imidazole fungicide prochloraz are androgen receptor antagonists. They have been shown to block androgen-driven development and compromise reproductive function. We tested the effect of prochloraz on cognitive behavior following exposure to this fungicide during the perinatal period. Pregnant Wistar rats were administered a 200 mg/kg dose of prochloraz on gestational day (GD) 7, GD11, and GD15. The social recognition test (SRT) was performed on 7-week-old male rat offspring. We found an increase in pregnancy length and a significantly reduced pup weight on PND15 and PND40 but no effect of prenatal prochloraz exposure on social investigation or acquisition of social-olfactory memory. Copyright © 2012 Elsevier GmbH. All rights reserved.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Glycophospholipid Formulation with NADH and CoQ10 Significantly Reduces Intractable Fatigue in Western Blot-Positive ‘Chronic Lyme Disease’ Patients: Preliminary Report

    Directory of Open Access Journals (Sweden)

    Garth L. Nicolson

    2012-03-01

    Full Text Available Background: An open label 8-week preliminary study was conducted in a small number of patients to determine if a combination oral supplement containing a mixture of phosphoglycolipids, coenzyme Q10 and microencapsulated NADH and other nutrients could affect fatigue levels in long-term, Western blot-positive, multi-symptom ‘chronic Lyme disease’ patients (also called ‘post-treatment Lyme disease’ or ‘post Lyme syndrome’ with intractable fatigue. Methods: The subjects in this study were 6 males (mean age = 45.1 ± 12.4 years and 10 females (mean age = 54.6 ± 7.4 years with ‘chronic Lyme disease’ (determined by multiple symptoms and positive Western blot analysis that had been symptomatic with chronic fatigue for an average of 12.7 ± 6.6 years. They had been seen by multiple physicians (13.3 ± 7.6 and had used many other remedies, supplements and drugs (14.4 ± 7.4 without fatigue relief. Fatigue was monitored at 0, 7, 30 and 60 days using a validated instrument, the Piper Fatigue Scale.Results: Patients in this preliminary study responded to the combination test supplement, showing a 26% reduction in overall fatigue by the end of the 8-week trial (p< 0.0003. Analysis of subcategories of fatigue indicated that there were significant improvements in the ability to complete tasks and activities as well as significant improvements in mood and cognitive abilities. Regression analysis of the data indicated that reductions in fatigue were consistent and occurred with a high degree of confidence (R2= 0.998. Functional Foods in Health and Disease 2012, 2(3:35-47 Conclusions: The combination supplement was a safe and effective method to significantly reduce intractable fatigue in long-term patients with Western blot-positive ‘chronic Lyme disease.’

  16. Long-term use of amiodarone before heart transplantation significantly reduces early post-transplant atrial fibrillation and is not associated with increased mortality after heart transplantation

    Directory of Open Access Journals (Sweden)

    Rivinius R

    2016-02-01

    group (P=0.0123. There was no statistically significant difference between patients with and without long-term use of amiodarone prior to HTX in 1-year (P=0.8596, 2-year (P=0.8620, 5-year (P=0.2737, or overall follow-up mortality after HTX (P=0.1049. Moreover, Kaplan–Meier survival analysis showed no statistically significant difference in overall survival (P=0.1786.Conclusion: Long-term use of amiodarone in patients before HTX significantly reduces early post-transplant AF and is not associated with increased mortality after HTX. Keywords: amiodarone, atrial fibrillation, heart failure, heart transplantation, mortality

  17. A proper choice of route significantly reduces air pollution exposure--a study on bicycle and bus trips in urban streets.

    Science.gov (United States)

    Hertel, Ole; Hvidberg, Martin; Ketzel, Matthias; Storm, Lars; Stausgaard, Lizzi

    2008-01-15

    A proper selection of route through the urban area may significantly reduce the air pollution exposure. This is the main conclusion from the presented study. Air pollution exposure is determined for two selected cohorts along the route going from home to working place, and back from working place to home. Exposure is determined with a street pollution model for three scenarios: bicycling along the shortest possible route, bicycling along the low exposure route along less trafficked streets, and finally taking the shortest trip using public transport. Furthermore, calculations are performed for the cases the trip takes place inside as well as outside the traffic rush hours. The results show that the accumulated air pollution exposure for the low exposure route is between 10% and 30% lower for the primary pollutants (NO(x) and CO). However, the difference is insignificant and in some cases even negative for the secondary pollutants (NO(2) and PM(10)/PM(2.5)). Considering only the contribution from traffic in the travelled streets, the accumulated air pollution exposure is between 54% and 67% lower for the low exposure route. The bus is generally following highly trafficked streets, and the accumulated exposure along the bus route is therefore between 79% and 115% higher than the high exposure bicycle route (the short bicycle route). Travelling outside the rush hour time periods reduces the accumulated exposure between 10% and 30% for the primary pollutants, and between 5% and 20% for the secondary pollutants. The study indicates that a web based route planner for selecting the low exposure route through the city might be a good service for the public. In addition the public may be advised to travel outside rush hour time periods.

  18. A Rosa canina - Urtica dioica - Harpagophytum procumbens/zeyheri Combination Significantly Reduces Gonarthritis Symptoms in a Randomized, Placebo-Controlled Double-Blind Study.

    Science.gov (United States)

    Moré, Margret; Gruenwald, Joerg; Pohl, Ute; Uebelhack, Ralf

    2017-12-01

    The special formulation MA212 (Rosaxan) is composed of rosehip ( Rosa canina L.) puree/juice concentrate, nettle ( Urtica dioica L.) leaf extract, and devil's claw ( Harpagophytum procumbens DC. ex Meisn. or Harpagophytum zeyheri Decne.) root extract and also supplies vitamin D. It is a food for special medical purposes ([EU] No 609/2013) for the dietary management of pain in patients with gonarthritis.This 12-week randomized, placebo-controlled double-blind parallel-design study aimed to investigate the efficacy and safety of MA212 versus placebo in patients with gonarthritis.A 3D-HPLC-fingerprint (3-dimensional high pressure liquid chromatography fingerprint) of MA212 demonstrated the presence of its herbal ingredients. Ninety-two randomized patients consumed 40 mL of MA212 (n = 46) or placebo (n = 44) daily. The Western Ontario and McMaster Universities Arthritis Index (WOMAC), quality-of-life scores at 0, 6, and 12 weeks, and analgesic consumption were documented. Statistically, the initial WOMAC subscores/scores did not differ between groups. During the study, their means significantly improved in both groups. The mean pre-post change of the WOMAC pain score (primary endpoint) was 29.87 in the MA212 group and 10.23 in the placebo group. The group difference demonstrated a significant superiority in favor of MA212 (p U  < 0.001; p t  < 0.001). Group comparisons of all WOMAC subscores/scores at 6 and 12 weeks reached same significances. Compared to placebo, both physical and mental quality of life significantly improved with MA212. There was a trend towards reduced analgesics consumption with MA212, compared to placebo. In the final efficacy evaluation, physicians (p Chi  < 0.001) and patients (p Chi  < 0.001) rated MA212 superior to placebo. MA212 was well tolerated.This study demonstrates excellent efficacy for MA212 in gonarthritis patients. Georg Thieme Verlag KG Stuttgart · New York.

  19. 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.

  20. Myocardial fatty acid imaging with 123I-BMIPP in patients with chronic right ventricular pressure overload. Clinical significance of reduced uptake in interventricular septum

    International Nuclear Information System (INIS)

    Hori, Yoshiro; Ishida, Yoshio; Fukuchi, Kazuki; Hayashida, Kouhei; Takamiya, Makoto

    2002-01-01

    Regionally reduced 123 I-beta-methyliodophenyl pentadecanoic acid (123I-BMIPP) uptake in the interventricular septum (SEP) is observed in some patients with chronic right ventricular (RV) pressure overload. We studied the significance of this finding by comparing it with mean pulmonary arterial pressure (mPAP). 123 I-BMIPP SPECT imaging was carried out in 21 patients with pulmonary hypertension (PH; 51+-14 years; 11 men and 10 women; 7 with primary pulmonary hypertension, 11 with pulmonary thromboembolism, and 3 with atrial septal defect). mPAP ranged from 25 to 81 mmHg (49±16 mmHg). Using a midventricular horizontal long-axis plane, regional BMIPP distributions in the RV free wall and SEP were estimated by referring to those in the LV free wall. Count ratios of the RV free wall and SEP to the LV free wall (RV/LV, SEP/LV) were determined by ROI analysis. RV/LV showed a linear correlation with mPAP (r=0.42). However, SEP/LV was inversely correlated with mPAP (r=-0.49). When SEP/RV was compared among three regions of SEP in each patient, basal SEP/RV was most sensitively decreased in response to increased mPAP (r=-0.70). These results suggest that the assessment of septal tracer uptake in 123 I-BMIPP SPECT imaging is useful for evaluating the severity of RV pressure overload in patients with PH. (author)

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

    Science.gov (United States)

    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.

  2. PARP-1 depletion in combination with carbon ion exposure significantly reduces MMPs activity and overall increases TIMPs expression in cultured HeLa cells

    International Nuclear Information System (INIS)

    Ghorai, Atanu; Sarma, Asitikantha; Chowdhury, Priyanka; Ghosh, Utpal

    2016-01-01

    Hadron therapy is an innovative technique where cancer cells are precisely killed leaving surrounding healthy cells least affected by high linear energy transfer (LET) radiation like carbon ion beam. Anti-metastatic effect of carbon ion exposure attracts investigators into the field of hadron biology, although details remain poor. Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors are well-known radiosensitizer and several PARP-1 inhibitors are in clinical trial. Our previous studies showed that PARP-1 depletion makes the cells more radiosensitive towards carbon ion than gamma. The purpose of the present study was to investigate combining effects of PARP-1 inhibition with carbon ion exposure to control metastatic properties in HeLa cells. Activities of matrix metalloproteinases-2, 9 (MMP-2, MMP-9) were measured using the gelatin zymography after 85 MeV carbon ion exposure or gamma irradiation (0- 4 Gy) to compare metastatic potential between PARP-1 knock down (HsiI) and control cells (H-vector - HeLa transfected with vector without shRNA construct). Expression of MMP-2, MMP-9, tissue inhibitor of MMPs such as TIMP-1, TIMP-2 and TIMP-3 were checked by immunofluorescence and western blot. Cell death by trypan blue, apoptosis and autophagy induction were studied after carbon ion exposure in each cell-type. The data was analyzed using one way ANOVA and 2-tailed paired-samples T-test. PARP-1 silencing significantly reduced MMP-2 and MMP-9 activities and carbon ion exposure further diminished their activities to less than 3 % of control H-vector. On the contrary, gamma radiation enhanced both MMP-2 and MMP-9 activities in H-vector but not in HsiI cells. The expression of MMP-2 and MMP-9 in H-vector and HsiI showed different pattern after carbon ion exposure. All three TIMPs were increased in HsiI, whereas only TIMP-1 was up-regulated in H-vector after irradiation. Notably, the expressions of all TIMPs were significantly higher in HsiI than H-vector at 4 Gy. Apoptosis was

  3. Symmetric dimeric bisbenzimidazoles DBP(n reduce methylation of RARB and PTEN while significantly increase methylation of rRNA genes in MCF-7 cancer cells.

    Directory of Open Access Journals (Sweden)

    Svetlana V Kostyuk

    Full Text Available Hypermethylation is observed in the promoter regions of suppressor genes in the tumor cancer cells. Reactivation of these genes by demethylation of their promoters is a prospective strategy of the anticancer therapy. Previous experiments have shown that symmetric dimeric bisbenzimidazoles DBP(n are able to block DNA methyltransferase activities. It was also found that DBP(n produces a moderate effect on the activation of total gene expression in HeLa-TI population containing epigenetically repressed avian sarcoma genome.It is shown that DBP(n are able to penetrate the cellular membranes and accumulate in breast carcinoma cell MCF-7, mainly in the mitochondria and in the nucleus, excluding the nucleolus. The DBP(n are non-toxic to the cells and have a weak overall demethylation effect on genomic DNA. DBP(n demethylate the promoter regions of the tumor suppressor genes PTEN and RARB. DBP(n promotes expression of the genes RARB, PTEN, CDKN2A, RUNX3, Apaf-1 and APC "silent" in the MCF-7 because of the hypermethylation of their promoter regions. Simultaneously with the demethylation of the DNA in the nucleus a significant increase in the methylation level of rRNA genes in the nucleolus was detected. Increased rDNA methylation correlated with a reduction of the rRNA amount in the cells by 20-30%. It is assumed that during DNA methyltransferase activity inhibition by the DBP(n in the nucleus, the enzyme is sequestered in the nucleolus and provides additional methylation of the rDNA that are not shielded by DBP(n.It is concluded that DBP (n are able to accumulate in the nucleus (excluding the nucleolus area and in the mitochondria of cancer cells, reducing mitochondrial potential. The DBP (n induce the demethylation of a cancer cell's genome, including the demethylation of the promoters of tumor suppressor genes. DBP (n significantly increase the methylation of ribosomal RNA genes in the nucleoli. Therefore the further study of these compounds is needed

  4. Holstein-Friesian calves selected for divergence in residual feed intake during growth exhibited significant but reduced residual feed intake divergence in their first lactation.

    Science.gov (United States)

    Macdonald, K A; Pryce, J E; Spelman, R J; Davis, S R; Wales, W J; Waghorn, G C; Williams, Y J; Marett, L C; Hayes, B J

    2014-03-01

    Residual feed intake (RFI), as a measure of feed conversion during growth, was estimated for around 2,000 growing Holstein-Friesian heifer calves aged 6 to 9 mo in New Zealand and Australia, and individuals from the most and least efficient deciles (low and high RFI phenotypes) were retained. These animals (78 New Zealand cows, 105 Australian cows) were reevaluated during their first lactation to determine if divergence for RFI observed during growth was maintained during lactation. Mean daily body weight (BW) gain during assessment as calves had been 0.86 and 1.15 kg for the respective countries, and the divergence in RFI between most and least efficient deciles for growth was 21% (1.39 and 1.42 kg of dry matter, for New Zealand and Australia, respectively). At the commencement of evaluation during lactation, the cows were aged 26 to 29 mo. All were fed alfalfa and grass cubes; it was the sole diet in New Zealand, whereas 6 kg of crushed wheat/d was also fed in Australia. Measurements of RFI during lactation occurred for 34 to 37 d with measurements of milk production (daily), milk composition (2 to 3 times per week), BW and BW change (1 to 3 times per week), as well as body condition score (BCS). Daily milk production averaged 13.8 kg for New Zealand cows and 20.0 kg in Australia. No statistically significant differences were observed between calf RFI decile groups for dry matter intake, milk production, BW change, or BCS; however a significant difference was noted between groups for lactating RFI. Residual feed intake was about 3% lower for lactating cows identified as most efficient as growing calves, and no negative effects on production were observed. These results support the hypothesis that calves divergent for RFI during growth are also divergent for RFI when lactating. The causes for this reduced divergence need to be investigated to ensure that genetic selection programs based on low RFI (better efficiency) are robust. Copyright © 2014 American Dairy

  5. 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.

    Directory of Open Access Journals (Sweden)

    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.

  6. 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...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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

  12. 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.

  13. Leukocyte-depletion of blood components does not significantly reduce the risk of infectious complications. Results of a double-blinded, randomized study

    DEFF Research Database (Denmark)

    Titlestad, I. L.; Ebbesen, L. S.; Ainsworth, A. P.

    2001-01-01

    Allogeneic blood transfusions are claimed to be an independent risk factor for postoperative infections in open colorectal surgery due to immunomodulation. Leukocyte-depletion of erythrocyte suspensions has been shown in some open randomized studies to reduce the rate of postoperative infection t...

  14. Reduced memory skills and increased hair cortisol levels in recent Ecstasy/MDMA users: significant but independent neurocognitive and neurohormonal deficits.

    Science.gov (United States)

    Downey, Luke A; Sands, Helen; Jones, Lewis; Clow, Angela; Evans, Phil; Stalder, Tobias; Parrott, Andrew C

    2015-05-01

    The goals of this study were to measure the neurocognitive performance of recent users of recreational Ecstasy and investigate whether it was associated with the stress hormone cortisol. The 101 participants included 27 recent light users of Ecstasy (one to four times in the last 3 months), 23 recent heavier Ecstasy users (five or more times) and 51 non-users. Rivermead paragraph recall provided an objective measure for immediate and delayed recall. The prospective and retrospective memory questionnaire provided a subjective index of memory deficits. Cortisol levels were taken from near-scalp 3-month hair samples. Cortisol was significantly raised in recent heavy Ecstasy users compared with controls, whereas hair cortisol in light Ecstasy users was not raised. Both Ecstasy groups were significantly impaired on the Rivermead delayed word recall, and both groups reported significantly more retrospective and prospective memory problems. Stepwise regression confirmed that lifetime Ecstasy predicted the extent of these memory deficits. Recreational Ecstasy is associated with increased levels of the bio-energetic stress hormone cortisol and significant memory impairments. No significant relationship between cortisol and the cognitive deficits was observed. Ecstasy users did display evidence of a metacognitive deficit, with the strength of the correlations between objective and subjective memory performances being significantly lower in the Ecstasy users. Copyright © 2015 John Wiley & Sons, Ltd.

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

    Science.gov (United States)

    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

  16. Metaldyne: Plant-Wide Assessment at Royal Oak Finds Opportunities to Improve Manufacturing Efficiency, Reduce Energy Use, and Achieve Significant Cost Savings

    Energy Technology Data Exchange (ETDEWEB)

    2005-05-01

    This case study prepared for the U.S. Department of Energy's Industrial Technologies Program describes a plant-wide energy assessment conducted at the Metaldyne, Inc., forging plant in Royal Oak, Michigan. The assessment focused on reducing the plant's operating costs, inventory, and energy use. If the company were to implement all the recommendations that came out of the assessment, its total annual energy savings for electricity would be about 11.5 million kWh and annual cost savings would be $12.6 million.

  17. The co registration of initial PET on the CT-radiotherapy reduces significantly the variabilities of anatomo-clinical target volume in the child hodgkin disease

    International Nuclear Information System (INIS)

    Metwally, H.; Blouet, A.; David, I.; Rives, M.; Izar, F.; Courbon, F.; Filleron, T.; Laprie, A.; Plat, G.; Vial, J.

    2009-01-01

    It exists a great interobserver variability for the anatomo-clinical target volume (C.T.V.) definition in children suffering of Hodgkin disease. In this study, the co-registration of the PET with F.D.G. on the planning computed tomography has significantly lead to a greater coherence in the clinical target volume definition. (N.C.)

  18. Soluble CD36 and risk markers of insulin resistance and atherosclerosis are elevated in polycystic ovary syndrome and significantly reduced during pioglitazone treatment

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Højlund, Kurt; Andersen, Marianne

    2007-01-01

    Objective: We investigated the relation between soluble CD36 (sCD36), risk markers of atherosclerosis and body composition, and glucose and lipid metabolism in polycystic ovary syndrome (PCOS) Research Design and Methods: Thirty PCOS patients were randomized to pioglitazone, 30 mg/day or placebo...... units), oxLDL (44.9 (26.9 - 75.1) vs. 36.1 (23.4 - 55.5) U/l), and hsCRP (0.26 (0.03 - 2.41) vs. 0.12 (0.02 - 0.81) mg/dl) were significantly increased in PCOS patients vs. controls (geometric mean (+/- 2SD)). In PCOS, positive correlations were found between central fat mass and sCD36 (r=0.43), hs......CRP (r=0.43), and IL-6 (r=0.42), all pPCOS patients and controls (n=44). sCD36 and oxLDL were significant...

  19. Does Liposomal Bupivacaine (Exparel) Significantly Reduce Postoperative Pain/Numbness in Symptomatic Teeth with a Diagnosis of Necrosis? A Prospective, Randomized, Double-blind Trial.

    Science.gov (United States)

    Glenn, Brandon; Drum, Melissa; Reader, Al; Fowler, Sara; Nusstein, John; Beck, Mike

    2016-09-01

    Medical studies have shown some potential for infiltrations of liposomal bupivacaine (Exparel; Pacira Pharmaceuticals, San Diego, CA), a slow-release bupivacaine solution, to extend postoperative benefits of numbness/pain relief for up to several days. Because the Food and Drug Administration has approved Exparel only for infiltrations, we wanted to evaluate if it would be effective as an infiltration to control postoperative pain. The purpose of this study was to compare an infiltration of bupivacaine with liposomal bupivacaine for postoperative numbness and pain in symptomatic patients diagnosed with pulpal necrosis experiencing moderate to severe preoperative pain. One hundred patients randomly received a 4.0-mL buccal infiltration of either bupivacaine or liposomal bupivacaine after endodontic debridement. For postoperative pain, patients were given ibuprofen/acetaminophen, and they could receive narcotic pain medication as an escape. Patients recorded their level of numbness, pain, and medication use the night of the appointment and over the next 5 days. Success was defined as no or mild postoperative pain and no narcotic use. The success rate was 29% for the liposomal group and 22% for the bupivacaine group, with no significant difference (P = .4684) between the groups. Liposomal bupivacaine had some effect on soft tissue numbness, pain, and use of non-narcotic medications, but it was not clinically significant. There was no significant difference in the need for escape medication. For symptomatic patients diagnosed with pulpal necrosis experiencing moderate to severe preoperative pain, a 4.0-mL infiltration of liposomal bupivacaine did not result in a statistically significant increase in postoperative success compared with an infiltration of 4.0 mL bupivacaine. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  20. 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.

  1. Reduced estimated glomerular filtration rate (eGFR 73 m2 ) at first transurethral resection of bladder tumour is a significant predictor of subsequent recurrence and progression.

    Science.gov (United States)

    Blute, Michael L; Kucherov, Victor; Rushmer, Timothy J; Damodaran, Shivashankar; Shi, Fangfang; Abel, E Jason; Jarrard, David F; Richards, Kyle A; Messing, Edward M; Downs, Tracy M

    2017-09-01

    To evaluate if moderate chronic kidney disease [CKD; estimated glomerular filtration rate (eGFR) 73 m 2 ] is associated with high rates of non-muscle-invasive bladder cancer (NMIBC) recurrence or progression. A multi-institutional database identified patients with serum creatinine values prior to first transurethral resection of bladder tumour (TURBT). The CKD-epidemiology collaboration formula calculated patient eGFR. Cox proportional hazards models evaluated associations with recurrence-free (RFS) and progression-free survival (PFS). In all, 727 patients were identified with a median (interquartile range [IQR]) patient age of 69.8 (60.1-77.6) years. Data for eGFR were available for 632 patients. During a median (IQR) follow-up of 3.7 (1.5-6.5) years, 400 (55%) patients had recurrence and 145 (19.9%) patients had progression of tumour stage or grade. Moderate or severe CKD was identified in 183 patients according to eGFR. Multivariable analysis identified an eGFR of 73 m 2 (hazard ratio [HR] 1.5, 95% confidence interval [CI]: 1.2-1.9; P = 0.002) as a predictor of tumour recurrence. The 5-year RFS rate was 46% for patients with an eGFR of ≥60 mL/min/1.73 m 2 and 27% for patients with an eGFR of 73 m 2 (P 73 m 2 (HR 3.7, 95% CI: 1.75-7.94; P = 0.001) was associated with progression to muscle-invasive disease. The 5-year PFS rate was 83% for patients with an eGFR of ≥60 mL/min/1.73 m 2 and 71% for patients with an eGFR of 73 m 2 (P = 0.01). Moderate CKD at first TURBT is associated with reduced RFS and PFS. Patients with reduced renal function should be considered for increased surveillance. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

  2. Glucagon-like peptide-1 acutely affects renal blood flow and urinary flow rate in spontaneously hypertensive rats despite significantly reduced renal expression of GLP-1 receptors.

    Science.gov (United States)

    Ronn, Jonas; Jensen, Elisa P; Wewer Albrechtsen, Nicolai J; Holst, Jens Juul; Sorensen, Charlotte M

    2017-12-01

    Glucagon-like peptide-1 (GLP-1) is an incretin hormone increasing postprandial insulin release. GLP-1 also induces diuresis and natriuresis in humans and rodents. The GLP-1 receptor is extensively expressed in the renal vascular tree in normotensive rats where acute GLP-1 treatment leads to increased mean arterial pressure (MAP) and increased renal blood flow (RBF). In hypertensive animal models, GLP-1 has been reported both to increase and decrease MAP. The aim of this study was to examine expression of renal GLP-1 receptors in spontaneously hypertensive rats (SHR) and to assess the effect of acute intrarenal infusion of GLP-1. We hypothesized that GLP-1 would increase diuresis and natriuresis and reduce MAP in SHR. Immunohistochemical staining and in situ hybridization for the GLP-1 receptor were used to localize GLP-1 receptors in the kidney. Sevoflurane-anesthetized normotensive Sprague-Dawley rats and SHR received a 20 min intrarenal infusion of GLP-1 and changes in MAP, RBF, heart rate, dieresis, and natriuresis were measured. The vasodilatory effect of GLP-1 was assessed in isolated interlobar arteries from normo- and hypertensive rats. We found no expression of GLP-1 receptors in the kidney from SHR. However, acute intrarenal infusion of GLP-1 increased MAP, RBF, dieresis, and natriuresis without affecting heart rate in both rat strains. These results suggest that the acute renal effects of GLP-1 in SHR are caused either by extrarenal GLP-1 receptors activating other mechanisms (e.g., insulin) to induce the renal changes observed or possibly by an alternative renal GLP-1 receptor. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  3. Human Tubal-Derived Mesenchymal Stromal Cells Associated with Low Level Laser Therapy Significantly Reduces Cigarette Smoke-Induced COPD in C57BL/6 mice.

    Directory of Open Access Journals (Sweden)

    Jean Pierre Schatzmann Peron

    Full Text Available Cigarette smoke-induced chronic obstructive pulmonary disease is a very debilitating disease, with a very high prevalence worldwide, which results in a expressive economic and social burden. Therefore, new therapeutic approaches to treat these patients are of unquestionable relevance. The use of mesenchymal stromal cells (MSCs is an innovative and yet accessible approach for pulmonary acute and chronic diseases, mainly due to its important immunoregulatory, anti-fibrogenic, anti-apoptotic and pro-angiogenic. Besides, the use of adjuvant therapies, whose aim is to boost or synergize with their function should be tested. Low level laser (LLL therapy is a relatively new and promising approach, with very low cost, no invasiveness and no side effects. Here, we aimed to study the effectiveness of human tube derived MSCs (htMSCs cell therapy associated with a 30mW/3J-660 nm LLL irradiation in experimental cigarette smoke-induced chronic obstructive pulmonary disease. Thus, C57BL/6 mice were exposed to cigarette smoke for 75 days (twice a day and all experiments were performed on day 76. Experimental groups receive htMSCS either intraperitoneally or intranasally and/or LLL irradiation either alone or in association. We show that co-therapy greatly reduces lung inflammation, lowering the cellular infiltrate and pro-inflammatory cytokine secretion (IL-1β, IL-6, TNF-α and KC, which were followed by decreased mucus production, collagen accumulation and tissue damage. These findings seemed to be secondary to the reduction of both NF-κB and NF-AT activation in lung tissues with a concomitant increase in IL-10. In summary, our data suggests that the concomitant use of MSCs + LLLT may be a promising therapeutic approach for lung inflammatory diseases as COPD.

  4. Peak medial (but not lateral) hamstring activity is significantly lower during stance phase of running. An EMG investigation using a reduced gravity treadmill.

    Science.gov (United States)

    Hansen, Clint; Einarson, Einar; Thomson, Athol; Whiteley, Rodney

    2017-09-01

    The hamstrings are seen to work during late swing phase (presumably to decelerate the extending shank) then during stance phase (presumably stabilizing the knee and contributing to horizontal force production during propulsion) of running. A better understanding of this hamstring activation during running may contribute to injury prevention and performance enhancement (targeting the specific role via specific contraction mode). Twenty active adult males underwent surface EMG recordings of their medial and lateral hamstrings while running on a reduced gravity treadmill. Participants underwent 36 different conditions for combinations of 50%-100% altering bodyweight (10% increments) & 6-16km/h (2km/h increments, i.e.: 36 conditions) for a minimum of 6 strides of each leg (maximum 32). EMG was normalized to the peak value seen for each individual during any stride in any trial to describe relative activation levels during gait. Increasing running speed effected greater increases in EMG for all muscles than did altering bodyweight. Peak EMG for the lateral hamstrings during running trials was similar for both swing and stance phase whereas the medial hamstrings showed an approximate 20% reduction during stance compared to swing phase. It is suggested that the lateral hamstrings work equally hard during swing and stance phase however the medial hamstrings are loaded slightly less every stance phase. Likely this helps explain the higher incidence of lateral hamstring injury. Hamstring injury prevention and rehabilitation programs incorporating running should consider running speed as more potent stimulus for increasing hamstring muscle activation than impact loading. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. 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.

    Science.gov (United States)

    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.

  6. 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

  7. 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.

  8. The chemical digestion of Ti6Al7Nb scaffolds produced by Selective Laser Melting reduces significantly ability of Pseudomonas aeruginosa to form biofilm.

    Science.gov (United States)

    Junka, Adam F; Szymczyk, Patrycja; Secewicz, Anna; Pawlak, Andrzej; Smutnicka, Danuta; Ziółkowski, Grzegorz; Bartoszewicz, Marzenna; Chlebus, Edward

    2016-01-01

    In our previous work we reported the impact of hydrofluoric and nitric acid used for chemical polishing of Ti-6Al-7Nb scaffolds on decrease of the number of Staphylococcus aureus biofilm forming cells. Herein, we tested impact of the aforementioned substances on biofilm of Gram-negative microorganism, Pseudomonas aeruginosa, dangerous pathogen responsible for plethora of implant-related infections. The Ti-6Al-7Nb scaffolds were manufactured using Selective Laser Melting method. Scaffolds were subjected to chemical polishing using a mixture of nitric acid and fluoride or left intact (control group). Pseudomonal biofilm was allowed to form on scaffolds for 24 hours and was removed by mechanical vortex shaking. The number of pseudomonal cells was estimated by means of quantitative culture and Scanning Electron Microscopy. The presence of nitric acid and fluoride on scaffold surfaces was assessed by means of IR and rentgen spetorscopy. Quantitative data were analysed using the Mann-Whitney test (P ≤ 0.05). Our results indicate that application of chemical polishing correlates with significant drop of biofilm-forming pseudomonal cells on the manufactured Ti-6Al-7Nb scaffolds ( p = 0.0133, Mann-Whitney test) compared to the number of biofilm-forming cells on non-polished scaffolds. As X-ray photoelectron spectroscopy revealed the presence of fluoride and nitrogen on the surface of scaffold, we speculate that drop of biofilm forming cells may be caused by biofilm-supressing activity of these two elements.

  9. Nuclear energy significantly reduces carbon dioxide emissions

    International Nuclear Information System (INIS)

    Koprda, V.

    2006-01-01

    This article is devoted to nuclear energy, to its acceptability, compatibility and sustainability. Nuclear energy is non-dispensable part of energy sources with vast innovation potential. The safety of nuclear energy, radioactive waste deposition, and prevention of risk from misuse of nuclear material have to be very seriously adjudged and solved. Nuclear energy is one of the ways how to decrease the contamination of atmosphere with carbon dioxide and it solves partially also the problem of global increase of temperature and climate changes. Given are the main factors responsible for the renaissance of nuclear energy. (author)

  10. 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

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. 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...

  15. 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

  16. 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...

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

    Science.gov (United States)

    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.

  18. 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.

  19. Pre-Treatment Deep Curettage Can Significantly Reduce Tumour Thickness in Thick Basal Cell Carcinoma While Maintaining a Favourable Cosmetic Outcome When Used in Combination with Topical Photodynamic Therapy

    International Nuclear Information System (INIS)

    Christensen, E.; Mork, C.; Foss, O. A.

    2011-01-01

    Topical photodynamic therapy (PDT) has limitations in the treatment of thick skin tumours. The aim of the study was to evaluate the effect of pre-PDT deep curettage on tumour thickness in thick (≥2 mm) basal cell carcinoma (BCC). Additionally, 3-month treatment outcome and change of tumour thickness from diagnosis to treatment were investigated. At diagnosis, mean tumour thickness was 2.3 mm (range 2.0-4.0). Pre- and post-curettage biopsies were taken from each tumour prior to PDT. Of 32 verified BCCs, tumour thickness was reduced by 50% after deep curettage (ρ≤0.001) . Mean tumour thickness was also reduced from diagnosis to treatment. At 3-month followup, complete tumour response was found in 93% and the cosmetic outcome was rated excellent or good in 100% of cases. In conclusion, deep curettage significantly reduces BCC thickness and may with topical PDT provide a favourable clinical and cosmetic short-term outcome.

  20. 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.

    Science.gov (United States)

    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.

  1. 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.

  2. 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.

  3. 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.

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    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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

    Directory of Open Access Journals (Sweden)

    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.

  9. Treatment with a belly-board device significantly reduces the volume of small bowel irradiated and results in low acute toxicity in adjuvant radiotherapy for gynecologic cancer: results of a prospective study

    International Nuclear Information System (INIS)

    Martin, Joseph; Fitzpatrick, Kathryn; Horan, Gail; McCloy, Roisin; Buckney, Steve; O'Neill, Louise; Faul, Clare

    2005-01-01

    Background and purpose: To determine whether treatment prone on a belly-board significantly reduces the volume of small bowel irradiated in women receiving adjuvant radiotherapy for gynecologic cancer, and to prospectively study acute small bowel toxicity using an accepted recording instrument. Material and methods: Thirty-two gynecologic patients underwent simulation with CT scanning supine and prone. Small bowel was delineated on every CT slice, and treatment was prone on the belly-board using 3-5 fields-typically Anterior, Right and Left Lateral, plus or minus Lateral Boosts. Median prescribed dose was 50.4 Gy and all treatments were delivered in 1.8 Gy fractions. Concomitant Cisplatin was administered in 13 patients with cervical carcinoma. Comparison of small bowel dose-volumes was made between supine and prone, with each subject acting as their own matched pair. Acute small bowel toxicity was prospectively measured using the Common Toxicity Criteria: Version 2.0. Results: Treatment prone on the belly-board significantly reduced the volume of small bowel receiving ≥100; ≥95; ≥90; and ≥80% of the prescribed dose, but not ≥50%. This was found whether volume was defined in cubic centimeters or % of total small bowel volume. Of 29 evaluable subjects, 2 (7%) experienced 1 episode each of grade 3 diarrhoea. All other toxicity events were grade 2 or less and comprised diarrhoea (59%), abdominal pain or cramping (48%), nausea (38%), anorexia (17%), vomiting (10%). There were no Grade 4 events and no treatment days were lost due to toxicity. Conclusions: Treatment prone on a belly-board device results in significant small bowel sparing, during adjuvant radiotherapy for gynecologic cancer. The absence of Grade 4 events or Treatment Days Lost compares favorably with the published literature

  10. 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.

    Science.gov (United States)

    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

  11. 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.

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

    Science.gov (United States)

    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

  13. 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

  14. 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

  15. Design and methods of the Echo WISELY (Will Inappropriate Scenarios for Echocardiography Lessen SignificantlY) study: An investigator-blinded randomized controlled trial of education and feedback intervention to reduce inappropriate echocardiograms.

    Science.gov (United States)

    Bhatia, R Sacha; Ivers, Noah; Yin, Cindy X; Myers, Dorothy; Nesbitt, Gillian; Edwards, Jeremy; Yared, Kibar; Wadhera, Rishi; Wu, Justina C; Wong, Brian; Hansen, Mark; Weinerman, Adina; Shadowitz, Steven; Johri, Amer; Farkouh, Michael; Thavendiranathan, Paaladinesh; Udell, Jacob A; Rambihar, Sherryn; Chow, Chi-Ming; Hall, Judith; Thorpe, Kevin E; Rakowski, Harry; Weiner, Rory B

    2015-08-01

    Appropriate use criteria (AUC) for transthoracic echocardiography (TTE) were developed to address concerns regarding inappropriate use of TTE. A previous pilot study suggests that an educational and feedback intervention can reduce inappropriate TTEs ordered by physicians in training. It is unknown if this type of intervention will be effective when targeted at attending level physicians in a variety of clinical settings. The aim of this international, multicenter study is to evaluate the hypothesis that an AUC-based educational and feedback intervention will reduce the proportion of inappropriate echocardiograms ordered by attending physicians in the ambulatory environment. In an ongoing multicentered, investigator-blinded, randomized controlled trial across Canada and the United States, cardiologists and primary care physicians practicing in the ambulatory setting will be enrolled. The intervention arm will receive (1) a lecture outlining the AUC and most recent available evidence highlighting appropriate use of TTE, (2) access to the American Society of Echocardiography mobile phone app, and (3) individualized feedback reports e-mailed monthly summarizing TTE ordering behavior including information on inappropriate TTEs and brief explanations of the inappropriate designation. The control group will receive no education on TTE appropriate use and order TTEs as usual practice. The Echo WISELY (Will Inappropriate Scenarios for Echocardiography Lessen Significantly in an education RCT) study is the first multicenter randomized trial of an AUC-based educational intervention. The study will examine whether an education and feedback intervention will reduce the rate of outpatient inappropriate TTEs ordered by attending level cardiologists and primary care physicians (www.clinicaltrials.gov identifier NCT02038101). Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Left-colon water exchange preserves the benefits of whole colon water exchange at reduced cecal intubation time conferring significant advantage in diagnostic colonoscopy - a prospective, randomized controlled trial.

    Science.gov (United States)

    Wang, Xiangping; Luo, Hui; Xiang, Yi; Leung, Felix W; Wang, Limei; Zhang, Linhui; Liu, Zhiguo; Wu, Kaichun; Fan, Daiming; Pan, Yanglin; Guo, Xuegang

    2015-07-01

    Whole-colon water exchange (WWE) reduces insertion pain, increases cecal intubation success and adenoma detection rate, but requires longer insertion time, compared to air insufflation (AI) colonoscopy. We hypothesized that water exchange limited to the left colon (LWE) can speed up insertion with equivalent results. This prospective, randomized controlled study (NCT01735266) allocated patients (18-80 years) to WWE, LWE or AI group (1:1:1). The primary outcome was cecal intubation time. Three hundred subjects were randomized to the WWE (n = 100), LWE (n = 100) or AI group (n = 100). Ninety-four to ninety-five per cent of patients underwent diagnostic colonoscopy. Baseline characteristics were balanced. The median insertion time was shorter in LWE group (4.8 min (95%CI: 3.2-6.2)) than those in WWE (7.5 min (95%CI: 6.0-10.3)) and AI (6.4 min (95%CI: 4.2-9.8)) (both p rates in unsedated patients of the two water exchange methods (WWE 99%, LWE 99%) were significantly higher than that (89.8%) in AI group (p = 0.01). The final success rates were comparable among the three groups after sedation was given. Maximum pain scores and number of patients needing abdominal compression between WWE and LWE groups were comparable, both lower than those in AI group (p higher in WWE group. By preserving the benefits of WWE and reducing insertion time, LWE is appropriate for diagnostic colonoscopy, especially in settings with tight scheduling of patients. The higher PDR in the right colon in WWE group deserves to be further investigated.

  17. 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.

  18. Policaptil Gel Retard significantly reduces body mass index and hyperinsulinism and may decrease the risk of type 2 diabetes mellitus (T2DM) in obese children and adolescents with family history of obesity and T2DM.

    Science.gov (United States)

    Stagi, Stefano; Lapi, Elisabetta; Seminara, Salvatore; Pelosi, Paola; Del Greco, Paolo; Capirchio, Laura; Strano, Massimo; Giglio, Sabrina; Chiarelli, Francesco; de Martino, Maurizio

    2015-02-15

    Treatments for childhood obesity are critically needed because of the risk of developing co-morbidities, although the interventions are frequently time-consuming, frustrating, difficult, and expensive. We conducted a longitudinal, randomised, clinical study, based on a per protocol analysis, on 133 obese children and adolescents (n = 69 males and 64 females; median age, 11.3 years) with family history of obesity and type 2 diabetes mellitus (T2DM). The patients were divided into three arms: Arm A (n = 53 patients), Arm B (n = 45 patients), and Arm C (n = 35 patients) patients were treated with a low-glycaemic-index (LGI) diet and Policaptil Gel Retard, only a LGI diet, or only an energy-restricted diet (ERD), respectively. The homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda, insulinogenic and disposition indexes were calculated at T0 and after 1 year (T1). At T1, the BMI-SD scores were significantly reduced from 2.32 to 1.80 (p 1) in Arm A and from 2.23 to 1.99 (p 13.2% to 5.6%; p 1) and B (p 1) and B (p obese children and adolescents with family history of obesity and T2DM.

  19. 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...

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

  3. 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

  4. Feasibility study of the immunogenicity and safety of a novel DTPw/Hib (PRP-T Brazilian combination compared to a licensed vaccine in healthy children at 2, 4, and 6 months of age Estudo de viabilidade de imunogenicidade e segurança de uma nova vacina brasileira combinada DTPw/Hib (PRP-T, comparada com uma vacina registrada, em crianças de 2, 4 e 6 meses de idade

    Directory of Open Access Journals (Sweden)

    SueAnn Costa Clemens

    2003-06-01

    Full Text Available Vaccination of infants with conjugated Haemophilus influenzae type b (Hib vaccines has been proven to reduce Hib meningitis by 95% and pneumoniae by 20%. The routine use of Hib vaccine is facilitated by the introduction of combination vaccines into the EPI (Expanded Plan of Immunization. The objective of this study was to compare the immunogenicity and reactogenicity of an extemporaneously mixed DTPw/Hib (diphtheria-tetanus-whole cell pertussis combination, using the technology of two Brazilian manufacturers, against a licensed DTPw/Hib European combination in 108 infants vaccinated at 2, 4 and 6 months according to the local national schedule. The Brazilian combination was highly immunogenic with Hib seroprotection rates (anti-PRP > 0.15 mg /ml of 98% after 2 doses and 100% after 3. Also for tetanus and pertussis the new Brazilian combination was as immunogenic as the European counterpart, except the diphtheria seroprotection rates and titers were lower. There was also no clinically relevant difference in reactogenicity. If these feasibility results are confirmed, the Brazilian DTPw/Hib combination should help to boost the uptake of Hib vaccination in Brazil.A vacinação contra (Haemophilus influenzae tipo b (Hib, utilizando vacinas conjugadas, provou reduzir em 95% os casos de meningite e em 20% as pneumonias por Hib. O uso rotineiro da vacina Hib foi facilitado pela introdução das vacinas combinadas no Programa Ampliado de Imunização (PAI. O objetivo deste estudo foi comparar a imunogenicidade e reatogenicidade da mistura extemporânea da vacina combinada contra difteria-tétano-pertussis de células inteiras/Haemophilus influenzae (DTPw/Hib, de tecnologia e produção de 2 fabricantes brasileiros, à vacina européia registrada DTPw/Hib. Estudo realizado em 108 crianças em idade de 2, 4 e 6 meses, seguindo o esquema nacional de imunização. A vacina combinada brasileira foi altamente imunogênica, apresentando taxas de soroprote

  5. Prostate health index significantly reduced unnecessary prostate biopsies in patients with PSA 2-10 ng/mL and PSA >10 ng/mL: Results from a Multicenter Study in China.

    Science.gov (United States)

    Na, Rong; Ye, Dingwei; Qi, Jun; Liu, Fang; Helfand, Brian T; Brendler, Charles B; Conran, Carly A; Packiam, Vignesh; Gong, Jian; Wu, Yishuo; Zheng, Siqun L; Mo, Zengnan; Ding, Qiang; Sun, Yinghao; Xu, Jianfeng

    2017-08-01

    The performance of prostate health index (phi) in predicting prostate biopsy outcomes has been well established for patients with prostate-specific antigen (PSA) values between 2 and 10 ng/mL. However, the performance of phi remains unknown in patients with PSA >10 ng/mL, the vast majority in Chinese biopsy patients. We aimed to assess the ability of phi to predict prostate cancer (PCa) and high-grade disease (Gleason Score ≥7) on biopsy in a Chinese population. This is a prospective, observational, multi-center study of consecutive patients who underwent a transrectal ultrasound guided prostate biopsy at four hospitals in Shanghai, China from August 2013 to December 2014. In the cohort of 1538 patients, the detection rate of PCa was 40.2%. phi had a significantly better predictive performance for PCa than total PSA (tPSA). The areas under the receiver operating characteristic curve (AUC) were 0.90 and 0.79 for phi and tPSA, respectively, P 10 ng/mL (N = 838, 54.5%). The detection rates of PCa were 35.9% and 57.7% in patients with tPSA 10.1-20 and 20.1-50 ng/mL, respectively. The AUCs of phi (0.79 and 0.89, for these two groups, respectively) were also significantly higher than tPSA (0.57 and 0.63, respectively), both P 10 ng/mL). © 2017 Wiley Periodicals, Inc.

  6. 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.

  7. IGOB131, a novel seed extract of the West African plant Irvingia gabonensis, significantly reduces body weight and improves metabolic parameters in overweight humans in a randomized double-blind placebo controlled investigation

    Directory of Open Access Journals (Sweden)

    Mbofung Carl MF

    2009-03-01

    Full Text Available Abstract Background A recent in vitro study indicates that IGOB131, a novel seed extract of the traditional West African food plant Irvingia gabonensis, favorably impacts adipogenesis through a variety of critical metabolic pathways including PPAR gamma, leptin, adiponectin, and glycerol-3 phosphate dehydrogenase. This study was therefore aimed at evaluating the effects of IGOB131, an extract of Irvingia gabonensis, on body weight and associated metabolic parameters in overweight human volunteers. Methods The study participants comprised of 102 healthy, overweight and/or obese volunteers (defined as BMI > 25 kg/m2 randomly divided into two groups. The groups received on a daily basis, either 150 mg of IGOB131 or matching placebo in a double blinded fashion, 30–60 minutes before lunch and dinner. At baseline, 4, 8 and 10 weeks of the study, subjects were evaluated for changes in anthropometrics and metabolic parameters to include fasting lipids, blood glucose, C-reactive protein, adiponectin, and leptin. Results Significant improvements in body weight, body fat, and waist circumference as well as plasma total cholesterol, LDL cholesterol, blood glucose, C-reactive protein, adiponectin and leptin levels were observed in the IGOB131 group compared with the placebo group. Conclusion Irvingia gabonensis administered 150 mg twice daily before meals to overweight and/or obese human volunteers favorably impacts body weight and a variety of parameters characteristic of the metabolic syndrome. This is the first double blind randomized placebo controlled clinical trial regarding the anti-obesity and lipid profile modulating effects of an Irvingia gabonensis extract. The positive clinical results, together with our previously published mechanisms of gene expression modulation related to key metabolic pathways in lipid metabolism, provide impetus for much larger clinical studies. Irvingia gabonensis extract may prove to be a useful tool in dealing with the

  8. A big oil company's approach to significantly reduce fatal incidents

    NARCIS (Netherlands)

    Peuscher, W.; Groeneweg, J.

    2012-01-01

    Within the Shell Group of companies (Shell), keeping people safe at work is a deeply held value and the company actively pursues the goal of no harm to people. Shell actively works to build a culture where every employee and contractor takes responsibility for making this goal possible - it is

  9. Significantly reducing registration time in IGRT using graphics processing units

    DEFF Research Database (Denmark)

    Noe, Karsten Østergaard; Denis de Senneville, Baudouin; Tanderup, Kari

    2008-01-01

    respiration phases in a free breathing volunteer and 41 anatomical landmark points in each image series. The registration method used is a multi-resolution GPU implementation of the 3D Horn and Schunck algorithm. It is based on the CUDA framework from Nvidia. Results On an Intel Core 2 CPU at 2.4GHz each...... registration took 30 minutes. On an Nvidia Geforce 8800GTX GPU in the same machine this registration took 37 seconds, making the GPU version 48.7 times faster. The nine image series of different respiration phases were registered to the same reference image (full inhale). Accuracy was evaluated on landmark...

  10. 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

  11. 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.

  12. GHRH, PRP-PACAP and GHRHR Target Sequencing via an Ion Torrent Personal Genome Machine Reveals an Association with Growth in Orange-Spotted Grouper (Epinephelus coioides

    Directory of Open Access Journals (Sweden)

    Liang Guo

    2015-11-01

    Full Text Available Growth hormone-releasing hormone (GHRH and the receptor, GHRHR, constitute important components of the hypothalamus-pituitary growth axis and act on the downstream growth hormone (GH. PACAP-related peptide/pituitary adenylate cyclase activating polypeptide (PRP-PACAP is a paralog of GHRH. These genes all play key roles in development and growth patterns. To improve the quality of cultured fish strains, natural genetic variation must be examined and understood. A mixed linear model has been widely used in association mapping, taking the population structures and pairwise kinship patterns into consideration. In this study, a mass cross population of orange-spotted grouper (Epinephelus coioides was examined. These candidate genes were found to harbor low nucleotide diversity (θw from 0.00154 to 0.00388 and linkage disequilibrium levels (delay of 50% within 2 kbp. Association mapping was employed, and two single-nucleotide polymorphisms (KR269823.1:g.475A>C and KR269823.1:g.2143T>C were found to be associated with growth (false discovery rate Q < 0.05, explaining 9.0%–17.0% of the phenotypic variance. The association of KR269823.1:g.2143T>C was also found via haplotype-based association (p < 0.05. The identified associations offer new insights into gene functions, and the associated single-nucleotide polymorphisms (SNPs may be used for breeding purposes.

  13. 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.

  14. Mouse-hamster chimeric prion protein (PrP) devoid of N-terminal residues 23-88 restores susceptibility to 22L prions, but not to RML prions in PrP-knockout mice.

    Science.gov (United States)

    Uchiyama, Keiji; Miyata, Hironori; Yano, Masashi; Yamaguchi, Yoshitaka; Imamura, Morikazu; Muramatsu, Naomi; Das, Nandita Rani; Chida, Junji; Hara, Hideyuki; Sakaguchi, Suehiro

    2014-01-01

    Prion infection induces conformational conversion of the normal prion protein PrPC, into the pathogenic isoform PrPSc, in prion diseases. It has been shown that PrP-knockout (Prnp0/0) mice transgenically reconstituted with a mouse-hamster chimeric PrP lacking N-terminal residues 23-88, or Tg(MHM2Δ23-88)/Prnp 0/0 mice, neither developed the disease nor accumulated MHM2ScΔ23-88 in their brains after inoculation with RML prions. In contrast, RML-inoculated Tg(MHM2Δ23-88)/Prnp 0/+ mice developed the disease with abundant accumulation of MHM2ScΔ23-88 in their brains. These results indicate that MHM2Δ23-88 itself might either lose or greatly reduce the converting capacity to MHM2ScΔ23-88, and that the co-expressing wild-type PrPC can stimulate the conversion of MHM2Δ23-88 to MHM2ScΔ23-88 in trans. In the present study, we confirmed that Tg(MHM2Δ23-88)/Prnp 0/0 mice remained resistant to RML prions for up to 730 days after inoculation. However, we found that Tg(MHM2Δ23-88)/Prnp 0/0 mice were susceptible to 22L prions, developing the disease with prolonged incubation times and accumulating MHM2ScΔ23-88 in their brains. We also found accelerated conversion of MHM2Δ23-88 into MHM2ScΔ23-88 in the brains of RML- and 22L-inoculated Tg(MHM2Δ23-88)/Prnp 0/+ mice. However, wild-type PrPSc accumulated less in the brains of these inoculated Tg(MHM2Δ23-88)/Prnp 0/+ mice, compared with RML- and 22L-inoculated Prnp 0/+ mice. These results show that MHM2Δ23-88 itself can convert into MHM2ScΔ23-88 without the help of the trans-acting PrPC, and that, irrespective of prion strains inoculated, the co-expressing wild-type PrPC stimulates the conversion of MHM2Δ23-88 into MHM2ScΔ23-88, but to the contrary, the co-expressing MHM2Δ23-88 disturbs the conversion of wild-type PrPC into PrPSc.

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

    Directory of Open Access Journals (Sweden)

    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

  16. Detecting Novelty and Significance

    Science.gov (United States)

    Ferrari, Vera; Bradley, Margaret M.; Codispoti, Maurizio; Lang, Peter J.

    2013-01-01

    Studies of cognition often use an “oddball” paradigm to study effects of stimulus novelty and significance on information processing. However, an oddball tends to be perceptually more novel than the standard, repeated stimulus as well as more relevant to the ongoing task, making it difficult to disentangle effects due to perceptual novelty and stimulus significance. In the current study, effects of perceptual novelty and significance on ERPs were assessed in a passive viewing context by presenting repeated and novel pictures (natural scenes) that either signaled significant information regarding the current context or not. A fronto-central N2 component was primarily affected by perceptual novelty, whereas a centro-parietal P3 component was modulated by both stimulus significance and novelty. The data support an interpretation that the N2 reflects perceptual fluency and is attenuated when a current stimulus matches an active memory representation and that the amplitude of the P3 reflects stimulus meaning and significance. PMID:19400680

  17. Significant NRC Enforcement Actions

    Data.gov (United States)

    Nuclear Regulatory Commission — This dataset provides a list of Nuclear Regulartory Commission (NRC) issued significant enforcement actions. These actions, referred to as "escalated", are issued by...

  18. Significant Tsunami Events

    Science.gov (United States)

    Dunbar, P. K.; Furtney, M.; McLean, S. J.; Sweeney, A. D.

    2014-12-01

    Tsunamis have inflicted death and destruction on the coastlines of the world throughout history. The occurrence of tsunamis and the resulting effects have been collected and studied as far back as the second millennium B.C. The knowledge gained from cataloging and examining these events has led to significant changes in our understanding of tsunamis, tsunami sources, and methods to mitigate the effects of tsunamis. The most significant, not surprisingly, are often the most devastating, such as the 2011 Tohoku, Japan earthquake and tsunami. The goal of this poster is to give a brief overview of the occurrence of tsunamis and then focus specifically on several significant tsunamis. There are various criteria to determine the most significant tsunamis: the number of deaths, amount of damage, maximum runup height, had a major impact on tsunami science or policy, etc. As a result, descriptions will include some of the most costly (2011 Tohoku, Japan), the most deadly (2004 Sumatra, 1883 Krakatau), and the highest runup ever observed (1958 Lituya Bay, Alaska). The discovery of the Cascadia subduction zone as the source of the 1700 Japanese "Orphan" tsunami and a future tsunami threat to the U.S. northwest coast, contributed to the decision to form the U.S. National Tsunami Hazard Mitigation Program. The great Lisbon earthquake of 1755 marked the beginning of the modern era of seismology. Knowledge gained from the 1964 Alaska earthquake and tsunami helped confirm the theory of plate tectonics. The 1946 Alaska, 1952 Kuril Islands, 1960 Chile, 1964 Alaska, and the 2004 Banda Aceh, tsunamis all resulted in warning centers or systems being established.The data descriptions on this poster were extracted from NOAA's National Geophysical Data Center (NGDC) global historical tsunami database. Additional information about these tsunamis, as well as water level data can be found by accessing the NGDC website www.ngdc.noaa.gov/hazard/

  19. Testing Significance Testing

    Directory of Open Access Journals (Sweden)

    Joachim I. Krueger

    2018-04-01

    Full Text Available The practice of Significance Testing (ST remains widespread in psychological science despite continual criticism of its flaws and abuses. Using simulation experiments, we address four concerns about ST and for two of these we compare ST’s performance with prominent alternatives. We find the following: First, the 'p' values delivered by ST predict the posterior probability of the tested hypothesis well under many research conditions. Second, low 'p' values support inductive inferences because they are most likely to occur when the tested hypothesis is false. Third, 'p' values track likelihood ratios without raising the uncertainties of relative inference. Fourth, 'p' values predict the replicability of research findings better than confidence intervals do. Given these results, we conclude that 'p' values may be used judiciously as a heuristic tool for inductive inference. Yet, 'p' values cannot bear the full burden of inference. We encourage researchers to be flexible in their selection and use of statistical methods.

  20. Safety significance evaluation system

    International Nuclear Information System (INIS)

    Lew, B.S.; Yee, D.; Brewer, W.K.; Quattro, P.J.; Kirby, K.D.

    1991-01-01

    This paper reports that the Pacific Gas and Electric Company (PG and E), in cooperation with ABZ, Incorporated and Science Applications International Corporation (SAIC), investigated the use of artificial intelligence-based programming techniques to assist utility personnel in regulatory compliance problems. The result of this investigation is that artificial intelligence-based programming techniques can successfully be applied to this problem. To demonstrate this, a general methodology was developed and several prototype systems based on this methodology were developed. The prototypes address U.S. Nuclear Regulatory Commission (NRC) event reportability requirements, technical specification compliance based on plant equipment status, and quality assurance assistance. This collection of prototype modules is named the safety significance evaluation system

  1. Predicting significant torso trauma.

    Science.gov (United States)

    Nirula, Ram; Talmor, Daniel; Brasel, Karen

    2005-07-01

    Identification of motor vehicle crash (MVC) characteristics associated with thoracoabdominal injury would advance the development of automatic crash notification systems (ACNS) by improving triage and response times. Our objective was to determine the relationships between MVC characteristics and thoracoabdominal trauma to develop a torso injury probability model. Drivers involved in crashes from 1993 to 2001 within the National Automotive Sampling System were reviewed. Relationships between torso injury and MVC characteristics were assessed using multivariate logistic regression. Receiver operating characteristic curves were used to compare the model to current ACNS models. There were a total of 56,466 drivers. Age, ejection, braking, avoidance, velocity, restraints, passenger-side impact, rollover, and vehicle weight and type were associated with injury (p < 0.05). The area under the receiver operating characteristic curve (83.9) was significantly greater than current ACNS models. We have developed a thoracoabdominal injury probability model that may improve patient triage when used with ACNS.

  2. Gas revenue increasingly significant

    International Nuclear Information System (INIS)

    Megill, R.E.

    1991-01-01

    This paper briefly describes the wellhead prices of natural gas compared to crude oil over the past 70 years. Although natural gas prices have never reached price parity with crude oil, the relative value of a gas BTU has been increasing. It is one of the reasons that the total amount of money coming from natural gas wells is becoming more significant. From 1920 to 1955 the revenue at the wellhead for natural gas was only about 10% of the money received by producers. Most of the money needed for exploration, development, and production came from crude oil. At present, however, over 40% of the money from the upstream portion of the petroleum industry is from natural gas. As a result, in a few short years natural gas may become 50% of the money revenues generated from wellhead production facilities

  3. A Fluorescent Oligothiophene-Bis-Triazine ligand interacts with PrP fibrils and detects SDS-resistant oligomers in human prion diseases.

    Science.gov (United States)

    Imberdis, Thibaut; Ayrolles-Torro, Adeline; Duarte Rodrigues, Alysson; Torrent, Joan; Alvarez-Martinez, Maria Teresa; Kovacs, Gabor G; Verdier, Jean-Michel; Robitzer, Mike; Perrier, Véronique

    2016-01-26

    Prion diseases are characterized by the accumulation in the central nervous system of an abnormally folded isoform of the prion protein, named PrP(Sc). Aggregation of PrP(Sc) into oligomers and fibrils is critically involved in the pathogenesis of prion diseases. Oligomers are supposed to be the key neurotoxic agents in prion disease, so modulation of prion aggregation pathways with small molecules can be a valuable strategy for studying prion pathogenicity and for developing new diagnostic and therapeutic approaches. We previously identified thienyl pyrimidine compounds that induce SDS-resistant PrP(Sc) (rSDS-PrP(Sc)) oligomers in prion-infected samples. Due to the low effective doses of the thienyl pyrimidine hits, we synthesized a quaterthiophene-bis-triazine compound, called MR100 to better evaluate their diagnostic and therapeutic potentials. This molecule exhibits a powerful activity inducing rSDS-PrP(Sc) oligomers at nanomolar concentrations in prion-infected cells. Fluorescence interaction studies of MR100 with mouse PrP fibrils showed substantial modification of the spectrum, and the interaction was confirmed in vitro by production of rSDS-oligomer species upon incubation of MR100 with fibrils in SDS-PAGE gel. We further explored whether MR100 compound has a potential to be used in the diagnosis of prion diseases. Our results showed that: (i) MR100 can detect rSDS-oligomers in prion-infected brain homogenates of various species, including human samples from CJD patients; (ii) A protocol, called "Rapid Centrifugation Assay" (RCA), was developed based on MR100 property of inducing rSDS-PrP(Sc) oligomers only in prion-infected samples, and avoiding the protease digestion step. RCA allows the detection of both PK-sensitive and PK-resistant PrP(Sc) species in rodents samples but also from patients with different CJD forms (sporadic and new variant); (iii) A correlation could be established between the amount of rSDS-PrP(Sc) oligomers revealed by MR100 and the

  4. Tumor significant dose

    International Nuclear Information System (INIS)

    Supe, S.J.; Nagalaxmi, K.V.; Meenakshi, L.

    1983-01-01

    In the practice of radiotherapy, various concepts like NSD, CRE, TDF, and BIR are being used to evaluate the biological effectiveness of the treatment schedules on the normal tissues. This has been accepted as the tolerance of the normal tissue is the limiting factor in the treatment of cancers. At present when various schedules are tried, attention is therefore paid to the biological damage of the normal tissues only and it is expected that the damage to the cancerous tissues would be extensive enough to control the cancer. Attempt is made in the present work to evaluate the concent of tumor significant dose (TSD) which will represent the damage to the cancerous tissue. Strandquist in the analysis of a large number of cases of squamous cell carcinoma found that for the 5 fraction/week treatment, the total dose required to bring about the same damage for the cancerous tissue is proportional to T/sup -0.22/, where T is the overall time over which the dose is delivered. Using this finding the TSD was defined as DxN/sup -p/xT/sup -q/, where D is the total dose, N the number of fractions, T the overall time p and q are the exponents to be suitably chosen. The values of p and q are adjusted such that p+q< or =0.24, and p varies from 0.0 to 0.24 and q varies from 0.0 to 0.22. Cases of cancer of cervix uteri treated between 1978 and 1980 in the V. N. Cancer Centre, Kuppuswamy Naidu Memorial Hospital, Coimbatore, India were analyzed on the basis of these formulations. These data, coupled with the clinical experience, were used for choice of a formula for the TSD. Further, the dose schedules used in the British Institute of Radiology fraction- ation studies were also used to propose that the tumor significant dose is represented by DxN/sup -0.18/xT/sup -0.06/

  5. Uranium chemistry: significant advances

    International Nuclear Information System (INIS)

    Mazzanti, M.

    2011-01-01

    The author reviews recent progress in uranium chemistry achieved in CEA laboratories. Like its neighbors in the Mendeleev chart uranium undergoes hydrolysis, oxidation and disproportionation reactions which make the chemistry of these species in water highly complex. The study of the chemistry of uranium in an anhydrous medium has led to correlate the structural and electronic differences observed in the interaction of uranium(III) and the lanthanides(III) with nitrogen or sulfur molecules and the effectiveness of these molecules in An(III)/Ln(III) separation via liquid-liquid extraction. Recent work on the redox reactivity of trivalent uranium U(III) in an organic medium with molecules such as water or an azide ion (N 3 - ) in stoichiometric quantities, led to extremely interesting uranium aggregates particular those involved in actinide migration in the environment or in aggregation problems in the fuel processing cycle. Another significant advance was the discovery of a compound containing the uranyl ion with a degree of oxidation (V) UO 2 + , obtained by oxidation of uranium(III). Recently chemists have succeeded in blocking the disproportionation reaction of uranyl(V) and in stabilizing polymetallic complexes of uranyl(V), opening the way to to a systematic study of the reactivity and the electronic and magnetic properties of uranyl(V) compounds. (A.C.)

  6. Meaning and significance of

    Directory of Open Access Journals (Sweden)

    Ph D Student Roman Mihaela

    2011-05-01

    Full Text Available The concept of "public accountability" is a challenge for political science as a new concept in this area in full debate and developement ,both in theory and practice. This paper is a theoretical approach of displaying some definitions, relevant meanings and significance odf the concept in political science. The importance of this concept is that although originally it was used as a tool to improve effectiveness and eficiency of public governance, it has gradually become a purpose it itself. "Accountability" has become an image of good governance first in the United States of America then in the European Union.Nevertheless,the concept is vaguely defined and provides ambiguous images of good governance.This paper begins with the presentation of some general meanings of the concept as they emerge from specialized dictionaries and ancyclopaedies and continues with the meanings developed in political science. The concept of "public accontability" is rooted in economics and management literature,becoming increasingly relevant in today's political science both in theory and discourse as well as in practice in formulating and evaluating public policies. A first conclusin that emerges from, the analysis of the evolution of this term is that it requires a conceptual clarification in political science. A clear definition will then enable an appropriate model of proving the system of public accountability in formulating and assessing public policies, in order to implement a system of assessment and monitoring thereof.

  7. Significant Radionuclides Determination

    Energy Technology Data Exchange (ETDEWEB)

    Jo A. Ziegler

    2001-07-31

    The purpose of this calculation is to identify radionuclides that are significant to offsite doses from potential preclosure events for spent nuclear fuel (SNF) and high-level radioactive waste expected to be received at the potential Monitored Geologic Repository (MGR). In this calculation, high-level radioactive waste is included in references to DOE SNF. A previous document, ''DOE SNF DBE Offsite Dose Calculations'' (CRWMS M&O 1999b), calculated the source terms and offsite doses for Department of Energy (DOE) and Naval SNF for use in design basis event analyses. This calculation reproduces only DOE SNF work (i.e., no naval SNF work is included in this calculation) created in ''DOE SNF DBE Offsite Dose Calculations'' and expands the calculation to include DOE SNF expected to produce a high dose consequence (even though the quantity of the SNF is expected to be small) and SNF owned by commercial nuclear power producers. The calculation does not address any specific off-normal/DBE event scenarios for receiving, handling, or packaging of SNF. The results of this calculation are developed for comparative analysis to establish the important radionuclides and do not represent the final source terms to be used for license application. This calculation will be used as input to preclosure safety analyses and is performed in accordance with procedure AP-3.12Q, ''Calculations'', and is subject to the requirements of DOE/RW-0333P, ''Quality Assurance Requirements and Description'' (DOE 2000) as determined by the activity evaluation contained in ''Technical Work Plan for: Preclosure Safety Analysis, TWP-MGR-SE-000010'' (CRWMS M&O 2000b) in accordance with procedure AP-2.21Q, ''Quality Determinations and Planning for Scientific, Engineering, and Regulatory Compliance Activities''.

  8. b型流感嗜血杆菌结合疫苗接种后婴幼儿安全性和免疫原性研究%Safety and immunogenicity in 3-5 months-old infants after primary and boosting immunization with Hib PRP-TT conjugate vaccine

    Institute of Scientific and Technical Information of China (English)

    叶强; 谢贵林; 李亚南; 赵志强; 李荣成; 何莉; 谭晓梅; 李艳萍; 杜送田; 李凤祥

    2012-01-01

    .48% respectively,with no significant difference.The local reactions including erythema,swelling and induration reported was 1.22% in study vaccine group.After 3 injections,the serum anti-Hib PRP IgG antibody GMC was 6.6686 μg/ml in study group and 7.5346 μg/ml in control group,with no significant difference in both of the antibody GMC (x2 =0.147,P=0.702).After one dose boosting injection,the serum antibody GMC in study group increased from 2.6396 μg/ml of preboosting to 6.2044 μg/ml of post-boosting.Conclusion The Hib-TT conjugate vaccine is proved to be safe in 3-5 months-old infants.The primary immune schedule for 3-5 months-old infants of 3 injections 1 month apart with the Hib-TT conjugate vaccine could induce IgG antibody response against Hib PRP with the GMC of long-term protection concentration in serum.A boosting dose after primary vaccination elicited obviously immunological memory.

  9. The energetic significance of cooking.

    Science.gov (United States)

    Carmody, Rachel N; Wrangham, Richard W

    2009-10-01

    While cooking has long been argued to improve the diet, the nature of the improvement has not been well defined. As a result, the evolutionary significance of cooking has variously been proposed as being substantial or relatively trivial. In this paper, we evaluate the hypothesis that an important and consistent effect of cooking food is a rise in its net energy value. The pathways by which cooking influences net energy value differ for starch, protein, and lipid, and we therefore consider plant and animal foods separately. Evidence of compromised physiological performance among individuals on raw diets supports the hypothesis that cooked diets tend to provide energy. Mechanisms contributing to energy being gained from cooking include increased digestibility of starch and protein, reduced costs of digestion for cooked versus raw meat, and reduced energetic costs of detoxification and defence against pathogens. If cooking consistently improves the energetic value of foods through such mechanisms, its evolutionary impact depends partly on the relative energetic benefits of non-thermal processing methods used prior to cooking. We suggest that if non-thermal processing methods such as pounding were used by Lower Palaeolithic Homo, they likely provided an important increase in energy gain over unprocessed raw diets. However, cooking has critical effects not easily achievable by non-thermal processing, including the relatively complete gelatinisation of starch, efficient denaturing of proteins, and killing of food borne pathogens. This means that however sophisticated the non-thermal processing methods were, cooking would have conferred incremental energetic benefits. While much remains to be discovered, we conclude that the adoption of cooking would have led to an important rise in energy availability. For this reason, we predict that cooking had substantial evolutionary significance.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Reducing Resistance

    DEFF Research Database (Denmark)

    Lindell, Johanna

    care may influence decisions on antibiotic use. Based on video-and audio recordings of physician-patient consultations it is investigated how treatment recommendations are presented, can be changed, are forecast and explained, and finally, how they seemingly meet resistance and how this resistance......Antibiotic resistance is a growing public health problem both nationally and internationally, and efficient strategies are needed to reduce unnecessary use. This dissertation presents four research studies, which examine how communication between general practitioners and patients in Danish primary...... is responded to.The first study in the dissertation suggests that treatment recommendations on antibiotics are often done in a way that encourages patient acceptance. In extension of this, the second study of the dissertation examines a case, where acceptance of such a recommendation is changed into a shared...

  12. Reducing costs by reducing size

    International Nuclear Information System (INIS)

    Hayns, M.R.; Shepherd, J.

    1991-01-01

    The present paper discusses briefly the many factors, including capital cost, which have to be taken into account in determining whether a series of power stations based on a small nuclear plant can be competitive with a series based on traditional large unit sizes giving the guaranteed level of supply. The 320 MWe UK/US Safe Integral Reactor is described as a good example of how the factors discussed can be beneficially incorporated into a design using proven technology. Finally it goes on to illustrate how the overall costs of a generating system can indeed by reduced by use of the 320 MWe Safe Integral Reactor rather than conventional units of around 1200 MWe. (author). 9 figs

  13. Historical Significant Volcanic Eruption Locations

    Data.gov (United States)

    Department of Homeland Security — A significant eruption is classified as one that meets at least one of the following criteriacaused fatalities, caused moderate damage (approximately $1 million or...

  14. Significance of irradiation of blood

    International Nuclear Information System (INIS)

    Sekine, Hiroshi; Gotoh, Eisuke; Mochizuki, Sachio

    1992-01-01

    Many reports of fatal GVHD occurring in non-immunocompromised patients after blood transfusion have been published in Japan. One explantation is that transfused lymphocytes were simulated and attack the recipient organs recognized as HLA incompatible. That is so called 'one-way matching'. To reduce the risk of post-transfusion GVHD, one of the most convenient methods is to irradiate the donated blood at an appropriate dose for inactivation of lymphocytes. Because no one knows about the late effect of irradiated blood, it is necessary to make the prospective safety control. (author)

  15. Significance evaluation in factor graphs

    DEFF Research Database (Denmark)

    Madsen, Tobias; Hobolth, Asger; Jensen, Jens Ledet

    2017-01-01

    in genomics and the multiple-testing issues accompanying them, accurate significance evaluation is of great importance. We here address the problem of evaluating statistical significance of observations from factor graph models. Results Two novel numerical approximations for evaluation of statistical...... significance are presented. First a method using importance sampling. Second a saddlepoint approximation based method. We develop algorithms to efficiently compute the approximations and compare them to naive sampling and the normal approximation. The individual merits of the methods are analysed both from....... Conclusions The applicability of saddlepoint approximation and importance sampling is demonstrated on known models in the factor graph framework. Using the two methods we can substantially improve computational cost without compromising accuracy. This contribution allows analyses of large datasets...

  16. Significant Lactic Acidosis from Albuterol

    Directory of Open Access Journals (Sweden)

    Deborah Diercks

    2018-03-01

    Full Text Available Lactic acidosis is a clinical entity that demands rapid assessment and treatment to prevent significant morbidity and mortality. With increased lactate use across many clinical scenarios, lactate values themselves cannot be interpreted apart from their appropriate clinical picture. The significance of Type B lactic acidosis is likely understated in the emergency department (ED. Given the mortality that sepsis confers, a serum lactate is an important screening study. That said, it is with extreme caution that we should interpret and react to the resultant elevated value. We report a patient with a significant lactic acidosis. Though he had a high lactate value, he did not require aggressive resuscitation. A different classification scheme for lactic acidosis that focuses on the bifurcation of the “dangerous” and “not dangerous” causes of lactic acidosis may be of benefit. In addition, this case is demonstrative of the potential overuse of lactates in the ED.

  17. The historical significance of oak

    Science.gov (United States)

    J. V. Thirgood

    1971-01-01

    A brief history of the importance of oak in Europe, contrasting the methods used in France and Britain to propagate the species and manage the forests for continued productivity. The significance of oak as a strategic resource during the sailing-ship era is stressed, and mention is made of the early development of oak management in North America. The international...

  18. Shrinkage Reducing Admixture for Concrete

    OpenAIRE

    ECT Team, Purdue

    2007-01-01

    Concrete shrinkage cracking is a common problem in all types of concrete structures, especially for structures and environments where the cracks are prevalent and the repercussions are most severe. A liquid shrinkage reducing admixture for concrete, developed by GRACE Construction Products and ARCO Chemical Company, that reduces significantly the shrinkage during concrete drying and potentially reduces overall cracking over time.

  19. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1994-03-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October - December 1993) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  20. Synthetic definition of biological significance

    International Nuclear Information System (INIS)

    Buffington, J.D.

    1975-01-01

    The central theme of the workshop is recounted and the views of the authors are summarized. Areas of broad agreement or disagreement, unifying principles, and research needs are identified. Authors' views are consolidated into concepts that have practical utility for the scientist making impact assessments. The need for decision-makers and managers to be cognizant of the recommendations made herein is discussed. Finally, bringing together the diverse views of the workshop participants, a conceptual definition of biological significance is synthesized

  1. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1992-11-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July - September 1992) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  2. 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).

  3. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1993-09-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April--June 1993) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  4. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1990-05-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1990) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. Also included are a number of enforcement actions that had been previously resolved but not published in this NUREG. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  5. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1991-05-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1991) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  6. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1991-02-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October--December 1990) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  7. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1990-03-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October--December 1989) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  8. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1990-11-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July--September 1990) and includes copies of letters, notices, and orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  9. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1992-08-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April--June 1992) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  10. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1990-09-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April--June 1990) and includes copies of letters, notices, and orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  11. Clinical significance of neonatal menstruation.

    Science.gov (United States)

    Brosens, Ivo; Benagiano, Giuseppe

    2016-01-01

    Past studies have clearly shown the existence of a spectrum of endometrial progesterone responses in neonatal endometrium, varying from proliferation to full decidualization with menstrual-like shedding. The bleedings represent, similar to what occurs in adult menstruation, a progesterone withdrawal bleeding. Today, the bleeding is completely neglected and considered an uneventful episode of no clinical significance. Yet clinical studies have linked the risk of bleeding to a series of events indicating fetal distress. The potential link between the progesterone response and major adolescent disorders requires to be investigated by prospective studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1993-06-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1993) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  13. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1992-05-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1992) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  14. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1993-12-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July--September 1993) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  15. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1993-03-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October--December 1992) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  16. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1991-07-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April-June 1991) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  17. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1991-11-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July--September 1991) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  18. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1992-03-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October--December 1991) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  19. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1989-06-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1989) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. Also included are a number of enforcement actions that had been previously resolved but not published in this NUREG. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  20. Enforcement actions: Significant actions resolved

    International Nuclear Information System (INIS)

    1989-12-01

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July--September 1989) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  1. The co registration of initial PET on the CT-radiotherapy reduces significantly the variabilities of anatomo-clinical target volume in the child hodgkin disease; La coregistration de la TEP initiale sur la scanographie de radiotherapie diminue significativement les variabilites de volume cible anatomoclinique dans la maladie de Hodgkin de l'enfant

    Energy Technology Data Exchange (ETDEWEB)

    Metwally, H.; Blouet, A.; David, I.; Rives, M.; Izar, F.; Courbon, F.; Filleron, T.; Laprie, A. [Institut Claudius-Regaud, 31 - Toulouse (France); Plat, G.; Vial, J. [CHU-hopital des Enfants, 31 - Toulouse (France)

    2009-10-15

    It exists a great interobserver variability for the anatomo-clinical target volume (C.T.V.) definition in children suffering of Hodgkin disease. In this study, the co-registration of the PET with F.D.G. on the planning computed tomography has significantly lead to a greater coherence in the clinical target volume definition. (N.C.)

  2. Moral significance of phenomenal consciousness.

    Science.gov (United States)

    Levy, Neil; Savulescu, Julian

    2009-01-01

    Recent work in neuroimaging suggests that some patients diagnosed as being in the persistent vegetative state are actually conscious. In this paper, we critically examine this new evidence. We argue that though it remains open to alternative interpretations, it strongly suggests the presence of consciousness in some patients. However, we argue that its ethical significance is less than many people seem to think. There are several different kinds of consciousness, and though all kinds of consciousness have some ethical significance, different kinds underwrite different kinds of moral value. Demonstrating that patients have phenomenal consciousness--conscious states with some kind of qualitative feel to them--shows that they are moral patients, whose welfare must be taken into consideration. But only if they are subjects of a sophisticated kind of access consciousness--where access consciousness entails global availability of information to cognitive systems--are they persons, in the technical sense of the word employed by philosophers. In this sense, being a person is having the full moral status of ordinary human beings. We call for further research which might settle whether patients who manifest signs of consciousness possess the sophisticated kind of access consciousness required for personhood.

  3. Clinical significance of the fabella

    International Nuclear Information System (INIS)

    Dodevski, A.; Lazarova-Tosovska, D.; Zhivadinovik, J.; Lazareska, M.

    2012-01-01

    Full text: Introduction: There is variable number of sesamoid bones in the human body; one of them is fabella, located in the tendon of the gastrocnemius muscle. Aim of this study was to investigate the frequency of occurrence of fabella in the Macedonian population and to discuss about clinical importance of this bone. Materials and methods: We retrospectively examined radiographs of 53 patients who had knee exams undertaken for a variety of clinical reasons, performed as a part of their medical treatment. Over a time span of six months, 53 patients (38 males and 15 females, age range 19-60 years, mean age of 36.7±12.3 years) were examined. Results: In seven (13.2%) patients of 53 analyzed reports, fabella was found in the lateral tendon of gastrocnemius muscle. We did not find a significant gender or side difference in the appearance of fabella. Conclusion: Although anatomic studies emphasized a lack of significance of the fabella, this bone has been associated with a spectrum of pathology affecting the knee as fabellar syndrome, perineal nerve injury and fracture. We should think of this sesamoid bone while performing diagnostic and surgical procedures

  4. The significance of small streams

    Science.gov (United States)

    Wohl, Ellen

    2017-09-01

    Headwaters, defined here as first- and secondorder streams, make up 70%‒80% of the total channel length of river networks. These small streams exert a critical influence on downstream portions of the river network by: retaining or transmitting sediment and nutrients; providing habitat and refuge for diverse aquatic and riparian organisms; creating migration corridors; and governing connectivity at the watershed-scale. The upstream-most extent of the channel network and the longitudinal continuity and lateral extent of headwaters can be difficult to delineate, however, and people are less likely to recognize the importance of headwaters relative to other portions of a river network. Consequently, headwaters commonly lack the legal protections accorded to other portions of a river network and are more likely to be significantly altered or completely obliterated by land use.

  5. No significant fuel failures (NSFF)

    International Nuclear Information System (INIS)

    Domaratzki, Z.

    1979-01-01

    It has long been recognized that no emergency core cooling system (ECCS) could be absolutely guaranteed to prevent fuel failures. In 1976 the Atomic Energy Control Board decided that the objective for an ECCS should be to prevent fuel failures, but if the objective could not be met it should be shown that the consequences are acceptable for dual failures comprising any LOCA combined with an assumed impairment of containment. Out of the review of the Bruce A plant came the definition of 'no significant fuel failures': for any postulated LOCA combined with any one mode of containment impairment the resultant dose to a person at the edge of the exclusion zone is less than the reference dose limits for dual failures

  6. Ritual Significance in Mycenaean Hairstyles

    Directory of Open Access Journals (Sweden)

    Hsu, Florence Sheng-chieh

    2012-04-01

    Full Text Available Although the frescoes excavated from Bronze Age sites on the Greek mainland provide evidence for female figures in the Mycenaean society, the hairstyles of these figures have not been studied in detail. As in many other ancient cultures, hairstyles were not only an exhibition of beauty and fashion, but they also represented certain age groups or a person’s social status. The Mycenaeans inherited many of their hairstyles from their Minoan predecessors, although differences existed as well. It is also possible there may have been a shift in meaning for seemingly similar looking hairstyles from the Minoan to the Mycenaean periods. Female figures, which compose most of the Mycenaean figures in frescoes known to date, are fine examples for discussing the artistic representation and potential significance of Mycenaean hairstyles. By comparing with Minoan hairstyles, discussions of Mycenaean examples lead to conclusions in the relationship between hairstyles and ritual activities in the Mycenaean society.

  7. Reducing rotor weight

    Energy Technology Data Exchange (ETDEWEB)

    Cheney, M.C. [PS Enterprises, Inc., Glastonbury, CT (United States)

    1997-12-31

    The cost of energy for renewables has gained greater significance in recent years due to the drop in price in some competing energy sources, particularly natural gas. In pursuit of lower manufacturing costs for wind turbine systems, work was conducted to explore an innovative rotor designed to reduce weight and cost over conventional rotor systems. Trade-off studies were conducted to measure the influence of number of blades, stiffness, and manufacturing method on COE. The study showed that increasing number of blades at constant solidity significantly reduced rotor weight and that manufacturing the blades using pultrusion technology produced the lowest cost per pound. Under contracts with the National Renewable Energy Laboratory and the California Energy Commission, a 400 kW (33m diameter) turbine was designed employing this technology. The project included tests of an 80 kW (15.5m diameter) dynamically scaled rotor which demonstrated the viability of the design.

  8. Significant biases affecting abundance determinations

    Science.gov (United States)

    Wesson, Roger

    2015-08-01

    I have developed two highly efficient codes to automate analyses of emission line nebulae. The tools place particular emphasis on the propagation of uncertainties. The first tool, ALFA, uses a genetic algorithm to rapidly optimise the parameters of gaussian fits to line profiles. It can fit emission line spectra of arbitrary resolution, wavelength range and depth, with no user input at all. It is well suited to highly multiplexed spectroscopy such as that now being carried out with instruments such as MUSE at the VLT. The second tool, NEAT, carries out a full analysis of emission line fluxes, robustly propagating uncertainties using a Monte Carlo technique.Using these tools, I have found that considerable biases can be introduced into abundance determinations if the uncertainty distribution of emission lines is not well characterised. For weak lines, normally distributed uncertainties are generally assumed, though it is incorrect to do so, and significant biases can result. I discuss observational evidence of these biases. The two new codes contain routines to correctly characterise the probability distributions, giving more reliable results in analyses of emission line nebulae.

  9. Astrobiological significance of chemolithoautotrophic acidophiles

    Science.gov (United States)

    Pikuta, Elena V.; Hoover, Richard B.

    2004-02-01

    For more than a century (since Winogradsky discovered lithautotrophic bacteria) there has been a dilemma in microbiology about life that first inhabited the Earth. Which types of life forms first appeared in the primordial oceans during the earliest geological period on Earth as the primary ancestors of modern biological diversity? How did a metabolism of ancestors evolve: from lithoautotrophic to lithoheterotrophic and organoheterotrophic or from organoheterotrophic to organautotrophic and lithomixotrophic types? At the present time, it is known that chemolithoheterotrophic and chemolithoautotrophic metabolizing bacteria are wide spread in different ecosystems. On Earth the acidic ecosystems are associated with geysers, volcanic fumaroles, hot springs, deep sea hydrothermal vents, caves, acid mine drainage and other technogenic ecosystems. Bioleaching played a significant roel on a global geological scale during the Earth's formation. This important feature of bacteria has been successfully applied in industry. The lithoautotrophs include Bacteria and Archaea belonging to diverse genera containing thermophilic and mesophilic species. In this paper we discuss the lithotrophic microbial acidophiles and present some data with a description of new acidophilic iron- and sulfur-oxidizing bacterium isolated from the Chena Hot Springs in Alaska. We also consider the possible relevance of microbial acidophiles to Venus, Io, and acidic inclusions in glaciers and icy moons.

  10. Determining Semantically Related Significant Genes.

    Science.gov (United States)

    Taha, Kamal

    2014-01-01

    GO relation embodies some aspects of existence dependency. If GO term xis existence-dependent on GO term y, the presence of y implies the presence of x. Therefore, the genes annotated with the function of the GO term y are usually functionally and semantically related to the genes annotated with the function of the GO term x. A large number of gene set enrichment analysis methods have been developed in recent years for analyzing gene sets enrichment. However, most of these methods overlook the structural dependencies between GO terms in GO graph by not considering the concept of existence dependency. We propose in this paper a biological search engine called RSGSearch that identifies enriched sets of genes annotated with different functions using the concept of existence dependency. We observe that GO term xcannot be existence-dependent on GO term y, if x- and y- have the same specificity (biological characteristics). After encoding into a numeric format the contributions of GO terms annotating target genes to the semantics of their lowest common ancestors (LCAs), RSGSearch uses microarray experiment to identify the most significant LCA that annotates the result genes. We evaluated RSGSearch experimentally and compared it with five gene set enrichment systems. Results showed marked improvement.

  11. Statistically significant relational data mining :

    Energy Technology Data Exchange (ETDEWEB)

    Berry, Jonathan W.; Leung, Vitus Joseph; Phillips, Cynthia Ann; Pinar, Ali; Robinson, David Gerald; Berger-Wolf, Tanya; Bhowmick, Sanjukta; Casleton, Emily; Kaiser, Mark; Nordman, Daniel J.; Wilson, Alyson G.

    2014-02-01

    This report summarizes the work performed under the project (3z(BStatitically significant relational data mining.(3y (BThe goal of the project was to add more statistical rigor to the fairly ad hoc area of data mining on graphs. Our goal was to develop better algorithms and better ways to evaluate algorithm quality. We concetrated on algorithms for community detection, approximate pattern matching, and graph similarity measures. Approximate pattern matching involves finding an instance of a relatively small pattern, expressed with tolerance, in a large graph of data observed with uncertainty. This report gathers the abstracts and references for the eight refereed publications that have appeared as part of this work. We then archive three pieces of research that have not yet been published. The first is theoretical and experimental evidence that a popular statistical measure for comparison of community assignments favors over-resolved communities over approximations to a ground truth. The second are statistically motivated methods for measuring the quality of an approximate match of a small pattern in a large graph. The third is a new probabilistic random graph model. Statisticians favor these models for graph analysis. The new local structure graph model overcomes some of the issues with popular models such as exponential random graph models and latent variable models.

  12. Statistical Significance for Hierarchical Clustering

    Science.gov (United States)

    Kimes, Patrick K.; Liu, Yufeng; Hayes, D. Neil; Marron, J. S.

    2017-01-01

    Summary Cluster analysis has proved to be an invaluable tool for the exploratory and unsupervised analysis of high dimensional datasets. Among methods for clustering, hierarchical approaches have enjoyed substantial popularity in genomics and other fields for their ability to simultaneously uncover multiple layers of clustering structure. A critical and challenging question in cluster analysis is whether the identified clusters represent important underlying structure or are artifacts of natural sampling variation. Few approaches have been proposed for addressing this problem in the context of hierarchical clustering, for which the problem is further complicated by the natural tree structure of the partition, and the multiplicity of tests required to parse the layers of nested clusters. In this paper, we propose a Monte Carlo based approach for testing statistical significance in hierarchical clustering which addresses these issues. The approach is implemented as a sequential testing procedure guaranteeing control of the family-wise error rate. Theoretical justification is provided for our approach, and its power to detect true clustering structure is illustrated through several simulation studies and applications to two cancer gene expression datasets. PMID:28099990

  13. Detection of significant protein coevolution.

    Science.gov (United States)

    Ochoa, David; Juan, David; Valencia, Alfonso; Pazos, Florencio

    2015-07-01

    The evolution of proteins cannot be fully understood without taking into account the coevolutionary linkages entangling them. From a practical point of view, coevolution between protein families has been used as a way of detecting protein interactions and functional relationships from genomic information. The most common approach to inferring protein coevolution involves the quantification of phylogenetic tree similarity using a family of methodologies termed mirrortree. In spite of their success, a fundamental problem of these approaches is the lack of an adequate statistical framework to assess the significance of a given coevolutionary score (tree similarity). As a consequence, a number of ad hoc filters and arbitrary thresholds are required in an attempt to obtain a final set of confident coevolutionary signals. In this work, we developed a method for associating confidence estimators (P values) to the tree-similarity scores, using a null model specifically designed for the tree comparison problem. We show how this approach largely improves the quality and coverage (number of pairs that can be evaluated) of the detected coevolution in all the stages of the mirrortree workflow, independently of the starting genomic information. This not only leads to a better understanding of protein coevolution and its biological implications, but also to obtain a highly reliable and comprehensive network of predicted interactions, as well as information on the substructure of macromolecular complexes using only genomic information. The software and datasets used in this work are freely available at: http://csbg.cnb.csic.es/pMT/. pazos@cnb.csic.es Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Reduced content of chloroatranol and atranol in oak moss absolute significantly reduces the elicitation potential of this fragrance material

    DEFF Research Database (Denmark)

    Andersen, Flemming; Andersen, Kirsten H; Bernois, Armand

    2015-01-01

    BACKGROUND: Oak moss absolute, an extract from the lichen Evernia prunastri, is a valued perfume ingredient but contains extreme allergens. OBJECTIVES: To compare the elicitation properties of two preparations of oak moss absolute: 'classic oak moss', the historically used preparation, and 'new o...

  16. Traditional Indian spices and their health significance.

    Science.gov (United States)

    Krishnaswamy, Kamala

    2008-01-01

    India has been recognized all over the world for spices and medicinal plants. Both exhibit a wide range of physiological and pharmacological properties. Current biomedical efforts are focused on their scientific merits, to provide science-based evidence for the traditional uses and to develop either functional foods or nutraceuticals. The Indian traditional medical systems use turmeric for wound healing, rheumatic disorders, gastrointestinal symptoms, deworming, rhinitis and as a cosmetic. Studies in India have explored its anti-inflammatory, cholekinetic and anti-oxidant potentials with the recent investigations focusing on its preventive effect on precarcinogenic, anti-inflammatory and anti atherosclerotic effects in biological systems both under in vitro and in vivo conditions in animals and humans. Both turmeric and curcumin were found to increase detoxifying enzymes, prevent DNA damage, improve DNA repair, decrease mutations and tumour formation and exhibit antioxidative potential in animals. Limited clinical studies suggest that turmeric can significantly impact excretion of mutagens in urine in smokers and regress precancerous palatal lesions. It reduces DNA adducts and micronuclei in oral epithelial cells. It prevents formation of nitroso compounds both in vivo and in vitro. It delays induced cataract in diabetes and reduces hyperlipidemia in obese rats. Recently several molecular targets have been identified for therapeutic / preventive effects of turmeric. Fenugreek seeds, a rich source of soluble fiber used in Indian cuisine reduces blood glucose and lipids and can be used as a food adjuvant in diabetes. Similarly garlic, onions, and ginger have been found to modulate favourably the process of carcinogenesis.

  17. Reducing infant mortality.

    Science.gov (United States)

    Johnson, T R

    1994-01-01

    Public health and social policies at the population level (e.g., oral rehydration therapy and immunization) are responsible for the major reduction in infant mortality worldwide. The gap in infant mortality rates between developing and developed regions is much less than that in maternal mortality rates. This indicates that maternal and child health (MCH) programs and women's health care should be combined. Since 1950, 66% of infant deaths occur in the 1st 28 days, indicating adverse prenatal and intrapartum events (e.g., congenital malformation and birth injuries). Infection, especially pneumonia and diarrhea, and low birth weight are the major causes of infant mortality worldwide. An estimated US$25 billion are needed to secure the resources to control major childhood diseases, reduce malnutrition 50%, reduce child deaths by 4 million/year, provide potable water and sanitation to all communities, provide basic education, and make family planning available to all. This cost for saving children's lives is lower than current expenditures for cigarettes (US$50 billion in Europe/year). Vitamin A supplementation, breast feeding, and prenatal diagnosis of congenital malformations are low-cost strategies that can significantly affect infant well-being and reduce child mortality in many developing countries. The US has a higher infant mortality rate than have other developed countries. The American College of Obstetricians and Gynecologists and the US National Institutes of Health are focusing on prematurity, low birth weight, multiple pregnancy, violence, alcohol abuse, and poverty to reduce infant mortality. Obstetricians should be important members of MCH teams, which also include traditional birth attendants, community health workers, nurses, midwives, and medical officers. We have the financial resources to allocate resources to improve MCH care and to reduce infant mortality.

  18. Regional and global significance of nuclear energy

    International Nuclear Information System (INIS)

    Schilling, H.D.

    1995-01-01

    Measures to combat poverty and improve the standard of living in countries of the Third World will inevitably boost global demand for energy, and energy conservation measures will not be able to offset this increase. Nuclear energy will regain significance in the framework of approaches adopted to resolve the energy problem, which primarily is an ecologic problem created by an extremely large flow of materials. The extraordinarily high energy density of nuclear fuels can contribute to markedly reduce the flow of materials; and at that, electric energy is an efficient substitute for primary energy forms. Thus nuclear electricity generation is of double benefit to the ecology. Engineering goals in nuclear technology thus gain a service aspect, with progress in power plant engineering and design aiming not only at enhanced engineered safety, but also at regaining public acceptance of and confidence in nuclear power plant technology. (orig./UA) [de

  19. Reducing Dysfunctional Beliefs about Sleep Does Not Significantly Improve Insomnia in Cognitive Behavioral Therapy

    OpenAIRE

    Okajima, Isa; Nakajima, Shun; Ochi, Moeko; Inoue, Yuichi

    2014-01-01

    The present study examined to examine whether improvement of insomnia is mediated by a reduction in sleep-related dysfunctional beliefs through cognitive behavioral therapy for insomnia. In total, 64 patients with chronic insomnia received cognitive behavioral therapy for insomnia consisting of 6 biweekly individual treatment sessions of 50 minutes in length. Participants were asked to complete the Athens Insomnia Scale and the Dysfunctional Beliefs and Attitudes about Sleep scale both at the...

  20. A novel 5-enolpyruvylshikimate-3-phosphate synthase from Rahnella aquatilis with significantly reduced glyphosate sensitivity.

    Directory of Open Access Journals (Sweden)

    Ri-He Peng

    Full Text Available The 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS; EC 2.5.1.19 is a key enzyme in the shikimate pathway for the production of aromatic amino acids and chorismate-derived secondary metabolites in plants, fungi, and microorganisms. It is also the target of the broad-spectrum herbicide glyphosate. Natural glyphosate resistance is generally thought to occur within microorganisms in a strong selective pressure condition. Rahnella aquatilis strain GR20, an antagonist against pathogenic agrobacterial strains of grape crown gall, was isolated from the rhizosphere of grape in glyphosate-contaminated vineyards. A novel gene encoding EPSPS was identified from the isolated bacterium by complementation of an Escherichia coli auxotrophic aroA mutant. The EPSPS, named AroA(R. aquatilis, was expressed and purified from E. coli, and key kinetic values were determined. The full-length enzyme exhibited higher tolerance to glyphosate than the E. coli EPSPS (AroA(E. coli, while retaining high affinity for the substrate phosphoenolpyruvate. Transgenic plants of AroA(R. aquatilis were also observed to be more resistant to glyphosate at a concentration of 5 mM than that of AroA(E. coli. To probe the sites contributing to increased tolerance to glyphosate, mutant R. aquatilis EPSPS enzymes were produced with the c-strand of subdomain 3 and the f-strand of subdomain 5 (Thr38Lys, Arg40Val, Arg222Gln, Ser224Val, Ile225Val, and Gln226Lys substituted by the corresponding region of the E. coli EPSPS. The mutant enzyme exhibited greater sensitivity to glyphosate than the wild type R. aquatilis EPSPS with little change of affinity for its first substrate, shikimate-3-phosphate (S3P and phosphoenolpyruvate (PEP. The effect of the residues on subdomain 5 on glyphosate resistance was more obvious.

  1. Long-term agricultural management maximizing hay production can significantly reduce belowground C storage

    Czech Academy of Sciences Publication Activity Database

    Sochorová, Lenka; Jansa, Jan; Verbruggen, E.; Hejcman, M.; Schellberg, J.; Kiers, E. T.; Johnson, N. C.

    2016-01-01

    Roč. 220, March (2016), s. 104-114 ISSN 0167-8809 R&D Projects: GA MŠk(CZ) LK11224 Institutional support: RVO:61388971 Keywords : Arbuscular mycorrhiza * Nitrogen * Phosphorus Subject RIV: EH - Ecology, Behaviour Impact factor: 4.099, year: 2016

  2. Clinical significance of reduced cerebral metabolism in multiple sclerosis. A combined PET and MRI study

    International Nuclear Information System (INIS)

    Sun, Xiayan; Tanaka, Makoto; Kondo, Susumu; Okamoto, Koichi; Hirai, Shunsaku

    1998-01-01

    Magnetic resonance imaging (MRI) in patients with multiple sclerosis (MS) has provided major insights into the disease's natural history, and many studies have focussed on possible correlations between MRI findings and the clinical manifestations of MS. In contrast, there are few reports on possible relationships between functional imaging data and cognitive function. The present study assessed the relationship between clinical presentation and combined anatomical and functional imaging data in MS. Twenty patients with definite MS underwent MRI and positron emission tomography (PET) to evaluate cerebral blood flow (rCBF) and oxygen metabolism (rCMRO 2 ). The relationships between these neuroimaging findings and clinical data, including the Expanded Disability Status Scale (EDSS), Mini-mental status scale, Hasegawa Dementia Scale and relapse time, were evaluated with Spearman's rank correlation coefficients. A general reduction in rCBF and rCMRO 2 in the gray and white matter were found in the MS patients. EDSS was correlated with the number and size of the lesions on MRI and was negatively correlated with rCMRO 2 . A correlation between the decrease in rCMRO 2 and the level of cognitive impairment was also found. The severity of cerebral hypometabolism was also related to the number of relapses. Morphological and functional findings obtained by MRI and PET are closely related to the clinical status in MS. Our results suggest that measurement of cerebral metabolism in MS has the potential to be an objective marker for monitoring disease activity and to provide prognostic information. (author)

  3. Synergy in Sulfur Cycle: The Biogeochemical Significance of Sulfate Reducing Bacteria in Syntrophic Associations

    Digital Repository Service at National Institute of Oceanography (India)

    LokaBharathi, P.A.

    . Consideration of the oasis analogy for chemosyntheticcommunities at Gulf of Mexico hydrocarbon vents. Geo. Mar. Lett. 14,149-159 Douglas, A.E.,2004. Strategies in antagonistic and cooperative interactions. Microbial Evolution. Gene Establishment, survival... and fuels. Plenum, New York, pp 277?296. MacAvoy, S.A., Macko, S.A., Joye, S.B., 2002. Fatty acid carbon isotope signatures in chemosynthetic mussels and tube worms from Gulf of Mexico hydrocarbon seep communities. Chem.Geol. 185, 1 ? 8. Michaelis, W...

  4. Long-term agricultural management maximizing hay production can significantly reduce belowground C storage

    NARCIS (Netherlands)

    Sochorová, L.; Jansa, J.; Verbruggen, E.; Hejcman, M.; Schellberg, J.; Kiers, E.T.

    2016-01-01

    Liming and fertilization of grasslands have been used for centuries to sustain hay production. Besides improving hay yields, these practices induce compositional shifts in plant and soil microbial communities, including symbiotic arbuscular mycorrhizal (AM) fungi. However, in spite of increasing

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

    OpenAIRE

    An, Chongwei; Li, Hequn; Ye, Baoyun; Wang, Jingyu

    2017-01-01

    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 sph...

  6. Mutation of NRAS but not KRAS significantly reduces myeloma sensitivity to single-agent bortezomib therapy

    NARCIS (Netherlands)

    G. Mulligan (George); D.I. Lichter (David); A.D. Bacco (Alessandra Di); S.J. Blakemore (Stephen); A. Berger (Allison); E. Koenig (Erik); H. Bernard (Hugues); W.L. Trepicchio (William); B. Li (Bin); R. Neuwirth (Rachel); N. Chattopadhyay (Nibedita); J.B. Bolen (Joseph); A.J. Dorner (Andrew); H. van de Velde (Helgi); D. Ricci (Deborah); S. Jagannath (Sundar); J.R. Berenson (James); P.G. Richardson (Paul Gerard); E.A. Stadtmauer (Edward); R.Z. Orlowski (Robert); S. Lonial (Sagar); K.C. Anderson (Kenneth); P. Sonneveld (Pieter); J.F. San Miguel (Jesús Fernando); D.-L. Esseltine (Dixie-Lee); M. Schu (Matthew)

    2014-01-01

    textabstractVarious translocations and mutations have been identified in myeloma, and certain aberrations, such as t(4;14) and del17, are linked with disease prognosis. To investigate mutational prevalence in myeloma and associations between mutations and patient outcomes, we tested a panel of 41

  7. Teenage Smoking: Higher Excise Tax Should Significantly Reduce the Number of Smokers

    Science.gov (United States)

    1989-06-30

    12 to 17, in the United States, about 3.5 million use tobacco products, almost 3 million smoke marijuana , 6 million drink alcohol, and 1 million use...particularly in indoor environments. As a result nonsmokers tend to face a greater risk of cancer and of becoming less healthy in general. (The details on

  8. Significant enhancement of the thermoelectric figure of merit of polycrystalline Si films by reducing grain size

    International Nuclear Information System (INIS)

    Valalaki, K; Nassiopoulou, A G; Vouroutzis, N

    2016-01-01

    The thermoelectric properties of p-type polycrystalline silicon thin films deposited by low pressure chemical vapour deposition (LPCVD) were accurately determined at room temperature and the thermoelectric figure of merit was deduced as a function of film thickness, ranging from 100 to 500 nm. The effect of film thickness on their thermoelectric performance is discussed. More than threefold increase in the thermoelectric figure of merit of the 100 nm thick polysilicon film was observed compared to the 500 nm thick film, reaching a value as high as 0.033. This enhancement is mainly the result of the smaller grain size in the thinner films. With the decrease in grain size the resistivity of the films is increased twofold and electrical conductivity decreased, however the Seebeck coefficient is increased by 30% and the thermal conductivity is decreased eightfold, being mainly at the origin of the increased figure of merit of the 100 nm film. Our experimental results were compared to known theoretical models and the possible mechanisms involved are presented and discussed. (paper)

  9. Microplastic contamination of river beds significantly reduced by catchment-wide flooding

    Science.gov (United States)

    Hurley, Rachel; Woodward, Jamie; Rothwell, James J.

    2018-04-01

    Microplastic contamination of the oceans is one of the world's most pressing environmental concerns. The terrestrial component of the global microplastic budget is not well understood because sources, stores and fluxes are poorly quantified. We report catchment-wide patterns of microplastic contamination, classified by type, size and density, in channel bed sediments at 40 sites across urban, suburban and rural river catchments in northwest England. Microplastic contamination was pervasive on all river channel beds. We found multiple urban contamination hotspots with a maximum microplastic concentration of approximately 517,000 particles m-2. After a period of severe flooding in winter 2015/16, all sites were resampled. Microplastic concentrations had fallen at 28 sites and 18 saw a decrease of one order of magnitude. The flooding exported approximately 70% of the microplastic load stored on these river beds (equivalent to 0.85 ± 0.27 tonnes or 43 ± 14 billion particles) and eradicated microbead contamination at 7 sites. We conclude that microplastic contamination is efficiently flushed from river catchments during flooding.

  10. Radiological significance of thorium processing in manufacturing

    International Nuclear Information System (INIS)

    Davis, M.W.

    1985-01-01

    The study of thorium processing in manufacturing comprised monitoring programs at a plant where thorium dioxide was in use and another where the use of thorium nitrate had been discontinued. The measurements of the solubility in simulated lung fluid proved that both materials belonged in the Y Class with dissolution half-times greater than 500 days. Bioassay measurements of 20 subjects from both facilities proved that in vitro monitoring methods, urine, feces, hair and nails analysis were not sufficient indicators of thorium uptake. In vivo monitoring by phoswich and large sodium iodide detectors were proven to be good methods of determining thorium lung burdens. The thoron in breath technique was shown to have a lower limit of sensitivity than lung counting, however, due to lack of information regarding the thoron escape rate from the thorium particles in the lungs the method is not as accurate as lung counting. Two subjects at the thorium dioxide facility had lung burdens of 21+- 16 Bq and 29+- 24 Bq Th 232 and one at the thorium nitrate facility had a lung burden of 37+- 13 Bq. Improvements in the procedures and use of a glove box were among the recommendations to reduce the inhalation of thorium by workers at the thorium dioxide facility. Decontamination of several rooms at the thorium nitrate facility and sealing of the walls and floors were recommended in order to reduce the escape of thoron gas into the room air. The risk to non Atomic Radiation Workers was primarily due to thoron daughters in air while gamma radiation and thorium in air were less important. Conversely, at the thorium dioxide facility the inhalation of thorium in air was the most significant exposure pathway

  11. 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.

  12. Reduced Rank Regression

    DEFF Research Database (Denmark)

    Johansen, Søren

    2008-01-01

    The reduced rank regression model is a multivariate regression model with a coefficient matrix with reduced rank. The reduced rank regression algorithm is an estimation procedure, which estimates the reduced rank regression model. It is related to canonical correlations and involves calculating...

  13. Global warming: the significance of methane

    International Nuclear Information System (INIS)

    Dessus, B.; Le Treut, H.; Laponche, B.

    2008-01-01

    the concept of Global Warming Potential (GWP) indicates the relative contribution to global warming over a given period (for example 100 years) of a pulse emission at the start of the period of 1 kg of a specific greenhouse gas (GHG) in comparison to the contribution, over the same period, of an emission of 1 kg of CO 2 . The GWPs calculated for different time intervals take into account the differences in atmospheric lifetimes of the different GHGs. Using the '100-year GWP' to measure non CO 2 GHG emissions is not well suited to the case of permanent or long lifetime measures whose effectiveness is to be assessed at a given time horizon. In this context, it contributes to significantly playing down the importance of reducing emissions of GHGs with short atmospheric lifetimes. Thus, for example, methane which is not emitted over the period 2020- 2100 as a result of a landfill site being closed in 2020 will have an impact (as opposed to if the site remained in operation) that would be far greater towards 2100 compared to a CO 2 emission source that has also been stopped permanently and whose climate impact is measured in an equivalent manner. Using the GWP is only appropriate if applied year after year to time horizons considered to be of concern or decisive by climate studies, thus in particular 2050, 2100 and 2150. This is all the more significant as climate experts' current concerns lead them not only to advocate long-term stabilisation of GHG concentrations but also to avoid as far as possible intermediate excess of these concentrations over the coming century. Finally, it is noted that CH 4 prevention policies implemented in the short term may continue to have a long-term impact greater than merely taking into account the current GWP would imply. To more or less ignore the impact of CH 4 as it is unsuitable for accounting purposes affects the exclusive character of the link that may exist between the issue of GHGs and that of energy. Furthermore, if the

  14. Prognostic significance of erythropoietin in pancreatic adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Thilo Welsch

    Full Text Available BACKGROUND: Erythropoietin (Epo administration has been reported to have tumor-promoting effects in anemic cancer patients. We investigated the prognostic impact of endogenous Epo in patients with pancreatic ductal adenocarcinoma (PDAC. METHODOLOGY: The clinico-pathological relevance of hemoglobin (Hb, n = 150, serum Epo (sEpo, n = 87 and tissue expression of Epo/Epo receptor (EpoR, n = 104 was analyzed in patients with PDAC. Epo/EpoR expression, signaling, growth, invasion and chemoresistance were studied in Epo-exposed PDAC cell lines. RESULTS: Compared to donors, median preoperative Hb levels were reduced by 15% in both chronic pancreatitis (CP, p<0.05 and PDAC (p<0.001, reaching anemic grade in one third of patients. While inversely correlating to Hb (r = -0.46, 95% of sEPO values lay within the normal range. The individual levels of compensation were adequate in CP (observed to predicted ratio, O/P = 0.99 but not in PDAC (O/P = 0.85. Strikingly, lower sEPO values yielding inadequate Epo responses were prominent in non-metastatic M0-patients, whereas these parameters were restored in metastatic M1-group (8 vs. 13 mU/mL; O/P = 0.82 vs. 0.96; p<0.01--although Hb levels and the prevalence of anemia were comparable. Higher sEpo values (upper quartile ≥ 16 mU/ml were not significantly different in M0 (20% and M1 (30% groups, but were an independent prognostic factor for shorter survival (HR 2.20, 10 vs. 17 months, p<0.05. The pattern of Epo expression in pancreas and liver suggested ectopic release of Epo by capillaries/vasa vasorum and hepatocytes, regulated by but not emanating from tumor cells. Epo could initiate PI3K/Akt signaling via EpoR in PDAC cells but failed to alter their functions, probably due to co-expression of the soluble EpoR isoform, known to antagonize Epo. CONCLUSION/SIGNIFICANCE: Higher sEPO levels counteract anemia but worsen outcome in PDAC patients. Further trials are required to clarify how overcoming a sEPO threshold

  15. Impact significance determination-Back to basics

    International Nuclear Information System (INIS)

    Lawrence, David P.

    2007-01-01

    Impact significance determination is widely recognized as a vital and critical EIA activity. But impact significance related concepts are poorly understood. And the quality of approaches for impact significance determination in EIA practice remains highly variable. This article seeks to help establish a sound and practical conceptual foundation for formulating and evaluating impact significance determination approaches. It addresses the nature (what is impact significance?), the core characteristics (what are the major properties of significance determination?), the rationale (why are impact significance determinations necessary?), the procedural and substantive objectives (what do impact significance determinations seek to achieve?), and the process for making impact significance judgments (how is impact significance determination conducted?). By identifying fundamental attributes and key distinctions associated with impact significance determinations, a basis is provided for designing and evaluating impact significance determination procedures at both the regulatory and applied levels

  16. Reduced abrasion drilling fluid

    NARCIS (Netherlands)

    2010-01-01

    A reduced abrasion drilling fluid system and method of drilling a borehole by circulating the reduced abrasion drilling fluid through the borehole is disclosed. The reduced abrasion drilling fluid comprises a drilling fluid, a first additive and a weighting agent, wherein the weighting agent has a

  17. Reduced abrasion drilling fluid

    NARCIS (Netherlands)

    2012-01-01

    A reduced abrasion drilling fluid system and method of drilling a borehole by circulating the reduced abrasion drilling fluid through the borehole is disclosed. The reduced abrasion drilling fluid comprises a drilling fluid, a first additive and a weighting agent, wherein the weighting agent has a

  18. Structural mode significance using INCA. [Interactive Controls Analysis computer program

    Science.gov (United States)

    Bauer, Frank H.; Downing, John P.; Thorpe, Christopher J.

    1990-01-01

    Structural finite element models are often too large to be used in the design and analysis of control systems. Model reduction techniques must be applied to reduce the structural model to manageable size. In the past, engineers either performed the model order reduction by hand or used distinct computer programs to retrieve the data, to perform the significance analysis and to reduce the order of the model. To expedite this process, the latest version of INCA has been expanded to include an interactive graphical structural mode significance and model order reduction capability.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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

  1. Rackspace: Significance of Cloud Computing to CERN

    CERN Multimedia

    CERN. Geneva

    2015-01-01

    The research collaboration between Rackspace and CERN is contributing to how OpenStack cloud computing will move science work around the world for CERN, and to reducing the barriers between clouds for Rackspace.

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

    Science.gov (United States)

    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.

  3. Creating Significant Learning Experiences across Disciplines

    Science.gov (United States)

    Levine, Laura E.; Fallahi, Carolyn R.; Nicoll-Senft, Joan M.; Tessier, Jack T.; Watson, Cheryl L.; Wood, Rebecca M.

    2008-01-01

    The purpose of this study was to use Fink's (2003) taxonomy of significant learning to redesign courses and assess student learning. Significant improvements were found across the semester for students in the six courses, but there were differences in which taxa showed improvement in each course. The meta-analysis showed significant, positive…

  4. 23 CFR 630.1010 - Significant projects.

    Science.gov (United States)

    2010-04-01

    ... 23 Highways 1 2010-04-01 2010-04-01 false Significant projects. 630.1010 Section 630.1010 Highways... PRECONSTRUCTION PROCEDURES Work Zone Safety and Mobility § 630.1010 Significant projects. (a) A significant project is one that, alone or in combination with other concurrent projects nearby is anticipated to cause...

  5. Role and significance of total phenols during rooting of Protea ...

    African Journals Online (AJOL)

    The high total phenol content was associated with significantly higher rooting percentage and increased the number of roots formed. Blanching reduced the time needed for the cuttings to root sufficiently to be transplanted to the field by 30 days. Analyses of different parts of cuttings throughout the entire rooting period ...

  6. Reducing the impact.

    Science.gov (United States)

    Mahathir, M

    1997-01-01

    In Asia, attempts to control HIV/AIDS through education have not achieved the necessary behavior changes. This is especially true for young women who are unable to apply their knowledge to their sex behavior because of inequalities in gender relations. Thus, the impact of AIDS on women is significantly greater in settings where the status of women is low. Women in developing countries are at greatest risk because the epidemic is fueled by poverty, lack of information, and lack of autonomy. Prosperity in a developing country, such as Malaysia, entails its own risks because it creates new social norms and values that exist in tandem with debilitating old norms, such as the patriarchy that disempowers women and a resurgence in polygamy and wife abandonment. Subservient gender roles not only increase women's chances of infection, they also target women as the primary caregivers for infected individuals. Young girls may have to abandon school to care for infected parents, and female health care providers are assigned to the lowest ranks of the profession. While most women have been infected by their husbands, they must also bear the stigma of being considered immoral infectors of their husbands. The futures of AIDS widows and orphans is jeopardized by the discrimination that attends the disease, and if the mother dies, her young children face a higher death rate. In settings new to the epidemic, it is difficult to convince men of the importance of addressing women's needs and of seeking the input of women in policy and program development. Only by empowering both sexes to work together to protect society will there be a reasonable chance of reducing the impact of HIV/AIDS.

  7. Reducible oxide based catalysts

    Science.gov (United States)

    Thompson, Levi T.; Kim, Chang Hwan; Bej, Shyamal K.

    2010-04-06

    A catalyst is disclosed herein. The catalyst includes a reducible oxide support and at least one noble metal fixed on the reducible oxide support. The noble metal(s) is loaded on the support at a substantially constant temperature and pH.

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

    Science.gov (United States)

    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.

  9. Direct oxide reducing method

    International Nuclear Information System (INIS)

    Tokiwai, Moriyasu.

    1995-01-01

    Calcium oxides and magnetic oxides as wastes generated upon direct reduction are subjected to molten salt electrolysis, and reduced metallic calcium and magnesium are separated and recovered. Then calcium and magnesium are used recyclically as the reducing agent upon conducting direct oxide reduction. Even calcium oxides and magnesium oxides, which have high melting points and difficult to be melted usually, can be melted in molten salts of mixed fluorides or chlorides by molten-salt electrolysis. Oxides are decomposed by electrolysis, and oxygen is removed in the form of carbon monoxide, while the reduced metallic calcium and magnesium rise above the molten salts on the side of a cathode, and then separated. Since only carbon monoxide is generated as radioactive wastes upon molten salt electrolysis, the amount of radioactive wastes can be greatly reduced, and the amount of the reducing agent used can also be decreased remarkably. (N.H.)

  10. Immunogenicity of a reduced schedule of meningococcal group C conjugate vaccine given concomitantly with the Prevenar and Pediacel vaccines in healthy infants in the United Kingdom.

    Science.gov (United States)

    Southern, Jo; Borrow, Ray; Andrews, Nick; Morris, Rhonwen; Waight, Pauline; Hudson, Michael; Balmer, Paul; Findlow, Helen; Findlow, Jamie; Miller, Elizabeth

    2009-02-01

    This study investigated the use of two doses of three different meningococcal group C conjugate (MCC) vaccines when given for primary immunization with a seven-valent pneumococcal conjugate vaccine (PCV7) and Pediacel, a combination product containing five acellular pertussis components, diphtheria and tetanus toxoids, Haemophilus influenzae type b (Hib) conjugate, and inactivated-poliovirus vaccine. The immune response after a single dose of MCC is also presented. Infants were randomized to receive two doses of one of the MCC vaccines and PCV7 at 2 and 3 months or at 2 and 4 months of age. Meningococcal group C serum bactericidal antibody (SBA) geometric mean titers, Hib-polyribosylribitol phosphate (PRP) immunoglobulin G (IgG) geometric mean concentrations (GMCs), and diphtheria and tetanus antitoxin GMCs, together with the proportions of infants achieving putative protective levels, were determined. A total of 393 infants were recruited. Following the first dose of NeisVac-C (MCC conjugated to tetanus toxoid), 97% of infants achieved protective levels (SBA titer of >or=8), compared with 80% and 53%, respectively, for Menjugate and Meningitec (both of which are conjugated to CRM(197)). SBA responses to MCC vaccines were not significantly different when administered at 2 and 3 or 2 and 4 months of age. Following two doses of each MCC, 98 to 100% of infants achieved protective levels. Both PRP IgG and tetanus responses were significantly enhanced when Pediacel was coadministered with NeisVac-C. This study demonstrates that NeisVac-C and Menjugate generate good immunogenicity after the first dose at 2 months of age when coadministered with PCV7 and Pediacel and merit further investigation in single-dose priming strategies.

  11. Methodology, theoretical framework and scholarly significance: An ...

    African Journals Online (AJOL)

    Methodology, theoretical framework and scholarly significance: An overview ... AFRICAN JOURNALS ONLINE (AJOL) · Journals · Advanced Search ... Keywords: Legal Research, Methodology, Theory, Pedagogy, Legal Training, Scholarship ...

  12. Impact significance determination-Pushing the boundaries

    International Nuclear Information System (INIS)

    Lawrence, David P.

    2007-01-01

    Impact significance determination practice tends to be highly variable. Too often insufficient consideration is given to good practice insights. Also, impact significance determinations are frequently narrowly defined addressing, for example, only individual, negative impacts, focusing on bio-physical impacts, and not seeking to integrate either the Precautionary Principle or sustainability. This article seeks to extend the boundaries of impact significance determination practice by providing an overview of good general impact significance practices, together with stakeholder roles and potential methods for addressing significance determination challenges. Relevant thresholds, criteria, contextual considerations and support methods are also highlighted. The analysis is then extended to address how impact significance determination practices change for positive as compared with negative impacts, for cumulative as compared with individual impacts, for socio-economic as compared with bio-physical impacts, when the Precautionary Principle is integrated into the process, and when sustainability contributions drive the EIA process and related impact significance determinations. These refinements can assist EIA practitioners in ensuring that the scope and nature of impact significance determinations reflect the broadened scope of emerging EIA requirements and practices. Suggestions are included for further refining and testing of the proposed changes to impact significance determination practice

  13. Regionally Significant Ecological Areas - MLCCS derived 2008

    Data.gov (United States)

    Minnesota Department of Natural Resources — This is an analysis of regionally significant Terrestrial and Wetland Ecological Areas in the seven county metropolitan area. Individual forest, grassland and...

  14. Central Region Regionally Ecological Significant Areas

    Data.gov (United States)

    Minnesota Department of Natural Resources — This is an analysis of regionally significant Terrestrial and Wetland Ecological Areas in the seven county metropolitan area. Individual forest, grassland and...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  17. Pipeline Drag Reducers

    International Nuclear Information System (INIS)

    Marawan, H.

    2004-01-01

    Pipeline drag reducers have proven to be an extremely powerful tool in fluid transportation. High molecular weight polymers are used to reduce the frictional pressure loss ratio in crude oil pipelines, refined fuel and aqueous pipelines. Chemical structure of the main used pipeline drag reducers is one of the following polymers and copolymers classified according to the type of fluid to ; low density polyethylene, copolymer of I-hexane cross linked with divinyl benzene, polyacrylamide, polyalkylene oxide polymers and their copolymers, fluorocarbons, polyalkyl methacrylates and terpolymer of styrene, alkyl acrylate and acrylic acid. Drag reduction is the increase in pump ability of a fluid caused by the addition of small amounts of an additive to the fluid. The effectiveness of a drag reducer is normally expressed in terms of percent drag reduction. Frictional pressure loss in a pipeline system is a waste of energy and it costly. The drag reducing additive minimizes the flow turbulence, increases throughput and reduces the energy costs. The Flow can be increased by more than 80 % with existing assets. The effectiveness of the injected drag reducer in Mostorod to Tanta crude oil pipeline achieved 35.4 % drag reduction and 23.2 % flow increase of the actual performance The experimental application of DRA on Arab Petroleum Pipeline Company (Summed) achieved a flow increase ranging from 9-32 %

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

    Directory of Open Access Journals (Sweden)

    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.

  19. The thresholds for statistical and clinical significance

    DEFF Research Database (Denmark)

    Jakobsen, Janus Christian; Gluud, Christian; Winkel, Per

    2014-01-01

    BACKGROUND: Thresholds for statistical significance are insufficiently demonstrated by 95% confidence intervals or P-values when assessing results from randomised clinical trials. First, a P-value only shows the probability of getting a result assuming that the null hypothesis is true and does...... not reflect the probability of getting a result assuming an alternative hypothesis to the null hypothesis is true. Second, a confidence interval or a P-value showing significance may be caused by multiplicity. Third, statistical significance does not necessarily result in clinical significance. Therefore...... of the probability that a given trial result is compatible with a 'null' effect (corresponding to the P-value) divided by the probability that the trial result is compatible with the intervention effect hypothesised in the sample size calculation; (3) adjust the confidence intervals and the statistical significance...

  20. What if there were no significance tests?

    CERN Document Server

    Harlow, Lisa L; Steiger, James H

    2013-01-01

    This book is the result of a spirited debate stimulated by a recent meeting of the Society of Multivariate Experimental Psychology. Although the viewpoints span a range of perspectives, the overriding theme that emerges states that significance testing may still be useful if supplemented with some or all of the following -- Bayesian logic, caution, confidence intervals, effect sizes and power, other goodness of approximation measures, replication and meta-analysis, sound reasoning, and theory appraisal and corroboration. The book is organized into five general areas. The first presents an overview of significance testing issues that sythesizes the highlights of the remainder of the book. The next discusses the debate in which significance testing should be rejected or retained. The third outlines various methods that may supplement current significance testing procedures. The fourth discusses Bayesian approaches and methods and the use of confidence intervals versus significance tests. The last presents the p...

  1. Reducing Pesticide Drift

    Science.gov (United States)

    Provides information about pesticide spray drift, including problems associated with drift, managing risks from drift and the voluntary Drift Reduction Technology program that seeks to reduce spray drift through improved spray equipment design.

  2. Reducing Childhood Obesity

    Science.gov (United States)

    ... Bar Home Current Issue Past Issues Reducing Childhood Obesity Past Issues / Summer 2007 Table of Contents For ... Ga. were the first three We Can! cities. Obesity Research: A New Approach The percentage of children ...

  3. Transdermal drug delivery: approaches and significance

    OpenAIRE

    Murthy, SATHYANARAYANA

    2012-01-01

    S Narasimha MurthyDepartment of Pharmaceutics, The University of Mississippi, USATransdermal drug delivery systems deliver drugs through the skin as an alternative to oral, intravascular, subcutaneous, and transmucosal routes. Potential advantages of transdermal delivery include, but are not limited to, elimination of first-pass metabolism, steady delivery/blood levels, better patient compliance, reduced systemic drug interactions, possible dose intervention, avoidance of medically assisted d...

  4. Encouraging generic use can yield significant savings.

    Science.gov (United States)

    Zimmerman, Christina

    2012-11-01

    Key findings. (1) Zero copayment for generic drugs is the greatest influencer of generic statin utilization. (2) Both higher copayments for generic drugs and lower copayments for competing brands are associated with a decreased probability of using generic statins. (3) Prior authorization and step therapy requirements for brand-name statins are associated with an increased use of generic drugs. (4) Greater use of generic statins should reduce costs for patients, plans, and Medicare.

  5. Reducing The Nuclear Danger

    Science.gov (United States)

    1995-10-01

    off convention • Eliminate the civil use of HEU (includes RERTR ) • Reduce stockpiles of civil HEU and plutonium • Promote alternatives to the...these countries. ANL supports the Department’s Reduced Enrichment for Research and Test Reactor ( RERTR ) Program by providing the technical means to...scientists and engineers at 60 institutes in Russia, Ukraine, Kazakhstan and Belarus. The United States and Russia have agreed to pursue a joint RERTR

  6. Using reduce in supersymmetry

    International Nuclear Information System (INIS)

    Santos, R.P. dos.

    1987-01-01

    A procedure which allows one to do Supersymmetry calculus in REDUCE is described. Using the concept of an eight-dimensional 'superspace' (spanned by four space-time and four anticommuting coordinates) and of 'superfields' (which represent an entire supermultiplet of particles that transform among themselves), covariant derivatives with respect to supersymmetry are defined. Then, combining the vector facility and LET statement in REDUCE, spinors are simulated in a way to control the algebraic manipulation. (G.D.F.) [pt

  7. Mining Significant Semantic Locations from GPS Data

    DEFF Research Database (Denmark)

    Cao, Xin; Cong, Gao; Jensen, Christian Søndergaard

    2010-01-01

    With the increasing deployment and use of GPS-enabled devices, massive amounts of GPS data are becoming available. We propose a general framework for the mining of semantically meaningful, significant locations, e.g., shopping malls and restaurants, from such data. We present techniques capable...... of extracting semantic locations from GPS data. We capture the relationships between locations and between locations and users with a graph. Significance is then assigned to locations using random walks over the graph that propagates significance among the locations. In doing so, mutual reinforcement between...

  8. Discovering the Significance of Scientific Design Practice

    DEFF Research Database (Denmark)

    Pries-Heje, Jan; Baskerville, Richard

    2016-01-01

    This paper discusses and defines the achievement of significance in design science research. We review the values and processes of old-science and how this mode of science attacks the complexity of scientific knowledge production through analysis. We then explain how new-science attacks...... the complexity of scientific knowledge production through synthesis. The work argues that significance of the new-science contribution in design science can be obfuscated when wrapped in old-science. This understanding helps reveal how new-science, such as design science research, constitutes its significance...

  9. Mining significant semantic locations from GPS data

    DEFF Research Database (Denmark)

    Cao, Xin; Cong, Gao; Jensen, Christian S.

    2010-01-01

    With the increasing deployment and use of GPS-enabled devices, massive amounts of GPS data are becoming available. We propose a general framework for the mining of semantically meaningful, significant locations, e.g., shopping malls and restaurants, from such data. We present techniques capable...... of extracting semantic locations from GPS data. We capture the relationships between locations and between locations and users with a graph. Significance is then assigned to locations using random walks over the graph that propagates significance among the locations. In doing so, mutual reinforcement between...

  10. SRS Process Facility Significance Fire Frequency

    Energy Technology Data Exchange (ETDEWEB)

    Sarrack, A.G. [Westinghouse Savannah River Company, AIKEN, SC (United States)

    1995-10-01

    This report documents the method and assumptions of a study performed to determine a site generic process facility significant fire initiator frequency and explains the proper way this value should be used.

  11. Can a significance test be genuinely Bayesian?

    OpenAIRE

    Pereira, Carlos A. de B.; Stern, Julio Michael; Wechsler, Sergio

    2008-01-01

    The Full Bayesian Significance Test, FBST, is extensively reviewed. Its test statistic, a genuine Bayesian measure of evidence, is discussed in detail. Its behavior in some problems of statistical inference like testing for independence in contingency tables is discussed.

  12. 40 CFR 1508.27 - Significantly.

    Science.gov (United States)

    2010-07-01

    ... Register of Historic Places or may cause loss or destruction of significant scientific, cultural, or... cultural resources, park lands, prime farmlands, wetlands, wild and scenic rivers, or ecologically critical...

  13. Economically Significant Sites - OSPR [ds356

    Data.gov (United States)

    California Natural Resource Agency — This point data set shows locations of Economically Significant Sites along the California coast from Del Norte to San Diego counties. Data for locating these points...

  14. Contribution of radiodiagnosis to genetically significant dose

    International Nuclear Information System (INIS)

    Pele, J.M.; Ouvrard, R.

    Surveys were carried out in France on 33,000 X-ray medical examinations. The genetically significant dose to the whole population from roentgenography and fluoroscopy, for typical examinations, should be about 65mrads [fr

  15. SRS Process Facility Significance Fire Frequency

    International Nuclear Information System (INIS)

    Sarrack, A.G.

    1995-10-01

    This report documents the method and assumptions of a study performed to determine a site generic process facility significant fire initiator frequency and explains the proper way this value should be used

  16. SIGWX Charts - High Level Significant Weather

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — High level significant weather (SIGWX) forecasts are provided for the en-route portion of international flights. NOAA's National Weather Service Aviation Center...

  17. Asymptomatic bacteriuria. Clinical significance and management.

    Science.gov (United States)

    Raz, Raul

    2003-10-01

    The clinical significance and management of asymptomatic bacteriuria (ASB) differs according to different groups of patients. ASB requires antibiotic treatment in pregnant women, children aged 5-6 years and prior to invasive genitourinary procedures. However, there is a consensus that ASB in the elderly, healthy school girls and young women, diabetic women and patients with indwelling catheters or intermittent catheterization has no clinical significance and antibiotic prescription is not indicated.

  18. Formal conditions for the significance-effect

    DEFF Research Database (Denmark)

    Thellefsen, Torkild Leo; Sørensen, Bent; Thellefsen, Martin

    2006-01-01

    The significance-effect is the right effect of meaning caused upon an interpreting mind. The right effect is understood as the right interpretation of an intended meaning caused by a sign communicated by an utterer. In the article, which is inspired by Charles S. Peirce's doctrine of signs, his s...... semeiotics and his theory of communication, we account for the formal conditions that have to be present for the release of the significance-effect....

  19. Significance of Hemispheric Security for Mexico

    Science.gov (United States)

    2003-04-07

    La Seguridad Internacional, la Nueva Geopolitica Continental y Mexico ,” Seminario Internacional sobre Misiones de Paz, Seguridad y Defensa, Rio de...USAWC STRATEGY RESEARCH PROJECT SIGNIFICANCE OF HEMISPHERIC SECURITY FOR MEXICO by LTC Enrique Garcia Jaramillo Cavalry, Mexican Army COL Joseph R...xx-xx-2002 to xx-xx-2003 4. TITLE AND SUBTITLE Significance of Hemispheric Security for Mexico Unclassified 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c

  20. Building stones can be of geoheritage significance

    Science.gov (United States)

    Brocx, Margaret; Semeniuk, Vic

    2017-04-01

    Building stones have generally been assigned values according to their cultural, aesthetic, and rarity significance, amongst other criteria, but they also may have geoheritage significance. This is akin to the geoheritage significance ascribed to minerals and fossils housed as ex situ specimens in museums. We proffer the notion that building stones can be of geoheritage value particularly where they comprise permanent buildings, they illustrate significant windows into the history of the Earth, and they can be visited as an ex situ museum locality (e.g., the "Blue Granite" of Iceland) for education as part of building-stone tours. For some rocks the quarries that supplied the building stone are no longer in existence and hence the building stones provide the only record of that type of material; for other rocks, the building stone may illustrate features in the lithology no longer present in the quarry itself (e.g., rare and large xenoliths). Building stones are particularly significant as they are often polished and manifest structures, fabrics, and textures not evident in outcrop. We illustrate here examples of building stone of geoheritage significance using Australian and International examples. Australian designated stones could include the "Sydney Sandstone" or "Victorian Bluestone". For international examples, there is the famous "Carrara Marble" in Italy and the widely known "Portland Limestone" from southern England, the latter having been utilized for St Pauls Cathedral in London and the UN building in New York City.

  1. Biomimetic Fluorocarbon Surfactant Polymers Reduce Platelet Adhesion on PTFE/ePTFE Surfaces

    Science.gov (United States)

    Wang, Shuwu; Gupta, Anirban Sen; Sagnella, Sharon; Barendt, Pamela M.; Kottke-Marchant, Kandice; Marchant, Roger E.

    2010-01-01

    We describe a series of fluorocarbon surfactant polymers designed as surface-modifying agents for improving the thrombogenicity of ePTFE vascular graft materials by the reduction of platelet adhesion. The surfactant polymers consist of a poly(vinyl amine) backbone with pendent dextran and perfluoroundecanoyl branches. Surface modification is accomplished by a simple dip-coating process in which surfactant polymers undergo spontaneous surface-induced adsorption and assembly on PTFE/ePTFE surface. The adhesion stability of the surfactant polymer on PTFE was examined under dynamic shear conditions in PBS and human whole blood with a rotating disk system. Fluorocarbon surfactant polymer coatings with three different dextran to perfluorocarbon ratios (1:0.5, 1:1 and 1:2) were compared in the context of platelet adhesion on PTFE/ePTFE surface under dynamic flow conditions. Suppression of platelet adhesion was achieved for all three coated surfaces over the shear-stress range of 0–75 dyn/cm2 in platelet-rich plasma (PRP) or human whole blood. The effectiveness depended on the surfactant polymer composition such that platelet adhesion on coated surfaces decreased significantly with increasing fluorocarbon branch density at 0 dyn/cm2. Our results suggest that fluorocarbon surfactant polymers can effectively suppress platelet adhesion and demonstrate the potential application of the fluorocarbon surfactant polymers as non-thrombogenic coatings for ePTFE vascular grafts. PMID:19323880

  2. Significance of Lead Residues in Mallard Tissues

    Science.gov (United States)

    Longcore, J.R.; Locke, L.N.; Bagley, George E.; Andrews, R.

    1974-01-01

    Tissues of adult, lead-dosed mallards that either died or were sacrificed were analyzed for lead. Lead levels in brains, tibiae, and breast muscle of ducks that died and in tibiae of ducks that were sacrificed increased significantly from dosage until death. Lead in the heart, lung, and blood from sacrificed ducks decreased significantly from dosage until death. Lead concentrations in tissues from ducks in the two groups were not significantly different except for the liver, kidney, and lung. Average lead levels in the livers and kidneys of ducks that died were significantly higher than those in ducks that were sacrificed. The mean concentration of lead in the lungs of the ducks sacrificed was significantly higher than the mean level in the lungs of ducks that died. Measurements of the lead concentrations in this study, when compared with lead levels reported in the literature